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Sample records for exerts cytoprotective effects

  1. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

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    Han, Jae Yun [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Seung Sik [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Da Eon [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Bang, Joon Seok [Graduate School of Clinical Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Jung, Young Suk [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  2. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Science.gov (United States)

    Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

    2015-01-01

    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

  3. AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in vitro.

    Science.gov (United States)

    Szczesny, Bartosz; Módis, Katalin; Yanagi, Kazunori; Coletta, Ciro; Le Trionnaire, Sophie; Perry, Alexis; Wood, Mark E; Whiteman, Matthew; Szabo, Csaba

    2014-09-15

    The purpose of the current study was to investigate the effect of the recently synthesized mitochondrially-targeted H2S donor, AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], on bioenergetics, viability, and mitochondrial DNA integrity in bEnd.3 murine microvascular endothelial cells in vitro, under normal conditions, and during oxidative stress. Intracellular H2S was assessed by the fluorescent dye 7-azido-4-methylcoumarin. For the measurement of bioenergetic function, the XF24 Extracellular Flux Analyzer was used. Cell viability was estimated by the combination of the MTT and LDH methods. Oxidative protein modifications were measured by the Oxyblot method. Reactive oxygen species production was monitored by the MitoSOX method. Mitochondrial and nuclear DNA integrity were assayed by the Long Amplicon PCR method. Oxidative stress was induced by addition of glucose oxidase. Addition of AP39 (30-300 nM) to bEnd.3 cells increased intracellular H2S levels, with a preferential response in the mitochondrial regions. AP39 exerted a concentration-dependent effect on mitochondrial activity, which consisted of a stimulation of mitochondrial electron transport and cellular bioenergetic function at lower concentrations (30-100 nM) and an inhibitory effect at the higher concentration of 300 nM. Under oxidative stress conditions induced by glucose oxidase, an increase in oxidative protein modification and an enhancement in MitoSOX oxidation was noted, coupled with an inhibition of cellular bioenergetic function and a reduction in cell viability. AP39 pretreatment attenuated these responses. Glucose oxidase induced a preferential damage to the mitochondrial DNA; AP39 (100 nM) pretreatment protected against it. In conclusion, the current paper documents antioxidant and cytoprotective effects of AP39 under oxidative stress conditions, including a protection against oxidative mitochondrial DNA damage. Copyright © 2014 Elsevier Inc. All

  4. Intracellular ATP concentration contributes to the cytotoxic and cytoprotective effects of adenosine.

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    Shujue Li

    Full Text Available Extracellular adenosine (ADE interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.

  5. NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

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    Chen, Zhi-Dong [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Xu, Liang [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Tang, Kan-Kai [Department of Critical Care Medicine, The First Affiliated Hospital of Huzhou Normal College, Huzhou 313000, Zhejiang (China); Gong, Fang-Xiao; Liu, Jing-Quan; Ni, Yin; Jiang, Ling-Zhi; Hong, Jun; Han, Fang; Li, Qian; Yang, Xiang-Hong [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Sun, Ren-Hua, E-mail: jqin168@hotmail.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China); Mo, Shi-Jing, E-mail: msj860307@163.com [Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang (China)

    2016-09-10

    Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a NF

  6. Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects.

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    Bolton, Judy L; Dunlap, Tareisha

    2017-01-17

    Quinones represent a class of toxicological intermediates, which can create a variety of hazardous effects in vivo including, acute cytotoxicity, immunotoxicity, and carcinogenesis. In contrast, quinones can induce cytoprotection through the induction of detoxification enzymes, anti-inflammatory activities, and modification of redox status. The mechanisms by which quinones cause these effects can be quite complex. The various biological targets of quinones depend on their rate and site of formation and their reactivity. Quinones are formed through a variety of mechanisms from simple oxidation of catechols/hydroquinones catalyzed by a variety of oxidative enzymes and metal ions to more complex mechanisms involving initial P450-catalyzed hydroxylation reactions followed by two-electron oxidation. Quinones are Michael acceptors, and modification of cellular processes could occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radical anions leading to the formation of reactive oxygen species (ROS) including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can alter redox balance within cells through the formation of oxidized cellular macromolecules including lipids, proteins, and DNA. This perspective explores the varied biological targets of quinones including GSH, NADPH, protein sulfhydryls [heat shock proteins, P450s, cyclooxygenase-2 (COX-2), glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1, (NQO1), kelch-like ECH-associated protein 1 (Keap1), IκB kinase (IKK), and arylhydrocarbon receptor (AhR)], and DNA. The evidence strongly suggests that the numerous mechanisms of quinone modulations (i.e., alkylation versus oxidative stress) can be correlated with the known pathology/cytoprotection of the parent compound(s) that is best described by an inverse U-shaped dose-response curve.

  7. Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.

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    Lucia Castro-Vazquez

    2016-01-01

    Full Text Available Grapefruit (Citrus paradisi Macf. is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf. peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies.

  8. Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

    Science.gov (United States)

    Li, Xia; Jiang, Xinwei; Sun, Jianxia; Zhu, Cuijuan; Li, Xiaoling; Tian, Lingmin; Liu, Liu; Bai, Weibin

    2017-06-01

    Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported. © 2017 New York Academy of Sciences.

  9. Evaluation of the antioxidant capacity, furan compounds and cytoprotective/cytotoxic effects upon Caco-2 cells of commercial Colombian coffee.

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    Bedoya-Ramírez, Daniel; Cilla, Antonio; Contreras-Calderón, José; Alegría-Torán, Amparo

    2017-03-15

    Antioxidant capacity (AC), total phenolics (TPs), furan compounds (HMF and furfural F) and cytoprotective/cytotoxic effects upon Caco-2 cells (MTT, cell cycle and reactive oxygen species (ROS)) were evaluated in Colombian coffee (2 ground and 4 soluble samples). The AC (ABTS and FRAP), TPs and HMF ranged between 124-722, 95-802μmoles Trolox/g, 21-100mg gallic acid/g and 69-2900mg/kg, respectively. Pretreatment of cells for 24h with lyophilized coffee infusions at the highest dose without cytotoxic effects (500μg/mL) significantly prevented the decrease in cell viability compared to control stress with H2O2 (5mM/2h), recovering viability to values between 34% and 45% and restoring the control values without stress induction in the G1 phase of cell cycle. After exposure to stress, four extracts decreased ROS values significantly to 22.5-24.9%. The coffee samples exerted a cytoprotective effect against oxidative stress, with improvement in cell viability and a reduction of intracellular ROS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

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    Nicola Pacini

    2016-03-01

    Full Text Available For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.

  11. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

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    Jorge Berlanga-Acosta

    2017-02-01

    Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

  12. Cytoprotective and antioxidant effects of the methanol extract of ...

    African Journals Online (AJOL)

    ... the whole plant methanol extract (100-200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic ...

  13. Cytoprotective effect of selective small-molecule caspase inhibitors against staurosporine-induced apoptosis

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    Wu J

    2014-05-01

    Full Text Available Jianghong Wu, Yuren Wang, Shuguang Liang, Haiching Ma Reaction Biology Corp, Malvern, PA, USA Abstract: Caspases are currently known as the central executioners of the apoptotic pathways. Inhibition of apoptosis and promotion of normal cell survival by caspase inhibitors would be a tremendous benefit for reducing the side effects of cancer therapy and for control of neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. The objective of this study was to discover small-molecule caspase inhibitors with which to achieve cytoprotective effect. We completed the high-throughput screening of Bionet's 37,500-compound library (Key Organics Limited, Camelford, Cornwall, UK against caspase-1, -3, and -9 and successfully identified 43 initial hit compounds. The 43 hit compounds were further tested for cytoprotective activity against staurosporine-induced cell death in NIH3T3 cells. Nineteen compounds were found to have significant cytoprotective effects in cell viability assays. One of the compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine-induced caspase-3 cleavage and activation. RBC1023 was also shown to protect against staurosporine-induced impairment of mitochondrial membrane potential. DNA microarray analysis demonstrated that staurosporine treatment induced broad global gene expression alterations, and RBC1023 co-treatment significantly restored these changes, especially of the genes that are related to cell growth and survival signaling such as Egr1, Cdc25c, cdkn3, Rhob, Nek2, and Taok1. Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced apoptosis via inhibiting caspase activity, restoring mitochondrial membrane potential, and possibly upregulating some cell survival-related gene expressions and pathways. Keywords: cell death, caspase inhibition, mitochondria, RBC1023

  14. Cytoprotective effect against mercury chloride and bioinsecticidal activity of Eugenia jambolana Lam.

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    Celestina E. Sobral-Souza

    2014-01-01

    Full Text Available The fruit fly Drosophila melanogaster is often utilized in genetic research, and in the last decades, it has become one of best organisms for studies of human diseases and toxicological research. Mercury chloride (HgCl2, the main representative of mercury compounds, is the target of numerous investigations, not only because of its intrinsic toxicity but also because it accounts for the toxicity of elemental mercury since the latter is converted to Hg+2 by oxidation. Eugenia jambolana Lam. Myrtaceae, known in Brazil as “jambolão”, is of great interest because of its medicinal applications, especially its leaves and fruits. The aim of this work was to characterize, by CG–MS, the chemical constituents of the essential oil of Eugenia jambolana and to evaluate its bioinsecticidal action in the Drosophila melanogaster model, as well as to determine the cytoprotective and chelating effect of the extract of E. jambolana. The results obtained here point to the potential of essential oils as a source in biological prospecting for bioinsecticides. Because of their biodegradability, essential oils can be important tools in the biological control of pests. The results demonstrated that the extract has an allelopathic effect on lettuce seeds and that its interaction with mercury chloride allows a greater growth of the radicle and plumule of Lactuta sativa seedlings, showing that this plant can provide an alternative solution to the problem of contamination by heavy metals, besides having cytoprotective potential and moderate chelating activity.

  15. R- and S-Equol have equivalent cytoprotective effects in Friedreich’s Ataxia

    Science.gov (United States)

    2012-01-01

    Background Estradiol (E2) is a very potent cytoprotectant against a wide variety of cellular insults in numerous different cell models, including a Friedreich’s ataxia (FRDA) model. Previously, we demonstrated that estrogen-like compounds are able to prevent cell death in an FRDA model independent of any known estrogen receptor (ER) by reducing reactive oxygen species (ROS) and the detrimental downstream effects of ROS buildup including oxidative damage to proteins and lipids and impaired mitochondrial function. Results We have previously demonstrated by western blot that our cell model lacks ERα and expresses only very low levels of ERβ. Using L-buthionine (S,R)-sulfoximine (BSO) to induce oxidative stress in human FRDA fibroblasts, we determine the potency and efficacy of the soy-derived ERβ agonist S-equol and its ERα-preferring enantiomer, R-equol in vitro on cell viability and ROS accumulation. Here we demonstrate that these equol biphenolic compounds, while significantly less potent and efficacious than E2, provide statistically similar attenuation of ROS and cytoprotection against a BSO-induced oxidative insult. Conclusions These preliminary data demonstrate that estrogen and soy-derived equols could have a beneficial effect in delaying the onset and decreasing the severity of symptoms in FRDA patients by an antioxidant mechanism. In addition, these data confirm that the protection seen previously with E2 was indeed unrelated to ER binding. PMID:23088310

  16. In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla

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    Sônia Pamplona

    2015-10-01

    Full Text Available Swietenia macrophylla (mahogany is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction and M2 (infusion, were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg. Under experimental sub-chronic conditions (72 h, concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL, strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.

  17. In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla.

    Science.gov (United States)

    Pamplona, Sônia; Sá, Paulo; Lopes, Dielly; Costa, Edmar; Yamada, Elizabeth; e Silva, Consuelo; Arruda, Mara; Souza, Jesus; da Silva, Milton

    2015-10-16

    Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.

  18. Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

    Science.gov (United States)

    Bouzenna, Hafsia; Hfaiedh, Najla; Bouaziz, Mouhamed; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

    2017-12-01

    Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

  19. Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury.

    Science.gov (United States)

    Chen, Howard H; Yuan, Hushan; Cho, Hoonsung; Feng, Yan; Ngoy, Soeun; Kumar, Anand T N; Liao, Ronglih; Chao, Wei; Josephson, Lee; Sosnovik, David E

    2017-01-01

    Extracellular nucleic acids are proinflammatory molecules that have been implicated in a diverse range of diseases. We report here the development of a multivalent nucleic acid scavenging nanoprobe, where the fluorochrome thiazole orange (TO) is conjugated to a polymeric 40 kDa dextran carrier. Dextran-TO (Dex-TO) has nanomolar affinity for mammalian and bacterial nucleic acids and attenuates the production of inflammatory cytokines from activated macrophages exposed to DNA and RNA. Mice with myocardial ischemia reperfusion that were treated with Dex-TO showed a decrease in myocardial macrophage infiltration at 24 hours (ptheranostic) utility in a broad range of conditions including ischemia, trauma, burns, sepsis and autoimmune disease.

  20. Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes

    NARCIS (Netherlands)

    Donatus, I A; Sardjoko,; Vermeulen, N P

    1990-01-01

    The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to

  1. Cytotoxic effects exerted by Tritrichomonas foetus pseudocysts.

    Science.gov (United States)

    Pereira-Neves, Antonio; Nascimento, Ligia Ferreira; Benchimol, Marlene

    2012-07-01

    The protozoan parasite Tritrichomonas foetus displays a pear-shaped form and a pseudocyst stage. However, little is known about the biology of the pseudocyst. The aim of this work was to assess whether pseudocysts exert cytotoxic effects during their interaction with MDCK cells (an epithelial kidney canine cell line) and compare their behavior to that of the pear-shaped parasites. Pseudocysts and pear-shaped parasites from both cultured and freshly isolated T. foetus were used. Electron microscopy revealed that the epithelial cells exhibited more signs of injury, such as depletion of microvilli, retraction from neighboring cells and swollen mitochondria with loss of electron density in the matrix, when the pseudocysts were used in interaction experiments. In addition, during the co-incubation with MDCK cells, pseudocysts exhibited a more intense amoeboid transformation than that found in pear-shaped parasites. The MTT viability assay demonstrated that the pseudocysts were more cytotoxic when in contact with host cells as compared to the flagellated pear-shaped parasites. The JC-1 viability assay revealed that pseudocysts induced a higher loss of mitochondrial membrane potential compared to pear-shaped parasites. Pseudocysts undergoing a budding process were observed after 2.5h of co-incubation with MDCK cells. Our results suggest that the T. foetus pseudocyst might be a more aggressive form. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. Cytoprotective effects of 4,6-bis(1H-pyrazol-1-yl)pyrimidine and related compounds on HCI.ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Ikeda, M; Maruyama, K; Nobuhara, Y; Yamada, T; Okabe, S

    1997-03-01

    Bis(1H-pyrazol-1-yl)- and bis(1H-imidazol-1-yl)pyrimidines were synthesized and evaluated for cytoprotective effects. Among them, 4,6-bis(1H-pyrazol-1-yl)pyrimidine (3) showed a potent inhibitory effect on the HCl.ethanol-, ethanol-, and water immersion stress-induced gastric lesions in rats, and a very low acute toxicity. One of the major factors responsible for the cytoprotective effects of 3 is the increase in the bicarbonate secretion. This compound appears to be a promising cytoprotective drug for the treatment of gastric mucosal ulcers.

  3. The Cytoprotective Effects of Morus Alba Leaves in Cultured Fetus Fibroblast Cells against Hyperglycemia

    Directory of Open Access Journals (Sweden)

    Mohammadreza Shams-Ardekani

    2013-11-01

    Full Text Available Background: Diabetes is a chronic disease characterized by high blood glucose levels. Medicinal plants have useful source of hypoglycemic compounds and play important role in preventing the progress of this disease. Morus alba leaves is natural therapeutic agent shown hypoglycemic effects. In this study, the protective effects of alcoholic extract Morus alba leaves on fetus fibroblast cells under hyperglycemic condition were assessed.Materials and Methods: In this experimental study the cells were treated with six different concentrations of extracts. The nontoxic concentration of plant extract was measured with MTT assay in fetus fibroblast cells. Then, the fetus fibroblast cells were incubated with high dose of glucose and plant extract at concentrations of 1000 ppm. DNA synthesis, as marker of cell proliferation was determined.Results: In this study treated with plant extract showed an increase in the level of DNA content. There were significant changes in cell proliferation in treated group with plant extract. Morus alba leaves could cause cell attachment and proliferation. The attachment of cells to culture plates has been shown to be affected by plant extract.Conclusion: The data obtained from this study approved that Morus alba leaves has cytoprotective effects against hyperglycemia.

  4. Understanding the cytotoxicity or cytoprotective effects of biological and synthetic quinone derivatives by redox mechanism.

    Science.gov (United States)

    Borges, Rosivaldo S; Carneiro, Agnaldo S; Barros, Tainá G; Barros, Carlos A L; Neto, Antonio M J Chaves; da Silva, Albérico B F

    2014-12-01

    Quinones represent an important class of biological compounds, but are also involved with toxicological intermediates and among their hazardous effects include cytotoxicity, immunotoxicity, and carcinogenesis. The structure-toxicity relationship for quinone derivatives has been used to cytotoxicity or cytoprotective effects by redox mechanism is determined using quantum chemical calculations through the density functional theory (DFT). According to our DFT study, the electron acceptance is related with LUMO, electron affinity, and stabilization energy values. The highest spin density distribution in the heteroatoms is more favored for the more cytotoxic compounds. The electrophilic capacities of these compounds have been related with LUMO values. The cytotoxic properties of quinones are related to the stabilization energy after electron accepting by redox mechanism. Electron affinity is the most relevant parameter related to toxicity mechanism. Regioisomers has different electrophilic capacity. The electrophilicity increases on molecules containing electron-withdrawing groups (EWG) and reduces on molecules containing electron-donating groups (EDG). These results explain the toxic difference between natural and synthetic quinone derivatives and can be used in the design and study of new drugs.

  5. Cytoprotective effect of autophagy on phagocytosis of apoptotic cells by macrophages.

    Science.gov (United States)

    Zhou, Pei; Tan, Yu-Zhen; Wang, Hai-Jie; Li, Ting; He, Tao; Yu, Ying; Zhang, Jian; Zhang, Dan

    2016-11-01

    Clearance of the apoptotic cells by phagocytes plays pivotal roles in maintenance of tissue homeostasis, promotion of immunological tolerance and anti-inflammatory response. Recent studies show that autophagy is involved in phagocytosis of the apoptotic cells. However, contribution of autophagy to phagocytosis of the apoptotic cells by macrophages is not clearly defined. Here, we assessed cytoprotective effect of autophagy on clearance of the apoptotic cells. Apoptosis of murine splenic lymphocytes and human T-cell leukemia cells was induced with cyclophosphamide. After engulfment of the apoptotic cells, expression of Belin-1 and LC3 in macrophages was upregulated, the number of MDC-positive vesicles, LC3-positive autophagosomes and autophagic ultrastructures increased significantly. Autophagosome was fused with phagosome containing fragments of the nuclei or other debris of the apoptotic cells to form amphisome. Some cells in macrophages phagocytosing the apoptotic cells became apoptotic. After autophagy of macrophages was inhibited with 3-MA, viability and survival of macrophages reduced, phagocytosis of the apoptotic cells by macrophages deceased significantly. These results demonstrate that autophagy plays an important role in promoting clearance of the apoptotic cells by protecting macrophages from apoptosis during phagocytosis as well as degrading the contents of phagosomes via amphisome formation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The cytoprotective effects of Δ-17 fatty acid desaturase on injured HUVECs and its underlying mechanism

    Directory of Open Access Journals (Sweden)

    Xiulan Zhang

    2017-05-01

    Full Text Available Endothelium toxicity has been involved in early endothelial dysfunction to show the pathogenesis of multiple cardiovascular disease that shows atherosclerosis and its complications. Saturated free fatty acids are the main inducing factors of endothelial cell apoptosis and inflammatory cytokines. In humans, stearoyl-CoA desaturase 1 (SCD-1 is a restriction step to saturation to unsaturated fatty acid desaturation, which plays a beneficial role protecting endothelial cells against lipotoxicity. Δ-17 fatty acid desaturase (FAD is a newly identified FAD which shares 55% identity at the amino acid level with SCD-1. Whether Δ-17 FAD has similar beneficial effect remains poorly understood. Oxidized low density lipoprotein (ox-LDL was used to induce lipotoxicity in human umbilical vein endothelial cells (HUVECs to establish a model of oxidative injury. Then HUVECs were transfected with FAD lentivirus to introduce cytoprotective effects. The alterations in cell proliferation and apoptosis, nitric oxide content, malonyldialdehyde (MDA content, SOD enzyme content, LDH content, GSH-PX level, vascular growth factor (VEGF expression were evaluated. Studies showed that ox-LDL-induced excess HUVEC apoptosis can be abrogated by upregulation of Δ-17 FAD. The nitric oxide content, GSH-PX content, and SOD enzyme content were increased and the activity of MDA was suppressed by upregulation of Δ-17 FAD. In addition, upregulation of Δ-17 FAD significantly increased VEGF expression. In vitro tube formation assay showed that Δ-17 FAD promoted angiogenesis to a significant degree. These results suggest that Δ-17 fatty acid desaturase may have beneficial action in the prevention of ox-LDL-induced cellular damage.

  7. β-CELL SPECIFIC CYTOPROTECTION BY PROLACTIN ON HUMAN ISLETS

    Science.gov (United States)

    Yamamoto, Toshiyuki; Ricordi, Camillo; Mita, Atsuyoshi; Miki, Atsushi; Sakuma, Yasunaru; Damaris Molano, R.; Fornoni, Alessia; Pileggi, Antonello; Inverardi, Luca; Ichii, Hirohito

    2008-01-01

    Many cytoprotective agents have been reported to improve islet isolation and transplantation outcomes. However, several cytoprotective agents may improve all cell subsets within an islet preparation, and selected non- β-cells components may have a negative effect on β-cell function and survival (e.g., acinar cells). In this study, we examined the effect of prolactin (PRL) supplementation to the culture medium, to determine whether it could exert β-cell-selective cytoprotection (islet viability and function) towards a possible use of PRL during pre transplant islet culture. Materials and Methods Human islets pre-cultured or not with recombinant human PRL (500 μg/L) for 48 hours. Non-β-cells and β-cell-specific fractional viability and cellular composition were assessed by FACS and Laser Scanning Cytometry (LSC). Islet potency was assessed in vivo by transplantation into chemically-induced diabetic immunodeficient mice. Results The relative viable β-cell mass and the relative islet β-cell content in PRL group were 28% higher (p=0.018) and 19% higher (p=0.029) than control group, respectively. All transplanted mice achieved normoglycemia in both groups, indicating that PRL treatment did not alter islet function. Conclusions PRL treatment improves β-cell-specific viability and survival in human islets in vitro. The development of novel β-cell-specific cytoprotective strategies will be of assistance in improving islet transplantation. PMID:18374075

  8. Jieyuanshen decoction exerts antidepressant effects on depressive ...

    African Journals Online (AJOL)

    Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. Keywords: Hypothalamic-pituitary-adrenal (HPA) axis; Glucocorticoid/ ...

  9. PROGESTERONE EXERTS NEUROPROTECTIVE EFFECTS AFTER BRAIN INJURY

    OpenAIRE

    Stein, Donald G.

    2007-01-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic...

  10. Progesterone exerts neuroprotective effects after brain injury.

    Science.gov (United States)

    Stein, Donald G

    2008-03-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic brain injury and other neural disorders in humans.

  11. Revised Robert's cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator.

    Science.gov (United States)

    Sikiric, Predrag; Seiwerth, Sven; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela

    2010-01-01

    The significance of cytoprotection and adaptive cytoprotection and the peptides importance remained to be not completely determined. BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, and stable in human gastric juice, with no toxicity being reported. It has a prominent effect on alcohol- lesions (i.e., induced acutely and chronically) and non-steroidal anti-inflammatory drugs-lesions (while interestingly BPC 157 may both prevent and reverse adjuvant arthritis). To review the importance of BPC 157, this review focused on Robert's cytoprotection concept described in rat stomach, reviewing our evidence that may resolve whether the cytoprotection and adaptive cytoprotection is an uniform phenomenon or not; whether the phenomenon or phenomena are endogenous or not, depending on nature of the irritants (mild or strong); whether this may contribute to stomach mucosa defense either when threaten by various ulcerogens or afforded by various antiulcer agents; whether these phenomena are uniform in whole gastrointestinal tract or not; whether they are interrelated or not. Finally, the importance of the cytoprotection phenomena and cytoprotection activity for skin wound healing, and wound healing in general was challenged. Thereby, this review focused on BPC 157 role in cytoprotection and adaptative cytoprotection suggesting that it may be the essential endogenous mediator able to mediate both cytoprotective and adaptive cytoprotective response in stomach and the whole gastrointestinal tract with significant importance in wound healing as well.

  12. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

    Science.gov (United States)

    Clafshenkel, William P; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Koepsel, Richard R; Russell, Alan J

    2016-01-01

    Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

  13. [COMPARISON OF CYTOPROTECTIVE EFFECTS OF HEMANTANE AND AMANTADINE UNDER CONDITIONS OF 6-HYDROXYDOPAMINE NEUROTOXIN ACTION ON CULTURED HUMAN NEUROBLASTOMA CELLS].

    Science.gov (United States)

    Logvinov, I O; Antipova, T A; Nepoklonov, A V; Valdman, E A

    2016-01-01

    Potential neuroprotective activity of the novel antiparkinsonian drug hemantane (hydrochloride N-2-(adamantyl)-hexamethylenimine) in comparison to amantadine has been studied in various regimes of administration on human neuroblastoma SH-SY5Y cell line injury induced by 6-hydroxydopamine (6-OHDA), which is used as in vitro model of dopaminergic neurons for Parkinson's disease. Two regimes of hemantane and amantadine administration in a range of final concentrations 10⁻⁶-10⁻⁸ M were used either prior to or immediately after 6-OHDA introduction. MTT colorimetric assay was used to assess the viability of test cells. Significant decrease in viability of SH-SY5Y cells treated with 6-OHDA was observed. The addition of hemantane to cell medium produced cytoprotective effects in both regimes of administration--before and after 6-OHDA--at concentrations 10⁻⁷ M and 10⁻⁶-10⁻⁸ M, respectively. Amantadine in con- centrations 10⁻⁷-10⁻⁸ M was effective to increase cell survival only when administered after 6-OHDA. These results show that hemantane has a greater neu-roprotective potential in comparison to amantadine.

  14. The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes

    Science.gov (United States)

    Clafshenkel, William P.; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Russell, Alan J.

    2016-01-01

    Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system. PMID:27331401

  15. 3D co-cultures of keratinocytes and melanocytes and cytoprotective effects on keratinocytes against reactive oxygen species by insect virus-derived protein microcrystals

    Energy Technology Data Exchange (ETDEWEB)

    Shimabukuro, Junji; Yamaoka, Ayako; Murata, Ken-ichi [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Kotani, Eiji [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan); Hirano, Tomoko [Venture Laboratory, Kyoto Institute of Technology, Kyoto (Japan); Nakajima, Yumiko [Functional Genomics Group, COMB, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa (Japan); Matsumoto, Goichi [Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, Yokohama (Japan); Mori, Hajime, E-mail: hmori@kit.ac.jp [Department of Applied Biology, Kyoto Institute of Technology, Kyoto (Japan); Insect Biomedical Research Center, Kyoto Institute of Technology, Kyoto (Japan)

    2014-09-01

    Stable protein microcrystals called polyhedra are produced by certain insect viruses. Cytokines, such as fibroblast growth factors (FGFs), can be immobilized within polyhedra. Here, we investigated three-dimensional (3D) co-cultures of keratinocytes and melanocytes on collagen gel containing FGF-2 and FGF-7 polyhedra. Melanocytes were observed to reside at the base of the 3D cell culture and melanin was also typically observed in the lower layer. The 3D cell culture model with FGF-2 and FGF-7 polyhedra was a useful in vitro model of the epidermis due to effective melanogenesis, proliferation and differentiation of keratinocytes. FGF-7 polyhedra showed a potent cytoprotective effect when keratinocytes were treated with menadione, which is a generator of reactive oxygen species. The cytoprotective effect was activated by the inositol triphosphate kinase–Akt pathway leading to upregulation of the antioxidant enzymes superoxide dismutase and peroxiredoxin 6. - Highlights: • 3D cultures using FGF-2 and FGF-7 microcrystals as a human skin model • Cytoprotection of keratinocytes against ROS by FGF-7 microcrystals • Overexpression of SOD and Prdx6 in keratinocytes by FGF-7 microcrystals.

  16. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  17. Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress

    Science.gov (United States)

    Bachar, Adi R.; Scheffer, Lea; Schroeder, Andreas S.; Nakamura, Hiromi K.; Cobb, Laura J.; Oh, Yun K.; Lerman, Lilach O.; Pagano, Richard E.; Cohen, Pinchas; Lerman, Amir

    2010-01-01

    Aims Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress. Methods and results HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 µM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by ∼50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by ∼20%. Conclusion The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans. PMID:20562421

  18. Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, K.; Nishiwaki, H.; Niida, H.; Okabe, S. (Kyoto Pharmaceutical Univ. (Japan))

    1990-02-01

    In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) at the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.

  19. Petiveria alliacea exerts mnemonic and learning effects on rats.

    Science.gov (United States)

    Silva, Mallone Lopes; Luz, Diandra Araújo; Paixão, Thiago Portal da; Silva, João Paulo Bastos; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Gonçalves, Ana Cristina Baetas; Fontes-Júnior, Enéas Andrade; de Andrade, Marciene Ataíde; Maia, Cristiane Socorro Ferraz

    2015-07-01

    Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub native to the Amazon region and other tropical areas such as Central America and the Caribbean. Popularly known as mucuracaá, P. alliacea is used in the folk medicine for a broad variety of therapeutic purpose and also in religious ceremonies by slaves as a sedative, which highlights its properties on the Central Nervous System (CNS). The present study evaluated the effects of the P. alliacea leaves hydroalcoholic extract (PaLHE) on the cognition, including learning and memory. Three-month-old male and female Wistar rats (n=8-10/group) were administered with 900mg/kg of PaLHE. The behavioral assays included Step-down Inhibitory avoidance (IA) and Morris Water Maze (MWM) tests. Consistent with our previous reports, P. alliacea improved long-term memory. It also exerted previously unreported effects on short-term and spatial memory improvement, and increased learning in the tasks. The P. alliacea extract elicited mnemonic effects and improved the learning process in both IA and MWM tests. Our results highlight the importance of further studies in order to identify the active substances of the PaLHE and investigate the pharmacological mechanisms that underlies the reported effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Cytoprotective effect of tocopherols in hepatocytes cultured with polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.

    1994-01-01

    When highly unsaturated fatty acids are added to cell cultures, it can become important to include antioxidants in the culture medium to prevent cytotoxic peroxidation. To find an optimal antioxidant for this purpose, the effect of 50 µM a-tocopherol, ¿-tocopherol, a-tocopheryl acetate, a...

  1. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

  2. Cytoprotective Effect of Hispidin against Palmitate-Induced Lipotoxicity in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Jun Myoung Park

    2015-03-01

    Full Text Available It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-κB translocation. Therefore, these results suggest that hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress.

  3. EFFECT OF CYTOPROTECTION ON THE OXIDATIVE PROCESSES AND ENDOTHELIAL FUNCTION IN ELDERLY PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    A. V. Shabalin

    2006-01-01

    Full Text Available Aim. To investigate the effects of cytoprotection with mildronate (Grindex, Latvia on oxidative processes and endothelial function in elderly patients with ischemic heart disease (IHD. Material and methods. 117 elderly (upwards 60 y.o. patients with IHD were included into controlled study. They were also suffering from heart failure II-III functional class (according to NYHA classification and from arterial hypertension (AH. All patients were randomized into 2 groups: 1 67 patients (75,4±0,5 y. o. were treated with mildronate 500 mg/day simultaneously with basic therapy during 12 weeks (the main group and 2 50 patients (74,0±0,6 y. o. were treated only with basic therapy during 12 weeks (the compare group. Total cholesterol (CH, triglycerides (TG, low density lipoprotein cholesterol (LDL, high density lipoprotein CH (HDL, LDL antioxidant potential (concentration of α-tocopherol and retinol in LDL, initial level of lipid peroxidation (LPO products in LDL, LDL resistance to oxidation and blood level of NO metabolites were determined before and after 4 and 12 weeks of the therapy. Results. Mildronate did not have any effect on the blood lipid profile in elderly patients with IHD. The initial level of LPO products in LDL was decreased by 33% and LDL resistance to oxidation was increased by 26% in the main group after 12 weeks of therapy in comparison with the same parameters before the study and in comparison with control group of patients (p<0,05. The blood level of NO metabolites was 1,4 fold higher in the main group of patients after 12 weeks of therapy in comparison with the same parameters before therapy and in comparison with control group of patients (p<0,05. More prominent growth of LDL resistance to oxidation after 12 week therapy with mildronate was revealed in men than in women, in patients with angina II class than in patients with angina III class, in patients with heart failure II class than in patients with heart failure III class

  4. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  5. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin.

    Science.gov (United States)

    Zhang, Li; Wang, Handong

    2015-07-14

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  6. A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui; Reddy, Shridhivya A.; Lee, Stephanie S-H.; Yang, Hong; Tan, Sock-Hoon [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Hayes, John D. [Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland (United Kingdom); Chui, Wai-Keung [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Chew, Eng-Hui, E-mail: phaceh@nus.edu.sg [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore)

    2013-11-01

    Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E{sub 2} (PGE{sub 2}) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. - Highlights:

  7. Effects of caffeine on session ratings of perceived exertion.

    Science.gov (United States)

    Killen, L G; Green, J M; O'Neal, E K; McIntosh, J R; Hornsby, J; Coates, T E

    2013-03-01

    This study examined effects of caffeine on session ratings of perceived exertion (RPE) following 30 min constant-load cycling. Individuals (n = 15) of varying aerobic fitness completed a [Formula: see text] max trial and two 30 min cycling bouts (double-blind, counterbalanced) following ingestion of 6 mL/kg of caffeine or matched placebo. RPE overall, legs and breathing were estimated every 5 min and session RPE was estimated 30 min post-exercise using the OMNI pictorial scale. Session RPE for caffeine and placebo trails were compared using paired t test. Between-trial comparisons of HR, RPE overall, RPE legs and RPE breathing were analyzed using an independent 2 (trial) × 6 (time point) repeated measures analysis of variance (ANOVA) for each dependent variable. Caffeine resulted in a significantly lower session RPE (p < 0.05) for caffeine (6.1 ± 2.2) versus placebo (6.8 ± 2.1). Acute perceptual responses were significantly lower for caffeine for RPE overall (15, 20, 25, and 30 min), RPE breathing (15, 20, 25, and 30 min) and RPE legs (20 and 30 min). Survey responses post-exercise revealed greater feelings of nervousness, tremors, restlessness and stomach distress following caffeine versus placebo. Blunted acute RPE and survey responses suggest participants responded to caffeine ingestion. Caffeine decreased acute RPE during exercise which could partially account for lower session RPE responses. However, decreased session RPE could also reveal a latent analgesic affect of caffeine extending into recovery. Extending the understanding of session RPE could benefit coaches in avoiding overtraining when adjusting training programs.

  8. Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

    Science.gov (United States)

    Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

    2007-03-01

    The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

  9. Cytoprotection by omega-3 fatty acids as a therapeutic drug vehicle when combined with nephrotoxic drugs in an intravenous emulsion: Effects on intraglomerular mesangial cells

    Directory of Open Access Journals (Sweden)

    Gabriel Alejandro Bonaterra

    2014-01-01

    Full Text Available During therapeutic interventions, blood concentrations of intravenously applied drugs are higher, and their onset of pharmacological action is faster than with other routes of drug administration. However, acute drug therapy often produces nephrotoxic side effects, as commonly seen after treatment with Ketorolac or Gentamicin leading to questions about their use, especially for patients at risk for acute renal failure. Omega-6(n-6 and omega-3(n-3 polyunsaturated fatty acids (PUFA affect eicosanoid metabolism, which plays a role in the regulation of inflammation. Eicosanoids derived from n-6 FA have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFA have anti-inflammatory and cytoprotective properties. We hypothesized that providing such injectable drugs with nephrotoxic potential in combination with n3-PUFAs from the outset, might afford rapid cytoprotection of renal cells, given the recent evidence that intravenously administered n3-PUFAs are rapidly incorporated into cell membranes. We used intraglomerular mesangial cells (MES13 that are sensitive to treatment with Ketorolac or Gentamicin instead of proximal tubular cells which do not respond to Ketorolac. We found a significant inhibition of Ketorolac (0.25, 0.5, 1 mM or Gentamicin (2.5, 5 mM induced cytotoxicity after pretreatment of MES13 cells with 0.01% of 20%w/v LipOmega-3 Emulsion 9/1, containing 90:10 wt/wt mixture of fish oil derived triglycerides to medium chain triglycerides.

  10. Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.

    Science.gov (United States)

    Singh, Rohit; Mishra, Vaibhav; Pandeti, Sukanya; Palit, Gautam; Barthwal, Manoj K; Pandey, Haushila Prasad; Narender, Tadigoppula

    2015-06-01

    Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in-vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice

    OpenAIRE

    Chen, Po-Sheng; Wang, Kuan-Chieh; Chao, Ting-Hsing; Chung, Hsing-Chun; Tseng, Shi-Ya; Luo, Chawn-Yau; Shi, Guey-Yueh; Wu, Hua-Lin; Li, Yi-Heng

    2017-01-01

    Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we f...

  12. Clinical bystander effect exerted by allergen immunotherapy: a hypothesis.

    Science.gov (United States)

    Ciprandi, G

    2015-03-01

    Allergen Immunotherapy (AIT) is able to restore a physiological Th1 response and Tregs function. This effect is allergen-specific, even though it has been reported that it may also be non-specific, such as also extended to allergens not used in AIT. This immunological phenomenon may also be of clinical nature. This case report shows that a poly-allergic patient, successfully treated with Parietaria extract, also achieved a clinical tolerance towards other causal allergens, such as mites and cat. Of course, this was an anecdote, but it is reasonable to prospect the hypothesis that a bystander clinical effect may be observed during AIT in poly-allergic patients.

  13. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    OpenAIRE

    Li Zhang; Handong Wang

    2015-01-01

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both i...

  14. Galectin-1 exerts inhibitory effects during DENV-1 infection.

    Directory of Open Access Journals (Sweden)

    Karina Alves Toledo

    Full Text Available Dengue virus (DENV is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1, we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1 inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

  15. Emotional stimuli exert parallel effects on attention and memory.

    Science.gov (United States)

    Talmi, Deborah; Ziegler, Marilyne; Hawksworth, Jade; Lalani, Safina; Herman, C Peter; Moscovitch, Morris

    2013-01-01

    Because emotional and neutral stimuli typically differ on non-emotional dimensions, it has been difficult to determine conclusively which factors underlie the ability of emotional stimuli to enhance immediate long-term memory. Here we induced arousal by varying participants' goals, a method that removes many potential confounds between emotional and non-emotional items. Hungry and sated participants encoded food and clothing images under divided attention conditions. Sated participants attended to and recalled food and clothing images equivalently. Hungry participants performed worse on the concurrent tone-discrimination task when they viewed food relative to clothing images, suggesting enhanced attention to food images, and they recalled more food than clothing images. A follow-up regression analysis of the factors predicting memory for individual pictures revealed that food images had parallel effects on attention and memory in hungry participants, so that enhanced attention to food images did not predict their enhanced memory. We suggest that immediate long-term memory for food is enhanced in the hungry state because hunger leads to more distinctive processing of food images rendering them more accessible during retrieval.

  16. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review

    Directory of Open Access Journals (Sweden)

    Mohammad Adawi

    2017-11-01

    Full Text Available Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest, using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1 Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2 Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3 In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4 In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5 In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6 Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers.

  17. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review.

    Science.gov (United States)

    Adawi, Mohammad; Watad, Abdulla; Brown, Stav; Aazza, Khadija; Aazza, Hicham; Zouhir, Mohamed; Sharif, Kassem; Ghanayem, Khaled; Farah, Raymond; Mahagna, Hussein; Fiordoro, Stefano; Sukkar, Samir Giuseppe; Bragazzi, Nicola Luigi; Mahroum, Naim

    2017-01-01

    Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: "fasting," "Ramadan," "Islam," and "immunity." Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers.

  18. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review

    Science.gov (United States)

    Adawi, Mohammad; Watad, Abdulla; Brown, Stav; Aazza, Khadija; Aazza, Hicham; Zouhir, Mohamed; Sharif, Kassem; Ghanayem, Khaled; Farah, Raymond; Mahagna, Hussein; Fiordoro, Stefano; Sukkar, Samir Giuseppe; Bragazzi, Nicola Luigi; Mahroum, Naim

    2017-01-01

    Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers. PMID:29230208

  19. Salidroside exerts angiogenic and cytoprotective effects on human bone marrowderived endothelial progenitor cells via Akt/mTOR/p70S6K and MAPK signalling pathways

    Science.gov (United States)

    Tang, Yubo; Vater, Corina; Jacobi, Angela; Liebers, Cornelia; Zou, Xuenong; Stiehler, Maik

    2014-01-01

    Background and Purpose With the increase of age, increased susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells (EPCs). The aim of this study was to investigate whether salidroside (SAL) can induce angiogenic differentiation and inhibit oxidative stress-induced apoptosis in bone marrow-derived EPCs (BM-EPCs), and if so, through what mechanism. Experimental Approach BM-EPCs were isolated and treated with different concentrations of SAL for up to 4 days. Cell proliferation, migration and tube formation ability were detected by DNA content quantification, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were assessed by qRT-PCR and Western blot respectively. Key Results Treatment with SAL promoted cellular proliferation and angiogenic differentiation of BM-EPCs, and increased VEGF and NO secretion, which in turn mediated the enhanced angiogenic differentiation of BM-EPCs. Furthermore, SAL significantly attenuated hydrogen peroxide (H2O2)-induced cell apoptosis, reduced the intracellular level of reactive oxygen species and restored the mitochondrial membrane potential of BM-EPCs. Moreover, SAL stimulated the phosphorylation of Akt, mammalian target of rapamycin and p70 S6 kinase, as well as ERK1/2, which is associated with cell migration and capillary tube formation. Additionally, SAL reversed the phosphorylation of JNK and p38 MAPK induced by H2O2 and suppressed the changes in the Bax/Bcl-xL ratio observed after stimulation with H2O2. Conclusions and Implications These findings identify novel mechanisms that regulate EPC function and suggest that SAL has therapeutic potential as a new agent to enhance vasculogenesis as well as protect against oxidative endothelial injury. PMID:24471788

  20. Potential antioxidant and cytoprotective effects of essential oil extracted from Cymbopogon citratus on OxLDL and H2O2 LDL induced Human Peripheral Blood Mononuclear Cells (PBMC

    Directory of Open Access Journals (Sweden)

    Jamuna S.

    2017-06-01

    Full Text Available Cymbopogon citratus (lemon grass is commonly used in traditional folk medicine. The essential oil extracted from C. citratus has been reported as a potential anti-oxidant and anti-inflammatory agent. This study has been designed to explore the protective effect of C. citratus (lemon grass against modified LDL (OxLDL and H2O2 LDL induced cytotoxicity in Peripheral Blood Mononuclear Cells (PBMC. The essential oil extracted from C. citratus (EOC was subjected to FT-IR spectroscopic analysis for the identification of functional groups. In vitro antioxidant assays were carried out to assess the electron donating capability of EOC as compared with a known standard L-ascorbic acid. The cytoprotective effects of EOC were determined in PBMC induced with modified LDL. Spectra obtained from FT-IR analysis showed the presence of functional groups in EOC such as H-bonded, OH stretching, NH stretching, aldehydeCH stretching, aldehyde/ketoneCO stretching, CC-stretching, CH3 bending, CH in plane bending. EOC has greater antioxidant property when compared with the standard L-ascorbic acid. EOC at all test concentrations demonstrated free radical scavenging activity and cytoprotective effect when challenged against modified LDL in PBMC. The above results show EOC as a promising antioxidant and cytoprotective agent.

  1. Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice.

    Science.gov (United States)

    Chen, Po-Sheng; Wang, Kuan-Chieh; Chao, Ting-Hsing; Chung, Hsing-Chun; Tseng, Shi-Ya; Luo, Chawn-Yau; Shi, Guey-Yueh; Wu, Hua-Lin; Li, Yi-Heng

    2017-06-12

    Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice.

  2. Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

    Science.gov (United States)

    Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

    2013-01-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

  3. Cytoprotective effect of bioactive sea buckthorn extract on paraquat-exposed A549 cells via induction of Nrf2 and its downstream genes.

    Science.gov (United States)

    Podder, Biswajit; Kim, Yong-Sik; Song, Ho-Yeon

    2013-12-01

    The extract of sea buckthorn (SBT) [Hippophae rhamnoides L. (Elaeagnaceae)], is used as a food supplement and traditional medicine in numerous countries. This study investigated the protective effects of the functional extract of SBT against paraquat (PQ)-induced toxicity via antioxidant mechanisms in A549 cells. The methanol extract of SBT (25-200 µg/ml) was used to protect cells against PQ (200 µM)-induced cell death. A viability assay was conducted using 3-(4,5-dimethylthioazol-2-ly)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase (LDH). Total intracellular reactive oxygen species (ROS) were measured and plotted. For validation of the SBT-induced expression of nuclear factor-E2-related factor 2 (Nrf2) and its target genes, western blot analysis and qPCR were performed. The present study showed that pretreatment of A549 cells with SBT extract significantly attenuated PQ (200 µM)-induced cellular toxicity. The maximum cytoprotective effect was identified using 200 µg/ml SBT extract; it began 24 h following exposure and was sustained up to 120 h (P<0.05). SBT extract significantly reduced LDH activity by 35.63% and ROS levels by 30.90% (P<0.05). Pretreatment with SBT extract activated Nrf2 mRNA and protein expression and its nuclear translocation. The SBT extract effectively induced Nrf2 target genes, such as NAD(P)H dehydrogenase quinone 1, glutathione peroxidase 1, glutathione reductase and catalase following treatment with PQ. Based on these results, it was hypothesized that SBT extract may be used as a potential therapeutic agent for the treatment of various oxidative stress-related diseases.

  4. Administration of a CXCL12 Analog in Endotoxemia Is Associated with Anti-Inflammatory, Anti-Oxidative and Cytoprotective Effects In Vivo.

    Directory of Open Access Journals (Sweden)

    Semjon Seemann

    Full Text Available The chemokine receptor CXCR4 is a multifunctional receptor which is activated by its natural ligand C-X-C motif chemokine 12 (CXCL12. As CXCR4 is part of the lipopolysaccharide sensing complex and CXCL12 analogs are not well characterized in inflammation, we aimed to uncover the systemic effects of a CXCL12 analog in severe systemic inflammation and to evaluate its impact on endotoxin induced organ damages by using a sublethal LPS dose.The plasma stable CXCL12 analog CTCE-0214D was synthesized and administered subcutaneously shortly before LPS treatment. After 24 hours, mice were sacrificed and blood was obtained for TNF alpha, IFN gamma and blood glucose evaluation. Oxidative stress in the liver and spleen was assessed and liver biotransformation capacity was determined. Finally, CXCR4, CXCL12 and TLR4 expression patterns in liver, spleen and thymus tissue as well as the presence of different markers for apoptosis and oxidative stress were determined by means of immunohistochemistry.CTCE-0214D distinctly reduced the LPS mediated effects on TNF alpha, IFN gamma, ALAT and blood glucose levels. It attenuated oxidative stress in the liver and spleen tissue and enhanced liver biotransformation capacity unambiguously. Furthermore, in all three organs investigated, CTCE-0214D diminished the LPS induced expression of CXCR4, CXCL12, TLR4, NF-κB, cleaved caspase-3 and gp91 phox, whereas heme oxygenase 1 expression and activity was induced above average. Additionally, TUNEL staining revealed anti-apoptotic effects of CTCE-0214D.In summary, CTCE-0214D displayed anti-inflammatory, anti-oxidative and cytoprotective features. It attenuated reactive oxygen species, induced heme oxygenase 1 activity and mitigated apoptosis. Thus, the CXCR4/CXCL12 axis seems to be a promising target in the treatment of acute systemic inflammation, especially when accompanied by a hepatic dysfunction and an excessive production of free radicals.

  5. Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell.) Ching on Human Umbilical Vein Endothelial Cells.

    Science.gov (United States)

    Liu, Dong-Mei; Sheng, Ji-Wen; Wang, Si-Hong; Zhang, Wei-Fen; Zhang, Wei; Zhang, Dai-Juan

    2016-09-24

    The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H₂O₂-treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01) when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05) and 3.1% ± 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H₂O₂. SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H₂O₂ and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 μM SA. The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides.

  6. Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell. Ching on Human Umbilical Vein Endothelial Cells

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    Dong-Mei Liu

    2016-09-01

    Full Text Available Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA obtained from the rhizomes of Athyrium multidentatum (Doell. Ching on human umbilical vein endothelial cells (HUVECs. Methods: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA fluorescent probe. Results: The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05. Meanwhile, SA augmented the cell viabilities in H2O2-treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01 when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05 and 3.1% ± 0.34% (p < 0.01, respectively, after treatment with SA alone or SA/H2O2. SA inhibited the overproduction of reactive oxygen species (ROS in HUVECs induced by H2O2 and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 μM SA. Conclusions: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides.

  7. Effects of fitness and self-confidence on time perception during exertion

    Directory of Open Access Journals (Sweden)

    2015-09-01

    Full Text Available Aims: Human physical and psychological features influence perceptions of the environment during activity. If during exercise an individual over-estimates time, they may interpret this as spending longer than necessary under a potentially aversive state of exertion. This may in turn decrease one’s sense of exercise success and tendency to persevere with exercise. We tested if experimentally manipulating sense of exercise self-efficacy would affect time perception during standardised physical exertion. Method: Exercise Self-Efficacy (ESE of 18 -73 year olds (N=51 was measured before and after an exercise challenge of moderate intensity. Height, weight and body fat composition were measured before participants were randomly allocated to one of three groups. After a 4-minute treadmill fitness test, participants were presented with either bogus feedback about their performance (positive or negative or no feedback (control. Before and during exercise, participants estimated a prescribed 2-minute time interval. Ratings of perceived exertion were also measured periodically. Results: Feedback on performance had no significant effect on time perception, even when controlling for individual exertion level. Reported ESE was also unaffected by whether someone received positive, negative or no feedback. Age was again found to be significantly correlated with VO2max, r(51 = .62, p < .001, but in contrast to prior findings, estimates of general fitness such as VO2max, BMI and waist circumference were unrelated to changes in time perception due to exertion. Conclusions: These findings failed to support prior findings and anecdotal evidence suggesting that exertion might alter one’s perception of time. We also failed to find any support for effects on ESE when participants were given explicit performance feedback. Finally, participants’ physical characteristics appear to be unrelated to time perception whilst exercising at moderate intensity.

  8. Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Stubbendorff, Christine; Meyer, Neele; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jacob

    We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the

  9. Gastric Cytoprotection and honey intake in Albino Rats | Alagwu ...

    African Journals Online (AJOL)

    Beneficial effect of honey has been widely reported particularly on wound healings, gastrointestinal disorders and as antibacterial agent. However, there is paucity of report on its cytoprotective effect on the gastric mucosa despite its common usage worldwide including Nigeria. This study was therefore carried out to ...

  10. Myocardial Opioid Receptors in Conditioning and Cytoprotection

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    Grant Williams-Pritchard

    2011-03-01

    Full Text Available Opioid compounds and G-protein coupled opioid receptors (ORs have been studied widely in terms of central nervous system (CNS actions relating to pain management and drug abuse. Opioids are also linked to induction of mammalian hibernation, a natural state of tolerance involving prolonged and orchestrated shifts in cellular metabolism, growth and stress resistance. It is not surprising then that OR agonism induces acute or delayed cytoprotective states in myocardium, rendering ORs an attractive target for protection of cardiac tissue from the potentially fatal consequences of ischemic heart disease. Cardiac ORs are implicated in triggering/mediating so-called ‘conditioning’ responses, in which powerful cytoprotection arises following transient receptor ligation prior to or immediately following ischemic insult. These responses involve one or more OR sub-types engaging pro-survival kinase cascades to ultimately modulate cell stress and mitochondrial end-effectors. However, important questions remain regarding the role of endogenous opioids, OR signalling, and the transduction and mediation of these protective responses. We briefly review opioid-mediated cardioprotection, focussing on recent developments in signal transduction, the role of receptor ‘cross-talk’, and the effects of sustained OR ligand activation.

  11. Effects of acclimation on water and electrolitic disbalance in soldiers during exertional heat stress

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    Radaković Sonja S.

    2007-01-01

    Full Text Available Background/Aim. Exertional heat stress is a common problem in military services. The aim of this study was to examine changes in body water and serum concentrations of some electrolites in soldiers during exertional heat stress (EHST, as well as effects of 10-day passive or active acclimation in a climatic chamber. Methods. Forty male soldiers with high aerobic capacity, performed EHST either in cool (20 ºC, 16 ºC WBGT-wet bulb globe temperature, or hot (40 ºC, 25 ºC WBGT environment, unacclimatized, or after 10 days of passive or active acclimation. The subjects were allowed to drink tap water ad libitum during EHST. Mean skin (Tsk and tympanic (Tty temperatures and heart rates (HR measured physiological strain, while sweat rate (SwR, and serum concentrations of sodium, potassium and osmolality measured changes in water and electrolyte status. Blood samples were collected before and immediately after the EHST. Results. Exertional heat stress in hot conditions induced physiological heat stress (increase in Tty, HR, and SwR, with significant decrease in serum sodium concentration (140.6±1.52 before vs 138.5±1.0 mmol/l after EHST, p < 0.01 and osmolality (280.7±3.8 vs 277.5±2.6 mOsm/kg, p < 0.05 in the unacclimatized group. The acclimated soldiers suffered no such effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty, HR and SwR. Conclusion. In the trained soldiers, 10-day passive or active acclimation in a climatic chamber can prevent disturbances in water and electrolytic balance, i.e. decrease in serum sodium concentrations and osmolality induced by exertional heat stress.

  12. Cytoprotective effect of trolox against oxidative damage and apoptosis in the NRK-52e cells induced by melamine.

    Science.gov (United States)

    Guo, Chengzhi; He, Zuping; Wen, Lixin; Zhu, Li; Lu, Yin; Deng, Sijun; Yang, Yang; Wei, Qiang; Yuan, Hui

    2012-02-01

    An outbreak of urinary stones associated with consumption of melamine-tainted milk products occurred in 2008 in China, leading to serious illness of many infants and even death. However, the toxicity of melamine in kidney epithelial cells remains unclear. We have explored the effects of melamine and trolox on renal NRK-52e (normal rat kidney 52e) cells. The IC(50) of melamine was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. Total SOD (superoxide dismutase) was determined by NBT (Nitro Blue Tetrazolium) staining method. GSH-Px (glutathione peroxidase) activity was detected by UV colorimetric assay, and MDA (malondialdehyde) content was determined by thiobarbituric acid assay. Apoptosis induced by melamine was determined by flow cytometry. The IC(50) increased when NRK-52e cells were treated with both melamine and trolox compared with melamine only. SOD and GSH-Px activities were decreased, but MDA content was increased by melamine in a dose-dependent manner. Trolox significantly enhanced SOD and GSH-Px activity in melamine-treated NRK-52e cells, but it decreased their MDA content. LDH (lactate dehydrogenase) activity and the level of ROS (reactive oxygen species) of the NRK-52e cells were enhanced by melamine compared with the control. Furthermore, the apoptosis rate increased in NRK-52e cells treated with melamine, whereas trolox was protective. These results show that melamine has an obvious adverse effect on proliferation of NRK-52e cells, causing oxidative damage and apoptosis, thus providing a novel insight into renal cytotoxicology of melamine. Trolox ameliorates the effect on melamine toxicity.

  13. Induction of Thioredoxin Reductase 1 by Korean Red Ginseng Water Extract Regulates Cytoprotective Effects on Human Endothelial Cells

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    Hye Rim Park

    2015-01-01

    Full Text Available Korean Red Ginseng is a popular herbal medicine and is widely used in many food products. KRG has biological benefits related to vascular diseases including diabetes, hypertension, atherosclerosis, and other cardiac diseases and KRG has antioxidant and anti-hyperlipidemic actions. KRG decreases the level of oxidative stress and suppresses proinflammatory cytokines and cell adhesion molecules, thus protecting endothelial dysfunction. Mammalian Thioredoxin reductase 1 is an NADPH-dependent selenoprotein, essential for antioxidant defense and DNA synthesis and repair, that regulates the redox system by modulating redox-sensitive transcription factors and thiol-containing proteins. Here, we show that KRG water extract increases the expression of TrxR1 in human umbilical vein endothelial cells via the p38 and PKC-δ signaling pathways. The induction of TrxR1 expression by KRG was confirmed by Western blot analysis and reverse transcription polymerase chain reaction. However, the increase in TrxR1 expression was abolished by specific silencing of the p38 and PKC-δ genes. In addition, we demonstrated that auranofin, a TrxR1 inhibitor, weakens the protective effect of KRG against H2O2-induced cell death as measured by the terminal transferase dUTP nick end labeling assay. These results suggest that KRG may have protective effects in vascular diseases by upregulating TrxR1 in endothelial cells, thereby inhibiting the generation of reactive oxygen species and cell death.

  14. The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3β Inactivation.

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    Hai-Yan Xing

    Full Text Available Glycogen synthase kinase-3β (GSK-3β acts as a negative regulator of NF-E2 related factor 2 (Nrf2 by inducing Nrf2 degradation and nuclear export. Our previous study demonstrated that the flavonoid hyperoside elicits cytoprotection against oxidative stress by activating the Keap1-Nrf2-ARE signaling pathway, thus increasing the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1, superoxide dismutase (SOD and catalase. However, the role of GSK-3β in hyperoside-mediated Nrf2 activation is unclear. Here, we demonstrate that in a normal human hepatocyte cell line, (L02, hyperoside is capable of inducing the phosphorylation of GSK-3β at Ser9 without affecting the protein levels of GSK-3β and its phosphorylation at Thr390. Lithium chloride (LiCl and short interfering RNA (siRNA-mediated inhibition of GSK-3β significantly enhanced the ability of hyperoside to protect L02 liver cells from H2O2-induced oxidative damage, leading to increased cell survival shown by the maintenance of cell membrane integrity and elevated levels of glutathione (GSH, one of the endogenous antioxidant biomarkers. Further study showed that LiCl and siRNA-mediated inhibition of GSK-3β increased hyperoside-induced HO-1 expression, and the effect was dependent upon enhanced Nrf2 nuclear translocation and gene expression. These activities were followed by ARE-mediated transcriptional activation in the presence of hyperoside, which was abolished by the transfection of the cells with Nrf2 siRNA. Furthermore, the siRNA-mediated inhibition of Keap1 also enhanced hyperoside-induced Nrf2 nuclear accumulation and HO-1 expression, which was relatively smaller than the effects obtained from GSK-3β siRNA administration. Moreover, Keap1 siRNA administration alone had no significant effect on the phosphorylation and protein expression of GSK-3β. Collectively, our data provide evidence that hyperoside attenuates H2O2 -induced L02 cell damage by activating the Nrf2-ARE

  15. Caffeine and theanine exert opposite effects on attention under emotional arousal.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

    2017-01-01

    Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p Caffeine reduced flanker conflict difference scores on the Attention Network Test (p caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

  16. Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

    OpenAIRE

    Saruta, Juri; To, Masahiro; Sugimoto, Masahiro; Yamamoto, Yuko; Shimizu, Tomoko; Nakagawa, Yusuke; Inoue, Hiroko; Saito, Ichiro; Tsukinoki, Keiichi

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemaggl...

  17. Effect of Stimulant Medication Use by Children with ADHD on Heart Rate and Perceived Exertion

    Science.gov (United States)

    Mahon, Anthony D.; Woodruff, Megan E.; Horn, Mary P.; Marjerrison, Andrea D.; Cole, Andrew S.

    2012-01-01

    The effect of stimulant medication use by children with attention deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)--heart rate (HR) relationship was examined. Children with ADHD (n = 20; 11.3 [plus or minus] 1.8 yrs) and children without ADHD (n = 25; 11.2 [plus or minus] 2.1 yrs) were studied. Children with ADHD…

  18. Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue

    Science.gov (United States)

    Lohse, Keith R.; Sherwood, David E.

    2011-01-01

    This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007a) compared to associative/dissociative (e.g., Stevinson and Biddle, 1998). In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task) to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type) increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors) in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies, and expectancies affected the time to failure and perceived exertion. PMID:22102843

  19. Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue.

    Directory of Open Access Journals (Sweden)

    Keith eLohse

    2011-11-01

    Full Text Available This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007 compared to associative/dissociative (e.g., Stevenson & Biddle, 1998. In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies and expectancies affected the time to failure and perceived exertion.

  20. [Role of membrane lipids in myocardial cytoprotection

    Science.gov (United States)

    Grynberg, A.

    2000-01-01

    The cardiomyocyte capacity to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. This process is based on a balanced fatty acid (FA) metabolism, because FA is the main fuel of the heart, although the most expensive one in oxygen. The pathway is, however, weakly controlled by the cardiac myocyte which can well regulate FA mitochondrial entry but not cell FA uptake. For this reason, several pathological situations often result from either harmful accumulation of FA and derivatives or excess FA-oxidation. Control of the FA/glucose balance by decreased energy production from FA would thus offer an alternative strategy in the treatment of ischaemia, providing the cardiomyocytes weak ability in handling the non-metabolised FA is controlled. The initiation and the regulation of cardiac contraction both result from membrane activity; the other major role of lipids in the heart is their contribution to membrane homeostasis through phospholipid synthesis pathways and phospholipases. The anti-anginal activity of Trimetazidine, reported as a cytoprotective effect without a haemo-dynamic component; is associated with reduced use of FA for energy. However, accumulation of FA and derivatives has never been observed. Trimetazidine is reported to increase significantly the synthesis of phospholipids without influencing the other lipid classes, thus increasing the incorporation of FA in membrane structures. This cytoprotection appears to be based on the redirection of the use of FA to phospholipid synthesis, which would decrease their availability for energy production. This class of compounds, with the same properties as Trimetazidine, offers a metabolic approach to the treatment of ischaemia.

  1. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Science.gov (United States)

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

    2010-01-01

    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  2. Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells.

    Science.gov (United States)

    de Quadros, Ana Paula Oliveira; Mazzeo, Dania Elisa Christofoletti; Marin-Morales, Maria Aparecida; Perazzo, Fábio Ferreira; Rosa, Paulo Cesar Pires; Maistro, Edson Luis

    2017-01-01

    Crataegus oxyacantha, a plant of the Rosaceae family also known "English hawthorn, haw, maybush, or whitethorn," has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.

  3. Dual Biological Functions of a Cytoprotective Effect and Apoptosis Induction by Bioavailable Marine Carotenoid Fucoxanthinol through Modulation of the Nrf2 Activation in RAW264.7 Macrophage Cells

    Directory of Open Access Journals (Sweden)

    Junsei Taira

    2017-10-01

    Full Text Available In this study, the function of fucoxanthinol (FxOH as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx, was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1–4 μM with a peroxyl radical scavenging capacity was proved by the ORAC (Oxygen Radical Absorbance Capacity method and an ESR study. Similar concentrations of the compound also activated the Nrf2-ARE signaling with the Nrf2 translocation into the nuclear, then the expression of the antioxidant protein HO-1 increased. On the other hand, the high concentrations of both compounds (>10 μM induced apoptosis with caspase 3/7 activation during suppression of the anti-apoptotic proteins, such as Bcl-XL and phosphorous Akt (pAkt. The Nrf2 expression was then activated in the nuclear, indicating that the Nrf2 plays a significant role in the cytoprotective effect against the toxicity of the compounds. These results indicated that the compounds have the dual functions of a cytoprotective effect and the apoptosis induction dependent on the treated concentrations through the Nrf2 activation. In addition, the results of all the assays involved in our previous studies suggested that the metabolite FxOH having a higher activity than the Fx, will be a bioavailable compound in biological systems.

  4. The effects of acclimatization on blood clotting parameters in exertional heat stress

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    Vesić Zoran

    2013-01-01

    Full Text Available Background/Aim. Exertional heat stress is a common problem in military services. Considering the coagulation abnormalities are of major importance in development of severe heat stroke, we wanted to examine changes in hemostatic parameters in soldiers during exertional heat stress test as well as the effects of a 10-day passive or active acclimatization in a climatic chamber. Methods. A total of 40 male soldiers with high aerobic capacity performed exertional heat stress test (EHST either in cool [20ºC, 16ºC wet bulb globe temperature (WBGT], or hot (40ºC, 29ºC, (WBGT environment, unacclimatized (U or after 10 days of passive (P or active (A acclimatization. Physiological strain was measured by tympanic temperatures (Tty and heart rates (HR. Platelet count (PC, antithrombin III (AT, and prothrombin time (PT were assessed in blood samples collected before and immediately after the EHST. Results. EHST in hot conditions induced physiological heat stress (increase in Tty and HR, with a significant increase in prothrombin time in the groups U and A. Platelet counts were significantly higher after the EHST compared to the basic levels in all the investigated groups, regardless environmental conditions and acclimatization state. Antithrombin levels were not affected by EHST whatsoever. Conclusion. In the trained soldiers, physiological heat stress caused mild changes in some serum parameters of blood clotting such as prothrombin time, while others such as antithrombin levels were not affected. Platelet counts were increased after EHST in all groups. A 10-day passive or active acclimatization in climatic chamber showed no effect on parameters investigated.

  5. H-Ras Exerts Opposing Effects on Type I Interferon Responses Depending on Its Activation Status.

    Science.gov (United States)

    Chen, Guann-An; Lin, Yun-Ru; Chung, Hai-Ting; Hwang, Lih-Hwa

    2017-01-01

    Using shRNA high-throughput screening, we identified H-Ras as a regulator of antiviral activity, whose depletion could enhance Sindbis virus replication. Further analyses indicated that depletion of H-Ras results in a robust increase in vesicular stomatitis virus infection and a decrease in Sendai virus (SeV)-induced retinoic acid-inducible gene-I-like receptor (RLR) signaling. Interestingly, however, ectopic expression of wild-type H-Ras results in a biphasic mode of RLR signaling regulation: while low-level expression of H-Ras enhances SeV-induced RLR signaling, high-level expression of H-Ras significantly inhibits this signaling. The inhibitory effects correlate with the activation status of H-Ras. As a result, oncogenic H-Ras, H-RasV12, strongly inhibits SeV-induced IFN-β promoter activity and type I interferon signaling. Conversely, the positive effects exerted by H-Ras on RLR signaling are independent of its signaling activity, as a constitutively inactive form of H-Ras, H-RasN17, also positively regulates RLR signaling. Mechanistically, we demonstrate that depletion of H-Ras reduces the formation of MAVS-TNF receptor-associated factor 3 signaling complexes. These results reveal that the H-Ras protein plays a role in promoting MAVS signalosome assembly in the mitochondria, whereas oncogenic H-Ras exerts a negative effect on type I IFN responses.

  6. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Directory of Open Access Journals (Sweden)

    Haule Emmanuel E

    2012-10-01

    Full Text Available Abstract Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich. Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae, Maytenus senegalensis (Lam. Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922, Salmonella typhi (NCTC 8385, Vibrio cholerae (clinical isolate, and Klebsiella pneumoniae (clinical isolate using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole

  7. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    Science.gov (United States)

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual

  8. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells

    Science.gov (United States)

    Theoduloz, Cristina; López-Alarcón, Camilo; Dorta, Eva

    2017-01-01

    The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM) and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs) from Chilean raspberries (Rubus geoides), strawberries (Fragaria chiloensis ssp. chiloensis f. chiloensis), and currants (Ribes magellanicum) and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML) and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis. This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food. PMID:28553436

  9. Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells

    Directory of Open Access Journals (Sweden)

    Felipe Ávila

    2017-01-01

    Full Text Available The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs from Chilean raspberries (Rubus geoides, strawberries (Fragaria chiloensis ssp. chiloensis f. chiloensis, and currants (Ribes magellanicum and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis. This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food.

  10. Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats.

    Science.gov (United States)

    Calcagnoli, Federica; Stubbendorff, Christine; Meyer, Neele; de Boer, Sietse F; Althaus, Monika; Koolhaas, Jaap M

    2015-03-01

    We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the present study, we targeted two critical brain areas, i.e. the central amygdala (CeA) and the dorsal raphe (DR), both containing high levels of OXT receptors (OXTRs) and constituting important nodes of the neural circuitry related to aggression. Behavioral effects of local micro-infusion of OXT and OXTR antagonist, L368.899, (alone and combined) were evaluated in resident male rats during confrontations with an unfamiliar male intruder. Our results show that OXT microinjected into the CeA markedly reduced resident's offensive behavior and facilitated social exploration, without affecting other non-aggressive behaviors. The receptor specificity of the behavioral effects was verified when a micro-infusion of a selective OXTR antagonist nullified the changes. Pharmacological blockade of CeA OXTRs per se was without clear behavioral effects suggesting that endogenous OXT within the CeA does not play a major inhibitory role on offensiveness. Anatomical specificity was also supported by the absence of relevant behavioral effects when OXT was microinjected into more medial sub-regions of the amygdala. Likewise, within the DR neither OXT nor OXTR exerted significant effects on offensive aggression, while microinjection of the 5-HT1A autoreceptor agonist in this region significantly suppressed aggression. In conclusion, our results point at the CeA as an important brain site of action for the anti-aggressive and pro-social explorative effects induced by exogenous enhancement of brain OXT levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Witnesses in action: the effect of physical exertion on recall and recognition.

    Science.gov (United States)

    Hope, Lorraine; Lewinski, William; Dixon, Justin; Blocksidge, David; Gabbert, Fiona

    2012-04-01

    Understanding memory performance under different operational conditions is critical in many occupational settings. To examine the effect of physical exertion on memory for a witnessed event, we placed two groups of law-enforcement officers in a live, occupationally relevant scenario. One group had previously completed a high-intensity physical-assault exercise, and the other had not. Participants who completed the assault exercise showed impaired recall and recognition performance compared with the control group. Specifically, they provided significantly less accurate information concerning critical and incidental target individuals encountered during the scenario, recalled less briefing information, and provided fewer briefing updates than control participants did. Exertion was also associated with reduced accuracy in identifying the critical target from a lineup. These results support arousal-based competition accounts proposing differential allocation of resources under physiological arousal. These novel findings relating to eyewitness memory performance have important implications for victims, ordinary citizens who become witnesses, and witnesses in policing, military, and related operational contexts.

  12. Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Piotr Kuropka

    2017-01-01

    Full Text Available The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

  13. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    Directory of Open Access Journals (Sweden)

    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  14. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    Science.gov (United States)

    Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine

  15. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    Science.gov (United States)

    Homberg, Judith R; Olivier, Jocelien D A; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

    2011-01-31

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A) receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine

  16. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer.

    Science.gov (United States)

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-04-05

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs.

  17. Ethanol exerts anti-inflammatory effects in human adipose tissue in vitro.

    Science.gov (United States)

    Wandler, Anne; Bruun, Jens M; Nielsen, Maria P; Richelsen, Bjørn

    2008-12-16

    Moderate alcohol consumption is suggested to be associated with reduced inflammation and morbidity. Human adipose tissue (AT) and obesity is characterised by low-grade inflammation, so the present study wanted to investigate the effects of ethanol on inflammation in human AT in vitro. Subcutaneous human AT was incubated with ethanol [11-88 mM] under non- or LPS-stimulated [50mg/mL] conditions. Protein and mRNA levels of adiponectin, IL-6, IL-8, TNF-alpha, MCP-1, and CD68 were assessed using ELISA and real-time RT-PCR, respectively. Non-stimulated, ethanol incubations up to 24h increased adiponectin release and mRNA expression (p0.05). In conclusion, ethanol exerts anti-inflammatory effects in human AT, suggesting that ethanol may attenuate whole-body inflammation.

  18. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    DEFF Research Database (Denmark)

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda

    2016-01-01

    ABSTRACT: Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic...... (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated......, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts....

  19. Effect of Bench Press Load Knowledge on Repetitions, Rating of Perceived Exertion, and Attentional Focus.

    Science.gov (United States)

    Beaudoin, Christina M; Cox, Zachary; Dundore, Tyler; Thomas, Tayler; Kim, Johnathon; Pillivant, Daniel

    2018-02-01

    Beaudoin, CM, Cox, Z, Dundore, T, Thomas, T, Kim, J, and Pillivant, D. Effect of bench press load knowledge on repetitions, rating of perceived exertion, and attentional focus. J Strength Cond Res 32(2): 514-519, 2018-Few studies have examined the role of the teleoanticipation during resistance training. The purpose of this study was to examine the effect of bench press (BP) load knowledge on repetitions completed, ratings of perceived exertion (RPEs), and attentional focus (% associative). Thirty-six recreationally active resistance-trained men (n = 25) and women (n = 11) participated in this study (age = 20.97 ± 1.87 years; ht = 174.12 ± 9.41 cm; and mass = 80.14 ± 14.03 kg). All subjects completed 3 testing sessions: (a) 1 repetition maximum (1RM) BP determination; (b) submaximal BP repetitions to fatigue known load (KL); and (c) submaximal BP repetitions to fatigue unknown load (UL). Known load and UL sessions were randomized and counterbalanced and both completed at 70% 1RM. An estimated weight ratio was computed using the subject's estimate of the UL weight relative to the KL weight. An independent samples t-test revealed no significant testing order difference for the estimated weight ratio. Two-way repeated-measures analysis of variances revealed no significant differences in the number of repetitions (p = 0.63), RPE (p = 0.18), or attentional focus (% associative) (p = 0.93) between the KL and UL conditions. Pearson correlations found a moderate positive association between KL repetitions completed and % associative focus when the UL was completed before the KL. Load knowledge did not influence the number of repetitions, RPE, or attentional focus while completing the BP. Further research examining the use of pacing strategies, RPE, and attentional focus during KL and UL conditions are warranted.

  20. Effects of music and video on perceived exertion during high-intensity exercise

    Directory of Open Access Journals (Sweden)

    Enoch C. Chow

    2017-03-01

    Conclusion: Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation. Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

  1. Effects of partial sleep restriction and subsequent daytime napping on prolonged exertional heat strain.

    Science.gov (United States)

    Tokizawa, Ken; Sawada, Shin-Ichi; Tai, Tetsuo; Lu, Jian; Oka, Tatsuo; Yasuda, Akinori; Takahashi, Masaya

    2015-07-01

    It is considered that sleep restriction is one of the risk factors for the development of exertional heat stroke and illness. However, how sleep restriction affects exertional heat strain and the nature of the coping strategy involved in this phenomenon remain unclear. Fourteen healthy subjects were studied on four occasions: after a night of normal sleep (NS, 7-8 h) and after a night of partial sleep restriction (PSR, 4 h), each with or without taking a daytime nap during the subsequent experimental day. The laboratory test consisted of two 40 min periods of moderate walking in a hot room in the morning and the afternoon. The increase in rectal temperature during walking was significantly greater in PSR than in NS in the afternoon. The rating scores for physical and psychological fatigue and sleepiness were significantly greater in PSR than in NS, both in the morning and in the afternoon. The reaction times and lapses in the psychomotor vigilance task (PVT) after walking were significantly worse in PSR than in NS in the morning and after lunch. The nap intervention attenuated significantly the scores for fatigue and sleepiness in PSR. Furthermore, the decreased PVT response in PSR was significantly reversed by the nap. These results suggest that PSR augments physiological and psychological strain and reduces vigilance in the heat. Taking a nap seemed to be effective in reducing psychological strain and inhibiting the decrease in vigilance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia

    Science.gov (United States)

    Kiers, Dorien; Gerretsen, Jelle; Janssen, Emmy; John, Aaron; Groeneveld, R.; van der Hoeven, Johannes G.; Scheffer, Gert-Jan; Pickkers, Peter; Kox, Matthijs

    2015-01-01

    Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy. PMID:26616217

  3. Visual color perception in green exercise: positive effects on mood and perceived exertion.

    Science.gov (United States)

    Akers, Adam; Barton, Jo; Cossey, Rachel; Gainsford, Patrick; Griffin, Murray; Micklewright, Dominic

    2012-08-21

    Positive effects of green exercise on physical and psychological wellbeing have been found, yet little is known about the underlying cognitive mechanisms responsible for such effects. The purpose of this visual sensation study was to establish the extent to which the color green, as a primitive visual feature of many natural environments, contributes to the green exercise effect. Fourteen participants performed three moderate-intensity 5-min cycling tasks (50% peak power output) while watching video footage of a rural cycling course that simulated cycling through a real natural environment. The three randomly counter-balanced video conditions were unedited (V(GREEN)), achromatic (V(GRAY)) or red filter (V(RED)). Lower total mood disturbance and ratings of perceived exertion were found during the V(GREEN) compared to V(GRAY) and V(RED). Feelings of anger were higher after V(RED) compared to the other conditions. Feelings of tension, depression, fatigue, vigor, and confusion did not differ among conditions. This is the first study to show that the color green, as a primitive feature of visual sensation, has a contributory effect toward positive green exercise outcomes.

  4. Notochordal-cell derived extracellular vesicles exert regenerative effects on canine and human nucleus pulposus cells.

    Science.gov (United States)

    Bach, Frances; Libregts, Sten; Creemers, Laura; Meij, Björn; Ito, Keita; Wauben, Marca; Tryfonidou, Marianna

    2017-10-24

    During intervertebral disc ageing, chondrocyte-like cells (CLCs) replace notochordal cells (NCs). NCs have been shown to induce regenerative effects in CLCs. Since vesicles released by NCs may be responsible for these effects, we characterized NC-derived extracellular vesicles (EVs) and determined their effect on CLCs. EVs were purified from porcine NC-conditioned medium (NCCM) through size exclusion chromatography, ultracentrifugation or density gradient centrifugation. Additionally, the EVs were quantitatively analyzed by high-resolution flow cytometry. The effect of NCCM-derived EVs was studied on canine and human CLC micro-aggregates in vitro and compared with NCCM-derived proteins and unfractionated NCCM. Porcine NCCM contained a considerable amount of EVs. NCCM-derived EVs induced GAG deposition in canine CLCs to a comparable level as NCCM-derived proteins and unfractionated NCCM, and increased the DNA and glycosaminoglycan (GAG) content of human micro-aggregates, although to a lesser extent than unfractionated NCCM. The biological EV effects were not considerably influenced by ultracentrifugation compared with size exclusion-based purification. Upon ultracentrifugation, interfering GAGs, but not collagens, were lost. Nonetheless, collagen type I or II supplemented to CLCs in a concentration as present in NCCM induced no anabolic effects. Porcine NCCM-derived EVs exerted anabolic effects comparable to NCCM-derived proteins, while unfractionated NCCM was more potent in human CLCs. GAGs and collagens appeared not to mediate the regenerative EV effects. Thus, NC-derived EVs have regenerative potential, and their effects may be influenced by the proteins present in NCCM. The optimal combination of NC-secreted factors needs to be determined to fully exploit the regenerative potential of NC-based technology.

  5. Dipeptidyl peptidase IV inhibition exerts renoprotective effects in rats with established heart failure

    Directory of Open Access Journals (Sweden)

    Daniel Francisco De Arruda Junior

    2016-07-01

    Full Text Available Circulating dipeptidyl peptidase IV (DPPIV activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for four weeks with vildagliptin (120 mg/kg/day or vehicle by oral gavage. Echocardiography was performed before (pretreatment and at the end of treatment (post-treatment to evaluate cardiac function. The fractional area change increased (34±5 vs. 45±3%, p<0.05, and the isovolumic relaxation time decreased (33±2 vs. 27±1 ms; p<0.05 in HF rats treated with vildagliptin (post-treatment vs. pretreatment. On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1 serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  6. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  7. Sesame oil consumption exerts a beneficial effect on endothelial function in hypertensive men.

    Science.gov (United States)

    Karatzi, Kalliopi; Stamatelopoulos, Kimon; Lykka, Maritta; Mantzouratou, Pigi; Skalidi, Sofia; Zakopoulos, Nikolaos; Papamichael, Christos; Sidossis, Labros S

    2013-04-01

    The aim of the study was to investigate the effects of sesame oil on endothelial function and to detect the underlying mechanisms, both in the postprandial state and after long-term consumption. We enrolled 30 hypertensive men in a two-phase study. In the first phase, 26 volunteers consumed 35 g of either sesame oil or control oil. Endothelial function, inflammatory activation and nitric oxide syntase (NOS) inhibition was assessed after a 12-hour fast and 2 hours after consumption of an oil-containing standardized meal. In the second phase, 30 volunteers consumed 35 g of sesame oil or control oil daily for 2 months and the above-mentioned parameters were assessed at baseline, 15, 30 and 60 days. Endothelial function was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery. Flow-mediated dilatation (FMD) improved significantly both after acute (p = 0.001) and long-term sesame oil consumption (p = 0.015, p = 0.005 and p = 0.011 for 15, 30 and 60 days respectively). Intracellular adhesion molecule (ICAM) levels decreased significantly after only 60 days of daily sesame oil intake (p = 0.014). By contrast, no changes were observed in the control group in either phase of the study. This is the first study to show that sesame oil consumption exerts a beneficial effect on endothelial function and this effect is sustained with long-term daily use.

  8. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

    Directory of Open Access Journals (Sweden)

    Shen X

    2017-02-01

    Full Text Available Xin Shen,1,* Nan Zhou,1,* Le Mi,1 Zishuo Hu,2 Libin Wang,1 Xueying Liu,1 Shengyong Zhang1 1Department of Medicinal Chemistry, School of Pharmacy, 2Student Brigade, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph. In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6 myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05 reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of T2D rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. Keywords: phloretin, diabetes, insulin sensitivity, blood glucose consumption, skeletal muscle

  10. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Directory of Open Access Journals (Sweden)

    Heidi Wichmann

    2016-05-01

    Full Text Available The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP, produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA, a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2. Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

  11. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Sangeetha Ravi Kumar

    2013-12-01

    Full Text Available Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

  12. Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

    Science.gov (United States)

    Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

    2012-01-01

    Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

  13. Effect of extremely weak pulsed magnetic field type Bemer 3000 on ratings of perceived exertion

    National Research Council Canada - National Science Library

    D Gazurek; K Spodaryk

    2008-01-01

    The aim of this study was to examine whether is an influence of the exposition on different inductions of magnetic fields on rating of perceived exertion during 10 min long standardised physical cycloergometer exercise...

  14. Polymyxin B, in combination with fluconazole, exerts a potent fungicidal effect

    Science.gov (United States)

    Zhai, Bing; Zhou, Henry; Yang, Liangpeng; Zhang, Jun; Jung, Kathy; Giam, Chou-Zen; Xiang, Xin; Lin, Xiaorong

    2010-01-01

    Objectives The objective of this study was to identify existing clinical compounds that either possess a fungicidal activity alone or can act synergistically with fungistatic antifungals. Methods We screened a clinical compound library for drugs that exhibited anti-Aspergillus activity. Among selected compounds, the cationic peptide antibiotic polymyxin B was chosen for further characterization because it can be used parenterally and topically. The fungicidal effect of polymyxin B and its synergistic interactions with azole antifungals were tested against a variety of fungal species. The toxicity of the drug combination of polymyxin B and fluconazole was compared with that of each drug alone in mammalian cell cultures. Results We found that polymyxin B possesses a broad-spectrum antifungal activity at relatively high concentrations. However, because of its synergistic interactions with azole antifungals, polymyxin B at much lower concentrations exerts a potent fungicidal effect against Cryptococcus neoformans, Candida albicans and non-albicans Candida species and moulds when combined with azoles. The combination of polymyxin B and fluconazole at concentrations within susceptible breakpoints is particularly potent against C. neoformans isolates, including fluconazole-resistant strains. The drug combination displayed no additional toxicity compared with polymyxin B alone when tested in cell culture. Conclusions The combination of polymyxin B and fluconazole has the potential to be used in the clinic to treat systemic cryptococcosis. Our findings suggest that combining cationic peptide antibiotics with azole antifungals could provide a new direction for developing novel antifungal therapies. PMID:20167587

  15. Effective range of reproductive interference exerted by an alien dandelion, Taraxacum officinale, on a native congener.

    Science.gov (United States)

    Takakura, Koh-Ichi; Matsumoto, Takashi; Nishida, Takayoshi; Nishida, Sachiko

    2011-03-01

    Reproductive interference (RI), defined as the fitness cost of interspecific sexual interactions, such as interspecific pollen transfer (IPT) in plants, is ecologically important. Theoretically, RI could result in competitive exclusion, as it operates in a frequency-dependent manner. Additionally, IPT may have a greater range than resource competition, although information about the range of IPT is lacking. In the present study, we measured the range of IPT exerted by Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We used two approaches. In one, we analyzed the RI effect on a native seed set at three spatial scales. In the second, we tracked IPT from alien to native flower heads using fluorescent pigments as markers. We estimated that pollination distances were in the order of several meters. These distances exceeded the mean distance from each native plant to the nearest alien. As hypothesized, the effect of RI reached farther than neighboring individuals. These data indicate the spatial range from which alien dandelions should be removed to allow the conservation of natives.

  16. Acute effects of exercise and active video games on adults' reaction time and perceived exertion.

    Science.gov (United States)

    Guzmán, José F; López-García, Jesús

    2016-11-01

    The purpose of the present study was to examine the acute effects of resting, aerobic exercise practised alone, and aerobic exercise with active video games (AVG), on complex reaction time (CRT) and the post-exercise acute rate of perceived exertion (RPE) in young healthy adults. The experimental group was composed of 92 healthy young adults, 78 males and 13 females (age M = 21.9 ± 2.7 years) who completed two sessions, A and B. In session A, participants rode 30 min on an ergometer, while in session B they exercised for 30 min on an ergometer while playing an AVG on a Wii. The control group was composed of 30 young adults, 26 males and 4 females (age M = 21.4 ± 2.9 years) who rested for 30 min. In each session, a CRT task was performed before and after exercising or resting, and post-exercise global RPE was noted. Repeated measures general linear model (GLM) and Wilcoxon tests were performed. (1) Both aerobic exercise alone and aerobic exercise combined with AVG improved CRT, while resting did not; (2) aerobic exercise combined with AVG did not improve CRT more than aerobic exercise only; and (3) RPE was lower after aerobic exercise combined with AVG compared with aerobic exercise only. In young adults, exercise produces acute benefits on CRT, and practising exercise with AVG helps to decrease RPE.

  17. Sam68 exerts separable effects on cell cycle progression and apoptosis

    Directory of Open Access Journals (Sweden)

    Resnick Ross J

    2004-01-01

    Full Text Available Abstract Background The RNA-binding protein Sam68 has been implicated in a number of cellular processes, including transcription, RNA splicing and export, translation, signal transduction, cell cycle progression and replication of the human immunodeficiency virus and poliovirus. However, the precise impact it has on essential cellular functions remains largely obscure. Results In this report we show that conditional overexpression of Sam68 in fibroblasts results in both cell cycle arrest and apoptosis. Arrest in G1 phase of the cell cycle is associated with decreased levels of cyclins D1 and E RNA and protein, resulting in dramatically reduced Rb phosphorylation. Interestingly, cell cycle arrest does not require the specific RNA binding ability of Sam68. In marked contrast, induction of apoptosis by Sam68 absolutely requires a fully-functional RNA binding domain. Moreover, the anti-cancer agent trichostatin A potentiates Sam68-driven apoptosis. Conclusions For the first time we have shown that Sam68, an RNA binding protein with multiple apparent functions, exerts functionally separable effects on cell proliferation and survival, dependent on its ability to bind specifically to RNA. These findings shed new light on the ability of signal transducing RNA binding proteins to influence essential cell function. Moreover, the ability of a class of anti-cancer therapeutics to modulate its ability to promote apoptosis suggests that Sam68 status may impact some cancer treatments.

  18. The effect of ramadan fasting on physical performances, mood state and perceived exertion in young footballers.

    Science.gov (United States)

    Chtourou, Hamdi; Hammouda, Omar; Souissi, Hichem; Chamari, Karim; Chaouachi, Anis; Souissi, Nizar

    2011-09-01

    This study was designed to assess the effects of Ramadan fasting on the profile of mood state and perceived exertion in young soccer players and aerobic and anaerobic performances during the Yo-Yo, repeated sprint ability (RSA) and the Wingate tests. Twenty junior male soccer players completed the Yo-Yo, the RSA, and the Wingate tests on three different occasions: one-week before Ramadan (BR), the second week (SWR) and the fourth week (ER) of Ramadan. The total distance (TD) covered and the estimated maximal aerobic velocity (MAV) during the Yo-Yo test were recorded. During the RSA test, peak power (PP) during each sprint, the percentage of decrement of PP (PD) and total work (Wtotal) were calculated. During the Wingate test, peak (P(peak)) and mean (P(mean)) powers and fatigue index (FI) were recorded. TD and MAV (P=0.01) during the Yo-Yo test and PP (P=0.01, P=0.004, P=0.001, P=0.01, P=0.03 for sprints 1, 2, 3, 4, and 5, respectively) and Wtotal (P=0.02) during the RSA test were significantly higher during BR than ER. Furthermore, muscle fatigue during the RSA test increased significantly from BR to ER (P=0.01). P(peak) and P(mean) during the Wingate test decreased significantly from BR to SWR and ER (Psoccer players.

  19. Effects of 12 months aerobic exercise intervention on work ability, need for recovery, productivity and rating of exertion among cleaners

    DEFF Research Database (Denmark)

    Lidegaard, Mark; Søgaard, Karen; Krustrup, Peter

    2017-01-01

    PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster-randomised (w......PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster...

  20. Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities

    Directory of Open Access Journals (Sweden)

    Miaw-Ling Chen

    2015-01-01

    Full Text Available This study was to investigate antiallergic effects of triterpenoids (Gt-TRE and polysaccharide (Gt-PS extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL- 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+ T cells cultures also confirmed that Gt-TRE (5~50 µg/mL significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

  1. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  2. Cytoprotective and antiulcer activities of the antacid magaldrate in the rat.

    Science.gov (United States)

    Borella, L E; DiJoseph, J F; Mir, G N

    1989-07-01

    The cytoprotective and antiulcer activities of the antacid magaldrate (ES Riopan) as well as its effects on gastric mucosal blood flow and mucus secretions, were determined in the rat. Magaldrate afforded protection against gastric necrotic lesions induced by absolute ethanol (ED50, as magaldrate, 419 mg/kg); gastric ulcers induced by acidified acetylsalicylic acid (ED50 540 mg/kg), stress (cold restraint, ED50 388 mg/kg), indometacin (ED50 281 mg/kg), and pylorus ligation; and intestinal ulcers induced by cysteamine (ED50 243 mg/kg) and indometacin (ED50 184 mg/kg). At a dose of 8 ml/kg (1728 mg/kg magaldrate), the cytoprotective effect of magaldrate against ethanol was evident 1 min after oral administration and lasted more than 8 h. The cytoprotection induced by magaldrate was decreased by pretreatments with the depletor of endogenous thiols, n-ethylmaleimide, or with the cyclooxygenase inhibitor, indometacin. Magaldrate did not affect gastric mucosal blood flow, but it increased gastric mucus secretion. This later effect may be a factor responsible for the cytoprotective activity of the agent. The efficacy of magaldrate may be due not only to its antacid, bile sequestering, and antipeptic activities, but also to its cytoprotective activity. The present results suggest that magaldrate could be effective in preventing gastric damage caused by alcohol and antiinflammatory drugs.

  3. The Cytoprotective Effects of E-α-(4-Methoxyphenyl-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC--A Novel and Non-Cytotoxic HO-1 Inducer.

    Directory of Open Access Journals (Sweden)

    Kai B Kaufmann

    Full Text Available Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1, is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  4. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as seen in diabetes.

  5. Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    Full Text Available The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP. Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

  6. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  7. Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver

    NARCIS (Netherlands)

    Wimmer, R.; Hohenester, S.; Pusl, T.; Denk, G. U.; Rust, C.; Beuers, U.

    2008-01-01

    OBJECTIVE: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKC alpha agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKC

  8. Ouabain exerts biphasic effects on connexin functionality and expression in vascular smooth muscle cells.

    Science.gov (United States)

    Martin, Patricia E M; Hill, Nathan S; Kristensen, Bo; Errington, Rachael J; Rachael J, Tudor M

    2004-01-01

    1. We have compared the effects of ouabain on the maintenance of gap junctional communication in rat aortic A7r5 smooth muscle cells, monkey COS-1 fibroblasts and human HeLa epithelial cells. 2. Ouabain (1 mM) interrupted dye coupling between confluent A7r5 cells within approximately 1 h, and high concentrations of ouabain were similarly required to reduce coupling between COS-1 cells selected to express the rat alpha1 Na+/K+-ATPase subunit, which is ouabain resistant. By contrast, low concentrations of ouabain (1-10 microM) attenuated dye transfer in wild-type COS-1 and HeLa cells, whose endogenous alpha1 subunits possess relatively high affinity for the glycoside (Ki approximately 0.3 vs approximately 100 microM) Ouabain-induced reductions in dye transfer therefore correlated with the ability of the glycoside to bind to the Na+/K+-ATPase isoenzymes expressed in these different cell lines. 3. No consistent relationship between inhibition of intercellular dye transfer and secondary changes in [Ca2+]i or pHi could be identified following incubation with ouabain. 4. In separate experiments, the effects of ouabain on real-time trafficking of connexin (Cx) protein were monitored by time-lapse microscopy of A7r5 cells transfected to express a fluorescent Cx43-green fluorescent protein (GFP) and the ability of the glycoside to modulate endogenous expression of Cx40 and Cx43 evaluated in A7r5 cells by immunochemical and Western blot analysis. 5. Ouabain (1 mM) depressed vesicular trafficking of Cx43-GFP after approximately 1 h, and caused a time-dependent loss of endogenous Cx40 and Cx43 protein that was first evident at 2 h and almost complete after 4 h. These effects of ouabain on Cx expression were reversed 90 min following washout of the glycoside. 6. We conclude that ouabain exerts biphasic effects on intercellular communication that involve an initial decrease in gap junctional permeability followed by a global reduction in the expression of Cx protein. Further

  9. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  10. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

  11. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  12. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; van Brunschot, C.; Schipper, P.; Korte-Bouws, G.; van Luijtelaar, G.; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac (R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  13. Effects of asymmetric dynamic and isometric liftings on strength/force and rating of perceived exertion.

    Science.gov (United States)

    Hattori, Y; Ono, Y; Shimaoka, M; Hiruta, S; Kamijima, M; Shibata, E; Ichihara, G; Ando, S; Villaneuva, M B; Takeuchi, Y

    1996-06-01

    A laboratory study was undertaken to determine the postural and physical characteristics and subjective stress during dynamic lifting of a usual load (10 kg) compared with during isometric lifting. The authors also aimed to clarify the effects of asymmetric lifting on these parameters. The subjects were thirteen male college students. They were asked to lift a box weighing 10 kg. They performed sixteen different lifting tasks from the floor to a height of 71 cm, involving a combination of three independent factors: two lifting modes (isometric lifting and dynamic lifting), four lifting angles in relation to the sagittal plane (sagittal plane, right 45 degree, right 90 degree and left 90 degree planes) and two lifting postures (squat and stoop). For each lifting task, strengths or forces and ground reaction forces were measured. At the end of each task, the authors asked the subjects to rate their perceived exertion (RPE) during lifting at ten sites of the body. Angle factor had a significant effect on isometric strengths and dynamic peak forces. Isometric strengths during the maximum 3 s were highest in lifting in the right 45 degree plane, followed by that in the sagittal plane, while those in the right 90 degree and left 90 degree planes were the lowest. However, peak forces in dynamic lifting were the highest in the lifting in the sagittal plane, followed by that in the right 45 degree plane, while those in the right 90 degree and left 90 degree planes were the lowest. Postural factor had a significant effect on height at peak force, which is higher in squat lifting than in stoop lifting. RPEs for the left arm, the backs and the right whole body in isometric lifting were significantly higher than in dynamic lifting of 10 kg. There were remarkably high RPEs for the ipsilateral thigh to the box in right 90 degree and left 90 degree planes during both isometric and dynamic liftings. Locations of the resultant force consisting of three component forces on the force

  14. Biliverdin reductase: A major physiologic cytoprotectant

    Science.gov (United States)

    Barañano, David E.; Rao, Mahil; Ferris, Christopher D.; Snyder, Solomon H.

    2002-01-01

    Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverdin reductase of biliverdin, a product of heme oxygenase activity. Bilirubin is a potent antioxidant that we show can protect cells from a 10,000-fold excess of H2O2. We report that bilirubin is a major physiologic antioxidant cytoprotectant. Thus, cellular depletion of bilirubin by RNA interference markedly augments tissue levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic antioxidant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxidant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin. PMID:12456881

  15. Epigenetic memory of oxidative stress: does nephrilin exert its protective effects via Rac1?

    Directory of Open Access Journals (Sweden)

    Mascarenhas DD

    2017-07-01

    Full Text Available Desmond D Mascarenhas,1,2 David N Herndon,3 Istvan Arany4 1Mayflower Organization for Research & Education, Sunnyvale, CA, 2Transporin, Inc., Sunnyvale, CA, 3Department of Surgery, The University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX, 4Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, USA Aim: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2, exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox via PKCs, Prex1 and p66shc. Methods: Given the wide range of animal models in which nephrilin peptide has previously demonstrated effectiveness in vivo, we chose three different experimental systems for this investigation: dermal fibroblasts, renal proximal tubule epithelial cells (PTECs, and kidney tissue and urine from an animal model of burn trauma in which nephrilin was previously shown to prevent loss of kidney function. Results: (1 Nephrilin protects dermal fibroblasts from loss of viability and collagen synthesis after ultraviolet A (UV-A or H2O2 insult. (2 Nephrilin reduces reactive oxygen species (ROS formation by H2O2–treated (PTECs with or without nicotine pretreatment. Using RNA arrays and pathway analysis we demonstrate that nicotine and H2O2-treated PTECs specifically induced Rac1 gene networks in these cells. (3 Using kidney tissue and urine from the burn trauma model we demonstrate significant elevations of [a] 8-aminoprostane in urine; [b] kidney tissue histone modification and DNA methylation; and [c] post-transcriptional phosphorylation events consistent with Rac1 activation in

  16. Exosomes Derived From Natural Killer Cells Exert Therapeutic Effect in Melanoma.

    Science.gov (United States)

    Zhu, Liya; Kalimuthu, Senthilkumar; Gangadaran, Prakash; Oh, Ji Min; Lee, Ho Won; Baek, Se Hwan; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2017-01-01

    imaging system and ultrasound imaging. Tumor mass was monitored after in vivo experiments. Results: RT-PCR and western blotting confirmed effluc gene expression and protein levels in B16F10/effluc cells. B16F10/effluc activity was found to increase with increasing cell numbers, using BLI assay. For NK-92 Exo characterization, western blotting was performed on both ultracentrifuged and density gradient-isolated exosomes. The results confirmed that NK cell-derived exosomes express two typical exosome proteins, namely CD63 and ALIX. We demonstrated by western blot analysis that NK-92 Exo presented two functional NK proteins, namely perforin and FasL. Moreover, we confirmed the membrane expression of FasL. The enzyme-linked immunosorbent assay results indicated that NK-92 Exo can secrete tumor necrosis factor (TNF)-α, which affected the cell proliferation signaling pathway. The antitumor effect of NK-92 Exo against B16F10/effluc cells in vitro was confirmed by BLI (p < 0.001) and CCK-8 assays (p < 0.001). Furthermore, in normal healthy cells, even after 24 h of co-culture, NK-92 Exo did not exhibit significant side effects. In the in vivo experiments, tumors in the vehicle control group were significantly increased, compared with those in the NK-92 Exo-treated group (p < 0.05). Conclusion: The results of the current study suggest that exosomes derived from NK cells exert cytotoxic effects on melanoma cells and thus warrant further development as a potential immunotherapeutic strategy for cancer.

  17. Effect of extremely weak pulsed magnetic field type Bemer 3000 on ratings of perceived exertion

    Directory of Open Access Journals (Sweden)

    D Gazurek

    2008-06-01

    Full Text Available The aim of this study was to examine whether is an influence of the exposition on different inductions of magnetic fields on rating of perceived exertion during 10 min long standardised physical cycloergometer exercise. The investigation was performed in 40 healthy, non-smoking, fit men, mean age 202. The participants were randomly attributed to 4 groups, each including 10 subjects. The first one (group E18 consisted of subjects exposed to the magnetic field with the intensity of 18 μT, the second one (group E64 exposed to the magnetic field with the intensity of 64 μT. Two control groups were formed to accompany these exposed to the magnetic field. In these placebo groups (S-T subjects were not exposed to the magnetic field (so called false therapy, „sham treatment”. The study consisted of 4 steps: pilot study, the first endurance test, exposure to the magnetic field, the second endurance test. The aim of the pilot study was to define subjective feelings of the participant during the effort, his reaction to the effort and also practical familiarization with the character and rules of the endurance test and Borg scale interpretation during 10 min of endurance cycloergometer test. The first endurance test was performed two days after the pilot study with the same rules and its goal was to measure the level of tiredness according to the Borg scale during 10 min long standardised physical effort. The second endurance test was performed according to the same rules as the first one and its goal was to analyse the effect of 20 exposures to the magnetic field with the intensity of 18 and 64 μT repeated daily on the perception of tiredness increase as expressed in the Borg scale when performing 10 min long standardised physical effort. In subjects exposed to 18 μT magnetic field neither changes in the perception of fatigue nor changes in the heart rate at particular levels of the Borg scale have been observed. When compared with both control

  18. Aromatic Amines Exert Contrasting Effects on the Anticoagulant Effect of Acetaldehyde upon APTT

    Directory of Open Access Journals (Sweden)

    La'Teese Hall

    2014-01-01

    Full Text Available The pharmacological effects of amphetamine, procaine, procainamide, DOPA, isoproterenol, and atenolol upon activated partial thromboplastin time in the absence and presence of acetaldehyde have been investigated. In the absence of acetaldehyde, amphetamine and isoproterenol exhibit a procoagulant effect upon activated partial thromboplastin time, whereas atenolol and procaine display anticoagulant effects upon activated partial thromboplastin time. DOPA and procainamide do not alter activated partial thromboplastin time. Premixtures of procaine with acetaldehyde produce an additive anticoagulant effect on activated partial thromboplastin time, suggesting independent action of these compounds upon clotting factors. Premixtures of amphetamine with acetaldehyde, as well as atenolol with acetaldehyde, generate a detoxication of the anticoagulant effect of acetaldehyde upon activated partial thromboplastin time. A similar statistically significant decrease in activated partial thromboplastin time is seen when procainamide is premixed with acetaldehyde for 20 minutes at room temperature. Premixtures of DOPA and isoproterenol with acetaldehyde do not affect an alteration in activated partial thromboplastin time relative to acetaldehyde alone. Hence, a selective interaction of atenolol, procaine, and amphetamine with acetaldehyde to produce detoxication of the acetaldehyde is suggested, undoubtedly due to the presence of amino, hydroxyl, or amide groups in these drugs.

  19. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells

    OpenAIRE

    Basile, John R.; Binmadi, Nada O.; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few...

  20. Effect of experimental modulation of mood on perception of exertional dyspnea in healthy subjects.

    Science.gov (United States)

    Sharma, Pramod; Morris, Norman R; Adams, Lewis

    2016-01-15

    In many diseases across a range of pathologies (e.g., cardiopulmonary, neuromuscular, and cancer), chronic dyspnea, particularly on exertion, is a major debilitating symptom often associated with clinical anxiety/depression. This study aims to explore the interaction between mood state and exertional dyspnea in a healthy population. Following familiarization, 20 healthy subjects (27-54 years old) performed six 5-min treadmill tests on three separate days. On each day subjects viewed randomly assigned images designed to induce positive, negative, or neutral mood states (International Affective Picture System). For each condition, at minute intervals, subjects rated dyspnea (sensory and affective domains) in the first test and mood (valence and arousal domains) in the second test. Oxygen uptake (V̇O2 , liters/min), carbon dioxide production (V̇CO2, liters/min), ventilation (V̇E, liters/min), respiratory frequency (f(R), beats/min), and heart rate (HR, bpm), were measured throughout the exercise. V̇O2, V̇CO2, V̇E, HR, and f(R) were not statistically significantly different among the three mood states (P > 0.05). Mood valence was significantly higher with parallel viewing of positive (last 2-min mean ± SE = 6.9 ± 0.2) compared with negative pictures (2.4 ± 0.2; P negative (sensory: 5.6 ± 0.3; affective: 3.3 ± 0.5) compared with positive mood (sensory: 4.4 ± 0.4, P positive mood alleviates both the sensory and affective domains of exertional dyspnea in healthy subjects. Thus the treatment of anxiety/depression in dyspenic populations could be a worthwhile therapeutic strategy in increasing symptom-limited exercise tolerance, thereby contributing to improved quality of life. Copyright © 2016 the American Physiological Society.

  1. Effect of traditional resistance and power training using rated perceived exertion for enhancement of muscle strength, power, and functional performance

    OpenAIRE

    Tiggemann, Carlos Leandro; Dias, Caroline Pieta; Radaelli, Regis; Massa, J?ssica Cassales; Bortoluzzi, Rafael; Schoenell, Maira Cristina Wolf; Noll, Matias; Alberton, Cristine Lima; Kruel, Luiz Fernando Martins

    2016-01-01

    The present study compared the effects of 12?weeks of traditional resistance training and power training using rated perceived exertion (RPE) to determine training intensity on improvements in strength, muscle power, and ability to perform functional task in older women. Thirty healthy elderly women (60?75?years) were randomly assigned to traditional resistance training group (TRT; n?=?15) or power training group (PT; n?=?15). Participants trained twice a week for 12?weeks using six exercises...

  2. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    Directory of Open Access Journals (Sweden)

    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  3. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    Science.gov (United States)

    Hegde, Pushpa; Maddur, Mohan S; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srini V

    2011-01-01

    Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  4. Menstrual cycle effects on perceived exertion and pain during exercise among sedentary women.

    Science.gov (United States)

    Hooper, Ann E Caldwell; Bryan, Angela D; Eaton, Melissa

    2011-03-01

    Increasing cardiovascular fitness through exercise participation among sedentary people is important for decreasing all-cause mortality. From an intervention perspective, identifying modifiable factors that maximize the successful initiation of exercise is of utmost importance. For women, cyclic hormonal variations can influence aspects of health and health behaviors, from smoking cessation efficacy to physiological responses to exercise. The purpose of this study was to examine the influence of menstrual cycle phase and hormonal contraceptive (HC) use on subjective response to an initial bout of moderate intensity exercise among previously sedentary women (n = 117). Women completed a treadmill exercise challenge session at 65% of their previously determined maximum oxygen consumption (Vo(2) max) during the early follicular, late follicular, or luteal phase. Participants reported ratings of perceived exertion and pain using Borg's Rating of Perceived Exertion (RPE) and CR10 scales at 10, 20, and 30 minutes during the exercise session. There was a significant menstrual phase x birth control interaction on change in RPE [F(2, 111) = 3.75, p cycle phase influence sedentary women's subjective response to exercise. These results have important implications for the timing of exercise interventions aimed at increasing exercise among sedentary women.

  5. The Effects of Initial Self-Control Exertion and Subsequent Glucose Consumption on Search Accuracy by Dogs

    Directory of Open Access Journals (Sweden)

    Miller, Holly C.

    2013-07-01

    Full Text Available Previous reports have suggested that canine self-control is sensitive to fatigue and that an initial act of behavioral inhibition (sit-stay 10 min relative to a control condition (cage 10 min can deplete self-control, increase risk-taking, and reduce subsequent persistence on a puzzle task. Glucose, but not a calorie-free placebo drink has been shown to replenish this depletion. The current study sought to complement and extend these findings by examining whether initial exertion of self-control would also affect canine working memory as measured by search accuracy on a subsequently administered invisible displacement rotation task. The results evidenced that initial self-control exertion (relative to the control condition resulted in poorer search accuracy. The consumption of glucose did not have a replenishing effect. If anything, glucose was associated with poorer search accuracy.

  6. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Ahern, Christopher A

    2011-01-01

    BACKGROUND: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently...... concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM. CONCLUSIONS: The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower...

  7. The effect of home-based inspiratory muscle training on exercise capacity, exertional dyspnea and pulmonary function in COPD patients.

    Science.gov (United States)

    Bavarsad, Maryam Bakhshandeh; Shariati, Abdolali; Eidani, Esmaeil; Latifi, Mahmud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of mortality worldwide. Patients with COPD experience periods of dyspnea, fatigue, and disability, which impact on their life. The objective of this study was to investigate the effect of short-term inspiratory muscle training on exercise capacity, exertional dyspnea, and pulmonary lung function. A randomized, controlled trial was performed. Thirty patients (27 males, 3 females) with mild to very severe COPD were randomly assigned to a training group (group T) or to a control group (group C). Patients in group T received training for 8 weeks (15 min/day for 6 days/week) with flow-volumetric inspiratory exerciser named (Respivol). Each patient was assessed before and after 8 weeks of training for the following clinical parameters: exercise capacity by 6-min walking test (6MWT), exertional dyspnea by Borg scale, and pulmonary lung function by spirometry. Patients used training together with medical treatment. The data were analyzed using paired t-test and independent t-test. Results showed statistically significant increase in 6MWT at the end of the training from 445.6 ± 22.99 to 491.06 ± 17.67 meters? (P training group but not in the control group. The values for exercise capacity and dyspnea improved after 8 weeks in group T in comparison with group C (P = 0.001 and P = 0.0001, respectively). No changes were observed in any measure of pulmonary function in both groups. Short-term inspiratory muscle training has beneficial effects on exercise capacity and exertional dyspnea in COPD patients.

  8. A mineral and antioxidant-rich extract from the red marine Algae Alsidium corallinum exhibits cytoprotective effects against potassium bromate-induced erythrocyte oxidative damages in mice.

    Science.gov (United States)

    Ben Saad, Hajer; Nasri, Imen; Elwej, Awatef; Krayem, Najeh; Jarraya, Raoudha; Kallel, Choumous; Zeghal, Najiba; Amara, Ibtissem Ben

    2014-07-01

    The present study was carried out to investigate potassium bromate toxicity in mice and the corrective effects of marine algae Alsidium corallinum. The red algae demonstrated its rich composition in phenols, triterpenes, flavonoids, alkaloids, tropolones, sodium, potassium, calcium, magnesium, iron, copper, and zinc. To confirm its antioxidant potential, an in vivo study was performed on adult mice. The animals were divided into four groups: group I were used as controls, group II received potassium bromate (0.5 g/L) via drinking water, group III received potassium bromate (0.5 g/L) by the same route as group II and 7% of A. corallinum ethanolic extract via their diet, and group IV received only 7% of algae. The potassium bromate-treated group showed a significant decrease in erythrocyte, platelet, hemoglobin, and hematocrit values and a significant increase in total white blood cells, compared to those of controls. While, superoxide dismutase, catalase, glutathione, and vitamin C values were decreased by potassium bromate treatment, lipid peroxidation (as malondialdehyde) and erythrocyte osmotic fragility values were increased. Interestingly, potassium bromate treatment showed significant genotoxic effects, as demonstrated by DNA degradation. These changes were confirmed by blood smears histopathological observations which were marked by a necrosis and a decrease of erythrocytes number. A. corallinum extract appeared to be effective against hematotoxic and genotoxic changes induced by potassium bromate, as evidenced by the improvement of the parameters cited above.

  9. Cytoprotection of pancreatic β-cells and hypoglycemic effect of 2-hydroxypropyl-β-cyclodextrin: sertraline complex in alloxan-induced diabetic rats.

    Science.gov (United States)

    Buko, Vyacheslav; Zavodnik, Ilya; Lukivskaya, Oxana; Naruta, Elena; Palecz, Bartlomiej; Belica-Pacha, Silwia; Belonovskaya, Elena; Kranc, Robert; Abakumov, Vladimir

    2016-01-25

    Sertraline, a selective inhibitor of serotonin reuptake, is widely used as antidepressant in diabetic patients for improvement of depression and glycemic control. Sertraline is poorly soluble in water, which limits its oral applicability. In this work we tried to improve the pharmaceutical properties of sertraline by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and evaluated the efficacy of the HPβCD:sertraline complex in prevention of alloxan-induced lesions in rats. The solubility of sertraline increased in the presence of HPβCD and the association constant for sertraline and HPβCD was equal to 4000 ± 1000 M(-1). Two-week treatment of diabetic animals with the HPβCD:sertraline complex improved pancreatic islet morphology and β-cell survival, which, in turn, reduced the severity of diabetes, as evidenced by lowering of blood glucose and glycated hemoglobin contents as well as normalization of serum insulin level and insulin sensitivity (HOMA-IR). The effect of the HPβCD:sertraline complex was strongly expressed in comparison with the antidiabetic effect of both the monopreparations, HPβCD and sertraline. It is suggested that the cyclodextrin derivative increased the pharmacological effect of sertraline, probably due to enhanced drug bioavailability. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. 4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.

    Science.gov (United States)

    Herencia, F; Ferrándiz, M L; Ubeda, A; Guillén, I; Dominguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    2001-01-01

    Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.

  11. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    Science.gov (United States)

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  12. Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-01-01

    Full Text Available Exertional heat stroke (EHS results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm was detected by a fluorescent probe. Intramitochondrial free Ca2+ concentration, mitochondrial respiratory control ratio (RCR, reactive oxygen species (ROS levels, superoxide dismutase (SOD, and malondialdehyde (MDA activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α and manganese form of SOD (MnSOD mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+ concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat.

  13. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

    Directory of Open Access Journals (Sweden)

    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  14. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

    Science.gov (United States)

    Basile, John R; Binmadi, Nada O; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  15. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

    Science.gov (United States)

    Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

    2016-04-01

    Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.

  16. Glucocorticoids exert context-dependent effects on cells of the joint in vitro

    DEFF Research Database (Denmark)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T

    2011-01-01

    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This st...

  17. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    Science.gov (United States)

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention.

  18. The Dipeptides Ile-Tyr and Ser-Tyr Exert Distinct Effects on Catecholamine Metabolism in the Mouse Brainstem.

    Science.gov (United States)

    Moriyasu, Kazuki; Ichinose, Takashi; Nakahata, Akane; Tanaka, Mitsuru; Matsui, Toshiro; Furuya, Shigeki

    2016-01-01

    Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone. In comparison, administration of Ser-Tyr induced significantly increasing noradrenaline turnover, while Tyr-Pro administration suppressed dopamine turnover. Therefore, oral administration of Ile-Tyr, Ser-Tyr, and Tyr-Pro differentially affected metabolism of dopamine and noradrenaline. These observations strongly suggest that Tyr-containing dipeptides exert distinct effects on catecholamine metabolism in the brainstem when ingested orally.

  19. Effects of ladder parameters on asymmetric patterns of force exertion during below-knee amputees climbing ladders.

    Science.gov (United States)

    Li, Weidong; Li, Shiqi; Fu, Yan; Chen, Jacon

    2017-03-01

    Different from walking, ladder climbing requires four-limb coordination and more energy exertion for below-knee amputees (BKAs). We hypothesized that functional deficiency of a disabled limb shall be compensated by the other three intact limbs, showing an asymmetry pattern among limbs. Hand and foot forces of six below-knee amputees and six able-bodied people were collected. Hand, foot and hand/foot sum force variances between groups (non-BKA, intact side and prosthetic side) were carefully examined. Our hypothesis was validated that there is asymmetry between prosthetic and intact side. Results further showed that the ipsilateral hand of the prosthetic leg is stronger than the hand on the intact side, compensating weakness of the prosthetic leg. Effects of ladder rung separations and ladder slant on asymmetric force distribution of BKAs were evaluated, indicating that rung separation has a more significant interactive effect on hand/foot force of BKAs than ladder slant.

  20. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects

    OpenAIRE

    Zhong, Jianxiang; Reece, E. Albert; Yang, Peixin

    2015-01-01

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whethe...

  1. Subliminal messages exert long-term effects on decision-making

    OpenAIRE

    Ruch, Simon; Züst, Marc; Henke, Katharina

    2016-01-01

    Subliminal manipulation is often considered harmless because its effects typically decay within a second. So far, subliminal long-term effects on behavior were only observed in studies which repeatedly presented highly familiar information such as single words. These studies suggest that subliminal messages are only slowly stored and might not be stored at all if they provide novel, unfamiliar information. We speculated that subliminal messages might affect delayed decision making especially ...

  2. R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Bharanidharan Shanmugasundaram

    Full Text Available Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP. Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT, and its phosphorylated form (ph-DAT in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

  3. HIV-1 Gp120 clade B/C induces a GRP78 driven cytoprotective mechanism in astrocytoma

    Science.gov (United States)

    López, Sheila N.; Rodríguez-Valentín, Madeline; Rivera, Mariela; Rodríguez, Maridaliz; Babu, Mohan; Cubano, Luis A.; Xiong, Huangui; Wang, Guangdi; Kucheryavykh, Lilia; Boukli, Nawal M.

    2017-01-01

    HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism. The differential effect of gp120 clade B and C was evaluated using for the first time a Tandem Mass Tag isobaric labeling quantitative proteomic approach. Flow cytometry analyses were performed for cell cycle and cell death identification. Among the proteins differentiated by HIV-1 gp120 proteins figure cytoskeleton, oxidative stress, UPR markers and numerous glycolytic metabolism enzymes. Our results demonstrate that HIV-1 gp120 B induced migration, proliferative and protective responses granted by the expression of GRP78, while HIV-1 gp120 C induced the expression of key inflammatory and pro-apoptotic markers. These novel findings put forward the first evidence that GRP78 is a key player in HIV-1 clade B and C neuropathogenic discrepancies and can be used as a novel target for immunotherapies. PMID:28978127

  4. Blockade of CD127 Exerts a Dichotomous Clinical Effect in Marmoset Experimental Autoimmune Encephalomyelitis

    NARCIS (Netherlands)

    Dunham, Jordon; Lee, Li-Fen; van Driel, Nikki; Laman, Jon D.; Ni, Irene; Zhai, Wenwu; Tu, Guang-Huan; Lin, John C.; Bauer, Jan; 't Hart, Bert A.; Kap, Yolanda S.

    Non-human primate models of human disease have an important role in the translation of a new scientific finding in lower species into an effective treatment. In this study, we tested a new therapeutic antibody against the IL-7 receptor alpha chain (CD127), which in a C57BL/6 mouse model of

  5. Native herbivore exerts contrasting effects on fire regime and vegetation structure

    Science.gov (United States)

    Jose L. Hierro; Kenneth L. Clark; Lyn C. Branch; Diego. Villarreal

    2011-01-01

    Although native herbivores can alter fire regimes by consuming herbaceous vegetation that serves as fine fuel and, less commonly, accumulating fuel as nest material and other structures, simultaneous considerations of contrasting effects of herbivores on fire have scarcely been addressed. We proposed that a colonial rodent, vizcacha (Lagostomus maximus...

  6. Does a low-salt diet exert a protective effect on endothelial function in normal rats?

    NARCIS (Netherlands)

    Boonstra, AH; Gschwend, S; Kocks, MJA; Buikema, H; de Zeeuw, D; Navis, GJ

    Sodium restriction is often used as an adjunct in the treatment of conditions characterized by endothelial dysfunction, such as hypertension and heart or kidney disease. However, the effect of sodium restriction on endothelial function is not known. Therefore, male Wistar rats were studied after a

  7. An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice.

    Science.gov (United States)

    Reynoso-Moreno, Inés; Najar-Guerrero, Israel; Escareño, Noé; Flores-Soto, Mario Eduardo; Gertsch, Jürg; Viveros-Paredes, Juan Manuel

    2017-11-01

    Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1% inhibition of inflammatory pain at 2.5 mg/kg ip and 50.0 ± 15.9% inhibition of edema formation at 5 mg/kg ip) and acute analgesia (66.1 ± 28.1% inhibition at 5.0 mg/kg ip) were observed. Moreover, guineensine inhibited proinflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy, but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant, but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels, and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A, and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.

  8. Sim;- jxi Tobacco is known to exert adverse effect on general and ...

    African Journals Online (AJOL)

    reflects the roles of tobacco in predisposing users to erect categories of periodontal diseases. Tobacco-induced alterations in microbial and host factors are major conuibutor to the deleterious periodontal effects.26 e lower report of tooth mobility. 1:2..21 dentinal sensitivity 2: tobacco users may appear inconsistent with the.

  9. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation.

    Science.gov (United States)

    Bort, Alicia; Spínola, Elena; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2017-10-20

    In this study, we investigated the antitumoral effects of combined treatment using sorafenib and capsaicin in hepatocellular carcinoma (HCC) cells. Here we showed that the combination of the two drugs had a much stronger inhibitory effect on both HepG2 and Huh-7 human HCC cells growth than either drug alone. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. In the combination treatment using capsaicin and sorafenib, increased apoptosis, followed by the activation of caspase-9 and PARP, was observed. In addition, the present study demonstrated that sorafenib treatment induces activation of Akt, probably as a mechanism of resistance, whereas capsaicin inhibits Akt providing a possible pathway whereby capsaicin sensitizes to sorafenib in HCC cells. Moreover, capsaicin singly and the combination of capsaicin and sorafenib induce AMPK activation and Acetyl CoA carboxylase phosphorylation in HCC cells. Knocking down of AMPK by selective siRNA abrogates capsaicin-induced Akt inhibition, suggesting the involvement of AMPK in the antiproliferative effect. In vivo experiments further showed that that the anti-tumor effect of sorafenib was enhanced by its combination with 2.5 mg/Kg of capsaicin. Overall, these results show that combined treatment with capsaicin and sorafenib might improve sorafenib sensitivity and therefore it represents a promising and attractive strategy for the treatment of HCC.

  10. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation.

    Science.gov (United States)

    Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra; Estevez-Braun, Ana; de las Heras, Beatriz; Hortelano, Sonsoles

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE(2) production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE(2) in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro.

    Science.gov (United States)

    Krychtiuk, Konstantin A; Watzke, Lukas; Kaun, Christoph; Buchberger, Elisabeth; Hofer-Warbinek, Renate; Demyanets, Svitlana; Pisoni, Julia; Kastl, Stefan P; Rauscher, Sabine; Gröger, Marion; Aliabadi, Arezu; Zuckermann, Andreas; Maurer, Gerald; de Martin, Rainer; Huber, Kurt; Wojta, Johann; Speidl, Walter S

    2015-02-01

    Levosimendan is a positive inotropic drug for the treatment of acute decompensated heart failure (HF). Clinical trials showed that levosimendan was particularly effective in HF due to myocardial infarction. Myocardial necrosis induces a strong inflammatory response, involving chemoattractants guiding polymorphonuclear neutrophils (PMN) into the infarcted myocardial tissue. Our aim was to examine whether levosimendan exhibits anti-inflammatory effects on human adult cardiac myocytes (HACM) and human heart microvascular endothelial cells (HHMEC). Cardiac myocytes and endothelial cells were stimulated with interleukin-1β (IL)-1β (200 U/ml) and treated with levosimendan (0.1-10 µM) for 2-48 hours. IL-1β strongly induced expression of IL-6 and IL-8 in HACM and E-selectin and intercellular adhesion molecule-1 (ICAM-1) in HHMEC and human umbilical vein endothelial cells (HUVEC). Treatment with levosimendan strongly attenuated IL-1β-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs. Levosimendan treatment further reduced adhesion of PMN to activated endothelial cells under both static and flow conditions by approximately 50 %. Incubation with 5-hydroxydecanoic acid, a selective blocker of mitochondrial ATP-dependent potassium channels, partly abolished the above seen anti-inflammatory effects. Additionally, levosimendan strongly diminished IL-1β-induced reactive oxygen species and nuclear factor-κB (NF-κB) activity through inhibition of S536 phosphorylation. In conclusion, levosimendan exhibits anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. These findings could explain, at least in part, the beneficial effects of levosimendan after myocardial infarction.

  12. Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain.

    Science.gov (United States)

    Hao, Wei; Chen, Lei; Wu, Li-Fang; Yang, Fan; Niu, Jian-Xiang; Kaye, Alan D; Xu, Shi-Yuan

    2016-01-01

    Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). To assess the antinociceptive effect of TSN IIA on CIBP. A randomized, double-blind, controlled animal trial was performed. University lab in China. A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain

  13. Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes.

    Directory of Open Access Journals (Sweden)

    Arturo Bravo-Nuevo

    Full Text Available Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129 administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications.

  14. The KCNE1 beta-subunit exerts a transient effect on the KCNQ1 K+ channel

    DEFF Research Database (Denmark)

    Poulsen, Asser Nyander; Klærke, Dan Arne

    2007-01-01

      The KCNE1 beta-subunit is a modulatory one-trans-membrane segment accessory protein that alters KCNQ1 K(+) channel current characteristics, though it is not required for channel expression. The KCNE1 and KCNQ1 interaction was investigated by looking for effects of expression time on channel...... currents in Xenopus laevis oocytes. We found that long-time expression of KCNQ1+KCNE1 (2-14 days) resulted in gradual changes in current characteristics resembling a disappearance of KCNE1 from the oocyte plasma membrane. Towards the end of the expression period the current of oocytes expressing KCNQ1+KCNE......1 was indistinguishable from those expressing KCNQ1 alone. No time dependent effect was seen in oocytes expressing KCNQ1 alone or a concatamer of KCNQ1 and KCNE1. Brefeldin A was tested, showing that measured current was independent of exocytosis (decreased capacitance) thus eliminating a continuous...

  15. Calcitriol exerts an anti-tumor effect in osteosarcoma by inducing the endoplasmic reticulum stress response.

    Science.gov (United States)

    Shimizu, Takatsune; Kamel, Walied A; Yamaguchi-Iwai, Sayaka; Fukuchi, Yumi; Muto, Akihiro; Saya, Hideyuki

    2017-09-01

    Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of Food and Drug Administration (FDA)-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS). Knockdown of Atf4 or Ddit3 restored cell viability after calcitriol treatment, indicating that the ER stress response was indeed responsible for the anti-proliferative effect in AXT cells. Notably, the ER stress response was induced to a lesser extent in human osteosarcoma than in AXT cells, consistent with the weaker suppressive effect on cell growth in the human cells. Thus, the magnitude of ER stress induced by calcitriol might be an index of its anti-osteosarcoma effect. Although mice treated with calcitriol exhibited weight loss and elevated serum calcium levels, a single dose was sufficient to decrease osteosarcoma tumor size in vivo. Our findings suggest that calcitriol holds therapeutic potential for treatment of osteosarcoma, assuming that techniques to diminish its toxicity could be established. In addition, our results show that calcitriol could still be safely administered to osteosarcoma patients for its original purposes, including treatment of osteoporosis. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. Sedum sarmentosum Bunge extract exerts renal anti-fibrotic effects in vivo and in vitro.

    Science.gov (United States)

    Bai, Yongheng; Lu, Hong; Zhang, Ge; Wu, Cunzao; Lin, Chengcheng; Liang, Yong; Chen, Bicheng

    2014-06-06

    Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on renal tissues. We investigated the effects of SSBE on aristolochic acid (AA)-induced injury to renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to-mesenchymal transition (EMT) and the accumulation of extracellular matrix (ECM) components. Furthermore, we examined the expression levels of TGF-β1 and its receptor. In cultured RTECs (NRK-52E), AA promoted renal EMT and ECM accumulation by up-regulating the expression of mesenchymal markers and ECM components and by down-regulating the expression of epithelial markers. In addition, AA induced an imbalance between MMP-2 and TIMP-2 and enhanced expression of TGF-β1 and its receptor. SSBE treatment significantly inhibited AA-induced TGF-β1 expression and prevented the induction of EMT and deposition of ECM. In the UUO rats, tubular injury and interstitial fibrosis were obviously increased. SSBE administration protected renal function, as indicated by reduced serum creatinine levels, and alleviated renal interstitial fibrosis. These anti-fibrotic effects were associated with a reduction in TGF-β1 expression and inhibition of EMT and ECM accumulation. These findings suggest that SSBE may have therapeutic potential for fibrotic kidney diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  18. Bixa orellana (annatto) exerts a sustained hypoglycemic effect in experimental diabetes mellitus in rats

    OpenAIRE

    Teles,Flávio; Anjos, Felipe Silveira dos; Machado, Tarcilo; Lima, Roberta

    2014-01-01

    OBJECTIVE: Bixa orellana (annatto) is a natural pigment and food colorant that has been used for a variety of therapeutic purposes. It has been suggested that annatto could have the property of reducing blood glucose levels. However, most previous studies have demonstrated a hypoglycemic effect in non-diabetic animals. We evaluated the impact of annatto on blood glucose levels in an experimental model of diabetes mellitus. METHOD: Male Wistar rats were made diabetic by a single dose of60 mg/...

  19. Imatinib mesylate inhibits proliferation and exerts an antifibrotic effect in human breast stroma fibroblasts.

    Science.gov (United States)

    Gioni, Vassiliki; Karampinas, Theodoros; Voutsinas, Gerassimos; Roussidis, Andreas E; Papadopoulos, Savvas; Karamanos, Nikos K; Kletsas, Dimitris

    2008-05-01

    Tumor stroma plays an important role in cancer development. In a variety of tumors, such as breast carcinomas, a desmoplastic response, characterized by stromal fibroblast and collagen accumulation, is observed having synergistic effects on tumor progression. However, the effect of known anticancer drugs on stromal cells has not been thoroughly investigated. Imatinib mesylate is a selective inhibitor of several protein tyrosine kinases, including the receptor of platelet-derived growth factor, an important mediator of desmoplasia. Recently, we have shown that imatinib inhibits the growth and invasiveness of human epithelial breast cancer cells. Here, we studied the effect of imatinib on the proliferation and collagen accumulation in breast stromal fibroblasts. We have shown that it blocks the activation of the extracellular signal-regulated kinase and Akt signaling pathways and up-regulates cyclin-dependent kinase inhibitor p21(WAF1), leading to the inhibition of fibroblast proliferation, by arresting them at the G(0)/G(1) phase of the cell cycle. Imatinib inhibits more potently the platelet-derived growth factor-mediated stimulation of breast fibroblast proliferation. By using specific inhibitors, we have found that this is due to the inhibition of the Akt pathway. In addition, imatinib inhibits fibroblast-mediated collagen accumulation. Conventional and quantitative PCR analysis, as well as gelatin zymography, indicates that this is due to the down-regulation of mRNA synthesis of collagen I and collagen III-the main collagen types in breast stroma-and not to the up-regulation or activation of collagenases matrix metalloproteinase 2 and matrix metalloproteinase 9. These data indicate that imatinib has an antifibrotic effect on human breast stromal fibroblasts that may inhibit desmoplastic reaction and thus tumor progression.

  20. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    Energy Technology Data Exchange (ETDEWEB)

    Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  1. Polysulfide exerts a protective effect against cytotoxicity caused by t-buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells.

    Science.gov (United States)

    Koike, Shin; Ogasawara, Yuki; Shibuya, Norihiro; Kimura, Hideo; Ishii, Kazuyuki

    2013-11-01

    Polysulfide is a bound sulfur species derived from endogenous H2S. When mouse neuroblastoma, Neuro2A cells were exposed to tert-butyl hydroperoxide after treatment with polysulfide, a significant decline in cell toxicity was observed. Rapid uptake of polysulfides induced translocation of Nrf2 into the nucleus, resulting in acceleration of GSH synthesis and HO-1 expression. We demonstrated that polysulfide reversibly modified Keap1 to form oxidized dimers and induced the translocation of Nrf2. Moreover, polysulfide treatment accelerated Akt phosphorylation, which is a known pathway of Nrf2 phosphorylation. Thus, polysulfide may mediate the activation of Nrf2 signaling, thereby exerting protective effects against oxidative damage in Neuro2A cells. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Capparis spinosa Fruit Ethanol Extracts Exert Different Effects on the Maturation of Dendritic Cells

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    Azeguli Hamuti

    2017-01-01

    Full Text Available Capparis spinosa L. (C. spinosa has been used as food and traditional medicine and shows anti-inflammatory and anti-oxidant activities. Here, we prepared the C. spinosa fruit ethanol extracts (CSEs using different procedures and investigated the effects of CSE on the maturation of mouse bone marrow-derived dendritic cells (DCs in the absence or presence of lipopolysaccharide (LPS. DC maturation and cytokine production were detected by flow cytometry and ELISA, respectively. We obtained three different CSEs and dissolved in water or DMSO, named CSE2W, CSEMW, CSE3W, CSE2D, CSEMD, and CSE3D, respectively. These CSEs showed different effects on DC maturation. CSEMW and CSEMD significantly increased the expressions of CD40, CD80, and CD86, in a dose-dependent manner. CSE2W and CSE2D also showed a modest effect on DC maturation, which enhanced the expression of CD40. CSE3W and CSE3D did not change DC maturation but suppressed LPS-induced DC maturation characterized by the decreased levels of CD40 and CD80. CSE3W and CSE3D also significantly inhibited the secretions of IL-12p40, IL-6, IL-1β, and TNF-α induced by LPS. CSE3W further increased the level of IL-10 induced by LPS. Moreover, CSE3D suppressed LPS-induced DC maturation in vivo, which decreased the expressions of CD40 and CD80. These results suggested that CSE3W and CSE3D might be used to treat inflammatory diseases.

  3. Capparis spinosa Fruit Ethanol Extracts Exert Different Effects on the Maturation of Dendritic Cells.

    Science.gov (United States)

    Hamuti, Azeguli; Li, Jinyu; Zhou, Fangfang; Aipire, Adila; Ma, Ji; Yang, Jianhua; Li, Jinyao

    2017-01-07

    Capparis spinosa L. (C. spinosa) has been used as food and traditional medicine and shows anti-inflammatory and anti-oxidant activities. Here, we prepared the C. spinosa fruit ethanol extracts (CSEs) using different procedures and investigated the effects of CSE on the maturation of mouse bone marrow-derived dendritic cells (DCs) in the absence or presence of lipopolysaccharide (LPS). DC maturation and cytokine production were detected by flow cytometry and ELISA, respectively. We obtained three different CSEs and dissolved in water or DMSO, named CSE2W, CSEMW, CSE3W, CSE2D, CSEMD, and CSE3D, respectively. These CSEs showed different effects on DC maturation. CSEMW and CSEMD significantly increased the expressions of CD40, CD80, and CD86, in a dose-dependent manner. CSE2W and CSE2D also showed a modest effect on DC maturation, which enhanced the expression of CD40. CSE3W and CSE3D did not change DC maturation but suppressed LPS-induced DC maturation characterized by the decreased levels of CD40 and CD80. CSE3W and CSE3D also significantly inhibited the secretions of IL-12p40, IL-6, IL-1β, and TNF-α induced by LPS. CSE3W further increased the level of IL-10 induced by LPS. Moreover, CSE3D suppressed LPS-induced DC maturation in vivo, which decreased the expressions of CD40 and CD80. These results suggested that CSE3W and CSE3D might be used to treat inflammatory diseases.

  4. Ginger and Propolis Exert Neuroprotective Effects against Monosodium Glutamate-Induced Neurotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Usama K. Hussein

    2017-11-01

    Full Text Available Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage. Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight of either ginger or propolis (600 mg/kg body weight once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and β-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products.

  5. Epigeic earthworms exert a bottleneck effect on microbial communities through gut associated processes.

    Directory of Open Access Journals (Sweden)

    María Gómez-Brandón

    Full Text Available BACKGROUND: Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei is capable of altering the microbiological properties of fresh organic matter through gut associated processes; and if these direct effects are related to the earthworm diet. METHODOLOGY: To address these questions we determined the microbial community structure (phospholipid fatty acid profiles and microbial activity (fluorescein diacetate hydrolysis in the earthworm casts derived from three types of animal manure (cow, horse and pig manure, which differed in microbial composition. PRINCIPAL FINDINGS: The passage of the organic material through the gut of E. andrei reduced the total microbial biomass irrespective of the type of manure, and resulted in a decrease in bacterial biomass in all the manures; whilst leaving the fungi unaffected in the egested materials. However, unlike the microbial biomass, no such reduction was detected in the total microbial activity of cast samples derived from the pig manure. Moreover, no differences were found between cast samples derived from the different types of manure with regards to microbial community structure, which provides strong evidence for a bottleneck effect of worm digestion on microbial populations of the original material consumed. CONCLUSIONS/SIGNIFICANCE: Our data reveal that earthworm gut is a major shaper of microbial communities, thereby favouring the existence of a reduced but more active microbial population in the egested materials, which is of great importance to understand how biotic interactions

  6. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects.

    Science.gov (United States)

    Zhong, Jianxiang; Reece, E Albert; Yang, Peixin

    2015-11-13

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 h with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 μM punicalagin. 10 μM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 μM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetes-induced NTDs. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Maria Simona Aguzzi

    Full Text Available Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field.

  8. TR alpha 2 exerts dominant negative effects on hypothalamic Trh transcription in vivo.

    Science.gov (United States)

    Guissouma, Hajer; Ghaddab-Zroud, Rym; Seugnet, Isabelle; Decherf, Stéphanie; Demeneix, Barbara; Clerget-Froidevaux, Marie-Stéphanie

    2014-01-01

    Mammalian thyroid hormone receptors (TRs) have multiple isoforms, including the bona fide receptors that bind T3 (TRα1, TRβ1 and TRβ2) and a non-hormone-binding variant, TRα2. Intriguingly, TRα2 is strongly expressed in the brain, where its mRNA levels exceed those of functional TRs. Ablation of TRα2 in mice results in over-expression of TRα1, and a complex phenotype with low levels of free T3 and T4, without elevated TSH levels, suggesting an alteration in the negative feedback at the hypothalamic-pituitary level. As the hypothesis of a potential TRH response defect has never been tested, we explored the functional role of TRα2 in negative feedback on transcription of hypothalamic thyrotropin, Trh. The in vivo transcriptional effects of TRα2 on hypothalamic Trh were analysed using an in vivo reporter gene approach. Effects on Trh-luc expression were examined to that of two, T3 positively regulated genes used as controls. Applying in vivo gene transfer showed that TRα2 over-expression in the mouse hypothαlamus abrogates T3-dependent repression of Trh and T3 activation of positively regulated promoters, blocking their physiological regulation. Surprisingly, loss of function studies carried out by introducing a shTRα2 construct in the hypothalamus also blocked physiological T3 dependent regulation. Thus, modulating hypothalamic TRα2 expression by either gain or loss of function abrogated T3 dependent regulation of Trh transcription, producing constant transcriptional levels insensitive to feedback. This loss of physiological regulation was reflected at the level of the endogenous Trh gene, were gain or loss of function held mRNA levels constant. These results reveal the as yet undescribed dominant negative role of TRα2 over TRα1 effect on hypothalamic Trh transcription.

  9. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages.

    Science.gov (United States)

    Talmon, Maria; Rossi, Silvia; Pastore, Anna; Cattaneo, Carlo Ignazio; Brunelleschi, Sandra; Fresu, Luigia Grazia

    2018-01-01

    A crosstalk between the immune system and depression has been postulated, with monocytes/macrophages and cytokines having a key role in this interaction. In this study, we examined whether vortioxetine, a multimodal anti-depressive drug, was endowed with anti-inflammatory and antioxidative activity, leading to immunomodulatory effects on human monocytes and macrophages. Human monocytes were isolated from buffy coats and used as such or differentiated into M1 and M2 macrophages. Cells were treated with vortioxetine before or after differentiation, and their responsiveness was evaluated. This included oxy-radical and TNFα production, TNFα and PPARγ gene expression and NF-κB translocation. Vortioxetine significantly reduced the PMA-induced oxidative burst in monocytes and in macrophages (M1 and M2), causing a concomitant shift of macrophages from the M1 to the M2 phenotype, demonstrated by a significant decrease in the expression of the surface marker CD86 and an increase in CD206. Moreover, treatment of monocytes with vortioxetine rendered macrophages derived from this population less sensitive to PMA, as it reduced the oxidative burst, NF-kB translocation, TNFα release and expression while inducing PPARγ gene expression. FACS analysis showed a significant decrease in the CD14+ /CD16+ /CD86+ M1 population. These results demonstrate that in human monocytes/macrophages, vortioxetine has antioxidant activity and anti-inflammatory effects driving the polarization of macrophages towards their alternative phenotype. These findings suggest that vortioxetine, alongside its antidepressive effect, may have immunomodulatory properties. © 2017 The British Pharmacological Society.

  10. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  11. Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture effects in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Pedersen, Mikael; Skov, Kasper

    2016-01-01

    pituitary-adrenal axis. In conclusion, our data suggest that mixtures of environmental chemicals at doses approaching high-end human exposure levels can cause a hormonal imbalance and disturb steroid hormones and their regulation. These effects may be non-monotonic and were observed at low doses. Whether......) at doses of 0.0125 (Low PFNA), 0.25 (Mid PFNA) and 5 (High PFNA) mg/kg bw/day by oral administration for 14 days in juvenile male rats. Indication of a toxicokinetic interaction was found, as simultaneous exposure to PFNA and the Mix caused a 2.8-fold increase in plasma PFNA concentrations at Low PFNA...

  12. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

    Science.gov (United States)

    Ma, Xian-Cang; Chu, Zheng; Zhang, Xiao-Ling; Jiang, Wen-Hui; Jia, Min; Dang, Yong-Hui; Gao, Cheng-Ge

    2016-06-01

    The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

  13. Garlic exerts allelopathic effects on pepper physiology in a hydroponic co-culture system

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    Haiyan Ding

    2016-05-01

    Full Text Available A hydroponic co-culture system was adopted to determine the allelopathic potential of garlic on the growth of pepper plants. Different numbers of garlic plants (0, 2, 4, 8 and 12 were hydroponically co-cultured with two pepper plants to investigate allelopathic effects on the growth attributes and antioxidative defense system of the test pepper plants. The responses of the pepper plants depended on the number of garlic plants included in the co-culture system, indicating an association of pepper growth with the garlic root exudate concentration. When grown at a pepper/garlic ratio of 1:1 or 1:2, the pepper plant height, chlorophyll content, and peroxidase (POD, catalase (CAT and phenylalanine ammonia-lyase (PAL activities were significantly increased after 30 days of co-culture; in contrast, reduction in methane dicarboxylic aldehyde (MDA content was observed. However, when the pepper/garlic ratio was 1:4 or higher, these morphological indices and protective enzyme activities were significantly inhibited, whereas MDA levels in the pepper leaves were significantly increased due to severe membrane lipid peroxidation. The results indicate that although low concentrations of garlic root exudates appear to induce protective enzyme systems and promote pepper growth, high concentrations have deleterious effects. These findings suggest that further investigations should optimize the co-culture pepper/garlic ratio to reduce continuous cropping obstacles in pepper production.

  14. Piperine exerts anti-seizure effects via the TRPV1 receptor in mice.

    Science.gov (United States)

    Chen, Chang-Yuan; Li, Wen; Qu, Kun-Peng; Chen, Chang-Rui

    2013-08-15

    The mechanisms involved in the anti-seizure property of piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]-(E,E)-piperidine, C17H19NO3) are still unclear. Piperine could activate transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, and the rapid activation of whole-cell currents is antagonized by the competitive TRPV1 antagonist capsazepine. Interestingly, recent studies have reported that TRPV1 may be a novel anti-epileptogenic target which led us to hypothesize that the anti-seizure property of piperine involves the TRPV1 receptor. To test this hypothesis, we examined the effect of piperine on seizures induced in mice and identified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) models. Piperine, administered at doses of 40 and 80 mg/kg, significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with the vehicle-treated animals. Piperine also significantly reduced the incidence of MES-induced tonic hindlimb extension (THE) and PTZ-induced Fos immunoreactivity in the dentate gyrus. The anti-seizure effects of piperine were blocked by a TRPV1-selective antagonist capsazepine. Taken together, these data support the further investigation of piperine as a TRPV1 agonist for anti-seizure therapy. © 2013 Elsevier B.V. All rights reserved.

  15. Plant Identity Exerts Stronger Effect than Fertilization on Soil Arbuscular Mycorrhizal Fungi in a Sown Pasture.

    Science.gov (United States)

    Zheng, Yong; Chen, Liang; Luo, Cai-Yun; Zhang, Zhen-Hua; Wang, Shi-Ping; Guo, Liang-Dong

    2016-10-01

    Arbuscular mycorrhizal (AM) fungi play key roles in plant nutrition and plant productivity. AM fungal responses to either plant identity or fertilization have been investigated. However, the interactive effects of different plant species and fertilizer types on these symbiotic fungi remain poorly understood. We evaluated the effects of the factorial combinations of plant identity (grasses Avena sativa and Elymus nutans and legume Vicia sativa) and fertilization (urea and sheep manure) on AM fungi following 2-year monocultures in a sown pasture field study. AM fungal extraradical hyphal density was significantly higher in E. nutans than that in A. sativa and V. sativa in the unfertilized control and was significantly increased by urea and manure in A. sativa and by manure only in E. nutans, but not by either fertilizers in V. sativa. AM fungal spore density was not significantly affected by plant identity or fertilization. Forty-eight operational taxonomic units (OTUs) of AM fungi were obtained through 454 pyrosequencing of 18S rDNA. The OTU richness and Shannon diversity index of AM fungi were significantly higher in E. nutans than those in V. sativa and/or A. sativa, but not significantly affected by any fertilizer in all of the three plant species. AM fungal community composition was significantly structured directly by plant identity only and indirectly by both urea addition and plant identity through soil total nitrogen content. Our findings highlight that plant identity has stronger influence than fertilization on belowground AM fungal community in this converted pastureland from an alpine meadow.

  16. Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

    Science.gov (United States)

    Wimmer, R; Hohenester, S; Pusl, T; Denk, G U; Rust, C; Beuers, U

    2008-10-01

    Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKC alpha agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKC alpha-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. In livers treated with TLCA (10 micromol/l)+TUDCA (25 micromol/l), combined inhibition of cPKC by the cPKC-selective inhibitor Gö6976 (100 nmol/l) or the non-selective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (pTLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKC alpha, nPKC epsilon, and PKA, respectively, in a staurosporine-sensitive manner. UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKC alpha-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.

  17. Ocean acidification exerts negative effects during warming conditions in a developing Antarctic fish.

    Science.gov (United States)

    Flynn, Erin E; Bjelde, Brittany E; Miller, Nathan A; Todgham, Anne E

    2015-01-01

    Anthropogenic CO2 is rapidly causing oceans to become warmer and more acidic, challenging marine ectotherms to respond to simultaneous changes in their environment. While recent work has highlighted that marine fishes, particularly during early development, can be vulnerable to ocean acidification, we lack an understanding of how life-history strategies, ecosystems and concurrent ocean warming interplay with interspecific susceptibility. To address the effects of multiple ocean changes on cold-adapted, slowly developing fishes, we investigated the interactive effects of elevated partial pressure of carbon dioxide (pCO2) and temperature on the embryonic physiology of an Antarctic dragonfish (Gymnodraco acuticeps), with protracted embryogenesis (∼10 months). Using an integrative, experimental approach, our research examined the impacts of near-future warming [-1 (ambient) and 2°C (+3°C)] and ocean acidification [420 (ambient), 650 (moderate) and 1000 μatm pCO2 (high)] on survival, development and metabolic processes over the course of 3 weeks in early development. In the presence of increased pCO2 alone, embryonic mortality did not increase, with greatest overall survival at the highest pCO2. Furthermore, embryos were significantly more likely to be at a later developmental stage at high pCO2 by 3 weeks relative to ambient pCO2. However, in combined warming and ocean acidification scenarios, dragonfish embryos experienced a dose-dependent, synergistic decrease in survival and developed more slowly. We also found significant interactions between temperature, pCO2 and time in aerobic enzyme activity (citrate synthase). Increased temperature alone increased whole-organism metabolic rate (O2 consumption) and developmental rate and slightly decreased osmolality at the cost of increased mortality. Our findings suggest that developing dragonfish are more sensitive to ocean warming and may experience negative physiological effects of ocean acidification only in

  18. Ethanol-extracted Cameroonian propolis exerts estrogenic effects and alleviates hot flushes in ovariectomized Wistar rats.

    Science.gov (United States)

    Zingue, Stéphane; Nde, Chantal Beatrice Magne; Michel, Thomas; Ndinteh, Derek Tantoh; Tchatchou, Jules; Adamou, Moïse; Fernandez, Xavier; Fohouo, Fernand-Nestor Tchuenguem; Clyne, Colin; Njamen, Dieudonné

    2017-01-21

    Since the biological properties of propolis depend to the plants that can be found in a specific region, propolis from unexplored regions attracts the attention of scientists. Ethanolic extract of Cameroonian propolis (EEP) is used to treat various ailments including gynecological problems and amenorrhea. Since there were no scientific data to support the above claims, the present study was therefore undertaken to assess estrogenic properties of Cameroonian propolis. To achieve our goal, the ability of EEP to induce MCF-7 cells proliferation in E-screen assay as well as to activate estrogen receptors α (ERα) and β (ERβ) in cell-based reporter gene assays using human embryonic kidney cells (HEK293T) transfected with ERs was tested. Further, a 3-day uterotrophic assay was performed and the ability of EEP to alleviate hot flushes in ovariectomized adult rats was evaluated. In vitro, EEP showed an antiestrogenic activity in both HEK293T ER-α and ER-β cells. In vivo, EEP induced a significant increase in a bell shape dose response manner of the uterine wet weight, the total protein levels in the uterus, the uterine and vaginal epithelium height and acini border cells of mammary gland with the presence of abundant eosinophil secretions. Moreover, EEP induced a significant decrease in the total number, average duration as well as frequency of hot flushes after 3 days of treatment in rat (equivalent to a month in woman). The dose of 150 mg/kg exhibited the most potent estrogenic effects among all the tested doses. The UPLC-HRMS analysis showed the presence of caffeic acid derivatives and trirtepernoids in EEP, which are well known endowed with estrogenic properties. These results suggest that Ethanolic extract of Cameroonian propolis has estrogen-like effects in vivo and may alleviate some menopausal problems such as vaginal dryness and hot flushes. Ethanol-extracted Cameroobian propolis exhibited in vitro and in vivo estrogen-like effects. This extract may contain

  19. Exertional Heat Injury: Effects of Adding Cold (4°C) Intravenous Saline to Prehospital Protocol.

    Science.gov (United States)

    Mok, Gordon; DeGroot, David; Hathaway, Nathanael E; Bigley, Daniel P; McGuire, Christopher S

    This article reviews current prehospital treatment for heat casualties and introduces a retrospective study on the addition of cold (4 °C) intravenous (IV) saline to prehospital treatment and its effect on morbidity. The study is a retrospective cohort reviewing electronic medical records of 290 heat casualties admitted to Martin Army Community Hospital, Ft. Benning, GA, comparing two treatment groups; U.S. Army Training and Doctrine Command (ice-sheeting and ambient temperature IV saline) versus Benning (ice-sheeting and cold IV saline). U.S. Army Training and Doctrine Command group significantly differed from Benning group on a number of measures, the median length of stay in the hospital was 3 and 2 d, respectively (P cold IV saline to ice-sheeting as a protocol reduces the length of hospitalization of heat casualties and lowers their peak creatinine values.

  20. High Hydrostatic Pressure Extract of Ginger Exerts Antistress Effects in Immobilization-Stressed Rats.

    Science.gov (United States)

    Moon, Sohee; Lee, Mak-Soon; Jung, Sunyoon; Kang, Bori; Kim, Seog-Young; Park, Seonyoung; Son, Hye-Yeon; Kim, Chong-Tai; Jo, Young-Hee; Kim, In-Hwan; Kim, Young Soon; Kim, Yangha

    2017-09-01

    Stress contributes to physiological changes such as weight loss and hormonal imbalances. The aim of the present study was to investigate antistress effects of high hydrostatic pressure extract of ginger (HPG) in immobilization-stressed rats. Male Sprague-Dawley rats (n = 24) were divided into three groups as follows: control (C), immobilization stress (2 h daily, for 2 weeks) (S), and immobilization stress (2 h daily, for 2 weeks) plus oral administration of HPG (150 mg/kg body weight/day) (S+G). Immobilization stress reduced the body weight gain and thymus weight by 50.2% and 31.3%, respectively, compared to the control group. The levels of serum aspartate transaminase, alanine transaminase, and corticosterone were significantly higher in the stress group, compared to the control group. Moreover, immobilization stress elevated the mRNA levels of tyrosine hydroxylase (Th), dopamine beta-hydroxylase (Dbh), and cytochrome P450 side-chain cleavage (P450scc), which are related to catecholamine and corticosterone synthesis in the adrenal gland. HPG administration also increased the body weight gain and thymus weight by 12.7% and 16.6%, respectively, compared to the stress group. Furthermore, the mRNA levels of Th, Dbh, phenylethanolamine-N-methyltransferase, and P450scc were elevated by the HPG treatment when compared to the stress group. These results suggest that HPG would have antistress effects partially via the reversal of stress-induced physiological changes and suppression of mRNA expression of genes related to corticosterone and catecholamine synthetic enzymes.

  1. Individual common variants exert weak effects on the risk for autism spectrum disorders

    Science.gov (United States)

    Anney, Richard; Klei, Lambertus; Pinto, Dalila; Almeida, Joana; Bacchelli, Elena; Baird, Gillian; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Casey, Jillian; Conroy, Judith; Correia, Catarina; Corsello, Christina; Crawford, Emily L.; de Jonge, Maretha; Delorme, Richard; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Green, Andrew; Green, Jonathan; Guter, Stephen J.; Heron, Elizabeth A.; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Jacob, Suma; Kenny, Graham P.; Kim, Cecilia; Kolevzon, Alexander; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Law-Smith, Miriam; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Liu, Xiao-Qing; Lombard, Frances; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Magalhaes, Tiago R.; Mantoulan, Carine; McDougle, Christopher J.; Melhem, Nadine M.; Merikangas, Alison; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Noakes, Carolyn; Nygren, Gudrun; Papanikolaou, Katerina; Pagnamenta, Alistair T.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Posey, David J.; Poustka, Fritz; Ragoussis, Jiannis; Regan, Regina; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Schlitt, Sabine; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Sykes, Nuala; Tancredi, Raffaella; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Vorstman, JAS; Wallace, Simon; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Bailey, Anthony J.; Battaglia, Agatino; Cantor, Rita M.; Coon, Hilary; Cuccaro, Michael L.; Dawson, Geraldine; Ennis, Sean; Freitag, Christine M.; Geschwind, Daniel H.; Haines, Jonathan L.; Klauck, Sabine M.; McMahon, William M.; Maestrini, Elena; Miller, Judith; Monaco, Anthony P.; Nelson, Stanley F.; Nurnberger, John I.; Oliveira, Guiomar; Parr, Jeremy R.; Pericak-Vance, Margaret A.; Piven, Joseph; Schellenberg, Gerard D.; Scherer, Stephen W.; Vicente, Astrid M.; Wassink, Thomas H.; Wijsman, Ellen M.; Betancur, Catalina; Buxbaum, Joseph D.; Cook, Edwin H.; Gallagher, Louise; Gill, Michael; Hallmayer, Joachim; Paterson, Andrew D.; Sutcliffe, James S.; Szatmari, Peter; Vieland, Veronica J.; Hakonarson, Hakon; Devlin, Bernie

    2012-01-01

    While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest. PMID:22843504

  2. Lutein exerts anti-inflammatory effects in patients with coronary artery disease.

    Science.gov (United States)

    Chung, Rosanna W S; Leanderson, Per; Lundberg, Anna K; Jonasson, Lena

    2017-07-01

    Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients. Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media. Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Fermentation metabolites from Lactobacillus gasseri and Propionibacterium freudenreichii exert bacteriocidal effects in mice.

    Science.gov (United States)

    Kato-Mori, Yuko; Orihashi, Takenori; Kanai, Yuta; Sato, Michiko; Sera, Kenji; Hagiwara, Katsuro

    2010-12-01

    Lactobacillus gasseri OLL 2716 promotes the elimination of Helicobacter pylori and is utilized in yogurts that are specifically labeled as health foods. On the other hand, milk whey fermented by Propionibacterium freudenreichii ET-3, which increases the numbers of Bifidobacterium, is effective for intestinal disorders. We previously demonstrated that oral administration of L. gasseri and P. freudenreichii fermentation metabolites (LP-FM) improved calf intestinal microflora and reduced the incidence of diarrhea. However, the detailed immunological mechanisms responsible for these effects remain to be fully understood. In this study, we investigated whether LP-FM stimulates the innate immune response and promotes the elimination of Listeria monocytogenes in mice. The C57BL/6 female mice that were treated with LP-FM or L. gasseri fermentation metabolites alone for 4 weeks had more peripheral white blood cells than the untreated control mice. In particular, LP-FM-treated mice had higher CD4- and CD8-positive T-cell counts. The levels of reactive oxygen and nitrogen species produced by peritoneal macrophages were also higher in LP-FM-treated mice. Furthermore, LP-FM-treated mice that were infected with L. monocytogenes exhibited significant enhancement of the elimination of Listeria from the spleen and the liver in comparison with untreated control mice infected with Listeria. The activation of innate immunity by LP-FM was increased by the combination of fermentation metabolites from P. freudenreichii. These results suggest that LP-FM, which contains metabolites from L. gasseri and P. freudenreichii, stimulates the function of the innate immune system, thereby significantly promoting the elimination of L. monocytogenes in mice.

  4. Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

    Science.gov (United States)

    Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

    2017-11-01

    Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

  5. Lactoferrin Exerts Antitumor Effects by Inhibiting Angiogenesis in a HT29 Human Colon Tumor Model.

    Science.gov (United States)

    Li, Hui-Ying; Li, Ming; Luo, Chao-Chao; Wang, Jia-Qi; Zheng, Nan

    2017-12-06

    To investigate the effect and potential mechanisms of lactoferrin on colon cancer cells and tumors, HT29 and HCT8 cells were exposed to varying concentrations of lactoferrin, and the impacts on cell proliferation, migration, and invasion were observed. Cell proliferation test showed that high dosage of lactoferrin (5-100 mg/mL) inhibited cell viability in a dose-dependent manner, with the 50% concentration of inhibition at 81.3 ± 16.7 mg/mL and 101 ± 23.8 mg/mL for HT29 and HCT8 cells, respectively. Interestingly, migration and invasion of the cells were inhibited dramatically by 20 mg/mL lactoferrin, consistent with the significant down regulation of VEGFR2, VEGFA, pPI3K, pAkt, and pErk1/2 proteins. HT29 was chosen as the sensitive cell line to construct a tumor-bearing nude mice model. Notably, HT29 tumor weight was greatly reduced in both the lactoferrin group (26.5 ± 6.7 mg) and the lactoferrin/5-Fu group (14.5 ± 5.1 mg), compared with the control one (39.3 ± 6.5 mg), indicating that lactoferrin functioned as a tumor growth inhibitor. Considering lactoferrin also reduced the growth of blood vessels and the degree of malignancy, we concluded that HT29 tumors were effectively suppressed by lactoferrin, which might be achieved by regulation of phosphorylation from various kinases and activation of the VEGFR2-PI3K/Akt-Erk1/2 pathway.

  6. Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function.

    Directory of Open Access Journals (Sweden)

    Javier R Ambrosio

    Full Text Available The effects of testosterone (T4 and dihydrotestosterone (DHT on the survival of the helminth cestode parasite Taenia crassiceps, as well as their effects on actin, tubulin and myosin expression and their assembly into the excretory system of flame cells are described in this paper. In vitro evaluations on parasite viability, flow cytometry, confocal microscopy, video-microscopy of live flame cells, and docking experiments of androgens interacting with actin, tubulin, and myosin were conducted. Our results show that T4 and DHT reduce T. crassiceps viability in a dose- and time-dependent fashion, reaching 90% of mortality at the highest dose used (40 ng/ml and time exposed (10 days in culture. Androgen treatment does not induce differences in the specific expression pattern of actin, tubulin, and myosin isoforms as compared with control parasites. Confocal microscopy demonstrated a strong disruption of the parasite tegument, with reduced assembly, shape, and motion of flame cells. Docking experiments show that androgens are capable of affecting parasite survival and flame cell morphology by directly interacting with actin, tubulin and myosin without altering their protein expression pattern. We show that both T4 and DHT are able to bind actin, tubulin, and myosin affecting their assembly and causing parasite intoxication due to impairment of flame cell function. Live flame cell video microscopy showing a reduced motion as well changes in the shape of flame cells are also shown. In summary, T4 and DHT directly act on T. crassiceps cysticerci through altering parasite survival as well as the assembly and function of flame cells.

  7. Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function

    Science.gov (United States)

    Ambrosio, Javier R.; Valverde-Islas, Laura; Nava-Castro, Karen E.; Palacios- Arreola, M. Isabel; Ostoa-Saloma, Pedro; Reynoso-Ducoing, Olivia; Escobedo, Galileo; Ruíz-Rosado, Azucena; Dominguez-Ramírez, Lenin; Morales-Montor, Jorge

    2015-01-01

    The effects of testosterone (T4) and dihydrotestosterone (DHT) on the survival of the helminth cestode parasite Taenia crassiceps, as well as their effects on actin, tubulin and myosin expression and their assembly into the excretory system of flame cells are described in this paper. In vitro evaluations on parasite viability, flow cytometry, confocal microscopy, video-microscopy of live flame cells, and docking experiments of androgens interacting with actin, tubulin, and myosin were conducted. Our results show that T4 and DHT reduce T. crassiceps viability in a dose- and time-dependent fashion, reaching 90% of mortality at the highest dose used (40 ng/ml) and time exposed (10 days) in culture. Androgen treatment does not induce differences in the specific expression pattern of actin, tubulin, and myosin isoforms as compared with control parasites. Confocal microscopy demonstrated a strong disruption of the parasite tegument, with reduced assembly, shape, and motion of flame cells. Docking experiments show that androgens are capable of affecting parasite survival and flame cell morphology by directly interacting with actin, tubulin and myosin without altering their protein expression pattern. We show that both T4 and DHT are able to bind actin, tubulin, and myosin affecting their assembly and causing parasite intoxication due to impairment of flame cell function. Live flame cell video microscopy showing a reduced motion as well changes in the shape of flame cells are also shown. In summary, T4 and DHT directly act on T. crassiceps cysticerci through altering parasite survival as well as the assembly and function of flame cells. PMID:26076446

  8. The effect of working position on trunk posture and exertion for routine nursing tasks: an experimental study.

    Science.gov (United States)

    Freitag, Sonja; Seddouki, Rachida; Dulon, Madeleine; Kersten, Jan Felix; Larsson, Tore J; Nienhaus, Albert

    2014-04-01

    To examine the influence of the two following factors on the proportion of time that nurses spend in a forward-bending trunk posture: (i) the bed height during basic care activities at the bedside and (ii) the work method during basic care activities in the bathroom. A further aim was to examine the connection between the proportion of time spent in a forward-bending posture and the perceived exertion. Twelve nurses in a geriatric nursing home each performed a standardized care routine at the bedside and in the bathroom. The CUELA (German abbreviation for 'computer-assisted recording and long-term analysis of musculoskeletal loads') measuring system was used to record all trunk inclinations. Each participant conducted three tests with the bed at different heights (knee height, thigh height, and hip height) and in the bathroom, three tests were performed with different work methods (standing, kneeling, and sitting). After each test, participants rated their perceived exertion on the 15-point Borg scale (6 = no exertion at all and 20 = exhaustion). If the bed was raised from knee to thigh level, the proportion of time spent in an upright position increased by 8.2% points. However, the effect was not significant (P = 0.193). Only when the bed was raised to hip height, there was a significant increase of 19.8% points (reference: thigh level; P = 0.003) and 28.0% points (reference: knee height; P < 0.001). Bathroom tests: compared with the standing work method, the kneeling and sitting work methods led to a significant increase in the proportion of time spent in an upright posture, by 19.4% points (P = 0.003) and 25.7% points (P < 0.001), respectively. The greater the proportion of time spent in an upright position, the lower the Borg rating (P < 0.001) awarded. The higher the proportion of time that nursing personnel work in an upright position, the less strenuous they perceive the work to be. Raising the bed to hip height and using a stool in the bathroom

  9. Inducible and neuronal nitric oxide synthases exert contrasting effects during rat intestinal recovery following fasting.

    Science.gov (United States)

    Ito, Junta; Uchida, Hiroyuki; Machida, Naomi; Ohtake, Kazuo; Saito, Yuki; Kobayashi, Jun

    2017-04-01

    We investigated the effects of endogenous inducible (iNOS) and neuronal nitric oxide synthase on recovery from intestinal mucosal atrophy caused by fasting-induced apoptosis and decreased cell proliferation during refeeding in rats. Rats were divided into five groups, one of which was fed ad libitum, and four of which underwent 72 h of fasting, followed by refeeding for 0, 6, 24, and 48 h, respectively. iNOS and neuronal nitric oxide synthase mRNA and protein levels in jejunal tissues were measured, and mucosal height was histologically evaluated. Apoptotic indices, interferon-γ (IFN-γ) transcription levels, nitrite levels (as a measure of nitric oxide [NO] production),8-hydroxydeoxyguanosine formation (indicating reactive oxygen species [ROS] levels), crypt cell proliferation, and the motility indices (MI) were also estimated. Associations between mucosal height and NOS protein levels were determined using Spearman's rank correlation test. Notably, we observed significant increases in mucosal height and in neuronal nitric oxide synthase mRNA and protein expression as refeeding time increased. Indeed, there was a significant positive correlation between neuronal nitric oxide synthase protein level and mucosal height during the 48-h refeeding period ( r = 0.725, P fasting. Our finding suggests that refeeding likely repairs fasting-induced jejunal atrophy by suppressing iNOS expression and subsequently inhibiting NO, ROS, and IFN-γ as apoptosis mediators, and by promoting neuronal nitric oxide synthase production and inducing crypt cell proliferation via mechanical stimulation. Impact statement Besides providing new data confirming the involvement of iNOS and nNOS in intestinal mucosal atrophy caused by fasting, this study details their expression and function during recovery from this condition following refeeding. We demonstrate a significant negative correlation between iNOS and nNOS levels during refeeding, and associate this with cell proliferation

  10. Growth hormone exerts no effect on the timing of the first zygotic cleavage in cattle.

    Science.gov (United States)

    Pers-Kamczyc, E; Warzych, E; Peippo, J; Lechniak, D

    2010-09-01

    Most of the protocols used for oocyte and embryo quality assessments are invasive and thus reduce embryo viability. Special interest has recently been placed on a search for non-invasive markers related to embryo quality. The characteristics of a non-invasive marker are met by the timing of the first zygotic cleavage (FZC). Therefore, the aim of the present study was to investigate whether growth hormone added to IVM medium influences the timing of the FZC in cattle and also the quality of resulting blastocysts. The novelty of this manuscript concerns two findings: 1) no effect of GH supplementation to IVM medium on the timing of the first zygotic cleavage in cattle, and 2) differences in the relative transcript abundance in bovine day 7.5 blastocysts derived from early and late cleaved zygotes. Cumulus-oocyte complexes aspirated from slaughterhouse ovaries were matured in TCM199 medium supplemented with growth hormone (GH+ 100 ng/ml, GH- control), inseminated, and cultured in sequential media for 7.5 d. Embryo selection was done at 30 hpi (early cleavers EC) and 48 hpi (non-early cleavers NEC). The blastocyst quality was assessed by the total and ICM:TE cell counts, dead cell index, and relative transcript abundance (RA) of five genes affecting embryo development (p66(shc), bax, bcl-2, survivin, Hsp 70.1). The results of this study showed that although GH added to the IVM medium significantly improved the quality of blastocysts on day 7.5 pi, it had no effect on the timing of the first zygotic cleavage expressed by the rate of EC zygotes. The quality of the four categories of blastocysts investigated in this study can be ranked as follows: GH+ EC, followed by GH+ NEC, and further by the GH- EC and GH- NEC embryos. It has to be mentioned, however that the quality of blastocysts derived from the NEC zygotes was significantly improved by the GH supplementation. This is particularly relevant, since those blastocysts were very few and usually characterized by an

  11. Does mental exertion alter maximal muscle activation?

    Directory of Open Access Journals (Sweden)

    Vianney eRozand

    2014-09-01

    Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

  12. Assessment of the mechanisms exerting glucose-lowering effects of dried peas in glucose-intolerant rats.

    Science.gov (United States)

    Whitlock, Kevin A; Kozicky, Lisa; Jin, Alena; Yee, Homun; Ha, Christine; Morris, Jill; Field, Catherine J; Bell, Rhonda C; Ozga, Jocelyn A; Chan, Catherine B

    2012-08-01

    The present study compared the effects of feeding uncooked pea fractions (embryo v. seed coat) on glucose homeostasis in glucose-intolerant rats and examined potential mechanisms influencing glucose homeostasis. Rats were made glucose intolerant by high-fat feeding, after which diets containing both high-fat and pea fractions were fed for 4 weeks. Rats fed diets containing uncooked pea seed coats low (non-coloured seed coat; NSC) or high (coloured seed coat; CSC) in proanthocyanidins but not embryos had improved oral glucose tolerance (P < 0·05). NSC also lowered fasting and glucose-stimulated insulin secretion (P < 0·05), decreased β-cell mass by 50 % (P < 0·05) and lowered levels of malondialdehyde, a marker of oxidative stress. Furthermore, NSC decreased the mucosal thickness of the colon by 25 % (P < 0·05), which might affect fibre fermentation and other gut functions. Small but statistically significant (P < 0·05) effects consistent with enhanced glucose transport or metabolism were observed in the skeletal muscle of rats fed NSC or CSC, for example, increased levels of AMP-dependent kinase or akt. We conclude that pea seed coats are the fraction exerting beneficial effects on glucose tolerance. Most of the changes were small in amplitude, suggesting that additive effects on multiple tissues may be important. NSC content appeared to have the most beneficial effects in improving glucose homeostasis but our ability to detect the effect of flavonoids may have been limited by their low concentration in the diet.

  13. Low Concentrations of Corticosterone Exert Stimulatory Effects on Macrophage Function in a Manner Dependent on Glucocorticoid Receptors

    Directory of Open Access Journals (Sweden)

    He-Jiang Zhong

    2013-01-01

    Full Text Available Endogenous glucocorticoids (GCs have both stimulatory and suppressive effects on immune cells depending on the concentration. However, the mechanisms underlying the stimulatory effects of GCs remain elusive. Rat peritoneal macrophages were treated with different concentrations of corticosterone (0, 30 nM, 150 nM, and 3 μM. To inhibit the glucocorticoid receptor (GR activity, macrophages were preincubated with the GR antagonist RU486 (mifepristone, 10 μM for 30 min before treatment with corticosterone (150 nM. In the absence of immune stimuli, the chemotactic and phagocytic activities of macrophages were markedly enhanced by low concentrations of corticosterone (30 and 150 nM when compared with vehicle-treated controls. However, these effects were not observed at a high concentration of corticosterone (3 μM. Furthermore, blocking GR activity inhibited 150 nM corticosterone-enhanced chemotaxis and phagocytosis of macrophages. Meanwhile, after treatment with corticosterone (150 nM for 1 h and 3 h, GR protein expression increased to 1.4- and 2.2-fold, respectively, compared to untreated macrophages. These effects were inhibited by RU486. However, mineralocorticoid receptor (MR protein expression was not influenced by 150 nM corticosterone. These results demonstrate that low concentrations of corticosterone exert stimulatory effects on macrophage function in the absence of immune stimuli, and GR is at least partially responsible for these effects.

  14. Egg-derived tri-peptide IRW exerts antihypertensive effects in spontaneously hypertensive rats.

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    Kaustav Majumder

    Full Text Available There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR, we tested the therapeutic potential of IRW in this well-established model of hypertension.16-17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW or a high dose (15 mg/Kg BW daily for 18 days. Blood pressure (BP and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis.Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.

  15. The Mucosal Adjuvant Cyclic di-AMP Exerts Immune Stimulatory Effects on Dendritic Cells and Macrophages

    Science.gov (United States)

    Libanova, Rimma; Lienenklaus, Stefan; Weiss, Siegfried; Guzmán, Carlos A.

    2014-01-01

    The cyclic di-nucleotide bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) is a candidate mucosal adjuvant with proven efficacy in preclinical models. It was shown to promote specific humoral and cellular immune responses following mucosal administration. To date, there is only fragmentary knowledge on the cellular and molecular mode of action of c-di-AMP. Here, we report on the identification of dendritic cells and macrophages as target cells of c-di-AMP. We show that c-di-AMP induces the cell surface up-regulation of T cell co-stimulatory molecules as well as the production of interferon-β. Those responses were characterized by in vitro experiments with murine and human immune cells and in vivo studies in mice. Analyses of dendritic cell subsets revealed conventional dendritic cells as principal responders to stimulation by c-di-AMP. We discuss the impact of the reported antigen presenting cell activation on the previously observed adjuvant effects of c-di-AMP in mouse immunization studies. PMID:24755640

  16. Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts.

    Science.gov (United States)

    Bengtsson, Torbjörn; Khalaf, Atika; Khalaf, Hazem

    2015-09-01

    Periodontal pathogens, including Porphyromonas gingivalis, can form biofilms in dental pockets and cause inflammation, which is one of the underlying mechanisms involved in the development of periodontal disease, ultimately leading to tooth loss. Although P. gingivalis is protected in the biofilm, it can still cause damage and modulate inflammatory responses from the host, through secretion of microvesicles containing proteinases. The aim of this study was to evaluate the role of cysteine proteinases in P. gingivalis colony growth and development, and subsequent immunomodulatory effects on human gingival fibroblast. By comparing the wild type W50 with its gingipain deficient strains we show that cysteine proteinases are required by P. gingivalis to form morphologically normal colonies. The lysine-specific proteinase (Kgp), but not arginine-specific proteinases (Rgps), was associated with immunomodulation. P. gingivalis with Kgp affected the viability of gingival fibroblasts and modulated host inflammatory responses, including induction of TGF-β1 and suppression of CXCL8 and IL-6 accumulation. These results suggest that secreted products from P. gingivalis, including proteinases, are able to cause damage and significantly modulate the levels of inflammatory mediators, independent of a physical host-bacterial interaction. This study provides new insight of the pathogenesis of P. gingivalis and suggests gingipains as targets for diagnosis and treatment of periodontitis. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.

    Science.gov (United States)

    Decherf, Stéphanie; Seugnet, Isabelle; Becker, Nathalie; Demeneix, Barbara A; Clerget-Froidevaux, Marie-Stéphanie

    2013-12-05

    How Retinoid X receptors (RXR) and thyroid hormone receptors (TR) interact on negative TREs and whether RXR subtype specificity is determinant in such regulations is unknown. In a set of functional studies, we analyzed RXR subtype effects in T3-dependent repression of hypothalamic thyrotropin-releasing hormone (Trh). Two-hybrid screening of a hypothalamic paraventricular nucleus cDNA bank revealed specific, T3-dependent interaction of TRs with RXRβ. In vivo chromatin immuno-precipitation showed recruitment of RXRs to the TRE-site 4 region of the Trh promoter in the absence of T3. In vivo overexpression of RXRα in the mouse hypothalamus heightened T3-independent Trh transcription, whereas RXRβ overexpression abrogated this activity. Loss of function of RXRα and β by shRNAs induced inverse regulations. Thus, RXRα and RXRβ display specific roles in modulating T3-dependent regulation of Trh. These results provide insight into the actions of these different TR heterodimerization partners within the context of a negatively regulated gene. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Direct contact of platelets and their released products exert different effects on human dendritic cell maturation

    Directory of Open Access Journals (Sweden)

    Delézay Olivier

    2008-09-01

    Full Text Available Abstract Background Dendritic cells (DCs are antigen presenting cells capable of inducing innate and adaptive immune responses. According to the stimulus and their maturation state, DCs induce immunogenic or tolerogenic responses. Platelets (PLTs, which are involved in haemostasis and inflammation, can also interact with DCs. In this study, we examined the effect of PLTs on DC maturation in vitro. Human monocyte-derived DCs were co-cultured for 2 days with homologous PLTs either in the same well or in 0.4 μm-pore size filter-separated compartments. Results Confocal microscopy showed the attachment of PLTs to DC membranes. The DC receptor involved in this interactions was found to be CD162. In addition, we observed that DCs co-cultured with PLTs in filter-separated compartments acquired a mature phenotype (high CD80, CD86, and intermediate CD83 expression; IL-12(p70 production; efficient stimulation of autologous CD4+ T cell proliferation, while DCs co-cultured with PLTs in the same compartment did not undergo phenotypic maturation, did not secrete IL-12(p70 or IL-1β, but instead induced moderate Th2-polarized T cell proliferation. Conclusion These data indicate that (i PLTs secrete a soluble DC-activating factor that was demonstrated not to be soluble CD40-Ligand (CD154; as could have been expected from in vivo and previous in vitro work but to be nucleotide, and (ii that cell-to-cell contact did not induce DC maturation, possibly because nucleotide release by PLTs was prevented by direct contact with DCs. This work demonstrates that PLTs are active elements of the immune system that might play a role in balancing the ability of DCs to polarize T cell responses, therefore making them critical factors in transfusion processes.

  19. Background noise exerts diverse effects on the cortical encoding of foreground sounds.

    Science.gov (United States)

    Malone, B J; Heiser, Marc A; Beitel, Ralph E; Schreiner, Christoph E

    2017-08-01

    In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions. NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may

  20. α-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated microglia activation.

    Science.gov (United States)

    Park, Sun Young; Park, Se Jin; Park, Nan Jeong; Joo, Woo Hong; Lee, Sang-Joon; Choi, Young-Whan

    2013-10-25

    Schisandra chinensis is commonly used for food and as a traditional remedy for the treatment of neuronal disorders. However, it is unclear which component of S. chinensis is responsible for its neuropharmacological effects. To answer this question, we isolated α-iso-cubebene, a dibenzocyclooctadiene lignin, from S. chinensis and determined if it has any anti-neuroinflammatory and neuroprotective properties against amyloid β-induced neuroinflammation in microglia. Microglia that are stimulated by amyloid β increased their production of pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO) and reactive oxygen species (ROS) and the enzymatic activity of matrix metalloproteinase 9 (MMP-9). We found this was all inhibited by α-iso-cubebene. Consistent with these results, α-iso-cubebene inhibited the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and MMP-9 in amyloid β-stimulated microglia. Subsequent mechanistic studies revealed that α-iso-cubebene inhibited the phosphorylation and degradation of IκB-α, the phosphorylation and transactivity of NF-κB, and the phosphorylation of MAPK in amyloid β-stimulated microglia. These results suggest that α-iso-cubebene impairs the amyloid β-induced neuroinflammatory response of microglia by inhibiting the NF-κB and MAPK signaling pathways. Importantly, α-iso-cubebene can provide critical neuroprotection for primary cortical neurons against amyloid β-stimulated microglia-mediated neurotoxicity. To the best of our knowledge, this is the first report showing that α-iso-cubebene can provide neuroprotection against, and influence neuroinflammation triggered by, amyloid β activation of microglia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Cytoprotective Efficacy of Amifostine Against Radiation- Induced Rectal Toxicity: Objective and Subjective Grading Scales for Radiomucositis

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    John R. Kouvaris

    2008-04-01

    Full Text Available Curative radiation therapy of pelvic malignancies, frequently results in doselimitingtoxicities such as serous, mucoid, or more rarely, bloody diarrhea. Several studieshave evaluated the cytoprotective effects of amifostine in preventing rectal mucositisassociated with radiation treatment. We searched Medline for published comparativestudies that evaluated the use of amifostine to reduce radiation-induced toxicity associatedwith pelvic irradiation. In ten studies there was an evidence-based cytoprotection (P less than 0.05by amifostine. Although results are variable, current evidence suggests that amifostine mayhave a radioprotective effect in the rectal mucosa, particularly when administeredintrarectally. Significant improvements were seen in both symptomatic and objective(rectosigmoidoscopy end points. There is a need to conduct well-designed clinical trialswith sufficient numbers of participants to confirm these findings together with a costbenefitstudy. Objective measurements using rectosigmoidoscopy are superior tosubjective measures such as WHO or RTOG/EORTC toxicity grading scales.

  2. The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn.

    Science.gov (United States)

    Lee, Hyung Gon; Choi, Jeong Il; Yoon, Myung Ha; Obata, Hideaki; Saito, Shigeru; Kim, Woong Mo

    2014-11-07

    The purpose of this study was to validate the effects of tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered tianeptine on mechanical allodynia were assessed. Dihydroergocristine or yohimbine, a serotonergic or α-2 adrenergic receptor antagonists, respectively, were intrathecally administered 10min before tianeptine to investigate its mechanism of action. Additionally microdialysis studies were performed to measure the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the spinal dorsal horn following tianeptine administration. Intrathecal tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Peptides from the N-terminal domain of chromogranin A (vasostatins) exert negative inotropic effects in the isolated frog heart.

    Science.gov (United States)

    Tota, Bruno; Mazza, Rosa; Angelone, Tommaso; Nullans, Gerard; Metz-Boutigue, Marie-Hélène; Aunis, Dominique; Helle, Karen B

    2003-07-15

    The negative inotropic effects of synthetic peptides derived from the N-terminus of chromogranin A (CgA) were studied in an avascular model of the vertebrate myocardium, the isolated working frog heart (Rana esculenta). The peptides were frog and bovine CgA(4-16) and CgA(47-66), and bovine CgA(1-40) with (CgA(1-40SS)) and without an intact disulfide bridge (CgA(1-40SH)). Under basal cardiac conditions, four of the peptides caused a concentration-dependent negative inotropism that was comparable to the negative inotropy reported for human recombinant vasostatin I (CgA(1-78)) and bovine CgA(7-57). By comparison of the structural characteristics of the bovine and frog sequences with their minimally effective concentrations ranging from 68 to 125 nM of peptide, the results were consistent with the natural structure (CgA(17-38SS)) being essential for the negative inotropism. In addition, the partial sequences of the frog and bovine vasostatin I were effective in counteracting the characteristic positive inotropism exerted by isoproterenol (1 nM) at minimally effective concentrations ranging from 45 to 272 nM. Taken together, these results extend the first evidence for a cardiosuppressive role of the N-terminal domain of chromogranin A known for its co-storage with catecholamines in the sympathoadrenal system of vertebrates.

  4. Salidroside exerts protective effects against chronic hypoxia-induced pulmonary arterial hypertension via AMPKα1-dependent pathways.

    Science.gov (United States)

    Chen, Mayun; Cai, Hui; Yu, Chang; Wu, Peiliang; Fu, Yangyang; Xu, Xiaomei; Fan, Rong; Xu, Cunlai; Chen, Yanfan; Wang, Liangxing; Huang, Xiaoying

    2016-01-01

    Salidroside, an active ingredient isolated from Rhodiola rosea, has shown to exert protective effects against chronic hypoxia-induced pulmonary arterial hypertension (PAH). However, the underlying mechanisms were not well known. Based on our recent reports, we predicted the involvement of adenosine monophosphate-activated protein kinase (AMPK) mediated effects in salidroside regulation of PAH. Firstly, to prove the hypothesis, rats were exposed to chronic hypoxia and treated with increasing concentrations of salidroside or a selective AMPK activator-5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) for 4 weeks. After salidroside or AICAR treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary artery remodeling were attenuated. Then the effects of salidroside or AICAR on hypoxia-induced excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs), which contributed to pulmonary arterial remodeling, were investigated. Our results suggested salidroside, as well as AICAR, reversed hypoxia-induced PASMCs proliferation and apoptosis resistance while AMPK inhibitor Compound C enhanced the effects of hypoxia. To reveal the potential cellular mechanisms, activation of AMPKα1 and expression of the genes related to proliferation and apoptosis were analyzed in PASMCs after salidroside treatment under hypoxia conditions. The results demonstrated salidroside as well as AICAR might inhibit chronic hypoxia-induced PASMCs proliferation via AMPKα1-P53-P27/P21 pathway and reverse apoptosis resistance via AMPKα1-P53-Bax/Bcl-2-caspase 9-caspase 3 pathway.

  5. Imidafenacin exerts the antidiuretic effect by enhancing vasopressin-related responses in orally water-loaded rats.

    Science.gov (United States)

    Yamazaki, Takanobu; Fukata, Ayako; Muraki, Yukiko

    2016-11-15

    Imidafenacin, an antimuscarinic agent for treating overactive bladder, has an antidiuretic effect, but the detailed mechanisms of action remain unclear. The cholinergic and vasopressin systems are known to interact, for example, in the suppression of vasopressin-induced water reabsorption through muscarinic stimulation in the renal collecting duct. We, therefore, investigated whether vasopressin signaling pathway would participate in the antidiuretic effect of imidafenacin. In female Sprague-Dawley rats, urine production was measured by collecting urine from cystostomy chatheter using a Bollman restraining cage for 2h after drug i.v. injection and water load (25ml/kg p.o.). Both imidafenacin and a vasopressin V2 receptor agonist desmopressin acetate (desmopressin) dose-dependently suppressed urine production. The combination of imidafenacin and desmopressin at the minimum effective doses suppressed the urine production more strongly than each alone. Mozavaptan hydrochloride (mozavaptan, 3mg/kg), a vasopressin V2 receptor antagonist, completely inhibited the antidiuretic effects of imidafenacin and desmopressin at their respective minimum effective doses. The antidiuretic effect of desmopressin emerged at the maximum antidiuretic dose level (0.1µg/kg) even under mozavaptan-treatment, whereas that of imidafenacin (300µg/kg) was still kept suppressed by mozavaptan. When 300µg/kg imidafenacin was added to the combination of mozavaptan 3mg/kg and desmopressin 0.1µg/kg, the antidiuretic effect was further enhanced. The present study suggests that vasopressin signaling pathway participates in the antidiuretic effect of imidafenacin, and that imidafenacin exerts its antidiuretic effects by enhancing some part of the vasopressin signaling pathway in orally water-loaded rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Quinone Methide Bioactivation Pathway: Contribution to Toxicity and/or Cytoprotection?

    OpenAIRE

    Bolton, Judy L.

    2014-01-01

    The formation of quinone methides (QMs) from either direct 2-electron oxidation of 2- or 4-alkylphenols, isomerization of o-quinones, or elimination of a good leaving group could explain the cytotoxic/cytoprotective effects of several drugs, natural products, as well as endogenous compounds. For example, the antiretroviral drug nevirapine and the antidiabetic agent troglitazone both induce idiosyncratic hepatotoxicity through mechanisms involving quinone methide formation. The anesthetic phen...

  7. Electroacupuncture Pretreatment at GB20 Exerts Antinociceptive Effects via Peripheral and Central Serotonin Mechanism in Conscious Migraine Rats

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    Lu Liu

    2016-01-01

    Full Text Available Background. While electroacupuncture (EA pretreatment in migraine has been found to attenuate pain and frequencies of attacks, the underlying mechanism of its antinociceptive effect remains poorly understood. Emerging evidence suggests that the serotonin system may be involved in migraine pathophysiology. Method. Forty male Sprague-Dawley rats were randomly assigned to Control, Model, EA, and sham acupuncture (SA groups. HomeCageScan was used to measure the effects on spontaneous nociceptive behaviors. Radioimmunoassay and high-performance liquid chromatography were used to evaluate the expression of 5-hydroxytryptamine (HT in the plasma and three-key structure of the descending pain modulatory system. Results. Our study showed that EA pretreatment could produce a significant reduction in resting, freezing, and grooming behavior and a significant increase in exploration behavior. Furthermore, we found that the level of 5-HT in plasma was significantly increased, and it was significantly decreased in the descending pain modulatory system in Model group. The aforementioned results were significantly reversed in EA group; that is, the level of 5-HT was increased in the rostroventromedial medulla (RVM and trigeminal nucleus caudalis (TNC region and decreased in the plasma. Conclusion. EA pretreatment exerts antinociceptive effects in a rat model of recurrent migraine, possibly via modulation of the serotonin system.

  8. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

    Science.gov (United States)

    Bae, Min-Jung; See, Hye-Jeong; Choi, Gyeyoung; Kang, Chang-Yuil; Shon, Dong-Hwa; Shin, Hee Soon

    2016-01-01

    The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  9. Bifidobacterium adolescentis Exerts Strain-Specific Effects on Constipation Induced by Loperamide in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    2017-02-01

    Full Text Available Constipation is one of the most common gastrointestinal complaints worldwide. This study was performed to determine whether Bifidobacterium adolescentis exerts inter-strain differences in alleviating constipation induced by loperamide in BALB/c mice and to analyze the main reasons for these differences. BALB/c mice underwent gavage with B. adolescentis (CCFM 626, 667, and 669 once per day for 17 days. The primary outcome measures included related constipation indicators, and the secondary outcome measures were the basic biological characteristics of the strains, the concentration changes of short-chain fatty acids in feces, and the changes in the fecal flora. B. adolescentis CCFM 669 and 667 relieved constipation symptoms by adhering to intestinal epithelial cells, growing quickly in vitro and increasing the concentrations of propionic and butyric acids. The effect of B. adolescentis on the gut microbiota in mice with constipation was investigated via 16S rRNA metagenomic analysis. The results revealed that the relative abundance of Lactobacillus increased and the amount of Clostridium decreased in the B. adolescentis CCFM 669 and 667 treatment groups. In conclusion, B. adolescentis exhibits strain-specific effects in the alleviation of constipation, mostly due to the strains’ growth rates, adhesive capacity and effects on the gut microbiome and microenvironment.

  10. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  11. Bifidobacterium adolescentis Exerts Strain-Specific Effects on Constipation Induced by Loperamide in BALB/c Mice.

    Science.gov (United States)

    Wang, Linlin; Hu, Lujun; Xu, Qi; Yin, Boxing; Fang, Dongsheng; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2017-02-20

    Constipation is one of the most common gastrointestinal complaints worldwide. This study was performed to determine whether Bifidobacterium adolescentis exerts inter-strain differences in alleviating constipation induced by loperamide in BALB/c mice and to analyze the main reasons for these differences. BALB/c mice underwent gavage with B. adolescentis (CCFM 626, 667, and 669) once per day for 17 days. The primary outcome measures included related constipation indicators, and the secondary outcome measures were the basic biological characteristics of the strains, the concentration changes of short-chain fatty acids in feces, and the changes in the fecal flora. B. adolescentis CCFM 669 and 667 relieved constipation symptoms by adhering to intestinal epithelial cells, growing quickly in vitro and increasing the concentrations of propionic and butyric acids. The effect of B. adolescentis on the gut microbiota in mice with constipation was investigated via 16S rRNA metagenomic analysis. The results revealed that the relative abundance of Lactobacillus increased and the amount of Clostridium decreased in the B. adolescentis CCFM 669 and 667 treatment groups. In conclusion, B. adolescentis exhibits strain-specific effects in the alleviation of constipation, mostly due to the strains' growth rates, adhesive capacity and effects on the gut microbiome and microenvironment.

  12. Soy-Leaf Extract Exerts Atheroprotective Effects via Modulation of Krüppel-Like Factor 2 and Adhesion Molecules

    Directory of Open Access Journals (Sweden)

    Jong-Min Han

    2017-02-01

    Full Text Available Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL in human umbilical vein endothelial cells (HUVECs and high-cholesterol diet (HCD-fed low-density lipoprotein receptor deficient (LDLR−/− mice. ESL induced the expression of Krüppel-like factor 2 (KLF2, an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS, and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α-stimulated HUVECs but also in 7-ketocholesterol (7-KC-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR−/− mice by 46% (p < 0.01 compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1, TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9, and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced atherosclerosis effectively.

  13. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Theumer, Anja; Gräfe, Christine; Bähring, Franziska [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Bergemann, Christian [Chemicell GmbH, Eresburgstrasse 22–23, 12103 Berlin (Germany); Hochhaus, Andreas [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Clement, Joachim H., E-mail: joachim.clement@med.uni-jena.de [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany)

    2015-04-15

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

  14. The effects of therapeutic instrumental music performance on endurance level, self-perceived fatigue level, and self-perceived exertion of inpatients in physical rehabilitation.

    Science.gov (United States)

    Lim, Hayoung A; Miller, Karen; Fabian, Chuck

    2011-01-01

    The present study investigated the effects of a Neurologic Music Therapy (NMT) sensory-motor rehabilitation technique, Therapeutic Instrumental Music Performance (TIMP) as compared to Traditional Occupational Therapy (TOT), on endurance, self-perceived fatigue, and self-perceived exertion of 35 hospitalized patients in physical rehabilitation. The present study attempted to examine whether an active musical experience such as TIMP with musical cueing (i.e., rhythmic auditory cueing) during physical exercises influences one's perception of pain, fatigue, and exertion. All participants were diagnosed with a neurologic disorder or had recently undergone orthopedic surgery. Investigators measured the effects of TOT and TIMP during upper extremity exercise of the less affected or stronger upper extremity. Results showed no significant difference on endurance measures between the 2 treatment conditions (TIMP and TOT). Statistically significant differences were found between TIMP and TOT when measuring their effects on perceived exertion and perceived fatigue. TIMP resulted in significantly less perception of fatigue and exertion levels than TOT. TIMP can be used foran effective sensory-motor rehabilitation technique to decrease perceived exertion and fatigue level of inpatients in physical rehabilitation.

  15. Effects of 12 months aerobic exercise intervention on work ability, need for recovery, productivity and rating of exertion among cleaners

    DEFF Research Database (Denmark)

    Lidegaard, Mark; Søgaard, Karen; Krustrup, Peter

    2018-01-01

    -randomised (work location; sex; age; length of service) to aerobic exercise [N = 57, 44.9 years, 75.4% female, body mass index (BMI) 26.2], receiving 2 weekly aerobic exercise sessions during 12 months, or a reference group (N = 59, 45.7 years, 76.3% female, BMI 27.1), receiving health-promoting lectures. Self......PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster....... Aerobic exercise adherence was 51% during the first 4 months. At 4 month follow-up no effects were found. At 12 month follow-up, work ability significantly increased by 0.59 on a 0-10 scale (95% CI 0.05-1.13) and need for recovery significantly decreased by - 11.0 on a 0-100 scale (95% CI - 19.8 to - 2...

  16. Effects on Volume Load and Ratings of Perceived Exertion in Individuals Advanced Weight-Training After Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Lattari, Eduardo; Rosa Filho, Blair José; Fonseca Junior, Sidnei Jorge; Murillo-Rodriguez, Eric; Rocha, Nuno; Machado, Sérgio; Maranhão Neto, Geraldo Albuquerque

    2018-01-11

    The aim of this study was investigate the effects of transcranial direct current stimulation (tDCS) on volume-load and ratings of perceived exertion. Fifteen young healthy individuals, aged between 20 and 30 years in advanced strength training were recruited. Test and retest of the 10 maximum repetitions (10RM) were performed to determine the reliability of load utilized. Subjects performed three experimental conditions in a randomized, double-blinded crossover design: anodic stimulation (a-tDCS), cathodic stimulation (c-tDCS) and sham (2 mA for 20 minutes targeting the dorsolateral prefrontal cortex cortex left). Immediately after the experimental conditions, subjects completed one set of maximum repetitions with 10RM load (volume-load) and answered to OMNI-RES (Post-stimulation) (level of significance p ≤ 0.05). The volume-load showed main effect for condition (F(2, 28)= 164.801; pload for the LP45 exercise. Moreover, higher-volume loads are necessary to maximize muscle strength and anabolism.

  17. Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

    Science.gov (United States)

    Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

    2017-12-01

    Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

  18. Pre-learning stress that is temporally removed from acquisition exerts sex-specific effects on long-term memory.

    Science.gov (United States)

    Zoladz, Phillip R; Warnecke, Ashlee J; Woelke, Sarah A; Burke, Hanna M; Frigo, Rachael M; Pisansky, Julia M; Lyle, Sarah M; Talbot, Jeffery N

    2013-02-01

    We have examined the influence of sex and the perceived emotional nature of learned information on pre-learning stress-induced alterations of long-term memory. Participants submerged their dominant hand in ice cold (stress) or warm (no stress) water for 3 min. Thirty minutes later, they studied 30 words, rated the words for their levels of emotional valence and arousal and were then given an immediate free recall test. Twenty-four hours later, participants' memory for the word list was assessed via delayed free recall and recognition assessments. The resulting memory data were analyzed after categorizing the studied words (i.e., distributing them to "positive-arousing", "positive-non-arousing", "negative-arousing", etc. categories) according to participants' valence and arousal ratings of the words. The results revealed that participants exhibiting a robust cortisol response to stress exhibited significantly impaired recognition memory for neutral words. More interestingly, however, males displaying a robust cortisol response to stress demonstrated significantly impaired recall, overall, and a marginally significant impairment of overall recognition memory, while females exhibiting a blunted cortisol response to stress demonstrated a marginally significant impairment of overall recognition memory. These findings support the notion that a brief stressor that is temporally separated from learning can exert deleterious effects on long-term memory. However, they also suggest that such effects depend on the sex of the organism, the emotional salience of the learned information and the degree to which stress increases corticosteroid levels. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol 3-kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets.

    Science.gov (United States)

    Beuers, Ulrich; Denk, Gerald U; Soroka, Carol J; Wimmer, Ralf; Rust, Christian; Paumgartner, Gustav; Boyer, James L

    2003-05-16

    Taurolithocholic acid (TLCA) is a potent cholestatic agent. Our recent work suggested that TLCA impairs hepatobiliary exocytosis, insertion of transport proteins into apical hepatocyte membranes, and bile flow by protein kinase Cepsilon (PKCepsilon)-dependent mechanisms. Products of phosphatidylinositol 3-kinases (PI3K) stimulate PKCepsilon. We studied the role of PI3K for TLCA-induced cholestasis in isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets (IRHC). In IPRL, TLCA (10 micromol/liter) impaired bile flow by 51%, biliary secretion of horseradish peroxidase, a marker of vesicular exocytosis, by 46%, and the Mrp2 substrate, 2,4-dinitrophenyl-S-glutathione, by 95% and stimulated PI3K-dependent protein kinase B, a marker of PI3K activity, by 154% and PKCepsilon membrane binding by 23%. In IRHC, TLCA (2.5 micromol/liter) impaired canalicular secretion of the fluorescent bile acid, cholylglycylamido fluorescein, by 50%. The selective PI3K inhibitor, wortmannin (100 nmol/liter), and the anticholestatic bile acid tauroursodeoxycholic acid (TUDCA, 25 micromol/liter) independently and additively reversed the effects of TLCA on bile flow, exocytosis, organic anion secretion, PI3K-dependent protein kinase B activity, and PKCepsilon membrane binding in IPRL. Wortmannin also reversed impaired bile acid secretion in IRHC. These data strongly suggest that TLCA exerts cholestatic effects by PI3K- and PKCepsilon-dependent mechanisms that are reversed by tauroursodeoxycholic acid in a PI3K-independent way.

  20. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells.

    Science.gov (United States)

    Plastina, Pierluigi; Bonofiglio, Daniela; Vizza, Donatella; Fazio, Alessia; Rovito, Daniela; Giordano, Cinzia; Barone, Ines; Catalano, Stefania; Gabriele, Bartolo

    2012-03-27

    Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer. In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer. We evaluated the effects of increasing concentrations of ZEs on ERα positive MCF-7 and ERα negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts. ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERα) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69μg/mL) and ERα negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70μg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities. Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

    Science.gov (United States)

    Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

    2017-12-01

    Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

  2. Acute Effects of Two Different Resistance Circuit Training Protocols on Performance and Perceived Exertion in Semiprofessional Basketball Players.

    Science.gov (United States)

    Freitas, Tomás T; Calleja-González, Julio; Alarcón, Francisco; Alcaraz, Pedro E

    2016-02-01

    This study aimed to investigate the acute effects of two different resistance circuit training protocols on basketball players' physical and technical performance and rating of perceived exertion (RPE). In a repeated-measures, crossover experimental design, 9 semiprofessional basketball players performed a Power Circuit Training (PCT; 45% 1RM) and a High-Resistance Circuit Training (HRC; 6RM), on consecutive weeks. Vertical and horizontal jump performance, 3-points shooting accuracy, repeated-sprint ability (RSA), agility, and upper body power output were measured before and after training. The RPE was assessed 20 minutes after resistance training. One-way repeated-measures analysis of variance showed performance decrements in vertical jump height and peak power, horizontal jump distance, 3-points percentage, bench-press power output, RSA total and ideal time, and agility T-Test at total time following HRC, but not PCT (p ≤ 0.05). The RPE was higher in HRC compared with PCT. The results of this study indicated that HRC was perceived as being harder and produced higher fatigue levels, which in turn lowered acute performance. However, low-to-moderate intensity loads did not negatively affect performance. Thus, completing a PCT session may be the most appropriate option before a practice or game as it avoids acute-resistance-training-induced performance decrements. However, if the objective of the basketball session is to develop or perfect technical skills during fatiguing conditions, HRC may be the more suitable option.

  3. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow.

    Science.gov (United States)

    Chung, Jihwa; Kim, Kyoung Hwa; Lee, Seok Cheol; An, Shung Hyun; Kwon, Kihwan

    2015-10-01

    Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

  4. Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yeyin Liang

    2017-01-01

    Full Text Available Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2 has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs. Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments.

  5. Maintenance chemotherapy in children with ALL exerts metronomic-like thrombospondin-1 associated anti-endothelial effect.

    Science.gov (United States)

    Andre, Nicolas; Cointe, Sylvie; Barlogis, Vincent; Arnaud, Laurent; Lacroix, Romaric; Pasquier, Eddy; Dignat-George, Françoise; Michel, Gérard; Sabatier, Florence

    2015-09-08

    Maintenance chemotherapy is an important part of the treatment of ALL in children. It relies on the long-term oral administration of daily low-dose mercaptopurin and weekly low-dose methotrexate. Although it has been used in the clinic for decades, its mechanisms of action remain unclear. Here, we investigated different angiogenic and immune biomarkers to gain insights into the mechanisms of action of maintenance therapy in children with ALL. We thus monitored circulating endothelial cells (CEC), endothelial progenitor cells (EPC) and endothelial microparticles (EMP), pro-angiogenic factors (VEGF, VEGFR-1 and Ang-2), anti-angiogenic factor thrombospondin-1 (THBS1) and regulatory T lymphocytes (Treg) in 47 children with ALL during the maintenance phase of their treatment (at treatment initiation and after 6, 12 and 18 months). We observed a statistically significant decrease in EPC and EMP counts throughout the maintenance phase associated with a significant increase in THBS1 levels. No significant change was detected in other angiogenic markers or in Treg numbers.The results presented here indicate that maintenance therapy in children with ALL exerts its antitumor activity at least in part through anti-angiogenic effects, similar to those induced by metronomic chemotherapy. Larger studies are now warranted to validate these findings and determine their clinical implications.

  6. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  7. Effect of traditional resistance and power training using rated perceived exertion for enhancement of muscle strength, power, and functional performance.

    Science.gov (United States)

    Tiggemann, Carlos Leandro; Dias, Caroline Pieta; Radaelli, Regis; Massa, Jéssica Cassales; Bortoluzzi, Rafael; Schoenell, Maira Cristina Wolf; Noll, Matias; Alberton, Cristine Lima; Kruel, Luiz Fernando Martins

    2016-04-01

    The present study compared the effects of 12 weeks of traditional resistance training and power training using rated perceived exertion (RPE) to determine training intensity on improvements in strength, muscle power, and ability to perform functional task in older women. Thirty healthy elderly women (60-75 years) were randomly assigned to traditional resistance training group (TRT; n = 15) or power training group (PT; n = 15). Participants trained twice a week for 12 weeks using six exercises. The training protocol was designed to ascertain that participants exercised at an RPE of 13-18 (on a 6-20 scale). Maximal dynamic strength, muscle power, and functional performance of lower limb muscles were assessed. Maximal dynamic strength muscle strength leg press (≈58 %) and knee extension (≈20 %) increased significantly (p training. Muscle power also increased with training (≈27 %; p training period (≈13 %; p strength, muscle power, and functional performance of lower limbs in elderly women.

  8. The effectiveness of session rating of perceived exertion to monitor resistance training load in acute burns patients.

    Science.gov (United States)

    Grisbrook, Tiffany L; Gittings, Paul M; Wood, Fiona M; Edgar, Dale W

    2017-02-01

    Session-rating of perceived exertion (RPE) is a method frequently utilised in exercise and sports science to quantify training load of an entire aerobic exercise session. It has also been demonstrated that session-RPE is a valid and reliable method to quantify training load during resistance exercise, in healthy and athletic populations. This study aimed to investigate the effectiveness of session-RPE as a method to quantify exercise intensity during resistance training in patients with acute burns. Twenty burns patients (mean age=31.65 (±10.09) years), with a mean TBSA of 16.4% (range=6-40%) were recruited for this study. Patients were randomly allocated to the resistance training (n=10) or control group (n=10). All patients completed a four week resistance training programme. Training load (session-RPE×session duration), resistance training session-volume and pre-exercise pain were recorded for each exercise session. The influence of; age, gender, %TBSA, exercise group (resistance training vs. control), pre-exercise pain, resistance training history and session-volume on training load were analysed using a multilevel mixed-effects linear regression. Session-volume did not influence training load in the final regression model, however training load was significantly greater in the resistance training group, compared with the control group (ptraining load, where increasing pain was associated with a higher session-RPE (p=0.004). Further research is indicated to determine the exact relationship between pain, resistance training history, exercise intensity and session-RPE and training load before it can be used as a method to monitor and prescribe resistance training load in acute burns patients. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  9. Pituitary adenylate cyclase activating polypeptide (PACAP signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target.

    Directory of Open Access Journals (Sweden)

    Tamás Juhász

    Full Text Available Pituitary adenylate cyclase activating polypeptide (PACAP is an important neurotrophic factor influencing differentiation of neuronal elements and exerting protecting role during traumatic injuries or inflammatory processes of the central nervous system. Although increasing evidence is available on its presence and protecting function in various peripheral tissues, little is known about the role of PACAP in formation of skeletal components. To this end, we aimed to map elements of PACAP signalling in developing cartilage under physiological conditions and during oxidative stress. mRNAs of PACAP and its receptors (PAC1,VPAC1, VPAC2 were detectable during differentiation of chicken limb bud-derived chondrogenic cells in micromass cell cultures. Expression of PAC1 protein showed a peak on days of final commitment of chondrogenic cells. Administration of either the PAC1 receptor agonist PACAP 1-38, or PACAP 6-38 that is generally used as a PAC1 antagonist, augmented cartilage formation, stimulated cell proliferation and enhanced PAC1 and Sox9 protein expression. Both variants of PACAP elevated the protein expression and activity of the Ca-calmodulin dependent Ser/Thr protein phosphatase calcineurin. Application of PACAPs failed to rescue cartilage formation when the activity of calcineurin was pharmacologically inhibited with cyclosporine A. Moreover, exogenous PACAPs prevented diminishing of cartilage formation and decrease of calcineurin activity during oxidative stress. As an unexpected phenomenon, PACAP 6-38 elicited similar effects to those of PACAP 1-38, although to a different extent. On the basis of the above results, we propose calcineurin as a downstream target of PACAP signalling in differentiating chondrocytes either in normal or pathophysiological conditions. Our observations imply the therapeutical perspective that PACAP can be applied as a natural agent that may have protecting effect during joint inflammation and/or may promote

  10. TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Cheng, Ming-Jun; Cao, Yun-Gui

    2017-07-03

    The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

  11. The endocannabinoid N-arachidonoyldopamine (NADA) exerts neuroprotective effects after excitotoxic neuronal damage via cannabinoid receptor 1 (CB(1)).

    Science.gov (United States)

    Grabiec, Urszula; Koch, Marco; Kallendrusch, Sonja; Kraft, Robert; Hill, Kerstin; Merkwitz, Claudia; Ghadban, Chalid; Lutz, Beat; Straiker, Alex; Dehghani, Faramarz

    2012-03-01

    Endocannabinoids exert numerous effects in the CNS under physiological and pathological conditions. The aim of the present study was to examine whether the endocannabinoid N-arachidonoyldopamine (NADA) may protect neurons in excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). OHSC were excitotoxically lesioned by application of N-methyl-d-aspartate (NMDA, 50 μM) for 4 h and subsequently treated with different NADA concentrations (0.1 pM-50 μM) alone or in combination with cannabinoid receptor antagonists. NADA protected dentate gyrus granule cells and caused a slight reduction in the number of microglial cells. The number of degenerated neurons significantly decreased between 100 pM and 10 μM NADA (p NADA mediated neuroprotection, we applied the cannabinoid (CB) receptor 1 (CB(1)) inverse agonist/antagonist AM251, CB(2) inverse agonist/antagonist AM630, abnormal-cannabidiol (abn-CBD)-sensitive receptor antagonist O-1918, transient receptor potential channel V1 (TRPV1) antagonist 6-iodonordihydrocapsaicin and A1 (TRPA1) antagonist HC-030031. Neuroprotective properties of low (1 nM) but not high (10 μM) NADA concentrations were solely blocked by AM251 and were absent in CB(1)(-/-) mice. AM630, O-1918, 6-iodonordihydrocapsaicin and HC-030031 showed no effects at all NADA concentrations applied. Our findings demonstrate that NADA protects dentate gyrus granule cells by acting via CB(1). NADA reduced the number of microglial cells at distinct concentrations. TRPV1 and TRPA1 were not involved in NADA mediated neuroprotection. Thus, our data implicate that NADA mediated activation of neuronal CB(1) may serve as a novel pharmacological target to mitigate symptoms of neuronal damage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice.

    Science.gov (United States)

    Cavalera, Michele; Axling, Ulrika; Rippe, Catarina; Swärd, Karl; Holm, Cecilia

    2017-06-01

    Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, Erica C; Valberg, Stephanie J; Godden, Sandra M; Finno, Carrie J; Murphy, Michael J

    2004-01-01

    To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). 2 healthy horses and 5 Thoroughbreds with RER. 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.

  14. Assessment of the toxic effect exerted by fluorescent pseudomonads on embryos and larvae of the sea urchin Strongylocentrotus nudus.

    Science.gov (United States)

    Beleneva, I A; Shamshurina, E V; Eliseikina, M G

    2015-05-01

    Strains of bacteria capable of growing on artificial culture media were isolated from the fouling of brass plates submerged in Nha Trang Bay, South China Sea, and from tissues of the seastar Distolasterias nipon, caught in Peter the Great Bay, Sea of Japan. According to the complex of data of genetic and physiological/biochemical analyzes, two strains of cultivated bacteria were identified by us as the species Pseudomonas aeruginosa, two strains as Pseudomonas fluorescens, and one strain as Ruegeria sp. It was shown that the cultivated strains of P. aeruginosa released exotoxins, particularly phenazine pigments, into the environment. Production of the toxins did not depend on presence of a target organism in the system and was aimed at regulation of interactions in the microbial community. The toxicity of the studied natural isolates of fluorescent pseudomonads was analyzed by using embryos and larvae of the sea urchin Strongylocentrotus nudus, which are the sensitive and dynamic toxicological sea-urchin embryo test (SET) system. As was established, exotoxins produced by the strains of P. aeruginosa inhibit activity of cilia in sea urchin larvae, as well as disturb processes of cell differentiation in embryos and larvae. Their toxic influence is accompanied by disturbances of protein synthesis and the disruptions of cytoskeleton in the course of zygote cleavage and larval development. Unlike P. aeruginosa, the strains of P. fluorescens and Ruegeria sp. did not exert the toxic effect on SET. The obtained data allow considering objects of the environment as the natural reservoir of opportunistic microorganisms posing a potential threat to human, whereas the use of SET for determination of toxicity of isolated bacteria provides an opportunity to study the mechanisms of their interactions with organisms in marine ecosystems. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effects of the workplace health promotion activities soccer and zumba on muscle pain, work ability and perceived physical exertion among female hospital employees

    DEFF Research Database (Denmark)

    Barene, Svein; Krustrup, Peter; Holtermann, Andreas

    2014-01-01

    Objectives: This 40-week workplace physical training RCT investigated the effect of soccer and Zumba, respectively, on muscle pain intensity and duration, work ability, and rating of perceived exertion (RPE) during work among female hospital employees. Methods: 107 hospital employees were cluster...

  16. DPP4 deficiency exerts protective effect against H2O2 induced oxidative stress in isolated cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Hui-Chun Ku

    Full Text Available Apart from the antihyperglycemic effects, DPP4 inhibitors and GLP-1 molecules are involved in the preservation of cardiac functions. We have demonstrated that DPP4-deficient rats possess resistance to endotoxemia and ischemia/reperfusion stress. However, whether the decrease of DPP4 activity simply augmented the GLP-1 signaling or that such decrease resulted in a change of cellular function remain unclear. Accordingly, we investigated the responses of H(2O(2-induced oxidative stress in adult wild-type and DPP4-deficient rats isolated cardiomyocytes. The coadministration of GLP-1 or DPP4 inhibitor was also performed to define the mechanisms. Cell viability, ROS concentration, catalase activity, glucose uptake, prosurvival, proapoptotic signaling, and contractile function were examined after cells exposed to H(2O(2. DPP4-deficient cardiomyocytes were found to be resistant to H(2O(2-induced cell death via activating AKT signaling, enhancing glucose uptake, preserving catalase activity, diminishing ROS level and proapoptotic signaling. GLP-1 concentration-dependently improved cell viability in wild-type cardiomyocyte against ROS stress, and the ceiling response concentration (200 nM was chosen for studies. GLP-1 was shown to decrease H(2O(2-induced cell death by its receptor-dependent AKT pathway in wild-type cardiomyocytes, but failed to cause further activation of AKT in DPP4-deficient cardiomyocytes. Acute treatment of DPP4 inhibitor only augmented the protective effect of low dose GLP-1, but failed to alter fuel utilization or ameliorate cell viability in wild-type cardiomyocytes after H(2O(2 exposure. The improvement of cell viability after H(2O(2 exposure was correlated with the alleviation of cellular contractile dysfunction in both DPP4-deficient and GLP-1 treated wild-type cardiomyocytes. These findings demonstrated that GLP-1 receptor-dependent pathway is important and exert protective effect in wild-type cardiomyocyte. Long term loss of

  17. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects

    Science.gov (United States)

    Xiong, Jie; Wang, Kezhou; Yuan, Chunxiao; Xing, Rong; Ni, Jianbo; Hu, Guoyong; Chen, Fengling; Wang, Xingpeng

    2017-01-01

    Reseda odorata L. has long been used in traditional Asian medicine for the treatment of diseases associated with oxidative injury and acute inflammation, such as endotoxemia, acute lung injury, acute myocardial infarction and hepatitis. Luteolin, the main component of Reseda odorata L., which is also widely found in many natural herbs and vege tables, has been shown to induce heme oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects. In this study, we aimed to examine the effects of luteolin on mice with severe acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Research (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry weight ratios, hematoxylin and eosin staining and pathological scores of pancreatic tissues were assessed and compared to those of the control mice. Amylase, lipase, nuclear factor-κB (NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were determined in serum and/or pancreatic tissue samples. SAP was successfully induced in male mice compared to normal control mice. The wet/dry weight ratios, pathological scores, and amylase and lipase activity, as well as the levels of TNFα and IL-6 were significantly reduced in the pancreatic tissues of the mice in the Lut group compared with those of the mice in the vehicle group. The Lut group exhibited a significant increase in HO-1 expression in the pancreas and enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPP group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues

  18. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    without submandibular glands. Exogenous EGF and saliva with a high but still physiological concentration of EGF significantly reduced the median area in the stomach displaying ulcers and ulcerations, whereas saliva without EGF had no effect. Although EGF is a known inhibitor of gastric acid secretion......, the dose used in the present study had no effect on gastric acid secretion in chronic gastric fistula rats; removal of the submandibular glands also did not have any such effect. We conclude that exocrine secretion of submandibular EGF has a cytoprotective function in the stomach, an effect that may...

  19. Protective effects of polyvinylpyrrolidone-wrapped fullerene against intermittent ultraviolet-A irradiation-induced cell injury in HaCaT cells.

    Science.gov (United States)

    Saitoh, Yasukazu; Ohta, Hiroaki; Hyodo, Sayuri

    2016-10-01

    To identify compounds that suppress UV irradiation-induced oxidative stress in the skin, various types of antioxidants have been studied. Polyvinylpyrrolidone-entrapped fullerene (C60/PVP) is known as a powerful antioxidant that exerts a cytoprotective effect against UV irradiation-induced cell injury in human skin cells and skin models. However, the effects of the alternate attractive C60/PVP feature, persistent antioxidant ability, on cytoprotection have rarely been ascertained. In this study we therefore investigated the efficacies of C60/PVP using an intermittently repeated UVA irradiation model wherein human keratinocytes were repeatedly exposed to UVA five times every 1h and compared the cytoprotective effects with those provided by ascorbic acid-2-O-phosphate-disodium salt (APS) and α-tocopherol (α-Toc). Our results demonstrated that C60/PVP yielded prominent cytoprotective effects against intermittently repeated UVA irradiation-induced injuries in a dose-dependent manner and suppressed intracellular superoxide anion radical (O2(-)) generation both during and after the repeated UVA irradiation. Additionally, C60/PVP also repressed the intermittent UVA irradiation-induced apoptosis via suppression of chromatin condensation and caspase-3/7 activation. Furthermore, the observed cytoprotective effects were superior to the effects of the typical antioxidants APS and α-Toc. These data suggest that C60/PVP might function as a potent cosmetic antioxidant against the effects of repeated and prolonged UVA irradiation through its persistent antioxidative property. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S-enantiomer of rasagiline.

    Directory of Open Access Journals (Sweden)

    Yaron D Barac

    Full Text Available TVP1022, the S-enantiomer of rasagiline (Azilect® (N-propargyl-1R-aminoindan, exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I(1 & I(2 are potential targets for TVP1022 (IC(50 =9.5E-08 M and IC(50 =1.4E-07 M, respectively. Western blotting analysis showed that TVP1022 (1-20 µM dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM. This effect of TVP1022 was significantly attenuated by efaroxan, a selective I(1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I(1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I(1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

  1. Effects of prismatic glasses including optometric correction on head and neck kinematics, perceived exertion and comfort during dental work in the oral cavity--a randomised controlled intervention.

    Science.gov (United States)

    Lindegård, A; Gustafsson, M; Hansson, G-Å

    2012-01-01

    To quantify the effects of using prismatic glasses including optometric correction, on head and neck kinematics, perceived exertion and comfort, during work in the oral cavity. The study population consisted of forty-five participants. After a basic ergonomic education, baseline measurements of head and neck kinematics were made using inclinometers. Perceived exertion and comfort were rated by the participants. An intervention group (n = 25), selected at random from the participants, received prismatic glasses and optometric correction when needed and were compared with a control group (n = 20). Follow up assessments were made after the intervention. At follow up there was a reduction in both the intervention group (8.7°) and in the control group (3.6°) regarding head flexion. Neck flexion was reduced by 8.2° in the intervention group and 3.3° in the control group. The difference between the intervention and the control groups, i.e. the effect of the intervention, was statistically significant for both head (5.1°; p = 0.009) and neck (4.9°; p = 0.045) flexion. No effect of the intervention was seen regarding perceived exertion and comfort. The reduction in head and neck flexion achieved by the prismatic glasses is likely to reduce the risk of neck pain during dental work. The effect of the prismatic lenses could not be separated from the effect of the optometric correction. The possible effect of the ergonomic education was not evaluated. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  2. Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat.

    Directory of Open Access Journals (Sweden)

    Yuri Kim

    Full Text Available The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors.

  3. Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

    Science.gov (United States)

    Kim, Dong-Hyun; Kim, Baek

    2011-01-01

    The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors. PMID:21765914

  4. The effects of training volume and repetition distance on session rating of perceived exertion and internal load in swimmers.

    Science.gov (United States)

    Barroso, Renato; Salgueiro, Diego F; do Carmo, Everton C; Nakamura, Fábio Y

    2015-10-01

    To assess swimmers' session rating of perceived exertion (sRPE) after standardized sets of interval swimming training performed at the same relative intensity but with different total volume and repetition distance. Thirteen moderately trained swimmers (21.1 ± 1.1 y, 178 ± 6 cm, 74.1 ± 8.3 kg, 100-m freestyle 60.2 ± 2.9 s) performed 4 standardized sets (10 × 100-m, 20 × 100-m, 10 × 200-m, and 5 × 400-m) at the same relative intensity (ie, critical speed), and 1 coach (age 31 y, 7 y coaching experience) rated their efforts. Swimmers' sRPE was assessed 30 min after the training session. Coach sRPE was collected before each training session. Internal load was calculated by multiplying sRPE by session duration. When bouts with the same repetition distance and different volumes (10 × 100-m vs 20 × 100-m) are compared, sRPE and internal load are higher in 20 × 100-m bouts. When maintaining constant volume, sRPE and internal load (20 × 100-m, 10 × 200-m, and 5 × 400-m) are higher only in 5 × 400-m bouts. The coach's and swimmers' sRPE differed in 10 × 200-m and 5 × 400-m. These results indicate that sRPE in swimming is affected not only by intensity but also by volume and repetition distance. In addition, swimmers' and the coach's sRPE were different when longer repetition distances were used during training sessions. Therefore, care should be taken when prescribing swimming sessions with longer volume and/or longer repetition distances.

  5. Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo.

    Science.gov (United States)

    Di Ianni, Mauro; Moretti, Lorenzo; Terenzi, Adelmo; Bazzucchi, Federico; Del Papa, Beatrice; Bazzucchi, Moira; Ciurnelli, Raffaella; Lucchesi, Alessandro; Sportoletti, Paolo; Rosati, Emanuela; Marconi, Pier Francesco; Falzetti, Franca; Tabilio, Antonio

    2009-01-01

    The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Freshly isolated CD3(+) T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index >30% was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

  6. Do sensory neurons mediate adaptive cytoprotection of gastric mucosa against bile acid injury?

    Science.gov (United States)

    Mercer, D W; Ritchie, W P; Dempsey, D T

    1992-01-01

    Pretreatment with the mild irritant 1 mmol acidified taurocholate protects the gastric mucosa from the injury induced by the subsequent application of 5 mmol acidified taurocholate, a phenomenon referred to as "adaptive cytoprotection." How this occurs remains an enigma. The purpose of this study was to investigate the role of sensory neurons and mucus secretion in this phenomenon. Prior to injury with 5 mmol acidified taurocholate (pH 1.2), the stomachs of six groups of rats were subjected to the following protocol. Two groups were topically pretreated with either saline or the mild irritant 1 mmol acidified taurocholate. Two other groups received the topical anesthetic 1% lidocaine prior to pretreatment with either saline or 1 mmol acidified taurocholate. The last two groups got the mucolytic agent 10% N-acetylcysteine (NAC) after pretreatment with either saline or 1 mmol acidified taurocholate. Injury was assessed by measuring net transmucosal ion fluxes, luminal appearance of deoxyribonucleic acid (DNA), and gross and histologic injury. Pretreatment with the mild irritant 1 mmol acidified taurocholate significantly decreased bile acid-induced luminal ion fluxes and DNA accumulation, suggesting mucosal protection (corroborated by gross and histologic injury analysis). This effect was negated by lidocaine but not by NAC. Thus, it appears that sensory neurons, and not increased mucus secretion, play a critical role in adaptive cytoprotection.

  7. EFFECT OF EXERCISE INTENSITY ON DIFFERENTIATED AND UNDIFFERENTIATED RATINGS OF PERCEIVED EXERTION DURING CYCLE AND TREADMILL EXERCISE IN RECREATIONALLY ACTIVE AND TRAINED WOMEN

    OpenAIRE

    Melinda R. Bolgar; Baker, Carol E.; GOSS, FREDRIC L.; Elizabeth Nagle; Robertson, Robert J.

    2010-01-01

    The purpose of the study is to examine the effect of aerobic exercise intensity on components of the differentiated perceived exertion model in young women performing weight bearing and non-weight bearing aerobic exercise. Subjects were 18-25 yr old women who were recreationally active (n = 19; VO2max = 33.40 ml·kg-1·min-1) and trained (N = 22; VO2max = 43.3 ml·kg-1·min-1). Subjects underwent two graded exercise tests (GXT) on a treadmill and bike which were separated by 48 hours. RPE-Overall...

  8. The hypercholesterolemic effect of dietary coconut fat versus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption.

    Science.gov (United States)

    Meijer, G W; Lemmens, A G; Versluis, A; Van Zutphen, L F; Beynen, A C

    1991-05-01

    In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturated versus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fat versus corn oil is not exerted by influencing cholesterol absorption.

  9. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females

    OpenAIRE

    Racil, G.; Coquart, J.B.; Elmontassar, W.; Haddad, M; Goebel, R.; Chaouachi, A; Amri, M; K. Chamari

    2016-01-01

    This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thr...

  10. Non-CpG Oligonucleotides Exert Adjuvant Effects by Enhancing Cognate B Cell-T Cell Interactions, Leading to B Cell Activation, Differentiation, and Isotype Switching

    Directory of Open Access Journals (Sweden)

    Melinda Herbáth

    2015-01-01

    Full Text Available Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11.10 mice and the ovalbumin peptide recognized by the TCR as model antigen. We followed early activation events by measuring CD69 expression, late activation by MHC class II expression, cell division and antibody production of switched, and nonswitched isotypes. We found that both of the tested non-CpG ODN exerted significant immunomodulatory effects on early T cell and on late B cell activation events. Importantly, a synergism between non-CpG effects and T cell help acting on B cells was observed, resulting in enhanced IgG production following cognate T cell-B cell interactions. We propose that non-CpG ODN may perform as better adjuvants when a strong antigen-independent immune activation, elicited by CpG ODNs, is undesirable.

  11. Non-CpG Oligonucleotides Exert Adjuvant Effects by Enhancing Cognate B Cell-T Cell Interactions, Leading to B Cell Activation, Differentiation, and Isotype Switching

    Science.gov (United States)

    Herbáth, Melinda; Papp, Krisztián; Erdei, Anna; Prechl, József

    2015-01-01

    Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN) with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11.10 mice and the ovalbumin peptide recognized by the TCR as model antigen. We followed early activation events by measuring CD69 expression, late activation by MHC class II expression, cell division and antibody production of switched, and nonswitched isotypes. We found that both of the tested non-CpG ODN exerted significant immunomodulatory effects on early T cell and on late B cell activation events. Importantly, a synergism between non-CpG effects and T cell help acting on B cells was observed, resulting in enhanced IgG production following cognate T cell-B cell interactions. We propose that non-CpG ODN may perform as better adjuvants when a strong antigen-independent immune activation, elicited by CpG ODNs, is undesirable. PMID:26380319

  12. The Effect of the Pressure Exerted on the Maternal Abdominal Wall by the US Probe on Fetal MCA Peak Systolic Velocity.

    Science.gov (United States)

    Alpert, Yoav; Ben-Moshe, Boaz; Shvalb, Nir; Piura, Esther; Tepper, Ronnie

    2017-01-01

    Purpose To quantify the pressure exerted on the maternal abdominal wall during ultrasound examination and evaluate its effect on the fetal middle cerebral artery (MCA) peak systolic velocity (PSV). Materials and Method Gravid women with singleton pregnancies in their 2nd-3 rd trimester undergoing fetal sonographic evaluation for various indications were recruited. Each subject underwent transabdominal US measuring fetal distance from the probe, abdominal thickness, amniotic fluid index and biophysical profile. The applied pressure was measured simultaneously using an electronic pressure sensor attached directly to the US probe. For each subject baseline values of the pressure required for proper visualization were obtained. Fetal MCA was then demonstrated using color Doppler US. The PSV was measured at different pressure ranges with each subject used as her own control. Care was taken not to exceed the baseline pressure for each subject. Results 29 women were recruited. 24 subjects (82.7 %) demonstrated a statistically significant positive correlation between the pressure exerted and MCA-PSV (R-0.37, p PSV values above 1.29 MOM and 5 subjects (17.2 %) demonstrated elevation of PSV values above 1.5 MOM for gestational age with increasing pressure. In total, 9 subjects (31 %) demonstrated significant changes in the MCA-PSV measurements (owing to increase in pressure applied) that could potentially falsely influence clinical obstetric diagnosis and management. Conclusion The pressure exerted on the maternal abdominal wall during US examination is an important parameter, producing clinically significant measurable changes in fetal MCA hemodynamics. Further study is needed in order to demonstrate the potential effect of pressure as a parameter influencing the diagnostic accuracy of the MCA-PSV in the setting of fetal anemia. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Chronic Exertional Compartment Syndrome.

    Science.gov (United States)

    Braver, Richard T

    2016-04-01

    Increased tissue pressure within a fascial compartment may be the result from any increase in volume within its contents, or any decrease in size of the fascial covering or its distensibility. This may lead to symptoms of leg tightness, pain or numbness brought about by exercise. There are multiple differential diagnoses of exercise induced leg pain and the proper diagnoses of chronic exertional compartment syndrome (CECS) is made by a careful history and by exclusion of other maladies and confirmed by compartment syndrome testing as detailed in this text. Surgical fasciotomies for the anterior, lateral, superficial and deep posterior compartments are described in detail along with ancillary procedures for chronic shin splints that should allow the athlete to return to competitive activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The effect of maximal vs submaximal exertion on postprandial lipid levels in individuals with and without coronary heart disease.

    Science.gov (United States)

    Aronov, David M; Bubnova, Marina G; Perova, Natalia V; Orekhov, Alexander N; Bobryshev, Yuri V

    Decisions about fat consumption and levels of physical activity are among the everyday choices we make in life and risk of coronary heart disease (CHD) can be affected by those choices. The purpose of this study was to investigate the influence of a standard fat load combined with physical exertion of different intensities on the plasma lipid profile of CHD patients and CHD-free individuals. This study looked at the influence of different intensities of physical exercise on postprandial lipid metabolism in 20 healthy men and 36 men with diagnosis of CHD. Venous blood samples were obtained after overnight fasting, 3 hours after standard fat load (before the physical load), and immediately after maximal or submaximal physical exercise on bicycle ergometer. After fat load total cholesterol (TC) concentration did not change in either group. However, after the addition of maximal exercise, TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (Apo) B increased significantly (P < .01) in both groups. After fat load and maximal exercise, there was no change in high-density lipoprotein cholesterol (HDL-C) in healthy men, but in men with CHD, HDL-C fell significantly (P < .01); and Apo AI rose in healthy men (P < .01) but dropped significantly (P < .01) in men with CHD. Submaximal physical exercise (60% of max VO2 load for 40 minutes) after fat load decreased TG level in CHD patients (P < .01) and improved other lipid parameters in both groups significantly (↓LDL-C, ↑HDL-C, ↑Apo AI, ↓Apo B, P < .01). We observed a worsening of physical work capacity in men with CHD (significant reduction of duration and total amount of work performed, maximal VO2, oxygen pulse), during maximal stress test performed 3 hours after fat load. There was a doubling of the number of abnormal stress test results (P < .01). Healthy persons showed an increase in respiratory parameters (ventilation, CO2 production, maximal VO2, and oxygen

  15. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  16. Radiation exposure exerts its adverse effects on sperm maturation through estrogen-induced hypothalamohypophyseal axis inhibition in rats

    CSIR Research Space (South Africa)

    Makinta, MJ

    2005-10-01

    Full Text Available Irradiation has adverse effects on reproductive aspects such as spermatogenic cell population and cell malformation, leading to reduced sperm count and non-viable spermatozoa. This has overshadowed possible effects of radiation exposure...

  17. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  18. [Psycho-physiological effects of pop music on cardiovascular parameters at rest and during exertion (author's transl)].

    Science.gov (United States)

    Liptak, V

    1979-05-30

    The effects of pop music on heart rate, systolic and diastolic blood pressure at rest, during exercise on a bicycle ergometer and in the recovery phase were investigated. The psychological effects of the music were analysed by means of a question sheet and correlated with the physiological effects. The psychological effects of the music points to a reduction of monotony and of fatigue. During exercise, especially during low physical strain, there was a good correlation between the psychological and the physiological parameters. The significant decrease of the cardiovascular parameters in the recovery phase demonstrates, that emotional stimuli are influencing the heart rate not only at rest and work, but also in the recovery phase. The results of the psycho-physiological experiments give rise to the conclusion, that individual attitude to music doesn't primarily influence the effects of music on physiological reactions.

  19. Cadmium exerts its toxic effects on photosynthesis via a cascade mechanism in the cyanobacterium, Synechocystis PCC 6803.

    Science.gov (United States)

    Tóth, Tünde; Zsiros, Ottó; Kis, Mihály; Garab, Győző; Kovács, László

    2012-12-01

    Despite intense research, the mechanism of Cd(2+) toxicity on photosynthesis is still elusive because of the multiplicity of the inhibitory effects and different barriers in plants. The quick Cd(2+) uptake in Synechocystis PCC 6803 permits the direct interaction of cadmium with the photosynthetic machinery and allows the distinction between primary and secondary effects. We show that the CO(2) -dependent electron transport is rapidly inhibited upon exposing the cells to 40 µm Cd(2+) (50% inhibition in ∼15 min). However, during this time we observe only symptoms of photosystem I acceptor side limitation and a build of an excitation pressure on the reaction centres, as indicated by light-induced P700 redox transients, O(2) polarography and changes in chlorophyll a fluorescence parameters. Inhibitory effects on photosystem II electron transport and the degradation of the reaction centre protein D1 can only be observed after several hours, and only in the light, as revealed by chlorophyll a fluorescence transients, thermoluminescence and immunoblotting. Despite the marked differences in the manifestations of these short- and long-term effects, they exhibit virtually the same Cd(2+) concentration dependence. These data strongly suggest a cascade mechanism of the toxic effect, with a primary effect in the dark reactions. © 2012 Blackwell Publishing Ltd.

  20. Human umbilical cord matrix-derived stem cells exert trophic effects on β-cell survival in diabetic rats and isolated islets

    Directory of Open Access Journals (Sweden)

    Yunting Zhou

    2015-12-01

    Full Text Available Human umbilical cord matrix-derived stem cells (uMSCs, owing to their cellular and procurement advantages compared with mesenchymal stem cells derived from other tissue sources, are in clinical trials to treat type 1 (T1D and type 2 diabetes (T2D. However, the therapeutic basis remains to be fully understood. The immunomodulatory property of uMSCs could explain the use in treating T1D; however, the mere immune modulation might not be sufficient to support the use in T2D. We thus tested whether uMSCs could exert direct trophic effects on β-cells. Infusion of uMSCs into chemically induced diabetic rats prevented hyperglycemic progression with a parallel preservation of islet size and cellularity, demonstrating the protective effect of uMSCs on β-cells. Mechanistic analyses revealed that uMSCs engrafted long-term in the injured pancreas and the engraftment markedly activated the pancreatic PI3K pathway and its downstream anti-apoptotic machinery. The pro-survival pathway activation was associated with the expression and secretion of β-cell growth factors by uMSCs, among which insulin-like growth factor 1 (IGF1 was highly abundant. To establish the causal relationship between the uMSC-secreted factors and β-cell survival, isolated rat islets were co-cultured with uMSCs in the transwell system. Co-culturing improved the islet viability and insulin secretion. Furthermore, reduction of uMSC-secreted IGF1 via siRNA knockdown diminished the protective effects on islets in the co-culture. Thus, our data support a model whereby uMSCs exert trophic effects on islets by secreting β-cell growth factors such as IGF1. The study reveals a novel therapeutic role of uMSCs and suggests that multiple mechanisms are employed by uMSCs to treat diabetes.

  1. Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats

    Science.gov (United States)

    Rezaei-Golmisheh, Ali; Malekinejad, Hassan; Asri-Rezaei, Siamak; Farshid, Amir Abbas; Akbari, Peyman

    2015-01-01

    Objective(s): The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. Materials and Methods: Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. Results: The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (PHawthorn’s extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. Conclusion: Data suggested that hawthorn’s extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat. PMID:26361538

  2. Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth.

    Science.gov (United States)

    Cheng, You-Shuang; Peng, Yin-Bo; Yao, Min; Teng, Ji-Ping; Ni, Da; Zhu, Zhi-Jun; Zhuang, Bu-Feng; Yang, Zhi-Yin

    2017-06-03

    Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm2) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Lactobacillus paracasei GMNL-32 exerts a therapeutic effect on cardiac abnormalities in NZB/W F1 mice.

    Science.gov (United States)

    Hu, Wei-Syun; Rajendran, Peramaiyan; Tzang, Bor-Show; Yeh, Yu-Lan; Shen, Chia-Yao; Chen, Ray-Jade; Ho, Tsung-Jung; Vijaya Padma, Viswanadha; Chen, Yi-Hsing; Huang, Chih-Yang

    2017-01-01

    Systemic lupus erythematosus (SLE) is a disease that mostly affects women. Accelerated atherosclerosis is a high-risk factor associated with SLE patients. SLE associated with cardiovascular disease is one of the most important causes of death. In this study, we demonstrated that Lactobacillus paracasei GMNL-32 (GMNL-32), a probiotic species, exhibits anti-fibrosis and anti-apoptotic effects on the cardiac tissue of NZB/WF1 mice. Female NZB/W F1 mice, a well-known and commonly used lupus-prone mouse strain, were treated with or without GMNL-32 administration for 12 weeks. Oral administration of GMNL-32 to NZB/WF1 mice significantly increased the ventricular thickness when compared to that of NZB/WF1 mice. Administration of GMNL-32 significantly attenuated the cardiac cell apoptosis that was observed in exacerbate levels in the control NZB/WF1 mice. Further, the cellular morphology that was slightly distorted in the NZB/WF1 was effectively alleviated in the treatment group mice. In addition, GMNL-32 reduced the level of Fas death receptor-related pathway of apoptosis signaling and enhanced anti-apoptotic proteins. These results indicate that GMNL-32 exhibit an effective protective effect on cardiac cells of SLE mice. Thus, GMNL-32 may be a potential therapeutic strategy against SLE associated arthrosclerosis.

  4. Bone Morphogenetic Protein-2, but Not Mesenchymal Stromal Cells, Exert Regenerative Effects on Canine and Human Nucleus Pulposus Cells

    NARCIS (Netherlands)

    Bach, Frances C.; Miranda-Bedate, Alberto; Van Heel, Ferdi W M; Riemers, Frank M.; Müller, Margot C M E; Creemers, Laura B.|info:eu-repo/dai/nl/162835884; Ito, Keita|info:eu-repo/dai/nl/345809610; Benz, Karin; Meij, Björn P.; Tryfonidou, Marianna A.

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  5. Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on canine and human nucleus pulposus cells

    NARCIS (Netherlands)

    Bach, Frances; Miranda-Bedate, Alberto; van Heel, Ferdi; Riemers, Frank; Muller, Margot; Creemers, Laura; Ito, Keita; Benz, Karin; Meij, Björn; Tryfonidou, M

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  6. Toxic effects exerted on methanogenic, nitrifying and denitrifying bacteria by chemicals used in a milk analysis laboratory

    NARCIS (Netherlands)

    Lopez-Fiuza, J.; Buys, B.; Mosquera-Corral, A.; Omil, F.; Mendez, R.

    2002-01-01

    The toxic effects caused by the chemicals contained in wastewaters generated by laboratories involved in raw milk analyses were assessed using batch assays. These assays were carried out separately with methanogenic, ammonium-oxidizing, nitrite-oxidizing and denitrifying bacteria. Since sodium azide

  7. Lactobacillus paracasei GMNL-32 exerts a therapeutic effect on cardiac abnormalities in NZB/W F1 mice.

    Directory of Open Access Journals (Sweden)

    Wei-Syun Hu

    Full Text Available Systemic lupus erythematosus (SLE is a disease that mostly affects women. Accelerated atherosclerosis is a high-risk factor associated with SLE patients. SLE associated with cardiovascular disease is one of the most important causes of death. In this study, we demonstrated that Lactobacillus paracasei GMNL-32 (GMNL-32, a probiotic species, exhibits anti-fibrosis and anti-apoptotic effects on the cardiac tissue of NZB/WF1 mice. Female NZB/W F1 mice, a well-known and commonly used lupus-prone mouse strain, were treated with or without GMNL-32 administration for 12 weeks. Oral administration of GMNL-32 to NZB/WF1 mice significantly increased the ventricular thickness when compared to that of NZB/WF1 mice. Administration of GMNL-32 significantly attenuated the cardiac cell apoptosis that was observed in exacerbate levels in the control NZB/WF1 mice. Further, the cellular morphology that was slightly distorted in the NZB/WF1 was effectively alleviated in the treatment group mice. In addition, GMNL-32 reduced the level of Fas death receptor-related pathway of apoptosis signaling and enhanced anti-apoptotic proteins. These results indicate that GMNL-32 exhibit an effective protective effect on cardiac cells of SLE mice. Thus, GMNL-32 may be a potential therapeutic strategy against SLE associated arthrosclerosis.

  8. Tanshinone IIA exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor.

    Science.gov (United States)

    Zhang, Xianxie; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Liu, Canglong; Tan, Hongling; Xiao, Chengrong; Zhang, Boli; Wang, Yuguang; Gao, Yue

    2015-04-22

    Tanshinone IIA (Tan IIA) is one of the main natural active ingredients purified from Salvia miltiorrhiza radix, which has long been used in clinical practice in China to treat diseases including liver fibrosis, Alzheimer׳s disease, and cardiovascular diseases. Tan IIA has hepatoprotective properties, and is an efficacious PXR agonist. Our study was designed to observe the function and mechanism of the hepatoprotective properties of Tan IIA. HepG2 cells were used to investigate the vitrol effects of Tan IIA on PXR and CYP3A4. Gut-formed LCA is hepatotoxic, and has been implicated in the pathogenesis of cholestatic diseases. To further investigate the hepatoprotective mechanisms of Tan IIA against LCA-induced cholestasis in vivo, we choose the normal mice and siRNA-treated mice. The in vitro study demonstrated that the effect of Tan IIA on CYP3A4 was mediated by transactivation of PXR in a dose- and time-dependent manner. The in vivo experiments using PXR siRNA revealed that Tan IIA could protect against LCA-induced hepatotoxicity and cholestasis in a dose-dependent manner. These effects were partially caused by the upregulation of PXR, as well as Cyp3a11, Cyp3a13, and Mdr1, which are the enzymes responsible for LCA metabolism. This is the first report showing that the hepatoprotective effects of Tan IIA are partly mediated by PXR. Copyright © 2015. Published by Elsevier Ireland Ltd.

  9. Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects.

    Science.gov (United States)

    van den Burg, Erwin H; Stindl, Julia; Grund, Thomas; Neumann, Inga D; Strauss, Olaf

    2015-12-01

    There is growing interest in anxiolytic and pro-social effects of the neuropeptide oxytocin (OXT), but the underlying intraneuronal mechanisms are largely unknown. Here we examined OXT-mediated anxiolysis in the hypothalamic paraventricular nucleus (PVN) of rats and effects of OXT administration on signaling events in hypothalamic primary and immortalized cells. In vivo, the application of SKF96365 prevented the anxiolytic activity of OXT in the PVN, suggesting that changes in intracellular Ca(2+) mediate the acute OXT behavioral effects. In vitro, mainly in the neurons with autonomous Ca(2+) oscillations, OXT increased intracellular Ca(2+) concentration and oscillation amplitude. Pharmacological intervention revealed OXT-dependent changes in Ca(2+) signaling that required activation of transient receptor potential vanilloid type-2 channel (TRPV2), mediated by phosphoinositide 3-kinase. TRPV2 induced the activation of the anxiolytic mitogen-activated protein kinase kinase (MEK1/2). In situ, immunohistochemistry revealed co-localization of TRPV2 and OXT in the PVN. Thus, functional and pharmacological analyses identified TRPV2 as a mediator of anxiolytic effects of OXT, conveying the OXT signal to MEK1/2 via modulation of intracellular Ca(2+).

  10. Skn-1a/Oct-11 and {Delta}Np63{alpha} exert antagonizing effects on human keratin expression

    Energy Technology Data Exchange (ETDEWEB)

    Lena, Anna Maria; Cipollone, Rita; Amelio, Ivano; Catani, Maria Valeria; Ramadan, Safaa [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy); Browne, Gareth [MRC Toxicology Unit, Leicester University, Leicester LE1 9HN (United Kingdom); Melino, Gerry [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy); MRC Toxicology Unit, Leicester University, Leicester LE1 9HN (United Kingdom); Candi, Eleonora, E-mail: candi@uniroma2.it [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy)

    2010-10-29

    Research highlights: {yields} Skn-1a markedly downregulates {Delta}Np63-driven K14 expression. {yields} {Delta}Np63 inhibits Skn-1a-mediated K10 expression. {yields} {Delta}Np63, mutated in SAM domain, is less effecting in K10 downregulation. {yields} Immunolocalization in human skin of the two transcription factors is partially overlapping. {yields} The antagonistic effects of Skn-1a and p63 is through competition for overlapping responsive elements or through an indirect interaction. -- Abstract: The formation of a stratified epidermis requires a carefully controlled balance between keratinocyte proliferation and differentiation. Here, we report the reciprocal effect on keratin expression of {Delta}Np63, pivotal in normal epidermal morphogenesis and maintenance, and Skn-1a/Oct-11, a POU transcription factor that triggers and regulates the differentiation of keratinocytes. The expression of Skn-1a markedly downregulated {Delta}Np63-driven K14 expression in luciferase reporter assays. The extent of downregulation was comparable to the inhibition of Skn-1a-mediated K10 expression upon expression of {Delta}Np63. {Delta}Np63, mutated in the protein-protein interaction domain (SAM domain; mutated in human ectodermal dysplasia syndrome), was significantly less effecting in downregulating K10, raising the possibility of a direct interaction among Skn-1a and {Delta}Np63. Immunolocalization in human skin biopsies revealed that the expression of the two transcription factors is partially overlapping. Co-immunoprecipitation experiments did not, however, demonstrate a direct interaction between {Delta}Np63 and Skn-1a, suggesting that the antagonistic effects of Skn-1a and p63 on keratin promoter transactivation is probably through competition for overlapping binding sites on target gene promoter or through an indirect interaction.

  11. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway.

    Science.gov (United States)

    Qi, Tianjie; Xu, Fei; Yan, Xixin; Li, Shuai; Li, Haitao

    2016-01-01

    Sulforaphane (1-isothiocyanate-4-methyl sulfonyl butane) is a plant extract (obtained from cruciferous vegetables, such as broccoli and cabbage) and is known to exert anticancer, antioxidant and anti-inflammatory effects. It stimulates the generation of human or animal cells, which is beneficial to the body. The aim of the current study was to determine whether sulforaphane protects against lipopolysaccharide (LPS)‑induced acute lung injury (ALI) through its anti-inflammatory effects, and to investigate the signaling pathways involved. For this purpose, male BALB/c mice were treated with sulforaphane (50 mg/kg) and 3 days later, ALI was induced by the administration of LPS (5 mg/kg) and we thus established the model of ALI. Our results revealed that sulforaphane significantly decreased lactate dehydrogenase (LDH) activity (as shown by LDH assay), the wet-to-dry ratio of the lungs and the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (measured by ELISA), as well as nuclear factor-κB protein expression in mice with LPS-induced ALI. Moreover, treatment with sulforaphane significantly inhibited prostaglandin E2 (PGE2) production, and cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9) protein expression (as shown by western blot analysis), as well as inducible nitric oxide synthase (iNOS) activity in mice with LPS-induced ALI. Lastly, we noted that pre-treatment with sulforaphane activated the nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in the mice with LPS-induced ALI. These findings demonstrate that sulforaphane exerts protective effects against LPS-induced ALI through the Nrf2/ARE pathway. Thus, sulforaphane may be a potential a candidate for use in the treatment of ALI.

  12. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seong-Il [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Ko, Hee-Chul [Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Lee, Nam-Ho [Department of Chemistry, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Kim, Se-Jae, E-mail: sjkim@jejunu.ac.kr [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of)

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  13. Healthy effects exerted by prebiotics, probiotics, and symbiotics with special reference to their impact on the immune system.

    Science.gov (United States)

    Jirillo, Emilio; Jirillo, Felicita; Magrone, Thea

    2012-06-01

    Pre-, pro-, and symbiotics are endowed with a broad spectrum of beneficial effects when administered to animals and humans. A series of experimental and clinical studies have clearly demonstrated that prebiotics, probiotics, or their combination are very effective in attenuating chronic inflammatory conditions such as inflammatory bowel disease or obesity. In addition, these natural products are able to prevent or arrest tumor development, acting on the intestinal microbiota as well as potentiating the immune response.Aging is characterized by a dramatic reduction of both innate and adaptive immune responses, the so-called immunosenescence. This leads to an increased incidence of infections, autoimmune diseases, and cancer in the elderly. Pre-, pro-, and symbiotic administration has been shown to ameliorate the immune response in aging. In particular, administration of a symbiotic to free-living elderly was able to potentiate the release of interleukin-8, thus increasing neutrophils in the host, perhaps explaining the reduced frequency of winter infections in the elderly.

  14. The effect of NGF depletion on the neurotropic influence exerted by the distal stump following nerve transection.

    OpenAIRE

    Doubleday, B; Robinson, P.P.

    1995-01-01

    Following nerve section, regenerating axons from the proximal stump grow preferentially towards the distal stump. It has been postulated that this may result from the release of a neurotropic factor. To investigate whether the protein nerve growth factor (NGF) plays such a role, we immunised adult rats against NGF and examined the effect on regeneration of sectioned nerves through Y-shaped silastic tubes towards either the distal stump or an empty arm. Regeneration through the tubes was asses...

  15. Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.

    Science.gov (United States)

    Barbosa Bezerra, Gislaine; de Menezes de Souza, Luana; Dos Santos, Adailma Santana; de Almeida, Grace Kelly Melo; Souza, Marília Trindade Santana; Santos, Sandra Lauton; Aparecido Camargo, Enilton; Dos Santos Lima, Bruno; de Souza Araújo, Adriano Antunes; Cardoso, Juliana Cordeiro; Gomes, Silvana Vieira Floresta; Gomes, Margarete Zanardo; de Albuquerque, Ricardo Luiz Cavalcanti

    2017-01-01

    Ulcerative colitis (UC) is a common intestinal inflammatory disease with an etiology that is not well understood. Although the anti-inflammatory and anti-oxidant effects of the hydroalcoholic extract of Brazilian red propolis (HERP) have been reported in various experimental models, its protective effect in models of UC have not been evaluated. The purpose of this study was to investigate the chemopreventive effect of hydroalcoholic extract of Brazilian red propolis (HERP) in acetic acid-induced colitis (AAIC) using a rodent model. The HERP was chemically characterised by HPLC/DAD analyses. Male rats were randomly assigned into four groups: sham, vehicle (with AAIC, treated with vehicle), P10 (with AAIC, treated with 10mg/kg HERP), and P100 (with AAIC, treated with 100mg/kg HERP). Treatments were performed for 7days, and colitis was induced on day seven. Animals were euthanized 24h after colitis induction and body weight, colon length, gross and histological scores, malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations in colon tissue, and the immunohistochemical expression of inducible nitric oxide synthase (iNOS) were assessed. The major compounds found in HERP were liquiritigenin (68.8mg/g), formononetin (54.29mg/g), biochanin A (30.97mg/g), and daidzein (19.90mg/g). Rats treated with 10mg/kg HERP demonstrated significant decreases in MPO concentrations, gross and histological scores of tissue damage, and iNOS expression (p<0.05). Similarly, rats treated with 100mg/kg HERP demonstrated significant decreases in MPO levels (p<0.05) and histological scores of tissue damage (p<0.05). The results of this study indicate that oral administration of HERP attenuates AAIC in rats, which may be due to anti-inflammatory effects related to iNOS inhibition. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

    OpenAIRE

    Abhilash Samykutty; Aditya Vittal Shetty; Gajalakshmi Dakshinamoorthy; Mary Margaret Bartik; Gary Leon Johnson; Brian Webb; Guoxing Zheng; Aoshuang Chen; Ramaswamy Kalyanasundaram; Gnanasekar Munirathinam

    2013-01-01

    Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited th...

  17. Old Drug Scaffold, New Activity: Thalidomide-Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression.

    Science.gov (United States)

    Iacopetta, Domenico; Carocci, Alessia; Sinicropi, Maria Stefania; Catalano, Alessia; Lentini, Giovanni; Ceramella, Jessica; Curcio, Rosita; Caroleo, Maria Cristina

    2017-03-07

    Thalidomide was first used for relief of morning sickness in pregnant women and then withdrawn from the market because of its dramatic effects on normal fetal development. Over the last decades, it has been used successfully for the treatment of several pathologies, including cancer. Many analogues with improved activity have been synthesized and tested. Herein we report some effects on the growth and progression of MCF-7 and MDA-MB-231 breast cancer cells by a small series of thalidomide-correlated compounds, which are very effective at inducing cancer cell death by triggering TNFα-mediated apoptosis. The most active compounds are able to drastically reduce the migration of breast cancer cells by regulation of the two major proteins involved in epithelial-mesenchymal transition (EMT): vimentin and E-cadherin. Moreover, these compounds diminish the intracellular biosynthesis of vascular endothelial growth factor (VEGF), which is primarily involved in the promotion of angiogenesis, sustaining tumor progression. The multiple features of these compounds that act on various key points of the tumorigenesis process make them good candidates for preclinical studies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  19. Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

    Directory of Open Access Journals (Sweden)

    Alejandro Silva-Palacios

    2017-08-01

    Full Text Available The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ, prior to 3-nitropropionic acid (3-NP insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NFκB are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NFκB nuclear accumulation was also evaluated.

  20. EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.

    Science.gov (United States)

    Zhang, Chao; Wang, Deng-Feng; Zhang, Zhuang; Han, Dong; Yang, Kan

    2017-03-28

    Ginkgo biloba extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

  1. Leonurine exerts anti-inflammatory effect by regulating inflammatory signaling pathways and cytokines in LPS-induced mouse mastitis.

    Science.gov (United States)

    Song, Xiaojing; Wang, Tiancheng; Zhang, Zecai; Jiang, Haichao; Wang, Wei; Cao, Yongguo; Zhang, Naisheng

    2015-02-01

    Bovine mastitis is defined as the inflammation of mammary gland and is the most multiple diseases in dairy cattle. There is still no effective treatment now. Leonurine, extracted from Leonurus cardiaca, has been proved to have anti-inflammatory effect. In the present study, we utilized a mouse mastitis model to study the effect of leonurine on LPS-induced mastitis. Leonurine was administered three times during the 24 h after inducing infection in the mammary gland. The results showed that leonurine significantly alleviated LPS-induced histopathological changes, downregulated the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), upregulated the level of anti-inflammatory cytokine interleukin-10 (IL-10), and inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further study revealed that leonurine inhibited the expression of Toll-like receptor 4 (TLR4) and the activation of nuclear factor-kappaB (NF-κB) and the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK). Therefore, the results demonstrated that leonurine could downregulate the expression of TNF-α, IL-6, iNOS, and COX-2 and upregulate the expression of IL-10 mainly by inhibiting the expression of TLR4 and the activation of NF-κB and the phosphorylation of p38, ERK, and JNK. Leonurine may be a potential agent for mastitis therapy.

  2. Long-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation.

    Science.gov (United States)

    Hsu, Yung-Ho; Cheng, Chung-Yi; Chen, Yen-Cheng; Chen, Tso-Hsiao; Sue, Yuh-Mou; Tsai, Wei-Lun; Chen, Cheng-Hsien

    2012-08-15

    Adipokine leptin reportedly acts on the kidney in pathophysiological states. However, the influence of leptin on renal tubular epithelial cells is still unclear. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. This study aims to investigate the influence of long-term leptin treatment on gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) and mice. We monitored apoptosis and molecular mechanisms using annexin V/ propidium iodide staining and small interfering RNA transfection. In NRK-52E cells, leptin reduced gentamicin-induced apoptosis at 24h, but significantly increased apoptosis at 48 h. Long-term treatment of leptin decreased Bcl-x(L) expression and increased caspase activity in gentamicin-treated NRK-52E cells. Leptin also increased the expression of cyclooxygenase-2 (COX-2) and its product, prostaglandin E(2) (PGE(2)), in a dose-dependent manner. The COX-2 inhibitor, NS398 (N-[2-(Cyclohexyloxy)-4- nitrophenyl]methanesulfonamide), blocked PGE(2) augmentation and the pro-apoptotic effects of leptin. The addition of PGE(2) recovered the pro-apoptotic effect of leptin in NS398-treated NRK-52E cells. In a mouse animal model, a 10 day leptin treatment significantly increased gentamicin-induced apoptotic cells in proximal tubules. NS398 treatment inhibited this in vivo pro-apoptotic effect of leptin. Results reveal that long-term elevation of leptin induces COX-2-mediated PGE(2) augmentation in renal tubular cells, and then increases these cells' susceptibility to gentamicin-induced apoptosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Severe exercise and exercise training exert opposite effects on human neutrophil apoptosis via altering the redox status.

    Directory of Open Access Journals (Sweden)

    Guan-Da Syu

    Full Text Available Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE usually impedes immunity, chronic moderate exercise (CME improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8 underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface along with redox-related parameters and mitochondria-related parameters. Our results showed that i the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation, and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii most effects of CME were unchanged after detraining; and iv CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H(2O(2, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.

  4. rBPI(21 promotes lipopolysaccharide aggregation and exerts its antimicrobial effects by (hemifusion of PG-containing membranes.

    Directory of Open Access Journals (Sweden)

    Marco M Domingues

    Full Text Available Antimicrobial peptides (AMPs are important potential alternatives to conventional therapies against bacterial infections. rBPI(21 is a 21 kDa peptide based on the N-terminal region of the neutrophil bactericidal/permeability-increasing protein (BPI. This AMP possesses highly selective bactericidal effects on Gram-negative bacteria and have affinity for lipopolysaccharide (LPS which is believed to be at the origin of its neutralizing effect of the LPS segregated into the bloodstream. We aim at understanding the molecular bases of rBPI(21 bactericidal and LPS neutralization actions, using biomembrane model systems. Using dynamic light scattering spectroscopy we demonstrate that rBPI(21 promotes aggregation of negatively charged large unilamellar vesicles (LUV, even in the absence of LPS, and LPS aggregates, while for zwitterionic phosphatidylcholine (POPC LUV the size remains unchanged. The peptide also promotes the fusion (or hemifusion of membranes containing phosphatidylglycerol (POPG. The aggregation and fusion of negatively charged LUV are peptide concentration-dependent until massive aggregation is reached, followed by sample flocculation/precipitation. Concomitantly, there is a progressive change in the zeta-potential of the LUV systems and LPS aggregates. LUV systems composed of phosphatidylglycerol (POPG and lipid mixtures with POPG have higher zeta-potential variations than in the absence of POPG. The interaction of rBPI(21 with lipid vesicles is followed by leakage, with higher effect in POPG-containing membranes. LPS aggregation can be related with a decreased toxicity, possibly by facilitating its clearance by macrophage phagocytosis and/or blocking of LPS specific receptor recognition. Our data indicate that rBPI(21 mechanism of action at the molecular level involves the interaction with the LPS of the outer membrane of Gram-negative bacteria, followed by internalization and leakage induction through the (hemifusion of the bacterial

  5. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis.

    Science.gov (United States)

    Li, H; Sun, J; Du, J; Wang, F; Fang, R; Yu, C; Xiong, J; Chen, W; Lu, Z; Liu, J

    2017-11-27

    Traumatic brain injury (TBI) is a common occurrence following gastrointestinal dysfunction. Recently, more and more attentions are being focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1) is considered as a mediator that links the gut-brain axis. The aim of this study was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain damage in a mouse model of TBI. Male C57BL/6 mice were subjected to a model of TBI-induced by weight-drop impact head injury and were treated intragastrically with Cb. The cognitive deficits, brain water content, neuronal death, and blood-brain barrier (BBB) permeability were evaluated. The expression of tight junction (TJ) proteins, Bcl-2, Bax, GLP-1 receptor (GLP-1R), and phosphorylation of Akt (p-Akt) in the brain were also measured. Moreover, the intestinal barrier permeability, the expression of TJ protein and GLP-1, and IL-6 level in the intestine were detected. Cb treatment significantly improved neurological dysfunction, brain edema, neurodegeneration, and BBB impairment. Meanwhile, Cb treatment also significantly increased the expression of TJ proteins (occludin and zonula occluden-1), p-Akt and Bcl-2, but decreased expression of Bax. Moreover, Cb treatment exhibited more prominent effects on decreasing the levels of plasma d-lactate and colonic IL-6, upregulating expression of Occludin, and protecting intestinal barrier integrity. Furthermore, Cb-treated mice showed increased the secretion of intestinal GLP-1 and upregulated expression of cerebral GLP-1R. Our findings demonstrated the neuroprotective effect of Cb in TBI mice and the involved mechanisms were partially attributed to the elevating GLP-1 secretion through the gut-brain axis. © 2017 John Wiley & Sons Ltd.

  6. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain.

    Science.gov (United States)

    Owen, M R; Doran, E; Halestrap, A P

    2000-01-01

    Although metformin is widely used for the treatment of non-insulin-dependent diabetes, its mode of action remains unclear. Here we provide evidence that its primary site of action is through a direct inhibition of complex 1 of the respiratory chain. Metformin(50 microM) inhibited mitochondrial oxidation of glutamate+malate in hepatoma cells by 13 and 30% after 24 and 60 h exposure respectively, but succinate oxidation was unaffected. Metformin also caused time-dependent inhibition of complex 1 in isolated mitochondria, whereas in sub-mitochondrial particles inhibition was immediate but required very high metformin concentrations (K(0.5),79 mM). These data are compatible with the slow membrane-potential-driven accumulation of the positively charged drug within the mitochondrial matrix leading to inhibition of complex 1. Metformin inhibition of gluconeogenesis from L-lactate in isolated rat hepatocytes was also time- and concentration-dependent, and accompanied by changes in metabolite levels similar to those induced by other inhibitors of gluconeogenesis acting on complex 1. Freeze-clamped livers from metformin-treated rats exhibited similar changes in metabolite concentrations. We conclude that the drug's pharmacological effects are mediated, at least in part, through a time-dependent, self-limiting inhibition of the respiratory chain that restrains hepatic gluconeogenesis while increasing glucose utilization in peripheral tissues. Lactic acidosis, an occasional side effect, canal so be explained in this way. PMID:10839993

  7. Geraniol attenuates fibrosis and exerts anti-inflammatory effects on diet induced atherogenesis by NF-κB signaling pathway.

    Science.gov (United States)

    Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

    2015-09-05

    Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammation, immune responses, cell survival and cell proliferation. Tissue remodeling plays a significant role during the phase of inflammation and oxidative stress. In our study we have evaluated the effect of geraniol (GOH), a natural terpenoid on oxidative stress, inflammation and tissue remodeling in experimental animals. Experimental animals (hamsters) were divided into four groups; group 1 were control animals; group 2 were animals fed GOH alone (100mg/kg b.w. p.o); group 3 were animals fed atherogenic diet (standard pellet diet+10% coconut oil+0.25% cholesterol); group 4 animals were fed atherogenic diet as in group 3+GOH (100mg/kg b.w). At the end of the experimental period animals were killed and liver, heart and aorta tissues were analyzed for lipid peroxidation markers, non enzymic antioxidants and collagen distribution using histological studies like Milligan's trichrome and Picrosirius red staining. As inflammation plays a key role in tissue remodeling we also targeted the key inflammatory cytokine, NF-κB. GOH supplementation greatly prevented the remodeling of tissues by enhancing the free radical scavenging and anti-inflammatory effects. Thus in conclusion it can be suggested that GOH (100mg/kg b.w) prevents the atherogenic diet induced fibrosis in experimental hamsters. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Do tetracyclines and erythromycin exert anti-acne effects by inhibition of P450-mediated degradation of retinoic acid?

    Science.gov (United States)

    Hellmann-Regen, Julian; Herzog, Irmelin; Fischer, Norina; Heuser, Isabella; Regen, Francesca

    2014-04-01

    For decades, retinoic acid (RA) is known as the most potent therapeutic option in the therapy of acne and altered homeostasis of endogenous retinoids has been discussed in the context of acne pathogenesis. Besides retinoids, antibiotics such as tetracyclines or erythromycin are well established in acne pharmacotherapy. Accumulating evidence points towards common molecular pathways being targeted by both RA and anti-acne antibiotics; however, a precise 'common denominator' connecting these chemically diverse anti-acne agents has not yet been identified. Interestingly, tetracyclines are associated with the occurrence of pseudotumor cerebri, a rare neurological side effect otherwise associated with retinoid intoxication or RA exposure. This association at the clinical level suggests an interaction between tetracyclines and endogenous RA signalling. As erythromycin does not cross the blood brain barrier, CNS side effects are not to be expected, yet not precluding a possible local interaction of erythromycin with endogenous RA metabolism in the skin. We hypothesize tetracyclines and erythromycin to locally inhibit endogenous RA metabolism in the skin and thus mimic therapeutic action of RA. This readily testable hypothesis suggests inhibition of endogenous RA metabolism and amplification of endogenous RA signalling as a mechanism underlying the biochemical actions of antibiotics in acne therapy. Elucidation of such interactions may ultimately enhance our understanding of acne therapy and pathogenesis and may yield a sound, scientific basis for hypothesis-driven development of novel therapeutic compounds. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease ☆

    Science.gov (United States)

    Secor, Eric R.; Carson, William F.; Cloutier, Michelle M.; Guernsey, Linda A.; Schramm, Craig M.; Wu, Carol A.; Thrall, Roger S.

    2008-01-01

    Objective Bromelain, a clinically used pineapple extract and natural product, has reported anti-inflammatory and immunomodulatory activities. The purpose of this study was to determine the effect of bromelain treatment in an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). Methods To establish AAD, mice were sensitized with intraperitoneal (i.p.) OVA/alum and challenged with daily OVA aerosols. Mice were treated i.p. with either saline, 2 or 6 mg/kg bromelain, twice daily for four consecutive days. Bronchoalveolar lavage leukocytes and cytokines, lung histology, airway hyperresponsiveness, and lymphocyte populations via flow cytometry were compared between groups. Results Bromelain treatment of AAD mice resulted in reduced total BAL leukocytes, eosinophils, CD4+ and CD8+ T lymphocytes, CD4+/CD8+ T cell ratio, and IL-13. Conclusion Bromelain attenuated development of AAD while altering CD4+ to CD8+ T lymphocyte populations. The reduction in AAD outcomes suggests that bromelain may have similar effects in the treatment of human asthma and hypersensitivity disorders. PMID:16337164

  10. Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids.

    Science.gov (United States)

    Chen, Yi-ching; Liu, Ya-lin; Li, Feng-yin; Chang, Chi-I; Wang, Sheng-yang; Lee, Kuo-yang; Li, Shun-lai; Chen, Yi-peng; Jinn, Tzyy-rong; Tzen, Jason T C

    2011-07-01

    To determine the active ingredient of Niuchangchih (Antrodia camphorata) responsible for its anti-inflammatory effects and the relevant molecular mechanisms. Five major antcins (A, B, C, H, and K) were isolated from fruiting bodies of Niuchangchih. Structural similarity between the antcins and 2 glucocorticoids (cortisone and dexamethasone) was compared. After incubation with each compound, the cytosolic glucocorticoid receptor (GR) was examined for its migration into the nucleus. Mo lecular docking was performed to model the tertiary structure of GR associated with antcins. Incubation with cortisone, dexamethasone or antcin A (but not antcins B, C, H, and K) led to the migration of glucocorticoid receptor into the nucleus. The minimal concentration of antcin A, cortisone and dexamethasone to induce nuclear migration of glucocorticoid receptor was 10, 1, and 0.1 mol/L, respectively. The results are in agreement with the simulated binding affinity scores of these three ligands docking to the glucocorticoid receptor. Molecular modeling indicates that C-7 of antcin A or glucocorticoids is exposed to a hydrophobic region in the binding cavity of the glucocorticoid receptor, and the attachment of a hydrophilic group to C-7 of the other four antcins presumably results in their being expelled when docking to the cavity. The anti-inflammatory effect of Niuchangchih is, at least, partly attributed to antcin A that mimics glucocorticoids and triggers translocation of glucocorticoid receptor into nucleus to initiate the suppressing inflammation.

  11. Hot water extracts of edible Chrysanthemum morifolium Ramat. exert antidiabetic effects in obese diabetic KK-Ay mice.

    Science.gov (United States)

    Yamamoto, Junpei; Tadaishi, Miki; Yamane, Takumi; Oishi, Yuichi; Shimizu, Makoto; Kobayashi-Hattori, Kazuo

    2015-01-01

    In this study, the antidiabetic effects of a hot water extract of edible Chrysanthemum morifolium Ramat. (HW-ECM) were investigated in type 2 diabetic mice. HW-ECM improved blood glucose levels and insulin resistance and increased adiponectin mRNA expression in adipose tissues and protein concentrations in the plasma. Moreover, it increased adipose mRNA and protein expressions of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adiponectin transcription, and mRNA expression of its downstream target genes. It also reduced the adipose cell size and attenuated the mRNA expression of pro-inflammatory adipocytokines in adipose tissues. These data presumably indicate a hypoglycemic mechanism of HW-ECM, involving increased PPARγ expression, decreased the adipocyte sizes, and suppression of chronic inflammation in adipose tissues. Finally, elevated adiponectin levels lead to amelioration of insulin resistance and the corresponding hypoglycemic effects. Therefore, HW-ECM indicates its potential as a functional food for type 2 diabetes.

  12. Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins exert similar effects in the lobster stomatogastric nervous system

    Science.gov (United States)

    Dickinson, Patsy S.; Kurland, Sienna C.; Qu, Xuan; Parker, Brett O.; Sreekrishnan, Anirudh; Kwiatkowski, Molly A.; Williams, Alex H.; Ysasi, Alexandra B.; Christie, Andrew E.

    2015-01-01

    ABSTRACT Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family. PMID:26206359

  13. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling.

    Science.gov (United States)

    Liu, Peng; Atkinson, Samuel J; Akbareian, Sophia E; Zhou, Zhigang; Munsterberg, Andrea; Robinson, Stephen D; Bao, Yongping

    2017-10-04

    Angiogenesis plays an important role in hepatocellular carcinoma (HCC), the inhibition of which is explored for cancer prevention and treatment. The dietary phytochemical sulforaphane (SFN) is known for its anti-cancer properties in vitro and in vivo; but until now, no study has focused on the role of SFN in HCC tumor angiogenesis. In the present study, in vitro cell models using a HCC cell line, HepG2, and human endothelial cells, HUVECs, as well as ex vivo and in vivo models have been used to investigate the anti-tumor and anti-angiogenic effect of SFN. The results showed that SFN decreased HUVEC cell viability, migration and tube formation, all of which are important steps in angiogenesis. More importantly, SFN markedly supressed HepG2-stimulated HUVEC migration, adhesion and tube formation; which may be due to its inhibition on STAT3/HIF-1α/VEGF signalling in HepG2 cells. In addition, SFN significantly reduced HepG2 tumor growth in a modified chick embryo chorioallantoic membrane (CAM) assay, associated with a decrease of HIF-1α and VEGF expression within tumors. Collectively, these findings provide new insights into the inhibitory effect of SFN on HCC tumor angiogenesis as well as tumor growth, and indicate that SFN has potential for the prevention and treatment of HCC.

  14. The Posterior Hypothalamus Exerts Opposing Effects on Nociception via the A7 Catecholamine Cell Group in Rat

    Science.gov (United States)

    Jeong, Younhee; Moes, Jesse R.; Wagner, Monica

    2012-01-01

    Stimulation of the posterior hypothalamic area (PH) produces antinociception in rats and humans, but the precise mechanisms are unknown. The PH forms anatomical connections with the parabrachial area, which contains the pontine A7 catecholamine cell group, a group of spinally projecting noradrenergic neurons known to produce antinociception in the dorsal horn. The aim of the present study was to determine whether PH-induced antinociception is mediated in part through connections with the A7 cell group in female Sprague-Dawley rats, as measured by the tail flick and foot withdrawal latency. Stimulation of the PH with the cholinergic agonist carbachol (125 nmol) produced antinociception that was blocked by pretreatment with atropine sulfate. Intrathecal injection of the α2-adrenoceptor antagonist yohimbine reversed PH-induced antinociception, but the α1-adrenoceptor antagonist WB4101 facilitated antinociception. Intrathecal injection of normal saline had no effect. In a separate experiment, cobalt chloride, which reversibly arrests synaptic activity, was microinjected into the A7 cell group and blocked PH-induced antinociception. These findings provide evidence that the PH modulates nociception in part through connections with the A7 catecholamine cell group through opposing effects. Antinociception occurs from actions at α2-adrenoceptors in the dorsal horn, while concurrent hyperalgesia occurs from actions of norepinephrine at α1-adrenoceptors. This hyperalgesic response likely attenuates antinociception from PH stimulation. PMID:23036619

  15. Strontium exerts dual effects on calcium phosphate cement: Accelerating the degradation and enhancing the osteoconductivity both in vitro and in vivo.

    Science.gov (United States)

    Kuang, Guan-Ming; Yau, W P; Wu, Jun; Yeung, Kelvin W K; Pan, Haobo; Lam, W M; Lu, W W; Chiu, K Y

    2015-05-01

    Calcium phosphate cements (CPCs) have long been used as osteoconductive bone substitutes in the treatment of bone defects. However, the degradation rate of CPC is typically too slow to match the new bone growth rate. It is known that strontium increases the solubility of hydroxyapatite as well as exerts both anabolic and anticatabolic effects on bone. Therefore, we hypothesized that the incorporation of strontium would accelerate the degradation rate and enhance the osteoconductivity of CPC. In this study, Three groups, CPC (0% Sr-CPC), 5% Sr-CPC, and 10% Sr-CPC, were prepared, with the total molar ratio for Sr/(Sr+Ca) in the cement powder phase being 0, 5, and 10%, respectively. In the immersion test, less residual weight was observed in both 5% Sr-CPC and 10% Sr-CPC groups than CPC group. In addition, a higher osteoblastic cell proliferation rate and alkaline phosphatase activity were obtained in the strontium groups. In a rat femur bone defect model comparing CPC with 10% Sr-CPC, at 2 weeks postoperation, early endochondral ossification was found in the 10% Sr-CPC group, whereas only fibrous tissue was observed in control group; at 4-16 weeks postoperation, progressive osteoconduction toward the cement was observed in both groups. At 32 weeks, a higher peri-cement bone area and reduced cement area were noted in the 10% Sr-CPC group. In conclusion, in the 10% Sr-CPC group, strontium exerts dual effects on CPC: accelerating degradation rate and enhancing osteoconductivity, as shown here both in vitro and in vivo. © 2014 Wiley Periodicals, Inc.

  16. Repeated treatment with haloperidol and clozapine exerts differential effects on dye coupling between neurons in subregions of striatum and nucleus accumbens.

    Science.gov (United States)

    Onn, S P; Grace, A A

    1995-11-01

    The delayed onset of action of antipsychotic drugs (APDs) during the treatment of schizophrenia has been hypothesized to temporally correlate with the induction of depolarization block in rat mesencephalic dopamine (DA) cell groups. Nevertheless, it is unknown whether these drugs also exert a delayed action on the dopaminoceptive postsynaptic target cells in the striatal complex. Using in vivo intracellular recording and dye labeling techniques, the effects of APDs on dye coupling were examined in subregions of the striatal complex defined by double staining for calbindin immunoreactivity. Rats treated repeatedly with APDs were found to exhibit a 66-71% higher incidence of coupling that occurred in a drug- and a region-specific manner, that is, both drug treatments increased dye coupling in the limbic-associated accumbens shell region whereas only haloperidol increased dye coupling in the motor-related striatal matrix and accumbens core regions. In addition, cells located in regions in which dye coupling was altered also showed significantly higher input resistance. These changes were not observed in response to DA receptor blockade by acute drug administration or when haloperidol was administered for a period sufficient to induce DA receptor supersensitivity but not DA cell depolarization block (i.e., 2 weeks). Therefore, alteration in dye coupling appears to be correlated temporally with the induction of DA cell depolarization block. The finding that both APDs exert a common action on neurons in the accumbens shell region is consistent with its identification as the site of therapeutic drug actions, whereas the capacity of haloperidol to also affect cells in the motor-related matrix and core regions correlates with its high propensity to induce extrapyramidal side effects.

  17. Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine

    DEFF Research Database (Denmark)

    Ardissino, D; Savonitto, S; Egstrup, K

    1991-01-01

    to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic......The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According...... episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week...

  18. Playing in parallel: the effects of multiplayer modes in active video game on motivation and physical exertion.

    Science.gov (United States)

    Peng, Wei; Crouse, Julia

    2013-06-01

    Although multiplayer modes are common among contemporary video games, the bulk of game research focuses on the single-player mode. To fill the gap in the literature, the current study investigated the effects of different multiplayer modes on enjoyment, future play motivation, and the actual physical activity intensity in an active video game. One hundred sixty-two participants participated in a one-factor between-subject laboratory experiment with three conditions: (a) single player: play against self pretest score; (b) cooperation with another player in the same physical space; (c) parallel competition with another player in separated physical spaces. We found that parallel competition in separate physical spaces was the optimal mode, since it resulted in both high enjoyment and future play motivation and high physical intensity. Implications for future research on multiplayer mode and play space as well as active video game-based physical activity interventions are discussed.

  19. Eugenia dysenterica DC. (Myrtaceae) exerts chemopreventive effects against hexavalent chromium-induced damage in vitro and in vivo.

    Science.gov (United States)

    Ávila, Renato Ivan de; Mattos Alvarenga, Cátia Belo; Ávila, Paulo Henrique Marcelino de; Moreira, Roger Cardoso; Arruda, Andréa Fernandes; Fernandes, Thaís de Oliveira; Rodrigues, Bruna Dos Santos; Andrade, Wanessa Machado; Batista, Aline Carvalho; Paula, José Realino de; Valadares, Marize Campos

    2016-11-01

    Eugenia dysenterica DC. (Myrtaceae) has been widely used in the folk medicine and it presents phytochemicals constituents associated to antioxidant properties. The objective of this study was to investigate the protective effects of E. dysenterica leaf hydroalcoholic extract (EDE) in vitro and in vivo using AMJ2-C11 cells and Swiss mice exposed to hexavalent chromium [Cr(VI)], respectively. AMJ2-C11 cells were pretreated with EDE and exposed to Cr(VI) to evaluate cytotoxicity and the pathways involved in the chemopreventive effects of the extract. Mice were daily pretreated with EDE and then exposed to Cr(VI). Survival analysis, histopathological examination and determination of Cr levels in biological tissues were carried out. In vitro studies showed that pretreatment of the AMJ2-C11 cells with EDE protected against the cytotoxicity and oxidative stress induced by Cr(VI). Consequently, the pretreatment with EDE reduced reactive oxygen species and apoptosis triggered by Cr(VI), probably by a marked antioxidant and chelating activities demonstrated by EDE. Regarding in vivo studies, pretreatment for 10 days with EDE increased survival of the mice exposed to Cr(VI). In addition, EDE prevented liver and kidney pathological damages, in parallel with reduction in chromium levels found in these organs and plasma. EDE also showed a marked antioxidant potential associated with the presence of polyphenols, especially flavonoids and tannins, as confirmed by HPLC-PDA. The study showed that EDE protects against Cr(VI)-induced damage in vitro and in vivo supporting further studies for the development of therapeutic products applied to prevent the damage induced by toxic metals, especially Cr(VI).

  20. Effectively Exerting the Reinforcement of Dopamine Reduced Graphene Oxide on Epoxy-Based Composites via Strengthened Interfacial Bonding.

    Science.gov (United States)

    Li, Wenbin; Shang, Tinghua; Yang, Wengang; Yang, Huichuan; Lin, Song; Jia, Xiaolong; Cai, Qing; Yang, Xiaoping

    2016-05-25

    The effects of dopamine reduced graphene oxide (pDop-rGO) on the curing activity and mechanical properties of epoxy-based composites were evaluated. Taking advantage of self-polymerization of mussel-inspired dopamine, pDop-rGO was prepared through simultaneous functionalization and reduction of graphene oxide (GO) via polydopamine coating. Benefiting from the universal binding ability of polydopamine, good dispersion of pDop-rGO in epoxy matrix was able to be achieved as the content of pDop-rGO being below 0.2 wt %. Curing kinetics of epoxy composites with pDop-rGO were systematically studied by nonisothermal differential scanning calorimetry (DSC). Compared to the systems of neat epoxy or epoxy composites containing GO, epoxy composites loaded with pDop-rGO showed lower activation energy (Eα) over the range of cure (α). It revealed that the amino-bearing pDop-rGO was able to react with epoxy matrix and enhance the curing reactions as an amine-type curing agent. The nature of the interactions at GO-epoxy interface was further evaluated by Raman spectroscopy, confirming the occurrence of chemical bonding. The strengthened interfacial adhesion between pDop-rGO and epoxy matrix thus enhanced the effective stress transfer in the composites. Accordingly, the tensile and flexural properties of EP/pDop-rGO composites were enhanced due to both the well dispersion and strong interfacial bonding of pDop-rGO in epoxy matrix.

  1. Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors.

    Science.gov (United States)

    Darling, Rebecca A; Zhao, Huan; Kinch, Dallas; Li, Ai-Jun; Simasko, Steven M; Ritter, Sue

    2014-07-01

    β-mercaptoacetate (MA) is a drug known to block mitochondrial oxidation of medium- and long-chain fatty acids (FAs) and to stimulate feeding. Because MA-induced feeding is vagally dependent, it has been assumed that the feeding response is mediated by MA's antimetabolic action at a peripheral, vagally innervated site. However, MA's site of action has not yet been identified. Therefore, we used fluorescent calcium measurements in isolated neurons from rat nodose ganglia to determine whether MA has direct effects on vagal sensory neurons. We found that MA alone did not alter cytosolic calcium concentrations in nodose neurons. However, MA (60 μM to 6 mM) significantly decreased calcium responses to both linoleic acid (LA; 10 μM) and caprylic acid (C8; 10 μM) in all neurons responsive to LA and C8. GW9508 (40 μM), an agonist of the FA receptor, G protein-coupled receptor 40 (GPR40), also increased calcium levels almost exclusively in FA-responsive neurons. MA significantly inhibited this response to GW9508. MA did not inhibit calcium responses to serotonin, high K(+), or capsaicin, which do not utilize GPRs, or to CCK, which acts on a different GPR. GPR40 was detected in nodose ganglia by RT-PCR. Results suggest that FAs directly activate vagal sensory neurons via GPR40 and that MA antagonizes this effect. Thus, we propose that MA's nonmetabolic actions on GPR40 membrane receptors, expressed by multiple peripheral tissues in addition to the vagus nerve, may contribute to or mediate MA-induced stimulation of feeding. Copyright © 2014 the American Physiological Society.

  2. Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Karine Andreau

    2012-01-01

    Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

  3. Milk basic protein supplementation exerts an anti-inflammatory effect in a food-allergic enteropathy model mouse.

    Science.gov (United States)

    Ono-Ohmachi, Aiko; Nakajima-Adachi, Haruyo; Morita, Yoshikazu; Kato, Ken; Hachimura, Satoshi

    2017-12-20

    To examine novel functions of milk basic protein (MBP) in T-cell-related inflammatory diseases, such as autoimmune diseases and allergies, we evaluated the effects of MBP on the causative responses of ovalbumin (OVA)-specific T cells in a food-allergic enteropathy model, OVA23-3 mice, which express an OVA-specific T-cell receptor gene. The OVA-specific CD4+ T cells of the mesenteric lymph nodes (MLN) from OVA23-3 mice were cultured with CD11c+ dendritic cells of MLN from BALB/cA mice in the absence or presence of MBP following stimulation with OVA; then the levels of CD69 expression and the levels of cytokine production by CD4+ T cells were measured to evaluate activation. The effects of MBP supplementation of OVA 23-3 mice were assessed by feeding a diet containing OVA (OVA diet) with or without MBP for 28 d. Intestinal inflammation, together with activation and cytokine production of CD4+ T cells by MLN, as well as femoral bone mineral density, were measured. In in vitro culture, MBP inhibited excess activation and IL-4 production by CD4+ T cells. The supplementation of MBP to the OVA diet attenuated OVA-specific IgE production in OVA-diet-fed OVA23-3 mice and slightly resolved developing enteropathy caused by excess IL-4 production by CD4+ T cells. Feeding OVA diet to OVA23-3 mice exhibited bone loss accompanied with enteropathy, whereas MBP supplementation prevented bone loss and increased osteoprotegerin, an osteoclastogenesis inhibitory factor, in the mice. The inhibition of T-cell-activation in both MLN and bone marrow by MBP supplementation may help prevent increased IgE levels caused by excessive IL-4 production and bone loss accompanied by enteropathy. Our findings show that MBP may help attenuate both T-cell-related inflammation and bone loss. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

    Science.gov (United States)

    Zhang, Li-Min; Sun, Cong-Cong; Mo, Ming-Shu; Cen, Luan; Wei, Lei; Luo, Fei-Fei; Li, Yi; Li, Guo-Fei; Zhang, Si-Yun; Yi, Li; Huang, Wei; Liu, Zhuo-Lin; Le, Wei-Dong; Xu, Ping-Yi

    2015-01-01

    Background: Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro. Methods: The mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level. Results: The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001). Conclusions: DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons. PMID:26112716

  5. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  6. Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Azad, Abul; Wang, Wang; Wang, Xiuhua; Murray, Allan G; Kassiri, Zamaneh

    2017-08-01

    Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) and structural remodeling, and left ventricular (LV) dilation and dysfunction. Tissue inhibitors of metalloproteinase (TIMPs) inhibit matrix metalloproteinases (MMPs), the main regulators of ECM turnover. TIMPs also have MMP-independent functions. TIMP3 levels are reduced in the heart within 24 h of MI in mice. We investigated if overexpression of TIMP3 post-MI limits adverse remodeling and LV dilation and dysfunction. MI was induced by left anterior descending coronary artery ligation in 10- to 12-wk-old male C57BL/6J mice, and adenoviral constructs expressing human (h)TIMP3 (Ad-hTIMP3) or no TIMP (Ad-Null) were injected in the peri-infarct zone (5.4 × 107 plaque-forming units/heart, 5 injections/heart). Cardiac function assessed by echocardiography showed improved LV physiology and reduced LV dilation after TIMP3 overexpression compared with the Ad-Null-MI group. Post-MI adverse remodeling was attenuated in the Ad-hTIMP3-MI group, as assessed by greater cardiomyocyte density, less infarct expansion, and ECM disruption. TIMP3 overexpression blunted the early rise in proteolytic activities post-MI. A higher density of coronary arteries and a greater number of proliferating endothelial cells were detected in the infarct and peri-infarct regions in the Ad-hTIMP3-MI group compared with the Ad-Null-MI group. In vitro three-dimensional angiogenesis assay confirmed that recombinant TIMP3 promotes angiogenesis in human endothelial cells, although biphasically and in a dose-dependent manner. Intriguingly, overexpression of Ad-hTIMP3 at 10-fold higher concentration had no beneficial effects, consistent with antiangiogenic effects of TIMP3 at higher doses. In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis.NEW & NOTEWORTHY Here, we report that

  7. Essential oils of Origanum compactum and Thymus vulgaris exert a protective effect against the phytopathogen Allorhizobium vitis.

    Science.gov (United States)

    Habbadi, Khaoula; Meyer, Thibault; Vial, Ludovic; Gaillard, Vincent; Benkirane, Rachid; Benbouazza, Abdellatif; Kerzaon, Isabelle; Achbani, El Hassan; Lavire, Céline

    2017-12-29

    Allorhizobium (Agrobacterium) vitis is a host-specific pathogenic bacterium that causes grapevine crown gall disease, affecting vine growth and production worldwide. The antibacterial activities of different aromatic plant essential oils were tested in vitro and in planta against A. vitis. Among the essential oils tested, those of Origanum compactum and Thymus vulgaris showed the most significant in vitro antibacterial activities, with a MIC of 0.156 and 0.312 mg/mL, respectively. A synergistic effect of these two essential oils (1:1) was observed and confirmed by the checkerboard test. Carvacrol (61.8%) and thymol (47.8%) are, respectively, the major compounds in the essential oils of O. compactum and T. vulgaris and they have been shown to be largely responsible for the antibacterial activities of their corresponding essential oils. Results obtained in vitro were reinforced by an in planta pathogenicity test. A mixture of O. compactum and T. vulgaris essential oils (1:1), inoculated into the injured stem of a tomato plant and a grapevine at 0.312 mg/mL as a preventive treatment, reduced both the number of plants developing gall symptoms and the size of the tumors.

  8. Piceatannol Exerts Anti-Obesity Effects in C57BL/6 Mice through Modulating Adipogenic Proteins and Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Yen-Chen Tung

    2016-10-01

    Full Text Available Obesity is a global health concern. Piceatannol (Pic, an analog of resveratrol (Res, has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD-induced obese animal model. The results showed that Pic significantly reduced mouse body weight in a dose-dependent manner without affecting food intake. Serum total cholesterol (TC, low-density lipoprotein (LDL, high-density lipoprotein (HDL levels, and blood glucose (GLU were significantly lowered in Pic-treated groups. Pic significantly decreased the weight of liver, spleen, perigonadal and retroperitoneal fat compared with the HFD group. Pic significantly reduced the adipocyte cell size of perigonadal fat and decreased the weight of liver. Pic-treated mice showed higher phosphorylated adenosine 5′-monophosphate-activated protein kinase (pAMPK and phosphorylated acetyl-CoA carboxylase (pACC protein levels and decreased protein levels of CCAAT/enhancer-binding protein C/EBPα, peroxisome proliferator-activated receptor PPARγ and fatty acid synthase (FAS, resulting in decreased lipid accumulation in adipocytes and the liver. Pic altered the composition of the gut microbiota by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes compared with the HFD group. Collectively, these results suggest that Pic may be a candidate for obesity treatment.

  9. Sea lamprey carcasses exert local and variable food web effects in a nutrient-limited Atlantic coastal stream

    Science.gov (United States)

    Weaver, Daniel M.; Coghlan, Stephen M.; Zydlewski, Joseph D.

    2016-01-01

    Resource flows from adjacent ecosystems are critical in maintaining structure and function of freshwater food webs. Migrating sea lamprey (Petromyzon marinus) deliver a pulsed marine-derived nutrient subsidy to rivers in spring when the metabolic demand of producers and consumers are increasing. However, the spatial and temporal dynamics of these nutrient subsidies are not well characterized. We used sea lamprey carcass additions in a small stream to examine changes in nutrients, primary productivity, and nutrient assimilation among consumers. Algal biomass increased 57%–71% immediately adjacent to carcasses; however, broader spatial changes from multiple-site carcass addition may have been influenced by canopy cover. We detected assimilation of nutrients (via δ13C and δ15N) among several macroinvertebrate families including Heptageniidae, Hydropsychidae, and Perlidae. Our research suggests that subsidies may evoke localized patch-scale effects on food webs, and the pathways of assimilation in streams are likely coupled to adjacent terrestrial systems. This research underscores the importance of connectivity in streams, which may influence sea lamprey spawning and elicit varying food web responses from carcass subsidies due to fine-scale habitat variables.

  10. IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway

    Directory of Open Access Journals (Sweden)

    Xinyuan Yang

    2014-01-01

    Full Text Available Mesenchymal stem cells (MSCs can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-γ would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM- derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-γ gene under the control of the EF1α promoter. The IFN-γ-modified MSCs effectively secreted functional IFN-γ, which led to long-term expression of TRAIL. More importantly, the IFN-γ-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-γ-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-γ-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-γ-modified MSCs.

  11. LPLRFamide exerts short-term anorexigenic effects that coincide with magnocellular division of the hypothalamic paraventricular nucleus activation.

    Science.gov (United States)

    Scheel, Amy; Deal, Nick; St John, Natalie; Wells, Amy; Caruso, Maggie; Gilbert, Elizabeth R; Cline, Mark

    2017-05-15

    LPLRFamide is a member of the RFamide peptide family that elicits an anorexigenic effect when centrally injected in chicks although the mechanism mediating this response is poorly understood. Therefore, the purpose of this experiment was to elucidate the hypothalamic mechanism of short-term anorexia after central administration of LPLRFamide in chicks. In Experiment 1 chicks centrally injected with LPLRFamide decreased food intake at 15min but not 30min following administration compared to vehicle-injected chicks. For Experiment 2, c-Fos immunoreactivity was quantified in several appetite-associated hypothalamic nuclei and in LPLRF-injected chicks, compared to vehicle-injected chicks, there was an increase in the number of reactive cells in the magnocellular division of the paraventricular nucleus. Lastly in Experiment 3, real time-PCR was performed and hypothalamic proopiomelanocortin (POMC) mRNA abundance was increased in LPRLFamide-injected chicks compared to vehicle-injected chicks. Thus, following central injection of LPLRFamide there is activation of the paraventricular nucleus of the hypothalamus and increased expression of hypothalamic POMC mRNA in chicks. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Science.gov (United States)

    Challis, Rosemary C; Tian, Huikai; Yin, Wenbin; Ma, Minghong

    2016-01-01

    We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII), a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE) 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter) and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found), similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice) have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  13. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Directory of Open Access Journals (Sweden)

    Rosemary C Challis

    Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  14. Puerarin Exerts an Antiinflammatory Effect by Inhibiting NF-kB and MAPK Activation in Staphylococcus aureus-Induced Mastitis.

    Science.gov (United States)

    Wu, Haichong; Zhao, Gan; Jiang, Kangfeng; Chen, Xiuying; Zhu, Zhe; Qiu, Changwei; Deng, Ganzhen

    2016-10-01

    Mastitis is defined as the inflammation of the mammary gland. There is generally no effective treatment for mastitis in animals. Puerarin, extracted from Radix puerariae, has been proven to possess many biological activities. The present study aims to reveal the potential mechanism that is responsible for the antiinflammatory action of puerarin in Staphylococcus aureus (S. aureus)-induced mastitis in mice. Histopathological changes showed that puerarin ameliorated the inflammatory injury induced by S. aureus. Quantitative real-time polymerase chain reaction and ELISA analysis indicated that puerarin not only suppressed the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 but also promoted the secretion of IL-10. Toll-like receptor 2 (TLR2) is important in the immune defense against S. aureus infection. Research in molecular biology has shown that the expression of TLR2 was inhibited with administration of puerarin. Further studies were performed on NF-kB and mitogen-activated protein kinase signaling pathways using western blot. The results demonstrated that puerarin suppressed phosphorylated IkBα, p65, p38, extracellular signal-regulated kinase 1and 2 (ERK), and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. All of the results suggested that puerarin may be a potential therapy for treating mastitis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Piceatannol Exerts Anti-Obesity Effects in C57BL/6 Mice through Modulating Adipogenic Proteins and Gut Microbiota.

    Science.gov (United States)

    Tung, Yen-Chen; Lin, Yu-Hsuan; Chen, Hong-Jhang; Chou, Shen-Chieh; Cheng, An-Chin; Kalyanam, Nagabhushanam; Ho, Chi-Tang; Pan, Min-Hsiung

    2016-10-25

    Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced mouse body weight in a dose-dependent manner without affecting food intake. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) levels, and blood glucose (GLU) were significantly lowered in Pic-treated groups. Pic significantly decreased the weight of liver, spleen, perigonadal and retroperitoneal fat compared with the HFD group. Pic significantly reduced the adipocyte cell size of perigonadal fat and decreased the weight of liver. Pic-treated mice showed higher phosphorylated adenosine 5'-monophosphate-activated protein kinase (pAMPK) and phosphorylated acetyl-CoA carboxylase (pACC) protein levels and decreased protein levels of CCAAT/enhancer-binding protein C/EBPα, peroxisome proliferator-activated receptor PPARγ and fatty acid synthase (FAS), resulting in decreased lipid accumulation in adipocytes and the liver. Pic altered the composition of the gut microbiota by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes compared with the HFD group. Collectively, these results suggest that Pic may be a candidate for obesity treatment.

  16. A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model.

    Science.gov (United States)

    Kang, Suk Woo; Kim, Kyung-A; Lee, Chung Hyun; Yang, Sung Jae; Kang, Tae Kyeom; Jung, Je Hyeong; Kim, Tae-Jin; Oh, Sang-Rok; Jung, Sang Hoon

    2017-12-27

    In contrast to other leguminous plants generally used as food, Rhynchosia volubilis Loureiro, a small soybean with a black seed coat, has been used as a traditional oriental remedy for various human diseases in Eastern Asia. In this study, we demonstrated the protective effect of R. volubilis against dry eye disease. We aimed to investigate whether a standardized ethanol extract of R. volubilis (EERV) can protect the cornea in a benzalkonium chloride (BAC)-induced mouse dry eye model. Experimental dry eye was induced by the instillation of 0.2% BAC on mouse cornea. A standardized ethanol extract of R. volubilis (EERV) was orally administered following BAC treatment. The positive control group was treated with commercial eye drops. Fluorescein staining, tear break-up time (BUT), and hematoxylin and eosin staining were evaluated on the ocular surface. Squamous metaplasia and apoptosis in the corneal epithelial layer were detected by immunostaining. Furthermore, the protein expression of cytochrome c, Bcl-2, and Bax was determined. EERV treatment significantly improved fluorescein scoring, BUT, and smoothness in the cornea compared to the vehicle group. In addition, EERV inhibited squamous metaplasia and apoptosis in the cornea. The expression of cytochrome c and Bax was upregulated, while that of Bcl-2 was downregulated in the vehicle group compared with that in the control group. However, EERV treatment inhibited the expression of cytochrome c and Bax, while that of Bcl-2 was improved. Standardized EERV could be a beneficial candidate for the treatment of dry eye disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. One minute static stretch of plantar flexors transiently increases H reflex excitability and exerts no effect on corticospinal pathways.

    Science.gov (United States)

    Budini, Francesco; Gallasch, Eugen; Christova, Monica; Rafolt, Dietmar; Rauscher, Andreas Benedikt; Tilp, Markus

    2017-08-01

    What is the central question of this study? What mediates neural responses following static stretching, and how long do these influences last? What is the main finding and its importance? This study shows that 1 min of static stretching inhibits the tendon tap reflex and facilitates the H reflex without influencing motor-evoked potentials. The results indicate that at least two different mechanisms mediate neural responses after static stretching. The purpose of this study was to determine whether the neural responses observed after static stretching are mediated by sensitivity of muscle spindles, spinal excitability or cortical excitability and how long these influences last. Nineteen volunteers (25.7 ± 5.6 years old) were tested for the tendon tap reflex (T-reflex), H reflex and motor-evoked potentials on ankle flexors and extensors immediately, 5 and 10 min after 1 min static stretching applied at individual maximal ankle dorsiflexion, as well as immediately, 5 and 10 min after a control period of the same duration. Comparison of measurements collected immediately after stretching or control conditions revealed that the T-reflex was weaker after stretching than after control (-59.2% P = 0.000). The T-reflex showed a slow recovery rate within the first 150 s after stretching, but 5 min after the inhibition had disappeared. The H reflex increased immediately after stretching (+18.3%, P = 0.036), showed a quick tendency to recover and returned to control values within 5 min from stretching. Motor-evoked potentials were not affected by the procedure. These results suggest that 1 min of static stretching primarily decreases muscle spindle sensitivity and facilitates the H reflex, whereas effects on the motor cortex can be excluded. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  18. PAF exerts a direct apoptotic effect on the rat H9c2 cardiomyocytes in Ca2+-dependent manner.

    Science.gov (United States)

    Zhao, Dan; Chu, Wen-Feng; Wu, Ling; Li, Jing; Liu, Qing-Mei; Lu, Yan-Jie; Qiao, Guo-Fen; Wang, Zhi-Guo; Zhang, Zhi-Ren; Yang, Bao-Feng

    2010-08-06

    Previous studies suggested that platelet-activating factor (PAF) plays an important role in ischemic diseases. Apoptosis has been implicated in myocardial infarction-related cell death. The present study was designed to determine whether PAF could induce apoptosis in cardiac myocytes and the underlying mechanisms by which PAF causes apoptosis. H9c2 cardiac myocytes were used to investigate the effect of PAF on intracellular calcium concentration, cell viability and cell apoptosis. Signaling pathway of caspase-3, cytochrome c and MAPK (ERK, JNK, p38) was determined during the PAF induced apoptosis. First, our results showed that treatment of H9c2 cardiomyocytes with PAF (0.2 to 20 microM) caused apoptosis in these cells and the apoptotic process was suppressed by either BN52021 (an antagonist of PAF receptor) or BAPTA/AM (an intracellular Ca2+ chelator), suggesting an involvement of PAF and its receptor mediated calcium-dependent signaling. Second, we found that activity of p38-MAPK (mitogen-activated protein kinase) and caspase-3 was elevated in the cells treated with PAF, without altering activity of ERK and JNK, and that PAF-induced enhancement of caspase-3 activity was attenuated by application of either BAPTA/AM or SB203580 (p38 inhibitor). Furthermore, PAF-induced apoptosis and release of cytochrome c from mitochondria was blunted by SB203580, and PAF-induced enhancement of p38 activity was also attenuated by BAPTA/AM. Our data implicate that a PAF and its receptor in triggering apoptosis occurs in cultured H9c2 cardiac myocytes via a calcium-dependent p38 MAPK activated cytochrome c/caspase-3 apoptosis signaling pathway. Crown Copyright (c) 2009. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Large Neutral Amino Acid Supplementation Exerts Its Effect through Three Synergistic Mechanisms: Proof of Principle in Phenylketonuria Mice.

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    Danique van Vliet

    Full Text Available Phenylketonuria (PKU was the first disorder in which severe neurocognitive dysfunction could be prevented by dietary treatment. However, despite this effect, neuropsychological outcome in PKU still remains suboptimal and the phenylalanine-restricted diet is very demanding. To improve neuropsychological outcome and relieve the dietary restrictions for PKU patients, supplementation of large neutral amino acids (LNAA is suggested as alternative treatment strategy that might correct all brain biochemical disturbances caused by high blood phenylalanine, and thereby improve neurocognitive functioning.As a proof-of-principle, this study aimed to investigate all hypothesized biochemical treatment objectives of LNAA supplementation (normalizing brain phenylalanine, non-phenylalanine LNAA, and monoaminergic neurotransmitter concentrations in PKU mice.C57Bl/6 Pah-enu2 (PKU mice and wild-type mice received a LNAA supplemented diet, an isonitrogenic/isocaloric high-protein control diet, or normal chow. After six weeks of dietary treatment, blood and brain amino acid and monoaminergic neurotransmitter concentrations were assessed.In PKU mice, the investigated LNAA supplementation regimen significantly reduced blood and brain phenylalanine concentrations by 33% and 26%, respectively, compared to normal chow (p<0.01, while alleviating brain deficiencies of some but not all supplemented LNAA. Moreover, LNAA supplementation in PKU mice significantly increased brain serotonin and norepinephrine concentrations from 35% to 71% and from 57% to 86% of wild-type concentrations (p<0.01, respectively, but not brain dopamine concentrations (p = 0.307.This study shows that LNAA supplementation without dietary phenylalanine restriction in PKU mice improves brain biochemistry through all three hypothesized biochemical mechanisms. Thereby, these data provide proof-of-concept for LNAA supplementation as a valuable alternative dietary treatment strategy in PKU. Based on these

  20. Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibodies and Inflammatory Mediators

    Science.gov (United States)

    Baghdadi, Hussam; Abdel-Aziz, Nada; Ahmed, Nagwa Sayed; Mahmoud, Hany Salah; Barghash, Ayman; Nasrat, Abdullah; Nabo, Manal Mohamed Helmy; El Sayed, Salah Mohamed

    2015-01-01

    Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients’ blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients’ blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: “Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize”. Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be

  1. Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

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    Shujing Shi

    Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

  2. Chamaejasmin B exerts anti-MDR effect in vitro and in vivo via initiating mitochondria-dependant intrinsic apoptosis pathway.

    Science.gov (United States)

    Wang, Ya Jie; Li, Qi; Xiao, Hong Bin; Li, Yu Jie; Yang, Qing; Kan, Xiao Xi; Chen, Ying; Liu, Xiao Ni; Weng, Xiao Gang; Chen, Xi; Cai, Wei Yan; Guo, Yan; Huang, He Fei; Zhu, Xiao Xin

    2015-01-01

    Multidrug resistance (MDR) is the main obstacle limiting the efficacy of cancer chemotherapy. Looking for novel anti-MDR agents is an important way to conquer cancer drug resistance. We recently established that chamaejasmin B (CHB), a natural biflavone from Stellera chamaejasme L., is the major active component. However, its anti-MDR activity is still unknown. This study investigated the anti-MDR effect of CHB and the underlying mechanisms. First, it was found that CHB inhibited the growth of both sensitive and resistant cell lines in vitro, and the average resistant factor (RF) of CHB was only 1.26. Furthermore, CHB also displayed favorable anti-MDR activity in KB and KBV200 cancer cells xenograft mice. Subsequent study showed that CHB induced G0/G1 cell cycle arrest as well as apoptosis both in KB and in resistant KBV200 cancer cells. Further studies showed that CHB had no influence on the level of Fas/FasL and activation of procaspase 8. However, CHB-induced apoptosis was dependent on the activation of caspase 9 and caspase 3. Moreover, CHB treatment resulted in the elevation of the Bax/Bcl-2 ratio, attenuation of mitochondrial membrane potential (ΔΨm), and release of cytochrome c and apoptosis-inducing factor from mitochondria into cytoplasm both in KB and KBV200 cells. In conclusion, CHB exhibited good anti-MDR activity in vitro and in vivo, and the underlying mechanisms may be related to the activation of mitochondrial-dependant intrinsic apoptosis pathway. These findings provide a new leading compound for MDR therapy and supply a new evidence for the potential of CHB to be employed in clinical trial of MDR therapy in cancers.

  3. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    Science.gov (United States)

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibodies and Inflammatory Mediators.

    Science.gov (United States)

    Baghdadi, Hussam; Abdel-Aziz, Nada; Ahmed, Nagwa Sayed; Mahmoud, Hany Salah; Barghash, Ayman; Nasrat, Abdullah; Nabo, Manal Mohamed Helmy; El Sayed, Salah Mohamed

    2015-04-01

    Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients' blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients' blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: "Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize". Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be promising

  5. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

    Science.gov (United States)

    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  6. Recombinant hamster oviductin is biologically active and exerts positive effects on sperm functions and sperm-oocyte binding.

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    Xiaojing Yang

    Full Text Available Studies carried out in several mammalian species suggest that oviductin, also known as oviduct-specific glycoprotein or OVGP1, plays a key role in sperm capacitation, fertilization, and development of early embryos. In the present study, we used recombinant DNA technology to produce, for the first time, recombinant hamster OVGP1 (rHamOVGP1 in human embryonic kidney 293 (HEK293 cells. rHamOVGP1 secreted in the culture medium was purified by affinity chromatography. The resulting protein migrated as a poly-dispersed band of 160-350 kDa on SDS-PAGE corresponding to the molecular mass of the native HamOVGP1. Subsequent mass spectrometric analysis of the purified rHamOVGP1 confirmed its identity as HamOVGP1. Immunocytochemistry demonstrated binding of rHamOVGP1 to the mid-piece and head of hamster sperm and to the zona pellucida (ZP of ovarian oocytes. In vitro functional experiments showed that addition of rHamOVGP1 in the capacitation medium further enhanced tyrosine phosphorylation of two sperm proteins of approximately 75 kDa and 83 kDa in a time-dependent manner. After 3 hours of incubation in the presence of rHamOVGP1, a significant increase in acrosome reaction was measured. Pretreatment of either sperm or oocyte with 20 μg/ml of rHamOVGP1 prior to sperm-egg binding assay significantly increased the number of sperm bound to the ZP. Addition of rHamOVGP1 in the medium during sperm-egg binding with either oocyte or sperm pretreated with rHamOVGP1 also saw an increase in the number of sperm bound to ZP. In all experimental conditions, the effect of rHamOVGP1 on sperm-oocyte binding was negated by the addition of monoclonal anti-HamOVGP1 antibody. The successful production and purification of a biologically active rHamOVGP1 will allow further exploration of the function of this glycoprotein in reproductive function.

  7. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells.

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    Abhilash Samykutty

    Full Text Available Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP. Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these

  8. Acute effectiveness of a "fat-loss" product on substrate utilization, perception of hunger, mood state and rate of perceived exertion at rest and during exercise.

    Science.gov (United States)

    Alkhatib, Ahmad; Seijo, Marcos; Larumbe, Eneko; Naclerio, Fernando

    2015-01-01

    Achieving fat-loss outcomes by ingesting multi-ingredient mixtures may be further enhanced during exercise. This study tested the acute thermogenic effectiveness of a commercially available multi-ingredient product (Shred-Matrix®), containing Green Tea Extract, Yerba Maté, Guarana Seed Extract, Anhydrous caffeine, Saw palmetto, Fo-Ti, Eleuthero root, Cayenne Pepper, and Yohimbine HCI, on fatty acid oxidation (FAO), perception of hunger, mood state and rate of perceived exertion (RPE) at rest and during 30 min of submaximal exercise. Following institutional ethical approval, twelve healthy recreationally active participants, five females and seven males, were randomized to perform two separate experimental ergometry cycling trials, and to ingest 1.5 g (3 × capsules) of either a multi-ingredient supplement (SHRED) or placebo (PL). Participants rested for 3 h, before performing a 30-min cycling exercise corresponding to their individually-determined intensity based on their maximal fat oxidation (Fatmax). Fatty acid oxidation (FAO) was determined at rest, 3 h before exercise (Pre1), immediately before exercise (Pre2) and during exercise (Post), using expired gasses and indirect calorimetry. Rate of perceived exertion (RPE) was measured every 3 min during the 30-min exercise. Additionally both mood state and perception of hunger were assessed at Pre1, Pre2 and Post exercise. A repeated measures ANOVA design and Cohen's d effect sizes were used to analyze potential differences between times and treatment conditions. FAO increased in SHRED from Pre1 to Pre2 [0.56 ± 0.26 to 0.96 ± 0.37, (p = 0.003, d =1.34)] but not in PL [0.67 ± 0.25 to 0.74 ± 0.19, (p = 0.334) d = 0.49], with no differences were found between conditions (p = 0.12, d = 0.49). However, Cohen's d = 0.77 revealed moderate effect size in favor of SHRED from Pre to Post exercise. RPE values were lower in SHRED compared to Pl (phunger were not different between conditions, with no interaction effects

  9. Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism – a role for Ca2+?

    Science.gov (United States)

    R. Oliveira, Sara; Queiroga, Cláudia S. F.

    2015-01-01

    Abstract Carbon monoxide (CO) is an endogenously produced gasotransmitter with important biological functions: anti‐inflammation, anti‐apoptosis, vasomodulation and cell metabolism modulation. The most recognized cellular target for CO is the mitochondria. Physiological concentrations of CO generate mitochondrial reactive oxygen species (ROS), which are signalling molecules for CO‐induced pathways. Indeed, small amounts of ROS promote cytoprotection by a preconditioning effect. Furthermore, CO prevents cell death by limiting mitochondrial membrane permeabilization, which inhibits the release of pro‐apoptotic factors into the cytosol; both events are ROS dependent. CO also increases the ability of mitochondria to take up Ca2+. Mitochondrial metabolism is modulated by CO, namely by increasing TCA cycle rate, oxidative phosphorylation and mitochondrial biogenesis, which, in turn, increases ATP production. CO's modulation of metabolism might be important for cellular response to diseases, namely cancer and ischaemic diseases. Finally, another cytoprotective role of CO involves the control of Ca2+ channels. By limiting the activity of T‐type and L‐type Ca2+ channels, CO prevents excitotoxicity‐induced cell death and modulates cell proliferation. Several questions concerning Ca2+ signalling, mitochondria and CO can be asked, for instance whether CO modulation of cell metabolism would be dependent on the mitochondrial Ca2+ uptake capacity, since small amounts of Ca2+ can increase mitochondrial metabolism. Whether CO controls Ca2+ communication between mitochondria and endoplasmic reticulum is another open field of research. In summary, CO emerges as a key gasotransmitter in the control of several cellular functions of mitochondria: metabolism, cell death and Ca2+ signalling. PMID:26377343

  10. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing

    Science.gov (United States)

    Souza, Mariana C.; Paixão, Flávio Henrique Marcolino; Ferraris, Fausto K.; Ribeiro, Isabela; Henriques, Maria das Graças M. O.

    2012-01-01

    Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs) in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1. PMID:23097741

  11. Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a nanoparticle drug.

    Science.gov (United States)

    Chen, Howard H; Yuan, Hushan; Cho, Hoonsung; Sosnovik, David E; Josephson, Lee

    2015-02-14

    We synthesized a cytoprotective magnetic nanoparticle by reacting a maleimide functionalized Feraheme (FH) with a disulfide linked dimer of a polyhis tagged annexin V. Following reductive cleavage of disulfide, the resulting annexin-nanoparticle (diameter = 28.0 ± 2.0 nm by laser light scattering, 7.6 annexin's/nanoparticle) was cytoprotective to cells subjected to plasma membrane disrupting chemotherapeutic or mechanical stresses, and significantly more protective than the starting annexin V. Annexin-nanoparticles provide an approach to the design of nanomaterials which antagonize the plasma membrane permeability characteristic of necrosis and which may have applications as cytoprotective agents.

  12. Effect of Caffeine on the Repeated Modified Agility Test from Some Cardiovascular Factors, Blood Glucose and Rating of Perceived Exertion in Young People

    Science.gov (United States)

    JEBABLI, Nidhal; OUERGHI, Nejmeddine; BOUABID, Jihen; BETTAIB, Ramzi

    2017-01-01

    Background: The aim of this study was to compare the effects of the ingestion of either the caffeine (CAF) or the placebo (PLA) on performance of repeated modified agility test (RMAT), some cardiovascular factors, metabolic and notes of perceived exertion (RPE) in young males and females. Methods: In a randomized double-blind study, we enrolled 18 active students (10 males and 8 females) in Sport Sciences pursuing degrees in Exercise Science and Physical Education at the University of Sports of Kef (Tunisia), during the academic year 2013–2014. All participants were ingested CAF (5 mg.kg−1) or PLA 60 min before performing an RMAT. Total times (TT), peak time (PT) and fatigue index (FI) were identified as the RMAT indices. Heart rate (HR), arterial pressures (PA), blood glucose (BG) and RPE were assessed before, during and after the RMAT. Results: Taking caffeine had been improved the performance by the significant decreased of TT on male gender better than female gender and the entire group. In addition, there was a significant improvement on HR during and after RMAT in both genders and the whole group, except after RMAT among male gender. However, the repeated measurement results had demonstrated no effect of caffeine on PA, BG and RPE. Conclusion: Caffeine supplement had a beneficial effect on agility performance and HR in male better than in female, although, there was no improvement in PA, BG and RPE. PMID:28828317

  13. Citrus junos Tanaka Peel Extract Exerts Antidiabetic Effects via AMPK and PPAR-γ both In Vitro and In Vivo in Mice Fed a High-Fat Diet

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    Sung Hee Kim

    2013-01-01

    Full Text Available The antidiabetic effect of the Citrus junos Tanaka (also known as yuja or yuzu was examined. Ethanol extract of yuja peel (YPEE significantly stimulated 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino]-2-deoxy-D-glucose (2-NBDG uptake in C2C12 myotubes. However, ethanol extract of yuja pulp (YpEE and water extract of yuja peel (YPWE or pulp (YpWE did not stimulate glucose uptake. In addition, peroxisome proliferator-activated receptor gamma (PPAR-γ and AMP-activated protein kinase (AMPK activities were increased by YPEE in a dose-dependent manner. Pretreatment of AMPK inhibitor decreased the glucose uptake stimulated by YPEE in C2C12 myotubes. We confirmed the anti-diabetic effect of YPEE in mice fed a high fat-diet (HFD. Compared with control mice on a normal diet (ND, these mice showed increased body weight, liver fat, insulin resistance, triacylglycerol (TG, and total cholesterol content. Addition of 5% YPEE significantly reduced the weight gain and rise in liver fat content, serum triacylglycerol (TG, total cholesterol, and insulin resistance found in mice fed a high-fat diet (HFD. Moreover, YPEE reduced the secretion of HFD-induced adipocytokines such as leptin and resistin. YPEE also resulted in increased phosphorylation of AMPK in muscle tissues. These results suggest that ethanol extract of yuja peel exerts anti-diabetic effects via AMPK and PPAR-γ in both cell culture and mouse models.

  14. Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men.

    Science.gov (United States)

    Yang, Shu-Yu; Li, Xue-Jun; Zhang, Wei; Liu, Chang-Qin; Zhang, Hui-Jie; Lin, Jin-Rong; Yan, Bing; Yu, Ya-Xin; Shi, Xiu-Lin; Li, Can-Dong; Li, Wei-Hua

    2012-06-01

    To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.

  15. Do psychosocial work factors and social relations exert independent effects on sickness absence? A six year prospective study of the GAZEL cohort.

    Science.gov (United States)

    Melchior, M; Niedhammer, I; Berkman, L F; Goldberg, M

    2003-04-01

    The objective of this prospective cohort study was to determine whether psychosocial work characteristics and social relations exert independent effects on the incidence of sickness absence in a population of middle aged French employees over six years of follow up. This study included 9631 men and 3595 women participating in the French GAZEL cohort. Social relations (social networks, personal social support, and social relations satisfaction) were measured in 1994 by self report. Psychosocial work characteristics (decision latitude, psychological demands, and social support at work) were ascertained in 1995. Sickness absence data were collected independently. The authors studied the incidence of short (>7 days), intermediate (7-21 days), and long (>21 days) spells of absence from 1995 to 31 December 2001. Rate ratios associated with psychosocial exposures, adjusted on sociodemographic characteristics, and health behaviours, were calculated by means of log-linear Poisson regression. A cohort of 20000 employees of France's national gas and electricity company (the GAZEL study). Among men and women, levels of decision latitude and personal social support below the median predicted 17% to 24% increases in absence rates. Low satisfaction with social relations and low social support at work lead to a 10% to 26% excess in sick leaves among men. No interactive effects were found between the variables under study. The quality of the work environment and of social relations affect sickness absence over an extended period of follow up. This study supports the hypothesis of independent, not interactive effects.

  16. Alpha-momorcharin (α-MMC) exerts effective anti-human breast tumor activities but has a narrow therapeutic window in vivo.

    Science.gov (United States)

    Cao, Dongliang; Sun, Yun; Wang, Ling; He, Qianchuan; Zheng, Juecun; Deng, Fei; Deng, Shanshan; Chang, ShuChing; Yu, XiaoPing; Li, Minhui; Meng, Yao; Jin, Jiagui; Shen, Fubing

    2015-01-01

    Alpha-momorcharin (α-MMC), a ribosome inactivating protein (RIP) extracted from the seeds of Momordica charantia, exerts anti-tumor, antiviral, and anti-fungal activities. However, α-MMC has an obvious toxicity that limits its clinical application. We examined the effect of α-MMC on the inhibition of human breast cancer and assessed its general toxicity to find the therapeutic window in vivo for its potential clinical use. It was purified using column chromatography, and then injected into the xenograft nude mouse model induced by MDA-MB-231 and MCF-7. The anti-tumor efficacy was evaluated with T/C%. Next, the α-MMC was injected at a series of doses to Balb/C mice to assess its general toxicity. The MTT assay, the apoptosis test, and the cell cycle inhibition of α-MMC in human breast cancer cells were performed. In the xenografted tumors induced by MDA-MB-231 and MCF-7, α-MMC exerted an obvious inhibition effects on tumor growth at the dosage of 1.2mg/kg and 0.8 mg/kg. For in vivo toxicity experiments of α-MMC in Balb/C mice, the minimal toxic dose of α-MMC was 1.2mg/kg. Alpha-MMC induced apoptosis by increasing caspase3 activities, and the cell cycle was arrested at the G0/G1 or G2/M phases. The measurements of IC50 were 15.07 μg/mL, 33.66 μg/mL, 42.94 μg/mL for MDA-MB-231, MCF-7 and MDA-MB-453 respectively. Alpha-MMC exhibits anti-tumor effects in human breast cancer in vivo and in vitro. It inhibits breast cancer cells through the inhibition of tumor growth and induction of cell apoptosis. However, due to its obvious toxicity, α-MMC has a relatively narrow therapeutic window in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. The effects of modified exponential tapering technique on perceived exertion, heart rate, time trial performance, VO2max and power output among highly trained junior cyclists.

    Science.gov (United States)

    Ishak, Asmadi; Hashim, Hairul A; Krasilshchikov, Oleksandr

    2016-09-01

    The present study investigated the effects of a 2-week modified exponential taper on physiological adaptation and time trial performance among junior cyclists. Participants (N.=27) with the mean age of 16.95±0.8 years, height of 165.6±6.1 cm and weight of 54.19±8.1 kg were matched into either modified exponential taper (N.=7), normal exponential taper (N.=7), or control (N.=7) groups using their initial VO2max values. Both experimental groups followed a 12-week progressive endurance training program and subsequently, a 2-week tapering phase. A simulated 20-km time trial performance along with VO2max, power output, heart rate and rating of perceived exertion were measured at baseline, pre and post-taper. One way ANOVA was used to analyze the difference between groups before the start of the intervention while mixed factorial ANOVA was used to analyze the difference between groups across measurement sessions. When homogeneity assumption was violated, the Greenhouse-Geisser Value was used for the corrected values of the degrees of freedom for the within subject factor the analysis. Significant interactions between experimental groups and testing sessions were found in VO2max (F=6.67, df=4, P<0.05), power output (F=5.02, df=4, P<0.05), heart rate (F=10.87, df=2.51, P<0.05) rating of perceived exertion (F=13.04, df=4, P<0.05) and 20KM time trial (F=4.64, df=2.63, P<0.05). Post-hoc analysis revealed that both types of taper exhibited positive effects compared to the non-taper condition in the measured performance markers at post-taper while no different were found between the two taper groups. It was concluded that both taper protocols successfully inducing physiological adaptations among the junior cyclists by reducing the volume and maintaining the intensity of training.

  18. Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers.

    Science.gov (United States)

    Ji, Wen-Tsai; Chuang, Yao-Chi; Chen, Han-Po; Lee, Ching-Chih; Chen, Jeff Yi-Fu; Yang, Sheng-Ru; Chen, Jung-Hua; Wang, Chun-Jen; Chen, Hau-Ren

    2014-01-01

    Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE) was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.

  19. Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers

    Directory of Open Access Journals (Sweden)

    Wen-Tsai Ji

    2014-01-01

    Full Text Available Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.

  20. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females.

    Science.gov (United States)

    Racil, G; Coquart, J B; Elmontassar, W; Haddad, M; Goebel, R; Chaouachi, A; Amri, M; Chamari, K

    2016-06-01

    This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

  1. The dopamine D1-D2 receptor heteromer exerts tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization

    Science.gov (United States)

    Shen, Maurice Y.F.; Perreault, Melissa L.; Fan, Theresa; George, Susan R.

    2014-01-01

    A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioural model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5 day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5 day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants. PMID:25444866

  2. The synthetic melanocortin (CKPV2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.

    Directory of Open Access Journals (Sweden)

    Hai-xia Ji

    Full Text Available In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH22 or (CKPV2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6 release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP production was also induced by (CKPV2 administration in macrophages. These above effects on macrophages by (CKPV2 were almost reversed by melanocortin receptor-1(MC1R siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.

  3. Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA

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    Taek-In Oh

    2017-09-01

    Full Text Available Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4; however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB, indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2 and tropomyosin-related kinase A (TRKA via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

  4. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Science.gov (United States)

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  5. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  6. Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity.

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    Kengo Azushima

    Full Text Available Accumulating evidence indicates that metabolic dysfunction with visceral obesity is a major medical problem associated with the development of hypertension, type 2 diabetes (T2DM and dyslipidemia, and ultimately severe cardiovascular and renal disease. Therefore, an effective anti-obesity treatment with a concomitant improvement in metabolic profile is important for the treatment of metabolic dysfunction with visceral obesity. Bofu-tsu-shosan (BOF is one of oriental herbal medicine and is clinically available to treat obesity in Japan. Although BOF is a candidate as a novel therapeutic strategy to improve metabolic dysfunction with obesity, the mechanism of its beneficial effect is not fully elucidated. Here, we investigated mechanism of therapeutic effects of BOF on KKAy mice, a model of human metabolic disorders with obesity. Chronic treatment of KKAy mice with BOF persistently decreased food intake, body weight gain, low-density lipoprotein cholesterol and systolic blood pressure. In addition, both tissue weight and cell size of white adipose tissue (WAT were decreased, with concomitant increases in the expression of adiponectin and peroxisome proliferator-activated receptors genes in WAT as well as the circulating adiponectin level by BOF treatment. Furthermore, gene expression of uncoupling protein-1, a thermogenesis factor, in brown adipose tissue and rectal temperature were both elevated by BOF. Intriguingly, plasma acylated-ghrelin, an active form of orexigenic hormone, and short-term food intake were significantly decreased by single bolus administration of BOF. These results indicate that BOF exerts a combinatorial favorable metabolic modulation including antihypertensive effect, at least partially, via its beneficial effect on adipose tissue function and its appetite-inhibitory property through suppression on the ghrelin system.

  7. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    Science.gov (United States)

    Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  8. Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

    Science.gov (United States)

    Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P

    1999-12-01

    Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control

  9. Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus Aspergillus sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

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    Dong-Cheol Kim

    2016-04-01

    Full Text Available In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus Aspergillus sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2 in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK and phosphatidylinositol 3-kinase (PI3K/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.

  10. The effects of different doses of caffeine on performance, rating of perceived exertion and pain perception in teenagers female karate athletes

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    Hamid Arazi

    Full Text Available ABSTRACT The present study set to examine the effects of different doses of caffeine on performance, rating of perceived exertion (RPE, and pain perception in female teenager athletes of karate. Ten female karate athletes (16.8±1.23 years; height 1.59±0.28 m; body-mass 57.73±8.33 kg; BMI 22.71±3.05 kg/m2 participated in the study. A double-blind, randomized, and crossover counterbalanced design was used. In three sessions (with an interval of seven days', ten female karate athletes ingested low dose (2 mg/kg, moderate dose (5 mg/kg caffeine, and placebo. Sixty minutes after consumption, they performed the tests as below: one repetition maximum and 60% of one repetition maximum in the leg press, explosive power test, and anaerobic RAST test. After the tests, the participants' RPE (6-20 scale and pain perception (0-10 scale were recorded using various categorical scales. The results showed that caffeine ingestion at moderate dose significantly reduced RPE and pain perception values compared with the placebo during muscular endurance test (P=0.0001 and P=0.039, respectively. The findings suggest that caffeine dose of 5 mg/kg body mass appears to improve RPE and pain perception in female teenager athletes of karate. The dose of 2 mg/kg body mass does not confer any additional improvement in performance.

  11. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes

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    Peter Draber

    2015-12-01

    Full Text Available Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1 ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC, at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC’s M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors.

  12. Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats.

    Science.gov (United States)

    Michelini, Luiz G B; Figueira, Tiago R; Siqueira-Santos, Edilene S; Castilho, Roger F

    2015-03-04

    Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of mitochondrial respiratory complex I, results in neurochemical, behavioral, and neuropathological features of Parkinson's disease. The aim of the present study was to evaluate whether brain mitochondria from old rats (24 months old) would be more susceptible to rotenone-induced inhibition of oxygen consumption and increased generation of H2O2 than mitochondria from young-adult rats (3-4 months old). Isolated brain mitochondria were incubated in the presence of different rotenone concentrations (5, 10, and 100nM), and oxygen consumption and H2O2 production were measured during respiratory states 3 (ADP-stimulated respiration) and 4 (resting respiration). Respiratory state 3 and citrate synthase activity were significantly lower in mitochondria from old rats. Mitochondria from young-adult and old rats showed similar sensitivity to rotenone-induced inhibition of oxygen consumption. Similarly, H2O2 production rates by both types of mitochondria were dose-dependently stimulated to the same extent by increasing concentrations of rotenone. We conclude that rotenone exerts similar effects on oxygen consumption and H2O2 production by isolated brain mitochondria from young-adult and old rats. Therefore, aging does not increase the mitochondrial H2O2 generation in response to complex I inhibition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Emotional changes occurring in women in pregnancy, parturition and lying-in period according to factors exerting an effect on a woman during the peripartum period.

    Science.gov (United States)

    Pięta, Beata; Jurczyk, Mieczysława Urszula; Wszołek, Katarzyna; Opala, Tomasz

    2014-01-01

    Pregnancy, parturition and childcare, which are important moments in a woman's life, are connected with many emotional states of a future mother, a pregnant woman and a lying-in woman. The perinatal period is the time when the risk of psychological disorders in a pregnant woman may increase by even several times. Objective. The objective of the study was recognition of the main emotional and psychological changes in pregnant women, those in labour and lying-in, according to the factors occurring during the peripartum period. The study was conducted in the form of a survey and covered a group of 108 mothers who were hospitalized in gynaecological-obstetric and obstetric wards in the Karol Marcinkowski Gynaecological-Obstetric University Hospital in Poznań. There are a number of factors which may exert a negative effect on the emotions of women in pregnancy, parturition, and during lying-in. The study showed that there is a close relationship between the occurrence of these factors and emotional states of the mothers after giving birth. Special attention should be given to women in whom already during pregnancy factors arise which may have a negative impact on their mental state. Emotions during pregnancy, parturition and lying-in are often quite extreme, and achieve a high intensity, as well being very variable within a short period of time.

  14. Emotional changes occurring in women in pregnancy, parturition and lying-in period according to factors exerting an effect on a woman during the peripartum period

    Directory of Open Access Journals (Sweden)

    Beata Pięta

    2014-09-01

    Full Text Available [b]Introduction[/b]. Pregnancy, parturition and childcare, which are important moments in a woman’s life, are connected with many emotional states of a future mother, a pregnant woman and a lying-in woman. The perinatal period is the time when the risk of psychological disorders in a pregnant woman may increase by even several times. [b]Objective.[/b] The objective of the study was recognition of the main emotional and psychological changes in pregnant women, those in labour and lying-in, according to the factors occurring during the peripartum period. [b]Material and method[/b]. The study was conducted in the form of a survey and covered a group of 108 mothers who were hospitalized in gynaecological-obstetric and obstetric wards in the Karol Marcinkowski Gynaecological-Obstetric University Hospital in Poznań. [b]Results[/b]. There are a number of factors which may exert a negative effect on the emotions of women in pregnancy, parturition, and during lying-in. The study showed that there is a close relationship between the occurrence of these factors and emotional states of the mothers after giving birth. [b]Conclusion[/b]. Special attention should be given to women in whom already during pregnancy factors arise which may have a negative impact on their mental state. Emotions during pregnancy, parturition and lying-in are often quite extreme, and achieve a high intensity, as well being very variable within a short period of time.

  15. Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production.

    Science.gov (United States)

    Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Kolling, Eduardo Antônio; Rybarczyk-Filho, José Luiz; Ambrosi, Priscilla; Terra, Silvia Resende; Pires, André Simões; da Rocha, João Batista Teixeira; Behr, Guilherme Antônio; Moreira, José Cláudio Fonseca

    2013-01-01

    To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.

  16. Syndecan-2 exerts antifibrotic effects by promoting caveolin-1-mediated transforming growth factor-β receptor I internalization and inhibiting transforming growth factor-β1 signaling.

    Science.gov (United States)

    Shi, Yuanyuan; Gochuico, Bernadette R; Yu, Guoying; Tang, Xiaomeng; Osorio, Juan C; Fernandez, Isis E; Risquez, Cristobal F; Patel, Avignat S; Shi, Ying; Wathelet, Marc G; Goodwin, Andrew J; Haspel, Jeffrey A; Ryter, Stefan W; Billings, Eric M; Kaminski, Naftali; Morse, Danielle; Rosas, Ivan O

    2013-10-01

    Alveolar transforming growth factor (TGF)-β1 signaling and expression of TGF-β1 target genes are increased in patients with idiopathic pulmonary fibrosis (IPF) and in animal models of pulmonary fibrosis. Internalization and degradation of TGF-β receptor TβRI inhibits TGF-β signaling and could attenuate development of experimental lung fibrosis. To demonstrate that after experimental lung injury, human syndecan-2 confers antifibrotic effects by inhibiting TGF-β1 signaling in alveolar epithelial cells. Microarray assays were performed to identify genes differentially expressed in alveolar macrophages of patients with IPF versus control subjects. Transgenic mice that constitutively overexpress human syndecan-2 in macrophages were developed to test the antifibrotic properties of syndecan-2. In vitro assays were performed to determine syndecan-2-dependent changes in epithelial cell TGF-β1 signaling, TGF-β1, and TβRI internalization and apoptosis. Wild-type mice were treated with recombinant human syndecan-2 during the fibrotic phase of bleomycin-induced lung injury. We observed significant increases in alveolar macrophage syndecan-2 levels in patients with IPF. Macrophage-specific overexpression of human syndecan-2 in transgenic mice conferred antifibrotic effects after lung injury by inhibiting TGF-β1 signaling and downstream expression of TGF-β1 target genes, reducing extracellular matrix production and alveolar epithelial cell apoptosis. In vitro, syndecan-2 promoted caveolin-1-dependent internalization of TGF-β1 and TβRI in alveolar epithelial cells, which inhibited TGF-β1 signaling and epithelial cell apoptosis. Therapeutic administration of human syndecan-2 abrogated lung fibrosis in mice. Alveolar macrophage syndecan-2 exerts antifibrotic effects by promoting caveolin-1-dependent TGF-β1 and TβRI internalization and inhibiting TGF-β1 signaling in alveolar epithelial cells. Hence, molecules that facilitate TβRI degradation via endocytosis

  17. Alternol, a natural compound, exerts an anti-tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways.

    Science.gov (United States)

    Zuo, Dongqing; Zhou, Zifei; Wang, Hongsheng; Zhang, Tao; Zang, Jie; Yin, Fei; Sun, Wei; Chen, Jiepeng; Duan, Lili; Xu, Jing; Wang, Zhuoying; Wang, Chongren; Lin, Binhui; Fu, Zeze; Liao, Yuxin; Li, Suoyuan; Sun, Mengxiong; Hua, Yingqi; Zheng, Longpo; Cai, Zhengdong

    2017-02-01

    Osteosarcoma (OS) is the most frequent primary malignant bone tumour. Alternol, a novel compound purified from microbial fermentation products exerts anti-tumour effects across several cancer types. The effect of alternol on human OS remains to be elucidated. We first evaluated the anti-tumour effect of alternol in several human OS cell lines in vitro and investigated its underlying mechanism. Alternol inhibited OS cell proliferation, migration and induced caspase-dependent apoptosis, G2/M cell cycle arrest in a dose and time-dependent manner. Moreover, alternol treatment inhibited signal transducer and activator of transcription-3 (STAT3) phosphorylation in 143B and MG63 human OS cells, as evaluated using a STAT3-dependent dual luciferase reporter system. Exposure to alternol resulted in excessive reactive oxygen species (ROS) generation and Jun amino-terminal kinases (JNK), extracellular signal-regulated kinases (ERK1/2) and p38 activation. Furthermore, alternol-induced cell death was significantly restored in the presence of the ROS scavenger, N-acetyl-l-cysteine (NAC) or a caspase inhibitor Z-VAD-FMK. NAC also prevented G2/M phase arrest and phosphorylation of mitogen-activated protein kinases (MAPK), but did not reverse STAT3 inactivation. Finally, alternol suppressed tumour growth in vivo in the nude mouse OS tibia orthotopic model. Immunohistochemistry revealed that alternol treatment resulted in down-regulation of phosph-STAT3 Tyr705 and up-regulation of cleaved caspase-3 and phosph-SAPK (Stress-activated protein kinases)/JNK expression. Taken together, our results reveal that alternol suppresses cell proliferation, migration and induces apoptosis, cell cycle arrest by modulating of ROS-dependent MAPK and STAT3 signalling pathways in human OS cells. Therefore, alternol is a promising candidate for developing anti-tumour drugs target OS. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

  18. A synthetic bioisoster of trimethadione and phenytoin elicits anticonvulsant effect, protects the brain oxidative damage produced by seizures and exerts antidepressant action in mice.

    Science.gov (United States)

    Pastore, Valentina; Wasowski, Cristina; Higgs, Josefina; Mangialavori, Irene C; Bruno-Blanch, Luis E; Marder, Mariel

    2014-08-01

    Epilepsy is recognized as one of the most common and serious neurological disorder affecting 1-2% of the world׳s population. The present study demonstrates that systemic administration of 3-butyl-5,5-dimethyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (DIOXIDE), a synthetic compound bioisoster of trimethadione and phenytoin (classical anticonvulsants), elicits a dose dependent anticonvulsant response in mice submitted to the subcutaneous pentylenetetrazole seizure test (scPTZ). Among various factors supposed to play role in epilepsy, oxidative stress and reactive species have strongly emerged. The protection exerted by DIOXIDE over the extent of brain oxidative damage produced by PTZ was determined, by measuring the levels of lipid peroxidation and reduced glutathione and the activity of Na(+)/K(+)-ATPase. Psychiatric disorders represent frequent comorbidities in persons with epilepsy. In this report, the potential anxiolytic and antidepressant activities of DIOXIDE were evaluated in several widely used models for assessing anxiolytic and antidepressant activities in rodents. Although DIOXIDE did not evidence anxiolytic activity at the doses tested, it revealed a significant antidepressant-like effect. Preliminary studies of its mechanism of action, by means of its capacity to act via the GABAA receptor (using the [(3)H]flunitrazepam binding assay in vitro and the picrotoxin test in vivo) and the Na(+) channel (using the alkaloid veratrine, a voltage-Na(+) channel agonist) demonstrated that the anticonvulsant effect is not likely related to the GABAergic pathway and the antidepressant-like effect could be due to its Na(+) channel blocking properties. The results for DIOXIDE suggested it as a new anticonvulsant-antioxidant and antidepressant compound that deserves further development. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  19. Effects of the Workplace Health Promotion Activities Soccer and Zumba on Muscle Pain, Work Ability and Perceived Physical Exertion among Female Hospital Employees.

    Science.gov (United States)

    Barene, Svein; Krustrup, Peter; Holtermann, Andreas

    2014-01-01

    This 40-week workplace physical training RCT investigated the effect of soccer and Zumba, respectively, on muscle pain intensity and duration, work ability, and rating of perceived exertion (RPE) during work among female hospital employees. 107 hospital employees were cluster-randomized into two training groups, and a control group. The training was conducted outside working hours as two-three 1-h sessions per week for the first 12 weeks, and continued as one-two 1-h sessions per week for the last 28 weeks. Muscle pain intensity and duration, work ability, and RPE during work were measured at baseline and after 12 and 40 weeks. After 12 weeks, both the soccer (-1.9, 95% CI, -3.0, -0.8, P = 0.001) and the Zumba group (-1.3, 95% CI, -2.3, -0.3, P = 0.01) reduced the pain intensity (on a scale from 0 to 10) in the neck-shoulder region (eta squared = 0.109), whereas only the soccer group (-1.9, 95% CI, -3.2, -0.7, P = 0.002, eta squared = 0.092) showed a reduction after 40 weeks referencing the control group. After 40 weeks, both the soccer (-16.4 days, 95% CI, -29.6, -3.2, Ppain duration during the past 3 months in the neck-shoulder region (eta squared = 0.077). No significant effects on intensity or duration of pain in the lower back, RPE during work or work ability were found. The present study indicates that workplace initiated soccer and Zumba training improve neck-shoulder pain intensity as well as duration among female hospital employees. International Standard Randomized Controlled Trial Number Register ISRCTN 61986892.

  20. The Effect of Recovery Duration on Vastus Lateralis Oxygenation, Heart Rate, Perceived Exertion and Time Motion Descriptors during Small Sided Football Games.

    Directory of Open Access Journals (Sweden)

    Scott McLean

    Full Text Available Small sided games (SSG of football are an effective and efficient format to simultaneously train the physiological, technical, and tactical components of football. The duration of the recovery period between bouts of SSG will affect the physiological response to subsequent bouts. It was hypothesised that decreasing the duration of recovery periods separating serial SSG bouts would increase physiological, and perceptual responses, and decrease high speed running, and distance during SSG bouts.Twelve experienced footballers (mean ± SD; age 21 ± 3 yrs; VO2peak 64 ± 7 ml·min·kg-1; playing experience 15 ± 3 yrs completed two SSG sessions. Each SSG consisted of 3 vs. 3 players and 6 bouts of 2 min duration, with bouts separated by either 30 s recovery (REC-30 or 120 s recovery (REC-120. Deoxygenated haemoglobin (HHb in the vastus lateralis (VL (using near infrared spectroscopy, heart rate (HR and time motion descriptors (TMD (speed and distance were measured continuously during the SSG sessions and perceived exertion (RPE was measured for each bout.During the recovery periods, in REC-30 compared to REC-120, there was a significant (p < 0.05 main effect of a higher HHb and HR. During the bouts, in REC-30 compared to REC-120, there were no significant differences in HHb, HR, RPE, or TMD, but within both REC-30 and REC-120 there were significant increases as a function of bout number in RPE.Although a four-fold increase in recovery period allowed a significant increase in the recovery of HHb and HR, this did not increase the physiological, and perceptual responses, or time motion descriptors during the bouts. These results could have been due to the regulation of effort (pacing, in these experienced players performing an exercise task to which they were well adapted.

  1. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

  2. External Hand Forces Exerted by Long-Term Care Staff to Push Floor-Based Lifts: Effects of Flooring System and Resident Weight.

    Science.gov (United States)

    Lachance, Chantelle C; Korall, Alexandra M B; Russell, Colin M; Feldman, Fabio; Robinovitch, Stephen N; Mackey, Dawn C

    2016-09-01

    The aim of this study was to investigate the effects of flooring type and resident weight on external hand forces required to push floor-based lifts in long-term care (LTC). Novel compliant flooring is designed to reduce fall-related injuries among LTC residents but may increase forces required for staff to perform pushing tasks. A motorized lift may offset the effect of flooring on push forces. Fourteen female LTC staff performed straight-line pushes with two floor-based lifts (conventional, motor driven) loaded with passengers of average and 90th-percentile resident weights over four flooring systems (concrete+vinyl, compliant+vinyl, concrete+carpet, compliant+carpet). Initial and sustained push forces were measured by a handlebar-mounted triaxial load cell and compared to participant-specific tolerance limits. Participants rated pushing difficulty. Novel compliant flooring increased initial and sustained push forces and subjective ratings compared to concrete flooring. Compared to the conventional lift, the motor-driven lift substantially reduced initial and sustained push forces and perceived difficulty of pushing for all four floors and both resident weights. Participants exerted forces above published tolerance limits only when using the conventional lift on the carpet conditions (concrete+carpet, compliant+carpet). With the motor-driven lift only, resident weight did not affect push forces. Novel compliant flooring increased linear push forces generated by LTC staff using floor-based lifts, but forces did not exceed tolerance limits when pushing over compliant+vinyl. The motor-driven lift substantially reduced push forces compared to the conventional lift. Results may help to address risk of work-related musculoskeletal injury, especially in locations with novel compliant flooring. © 2016, Human Factors and Ergonomics Society.

  3. Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress.

    Science.gov (United States)

    Xia, Nan; Li, Jie; Wang, Hongwei; Wang, Jian; Wang, Yangtian

    2016-01-01

    The aim of the present study was to investigate the effects of Schisandra chinensis (S. chinensis) and Rhodiola rosea (R. rosea) on rats subjected to 5 h of stress, induced by water-floating followed by treadmill exercise. Hypothalamus-pituitary-adrenal (HPA) activity and c-Fos and Fos-related antigen 2 (Fra-2) mRNA expression levels in the hypothalamus of the rats were evaluated. Rats were distributed into four groups: S. chinensis (n=12), R. rosea (n=10), stress control (n=10) and quiet control (n=8). Following a training period of 6 consecutive days, the S. chinensis, R. rosea and stress control groups underwent a 3-h water-floating session in the presence of feline predators immediately followed by 2 h treadmill running to induce psychological and physical stress. Following compound stress induction, the serum levels of corticosterone (CORT), adrenocorticotropic hormone and interleukin-1β and the mRNA expression levels of hypothalamic corticotropin-releasing hormone (CRH), neuropeptide-Y, c-Fos and Fra-2 were evaluated using enzyme-linked immunosorbent assay, radioimmunoassay and quantitative polymerase chain reaction, respectively. The results indicated that S. chinensis and R. rosea markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. The mRNA expression levels of c-Fos and Fra-2 in the hypothalamus were significantly increased after 5 h compound stress, and reduced levels of c-Fos expression were detected in rats treated with R. rosea. Thus, S. chinensis and R. rosea exert an anti-stress effect in rats subjected to stress by balancing the HPA axis, and possibly by reducing the expression of c-Fos in the hypothalamus.

  4. Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

    Directory of Open Access Journals (Sweden)

    Kumiko Tamaki

    2012-01-01

    Full Text Available Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43, a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6. Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

  5. Effects of perceived and exerted pain control on neural activity during pain relief in experimental heat hyperalgesia: a fMRI study.

    Science.gov (United States)

    Mohr, C; Leyendecker, S; Petersen, D; Helmchen, C

    2012-04-01

    Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex. © 2011 European Federation of International Association for the Study of Pain Chapters.

  6. Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra.

    Science.gov (United States)

    Nishikawa, Yoshifumi; Furukawa, Ayumi; Shiga, Ikumi; Muroi, Yoshikage; Ishii, Toshiaki; Hongo, Yayoi; Takahashi, Shunya; Sugawara, Tatsuya; Koshino, Hiroyuki; Ohnishi, Masao

    2015-01-01

    Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress.

  7. Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Nishikawa

    Full Text Available Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress.

  8. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

    Science.gov (United States)

    Bath, Sundeep

    2015-01-01

    Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

  9. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

    Directory of Open Access Journals (Sweden)

    Ashim Malhotra

    2015-01-01

    Full Text Available Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson’s and Alzheimer’s disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment.

  10. Major Components of Energy Drinks (Caffeine, Taurine, and Guarana Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

    Directory of Open Access Journals (Sweden)

    Fares Zeidán-Chuliá

    2013-01-01

    Full Text Available Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs. Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL, taurine (1–16 mg/mL, and guarana (3.125–50 mg/mL showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD and catalase (CAT activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”, could be a cause of in vitro toxicity induced by these drugs.

  11. Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

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    Pia Rademann

    2017-01-01

    Full Text Available Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90 underwent cecal ligation and puncture (CLP and received SkQ1 (5 nmol/kg, MitoTEMPO (50 nmol/kg, or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments.

  12. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Energy Technology Data Exchange (ETDEWEB)

    Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

    2014-08-15

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  13. Interaction of Cytotoxic and Cytoprotective Bile Acids with Model Membranes: Influence of the Membrane Composition.

    Science.gov (United States)

    Esteves, M; Ferreira, M J; Kozica, A; Fernandes, A C; Gonçalves da Silva, A; Saramago, B

    2015-08-18

    To understand the role of bile acids (BAs) in cell function, many authors have investigated their effect on biomembrane models which are less complex systems, but there are still many open questions. The present study aims to contribute for the deepening of the knowledge of the interaction between BAs and model membranes, in particular, focusing on the effect of BA mixtures. The cytotoxic deoxycholic acid (DCA), the cytoprotective ursodeoxycholic acid (UDCA), and the equimolar mixture (DCA + UDCA) were investigated. Monolayers and liposomes were taken as model membranes with two lipid compositions: an equimolar mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol)) traditionally associated with the formation of lipid rafts and an equimolar POPC/SM binary mixture. The obtained results showed that DCA causes the fluidization of monolayers and bilayers, leading to the eventual rupture of POPC/SM liposomes at high concentration. UDCA may provide a stabilization of POPC/SM membranes but has a negligible effect on the Chol-containing liposomes. In the case of equimolar mixture DCA/UDCA, the interactions depend not only on the lipid composition but also on the design of the experiment. The BA mixture has a greater impact on the monolayers than do pure BAs, suggesting a cooperative DCA-UDCA interaction that enhances the penetration of UDCA in both POPC/SM and POPC/SM/Chol monolayers. For the bilayers, the presence of UDCA in the mixture decreases the disturbing effect of DCA.

  14. Suplementação com ácido ascórbico tem efeito citoprotetor na cirrose biliar secundária: estudo experimental em ratos jovens Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

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    Cynthia R. Matos Silva Passoni

    2008-12-01

    Full Text Available OBJETIVO: Testar se a suplementação com ácido ascórbico tem algum afeito citoprotetor em um modelo de cirrose biliar secundária em ratos jovens. MÉTODOS: Foram estudados 40 ratos Wistar desmamados no 21º dia pós-natal. Cada grupo de 10 foi submetido a um dos seguintes quatro tratamentos, até o 49º dia pós-natal, quando foram submetidos a eutanásia: 1 LC - ligadura dupla e ressecção do ducto biliar comum e administração diária de ácido ascórbico [100 mg/g de peso corporal (pc]; 2 LA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc; 3 SC - operação simulada e administração diária de ácido ascórbico (100 mg/g pc; 4 SA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc. Os ratos eram pesados diariamente. No 27º dia pós-operatório, eles receberam injeção intraperitoneal de 1,5 mg/g pc de pentobarbital sódico, e o tempo de sono induzido pelo pentobarbital foi medido. Coletou-se sangue para determinação de atividade sérica de alanina aminotransferase e de aspartato aminotransferase, níveis de albumina e globulina séricas, e o fígado foi analisado quanto à conteúdo de água e gordura. Os dados foram submetidos à ANOVA two-way, e comparações pareadas entre grupos foram testadas com o método de SNK. O nível de significância foi estabelecido em 0,05. RESULTADOS: A suplementação com ácido ascórbico atenuou os efeitos da colestase: reduziu o tempo de anestesia pelo pentobarbital, globulina sérica e o conteúdo de gordura no fígado. CONCLUSÕES: Nossos resultados corroboram a hipótese de que a suplementação com ácido ascórbico tem um efeito citoprotetor na cirrose biliar secundária.OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal

  15. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females

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    G Racil

    2016-04-01

    Full Text Available This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS or high-intensity interval training (HIIT at 100% MAS, with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p˂0.05 body mass (BM, BMI Z-score, and percentage of body fat (%BF. Only the HIIT group showed decreased waist circumference (WC (p=0.017. The effect of exercise on maximal oxygen uptake (VO2max was significant (p=0.019, ES=0.48 and p=0.010, ES=0.57, HIIT and MIIT, respectively. The decrease of rate-pressure product (RPP (p<0.05, ES=0.53 and ES=0.46, HIIT and MIIT, respectively followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p<0.05 in both training groups. Significant decreases occurred in blood leptin (p=0.021, ES=0.67 and p=0.011, ES=0.73 and in RPE (p=0.001, ES=0.76 and p=0.017, ES=0.57 in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p<0.001 and VO2max (p<0.01 in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p<0.01 in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

  16. A NEW CLASS OF THE ANTI-ISCHEMIC MEDICAMENTS - METABOLIC CYTOPROTECTIVE OF THE CARDIOMYOCYTE

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    Svetlana Apostolovic

    2000-09-01

    Full Text Available A great imporfance of The coronary disease makes welcome any rationalinnovation in the therapy as is the case with a group of medicaments for the myocardecytoprotection primary!y by the metabolic effect; the best known of them istrimethazidine. The demand for it is obvious since even about 40% of the patientssuffering from a coronary disease tend to have residual ischemia despite the fact that the međicaments lead lo the loss of anginous symptoms. Since there are no papers ontrimethazidine (except for ours in domestic journals, the aim of the paper is to give asurvey of contemporary literature dealing with it, to report on six years' experiencewith the safe application of trimethazidine and to analyze its effect upon the basicparameters of chemodynamics.Numerous double-blind studies point to the efficiency of this medicament thatis comparable to that of thc basic anti-ischemic medicaments. Trimethazidine canreinforce the effect of other medicaments. We conclude that it is possible, to acceptthe suggestion about the benefits of the metabolic myocarde cytoprotective from themedicine publications since the medicament can be exceptionally well endured andthat is of especial importance for hypotensive coronary patients.

  17. Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat.

    Science.gov (United States)

    Pilehvar-Soltanahmadi, Younes; Nouri, Mohammad; Martino, Mikaël M; Fattahi, Amir; Alizadeh, Effat; Darabi, Masoud; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah

    2017-08-15

    Electrospun nanofibrous scaffolds containing natural substances with wound healing properties such as Emu oil (EO) may have a great potential for increasing the efficiency of stem cell-based skin bioengineering. For this purpose, EO blended PCL/PEG electrospun nanofibrous mats were successfully fabricated and characterized using FE-SEM, FTIR and Universal Testing Machine. The efficiency of the scaffolds in supporting the adherence, cytoprotection, proliferation and differentiation of adipose tissue-derived stem cells (ADSCs) to keratinocyte was evaluated. GC/MS and HPLC were used to determine the composition of pure EO, which revealed to be mainly fatty acids and carotenoids. FE-SEM and cell proliferation assays showed that adhesion and proliferation of ADSCs on EO-PCL/PEG nanofibers was significantly higher than on PCL/PEG nanofibers. Additionally, EO-PCL/PEG nanofibers with free radical scavenging properties conferred a cytoprotective effect against cell-damaging free radicals, while the ability to support cell adhesion and growth was maintained or even improved. Immunostaining of ADSCs on EO-PCL/PEG nanofibers confirmed the change in morphology of ADSCs from spindle to polygonal shape suggesting their differentiation toward an epidermal linage. Moreover, the expression levels of the keratin 10, filaggrin, and involucrin that are involved in epidermal differentiation were upregulated in a stage-specific manner. This preliminary study shows that EO-PCL/PEG nanofibers could be a good candidate for the fabrication of wound dressings and skin bioengineered substitutes with ADSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. In Vitro Evaluation of the Antioxidant, Cytoprotective, and Antimicrobial Properties of Essential Oil from Pistacia vera L. Variety Bronte Hull

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    Antonella Smeriglio

    2017-06-01

    Full Text Available Although the chemical composition and biological properties of some species of the genus Pistacia has been investigated, studies on hull essential oil of Pistacia vera L. variety Bronte (HEO are currently lacking. In this work, we have carried out an in-depth phytochemical profile elucidation by Gas Chromatography-Mass Spectrometry (GC-MS analysis, and an evaluation of antioxidant scavenging properties of HEO, using several different in vitro methods, checking also its cytoprotective potential on lymphocytes treated with tert-butyl hydroperoxide. Moreover, the antimicrobial activity against Gram-positive and Gram-negative strains, both American Type Culture Collection (ATCC and clinical isolates, was also investigated. GC-MS analysis highlighted the richness of this complex matrix, with the identification of 40 derivatives. The major components identified were 4-Carene (31.743%, α-Pinene (23.584%, d-Limonene (8.002%, and 3-Carene (7.731%. The HEO showed a strong iron chelating activity and was found to be markedly active against hydroxyl radical, while scarce effects were found against 2,2-diphenyl-1-picrylhydrazyl (DPPH radical. Moreover, pre-treatment with HEO was observed to significantly increase the cell viability, decreasing the lactate dehydrogenase (LDH release. HEO was bactericidal against all the tested strains at the concentration of 7.11 mg/mL, with the exception of Pseudomonas aeruginosa ATCC 9027. The obtained results demonstrate the strong free-radical scavenging activity of HEO along with remarkable cytoprotective and antimicrobial properties.

  19. Heat or Cold: Which One Exerts Greater Deleterious Effects on Health in a Basin Climate City? Impact of Ambient Temperature on Mortality in Chengdu, China.

    Science.gov (United States)

    Cui, Yan; Yin, Fei; Deng, Ying; Volinn, Ernest; Chen, Fei; Ji, Kui; Zeng, Jing; Zhao, Xing; Li, Xiaosong

    2016-12-10

    Background: Although studies from many countries have estimated the impact of ambient temperature on mortality, few have compared the relative impacts of heat and cold on health, especially in basin climate cities. We aimed to quantify the impact of ambient temperature on mortality, and to compare the contributions of heat and cold in a large basin climate city, i.e., Chengdu (Sichuan Province, China); Methods: We estimated the temperature-mortality association with a distributed lag non-linear model (DLNM) with a maximum lag-time of 21 days while controlling for long time trends and day of week. We calculated the mortality risk attributable to heat and cold, which were defined as temperatures above and below an "optimum temperature" that corresponded to the point of minimum mortality. In addition, we explored effects of individual characteristics; Results: The analysis provides estimates of the overall mortality burden attributable to temperature, and then computes the components attributable to heat and cold. Overall, the total fraction of deaths caused by both heat and cold was 10.93% (95%CI: 7.99%-13.65%). Taken separately, cold was responsible for most of the burden (estimate 9.96%, 95%CI: 6.90%-12.81%), while the fraction attributable to heat was relatively small (estimate 0.97%, 95%CI: 0.46%-2.35%). The attributable risk (AR) of respiratory diseases was higher (19.69%, 95%CI: 14.45%-24.24%) than that of cardiovascular diseases (11.40%, 95%CI: 6.29%-16.01%); Conclusions: In Chengdu, temperature was responsible for a substantial fraction of deaths, with cold responsible for a higher proportion of deaths than heat. Respiratory diseases exert a larger effect on death than other diseases especially on cold days. There is potential to reduce respiratory-associated mortality especially among the aged population in basin climate cities when the temperature deviates beneath the optimum. The result may help to comprehensively assess the impact of ambient temperature

  20. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

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    Gao F

    2014-11-01

    hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden. Keywords: status epilepticus, pilocarpine, memory impairment, oxidative stress, neuroprotection

  1. MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo

    KAUST Repository

    Yang, Guang

    2014-01-23

    BackgroundRecent studies have revealed that miR-196a is upregulated in glioblastoma multiforme (GBM) and that it correlates with the clinical outcome of patients with GBM. However, its potential regulatory mechanisms in GBM have never been reported.MethodsWe used quantitative real-time PCR to assess miR-196a expression levels in 132 GBM specimens in a single institution. Oncogenic capability of miR-196a was detected by apoptosis and proliferation assays in U87MG and T98G cells. Immunohistochemistry was used to determine the expression of IκBα in GBM tissues, and a luciferase reporter assay was carried out to confirm whether IκBα is a direct target of miR-196a. In vivo, xenograft tumors were examined for an antiglioma effect of miR-196a inhibitors.ResultsWe present for the first time evidence that miR-196a could directly interact with IκBα 3′-UTR to suppress IκBα expression and subsequently promote activation of NF-κB, consequently promoting proliferation of and suppressing apoptosis in GBM cells both in vitro and in vivo. Our study confirmed that miR-196a was upregulated in GBM specimens and that high levels of miR-196a were significantly correlated with poor outcome in a large cohort of GBM patients. Our data from human tumor xenografts in nude mice treated with miR-196 inhibitors demonstrated that inhibition of miR-196a could ameliorate tumor growth in vivo.ConclusionsMiR-196a exerts its oncogenic effect in GBM by inhibiting IκBα both in vitro and in vivo. Our findings provide new insights into the pathogenesis of GBM and indicate that miR-196a may predict clinical outcome of GBM patients and serve as a new therapeutic target for GBM. © 2014 © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. EFFECT OF EXERCISE INTENSITY ON DIFFERENTIATED AND UNDIFFERENTIATED RATINGS OF PERCEIVED EXERTION DURING CYCLE AND TREADMILL EXERCISE IN RECREATIONALLY ACTIVE AND TRAINED WOMEN

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    Melinda R. Bolgar

    2010-12-01

    Full Text Available The purpose of the study is to examine the effect of aerobic exercise intensity on components of the differentiated perceived exertion model in young women performing weight bearing and non-weight bearing aerobic exercise. Subjects were 18-25 yr old women who were recreationally active (n = 19; VO2max = 33.40 ml·kg-1·min-1 and trained (N = 22; VO2max = 43.3 ml·kg-1·min-1. Subjects underwent two graded exercise tests (GXT on a treadmill and bike which were separated by 48 hours. RPE-Overall, -Legs, and -Chest, as well as oxygen uptake (VO2 and heart rate were recorded each minute. Individual regression analyses were used to identify RPE-Overall,-Legs, and -Chest at 40, 60, 80% VO2max/peak. Separate two factor (site (3 x intensity (3 ANOVAs with repeated measures on site and intensity were computed for each training status. Furthermore, RPE responses were also examined with a one factor (site (3 within subject ANOVA with repeated measure on site at the ventilatory breakpoint. For both the recreationally active and trained groups no significant differences were observed for RPE-Overall, -Legs, and -Chest during treadmill exercise. However, for cycling exercise results indicated that RPE-Legs was significantly greater at all exercise intensities than RPE-Overall and RPE-Chest for trained subjects while for recreationally active subjects RPE-Legs was only significantly higher at the highest exercise intensity. Responses at the ventilatory breakpoint during cycle exercise indicated that RPE-Legs was significantly greater than RPE-Chest and RPE-Overall for trained subjects but not for recreationally active subjects. Signal dominance was not observed at an intensity equivalent to the ventilatory breakpoint during treadmill exercise in either of the groups. In recreationally active and trained females signal dominance was demonstrated only during cycling exercise, but not during treadmill exercise. Signal integration could not be demonstrated during

  3. ACUTE EFFECTS OF THREE DIFFERENT CIRCUIT WEIGHT TRAINING PROTOCOLS ON BLOOD LACTATE, HEART RATE, AND RATING OF PERCEIVED EXERTION IN RECREATIONALLY ACTIVE WOMEN

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    Brook L. Skidmore

    2012-12-01

    Full Text Available Interval and circuit weight training are popular training methods for maximizing time-efficiency, and are purported to deliver greater physiological benefits faster than traditional training methods. Adding interval training into a circuit weight-training workout may further enhance the benefits of circuit weight training by placing increased demands upon the cardiovascular system. Our purpose was to compare acute effects of three circuit weight training protocols 1 traditional circuit weight training, 2 aerobic circuit weight training, and 3 combined circuit weight-interval training on blood lactate (BLA, heart rate (HR, and ratings of perceived exertion (RPE. Eleven recreationally active women completed 7 exercise sessions. Session 1 included measurements of height, weight, estimated VO2max, and 13 repetition maximum (RM testing of the weight exercises. Sessions 2-4 were held on non-consecutive days for familiarization with traditional circuit weight training (TRAD, aerobic circuit weight training (ACWT, and combined circuit weight-interval training (CWIT protocols. In sessions 5-7, TRAD, ACWT, and CWIT were performed in a randomized order > 72 hr apart for measures of BLA, HR, and RPE at pre-exercise and following each of three mini-circuit weight training stations. Repeated-measures ANOVAs yielded significant interactions (p < 0.05 in BLA, HR, and RPE. Combined circuit weight- interval training (CWIT produced higher BLA (7.31 ± 0.37 vs. TRAD: 3.99 ± 0.26, ACWT: 4.54 ± 0.31 mmol.L-1, HR (83.51 ± 1.18 vs. TRAD: 70.42 ± 1.67, ACWT: 74.13 ± 1.43 beats.min-1 and RPE (8.14 ± 0.41 vs. TRAD: 5.06 ± 0.43, ACWT: 6.15 ± 0.42 at all measures. Aerobic circuit weight training (ACWT elicited greater RPE than traditional circuit weight training (TRAD at all measures. Including combined circuit weight-interval training (CWIT workouts into exercise programming may enhance fitness benefits and maximize time-efficiency more so than traditional circuit

  4. Psychological stress exerts effects on pathogenesis of hepatitis B via type-1/type-2 cytokines shift toward type-2 cytokine response.

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    YingLi He

    Full Text Available BACKGROUND: Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV infection, little is known about whether and how stress exerts an effect on the course of hepatitis B. METHODS: Eighty patients with chronic hepatitis B(CHB completed the Perceived Stress Scale-10(PSS-10 and State-Trait Anxiety Inventory(STAI. Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at -80 °C were thawed for cytokines, alanine aminotransferase (ALT, and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared. RESULTS: Firstly, a negative association between ALT and stress (t =  -4.308; p =  .000, state anxiety (t =  -3.085; p =  .003 and trait anxiety (t =  -4.925; p =  .000 were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10 level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000, and type-1 cytokine interferon-gamma (IFN-γ level shown a decreased tendency in high stress group (t =  -1.702; p = 0.093. Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t =  -4.606; p = 0.000, state anxiety(t =  -5.126; p = 0.000 and trait anxiety(t =  -4.670; p = 0.000 groups relative to low counterparts. CONCLUSION: Our data show stress is not related to the lymphocyte cells

  5. Nucleotide pyrophosphatase/phosphodiesterase 1 exerts a negative effect on starch accumulation and growth in rice seedlings under high temperature and CO2 concentration conditions.

    Science.gov (United States)

    Kaneko, Kentaro; Inomata, Takuya; Masui, Takahiro; Koshu, Tsutomu; Umezawa, Yukiho; Itoh, Kimiko; Pozueta-Romero, Javier; Mitsui, Toshiaki

    2014-02-01

    Nucleotide pyrophosphatase/phosphodiesterase (NPP) is a widely distributed enzymatic activity occurring in both plants and mammals that catalyzes the hydrolytic breakdown of the pyrophosphate and phosphodiester bonds of a number of nucleotides. Unlike mammalian NPPs, the physiological function of plant NPPs remains largely unknown. Using a complete rice NPP1-encoding cDNA as a probe, in this work we have screened a rice shoot cDNA library and obtained complete cDNAs corresponding to six NPP genes (NPP1-NPP6). As a first step to clarify the role of NPPs, recombinant NPP1, NPP2 and NPP6 were purified from transgenic rice cells constitutively expressing NPP1, NPP2 and NPP6, respectively, and their enzymatic properties were characterized. NPP1 and NPP6 exhibited hydrolytic activities toward ATP, UDP-glucose and the starch precursor molecule, ADP-glucose, whereas NPP2 did not recognize nucleotide sugars as substrates, but hydrolyzed UDP, ADP and adenosine 5'-phosphosulfate. To gain insight into the physiological function of rice NPP1, an npp1 knockout mutant was characterized. The ADP-glucose hydrolytic activities in shoots of npp1 rice seedlings were 8% of those of the wild type (WT), thus indicating that NPP1 is a major determinant of ADP-glucose hydrolytic activity in rice shoots. Importantly, when seedlings were cultured at 160 Pa CO2 under a 28°C/23°C (12 h light/12 h dark) regime, npp1 shoots and roots were larger than those of wild-type (WT) seedlings. Furthermore, the starch content in the npp1 shoots was higher than that of WT shoots. Growth and starch accumulation were also enhanced under an atmospheric CO2 concentration (40 Pa) when plants were cultured under a 33°C/28°C regime. The overall data strongly indicate that NPP1 exerts a negative effect on plant growth and starch accumulation in shoots, especially under high CO2 concentration and high temperature conditions.

  6. Various Mechanisms Involve the Nuclear Factor (Erythroid-Derived 2-Like (NRF2 to Achieve Cytoprotection in Long-Term Cisplatin-Treated Urothelial Carcinoma Cell Lines

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    Margaretha A. Skowron

    2017-08-01

    Full Text Available Therapeutic efficacy of cisplatin-based chemotherapy for advanced-stage urothelial carcinoma (UC is limited by drug resistance. The nuclear factor (erythroid-derived 2-like 2 (NRF2 pathway is a major regulator of cytoprotective responses. We investigated its involvement in cisplatin resistance in long-term cisplatin treated UC cell lines (LTTs. Expression of NRF2 pathway components and targets was evaluated by qRT-PCR and western blotting in LTT sublines from four different parental cells. NRF2 transcriptional activity was determined by reporter assays and total glutathione (GSH was quantified enzymatically. Effects of siRNA-mediated NRF2 knockdown on chemosensitivity were analysed by viability assays, γH2AX immunofluorescence, and flow cytometry. Increased expression of NRF2, its positive regulator p62/SQSTM1, and elevated NRF2 activity was observed in 3/4 LTTs, which correlated with KEAP1 expression. Expression of cytoprotective enzymes and GSH concentration were upregulated in some LTTs. NRF2 knockdown resulted in downregulation of cytoprotective enzymes and resensitised 3/4 LTTs towards cisplatin as demonstrated by reduced IC50 values, increased γH2AX foci formation, and elevated number of apoptotic cells. In conclusion, while LTT lines displayed diversity in NRF2 activation, NRF2 signalling contributed to cisplatin resistance in LTT lines, albeit in diverse ways. Accordingly, inhibition of NRF2 can be used to resensitise UC cells to cisplatin, but responses in patients may likewise be variable.

  7. Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial.

    Science.gov (United States)

    Olafiranye, Oladipupo; Hostler, David; Winger, Daniel G; Wang, Li; Reis, Steven E

    2015-06-01

    Peripheral arterial stiffness and endothelial function, which are independent predictors of cardiac events, are abnormal in firefighters. We examined the effects of aspirin on peripheral arterial stiffness and endothelial function in firefighters. Fifty-two firefighters were randomized to receive daily 81 mg aspirin or placebo for 14 days before treadmill exercise in thermal protection clothing, and a single dose of 325 mg aspirin or placebo immediately following exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75 (AI75) and reactive hyperemia index (RHI) were determined immediately before, and 30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower AI75 (-15.25±9.25 vs -8.08±10.70, p=0.014) but not RHI. On repeated measures analysis, treatment with low-dose aspirin before, but not single-dose aspirin after exertion, was associated with lower AI75 following exertional heat stress (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave reflection but not endothelial function in firefighters. © The Author(s) 2015.

  8. Prior Acute Mental Exertion in Exercise and Sport.

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    Silva-Júnior, Fernando Lopes E; Emanuel, Patrick; Sousa, Jordan; Silva, Matheus; Teixeira, Silmar; Pires, Flávio; Machado, Sérgio; Arias-Carrion, Oscar

    2016-01-01

    Mental exertion is a psychophysiological state caused by sustained and prolonged cognitive activity. The understanding of the possible effects of acute mental exertion on physical performance, and their physiological and psychological responses are of great importance for the performance of different occupations, such as military, construction workers, athletes (professional or recreational) or simply practicing regular exercise, since these occupations often combine physical and mental tasks while performing their activities. However, the effects of implementation of a cognitive task on responses to aerobic exercise and sports are poorly understood. Our narrative review aims to provide information on the current research related to the effects of prior acute mental fatigue on physical performance and their physiological and psychological responses associated with exercise and sports. The literature search was conducted using the databases PubMed, ISI Web of Knowledge and PsycInfo using the following terms and their combinations: "mental exertion", "mental fatigue", "mental fatigue and performance", "mental exertion and sports" "mental exertion and exercise". We concluded that prior acute mental exertion affects effectively the physiological and psychophysiological responses during the cognitive task, and performance in exercise. Additional studies involving prior acute mental exertion, exercise/sports and physical performance still need to be carried out in order to analyze the physiological, psychophysiological and neurophysiological responses subsequently to acute mental exertion in order to identify cardiovascular factors, psychological, neuropsychological associates.

  9. HLA-A*0206 with TLR3 polymorphisms exerts more than additive effects in Stevens-Johnson syndrome with severe ocular surface complications.

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    Mayumi Ueta

    Full Text Available BACKGROUND: Stevens-Johnson syndrome (SJS is an acute inflammatory vesiculobullous reaction of the skin and mucosa, often including the ocular surface, and toxic epidermal necrolysis (TEN occurs with its progression. Although SJS/TEN is thought to be initiated by certain types of medication coupled with possible infection. In the present study we examined the multiplicative interaction(s between HLA-A*0206 and 7 Toll-like receptor 3 (TLR3 Single-nucleotide polymorphisms (SNPs in patients with SJS/TEN. PRINCIPAL FINDINGS: We analyzed the genotypes for HLA-A and 7 TLR3 SNPs in 110 Japanese SJS/TEN patients with severe ocular complications and 206 healthy volunteers to examine the interactions between the two loci. We found that HLA-A*0206 exhibited a high odds ratio for SJS/TEN (carrier frequency: OR = 5.1; gene frequency: OR = 4.0 and that there was a strong association with TLR3 rs.5743312T/T SNP (OR = 7.4, TLR3 rs.3775296T/T SNP (OR = 5.8, TLR3 rs.6822014G/G SNP (OR = 4.8, TLR3 rs.3775290A/A SNP (OR = 2.9, TLR3 rs.7668666A/A SNP (OR = 2.7, TLR3 rs.4861699G/G SNP (OR = 2.3, and TLR3 rs.11732384G/G SNP (OR = 1.9. There was strong linkage disequilibrium (LD between rs.3775296 and rs.5743312 and between rs.7668666 and rs.3775290. The results of interaction analysis showed that the pair, HLA-A*0206 and TLR3 SNP rs3775296T/T, which exhibited strong LD with TLR3 rs.5743312, exerted more than additive effects (OR = 47.7. The other pairs, HLA-A*0206 and TLR3 rs.3775290A/A SNP (OR = 11.4 which was in strong LD with TLR3 rs7668666A/A SNP, and TLR3 rs4861699G/G SNP (OR = 7.6 revealed additive effects. Moreover, the combination HLA-A*0206 and TLR3 rs3775296T/T was stronger than the TLR3 rs6822014G/G and TLR3 rs3775290A/A pair, which reflected the interactions within the TLR3 gene alone. SIGNIFICANCE: By interaction analysis, HLA-A*0206 and TLR3 SNP rs3775296T/T, which were in strong LD with TLR3 SNP rs5743312T/T, manifested more than additive effects that

  10. Ratings of Perceived Exertion and Self-reported Mood State in Response to High Intensity Interval Training. A Crossover Study on the Effect of Chronotype

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    Jacopo A. Vitale

    2017-07-01

    Full Text Available The aim of this study was to investigate the influence of chronotype on mood state and ratings of perceived exertion (RPE before and in response to acute high intensity interval exercise (HIIE performed at different times of the day. Based on the morningness–eveningness questionnaire, 12 morning-types (M-types; N = 12; age 21 ± 2 years; height 179 ± 5 cm; body mass 74 ± 12 kg and 11 evening-types (E-types; N = 11; age 21 ± 2 years; height 181 ± 11 cm; body mass 76 ± 11 kg were enrolled in a randomized crossover study. All subjects underwent measurements of Profile of Mood States (POMS, before (PRE, after 12 (POST12 and 24 h (POST24 the completion of both morning (08.00 am and evening (08.00 p.m. training. Additionally, Global Mood Disturbance and Energy Index (EI were calculated. RPE was obtained PRE and 30 min POST HIIE. Two-way ANOVA with Tukey’s multiple comparisons test of POMS parameters during morning training showed significant differences in fatigue, vigor and EI at PRE and POST24 between M-types and E-types. In addition, significant chronotype differences were found only in POST12 after the evening HIIE for fatigue, vigor and EI. For what concerns Borg perceived exertion, comparing morning versus evening values in PRE condition, a higher RPE was observed in relation to evening training for M-types (P = 0.0107 while E-types showed higher RPE values in the morning (P = 0.008. Finally, intragroup differences showed that E-types had a higher RPE respect to M-types before (P = 0.002 and after 30 min (P = 0.042 the morning session of HIIE. No significant changes during the evening training session were found. In conclusion, chronotype seems to significantly influence fatigue values, perceived exertions and vigor in relation to HIIE performed at different times of the day. Specifically, E-types will meet more of a burden when undertaking a physical task early in the day. Practical results suggest that performing a HIIE at those times

  11. Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect.

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    Aldini, Rita; Budriesi, Roberta; Roda, Giulia; Micucci, Matteo; Ioan, Pierfranco; D'Errico-Grigioni, Antonia; Sartini, Alessandro; Guidetti, Elena; Marocchi, Margherita; Cevenini, Monica; Rosini, Francesca; Montagnani, Marco; Chiarini, Alberto; Mazzella, Giuseppe

    2012-01-01

    Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

  12. Exenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium.

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    Wallner, Markus; Kolesnik, Ewald; Ablasser, Klemens; Khafaga, Mounir; Wakula, Paulina; Ljubojevic, Senka; Thon-Gutschi, Eva Maria; Sourij, Harald; Kapl, Martin; Edmunds, Nicholas J; Kuzmiski, J Brent; Griffith, David A; Knez, Igor; Pieske, Burkert; von Lewinski, Dirk

    2015-12-01

    Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart

  13. Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts

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    Matteo Micucci

    2015-01-01

    Full Text Available This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE, of a Hibiscus sabdariffa L. flower extract (HSE, and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

  14. Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts.

    Science.gov (United States)

    Micucci, Matteo; Malaguti, Marco; Toschi, Tullia Gallina; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto; Budriesi, Roberta; Hrelia, Silvana

    2015-01-01

    This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

  15. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis—A Pilot Study

    Science.gov (United States)

    Aboodi, Guy M.; Sima, Corneliu; Moffa, Eduardo B.; Crosara, Karla T. B.; Xiao, Yizhi; Siqueira, Walter L.; Glogauer, Michael

    2016-01-01

    Objective: The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. Study design: We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Results: Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Conclusions: Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. Clinical relevance: We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active. PMID:26779447

  16. Salivary Cytoprotective Proteins in Inflammation and Resolution during Experimental Gingivitis--A Pilot Study.

    Science.gov (United States)

    Aboodi, Guy M; Sima, Corneliu; Moffa, Eduardo B; Crosara, Karla T B; Xiao, Yizhi; Siqueira, Walter L; Glogauer, Michael

    2015-01-01

    The protective mechanisms that maintain periodontal homeostasis in gingivitis and prevent periodontal tissue destruction are poorly understood. The aim of this study was to identify changes in the salivary proteome during experimental gingivitis. We used oral neutrophil quantification and whole saliva (WS) proteomics to assess changes that occur in the inflammatory and resolution phases of gingivitis in healthy individuals. Oral neutrophils and WS samples were collected and clinical parameters measured on days 0, 7, 14, 21, 28, and 35. Increased oral neutrophil recruitment and salivary cytoprotective proteins increased progressively during inflammation and decreased in resolution. Oral neutrophil numbers in gingival inflammation and resolution correlated moderately with salivary β-globin, thioredoxin, and albumin and strongly with collagen alpha-1 and G-protein coupled receptor 98. Our results indicate that changes in salivary cytoprotective proteins in gingivitis are associated with a similar trend in oral neutrophil recruitment and clinical parameters. We found moderate to strong correlations between oral neutrophil numbers and levels of several salivary cytoprotective proteins both in the development of the inflammation and in the resolution of gingivitis. Our proteomics approach identified and relatively quantified specific cytoprotective proteins in this pilot study of experimental gingivitis; however, future and more comprehensive studies are needed to clearly identify and validate those protein biomarkers when gingivitis is active.

  17. Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors.

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    Eléonore Otjacques

    Full Text Available Mithramycin (MTM, a cytotoxic compound, is currently being investigated for its anti-angiogenic activity that seems to be mediated through an inhibition of the transcription factor SP1. In this study we evaluated its anti-myeloma effects in the syngenic 5TGM1 model in vitro as well as in vivo. In vitro, MTM inhibited DNA synthesis of 5TGM1 cells with an IC50 of 400 nM and induced an arrest in cell cycle progression at the G1/S transition point. Western-blot revealed an up-regulation of p53, p21 and p27 and an inhibition of c-Myc, while SP1 remained unaffected. In rat aortic ring assays, a strong anti-angiogenic effect was seen, which could be explained by a decrease of VEGF production and an up-regulation of anti-angiogenic proteins such as IP10 after MTM treatment. The administration of MTM to mice injected with 5TGM1 decreased 5TGM1 cell invasion into bone marrow and myeloma neovascularisation. These data suggest that MTM displays anti-myeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation.

  18. Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts

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    Craciunescu Oana

    2012-09-01

    Full Text Available Abstract Background Arnica montana L. and Artemisia absinthium L. (Asteraceae are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study, A. montana and A. absinthium ethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. Results A. absinthium extract showed a higher antioxidant capacity than A. montana extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10–100 mg/L A. montana and 10–500 mg/L A. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/L A. montana and 10–300 mg/L A. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and A. absinthium extracts restored the proportion of cells in each phase of the cell cycle. Conclusions A. montana and A. absinthium extracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use of A. montana and A. absinthium in treatment of skin disorders.

  19. Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts.

    Science.gov (United States)

    Craciunescu, Oana; Constantin, Daniel; Gaspar, Alexandra; Toma, Liana; Utoiu, Elena; Moldovan, Lucia

    2012-09-09

    Arnica montana L. and Artemisia absinthium L. (Asteraceae) are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study, A. montana and A. absinthium ethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. A. absinthium extract showed a higher antioxidant capacity than A. montana extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10-100 mg/L A. montana and 10-500 mg/L A. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/L A. montana and 10-300 mg/L A. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and A. absinthium extracts restored the proportion of cells in each phase of the cell cycle. A. montana and A. absinthium extracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use of A. montana and A. absinthium in treatment of skin disorders.

  20. The Effects of Supplementation with a Vitamin and Mineral Complex with Guaraná Prior to Fasted Exercise on Affect, Exertion, Cognitive Performance, and Substrate Metabolism: A Randomized Controlled Trial.

    Science.gov (United States)

    Veasey, Rachel C; Haskell-Ramsay, Crystal F; Kennedy, David O; Wishart, Karl; Maggini, Silvia; Fuchs, Caspar J; Stevenson, Emma J

    2015-07-27

    Exercise undertaken in a fasted state can lead to higher post-exercise mental fatigue. The administration of a vitamin and mineral complex with guaraná (MVM + G) has been shown to attenuate mental fatigue and improve performance during cognitively demanding tasks. This placebo-controlled, double-blind, randomized, balanced cross-over study examined the effect of MVM + G consumed prior to morning exercise on cognitive performance, affect, exertion, and substrate metabolism. Forty active males (age 21.4 ± 3.0 year; body mass index (BMI) 24.0 ± 2.4 kg/m2; maximal oxygen consumption (V̇O2max) 57.6 ± 7.3 mL/min/kg) completed two main trials, consuming either MVM + G or placebo prior to a 30-min run at 60% V̇O2max. Supplementation prior to exercise led to a small but significant reduction in Rating of Perceived Exertion (RPE) during exercise compared to the placebo. The MVM + G combination also led to significantly increased accuracy of numeric working memory and increased speed of picture recognition, compared to the placebo. There were no significant effects of supplementation on any other cognitive or mood measures or on substrate metabolism during exercise. These findings demonstrate that consuming a vitamin and mineral complex containing guaraná, prior to exercise, can positively impact subsequent memory performance and reduce perceived exertion during a moderate-intensity run in active males.

  1. The Effects of Supplementation with a Vitamin and Mineral Complex with Guaraná Prior to Fasted Exercise on Affect, Exertion, Cognitive Performance, and Substrate Metabolism: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rachel C. Veasey

    2015-07-01

    Full Text Available Exercise undertaken in a fasted state can lead to higher post-exercise mental fatigue. The administration of a vitamin and mineral complex with guaraná (MVM + G has been shown to attenuate mental fatigue and improve performance during cognitively demanding tasks. This placebo-controlled, double-blind, randomized, balanced cross-over study examined the effect of MVM + G consumed prior to morning exercise on cognitive performance, affect, exertion, and substrate metabolism. Forty active males (age 21.4 ± 3.0 year; body mass index (BMI 24.0 ± 2.4 kg/m2; maximal oxygen consumption (V̇O2max 57.6 ± 7.3 mL/min/kg completed two main trials, consuming either MVM + G or placebo prior to a 30-min run at 60% V̇O2max. Supplementation prior to exercise led to a small but significant reduction in Rating of Perceived Exertion (RPE during exercise compared to the placebo. The MVM + G combination also led to significantly increased accuracy of numeric working memory and increased speed of picture recognition, compared to the placebo. There were no significant effects of supplementation on any other cognitive or mood measures or on substrate metabolism during exercise. These findings demonstrate that consuming a vitamin and mineral complex containing guaraná, prior to exercise, can positively impact subsequent memory performance and reduce perceived exertion during a moderate-intensity run in active males.

  2. Characterizing the cytoprotective activity of Sarracenia purpurea L., a medicinal plant that inhibits glucotoxicity in PC12 cells

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    Harris Cory S

    2012-12-01

    Full Text Available Abstract Background The purple pitcher plant, Sarracenia purpurea L., is a widely distributed species in North America with a history of use as both a marketed pain therapy and a traditional medicine in many aboriginal communities. Among the Cree of Eeyou Istchee in northern Québec, the plant is employed to treat symptoms of diabetes and the leaf extract demonstrates multiple anti-diabetic activities including cytoprotection in an in vitro model of diabetic neuropathy. The current study aimed to further investigate this activity by identifying the plant parts and secondary metabolites that contribute to these cytoprotective effects. Methods Ethanolic extracts of S. purpurea leaves and roots were separately administered to PC12 cells exposed to glucose toxicity with subsequent assessment by two cell viability assays. Assay-guided fractionation of the active extract and fractions was then conducted to identify active principles. Using high pressure liquid chromatography together with mass spectrometry, the presence of identified actives in both leaf and root extracts were determined. Results The leaf extract, but not that of the root, prevented glucose-mediated cell loss in a concentration-dependent manner. Several fractions elicited protective effects, indicative of multiple active metabolites, and, following subfractionation of the polar fraction, hyperoside (quercetin-3-O-galactoside and morroniside were isolated as active constituents. Phytochemical analysis confirmed the presence of hyperoside in the leaf but not root extract and, although morroniside was detected in both organs, its concentration was seven times higher in the leaf. Conclusion Our results not only support further study into the therapeutic potential and safety of S. purpurea as an alternative and complementary treatment for diabetic complications associated with glucose toxicity but also identify active principles that can be used for purposes of standardization and quality

  3. Disrupted chronobiology of sleep and cytoprotection in obesity: possible therapeutic value of melatonin.

    Science.gov (United States)

    Cardinali, Daniel P; Pagano, Eleonora S; Scacchi Bernasconi, Pablo A; Reynoso, Roxana; Scacchi, Pablo

    2011-01-01

    From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.

  4. Cytoprotection of human endothelial cells against oxidative stress by 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im): application of systems biology to understand the mechanism of action.

    Science.gov (United States)

    Wang, Xinyu; Bynum, James A; Stavchansky, Solomon; Bowman, Phillip D

    2014-07-05

    Cellular damage from oxidative stress, in particular following ischemic injury, occurs during heart attack, stroke, or traumatic injury, and is potentially reducible with appropriate drug treatment. We previously reported that caffeic acid phenethyl ester (CAPE), a plant-derived polyphenolic compound, protected human umbilical vein endothelial cells (HUVEC) from menadione-induced oxidative stress and that this cytoprotective effect was correlated with the capacity to induce heme oxygenase-1 (HMOX1) and its protein product, a phase II cytoprotective enzyme. To further improve this cytoprotective effect, we studied a synthetic triterpenoid, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), which is known as a potent phase II enzyme inducer with antitumor and anti-inflammatory activities, and compared it to CAPE. CDDO-Im at 200nM provided more protection to HUVEC against oxidative stress than 20μM CAPE. We explored the mechanism of CDDO-Im cytoprotection with gene expression profiling and pathway analysis and compared to that of CAPE. In addition to potent up-regulation of HMOX1, heat shock proteins (HSP) were also found to be highly induced by CDDO-Im in HUVEC. Pathway analysis results showed that transcription factor Nrf2-mediated oxidative stress response was among the top canonical pathways commonly activated by both CDDO-Im and CAPE. Compared to CAPE, CDDO-Im up-regulated more HSP and some of them to a much higher extent. In addition, CDDO-Im treatment affected Nrf2 pathway more significantly. These findings may provide an explanation why CDDO-Im is a more potent cytoprotectant than CAPE against oxidative stress in HUVEC. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Can emotive imagery aid in tolerating exertion efficiently?

    Science.gov (United States)

    Coote, D; Tenenbaum, G

    1998-12-01

    The study examined the role of relaxation and aggressive types of imagery and the effect of goal orientations, self efficacy, self control, and determination on exertion tolerance. the participants underwent an exertive task in which they were required to squeeze a dynamometer, at 50% of their maximal hand-grip capacity, for as long as they could. Perceived exertion was measured every 15 sec during the task. The time that elapsed between rating exertion as "strong", and dropping the handbar under 10% of the designated 50% criterion, was considered as the "zone of exertion tolerance". forty-eight female university students were randomly assigned into 3 groups. two imagery techniques, one under relaxing and one under aggressive conditions were taught and then applied. In the control condition, discussions were conducted. traits such as goal orientation (task and ego), physical self-efficacy and self-control were measured prior to performing the task, while rate of perceived exertion task-specific determination (i.e., task-related confidence, commitment, exertion tolerance, and effort investment) were measured before, during and after the task. The results showed an average of 31% and 28% increase in exertion tolerance in participants who used aggressive and relaxation imagery techniques respectively, compared to 4% reduction in the controls. RM ANOVA indicated equality between the two imagery groups but both were significantly different from the control group. Physical self-efficacy, self-control, and task-specific determination were found nonsignificant, but their important roles in coping with aversive stimuli are highlighted. It was evident that the "coping" mechanism rather than the "distraction" mechanism accounted for the larger sustain in the "zone of exertion tolerance". Imagery can be used efficiently in exertion tolerance but more studies are needed on athletes.

  6. Musical agency reduces perceived exertion during strenuous physical performance

    OpenAIRE

    Fritz, T; Hardikar, S.; Demoucron, M.; Niessen, M.; Demey, M.; O. Giot; Li, Y.; Haynes, J; Villringer, A; Leman, M.

    2013-01-01

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from i...

  7. Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol, heart rate and nocturnal urinary melatonin in humans

    Science.gov (United States)

    Mori, Yuki; Kioka, Etsuko; Tokura, Hiromi

    2002-09-01

    The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.

  8. Musical agency reduces perceived exertion during strenuous physical performance.

    Science.gov (United States)

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-10-29

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

  9. Musical agency reduces perceived exertion during strenuous physical performance

    Science.gov (United States)

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-01-01

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting. PMID:24127588

  10. Exertional desaturation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Panos, Ralph J; Eschenbacher, William

    2009-12-01

    Although the Centers for Medicare and Medicaid Services oxygen prescription guidelines utilize a threshold arterial oxygen tension patients with chronic obstructive pulmonary disease (COPD). There is no uniform definition of exertional hypoxemia or standardized exercise protocol to elicit decreases in oxygen levels in individuals with COPD. The causes for exertional desaturation in patients with COPD are multifactorial with ventilation-perfusion mismatching, diffusion-type limitation, shunting and reduced oxygen content of mixed venous blood all contributing to some degree. Neither resting oxygen saturation nor pulmonary function studies can reliably predict which patients with COPD will develop exertional desaturation. However, preserved pulmonary function, especially diffusing capacity, reliably predicts which patients with COPD will sustain oxygenation during exercise. Although exertional desaturation in patients with COPD appears to portend a poor prognosis, there is no evidence that maintenance of normoxemia during exercise improves the survival of these patients. Studies of the effect of supplemental oxygen on exercise performance in individuals with COPD who desaturate with exertion have yielded conflicting results. The use of short-term or "burst" oxygen either prior to or after exertion may not have significant clinical benefit. Differences in the definition of desaturation, mode of exercise, and characteristics of the patient population make it difficult to compare studies of exertional desaturation and its treatment and to determine their applicability to clinical practice.

  11. Surgical management of exertional anterior compartment syndrome of the leg.

    Science.gov (United States)

    Ali, T; Mohammed, F; Mencia, M; Maharaj, D; Hoford, R

    2013-07-01

    To describe the characteristic presentation of exertional leg pain in athletes and to discuss the diagnostic options and surgical management of exertional anterior compartment syndrome of the leg in this group of patients. Data from a series of athletes presenting with exertional leg pain were analysed and categorized according to aetiology. Sixty-six athletes presenting with exertional leg pain in 102 limbs were analysed. Sixteen patients in a first group of 20 patients with a provisional diagnosis of exertional anterior compartment syndrome of the leg underwent a closed fasciotomy with complete resolution of symptoms. A second group of 42 patients were diagnosed as medial tibial stress syndrome and a third group of four patients had confirmed stress fracture of the tibia. Exertional leg pain is a common presenting complaint of athletes to sports physicians and physiotherapists. Careful analysis can lead to an accurate diagnosis and commencement of effective treatment. Exertional anterior compartment syndrome can be successfully treated utilizing a closed fasciotomy with a rapid return to sport.

  12. Do placebo expectations influence perceived exertion during physical exercise?

    Science.gov (United States)

    Mothes, Hendrik; Leukel, Christian; Seelig, Harald; Fuchs, Reinhard

    2017-01-01

    This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a) the effects of exercise and b) the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE) measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment) would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels) in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

  13. Cytoprotective alginate/polydopamine core/shell microcapsules in microbial encapsulation.

    Science.gov (United States)

    Kim, Beom Jin; Park, Taegyun; Moon, Hee Chul; Park, So-Young; Hong, Daewha; Ko, Eun Hyea; Kim, Ji Yup; Hong, Jong Wook; Han, Sang Woo; Kim, Yang-Gyun; Choi, Insung S

    2014-12-22

    Chemical encapsulation of microbes in threedimensional polymeric microcapsules promises various applications, such as cell therapy and biosensors, and provides a basic platform for studying microbial communications. However, the cytoprotection of microbes in the microcapsules against external aggressors has been a major challenge in the field of microbial microencapsulation, because ionotropic hydrogels widely used for microencapsulation swell uncontrollably, and are physicochemically labile. Herein, we developed a simple polydopamine coating for obtaining cytoprotective capability of the alginate capsule that encapsulated Saccharomyces cerevisiae. The resulting alginate/ polydopamine core/shell capsule was mechanically tough, prevented gel swelling and cell leakage, and increased resistance against enzymatic attack and UV-C irradiation. We believe that this multifunctional core/shell structure will provide a practical tool for manipulating microorganisms inside the microcapsules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Phenolic Composition and Evaluation of Antioxidant and Cytoprotective Activity of Chiliadenus montanus

    OpenAIRE

    Tarek F. Eissa; Elena González-Burgos; M. Emilia Carretero; M. Pilar Gómez-Serranillos

    2013-01-01

    The antioxidant and cytoprotective activities of the hydroalcoholic extract of Chiliadenus montanus, widely used in Egyptian traditional medicine, were investigated. The antioxidant potential, determined using ORAC assay, revealed that Chiliadenus montanus extracts are active radical scavengers (ORAC value 1.720 µmol TE/mg sample). Total phenolic content, measured by Folin-Ciocalteau, was 107.4 mg galic acid/g sample. HPLC and HPLC-MS analysis allowed individual polyphenolic compounds to be i...

  15. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-01-15

    pathways in diabetic conditions. ► Taurine exerts antioxidant, antihyperlipidemic and antiinflammatory activities. ► It protects cardiac apoptosis by regulating Bcl2 family and caspase 9/3 proteins.

  16. Decreasing sprint duration from 20 to 10 s during reduced-exertion high-intensity interval training (REHIT) attenuates the increase in maximal aerobic capacity but has no effect on affective and perceptual responses.

    Science.gov (United States)

    Nalcakan, Gulbin R; Songsorn, Preeyaphorn; Fitzpatrick, Ben L; Yuzbasioglu, Yasin; Brick, Noel E; Metcalfe, Richard S; Vollaard, Niels Bj

    2017-11-24

    Recent studies have demonstrated that modifying the 'classic' 6x30-s 'all-out' sprint interval training (SIT) protocol by incorporating either shorter sprints (6x10-s or 15-s sprints) or fewer sprints (e.g. 2x20-s sprints; reduced-exertion high-intensity interval training (REHIT)) does not attenuate the training-induced improvements in maximal aerobic capacity (V̇O2max). The aim of the present study was to determine whether reducing the sprint duration in the REHIT protocol from 20 s to 10 s per sprint influences acute affective responses and the change in V̇O2max following training. Thirty-six sedentary or recreationally active participants (17 women; mean±SD age: 22±3 y, BMI: 24.5±4.6 kg·m-2, V̇O2max: 37±8 mL·kg-1·min-1) were randomised to a group performing a 'standard' REHIT protocol involving 2x20-s sprints or a group who performed 2x10-s sprints. V̇O2max was determined before and after 6 weeks of 3 weekly training sessions. Acute affective responses and perceived exertion were assessed during training. Greater increases in V̇O2max were observed for the group performing 20-s sprints (2.77±0.75 to 3.04±0.75 L·min-1; +10%) compared to the group performing 10-s sprints (2.58±0.57 vs. 2.67±3.04 L·min-1; +4%; group×time interaction effect: ps to 10 s attenuates improvements in V̇O2max, and does not result in more positive affective responses or lower perceived exertion.

  17. Cytoprotective and healing properties of Musa paradisiacal Linn on ...

    African Journals Online (AJOL)

    This study was designed to investigate the potential preventive and healing effects of the methanolic extract of Musa paradisiacal and its effects in combination with catecholamine on indomethacin-induced peptic ulcer. Forty wistar rats (150 – 250 g) of both sexes were used for the experiments: 20 rats for prophylaxis and 20 ...

  18. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...... million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified......, and a standard case-referent analysis) were applied to overcome the threat of misclassification of control exposure information. A case-crossover analysis in a random sample of healthy subjects resulted in a relative risk close to unity, as expected....

  19. The Cotransplantation of Olfactory Ensheathing Cells with Bone Marrow Mesenchymal Stem Cells Exerts Antiapoptotic Effects in Adult Rats after Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Shifeng Wu

    2015-01-01

    Full Text Available The mechanisms behind the repairing effects of the cotransplantation of olfactory ensheathing cells (OECs with bone marrow mesenchymal stromal cells (BMSCs have not been fully understood. Therefore, we investigated the effects of the cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for which the models of SCI are induced. We examined the changes in body weight, histopathological changes, apoptosis, and the expressions of apoptosis-related proteins after 14 days and 28 days after transplantation. We also assessed animal locomotion using BBB test. We found that treatment with OECs and BMSCs had a remissive effect on behavioral outcome and histopathological changes induced SCI. Furthermore, we observed the significant antiapoptotic effect on cotransplant treated group. In addition, cotransplantation of OECs with BMSCs was found to have more significant repairing effect than that of OECs or BMSCs alone. Furthermore, the recovery of hind limb could be related to antiapoptotic effect of OECs and BMSCs through downregulating the apoptotic pathways. Finally, our data suggested the cotransplantation of OECs w