Balanced Physical Exercise Increase Physical Fitness, Optimize Endorphin Levels, and Decrease Malondialdehyde Levels

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Erwin Adams Pangkahila

2016-10-01

Full Text Available Background: Physical fitness determines the level of human health. A good physical fitness can be achieved if conducted with a balance and active physical fitness. The aims of this study was to elucidate the effect of balanced physical exercise on physical fitness, endorphin levels, and malondialdehyde (MDA levels. Methods: This study was a true experimental with pretest-posttest control group design using 24 students of IKIP PGRI Denpasar. Selected samples divided into two groups: the control group given conventional physical training (P0 and the treatment group given balanced physical training (P1. Physical fitness tests was performed using Cooper method and blood sampling was done to evaluate the level of endorphins and MDA before (pre test and after (post test treatment of 8 weeks. The data of endorphin and MDA levels were analyzed using independent T test. Whereas, the physical fitness was analyzed using Mann-Whitney U test. Results: Physical fitness of the group given a balanced physical training was significantly higher compare to the group given a conventional physical training (p < 0.05. Balanced physical training was proven to enhance physical fitness as measured by the Cooper method better than conventional physical training. In contrast, the levels of endorphins of the balanced physical training group did not different with the conventional physical training group (p > 0.05. Levels of MDA of balanced physical training group also did not different with the conventional physical training group (p > 0.05. Conclusions: balanced physical training can maintain physical fitness of people and improve the health and quality of life. 

Analytical method of CIM to PIM transformation in Model Driven Architecture (MDA

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Martin Kardos

2010-06-01

Full Text Available Information system’s models on higher level of abstraction have become a daily routine in many software companies. The concept of Model Driven Architecture (MDA published by standardization body OMG1 since 2001 has become a concept for creation of software applications and information systems. MDA specifies four levels of abstraction: top three levels are created as graphical models and the last one as implementation code model. Many research works of MDA are focusing on the lower levels and transformations between each other. The top level of abstraction, called Computation Independent Model (CIM and its transformation to the lower level called Platform Independent Model (PIM is not so extensive research topic. Considering to a great importance and usability of this level in practice of IS2Keywords: transformation, MDA, CIM, PIM, UML, DFD. development now our research activity is focused to this highest level of abstraction – CIM and its possible transformation to the lower PIM level. In this article we are presenting a possible solution of CIM modeling and its analytic method of transformation to PIM.

Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment

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Dönmezdil N

2016-04-01

Full Text Available Nilüfer Dönmezdil, Mehmet Uğur Çevik, Hasan Hüseyin Özdemir, Muhterem Taşin Department of Neurology, Dicle University, Diyarbakır, Turkey Purpose: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments.Methods: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA levels and paraoxonase 1 (PON1 activity were carried out in the biochemistry laboratory.Results: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL, there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17 was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L. Nonetheless, it was not so low as to have significance from a statistical point of view.Conclusion: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment. Keywords: epilepsy, paraoxonase 1, malondialdehyde, oxidative stress, epilepsy, biochemical marker

Improved multiple displacement amplification (iMDA) and ultraclean reagents.

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Motley, S Timothy; Picuri, John M; Crowder, Chris D; Minich, Jeremiah J; Hofstadler, Steven A; Eshoo, Mark W

2014-06-06

Next-generation sequencing sample preparation requires nanogram to microgram quantities of DNA; however, many relevant samples are comprised of only a few cells. Genomic analysis of these samples requires a whole genome amplification method that is unbiased and free of exogenous DNA contamination. To address these challenges we have developed protocols for the production of DNA-free consumables including reagents and have improved upon multiple displacement amplification (iMDA). A specialized ethylene oxide treatment was developed that renders free DNA and DNA present within Gram positive bacterial cells undetectable by qPCR. To reduce DNA contamination in amplification reagents, a combination of ion exchange chromatography, filtration, and lot testing protocols were developed. Our multiple displacement amplification protocol employs a second strand-displacing DNA polymerase, improved buffers, improved reaction conditions and DNA free reagents. The iMDA protocol, when used in combination with DNA-free laboratory consumables and reagents, significantly improved efficiency and accuracy of amplification and sequencing of specimens with moderate to low levels of DNA. The sensitivity and specificity of sequencing of amplified DNA prepared using iMDA was compared to that of DNA obtained with two commercial whole genome amplification kits using 10 fg (~1-2 bacterial cells worth) of bacterial genomic DNA as a template. Analysis showed >99% of the iMDA reads mapped to the template organism whereas only 0.02% of the reads from the commercial kits mapped to the template. To assess the ability of iMDA to achieve balanced genomic coverage, a non-stochastic amount of bacterial genomic DNA (1 pg) was amplified and sequenced, and data obtained were compared to sequencing data obtained directly from genomic DNA. The iMDA DNA and genomic DNA sequencing had comparable coverage 99.98% of the reference genome at ≥1X coverage and 99.9% at ≥5X coverage while maintaining both balance

Effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid

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Ya-Ling Wang

2016-09-01

Full Text Available Objective: To investigate the effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid. Methods: A total of 80 patients with dental porcelain crowns at front teeth during February 2013 to February 2016 were randomly divided into cobalt-chromium alloy PFM group (n=40 and gold alloy PFM group (n=40. After 6 months, the amount of gingival crevicular fluid, GI, PD, AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid were recorded and analyzed. Results: There were no differences in amount of gingival crevicular fluid, GI and PD before treatment of the two groups (P>0.05. After treatment, the amount of gingival crevicular fluid, GI and PD of the two groups were significantly higher than before treatment (P0.05. After treatment, the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid of the two groups were significantly higher than before treatment (P<0.05, but that of the gold alloy PFM group were significantly lower than cobalt-chromium alloy PFM group (P<0.05. After treatment, the GP-x level in gingival crevicular fluid of the two groups were significantly lower than before treatment (P<0.05, but that of the gold alloy PFM group were significantly higher than cobalt-chromium alloy PFM group (P<0.05. Conclusions: Gold alloy PFM can significantly reduce the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid, improve the GP-x level in gingival crevicular fluid, shows better biocompatibility and clinical outcomes than cobalt-chromium alloy PFM.

Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231

International Nuclear Information System (INIS)

Turturro, Francesco; Friday, Ellen; Welbourne, Tomas

2007-01-01

We studied the RNA expression of the genes in response to glucose from 5 mM (condition of normoglycemia) to 20 mM (condition of hyperglycemia/diabetes) by microarray analysis in breast cancer derived cell line MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP), whose RNA level increased as a gene product particularly sensitive to the variation of the level of glucose in culture media. We investigated the kinesis of the TXNIP RNA and protein in response to glucose and the relationship between this protein and the related thioredoxin (TRX) in regulating the level of reactive oxygen species (ROS) in MDA-MB-231 cells. MDA-MB-231 cells were grown either in 5 or 20 mM glucose chronically prior to plating. For glucose shift (5/20), cells were plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with Affymetrix Human U133A microarray chip and gene expression profile was obtained. Semi-quantitative RT-PCR and Western blot was used to validate the expression of TXNIP RNA and protein in response to glucose, respectively. ROS were detected by CM-H2DCFDA (5–6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and measured for mean fluorescence intensity with flow cytometry. TRX activity was assayed by the insulin disulfide reducing assay. We found that the regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly within 6 h of its increased level (20 mM glucose) and persists through the duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1 by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity. In this study we show that TXNIP is an oxidative stress responsive gene and its expression is exquisitely regulated by

Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP in metastatic breast cancer-derived cells MDA-MB-231

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Friday Ellen

2007-06-01

Full Text Available Abstract Background We studied the RNA expression of the genes in response to glucose from 5 mM (condition of normoglycemia to 20 mM (condition of hyperglycemia/diabetes by microarray analysis in breast cancer derived cell line MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP, whose RNA level increased as a gene product particularly sensitive to the variation of the level of glucose in culture media. We investigated the kinesis of the TXNIP RNA and protein in response to glucose and the relationship between this protein and the related thioredoxin (TRX in regulating the level of reactive oxygen species (ROS in MDA-MB-231 cells. Methods MDA-MB-231 cells were grown either in 5 or 20 mM glucose chronically prior to plating. For glucose shift (5/20, cells were plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with Affymetrix Human U133A microarray chip and gene expression profile was obtained. Semi-quantitative RT-PCR and Western blot was used to validate the expression of TXNIP RNA and protein in response to glucose, respectively. ROS were detected by CM-H2DCFDA (5–6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and measured for mean fluorescence intensity with flow cytometry. TRX activity was assayed by the insulin disulfide reducing assay. Results We found that the regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly within 6 h of its increased level (20 mM glucose and persists through the duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1 by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity. Conclusion In this study we show that TXNIP is an oxidative stress responsive

OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

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Muñiz P

2014-05-01

Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

Characterization and immune response expression of the Rig-I-like receptor mda5 in common carp Cyprinus carpio.

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Zhu, Y Y; Xing, W X; Shan, S J; Zhang, S Q; Li, Y Q; Li, T; An, L; Yang, G W

2016-06-01

In this study, the full-length complementary (c)DNA of common carp Cyprinus carpio melanoma differentiation-associated gene 5 (mda5) was cloned. The complete open reading frame of C. carpio mda5 contained 2982 bp and encodes 993 amino acids. The deduced amino acids contained six functional domains: two caspase activation and recruitment domains (CARD), a conserved restriction domain of bacterial type III restriction enzyme (ResIII), a DExD/H box-containing domain (DEXDc), a helicase super family C-terminal domain (HELICc) and a C-terminal regulatory domain (RD). The mda5 gene was expressed in all tested tissues, with high levels in the gills and spleen, while lower expressed in gonad and blood. The copy numbers of mda5 were increased in the liver, spleen, head kidney and the mucosal-associated immune tissues such as the foregut, hindgut, gills and skin after stimulation with polyinosinic polycytidylic [poly(I:C)] and Aeromonas hydrophila. The myxovirus resistance gene (mx) messenger (m)RNA levels in the spleen, head kidney, foregut and gills were significantly up-regulated after poly(I:C) injection. When injected with poly(I:C), mda5 and mx transcripts were also significantly induced in vitro. These results implied that mda5 might be involved in both antiviral and antibacterial innate immune processes in C. carpio. © 2016 The Authors. Journal of Fish Biology © 2016 The Fisheries Society of the British Isles. © 2016 The Fisheries Society of the British Isles.

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

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Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

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Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao

2014-01-01

The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Digital Droplet Multiple Displacement Amplification (ddMDA for Whole Genome Sequencing of Limited DNA Samples.

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Minsoung Rhee

Full Text Available Multiple displacement amplification (MDA is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently, the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet, ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.

Arsenicosis status and urinary malondialdehyde (MDA) in people exposed to arsenic contaminated-coal in China

Energy Technology Data Exchange (ETDEWEB)

Wang, J.P.; Maddalena, R.; Zheng, B.S.; Zai, C.; Liu, F.Y.; Ng, J.C. [University of Queensland, Brisbane, Qld. (Australia)

2009-04-15

The current arsenic exposure condition, arsenicosis prevalence. urinary arsenic and MDA (malondialdehyde) concentrations in people were studied. The study area, a village in Xing Ren County in Guizhou Province, PR China, is a coal-borne arsenicosis endemic area that was identified several decades ago. The residents in Xing Ren have been using coal containing high arsenic levels all their life. Urinary arsenic levels of villagers were 192.2 {+-} 22 {mu} g/g creatinine (n=113) in the coal-borne endemic area (Xing Ren county) and were significantly higher than 63.6 {+-} 5.9 {mu} g/g creatinine (n=30) in a neighbouring control site (a village in Xing Yi county). The urinary MDA concentrations of villagers from the endemic area were also significantly higher compared to those of the control area. There was a strong correlation between age and urinary arsenic and MDA concentrations in the endemic area of Xing Ren: urinary arsenic and MDA levels decreased with age. Fifty out of 113 (44.3%) villagers in the endemic area had arsenicosis symptoms and the prevalence in villagers older than 40 y was 100% in male (92.2% overall). Urinary MDA concentration was significantly higher in people with arsenicosis symptoms in the endemic areas. Oxidative stress (urinary MDA concentration) was strongly related to arsenic exposure but not to the age and smoking habit. Higher urinary arsenic and MDA levels in younger villagers from the endemic area suggest that they are having a higher exposure to coal-borne emitted arsenic because they spend more time indoor. There is an urgent need to develop proper intervention methods in the Guizhou endemic areas in order to reduce the risk to the local communities who are still using arsenic contaminated-coal.

Towards an MDA-based development methodology

NARCIS (Netherlands)

Gavras, Anastasius; Belaunde, Mariano; Ferreira Pires, Luis; Andrade Almeida, João; Oquendo, Flavio; Warboys, Brian C.; Morrison, Ron

2004-01-01

This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

Energy Technology Data Exchange (ETDEWEB)

Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I., E-mail: evfrolova@UAB.edu

2016-01-15

Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. - Highlights: • Both RIG-I and MDA5 detect alphavirus replication. • Alphavirus-induced transcriptional shutoff affects type I IFN induction. • Sensing of alphavirus replication by RIG-I and MDA5 depends on their concentrations. • High basal level of RIG-I and MDA5 allows IFN induction by pathogenic alphaviruses. • This dependence determines the discrepancy between the in vivo and in vitro data.

Antitumor Activity of Chinese Propolis in Human Breast Cancer MCF-7 and MDA-MB-231 Cells

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Hongzhuan Xuan

2014-01-01

Full Text Available Chinese propolis has been reported to possess various biological activities such as antitumor. In present study, anticancer activity of ethanol extract of Chinese propolis (EECP at 25, 50, 100, and 200 μg/mL was explored by testing the cytotoxicity in MCF-7 (human breast cancer ER(+ and MDA-MB-231 (human breast cancer ER(− cells. EECP revealed a dose- and time-dependent cytotoxic effect. Furthermore, annexin A7 (ANXA7, p53, nuclear factor-κB p65 (NF-κB p65, reactive oxygen species (ROS levels, and mitochondrial membrane potential were investigated. Our data indicated that treatment of EECP for 24 and 48 h induced both cells apoptosis obviously. Exposure to EECP significantly increased ANXA7 expression and ROS level, and NF-κB p65 level and mitochondrial membrane potential were depressed by EECP dramatically. The effects of EECP on p53 level were different in MCF-7 and MDA-MB-231 cells, which indicated that EECP exerted its antitumor effects in MCF-7 and MDA-MB-231 cells by inducing apoptosis, regulating the levels of ANXA7, p53, and NF-κB p65, upregulating intracellular ROS, and decreasing mitochondrial membrane potential. Interestingly, EECP had little or small cytotoxicity on normal human umbilical vein endothelial cells (HUVECs. These results suggest that EECP is a potential alternative agent on breast cancer treatment.

Plasma Malondialdehyde (MDA): an indication of liver damage in ...

African Journals Online (AJOL)

Non-pregnant women were selected from volunteered members of staff. Malondialdehyde (MDA), aspartate transaminase (AST) and alanine transaminase (ALT) analyses were determined on collected venous blood sample. Statistical analyses of variables were done using SPSS 17 taking level of significance to be p<0.05.

Pengaruh pemberian kecambah kacang hijau (Phaseolus radiatus (L. terhadap kadar malondealdehid (MDA plasma dan jaringan hati tikus Sprague Dawley yang diberi pakan lemak tinggi

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Novidiyanto Novidiyanto

2016-10-01

Conclusion: Level of MDA plasma and liver tissue of rat in group P1 and P2 was lower than a level of MDA plasma and liver tissue of rat in group K1, but higher than the level of MDA plasma and liver tissue of rat in group P3. There was a very strong correlation between the level of MDA plasma and liver tissue of rat was given the mung bean sprouts and high-fat diet.

Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion.

Science.gov (United States)

Larsson, Karin; Harrysson, Hanna; Havenaar, Robert; Alminger, Marie; Undeland, Ingrid

2016-02-01

Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ∼ 25 μM MDA and ∼ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ≫ herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids.

ESTRÉS OXIDATIVO Y DAÑO VASCULAR EN PROCESOS DE HIPOXIA. MALONDIALDEHIDO (MDA COMO BIOMARCADOR DE DAÑO OXIDATIVO

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Muñiz P

2014-05-01

Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

Δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

International Nuclear Information System (INIS)

Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J.; Aramaki, Hironori

2014-01-01

We recently reported that Δ 9 -tetrahydrocannabinol (Δ 9 -THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ 9 -THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ 9 -THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ 9 -THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ 9 -THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ 9 -THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ 9 -THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ 9 -THC up-regulation of FA2H in MDA-MB-231 cells

Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.

Science.gov (United States)

Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J; Aramaki, Hironori

2014-12-04

We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ(9)-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ(9)-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ(9)-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ(9)-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ(9)-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ(9)-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ(9)-THC up-regulation of FA2H in MDA-MB-231 cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

IPOMOEA BATATAS SYRUP DECREASE MALONDIALDEHYDE AND INCREASE NITROUS OXIDE PLASMA LEVELS AMONGST MODERATE SMOKER WORKERS AT DENPASAR

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I Dewa Ayu Intan Dwi-Primayanti

2012-09-01

Full Text Available Objective: Cells and tissues are continuously damaged by reactive oxygen species. Cigarette smoke is one of an exogenous source of free radical containing more than 4000 chemical compounds, that triggering the formation of free radicals related to diseases and aging process. Anthocyanins are potent antioxidants that are widely distributed in fruit, vegetables, red wines and Ipomea batatas. The aim of this study was to determine the effect of Ipomea batatas as a source of antioxidants in decreasing levels of alondialdehyde (MDA and increasing of Nitrous oxide (nitrite/nitrate/NOxplasma in moderate smokers of workers at Denpasar.Method: This was an experimental study with a pretest-posttest control groups design. There are 33 moderate smokers who were divided into three groups, control group (placebo, treatment group with 15 ml purple sweet potato syrup (P1 and 30 ml (P2, for 14 days. All groups were performed the laboratory examinations for MDA and NOx plasma before and after the treatment.Results: This study showed that there were significant differences (p<0.05 both in MDA and NOx plasma levels in the control group, P1 and P2. The decrease of MDAlevels on P1 was 35.39% and on P2 was 49.87%. The increase of NOx plasma levels was 7.78% for P1 and 14.68% for P2.Conclusion: From this study, it can be concluded that Ipomea batatas syrup contains of 8mg/mL anthocyanins, probably play a role in reducing the free radical and thus reducingthe risk of disease and slowing the aging process.

Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

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Takeda, Shuso [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan); Ikeda, Eriko [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Su, Shengzhong [Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802 (United States); Harada, Mari [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Okazaki, Hiroyuki [Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Watanabe, Kazuhito [Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181 (Japan); Omiecinski, Curtis J. [Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802 (United States); Aramaki, Hironori [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)

2014-12-04

We recently reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ{sup 9}-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ{sup 9}-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ{sup 9}-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ{sup 9}-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ{sup 9}-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ{sup 9}-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ{sup 9}-THC up-regulation of FA2H in MDA-MB-231 cells.

Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration

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Toshiyuki Matsuura

2017-01-01

Full Text Available Purpose. To compare serum levels of malondialdehyde (MDA in patients with wet age-related macular degeneration (wAMD, patients with dry AMD (dAMD, and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group, and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

Improved quantification of a commercial enzyme-linked immunosorbent assay kit for measuring anti-MDA5 antibody.

Science.gov (United States)

Gono, Takahisa; Okazaki, Yuka; Murakami, Akihiro; Kuwana, Masataka

2018-04-09

To compare the quantitative performance for measuring anti-MDA5 antibody titer of two enzyme-linked immunosorbent assay (ELISA) systems: an in-house ELISA and the commercial MESACUP TM anti-MDA5 test. Anti-MDA5 antibody titer was measured in sera from 70 patients with dermatomyositis using an in-house ELISA and the MESACUP TM anti-MDA5 test side-by-side. For the commercial ELISA kit, serum samples diluted 1:101 were used according to the manufacturer's protocol, but serial dilutions of sera were also examined to identify the optimal serum dilution for quantification. The anti-MDA5 antibody titers measured by the in-house and commercial ELISAs were positively correlated with each other (r = 0.53, p = .0001), but the antibody titer measured by the commercial ELISA was less sensitive to change after medical treatment, and 37 (80%) of 46 anti-MDA5-positive sera had antibody titer exceeding the quantification range specified by the manufacturer (≥150 index). Experiments using diluted serum samples revealed that diluting the sera 1:5050 improved the quantitative performance of the MESACUP TM anti-MDA5 test, including a better correlation with the in-house ELISA results and an increased sensitivity to change. We improved the ability of the commercial ELISA kit to quantify anti-MDA5 antibody titer by altering its protocol.

MDA and GSH-Px activity in transition dairy cows under seasonal variations and their relationship with reproductive performance

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Colakoglu Hatice Esra

2017-12-01

Full Text Available Introduction: The purpose of the current study was to evaluate the blood glutathione peroxidase (GSH-Px and malondialdehyde (MDA levels under seasonal variations in dairy cows during transition period, and to assess the relationship between chosen reproductive parameters, GSH-Px, and MDA.

Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

Science.gov (United States)

McNamara, Ruth; Kerans, Aoife; O'Neill, Barry; Harkin, Andrew

2006-01-01

The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of

Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

Science.gov (United States)

Chen, Xiao-Xin; Leung, George Pak-Heng; Zhang, Zhang-Jin; Xiao, Jian-Bo; Lao, Li-Xing; Feng, Feng; Mak, Judith Choi-Wo; Wang, Ying; Sze, Stephen Cho-Wing; Zhang, Kalin Yan-Bo

2017-09-01

Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

International Nuclear Information System (INIS)

Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan

2014-01-01

Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation

Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

Energy Technology Data Exchange (ETDEWEB)

Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

2014-05-15

Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.

On the notion of abstract platform in MDA development

NARCIS (Netherlands)

Andrade Almeida, João; Dijkman, R.M.; van Sinderen, Marten J.; Ferreira Pires, Luis

2004-01-01

Although platform-independence is a central property in MDA models, the study of platform-independence has been largely overlooked in MDA. As a consequence, there is a lack of guidelines to select abstraction criteria and modelling concepts for platform-independent design. In addition, there is

Towards an MDA-based development methodology for distributed applications

NARCIS (Netherlands)

van Sinderen, Marten J.; Gavras, A.; Belaunde, M.; Ferreira Pires, Luis; Andrade Almeida, João

2004-01-01

This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

Automated code generation support for BI with MDA TALISMAN

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Óscar Sanjuan-Martínez

2009-12-01

Full Text Available Model Driven Engineering (MDE is gaining ever more strength due to the fact that with MDE the software development can be much more productive and this is the way to go closer to real software industrialization. With MDA TALISMAN, we have succeeded in creating complex software solutions for food traceability adapted to different customers, ready to be deployed. We rely on the approach to MDE most extended at present, MDA (Model-Driven Development but as we shall see, we also use the main pillars that support the Software Factories, The proposal from Microsoft to MDE. Besides, in this paper we present five cases of success with MDA TALISMAN.

Exploring a model-driven architecture (MDA) approach to health care information systems development.

Science.gov (United States)

Raghupathi, Wullianallur; Umar, Amjad

2008-05-01

To explore the potential of the model-driven architecture (MDA) in health care information systems development. An MDA is conceptualized and developed for a health clinic system to track patient information. A prototype of the MDA is implemented using an advanced MDA tool. The UML provides the underlying modeling support in the form of the class diagram. The PIM to PSM transformation rules are applied to generate the prototype application from the model. The result of the research is a complete MDA methodology to developing health care information systems. Additional insights gained include development of transformation rules and documentation of the challenges in the application of MDA to health care. Design guidelines for future MDA applications are described. The model has the potential for generalizability. The overall approach supports limited interoperability and portability. The research demonstrates the applicability of the MDA approach to health care information systems development. When properly implemented, it has the potential to overcome the challenges of platform (vendor) dependency, lack of open standards, interoperability, portability, scalability, and the high cost of implementation.

Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients.

Science.gov (United States)

Wang, Sheng-Lan; Zhu, Xin-Yan; Zhang, Dong-Wei; Zhang, Zhao-Jie; Gao, Heng-Jun; Yang, Chang-Qing

2015-01-01

Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. The MDA plasma level of cirrhotic patients was significantly higher than the controls (Pportal hypertension (Pportal vein (r=0.652, Pportal hypertension. Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients.

Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

Science.gov (United States)

Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

2016-02-01

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

THE EFFECT OF WEIGHT LOSS ON PLASMA MDA, LIPIDS PROFILE AND APOA AND APOB IN OBESE WOMAN

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Fatemeh Ramezani

2010-12-01

Full Text Available Abstract   INTRODUCTION: Obesity increased reactive oxygen species generation that it result in oxidative injury on lipids profile and lipoproteins that all of which insert atherosclerotic effect. Nutritional intervention by means of a hypocaloric diet could produce protective effects against the redox unbalance.  In this context, the aim of this intervention trial was to estimate the ability of weight loss to improve oxidative stress biomarkers related to lipids peroxidation and lipid profile and apoproteins concentrations of serum in obese women.   METHODS: Thirties eight obese women, 15-45 years old, with body mass index (BMI <30 kg/m2 were recruited. The obese women were assigned to energy-restricted dietary treatments for 12 week. Before and after nutritional intervention and 10% weight reduction, anthropometric measurements were taken and fasting blood was drawn. Plasma levels of (MDA determined with TBAR and triglyceride, total cholesterol and HDL cholesterol. Keywords: MDA, lipid profile, obese woman, Weight loss.

Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress.

Science.gov (United States)

Erem, Cihangir; Suleyman, Akile Karacin; Civan, Nadim; Mentese, Ahmet; Nuhoglu, İrfan; Uzun, Aysegul; Ersoz, Halil Onder; Deger, Orhan

2015-01-01

The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. Forty-five untreated patients with overt hyperthyroidism (OHyper), 20 untreated patients with subclinical hyperthyroidism (SHyper) and 30 age-and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, the levels of MDA, glucose and TG were significantly increased in patients with SHyper (p<0.05), whereas LDL-C levels were significantly decreased (p<0.01). Patients with OHyper showed significantly elevated MDA and glucose levels (p<0.001) and significantly decreased LDL-C and HDL-C levels compared with the controls (p<0.01). In patients with Graves' disease, serum TSH levels were inversely correlated with plasma MDA levels (r: -0.42, p<0.05). Plasma MDA levels significantly decreased and levels of TC, LDL-C and HDL-C significantly increased in the groups of OHyper and SHyper after treatment. Serum IMA levels did not significantly change at baseline and with the therapy in all subjects. In conclusion, increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis in these patients. Increased oxidative stress in patients with SHyper and OHyper could be improved by ATD therapy. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Critical review for the determination of the minimum detectable activity (MDA) of alpha-emitter radionuclides in environmental samples

International Nuclear Information System (INIS)

Gasco, C.; Anton, M.P.

1996-12-01

Different criteria for the calculation of the Minimum Detectable Activity (MDA) of an alpha emitter in environmental levels are reviewed in this report. Practical examples of its application to previously analyzed samples are shown. The authors propose a criteria based on prior calculations that applies to the radiochemical activities performed in the laboratory. The calculation procedure has been discussed with scientist from other laboratories in order to establish a general criteria to calculate the MDA

Pengaruh ekstrak teh hijau (Camellia sinensis terhadap kadar malondialdehid (MDA plasma dan kekuatan genggam tangan lanjut usia

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Fera Nofiartika

2016-10-01

Method: This was a double-blind experimental with pre-post test and control group. Fifty-seven elderly people from Balai Pelayanan Social Tresna Wredha (BPSTW Abiyoso and Budi Luhur who met inclusion and exclusion criteria were divided into 2 groups. During 30 days, the first group was given 2 capsules of GTE a day (±168 mg catechin and 95 mg Epigallocatechin gallate (EGCG and the second group was given a placebo. MDA was measured by thiobarbituric acid  (TBAmethod and hand grip strength was measured by handgrip hand grip dynamometer. Results: There was a significant decreasing MDA (p<0,05 in the GTE group, but not in the placebo group. There was also increasing handgrip strength in the GTE group but not in the placebo group. Conclusion: Green tea extract can prevent increasing MDA and declining physical handgrip strength in elderly.

Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

DEFF Research Database (Denmark)

Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

2004-01-01

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

KADAR MDA DAN HSP 70 PADA PLASENTA PENDERITA PREEKLAMPSIA

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Arleni

2008-12-01

Full Text Available The MDA and HSP70 Concentration in Preeclamptic Patient Placenta’s. Objective: Preeclampsia is a disease in pregnancy and characterized by hypertension and proteinuria. Preeclampsia and eclampsia are the most causes of maternal and fetal mortality and morbidity in Indonesia. Placental and systemic oxidative stress caused endothelial cell dysfunction and injury. Placental oxidative stress also linked to fetal growth restriction. HSP70 is essential for cellular recovery, survival and maintenance of homeostasis. The purpose of this study was to compare the MDA, a marker for oxidative stress and HSP70 production in placental of severe preeclampsia, mild preeclampsia and normotensive pregnant women. Placenta were collected after delivery from normotensive pregnancies (N=10, severe preeclampsia (N=10 and mild preeclampsia (N=10. Placenta was cultured in RPMI and 20% FBS, and supernatant were collected in day 3. MDA was measured using spectrophotometer and absorbance read in 530nm. HSP70 was measured using enzyme-linked immunosorbent assay. The mean MDA concentration did not differ significantly between patients with severe preeclampsia (7.13+5.36 nmol/ml and mild preeclampsia (4.82+2.47 nmol/ml when compared with normotensive pregnancies (4.57+2.4 nmol/ml. The mean HSP70 concentration in mild preeclampsia is highest (10.15+12.39 nmo/ml when compared with severe preeclampsia (3.78 +3.07 nmol/ml and normotensive pregnant women (3.76+4.65nmol/ml, but the difference was not significant. Although the difference was not significant, is indicates homeostasis response in mild preclampsia women is relative good. This response was abated in severe preeclampstic women. Although MDA and HSP70 concentration did not differ significantly between groups, however the high HSP70 concentration is indicates homeostasis response relatively good in mild preeclamptic women.

DMPD: MDA5/RIG-I and virus recognition. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18272355 MDA5/RIG-I and virus recognition. Takeuchi O, Akira S. Curr Opin Immunol. ...2008 Feb;20(1):17-22. Epub 2008 Feb 12. (.png) (.svg) (.html) (.csml) Show MDA5/RIG-I and virus recognition.... PubmedID 18272355 Title MDA5/RIG-I and virus recognition. Authors Takeuchi O, Akira S. Publication Curr Opi

Ovarian cancer targeted adenoviral-mediated mda-7/IL-24 gene therapy

NARCIS (Netherlands)

Mahasreshti, PJ; Kataram, M; Wu, HJ; Yalavarthy, LP; Carey, D; Dent, P; Chada, S; Alvarez, RD; Haisma, HJ; Fisher, PB; Curiel, DT

Objective. We have previously shown that adenoviral-mediated melanoma differentiation-associated gene-7 (Ad.mda-7) therapy induces apoptosis in ovarian cancer cells. However, the apoptosis induction was low and directly correlated with infectivity of Ad.mda-7. The objective of this study was to

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

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Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

2013-01-01

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

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Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

2013-12-10

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

On MDA - SOA based Intercloud Interoperability framework

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Tahereh Nodehi

2013-01-01

Full Text Available Cloud computing has been one of the latest technologies which assures reliable delivery of on - demand computing services over the Internet. Cloud service providers have established geographically distributed data centers and computing resources, which are available online as service. The clouds operated by different service providers working together in collaboration can open up lots more spaces for innovative scenarios with huge amount of resources provisioning on demand. However, current cloud systems do not support intercloud interoperability. This paper is thus motivated to address Intercloud Interoperabilityby analyzing different methodologies that have been applied to resolve various scenarios of interoperability. Model Driven Architecture (MDA and Service Oriented Architecture (SOA method have been used to address interoperability in various scenarios, which also opens up spaces to address intercloud interoperability by making use of these well accepted methodologies. The focus of this document is to show Intercloud Interoperability can be supported through a Model Driven approach and Service Oriented systems. Moreover, the current state of the art in Intercloud, concept and benefits of MDA and SOA are discussed in the paper. At the same time this paper also proposes a generic architecture for MDA - SOA based framework, which can be useful for developing applications which will require intercloud interoperability. The paper justi fies the usability of the framework by a use - case scenario for dynamic workload migration among heterogeneous clouds.

Transforming growth factor expression (TGF-β) correlate with serum level of malondialdehyde (MDA) after EVOO administration in preclinical rat models of preeclampsia

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Ilyas, Syafruddin; Hutahaean, Salomo; Evi Irianti, dan

2018-03-01

Preeclampsia can cause cell death either apoptosis or necrosis. One cause is the disturbance of the emergence of malondialdehyde (MDA). Very few reports on the role of Transforming Growth Factor Expression (TGF-β) in the remodeling process of placental cells and their association with serum MDA content. Research of true experiment with complete randomized design (CRD) with five treatment groups. The first group, preeclampsia negative control (T0). The second group, preeclamptic rats model (T1). The third group, preeclamptic rats model+EVOO 0.45g/kg-Body Weight/day (T2). The fourth group, preeclamptic rats model+EVOO 0.90g/kg-BW/day (T3). The fifth group, preeclamptic rats model+EVOO 1.8 g/kg-BW/day (T4). The results showed a significant effect of EVOO on TGF-β expression in preeclampsia rats, meaning that there was a role of TGF-β against pre-eclampsia placenta remodeling. There was a positive and strong relationship (r=0.494) as well as a very significant relationship (p<0.01) between TGF-β and the serum MDA.

Degree of neutrophil, atrophy, and metaplasia intestinal were associate with malondialdehyde level in gastritis patients

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Siregar, G. A.; Sari, D. K.; Sungkar, T.

2018-03-01

The main pathogenesis of gastritis is inflammation that closely related to free radicals. Malondialdehyde (MDA) is a free radical biomarker and is found to increase in gastritis patients. However, these studies are generally performed on experimental animals as well as MDA examination in gastric mucosa. This study aim was to determine the association of degrees of gastritis (degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia) with plasma MDA level. A cross-sectional study of 80 consecutive gastritis patients who came to an endoscopic unit of Adam Malik General Hospital in Medan, Indonesia, from May–September 2017. Assessed for severity of chronic inflammatory, neutrophil activity, atrophy, and intestinal metaplasia refers to Updated Sydney System. Plasma MDA levels were examined using an HPLC MDA kit. Univariate analysis, bivariate (chi-square and Fisher exact test), and multivariate (binary logistic regression test) were programmed with SPSS version 22. There was no significant association between degree of lymphocyte infiltration with MDA level. There were significant associations between degree of neutrophil activity, atrophy, and intestinal metaplasia with MDA level (p=0.039, 0.003, 0.021; respectively). The moderate+severe degree of neutrophil activity, atrophy, and intestinal metaplasia were associated with high level of MDA.

Effect of Adalimumab on Refractory Arthritis in Juvenile Idiopathic Inflammatory Myopathy with Anti-MDA5 Autoantibody

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Takako Miyamae

2018-01-01

Full Text Available A 10-year-old girl manifested persistent fever, skin rash, leg pain, fatigue, and joint pain. Based on muscle weakness, elevated muscle-derived enzymes, magnetic resonance imaging, and skin biopsy results, the diagnosis was juvenile idiopathic inflammatory myopathies (JIIM. Chest CT was normal; the anti-melanoma differentiation-associated protein-5 (anti-MDA5 autoantibody was positive. Initial manifestations subsided after prednisolone (PSL and methotrexate treatment. After the PSL dosage was decreased, the patient presented with metacarpophalangeal (MCP joint pain and swelling in both index fingers, synovial fluid, and signals on power Doppler ultrasound. The arthritis was refractory to cyclosporine and tacrolimus. Radiography showed progressive MCP joint space narrowing and joint erosion. Adalimumab was initiated 14 months after disease onset. There was a mildly increased matrix metalloproteinase-3 (MMP3 level, an erythrocyte sedimentation ratio (ESR, and a normal CRP level. Adalimumab resulted in decreased MCP joint pain and swelling. PSL was discontinued 10 months after adalimumab initiation; after 9 more months of adalimumab, there were no significant ultrasonography findings. MMP3 and ESR levels normalized during treatment. Radiography after 2 years of adalimumab showed further progressive MCP joint space narrowing restricting dorsiflexion. This report clarified that anti-MDA5-positive JIIM joint manifestations were due to active synovitis and that adalimumab is required for severe cases. Further experience is needed to determine the pathology, severity, and prognosis of this type of arthritis.

Lowered quality of life in mood disorders is associated with increased neuro-oxidative stress and basal thyroid-stimulating hormone levels and use of anticonvulsant mood stabilizers.

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Nunes, Caroline Sampaio; Maes, Michael; Roomruangwong, Chutima; Moraes, Juliana Brum; Bonifacio, Kamila Landucci; Vargas, Heber Odebrecht; Barbosa, Decio Sabbatini; Anderson, George; de Melo, Luiz Gustavo Piccoli; Drozdstoj, Stoyanov; Moreira, Estefania; Carvalho, André F; Nunes, Sandra Odebrecht Vargas

2018-04-17

Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH. © 2018 John Wiley & Sons, Ltd.

Coverage and compliance MDA programme for lymphatic filariasis in Bidar district, Karnataka, India

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Dharukaswami. Mallayya. Koradhanyamath

2012-08-01

Full Text Available Objective: To describe the socio demographic characteristics of beneficiaries of the Mass Drug Administration (MDA programme, to assess the coverage, compliance and causes for noncompliance towards MDA in the district, to assess the awareness regarding elephantiasis among beneficiaries and to assess the knowledge of drug distributors towards the filariasis and MDA programme. Methods: This cross sectional study was conducted in 3 rural and 1 urban clusters in Bidar district for the period of 1 week. 50 houses were selected in each cluster by systematic random sampling method and data was collected in a structured proforma by interview technique. Results: Majority of beneficiaries were at the age group of 15-60 years (72.3% and male (53%. The overall coverage of MDA in Bidar district was 62.3%. Compliance among those who had received the tablets was 60.4%. Coverage and compliance was more in rural areas compared to urban. The most common reason quoted for not consuming drugs was fear of adverse effects (72.2% The incidence of adverse events was 0.2%. Even though 75% of them were aware of the disease elephantiasis, only 45.4% had knowledge regarding MDA programme. The knowledge of drug distributors towards MDA and filariasis was found to be adequate. Conclusions: Coverage and compliance towards MDA in Bidar district was poor. The coverage and compliance in rural areas was higher compared to the urban areas.

[Knock-down of BCL11A expression in breast cancer cells promotes MDA-MB-231 cell apoptosis].

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Li, Hongli; Gui, Chen; Yan, Lijun

2016-11-01

Objective To detect the expression and pathological significance of B-cell CLL/lymphoma 11A (BCL11A) in breast cancer and investigate the effect of its silencing on the apoptosis of human MDA-MB-231 breast cancer cells. MethodsImmunohistochemistry was used to detect the expression of BCL11A in 62 cases of human breast cancer tissues and 8 cases of normal tissues. We synthesized siRNA targeting BCL11A, and then siRNA was transfected into MDA-MB-231 cells. Forty-eight hours later, the suppression effect of siRNA on BCL11A was determined by quantitative real-time PCR and Western blotting. The apoptosis of MDA-MB-231 cells was detected by flow cytometry. Results The BCL11A protein was mainly expressed in cytoplasm. The expression level of BCL11A in breast cancer tissues was higher than that in paracancerous tissues. The expression had correlations with tumor grade, tumor stage, while it had no correlations with the patients' age and tumor size. BCL11A-siRNA significantly suppressed the expression of BCL11A mRNA and protein as compared with the control group. MDA-MB-231 cells transfected with BCL11A-siRNA had higher apoptosis rate compared with the control group. Conclusion The BCL11A protein is highly expressed in breast cancer and knock-down of BCL11A promotes the apoptosis of MDA-MB-231 cells.

Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells

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Jackson, Nicole M.; Ceresa, Brian P., E-mail: brian.ceresa@louisville.edu

2016-08-15

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper-expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR-mediated apoptosis in response to EGF ligand. The goal of this study was to identify the kinases that could be potential intermediates for the EGFR-mediated induction of apoptosis intracellularly. After identifying Cyclic GMP-dependent Protein Kinase G (PKG) as a plausible intermediate, we wanted to determine the temporal relationship of these two proteins in the induction of apoptosis. We observed a dose-dependent decrease in MDA-MB-468 cell viability, which was co-incident with increased PKG activity as measured by VASPSer239 phosphorylation. In addition, we observed a dose dependent decrease in cell viability, as well as an increase in apoptosis, in response to two different PKG agonists, 8-Bromo-cGMP and 8-pCPT-cGMP. MDA-MB-468 cells with reduced PKG activity had attenuated EGFR-mediated apoptosis. These findings indicate that PKG does not induce cell death via transphosphorylation of the EGFR. Instead, PKG activity occurs following EGFR activation. Together, these data indicate PKG as an intermediary in EGFR-mediated cell death, likely via apoptotic pathway.

The Association between PAI-1 Gene Promoter Polymorphism and Serum Serpin E1, MDA, and Hs-CRP Levels in Coronary Artery Disease

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Ansar Karimian

2016-09-01

Full Text Available Background: Coronary Artery Disease (CAD is caused by atherosclerosis. Studies have shown that a number of factors, including cellular binding molecules such as Plasminogen Activator Inhibitor-1 (PAI-1, lipid peroxidation, inflammation, and hemostasis, are closely related to development and progression of CAD. Objectives: The present case-control study aimed to evaluate the association between Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G polymorphism and oxidative stress markers and Coronary Artery Disease (CAD. Patients and Methods: Blood was drawn and DNA was extracted from 90 subjects (46 patients with angiographically diagnosed CAD and 44 age- and sex-matched healthy controls. The 4G/5G polymorphism of PAI-1 was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP analysis. Besides, the risk factors, serpin E1, Malondialdehyde (MDA, high-sensitivity C-Reactive Protein (hs-CRP, and lipid profile serum levels were measured by standard methods and were compared between the two study groups using independent samples t-test, one-way ANOVA, and Mann-Whitney U test as appropriated. Results: Results: The frequency of 4G/4G genotype of PAI-1 gene was higher in the CAD patients than in the controls (28/46 (60.87% vs. 8/44 (18.18%, P < 0.01. Additionally, the serpin E1 plasma level was significantly higher in the CAD group carrying the 4G allele compared to those homozygous for the 5G allele (P = 0.016. Besides, a significant difference was found between the 4G/4G and 5G/5G subjects of the CAD group regarding plasma High-Density Lipoprotein (HDL (P < 0.01. Also, significant differences were observed among the three genotypes of both groups concerning the plasma levels of cholesterol, triglyceride, and Low-Density Lipoprotein (LDL. However, no significant correlation was found between PAI-1 gene polymorphism and MDA serum level, hs-CRP, and risk of CAD. Conclusion: The findings of this study suggested that 4G/4G PAI

MDA Y EL PAPEL DE LOS MODELOS EN EL PROCESO DE DESARROLLO DE SOFTWARE

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Juan Bernardo Quintero

2007-12-01

Full Text Available El papel de los modelos es fundamental en el desarrollo de software para potenciar el reúso de los diferentes elementos del software y facilitar la labor de los diferentes roles que participan del proceso. La Arquitectura Dirigida por Modelos (MDA propone un proceso de desarrollo basado en la realización y transformación de modelos. Los principios en los que se fundamenta MDA son la abstracción, la automatización y la estandarización. El proceso central de MDA es la transformación de modelos que parten del espacio del problema (CIM hasta modelos específicos de la plataforma (PSM, pasando por modelos que describen una solución independientemente de la computación (PIM. Para explicar el papel de los modelos en el proceso de desarrollo de software este artículo explora los principales conceptos presentados en la propuesta de MDA.The role of models is critical in software development to enable the reuse of different software elements and to aid the work of several roles involved in the process. Model Driven Architecture (MDA suggests a development process based on models realization and transformation. The principles in which MDA is based are abstraction, automation, and standardization. The central process of MDA is the transformation of models from the problem space (CIM to platform specific models (PSM, passing across models describing a platform independent solution (PIM. In order to explain the model role in the software process development, this paper explores the main concept presented in the MDA proposal.

Isolation of low density lipoprotein (LDL with its modification by Copper ion and Malondialdehyde (MDA

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Doosty M

1999-06-01

Full Text Available Oxidation of low density lipoproteins (LDLs is belived to be an important step in the pathogenesis of atherosclerosis. During oxidation, LDL particle undergoes a large number of structural changes that alters its biological properties, so it becomes atherogenic. To study atherogenic proteins, usually two forms of modified LDLs, including Cu2+-oxidized LDL (ox-LDL and malondialdehyde (MDA modified LDL (mal-LDL are used. In this study, LDL was isolated from 72 ml freshly prepared plasma by sequential Floatation Ultracentrifugation (SFU, which resulted in separation of 12.5 mg LDL protein. LDL oxidation was accomplished in Phosphate Buffered Saline (PBS with 2µM cupric sulfate, and mal-LDL was prepared by incubating LDL in PBS with 0.5 M solution of freshly prepared MDA. These modifications were evaluated by measuring optical density at 234 nm, Thiobarbitoric Acid Reactive Substances (TBARS, and electrophoretic mobility at pH 8.6. The increase of 234 nm absorption reflected initiation of LDL oxidation. TBARS of ox-LDL and mal-LDL was 80 Nm MAD/mg LDL protein and 400 nm MDA/mg LDL protein, respectively. Electrophoretic mobility of ox-LDL and mal-LDL, in respect to native LDL (n-LDL, were increased.

Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy.

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de Carvalho, Luciana Martins; Ngoumou, Gonza; Park, Ji Woo; Ehmke, Nadja; Deigendesch, Nikolaus; Kitabayashi, Naoki; Melki, Isabelle; Souza, Flávio Falcäo L; Tzschach, Andreas; Nogueira-Barbosa, Marcello H; Ferriani, Virgínia; Louzada-Junior, Paulo; Marques, Wilson; Lourenço, Charles M; Horn, Denise; Kallinich, Tilmann; Stenzel, Werner; Hur, Sun; Rice, Gillian I; Crow, Yanick J

2017-10-01

To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy. We identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells. We recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5. These cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy. © 2017, American College of Rheumatology.

Protein Carbamylation: A Marker Reflecting Increased Age-Related Cell Oxidation

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Julia Carracedo

2018-05-01

Full Text Available Carbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a “hallmark of aging”. The molecular mechanisms associated with aging are related to an increased release of free radicals. We have studied whether carbamylated proteins from the peripheral blood of healthy subjects are related to oxidative damage and aging, taking into account the gender and the immune profile of the subjects. The study was performed in healthy human volunteers. The detection of protein carbamylation and malondialdehyde (MDA levels was evaluated using commercial kits. The immune profile was calculated using parameters of immune cell function. The results show that the individuals from the elderly group (60–79 years old have increased carbamylated protein and MDA levels. When considered by gender, only men between 60 and 79 years old showed significantly increased carbamylated proteins and MDA levels. When those subjects were classified by their immune profile, the carbamylated protein levels were higher in those with an older immune profile. In conclusion, the carbamylation of proteins in peripheral blood is related to age-associated oxidative damage and to an aging functional immunological signature. Our results suggest that carbamylated proteins may play an important role at the cellular level in the aging process.

Evaluation of 3M molecular detection assay (MDA) Salmonella for the detection of Salmonella in selected foods: collaborative study.

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Bird, Patrick; Fisher, Kiel; Boyle, Megan; Huffman, Travis; Benzinger, M Joseph; Bedinghaus, Paige; Flannery, Jonathan; Crowley, Erin; Agin, James; Goins, David; Benesh, DeAnn; David, John

2013-01-01

The 3M Molecular Detection Assay (MDA) Salmonella is used with the 3M Molecular Detection System for the detection of Salmonella spp. in food, food-related, and environmental samples after enrichment. The assay utilizes loop-mediated isothermal amplification to rapidly amplify Salmonella target DNA with high specificity and sensitivity, combined with bioluminescence to detect the amplification. The 3M MDA Salmonella method was compared using an unpaired study design in a multilaboratory collaborative study to the U.S. Department of Agriculture/Food Safety and Inspection Service-Microbiology Laboratory Guidebook (USDA/FSIS-MLG 4.05), Isolation and Identification of Salmonella from Meat, Poultry, Pasteurized Egg and Catfish Products for raw ground beef and the U.S. Food and Drug Administration/Bacteriological Analytical Manual (FDA/BAM) Chapter 5 Salmonella reference method for wet dog food following the current AOAC guidelines. A total of 20 laboratories participated. For the 3M MDA Salmonella method, raw ground beef was analyzed using 25 g test portions, and wet dog food was analyzed using 375 g test portions. For the reference methods, 25 g test portions of each matrix were analyzed. Each matrix was artificially contaminated with Salmonella at three inoculation levels: an uninoculated control level (0 CFU/test portion), a low inoculum level (0.2-2 CFU/test portion), and a high inoculum level (2-5 CFU/test portion). In this study, 1512 unpaired replicate samples were analyzed. Statistical analysis was conducted according to the probability of detection (POD). For the low-level raw ground beef test portions, the following dLPOD (difference between the POD of the reference and candidate method) values with 95% confidence intervals were obtained: -0.01 (-0.14, +0.12). For the low-level wet dog food test portions, the following dLPOD with 95% confidence intervals were obtained: -0.04 (-0.16, +0.09). No significant differences were observed in the number of positive

Gonadotropin-releasing hormone receptor activates GTPase RhoA and inhibits cell invasion in the breast cancer cell line MDA-MB-231

International Nuclear Information System (INIS)

Aguilar-Rojas, Arturo; Huerta-Reyes, Maira; Maya-Núñez, Guadalupe; Arechavaleta-Velásco, Fabián; Conn, P Michael; Ulloa-Aguirre, Alfredo; Valdés, Jesús

2012-01-01

Gonadotropin-releasing hormone (GnRH) and its receptor (GnRHR) are both expressed by a number of malignant tumors, including those of the breast. In the latter, both behave as potent inhibitors of invasion. Nevertheless, the signaling pathways whereby the activated GnRH/GnRHR system exerts this effect have not been clearly established. In this study, we provide experimental evidence that describes components of the mechanism(s) whereby GnRH inhibits breast cancer cell invasion. Actin polymerization and substrate adhesion was measured in the highly invasive cell line, MDA-MB-231 transiently expressing the wild-type or mutant DesK191 GnRHR by fluorometry, flow cytometric analysis, and confocal microscopy, in the absence or presence of GnRH agonist. The effect of RhoA-GTP on stress fiber formation and focal adhesion assembly was measured in MDA-MB-231 cells co-expressing the GnRHRs and the GAP domain of human p190Rho GAP-A or the dominant negative mutant GAP-Y1284D. Cell invasion was determined by the transwell migration assay. Agonist-stimulated activation of the wild-type GnRHR and the highly plasma membrane expressed mutant GnRHR-DesK191 transiently transfected to MDA-MB-231 cells, favored F-actin polymerization and substrate adhesion. Confocal imaging allowed detection of an association between F-actin levels and the increase in stress fibers promoted by exposure to GnRH. Pull-down assays showed that the effects observed on actin cytoskeleton resulted from GnRH-stimulated activation of RhoA GTPase. Activation of this small G protein favored the marked increase in both cell adhesion to Collagen-I and number of focal adhesion complexes leading to inhibition of the invasion capacity of MDA-MB-231 cells as disclosed by assays in Transwell Chambers. We here show that GnRH inhibits invasion of highly invasive breast cancer-derived MDA-MB-231 cells. This effect is mediated through an increase in substrate adhesion promoted by activation of RhoA GTPase and formation of

Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468).

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Mohammadi, A; Mansoori, B; Goldar, S; Shanehbandi, D; Khaze, V; Mohammadnejad, L; Baghbani, E; Baradaran, B

2016-02-29

Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma.

Serum and Ascitic Fluid Superoxide Dismutase and Malondialdehyde Levels in Patients with Cirrhosis

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Ugur Coskun

2008-01-01

Full Text Available Serum and ascitic fluid superoxide dismutase (SOD and malondialdehyde (MDA levels were measured in 43 patients with cirrhosis and in a 10 healthy control group. Compensated cirrhotic patients had no clinically detectable ascites, but decompensated patients had massive ascites. Cirrhotic patients were divided into three groups: patients with compensated cirrhosis (n = 16, patients with decompensated cirrhosis with Spontaneous bacterial peritonitis (SBP (n = 14, and patients with decompensated cirrhosis without SBP (n = 13. All cirrhotic patients in the experimental group had significantly higher serum SOD (p 0.05. These results suggest that the increase in serum SOD and MDA levels are not related to the presence of SBP and the status of liver cirrhosis. To sum up, clarifying the impact of increased serum SOD and MDA levels in cirrhotic patients needs further investigation.

Increasing compliance with mass drug administration programs for lymphatic filariasis in India through education and lymphedema management programs.

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Paul T Cantey

2010-06-01

Full Text Available Nearly 45% of people living at risk for lymphatic filariasis (LF worldwide live in India. India has faced challenges obtaining the needed levels of compliance with its mass drug administration (MDA program to interrupt LF transmission, which utilizes diethylcarbamazine (DEC or DEC plus albendazole. Previously identified predictors of and barriers to compliance with the MDA program were used to refine a pre-MDA educational campaign. The objectives of this study were to assess the impact of these refinements and of a lymphedema morbidity management program on MDA compliance.A randomized, 30-cluster survey was performed in each of 3 areas: the community-based pre-MDA education plus community-based lymphedema management education (Com-MDA+LM area, the community-based pre-MDA education (Com-MDA area, and the Indian standard pre-MDA education (MDA-only area. Compliance with the MDA program was 90.2% in Com-MDA+LM, 75.0% in Com-MDA, and 52.9% in the MDA-only areas (p<0.0001. Identified barriers to adherence included: 1 fear of side effects and 2 lack of recognition of one's personal benefit from adherence. Multivariable predictors of adherence amenable to educational intervention were: 1 knowing about the MDA in advance of its occurrence, 2 knowing everyone is at risk for LF, 3 knowing that the MDA was for LF, and 4 knowing at least one component of the lymphedema management techniques taught in the lymphedema management program.This study confirmed previously identified predictors of and barriers to compliance with India's MDA program for LF. More importantly, it showed that targeting these predictors and barriers in a timely and clear pre-MDA educational campaign can increase compliance with MDA programs, and it demonstrated, for the first time, that lymphedema management programs may also increase compliance with MDA programs.

Duration of detection of anti-BmR1 IgG4 antibodies after mass-drug administration (MDA) in Sarawak, Malaysia.

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Noordin, R; Muhi, J; Md Idris, Z; Arifin, N; Kiyu, A

2012-03-01

The detection rates of brugian filariasis in three regions of Sarawak namely Central, North and South after three courses of mass drug administration (MDA) from year 2004 to 2006 was investigated. A recombinant BmR1 antigen-based IgG4 detection test, named Brugia Rapid and night blood smear for microfilaria (mf) detection were used. All three regions recorded a sharp fall in mf positive rates after a year post-MDA. Meanwhile Brugia Rapid positive rates declined more gradually to 3.8% and 5.6% of the pre-MDA levels in the Central and North regions, respectively. This study showed that in filariasis endemic areas in Sarawak, anti-filarial IgG4 antibodies to BmR1, as detected by the Brugia Rapid test, were positive for one to two years after mf disappearance.

Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts

DEFF Research Database (Denmark)

Gonen, Ayelet; Hansen, Lotte; Turner, William W

2014-01-01

as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought......Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use...... responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do...

Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

International Nuclear Information System (INIS)

Fonsart, Julien; Menet, Marie-Claude; Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier

2009-01-01

The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC last and C max were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C max and AUC last were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC last and t 1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA C max and AUC last were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC last of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

A Creative Partnership: The Spiritual and the Sexual in Novels by Zakes Mda

NARCIS (Netherlands)

Visser, I.

2012-01-01

Spirituality and sexuality are key notions in the novels of Zakes Mda, one of South Africa's leading contemporary authors. In Mda's novels the mysterious interrelatedness of the spiritual and the sexual, in which art and creativity are vital elements, functions as a catalyst in individual and

MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

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Qian Feng

2012-11-01

Full Text Available RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C, a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.

Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model.

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Aurigena Antunes de Araújo

Full Text Available Oral mucositis (OM is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT, an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU-induced oral mucositis (OM in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60 mg/Kg and 2 (40 mg/Kg. Animals were pretreated with oral AZT (1, 5, or 10 mg/kg or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012 of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO, Malonyldialdehyde (MDA, interleukin-1 beta (IL-1β, interleukin-10 (IL-10, and tumour necrosis factor-alpha (TNF-α were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, and transforming growth factor (TGF-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni's test was used to calculate the means of intergroup differences (p ≤ 0.05. Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01, MDA (p<0.5 and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05 and IL-1β (p<0.05 levels, increased the cheek pouch levels of IL-10 (p<0.01, and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models.

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Tullberg, Cecilia; Larsson, Karin; Carlsson, Nils-Gunnar; Comi, Irene; Scheers, Nathalie; Vegarud, Gerd; Undeland, Ingrid

2016-03-01

In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy-trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 μM of MDA, 0.96 μM of HHE, and 1.6 μM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 μM of MDA; 0.16, and 0.026 μM of HHE; 0.23, and 0.005 μM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies.

Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells.

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Park, Eun-Ji; Lee, Dahae; Baek, Seon-Eun; Kim, Ki Hyun; Kang, Ki Sung; Jang, Tae Su; Lee, Hye Lim; Song, Ji Hoon; Yoo, Jeong-Eun

2017-09-15

Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting.

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Bartsch, Sarah M; Hotez, Peter J; Hertenstein, Daniel L; Diemert, David J; Zapf, Kristina M; Bottazzi, Maria Elena; Bethony, Jeffrey M; Brown, Shawn T; Lee, Bruce Y

2016-04-27

Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤ $790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤ $444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) versus annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0% and nearly eliminated hookworm infection in children. Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health

Evaluating Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA and the Histological Changes of the Lung Tissue after γ-Irradiation in Rats

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Abolhasan Rezaeyan

2016-09-01

Full Text Available Background & Objective: The lung is a radiosensitive organ and its damage is a dose-limiting factor in radiotherapy. Different side effects such as pneumonia and lung fibrosis are found in patients with thorax irradiation. The objective of the present study is to evaluate the effects of γ-irradiation on acute and chronic injuries of lung tissue in rats. Materials & Methods: 32 rats were divided into two groups. Control group consisted of 14 rats that underwent shame irradiation. In radiation group, 18 rats underwent γ-irradiation. The rats were exposed to γ-irradiation 18 Gy using a single fraction cobalt-60 unit. Eight rats in each group were sacrificed 24 hours after radiotherapy for determining Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA, and histopathological evaluations. Remained animals were sacrificed eight weeks after radiotherapy for histopathological evaluation. Results: Compared to control group, the level of SOD and GSH significantly decreased and MDA level significantly increased in radiation group 24 hours following irradiation, (p=0.001, p<0.001, p=0.001 respectively. Early histopathological results after 24 hours showed that radiation increases neutrophil, macrophage, and inflammation incidence compared to control group (p<0.05. Late histopathological evaluation after eight weeks revealed significant increase in factors including mast cells, pulmonary edema, vascular thickness, vascular damage, and also inflammation and fibrosis incidence in case group compared to radiation group  (p<0.05. Conclusion: Localized chest radiation with dose of 18 Gy induces changes in oxidative stress indices and histopathological lung tissue damage in short and long term.

Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells.

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Reithmeier, Anja; Panizza, Elena; Krumpel, Michael; Orre, Lukas M; Branca, Rui M M; Lehtiö, Janne; Ek-Rylander, Barbro; Andersson, Göran

2017-09-15

Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes. We identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGFβ) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGFβ isoform 2 (TGFβ2), TGFβ receptor type 1 (TβR1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

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Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

2011-06-01

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231.

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Russo-Abrahão, Thais; Lacerda-Abreu, Marco Antônio; Gomes, Tainá; Cosentino-Gomes, Daniela; Carvalho-de-Araújo, Ayra Diandra; Rodrigues, Mariana Figueiredo; Oliveira, Ana Carolina Leal de; Rumjanek, Franklin David; Monteiro, Robson de Queiroz; Meyer-Fernandes, José Roberto

2018-01-01

Recent studies demonstrate that interstitial inorganic phosphate is significantly elevated in the breast cancer microenvironment as compared to normal tissue. In addition it has been shown that breast cancer cells express high levels of the NaPi-IIb carrier (SLC34A2), suggesting that this carrier may play a role in breast cancer progression. However, the biochemical behavior of inorganic phosphate (Pi) transporter in this cancer type remains elusive. In this work, we characterize the kinetic parameters of Pi transport in the aggressive human breast cancer cell line, MDA-MB-231, and correlated Pi transport with cell migration and adhesion. We determined the influence of sodium concentration, pH, metabolic inhibitors, as well as the affinity for inorganic phosphate in Pi transport. We observed that the inorganic phosphate is dependent on sodium transport (K0,5 value = 21.98 mM for NaCl). Furthermore, the transport is modulated by different pH values and increasing concentrations of Pi, following the Michaelis-Menten kinetics (K0,5 = 0.08 mM Pi). PFA, monensin, furosemide and ouabain inhibited Pi transport, cell migration and adhesion. Taken together, these results showed that the uptake of Pi in MDA-MB-231 cells is modulated by sodium and by regulatory mechanisms of intracellular sodium gradient. General Significance: Pi transport might be regarded as a potential target for therapy against tumor progression.

Low expression of Mda-7/IL-24 and high expression of C-myb in tumour tissues are predictors of poor prognosis for Burkitt lymphoma patients.

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Ma, Ming; Zhao, Riyang; Yang, Xingxiao; Zhao, Lianmei; Liu, Lihua; Zhang, Cong; Wang, Xuexiao; Shan, Baoen

2018-02-08

Burkitt lymphoma is one of the most common types of haematopoietic malignancy in children and adolescents. Mda-7/IL-24 had been identified as a differentiation inducer of Burkitt lymphoma cells. Previous studies have revealed that knockdown of C-myb can also lead to the terminal differentiation of Burkitt lymphoma cells. The aim of the present study was to investigate the correlation between the expression of Mda-7/IL-24 and C-myb, as well as their prognostic significance, for Burkitt lymphoma patients. The tumour tissues were collected from 59 cases of Burkitt lymphoma patients and detected with Western blotting and immunohistochemistry. The results showed that the expression of Mda-7/IL-24 was lower, whereas the expression of C-myb was higher in Burkitt lymphoma tissues compared to specimens of normal lymph node tissues. Furthermore, C-myb expression was negatively correlated with Mda-7/IL-24 expression at the protein level in Burkitt lymphoma tissues and cell lines. Both the expression of Mda-7/IL-24 and C-myb in Burkitt lymphoma tissues was associated with some clinicopathological parameters, such as clinical stage, infiltration in the bone marrow, Ki67 and overall survival rates. These results indicated that low expression of Mda-7/IL-24 along with high expression of C-myb are predictors for poor prognosis of Burkitt lymphoma patients; this outcome suggests that Mda-7/IL-24 and C-myb might be potential targets for clinical treatment of Burkitt lymphoma. Mda-7/IL-24: melanoma differentiation associated gene7/interleukin 24; FCM: flow cytometry; Ecog: Eastern Cooperative Oncology Group; IPI: International lymphoma prognosis index.

Engineering Runtime Requirements-Monitoring Systems Using MDA Technologies

Science.gov (United States)

Skene, James; Emmerich, Wolfgang

The Model-Driven Architecture (MDA) technology toolset includes a language for describing the structure of meta-data, the MOF, and a language for describing consistency properties that data must exhibit, the OCL. Off-the-shelf tools can generate meta-data repositories and perform consistency checking over the data they contain. In this paper we describe how these tools can be used to implement runtime requirements monitoring of systems by modelling the required behaviour of the system, implementing a meta-data repository to collect system data, and consistency checking the repository to discover violations. We evaluate the approach by implementing a contract checker for the SLAng service-level agreement language, a language defined using a MOF meta-model, and integrating the checker into an Enterprise JavaBeans application. We discuss scalability issues resulting from immaturities in the applied technologies, leading to recommendations for their future development.

Controlled formation of emulsion gels stabilized by salted myofibrillar protein under malondialdehyde (MDA)-induced oxidative stress.

Science.gov (United States)

Zhou, Feibai; Sun, Weizheng; Zhao, Mouming

2015-04-15

This study presented the cold-set gelation of emulsions stabilized by salted myofibrillar protein (MP) under oxidative stress originated from malondialdehyde (MDA). Gel properties were compared over a range of MDA/NaCl concentrations including gel viscoelastic properties, strength, water-holding capacity (WHC), amount of protein entrapped, and microstructure. The oxidative stability of emulsion gels as indicated by lipid hydroperoxide was further determined and compared. Results indicated that emulsion stabilized by MP at swollen state under certain ionic strengths (0.2-0.6 M) was the premise of gel formation under MDA. In the presence of intermediate MDA concentrations (2.5-10 mM), the emulsion gels showed an improved elasticity, strength, WHC, and oxidative stability. This improvement should be mainly attributed to the enhanced protein-protein cross-linkings via MDA, which were homogeneously formed among absorbed and/or unabsorbed proteins, entrapping a greater amount and fractions of protein within network. Therefore, the oil droplets were better adherent to the gel matrix. Nevertheless, addition of high MDA concentrations (25-50 mM) led to the formation of excessive covalent bonds, which might break protein-protein bonds and trigger the desorption of protein from the interface. This ultimately caused "oil leak" phenomena as well as the collapse of gel structure and, thus, overall decreased gel properties and oxidative stability.

Withaferin A Induces ROS-Mediated Paraptosis in Human Breast Cancer Cell-Lines MCF-7 and MDA-MB-231.

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Kamalini Ghosh

Full Text Available Advancement in cancer therapy requires a better understanding of the detailed mechanisms that induce death in cancer cells. Besides apoptosis, themode of other types of cell death has been increasingly recognized in response to therapy. Paraptosis is a non-apoptotic alternative form of programmed cell death, morphologically distinct from apoptosis and autophagy. In the present study, Withaferin-A (WA induced hyperpolarization of mitochondrial membrane potential and formation of many cytoplasmic vesicles. This was due to progressive swelling and fusion of mitochondria and dilation of endoplasmic reticulum (ER, forming large vacuolar structures that eventually filled the cytoplasm in human breast cancer cell-lines MCF-7 and MDA-MB-231. The level of indigenous paraptosis inhibitor, Alix/AIP-1 (Actin Interacting Protein-1 was down-regulated by WA treatment. Additionally, prevention of WA-induced cell death and vacuolation on co-treatment with protein-synthesis inhibitor indicated requirement of de-novo protein synthesis. Co-treatment with apoptosis inhibitor resulted in significant augmentation of WA-induced death in MCF-7 cells, while partial inhibition in MDA-MB-231 cells; implyingthat apoptosis was not solely responsible for the process.WA-mediated cytoplasmic vacuolationcould not be prevented by autophagy inhibitor wortmanninas well, claiming this process to be a non-autophagic one. Early induction of ROS (Reactive Oxygen Speciesby WA in both the cell-lines was observed. ROS inhibitorabrogated the effect of WA on: cell-death, expression of proliferation-associated factor andER-stress related proteins,splicing of XBP-1 (X Box Binding Protein-1 mRNA and formation of paraptotic vacuoles.All these results conclusively indicate thatWA induces deathin bothMCF-7 and MDA-MB-231 cell lines byROS-mediated paraptosis.

PEA3 activates CXCR4 transcription in MDA-MB-231 and MCF7 breast cancer cells

Institute of Scientific and Technical Information of China (English)

Shengmei Gu; Li Chen; Qi Hong; Tingting Yan; Zhigang Zhuang; Qiaoqiao wang; Wei Jin; Hua Zhu; Jiong Wu

2011-01-01

CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been shown to mediate the metastasis of many solid tumors including lung,breast,kidney,and prostate tumors.In this study,we found that overexpression of ets variant gene 4 (PEA3) could elevate CXCR4 mRNA level and CXCR4 promoter activity in human MDA-MB-231 and MCF-7 breast cancer cells.PEA3 promoted CXCR4 expression and breast cancer metastasis.Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the CXCR4 promoter in the cells transfected with PEA3 expression vector.PEA3 siRNA attenuated CXCR4 promoter activity and the binding of PEA3 to the CXCR4 promoter in MDA-MB-231 and MCF-7 cells.These results indicated that PEA3 could activate CXCR4 promoter transcription and promote breast cancer metastasis.

Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms

Energy Technology Data Exchange (ETDEWEB)

Grotto, Denise; Barcelos, Gustavo R.M.; Barbosa, Fernando [Universidade de Sao Paulo, Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, SP (Brazil); Castro, Michele M. de [Universidade de Sao Paulo, Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, SP (Brazil); Garcia, Solange C. [Universidade Federal de Santa Maria, Departamento de Analises Clinicas e Toxicologicas, Santa Maria, Rio Grande do Sul (Brazil)

2009-07-15

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 {mu}g/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r=-0.67; P=0.001), and a positive correlation between MDA and systolic blood pressure (r=0.61; P=0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability. (orig.)

Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells.

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Czarnomysy, Robert; Surażyński, Arkadiusz; Popławska, Bożena; Rysiak, Edyta; Pawłowska, Natalia; Czajkowska, Anna; Bielawski, Krzysztof; Bielawska, Anna

2017-03-01

The aim of our study was to determine whether the use of cisplatin in the presence echistatin in MDA-MB-231 breast cancer cells leads to a reduction of toxic effects associated with the use of cisplatin. The expression of β 1 -integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: protein kinase B (AKT), mitogen-activated protein kinases (ERK1/ERK2), nuclear factor kappa B (NFκB), and caspase-3 and -9 activity was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The viability of MDA-MB-231 breast cancer cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Annexin V-FITC/propidium iodide staining assay was performed to detect the induction of apoptosis. Inhibition DNA biosynthesis was determined by [ 3 H]thymidine incorporation into DNA. The expression of of β 1 -integrin, IGF-IR, AKT, ERK1/ERK2, NFκB, caspase-3 and -9 was evaluated using Western blot. The results suggest that treatment of MDA-MB-231 breast cancer cells for 24 h cisplatin plus echistatin severely inhibits cell growth and activates apoptosis by upregulation of caspase-3 and -9 expressions. The effect was stronger than treatment cisplatin and echistatin alone. In this study, we have found that cisplatin plus echistatin treatment decreases collagen biosynthesis in MDA-MB-231 breast cancer cells stronger than the individual compounds. The inhibition was found to be dependent on the β 1 -integrin and IGF receptor activation. A significant reduction of ERK1/ERK2, AKT expression in cancer cells after cisplatin plus echistatin treatment was also found. The cancer cells treated by echistatin, cisplatin, and in particular the combination of both compounds drastically increased expression of NFκB transcription factor. Our results suggest that combined therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin. This

Lipid peroxidation is increased in tears from the elderly.

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Benlloch-Navarro, Soledad; Franco, Ilenia; Sánchez-Vallejo, Violeta; Silvestre, Dolores; Romero, Francisco Javier; Miranda, María

2013-10-01

We describe a procedure in which tears, obtained from Schirmer strips, are used to measure a marker of lipid peroxidation, malondialdehyde (MDA). We also compared the levels of proteins and MDA in tears from two groups of people: young adults (18-30 years old) and elderly adults (65-85 years old), because the data related to total protein concentration of human tears vary widely and because the majority of people over the age of 65 experience some symptoms of dry eyes and this condition has been recognized as an oxidative stress-induced disease. Our results show a significant difference in the protein concentration of the tears taken from the two age categories, younger adults (18-30 years old) and older adults (65-85 years old). Herein, we report for the first time an increase in MDA concentrations determined by HPLC in human tears based on age. It is possible that alterations in the tear lipid layer may lead to an increase in lipid peroxidation. Further studies are needed to understand the nature and function of tear film and stability in order to obtain new methods to analyze tears in patients with different diseases. In this sense, it would be interesting to compare MDA concentration in tears from control subjects and from people with meibomian gland dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): Novel gene therapeutic for metastatic melanoma

International Nuclear Information System (INIS)

Fisher, Paul B.; Sarkar, Devanand; Lebedeva, Irina V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su Zaozhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

2007-01-01

A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed 'differentiation therapy of cancer' with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display elevated expression in normal melanocytes and nevi with progressive loss of expression as a consequence of melanoma development and progression to metastasis. Based on structure, biochemical properties and chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a member of the expanding IL-10 family of cytokines. In vitro cell culture and in vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell death (apoptosis) in multiple human cancers (including melanomas), without harming normal cells, and promotes profound anti-tumor activity in nude mice containing human tumor xenografts. Based on these remarkable properties, a Phase I clinical trial was conducted to test the safety of administration of mda-7/IL-24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and to promote significant clinical activity, particularly in the context of patients with metastatic melanoma. These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the 'bench to the bedside.'

Evaluation of the Erythrocyte Malondialdehyde (MDA) Release Assay.

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1987-01-01

MDA vs. Cholesterol A It.M U Control indicated that there was alsc: a p-sit ive .. r i Piat i r, 0.58) between cholestetol an’] I I asma ::im E...N Engl J Med 310, 1209-1212(1984). 58. Hess AF. Involvement of the blood and blood vessels in infantile scurvy. Proc Soc Exp Biol Med 11, 130-132

Medical Data Architecture (MDA) Project Status

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Krihak, M.; Middour, C.; Gurram, M.; Wolfe, S.; Marker, N.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2018-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current in-flight medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are a variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable a more medically autonomous crew than the current paradigm. The medical system requirements are being developed in parallel with the exploration mission architecture and vehicle design. ExMC has recognized that in order to make informed decisions about a medical data architecture framework, current methods for medical data management must not only be understood, but an architecture must also be identified that provides the crew with actionable insight to medical conditions. This medical data architecture will provide the necessary functionality to address the challenges of executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. Hence, the products supported by current prototype development will directly inform exploration medical system requirements.

Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial fibroblasts.

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Olga N Karpus

Full Text Available CD55 (decay-accelerating factor is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS. CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS.FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (dsRNA sensors melanoma differentiation-associated gene 5 (MDA5 and retinoic acid-inducible gene-I (RIG-I. CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry.CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA, osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C. Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55.Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes.

Study of serum Malondialdehyde, Nitric oxide, Vitamin E levels in patients with rheumatoid arthritis

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Jambale Triveni A, Halyal SS, Jayaprakash Murthy DS

2014-04-01

Full Text Available Background: Rheumatoid arthritis (RA is a chronic progressive autoimmune disorder characterized by symmetric erosive synovitis and sometimes shows multisystem involvement. The long-term outcome of the disease is characterized by significant morbidity and increased mortality. Elevated free radical generations in inflamed joints and impaired antioxidant system have been implicated in RA. Nitric oxide (NO can also induce tissue damage, especially after conversion into peroxynitrite radical (ONOO·. Aims: To estimate the serum levels of MDA, Nitric Oxide (NO and Vitamin E in patients with Rheumatoid Arthritis. Materials and Methods: The study includes 50 RA patients who were fulfilling the American Rheumatism Association 1987 revised criteria for classification of RA and 50 age and sex matched healthy subjects without any major illness were considered as controls. MDA, NO and Vitamin E were estimated in serum. Results: The estimated mean levels (mean ± SD of serum MDA, NO, Vitamin E, in control group were 3.55 ± 0.30, 36.23 ± 7.03, 14.61 ± 1.74, respectively and in patients with RA they were 5.39 ± 0.79, 78.81 ± 8.56, 10.56 ± 1.72, respectively. The statistical analysis by unpaired t-test shows that the levels of serum MDA and NO significantly increased (p< 0.001 and the vitamin E levels were significantly decreased (p < 0.001 in RA patients when compared to healthy controls. Conclusion: The serum values of MDA, NO and Vitamin E all together provided fairly useful index of oxidative stress in RA patients. The results of current study support the concept of oxidative stress leading to tissue damage.

Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines

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Yerly Vargas Casanova

2017-09-01

Full Text Available Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922 and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.

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Vargas Casanova, Yerly; Rodríguez Guerra, Jorge Antonio; Umaña Pérez, Yadi Adriana; Leal Castro, Aura Lucía; Almanzar Reina, Giovanni; García Castañeda, Javier Eduardo; Rivera Monroy, Zuly Jenny

2017-09-29

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

Comparing of Cu/Zn SOD Gene Expression of Lymphocyte Cell and Malondialdehyde Level in Active Men and Women after Physical Training

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Bakhtiar Tartibian

2012-07-01

Full Text Available Background: The purpose of this study is to compare Cu/Zn SOD mRNA and MDA level as a result of a session incremental exercise in active women and men. Materials and Methods: This research is a quasi-experimental study with repeated measurements in which 14 active female and 13 male subjects with age range 22-24 participated voluntarily. Then, blood was taken from brachial vein of the subjects in three stages before and after GXT (Graded exercise test and 3 hours after that and SYBER Green PCR Master mix reagent Kit and Real time-PCR were used to measure Cu/Zn SOD mRNA and spectrophotometer was used to measure MDA level.Results: MDA levels increased significantly in men during the recovery stage and after the exercise (p1=0.012 and p2 =0.014, but it did not increase significantly in active women. Also, MDA difference between the two genders was not reported significant in any of the exercise stages. Cu/Zn SOD gene expression did not increase significantly in either sex.Conclusion: The risk of injury from free radicals is more probable in active men than active women and vigorous physical activity does not significantly increase the Cu/Zn SOD gene expression.

Antisense imaging of epidermal growth factor-induced p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 human breast cancer xenografts

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Wang, Judy; Chen, Paul; Mrkobrada, Marko [Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, M5S 2S2, Toronto, Ontario (Canada); Hu, Meiduo [Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, M5S 2S2, Toronto, Ontario (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario (Canada); Vallis, Katherine A. [Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Reilly, Raymond M. [Department of Medical Imaging, University of Toronto, Toronto, Ontario (Canada)

2003-09-01

Molecular imaging of the expression of key genes which determine the response to DNA damage following cancer treatment may predict the effectiveness of a particular treatment strategy. A prominent early response gene for DNA damage is the gene encoding p21{sup WAF-1/CIP-1}, a cyclin-dependent kinase inhibitor that regulates progression through the cell cycle. In this study, we explored the feasibility of imaging p21{sup WAF-1/CIP-1} gene expression at the mRNA level using an 18-mer phosphorothioated antisense oligodeoxynucleotide (ODN) labeled with {sup 111}In. The known induction of the p21{sup WAF-1/CIP-1} gene in MDA-MB-468 human breast cancer cells following exposure to epidermal growth factor (EGF) was used as an experimental tool. Treatment of MDA-MB-468 cells in vitro with EGF (20 nM) increased the ratio of p21{sup WAF-1/CIP-1} mRNA/{beta}-actin mRNA threefold within 2 h as measured by the reverse transcription polymerase chain reaction (RT-PCR). A concentration-dependent inhibition of EGF-induced p21{sup WAF-1/CIP-1} protein expression was achieved in MDA-MB-468 cells by treatment with antisense ODNs with up to a tenfold decrease observed at 1 {mu}M. There was a fourfold lower inhibition of p21{sup WAF-1/CIP-1} protein expression by control sense or random sequence ODNs. Intratumoral injections of EGF (15 {mu}g/day x 3 days) were employed to induce p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 xenografts implanted subcutaneously into athymic mice. RT-PCR of explanted tumors showed a threefold increased level of p21{sup WAF-1/CIP-1} mRNA compared with normal saline-treated tumors. Successful imaging of EGF-induced p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 xenografts was achieved at 48 h post injection of {sup 111}In-labeled antisense ODNs (3.7 MBq; 2 {mu}g). Tumors displaying basal levels of p21{sup WAF-1/CIP-1} gene expression in the absence of EGF treatment could not be visualized. Biodistribution studies showed a significantly higher tumor

Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

International Nuclear Information System (INIS)

Voss, Melanie J; Möller, Mischa F; Powe, Desmond G; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

2011-01-01

Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines. Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested. Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration. Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients

Development, validation and biomedical applications of stable-isotope dilution GC-MS and GC-MS/MS techniques for circulating malondialdehyde (MDA) after pentafluorobenzyl bromide derivatization: MDA as a biomarker of oxidative stress and its relation to 15(S)-8-iso-prostaglandin F2α and nitric oxide (NO).

Science.gov (United States)

Tsikas, Dimitrios; Rothmann, Sabine; Schneider, Jessica Y; Suchy, Maria-Theresia; Trettin, Arne; Modun, Darko; Stuke, Nadine; Maassen, Norbert; Frölich, Jürgen C

2016-04-15

Malondialdehyde (MDA, CH2(CHO)2) is one of the best investigated and most frequently measured biomarkers of lipid peroxidation in biological fluids, a constituent of the so called thiobarbituric acid reactive substances (TBARS). The reaction of thiobarbituric acid with MDA and other carbonyl compounds is the basis for the batch TBARS assay, one of the most commonly and widely used assays of oxidative stress. Yet, the TBARS assay lacks specificity even if combined with HPLC separation prior to visible absorbance or fluorescence detection. In this article, we report highly specific and sensitive stable-isotope dilution GC-MS and GC-MS/MS methods for the quantitative determination of MDA in human plasma (0.1 mL). These methods utilize the acidity (pKa, 4.46) of the two methylene H protons of MDA in aqueous solution, which are as acidic as acetic acid. Endogenous MDA in native plasma and the externally added internal standard [1,3-(2)H2]-MDA (d2-MDA, CH2(CDO)2) are derivatized in aqueous acetone (400 μL) with pentafluorobenzyl (PFB) bromide (10 μL). The reaction products were identified as C(PFB)2(CHO)2 (molecular weight, 432) and C(PFB)2(CDO)2) (molecular weight, 434), respectively. After solvent extraction with toluene (1 mL) quantification is performed by selected-ion monitoring (SIM) in GC-MS and by selected-reaction monitoring (SRM) in GC-MS/MS in the electron-capture negative-ion chemical ionization (ECNICI) mode. In the SIM mode, the anions [M-PFB](-) at m/z 251 for MDA and m/z 253 for d2-MDA are detected. In the SRM mode, the mass transitions m/z 251 to m/z 175 for MDA and m/z 253 to m/z 177 for d2-MDA are monitored. The method was thoroughly validated in human plasma. Potential interfering substances including anticoagulants and commercially available monovettes commonly used for blood sampling were tested. The lowest MDA concentrations were measured in serum followed by heparinized and EDTA plasma. The GC-MS and GC-MS/MS methods were found to be specific

PENGARUH MINUMAN DIPERKAYA CINNULIN TERHADAP MDA DAN SENYAWA INFLAMASI PLASMA PENDERITA DMT2

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Nawasari Indah Putri S

2016-06-01

Full Text Available Cinnamon has been used as a traditional treatment for thousands of years. Aqueous cinnamon extract namely cinnulin is known to have positive effects on type-2 diabetes mellitus (T2DM. We aimed to study the effect of cinnulin enriched drink rich in polyphenols on plasma malondialdehyde (MDA, interleukin-6 (IL-6 and cyclooxygenase-2 (COX-2 in T2DM patients. 255 mg of cinnulin was mixed with tea extract into a 2.5 gram of instant drink with alumunium foil as the packaging material. A single blind study were performed on 33 respondents with T2DM from Dramaga District. Respondents were divided into three groups, i.e. group given cinnulin enriched drink (1, instant tea drink (2, and none of the products (control (3. Group 1 and 2 were assigned to drink two sachetsof the products a day for 5 weeks. The MDA content of all groups remain unchanged after treatment although slightly increased (Wilcoxon, P>0.050 and no differences between groups was observed (P>0.050 suggesting that high phenolic content in the producst cause a reverse effect. Both inflammation marker (IL-6 and COX-2 decreased significantly for groups given cinnulin enriched drink and instant tea, whereas there is a significant increase for IL-6 and a significant decrease for COX-2 in control group. These results conclude that cinnulin enriched drink can be used as an antiinflammation drink for T2DM.

Decatropis bicolor (Zucc.) Radlk essential oil induces apoptosis of the MDA-MB-231 breast cancer cell line.

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Estanislao Gómez, C C; Aquino Carreño, A; Pérez Ishiwara, D G; San Martín Martínez, E; Morales López, J; Pérez Hernández, N; Gómez García, M C

2016-08-05

Decatropis bicolor (Zucc.)Radlk is a plant that has been traditionally used for the treatment of breast cancer in some communities of Mexico. So, the aim of this study was to determine the cytotoxic and apoptotic effect of the essential oil of Decatropis bicolor against breast cancer cell line, MDA-MB-231. The essential oil obtained from hydrodestillation of leaves of Decatropis bicolor was studied for its biological activity against breast cancer cells MDA-MB-231 by MTT assay, Hematoxylin-eosin stain, Annexin V-FITC, TUNEL and western blot assays and for its chemical composition by GC-MS. The results showed a relevant cytotoxic effect of the essential oil towards MDA-MB-231 cells in a dose- and time- dependent manner, with an IC50 of 53.81 ± 1.691 μg/ml but not in the epithelial mammary cell line MCF10A (207.51 ± 3.26 μg/ml). Morphological examination displayed apoptotic characteristics in the treated cells like cell size reduction, membrane blebbing and apoptotic bodies. In addition, the apoptotic rate significantly increased as well as DNA fragmentation and western blot analysis revealed that the essential oil induced apoptosis in the MDA-MB-231 cells via intrinsic pathways due to the activation of Bax, caspases 9 and 3. Phytochemical analysis of the Decatropis bicolor essential oil showed the presence of twenty-three compounds. Major components of the oil were 1,5-cyclooctadiene,3-(methyl-2)propenyl (18.38 %), β-terpineol (8.16 %) and 1-(3-methyl-cyclopent-2-enyl)-cyclohexene (6.12 %). This study suggests that essential oil of Decatropis bicolor has a potential cytotoxic and antitumoral effect against breast cancer cells, with the presence of potential bioactive compounds. Our results contribute to the validation of the anticancer activity of the plant in Mexican traditional medicine.

Plasma oxidative stress level of IgA nephropathy in children and the effect of early intervention with angiotensin-converting enzyme inhibitors.

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Pei, Yuxin; Xu, Yuanyuan; Ruan, Jingwei; Rong, Liping; Jiang, Mengjie; Mo, Ying; Jiang, Xiaoyun

2016-01-01

The purpose of this study was to investigate the change of the plasma oxidative stress level in children with IgA nephropathy (IgAN) and analyze its relativity to the clinical and pathological classification. To discuss the early effects of angiotensin-converting enzyme inhibitors (ACEIs) on the plasma oxidative stress level in children with IgA nephropathy. Thirty-eight children with IgAN were divided into groups according to their clinical features, pathologic grades, and treatments. Twenty healthy children were included in the control group. The plasma level of advanced oxidation protein products (AOPPs), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected. The plasma level of oxidative stress was significantly increased in the IgAN group, including a higher plasma level of AOPP and MDA and a lower plasma level of SOD. After treatment, the plasma level of oxidative stress was significantly decreased in the ACEI group. The children with IgAN had an increase in the plasma level of oxidative stress, expressed as an increased plasma level of AOPP and MDA and a decreased plasma level of SOD. Oxidative stress was associated with the progression of IgAN in children. Early treatment with ACEI therapy can significantly reduce the plasma level of oxidative stress in children with IgAN. © The Author(s) 2016.

Applying MDA to SDR for Space to Model Real-time Issues

Science.gov (United States)

Blaser, Tammy M.

2007-01-01

NASA space communications systems have the challenge of designing SDRs with highly-constrained Size, Weight and Power (SWaP) resources. A study is being conducted to assess the effectiveness of applying the MDA Platform-Independent Model (PIM) and one or more Platform-Specific Models (PSM) specifically to address NASA space domain real-time issues. This paper will summarize our experiences with applying MDA to SDR for Space to model real-time issues. Real-time issues to be examined, measured, and analyzed are: meeting waveform timing requirements and efficiently applying Real-time Operating System (RTOS) scheduling algorithms, applying safety control measures, and SWaP verification. Real-time waveform algorithms benchmarked with the worst case environment conditions under the heaviest workload will drive the SDR for Space real-time PSM design.

Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs.

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Chiu, Jen-Hwey; Chen, Fang-Pey; Tsai, Yi-Fang; Lin, Man-Ting; Tseng, Ling-Ming; Shyr, Yi-Ming

2017-08-12

Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and real-time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on cancer cell/endothelial cell interactions was assessed using co-culture and ELISA. In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells. We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast

The effect of copper, MDA, and accelerated aging on jet fuel thermal stability as measured by the gravimetric JFTOT

Energy Technology Data Exchange (ETDEWEB)

Pande, S.G. [Geo-Centers, Inc., Ft. Washington, MD (United States); Hardy, D.R. [Navy Technology Center for Safety and Survivability, Washington, DC (United States)

1995-05-01

Thermally unstable jet fuels pose operational problems. In order to adequately identify such fuels, factors that realistically impact on thermal stability were examined. Evaluation was based on a quantitative method of measuring thermal stability, viz., NRL`s recently developed gravimetric JFTOT. This method gives a quantitative measurement of both the strip deposit and filterables formed. The pertinent factors examined, included the individual and interactive effects of: soluble copper, MDA (metal deactivator), and aging. The latter was accelerated to simulate field conditions of approximately six months aging at ambient temperature and pressure. The results indicate that the individual and interactive effects of copper, MDA, and accelerated aging appear to be fuel dependent. Based on the results, the three test fuels examined (one JP-8 and two JP-5s) were categorized as exhibiting very good, typical, and poor thermal stabilities, respectively. For both the very good and poor thermal stability fuels, the effect of copper in conjunction with accelerated aging did not significantly increase the total thermal deposits of the neat fuels. In contrast, for the typical thermal stability fuel, the combined effects of copper and accelerated aging, did. Furthermore, the addition of MDA prior to aging of the copper-doped, typical stability fuel significantly counteracted the adverse effect of copper and aging. A similar beneficial effect of MDA was not observed for the poor stability fuel. These results focus on the compositional differences among fuels and the need to elucidate these differences (physical and chemical) for a better understanding and prediction of their performance.

Antagonism of the Phosphatase PP1 by the Measles Virus V Protein Is Required for Innate Immune Escape of MDA5

NARCIS (Netherlands)

Davis, Meredith E.; Wang, May K.; Rennick, Linda J.; Full, Florian; Gableske, Sebastian; Mesman, Annelies W.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.; Duprex, W. Paul; Gack, Michaela U.

2014-01-01

The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the

Evaluation of Modification of the 3M™ Molecular Detection Assay (MDA) Salmonella Method (2013.09) for the Detection of Salmonella in Selected Foods: Collaborative Study.

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Bird, Patrick; Fisher, Kiel; Boyle, Megan; Huffman, Travis; Benzinger, M Joseph; Bedinghaus, Paige; Flannery, Jonathon; Crowley, Erin; Agin, James; Goins, David; Benesh, DeAnn; David, John

2014-01-01

The 3M(™) Molecular Detection Assay (MDA) Salmonella utilizes isothermal amplification of nucleic acid sequences with high specificity, efficiency, rapidity and bioluminescence to detect amplification of Salmonella spp. in food, food-related, and environmental samples after enrichment. A method modification and matrix extension study of the previously approved AOAC Official Method(SM) 2013.09 was conducted, and approval of the modification was received on March 20, 2014. Using an unpaired study design in a multilaboratory collaborative study, the 3M MDA Salmonella method was compared to the U.S. Department of Agriculture/Food Safety and Inspection Service (USDA/FSIS) Microbiology Laboratory Guidebook (MLG) 4.05 (2011), Isolation and Identification of Salmonella from Meat, Poultry, Pasteurized Egg, and Catfish Products for raw ground beef and the U.S. Food and Drug Administration (FDA)/Bacteriological Analytical Manual (BAM) Chapter 5, Salmonella reference method for wet dog food following the current AOAC guidelines. A total of 20 laboratories participated. For the 3M MDA Salmonella method, raw ground beef was analyzed using 25 g test portions, and wet dog food was analyzed using 375 g test portions. For the reference methods, 25 g test portions of each matrix were analyzed. Each matrix was artificially contaminated with Salmonella at three inoculation levels: an uninoculated control level (0 CFU/test portion), a low inoculum level (0.2-2 CFU/test portion), and a high inoculum level (2-5 CFU/test portion). In this study, 1512 unpaired replicate samples were analyzed. Statistical analysis was conducted according to the probability of detection (POD). For the low-level raw ground beef test portions, the following dLPOD (difference between the LPODs of the reference and candidate method) values with 95% confidence intervals were obtained: -0.01 (-0.14, +0.12). For the low-level wet dog food test portions, the following dLPOD with 95% confidence intervals were

Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

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Leonardo Lorente

2016-04-01

Full Text Available Previous studies have found higher levels of serum malondialdehyde (MDA in hepatocellular carcinoma (HCC patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02. Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI = from 1.580 to infinite; p = 0.007 adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.

Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

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Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Abreu-González, Pedro; Díaz, Dácil; Moreno, Antonia M.; Borja, Elisa; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT. PMID:27058525

A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations

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Ninuo Xia

2017-03-01

Full Text Available Generation of midbrain dopaminergic (mDA neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson’s disease (PD. However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC line with a tyrosine hydroxylase (TH-RFP (red fluorescent protein reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC] at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.

A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations.

Science.gov (United States)

Xia, Ninuo; Fang, Fang; Zhang, Pengbo; Cui, Jun; Tep-Cullison, Chhavy; Hamerley, Tim; Lee, Hyun Joo; Palmer, Theo; Bothner, Brian; Lee, Jin Hyung; Pera, Renee Reijo

2017-03-07

Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC]) at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Six weeks of aerobic dance exercise improves blood oxidative stress status and increases interleukin-2 in previously sedentary women.

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Leelarungrayub, Donrawee; Saidee, Kunteera; Pothongsunun, Prapas; Pratanaphon, Sainetee; YanKai, Araya; Bloomer, Richard J

2011-07-01

This study evaluated the change in blood oxidative stress, blood interleukin-2, and physical performance following 6 weeks of moderate intensity and duration aerobic dance exercise in 24 sedentary women. Blood samples were collected at rest twice before (baseline) and after the 6-week intervention for analysis of protein hydroperoxide (PrOOH), malondialdehyde (MDA), total anti-oxidant capacity (TAC), and interleukin-2 (IL-2) levels. Maximal treadmill run time (Time(max)) and maximal oxygen consumption (VO(2max)) were also measured. All variables were statistically analyzed with a repeated measurement ANOVA and Tukey post hoc. No differences were noted in any variable during the baseline period (p > 0.05). After aerobic dance exercise, VO(2max), Time(max), TAC and IL-2 were significantly increased, whereas MDA levels were decreased significantly (p exercise. It can be concluded that aerobic dance exercise at a moderate intensity and duration can improve physical fitness, decrease MDA, and increase TAC and IL-2 in previously sedentary women. Copyright © 2010 Elsevier Ltd. All rights reserved.

Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and MDA5.

Science.gov (United States)

Louber, Jade; Brunel, Joanna; Uchikawa, Emiko; Cusack, Stephen; Gerlier, Denis

2015-07-28

The cytoplasmic RIG-like receptors are responsible for the early detection of viruses and other intracellular microbes by activating the innate immune response mediated by type I interferons (IFNs). RIG-I and MDA5 detect virus-specific RNA motifs with short 5'-tri/diphosphorylated, blunt-end double-stranded RNA (dsRNA) and >0.5-2 kb long dsRNA as canonical agonists, respectively. However, in vitro, they can bind to many RNA species, while in cells there is an activation threshold. As SF2 helicase/ATPase family members, ATP hydrolysis is dependent on co-operative RNA and ATP binding. Whereas simultaneous ATP and cognate RNA binding is sufficient to activate RIG-I by releasing autoinhibition of the signaling domains, the physiological role of the ATPase activity of RIG-I and MDA5 remains controversial. A cross-analysis of a rationally designed panel of RNA binding and ATPase mutants and truncated receptors, using type I IFN promoter activation as readout, allows us to refine our understanding of the structure-function relationships of RIG-I and MDA5. RNA activation of RIG-I depends on multiple critical RNA binding sites in its helicase domain as confirmed by functional evidence using novel mutations. We found that RIG-I or MDA5 mutants with low ATP hydrolysis activity exhibit constitutive activity but this was fully reverted when associated with mutations preventing RNA binding to the helicase domain. We propose that the turnover kinetics of the ATPase domain enables the discrimination of self/non-self RNA by both RIG-I and MDA5. Non-cognate, possibly self, RNA binding would lead to fast ATP turnover and RNA disassociation and thus insufficient time for the caspase activation and recruitment domains (CARDs) to promote downstream signaling, whereas tighter cognate RNA binding provides a longer time window for downstream events to be engaged. The exquisite fine-tuning of RIG-I and MDA5 RNA-dependent ATPase activity coupled to CARD release allows a robust IFN response

Enterovirus 2Apro targets MDA5 and MAVS in infected cells

NARCIS (Netherlands)

Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

2014-01-01

RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress

Enterovirus 2Apro targets MDA5 and MAVS in infected cells

NARCIS (Netherlands)

Feng, Qian; Langereis, Martijn A; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M

2014-01-01

UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses

The influence of random and systematic errors on a general definition of minimum detectable amount (MDA) applicable to all radiobioassay measurements

International Nuclear Information System (INIS)

Brodsky, A.

1985-01-01

An approach to defining minimum detectable amount (MDA) of radioactivity in a sample will be discussed, with the aim of obtaining comments helpful in developing a formulation of MDA that will be broadly applicable to all kinds of radiobioassay measurements, and acceptable to the scientists who make these measurements. Also, the influence of random and systematic errors on the defined MDA are examined

Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

Science.gov (United States)

Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

2016-12-29

To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO 4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

Apoptotic Effect of the Urtica Dioica Plant Extracts on Breast Cancer Cell Line (MDA- MB- 468

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A Mohammadi

2015-09-01

Full Text Available Background & objectives: Cancer is one of the most causes of mortality in worldwide. Components derived from natural plants that induce apoptosis are used for cancer treatment. Therefore investigation of different herbal components for new anti-cancer drug is one of the main research activities throughout the world. According to low cost, oral consumption and easy access to the public extracts of Urtica dioica, in this study we aimed to investigate the effectiveness of this herb on MDA-MB-468 breast cancer cells.   Methods: Cytotoxic effect of Urtica dioica extract was measured using MTT assays. To show induction of apoptosis by this plant TUNEL and DNA Fragmentation test were performed.   Results: In the present study dichloromethane extracts noticeably killed cancer cells. IC50 values related to human breast adenocarcinoma cell line MDA-MB-468 were 29.46±1.05 µg/ml in 24 hours and 15.54±1.04 µg/ml in 48 hours. TUNEL test and DNA Fragmentation assay showed apoptotic characteristic in the extract treated cells.   Conclusion: The results showed that MDA-MB-468 cells after treatment with dichloromethane extract of Urtica dioica, induces apoptosis in MDA-MB-468 cancer cells which may be useful in the treatment of cancer.

Low-level lasers on microRNA and uncoupling protein 2 mRNA levels in human breast cancer cells

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Canuto, K. S.; Teixeira, A. F.; Rodrigues, J. A.; Paoli, F.; Nogueira, E. M.; Mencalha, A. L.; Fonseca, A. S.

2017-06-01

MicroRNA is short non-coding RNA and is a mediator of post-transcriptional regulation of gene expression. In addition, uncoupling proteins (UCPs) regulate thermogenesis, metabolic and energy balance, and decrease reactive oxygen species production. Both microRNA and UCP2 expression can be altered in cancer cells. At low power, laser wavelength, frequency, fluence and emission mode deternube photobiological responses, which are the basis of low-level laser therapy. There are few studies on miRNA and UCP mRNA levels after low-level laser exposure on cancer cells. In this work, we evaluate the micrRNA (mir-106b and mir-15a) and UCP2 mRNA levels in human breast cancer cells exposed to low-level lasers. MDA-MB-231 human breast cancer cells were exposed to low-level red and infrared lasers, total RNA was extracted for cDNA synthesis and mRNA levels by real time quantitative polymerase chain reaction were evaluated. Data show that mir-106b and mir-15a relative levels are not altered, but UCP2 mRNA relative levels are increased in MDA-MB-231 human breast cancer cells exposed to low-level red and infrared lasers at fluences used in therapeutic protocols.

Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

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Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

2014-01-01

The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231.

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Mohsen Marvibaigi

Full Text Available Scurrula ferruginea (Jack Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231 and non-cancer human skin fibroblast cells (HSF-1184. The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract and flavonoid contents (163.41 ± 4.62 mg catechin/g extract and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL and metal chelation activity (IC50 = 80.20 μg/mL. The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.

Comparison of the effects of three different Baccaurea angulata whole fruit juice doses on plasma, aorta and liver MDA levels, antioxidant enzymes and total antioxidant capacity.

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Ibrahim, Muhammad; Mikail, Maryam Abimbola; Ahmed, Idris Adewale; Hazali, Norazlanshah; Abdul Rasad, Mohammad Syaiful Bahari; Abdul Ghani, Radiah; Hashim, Ridzwan; Arief, Solachuddin Jahuari; Md Isa, Muhammad Lokman; Draman, Samsul

2017-05-17

Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet. Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice. The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent. Higher doses of B. angulata juice exerted better antioxidant activity.

The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells.

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Mohammadi, Ali; Mansoori, Behzad; Aghapour, Mahyar; Shirjang, Solmaz; Nami, Sanam; Baradaran, Behzad

2016-10-01

Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acute effects of low-level laser therapy (660 nm) on oxidative stress levels in diabetic rats with skin wounds.

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Denadai, Amanda Silveira; Aydos, Ricardo Dutra; Silva, Iandara Schettert; Olmedo, Larissa; de Senna Cardoso, Bruno Mendonça; da Silva, Baldomero Antonio Kato; de Carvalho, Paulo de Tarso Camillo

2017-09-01

Laser therapy influences oxidative stress parameters such as the activity of antioxidant enzymes and the production of reactive oxygen species. To analyze the effects of low-level laser therapy on oxidative stress in diabetics rats with skin wounds. Thirty-six animals were divided into 4 groups: NDNI: non-diabetic rats with cutaneous wounds that not received laser therapy; NDI: non-diabetic rats with cutaneous wounds that received laser therapy; DNI: diabetic rats with skin wounds who did not undergo laser therapy; DI: rats with diabetes insipidus and cutaneous wounds and received laser therapy. The animals were treated with LLLT (660 nm, 100 mW, 6 J/cm, spot size 0.028 cm). On the day of killing the animals, tissue-wrapped cutaneous wounds were collected and immediately frozen, centrifuged, and stored to analyze malondialdehyde (MDA) levels. Significant difference was observed within the groups of MDA levels (ANOVA, p = 0.0001). Tukey's post-hoc test showed significantly lower values of MDA in irradiated tissues, both in diabetic and non-diabetic rats. ANOVA of the diabetic group revealed a significant difference (p < 0.01) when all groups, except NDI and DI, were compared. LLLT was effective in decreasing MDA levels in acute surgical wounds in diabetic rats.

HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.

Science.gov (United States)

Chen, Zhiyong; Wang, Yan; Kuwana, Masataka; Xu, Xue; Hu, Wei; Feng, Xuebing; Wang, Hong; Kimura, Akinori; Sun, Lingyun

2017-09-01

Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (p c ) = 3.8 × 10 -8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, p c = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10 -6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10 -4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD. DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.

CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells

International Nuclear Information System (INIS)

Androutsopoulos, Vasilis P.; Ruparelia, Ketan; Arroo, Randolph R.J.; Tsatsakis, Aristidis M.; Spandidos, Demetrios A.

2009-01-01

Among the different mechanisms proposed to explain the cancer-protecting effect of dietary flavonoids, substrate-like interactions with cytochrome P450 CYP1 enzymes have recently been explored. In the present study, the metabolism of the flavonoids chrysin, baicalein, scutellarein, sinensetin and genkwanin by recombinant CYP1A1, CYP1B1 and CYP1A2 enzymes, as well as their antiproliferative activity in MDA-MB-468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolin were the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes, respectively, while baicalein itself was not metabolized further. Sinensetin and genkwanin produced a greater number of metabolites and were shown to inhibit strongly in vitro proliferation of MDA-MB-468 cells at submicromolar and micromolar concentrations, respectively, without essentially affecting the viability of MCF-10A cells. Cotreatment of the CYP1 family inhibitor acacetin reversed the antiproliferative activity noticed for the two flavones in MDA-MB-468 cells to 13 and 14 μM respectively. In contrast chrysin, baicalein and scutellarein inhibited proliferation of MDA-MB-468 cells to a lesser extent than sinensetin and genkwanin. The metabolism of genkwanin to apigenin and of chrysin to baicalein was favored by CYP1B1 and CYP1A1, respectively. Taken together the data suggests that CYP1 family enzymes enhance the antiproliferative activity of dietary flavonoids in breast cancer cells, through bioconversion to more active products.

Effect of high-dose lidocaine treatment on superoxide dismutase and malon dialdehyde levels in seven diabetic patients.

Science.gov (United States)

Celebi, H; Bozkirli, F; Günaydin, B; Bilgihan, A

2000-01-01

We report on the use of intravenous (IV) high-dose lidocaine to relieve diabetic neuropathic pain, and the technique's effects on clinical measures of lipid peroxidation. Under continuous electrocardiogram monitoring, IV lidocaine (5 mg kg(-1) in 100 mL saline) was administered over 30 minutes to 7 non-insulin-dependent diabetic patients suffering from neuropathic pain who reported increased pain within the preceding 6 months. This treatment was performed once a week for 1 month. Blood samples were collected from the contralateral limb to determine plasma superoxide dismutase (SOD) and malondialdehyde (MDA) levels on admission and following the final lidocaine administration. Plasma MDA concentrations significantly decreased after the final IV lidocaine treatment (P < .05, paired t-test), whereas SOD levels did not show a statistically significant difference compared with baseline levels. High-dose lidocaine treatment lessens MDA levels, a marker of free-radical-mediated cell damage. This suggests that one of lidocaine's mechanism of action may be its effect on oxygen free radicals, which in turn impacts lipid peroxidation.

Study on the Mission, Roles, and Structure of the Missile Defense Agency (MDA)

National Research Council Canada - National Science Library

Welch, Larry D; Briggs, David L; Bleach, R. D; Canavan, G. H; Clark-Sestak, S. L; Constantine, R. W; Cook, C. W; Fries, M. S; Frost, D. E; Graham, D. R; Keane, D. J; Kramer, S. D; Major, P. L; Primmerman, C. A; Ruddy, J. M; Schneiter, G. R; Seng, J. M; Stein, R. M; Weiner, S. D; Williams, J. D

2008-01-01

...) was tasked by the Department of Defense to carry out an independent study to examine and make recommendations with respect to the long-term missions, roles, and structure of the Missile Defense Agency (MDA...

The Effect of Systemic Amantadine Sulfate on Malondialdehyde and Total Thiol Levels in Rat Corneas

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Züleyha Yalniz-Akkaya

2014-01-01

Full Text Available Purpose: To evaluate the malondialdehyde (MDA and total thiol (sulfhydryl, SH levels in rat corneas after intraperitoneal injection of amantadine sulfate. Methods: A total of 12 Wistar albino rats were divided into two groups: control group (n = 6 and amantadine group (n = 6. Balanced salt solution (1 mL, 0.9% NaCl, twice/day was injected into rats in control group. Amantadine sulfate (2 mg/1 mL, twice/day was injected into rats in amantadine group. In each group, two rats were injected for 1 week, two received injections for 1 month, and two rats received injections for 3 months. The corneas were homogenized and MDA and SH levels were measured spectroflourometrically. Results: In control group, median MDA and SH levels were 2.37 (range, 0.92-3.60 and 25.35 (range, 6.30-54.0 nmol/mg, respectively. In amantadine group, median MDA and SH levels were 3.57 (range, 1.25-5.92 and 32.65 (range, 3.30-48.3 nmol/mg, respectively. The difference between this two groups regarding MDA (P = 0.14 and SH (P = 1.0 levels was statistically insignificant. Conclusion: Systemically administered amantadine sulfate seems not to cause MDA and SH imbalance in rat corneas.

Low-level lasers alter mRNA levels from traditional reference genes used in breast cancer cells

Science.gov (United States)

Teixeira, A. F.; Canuto, K. S.; Rodrigues, J. A.; Fonseca, A. S.; Mencalha, A. L.

2017-07-01

Cancer is among the leading causes of mortality worldwide, increasing the importance of treatment development. Low-level lasers are used in several diseases, but some concerns remains on cancers. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is a technique used to understand cellular behavior through quantification of mRNA levels. Output data from target genes are commonly relative to a reference that cannot vary according to treatment. This study evaluated reference genes levels from MDA-MB-231 cells exposed to red or infrared lasers at different fluences. Cultures were exposed to red and infrared lasers, incubated (4 h, 37 °C), total RNA was extracted and cDNA synthesis was performed to evaluate mRNA levels from ACTB, GUSB and TRFC genes by RT-qPCR. Specific amplification was verified by melting curves and agarose gel electrophoresis. RefFinder enabled data analysis by geNorm, NormFinder and BestKeeper. Specific amplifications were obtained and, although mRNA levels from ACTB, GUSB or TRFC genes presented no significant variation through traditional statistical analysis, Excel-based tools revealed that the use of these reference genes are dependent of laser characteristics. Our data showed that exposure to low-level red and infrared lasers at different fluences alter the mRNA levels from ACTB, GUSB and TRFC in MDA-MB-231 cells.

Functional effects of Toll-like receptor (TLR3, 7, 9, RIG-I and MDA-5 stimulation in nasal epithelial cells.

Directory of Open Access Journals (Sweden)

Lotta Tengroth

Full Text Available The human nasal epithelium is an important physical barrier, and a part of the innate immune defense that protect against pathogens. The epithelial cells recognize microbial components by pattern-recognition receptors (PRRs, and thereby trigger an immune response. Even though TLR3, TLR7, TLR9, RIG-I and MDA-5 are all known to respond to viral stimulation, their potential role in chronic airway inflammation triggered by local cytokine release remains to be established.mRNA and corresponding protein expression of TLR3, TLR7, TLR9, RIG-I and MDA-5 were analyzed in nasal biopsies and various upper airway epithelial cell lines using real-time reverse transcription PCR, immunohistochemistry and flow cytometry. Ligand induced, cytokine release, was evaluated with ELISA.Nasal biopsies were found to express TLR3, TLR7, TLR9, RIG-I and MDA-5, with the most abundant expression in the surface epithelium. These receptors were verified in primary human nasal epithelial cell (HNEC as well as in the airway epithelial cell lines Detroit-562 and FaDu. Poly(I:C (TLR3 and R-837 (TLR7 stimulation increased secretion of IL-6 and GM-CSF from the nasal mucosa and the epithelial cell lines. CpG (TLR9 stimulation caused release of IL-8 in the nasal mucosa and in FaDu. Poly(I:C/LyoVec (RIG-I/MDA-5 stimulation activated the secretion of IFN-β in the nasal mucosa. A corresponding release was also detected from HNEC and Detroit-562.The nasal epithelium has the ability to recognize viral intrusion through TLR and RLR receptors, and the subsequent response might have a role in exacerbation of inflammatory diseases like allergic rhinitis and chronic rhinosinusitis.

MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens.

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Matthias Liniger

Full Text Available Chickens lack the retinoic acid-inducible gene I (RIG-I and sense avian influenza virus (AIV infections by means of the melanoma differentiation-associated gene 5 product (chMDA5. Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483 expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483 were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483 expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.

Evaluation of the 3M™ Molecular Detection Assay (MDA) 2 - Salmonella for the Detection of Salmonella spp. in Select Foods and Environmental Surfaces: Collaborative Study, First Action 2016.01.

Science.gov (United States)

Bird, Patrick; Flannery, Jonathan; Crowley, Erin; Agin, James R; Goins, David; Monteroso, Lisa

2016-07-01

The 3M™ Molecular Detection Assay (MDA) 2 - Salmonella uses real-time isothermal technology for the rapid and accurate detection of Salmonella spp. from enriched select food, feed, and food-process environmental samples. The 3M MDA 2 - Salmonella was evaluated in a multilaboratory collaborative study using an unpaired study design. The 3M MDA 2 - Salmonella was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual Chapter 5 reference method for the detection of Salmonella in creamy peanut butter, and to the U.S. Department of Agriculture, Food Safety and Inspection Service Microbiology Laboratory Guidebook Chapter 4.08 reference method "Isolation and Identification of Salmonella from Meat, Poultry, Pasteurized Egg and Catfish Products and Carcass and Environmental Samples" for the detection of Salmonella in raw ground beef (73% lean). Technicians from 16 laboratories located within the continental United States participated. Each matrix was evaluated at three levels of contamination: an uninoculated control level (0 CFU/test portion), a low inoculum level (0.2-2 CFU/test portion), and a high inoculum level (2-5 CFU/test portion). Statistical analysis was conducted according to the probability of detection (POD) statistical model. Results obtained for the low inoculum level test portions produced difference in collaborator POD values of 0.03 (95% confidence interval, -0.10 to 0.16) for raw ground beef and 0.06 (95% confidence interval, -0.06 to 0.18) for creamy peanut butter, indicating no statistically significant difference between the candidate and reference methods.

Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

Science.gov (United States)

Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

2015-01-01

Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.

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José M Alvarez-Suarez

Full Text Available BACKGROUND AND AIM: Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. METHODS/PRINCIPAL FINDINGS: Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. CONCLUSIONS: Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

Science.gov (United States)

Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

2011-01-01

Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

Changes in taste sensation of sour, salty, sweet, bitter, umami, and spicy, as well as levels of malondialdehyde serum in radiographers

Directory of Open Access Journals (Sweden)

Agniz Nur Aulia

2016-06-01

on the effects of radiation on cancer patients show that radiation can cause an increase in bitterness and metal taste [in cancer patients] leading to discomfort in the oral cavity. In body, free radicals then can cause lipid peroxidation process. Lipid peroxidation is an oxidative destruction of polyunsaturated fatty acid producing malondialdehyde (MDA. Purpose: This study aimed to determine the effects of radiation on changes in the taste sensation of sour, salty, sweet, bitter, umami, and spicy as well as the levels of MDA serum in radiographers. Method: This study was an observational laboratory research using post- test control design. Samples were selected using simple random sampling technique. The samples were seven radiographers who have been working for five years in the laboratory and radiographic units in Surabaya. Result: Based on the results of statistical tests, it showed that there were no differences in the sensitivity of all tastes between the groups tested. Moreover, the results also depicted considerable value for the sour taste was 0.550, the saltiness was 0.775, the sweetness was 0.294, the bitter taste was 0.065, the umami taste was 0.705, and the spicy taste was 0.319 (p>0.05. However, the dramatic increase was higlighted in levels of MDA serum with a significant value of 0.065 (p>0.005. Conclusion. There were no changes in the sensitivity of sour, salty, sweet, bitter, umami, and spicy tastes, but there was a significant increased in level of MDA serum in the radiographers compared to the control group.

Evaluation of the Level of Zinc and Malondialdehyde in Basal Cell Carcinoma.

Science.gov (United States)

Majidi, Ziba; Djalali, Mahmoud; Javanbakht, Mohammad Hasan; Fathi, Mojtaba; Zarei, Mahnaz; Foladsaz, Koorosh

2017-08-01

Basal Cell Carcinoma (BCC) is one of the most common skin cancers in the world and that use to lifestyle, increasing chemical pollutions, environmental factors and poor nutrition. The most important cause of this cancer is oxidative stress and free radicals so antioxidant activities for the body are so important. The aim of this study was to determine the variation of zinc and (Malondialdehyde) MDA in BCC patients. This study has been performed on case and control patients from 2013 to 2014. The samples were collected from cell carcinoma patients at Razi Hospital in Tehran, Iran. We evaluated the level of zinc with the use of Atomic Absorption Spectroscopy (AAS) method. Besides, we evaluated MDA with colorimetric assay. The concentration of MDA was significantly higher in case group in comparison to control group ( P =0.001). In addition, case group had lower concentration of zinc than the control group ( P =0.000). There was no correlation between MDA and body mass index (BMI) and between zinc and BMI. All the patients with BCC showed a significant MDA serum in comparison with control group. However, significant decrease in zinc serum of the patients was seen that is because of consuming zinc during oxidative stress process so topical use of zinc in the form of 2+ ions could be effective on antioxidant protection against the sun UV radiation.

Modeling the Interaction Between Semantic Agents and Semantic Web Services Using MDA Approach

NARCIS (Netherlands)

Kardas, Geylani; Göknil, Arda; Dikenelli, Oguz; Topaloglu, N. Yasemin

2007-01-01

In this paper, we present our metamodeling approach for integrating semantic web services and semantic web enabled agents under Model Driven Architecture (MDA) view which defines a conceptual framework to realize model driven development. We believe that agents must have well designed environment

Killing of Human Melanoma Cells Induced by Activation of Class I Interferon–Regulated Signaling Pathways via MDA-7/IL-24

Science.gov (United States)

Ekmekcioglu, Suhendan; Mumm, John B.; Udtha, Malini; Chada, Sunil; Grimm, Elizabeth A.

2008-01-01

Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1–regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN alfa) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of Class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN beta induction followed by IRF regulation and TRAIL/FasL system activation. PMID:18511292

The physiological responses of Vallisneria natans to epiphytic algae with the increase of N and P concentrations in water bodies.

Science.gov (United States)

Song, Yu-Zhi; Wang, Jin-Qi; Gao, Yong-Xia; Xie, Xue-Jian

2015-06-01

To reveal the mechanism of submerged plants decline in progressively eutrophicated freshwaters, physiological responses of Vallisneria natans to epiphytic algae were studied in simulation lab by measuring plant physiological indexes of chlorophyll content, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity based on a 2 × 4 factorial design with two epiphytic conditions (with epiphytic algae and without) and four levels of N and P concentrations in water (N-P[mg.L(-1)]: 0.5, 0.05; 2.5, 0.25; 4.5, 0.45; 12.5, 1.25). Compared with control (non-presence of epiphytic algae), chlorophyll contents of V. natans were significantly decreased (p algae under any concentrations of N and P in water bodies. While the presence of epiphytic algae induced peroxidation of membrane lipids, MDA contents of V. natans had significantly increased (p algae in the treatments of T2 and T3 in the whole culture process by comparing with control, sometimes reaching an extremely significant level (p algae (p algae on chlorophyll content and SOD activity in the leaves of V. natans were increased at first and then decreased with the concentrations of N and P in water, and MDA content became higher with the increase of N and P. concentrations. Repeated measurement data testing showed that the effects of epiphytic algae on the chlorophyll content and MDA content and SOD activity were significant, respectively (p algae were combining with effects of concentrations of N and P (p algae directly produced adverse effects on physiology of V. natans and epiphytic algal biomass were positively correlated with nutrient available in the water column.

Study on the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver

International Nuclear Information System (INIS)

Li Yuqiang; Niu Guoping

2006-01-01

Objective: To assess the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver. Methods: Serum TNF-α, IGF-I (with RIA) levels were examined in 44 patients with fatty liver and 30 controls. Ser- um levels of malondialdehyde (MDA), superoxidase (SOD) were measured with chemocolorimetry in these subjects. Results: Serum levels of TNF-α, IGF-I were significantly higher in patients with fatty liver than those in controls P<0.01 ), while the serum levels of MDA, SOD were significantly lower (P<0.01). Serum levels of IGF-I were negatively correlated with MDA levels ( r -0. 4132, P<0.05), TNF-α levels were positive correlated with MDA levels (r=0.4318, P<0.05). Conclusion: Lipid peroxidation was present in patients with fatty liver, with correlated changes of TNF-α and IGF-I levels. (authors)

Infectivity enhanced adenoviral-mediated mda-7/IL-24 gene therapy for ovarian carcinoma

NARCIS (Netherlands)

Leath, CA; Kataram, M; Bhagavatula, P; Gopalkrishnan, RV; Dent, P; Fisher, PB; Pereboev, A; Carey, D; Lebedeva, [No Value; Haisma, HJ; Alvarez, RD; Curiel, DT; Mahasreshti, PJ

Objective. Melanoma differentiation associated gene-7 [mda-7/interleukin (IL)-24] has been identified as a novel anti-cancer agent, which specifically induces apoptosis in cancer cells but not in normal epithelial, endothelial and fibroblast cells. The objective of this study was to evaluate the

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

Energy Technology Data Exchange (ETDEWEB)

Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

International Nuclear Information System (INIS)

Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

2012-01-01

Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin’s ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

Effects of Shenlong Decoction on Learning and Memory Abilities as well as SOD and MDA in Brain-aging Model Mice Induced by D-Galactose

Institute of Scientific and Technical Information of China (English)

Liu Yi; Wang Fawei; Yang Minghui; Zheng Qingping; Wang Youjing

2006-01-01

@@ Brain aging (dementia) model mice were made by cervical subcutaneous injection of D-galactose solution.Learning and memory abilities were detected with water maze test and superoxide dismulase(SOD)activities and malondiadehyde (MDA) contents in the liver and brain were determined after intragastrical administration of Shenlong Decoction (参龙汤) for 6 weeks. The results indicated that the swimming time was shortened and the correct swimming times increased, SOD activity raised and MDA content decreased in the three Shenlong Decoction groups with different doses as compared with the model group. It is concluded that Shenlong Decoction has the effects of anti-free radical injuries and improving the learning and memory abilities of the brain-aging mice induced by D-galactose.

Increase of hepatic nitric oxide levels in a nutritional model of fatty ...

African Journals Online (AJOL)

GREGORY

2010-08-30

Aug 30, 2010 ... (MDA) and protein carbonyl (PC), and also nitric oxide (NO) in over fed broiler breeder hens, 198 hens. (30 weeks old) .... The total protein in the liver tissue was determined by a method ... Table 1. Egg production and LHS in broiler breeder hens .... trations of nitric oxide metabolites (nitrates-nitrites) in rat.

Radioprotective effect of Haberlea rhodopensis (Friv.) leaf extract on gamma-radiation-induced DNA damage, lipid peroxidation and antioxidant levels in rabbit blood.

Science.gov (United States)

Georgieva, Svetlana; Popov, Borislav; Bonev, Georgi

2013-01-01

Different concentrations of H. rhodopensis total extract (HRE; 0.03, 0.06 and 0.12 g/kg body weight) were injected im, into rabbits 2 h before collecting the blood samples. The whole blood samples were exposed in vitro to 2.0 Gy 60Co gamma-radiation. The radiation-induced changes were estimated by using the chromosome aberration test (CA) and cytokinesis blocked micronucleus assay (CBMN) in peripheral lymphocytes, and by determining the malondialdehyde levels (MDA) in blood plasma and the superoxide dismutase (SOD) and catalase (CAT) activity in erythrocytes. Radiation significantly increased the chromosome aberration and micronuclei frequencies as well as MDA levels and decreased the antioxidant enzyme activity. On the other hand, the HRE pretreatment significantly decreased the CA, MN frequencies and MDA levels and increased the SOD and CAT activity in a concentration dependent manner. The most effective was the highest concentration of HRE (0.12 g/kg body weight). The results suggest that HRE as a natural product with a nantioxidant capacity could play a modulatory role against the cellular damage induced by gamma-irradiation. The possible mechanism involved in the radioprotective potential of HRE is discussed.

Radioprotective effect of Haberlea rhodopensis (Friv.) leaf extract on γ-radiation-induced DNA damage, lipid peroxidation and antioxidant levels in rabbit blood

International Nuclear Information System (INIS)

Georgieva, Svetlana; Bonev, Georgi; Popov, Borislav

2013-01-01

Different concentrations of H. rhodopensis total extract (HRE; 0.03, 0.06 and 0.12 g/kg body weight) were injected im, into rabbits 2 h before collecting the blood samples. The whole blood samples were exposed in vitro to 2.0 Gy 60 Co γ-radiation. The radiation-induced changes were estimated by using the chromosome aberration test (CA) and cytokinesis blocked micronucleus assay (CBMN) in peripheral lymphocytes, and by determining the malondialdehyde levels (MDA) in blood plasma and the superoxide dismutase (SOD) and catalase (CAT) activity in erythrocytes. Radiation significantly increased the chromosome aberration and micronuclei frequencies as well as MDA levels and decreased the antioxidant enzyme activity. On the other hand, the HRE pretreatment significantly decreased the CA, MN frequencies and MDA levels and increased the SOD and CAT activity in a concentration dependent manner. The most effective was the highest concentration of HRE (0.12 g/kg body weight). The results suggest that HRE as a natural product with an antioxidant capacity could play a modulatory role against the cellular damage induced by γ-irradiation. The possible mechanism involved in the radioprotective potential of HRE is discussed. (author)

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/tk-luc human breast cancer xenografts

Energy Technology Data Exchange (ETDEWEB)

Chang, Y.-F. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Lin, Y.-Y. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Wang, H.-E. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Nuclear Medicine Department, Veterans General Hospital, Taipei, Taiwan (China); Pang Fei [Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Hwang, J.-J. [Department of Radiological Sciences, National Yang-Ming University, 155, Sec. 2, Li-Nong Street, Pei-tou 112, Taipei, Taiwan (China)]. E-mail: jjhwang@ym.edu.tw

2007-02-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1-tk) and luciferase (luc). Both {sup 131}I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/tk-luc human breast cancer xenografts

International Nuclear Information System (INIS)

Chang, Y.-F.; Lin, Y.-Y.; Wang, H.-E.; Liu, R.-S.; Pang Fei; Hwang, J.-J.

2007-01-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1-tk) and luciferase (luc). Both 131 I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis

Lactulose mediates suppression of dextran sodium sulfate-induced colon inflammation by increasing hydrogen production.

Science.gov (United States)

Chen, Xiao; Zhai, Xiao; Shi, Jiazi; Liu, Wen Wu; Tao, Hengyi; Sun, Xuejun; Kang, Zhimin

2013-06-01

Molecular hydrogen (H2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H2 inducer, is digested by colon microflora and significantly increases H2 production, indicating its potential anti-inflammatory action. To evaluate the anti-inflammatory effects of lactulose on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were randomly assigned into seven groups, receiving regular distilled water, H2-rich saline (peritoneal injection), DSS, oral lactulose (0.1, 0.15, 0.2 ml/10 g, respectively), and lactulose (0.2 ml/10 g) + oral antibiotics. The mouse model of human ulcerative colitis was established by supplying mice with water containing DSS. The H2 breath test was used to determine the exhaled H2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), maleic dialdehyde (MDA) and marrow peroxidase (MPO) levels in colon lesions were evaluated. After 7 days, DSS-induced loss of body weight, increase of colitis score, shortening of colon length, pathological changes and elevated levels of TNF-α, IL-1β, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H2 production. Lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress in the colon, as measured by MDA and MPO, probably by increasing endogenous H2 production.

Going Concern Opinions and Management's Forward Looking Disclosures: Evidence from the MD&A

NARCIS (Netherlands)

Enev, M.; Geiger, Marshall; Gold, A.H.; Wallage, P.

In this study we examine the relationship between the auditor’s going concern opinion and management’s forward-looking disclosures in the Management’s Discussion and Analysis (MD&A) section of 10-K filings. The research objective is two-fold and addresses whether the presence of a going concern

Chemical hazard evaluation of material disposal area (MDA) B closure project

Energy Technology Data Exchange (ETDEWEB)

Laul, Jagdish C [Los Alamos National Laboratory

2010-04-19

TA-21, MDA-B (NES) is the 'contaminated dump,' landfill with radionuclides and chemicals from process waste disposed in 1940s. This paper focuses on chemical hazard categorization and hazard evaluation of chemicals of concern (e.g., peroxide, beryllium). About 170 chemicals were disposed in the landfill. Chemicals included products, unused and residual chemicals, spent, waste chemicals, non-flammable oils, mineral oil, etc. MDA-B was considered a High hazard site. However, based on historical records and best engineering judgment, the chemical contents are probably at best 5% of the chemical inventory. Many chemicals probably have oxidized, degraded or evaporated for volatile elements due to some fire and limited shelf-life over 60 yrs, which made it possible to downgrade from High to Low chemical hazard site. Knowing the site history and physical and chemical properties are very important in characterizing a NES site. Public site boundary is only 20 m, which is a major concern. Chemicals of concern during remediation are peroxide that can cause potential explosion and beryllium exposure due to chronic beryllium disease (CBD). These can be prevented or mitigated using engineering control (EC) and safety management program (SMP) to protect the involved workers and public.

Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

International Nuclear Information System (INIS)

Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

2005-01-01

A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables

Study of the Role of siRNA Mediated Promoter Methylation in DNMT3B Knockdown and Alteration of Promoter Methylation of CDH1, GSTP1 Genes in MDA-MB -453 Cell Line.

Science.gov (United States)

Naghitorabi, Mojgan; Mir Mohammad Sadeghi, Hamid; Mohammadi Asl, Javad; Rabbani, Mohammad; Jafarian-Dehkordi, Abbas

2017-01-01

Promoter methylation is one of the main epigenetic mechanisms that leads to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifically knock down the DNMTs at mRNA level. Also many studies have focused on transcriptional gene silencing in mammalian cells via siRNA mediated promoter methylation. The present study was designed to assess the role of siRNA mediated promoter methylation in DNMT3B knockdown and alteration of promoter methylation of Cadherin-1 (CDH1), Glutathione S-Transferase Pi 1(GSTP1), and DNMT3B genes in MDA-MB-453 cell line. MDA-MB-453 cells were transfected with siDNMT targeting DNMT3B promoter and harvested at 24 and 48 h post transfection to monitor gene silencing and promoter methylation respectively. DNMT3B expression was monitored by quantitative RT-PCR method. Promoter methylation was quantitatively evaluated using differential high resolution melting analysis. A non-significant 20% reduction in DNMT3B mRNA level was shown only after first transfection with siDNMT, which was not reproducible. Promoter methylation levels of DNMT3B, CDH1, and GSTP1 were detected at about 15%, 70% and 10% respectively, in the MDA-MB-453 cell line, with no significant change after transfection. Our results indicated that siDNMT sequence were not able to affect promoter methylation and silencing of DNMT3B in MDA-MB-453 cells. However, quantitation of methylation confirmed a hypermethylated phenotype at CDH1 and GSTP1 promoters as well as a differential methylation pattern at DNMT3B promoter in breast cancer.

Impaired inflammatory response and increased oxidative stress and neurodegeneration after brain injury in interleukin-6-deficient mice

DEFF Research Database (Denmark)

Penkowa, M; Giralt, M; Carrasco, J

2000-01-01

of the antioxidants Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, and catalase remained unaffected by the IL-6 deficiency. The lesioned mice showed increased oxidative stress, as judged by malondialdehyde (MDA) and nitrotyrosine (NITT) levels and by formation of inducible nitric oxide synthase (iNOS). IL-6KO mice...

Serum telomerase levels in smokers and smokeless tobacco users as Maras powder.

Science.gov (United States)

Bozkuş, Fulsen; Atilla, Nurhan; Şimşek, Seçil; Kurutaş, Ergül; Samur, Anıl; Arpağ, Hüseyin; Kahraman, Hasan

2017-09-01

To the best of our knowledge, no previous study regarding the serum telomerase levels in Maras powder users (MPUs) has been founded. The aim of the current study was to investigate serum telomerase levels in smokers and MPUs. The study was carried out with 98 patients (36 MPUs, 32 smokers and 30 non-smokers). Blood samples were collected, and after having measured the serum telomerase and malondialdehyde (MDA) levels of the patients, comparison were made between the groups. It has been observed that the serum telomerase and MDA levels of smokers (pnon-smoker control subjects. In addition, the levels of serum telomerase and MDA were observed to be higher in the MPU group compared to those of the smoker group (psmokers. In this context, it may be useful to further measure and assess telomerase activity in such patients in order to better determine the harmful effects associated with these habits.

Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

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Kristen Ashley eHorner

2011-05-01

Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

Irradiation effect on the seed vigor, SOD activity and MDA content in germinating seeds of yellow-seeded and black-seeded rape seed (Brassica napus L.)

International Nuclear Information System (INIS)

Han Jixiang; Hu Danhong; Liu Houli

1993-01-01

Seeds of a set of near-isogenic lines (Brassica napus L.) with different seed coat color from yellow to black were irradiated by 60 Co γ-rays of 150 krad. Seed vigor, superoxide dismutase (SOD) and malondialdehyde (MDA) in germinating seeds were analysed. In these characters, no significant difference between yellow-seeded lines (YLs) and black-seeded lines (BLs) showed before irradiation. But after irradiation, SOD activity in YLs was lower than that in BLs. While MDA content in YLs was obviously higher that that in DLs. As a result of irradiation, seed vigor of YLs was lower than that in BLs. these results indicated that the irradiation resistance of rape seed was related to the level of SOD as well as protective structure or substances in seed coat and that the radiosensitivity of YLs was higher than that of DLs

Effects of exosomes derived from MDA-MB-231 on proliferation of endothelial cells and the role of MAPK/ERK and PI3K/Akt pathways

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Shuang LONG

2012-11-01

Full Text Available Objective 　To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on proliferation of human umbilical cord vein endothelial cells (HUVECs, and evaluate the role of MAPK/ERK and PI3K/Akt signal transduction pathway during the process. Methods 　Exosomes were derived and purified from MDA-MB-231 by cryogenic ultracentrifugation and density gradient centrifugation. MTT assay was carried out for measurement of cell proliferation in HUVECs with exosome of 50, 100, 200 and 400μg/ml. The states of cell cycle of HUVECs co-cultured with 200μg/ml exosomes were detected by flow cytometry. The effects of 200μg/ml exosomes on the expression of ERK, Akt and phosphorylated ERK, Akt in HUVECs were detected with Western blotting. Results 　Exosomes derived from MDA-MB-231 significantly promoted HUVECs proliferation in a classical time-and dose-dependent manner. Flow cytometry revealed that, co-cultured with 200μg/ml exosomes for 24h, S-phase cells in HUVECs increased, while G1/S phase cells in HUVECs decreased. Western blotting showed that, cocultured with 200μg/ml exosomes for 24h, 48h and 72h, the expressions of phosphorylated ERK and Akt were up-regulated in a time-dependent manner. Conclusion 　Exosomes derived from breast cancer cell line MDA-MB-231 may promote HUVECs proliferation, the changes in cell cycle and the continuous activation of the MAPK/ERK and PI3K/Akt signal transduction pathways may be the underlying mechanism.

Local and systemic oxidative stress and glucocorticoid receptor levels in chronic obstructive pulmonary disease patients

Science.gov (United States)

Zeng, Mian; Li, Yue; Jiang, Yujie; Lu, Guifang; Huang, Xiaomei; Guan, Kaipan

2013-01-01

BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients. PMID:23457673

Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with β-thalassemia major.

Science.gov (United States)

Mirlohi, Maryam Sadat; Yaghooti, Hamid; Shirali, Saeed; Aminasnafi, Ali; Olapour, Samaneh

2018-04-01

The impaired biosynthesis of the β-globin chain in β-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major β-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in β-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the β-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P overload in β-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of β-thalassemia major.

Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus.

Science.gov (United States)

Kotla, Swathi; Gustin, Kurt E

2015-10-06

The type I interferon (IFN) response is a critical component of the innate immune response to infection by RNA viruses and is initiated via recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of these receptors in the cytoplasm initiates a signal transduction pathway leading to activation of the transcription factors NF-κB, ATF-2 and IRF-3 that coordinately upregulate transcription of type I IFN genes, such as that encoding IFN-β. In this study the impact of poliovirus infection on the type I interferon response has been examined. The type I IFN response was assessed by measuring IFN-β mRNA levels using qRT-PCR and normalizing to levels of β-actin mRNA. The status of host factors involved in activation of the type I IFN response was examined by immunoblot, immunofluorescence microcopy and qRT-PCR. The results show that poliovirus infection results in induction of very low levels of IFN-β mRNA despite clear activation of NF-κB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected cells to poly(I:C) results in lower levels of IFN-β mRNA synthesis and IRF-3 activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed that these components of the RLR pathway were largely intact at times when the type I IFN response was suppressed. Collectively, these results demonstrate that poliovirus infection actively suppresses the host type I interferon response by blocking activation of IRF-3 and suggests that this is not mediated by cleavage of MDA-5 or IPS-1.

Expression and Functional Characterization of the RIG-I-Like Receptors MDA5 and LGP2 in Rainbow Trout (Oncorhynchus mykiss) ▿ †

Science.gov (United States)

Chang, Mingxian; Collet, Bertrand; Nie, Pin; Lester, Katherine; Campbell, Scott; Secombes, Christopher J.; Zou, Jun

2011-01-01

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) comprise three homologues: RIG-I, melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). They activate the host interferon (IFN) system upon recognition of viral RNA pathogen-associated molecular patterns (PAMPs) in the cytoplasm. Bioinformatic analysis of the sequenced vertebrate genomes suggests that the cytosolic surveillance system is conserved in lower vertebrates, and recent functional studies have confirmed that RIG-I is important to fish antiviral immunity. In this study, we have identified MDA5 and LGP2 homologues from rainbow trout Oncorhynchus mykiss and an additional LGP2 variant with an incomplete C-terminal domain of RIG-I. Trout MDA5 and LGP2 were constitutively produced in fibroblast and macrophage cell lines and upregulated by poly(I:C), recombinant IFN, or infection by RNA viruses (viral hemorrhagic septicemia virus and salmon alphavirus) with a single-stranded positive or negative genome. Overexpression of MDA5 and LGP2 but not of the LGP2 variant resulted in significant accumulation of Mx transcripts in cultured cells, which correlated with a marked enhancement of protection against viral infection. These results demonstrate that both MDA5 and LGP2 are important RLRs in host surveillance against infection of both negative and positive viruses and that the LGP2 variant with a deletion of 54 amino acids at the C terminus acts as a negative regulator for LGP2-elicited antiviral signaling by competing for the viral RNA PAMPs. Interestingly, MDA5 expression was not affected by overexpressed LGP2 in transfected cells and vice versa, suggesting that they likely act in parallel as positive regulators for IFN production. PMID:21680521

Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

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Amanda L. Peterson

2016-09-01

Full Text Available Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect—an increase in glycolytic activity at the expense of oxidative phosphorylation—and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

A HIGHER PROPORTION OF PUFA IN DIET INCREASES THE PUFA CONTENT IN RABBIT MEAT, BUT REDUCES THE OXIDATIVE STABILITY OF MEAT

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Tina Trebušak

2015-09-01

Full Text Available The aim of our study was to determine the changes in the fatty acid composition of rabbit meat, if palm fat (99% of saturated fatty acids (SFA, as a source of fat in rabbit diet, was replaced with linseed oil (71% of polyunsaturated fatty acids (PUFA, containing 52% of α-linolenic acid (n-3 PUFA. The Ganoderma lucidum or olive leaves were added in the diet as potential antioxidant in order to protect the PUFA against oxidation. 48 SIKA rabbits were randomly divided by mass and gender in four groups: CONT- 6% palm fat, CONT+ 6% linseed oil, REISHI 6% linseed oil and 1% Ganoderma lucidum, OLIVE 6% linseed oil and 1% olive leaves. After 22 days of the experimental procedure, the samples of back muscle were taken and divided in 7 portions. One was for fatty acid determination, other six for malondialdehyde (MDA determination after different storage condition; fresh, 6 days at 4°C or 3 months at -20°C, raw or cooked (60 minutes, 85°C. Addition of linseed oil resulted in a significant higher proportion of PUFA (n-3 PUFA and monounsaturated fatty acid (MUFA and lower proportion of SFA in the back muscle, but the oxidative stability of meat was reduced, since the level of MDA was significantly higher. After cooking, the level of MDA increased in all the groups, but more in the groups with linseed oil in the diet, the addition of Ganoderma lucidum or olive leaves slightly decreased the level of MDA, but the difference was not significant.

Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

Energy Technology Data Exchange (ETDEWEB)

Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

2017-03-15

A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.

Morbillivirus control of the interferon response: relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets.

Science.gov (United States)

Svitek, Nicholas; Gerhauser, Ingo; Goncalves, Christophe; Grabski, Elena; Döring, Marius; Kalinke, Ulrich; Anderson, Danielle E; Cattaneo, Roberto; von Messling, Veronika

2014-03-01

The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus Morbillivirus interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties. The V proteins of paramyxoviruses interfere with the recognition of the virus by the immune system of the host. For morbilliviruses, the V protein is known to interact with the signal transducer and activator of transcription 1 (STAT1) and STAT2 and the melanoma differentiation-associated protein 5 (mda5), which are involved in interferon signaling. Here, we examined the contribution of each of these signaling pathways to the pathogenesis of the carnivore morbillivirus canine distemper virus. Using viruses selectively unable to interfere with the respective signaling pathway to infect ferrets, we found that

Enfoque MDA para el diseño de un data warehouse difuso A model driven approach for fuzzy data warehouse design

Directory of Open Access Journals (Sweden)

Carolina Zambrano Matamala

2012-04-01

development life cycle are considered different methodologies and models that have the disadvantage that do not integrate the different levels of abstraction or the DW design process. However, MDA is an alternative approach to integration for the development of DW as it gives a comprehensive development framework based on the architecture of models and transformations between different levels of abstraction. This article presents a Fuzzy MDA approach to design fuzzy measures, fuzzy relations and fuzzy levels. For which we propose a Fuzzy OLAP CWM metamodel, QVT rules and an example of rule. Is the sequence methodology for applying the rules QVT. Finally, it provides a case study analysis in the field of education.

Mentha arvensis (Linn.-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells

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Banerjee PP

2017-04-01

exhibited significant cytotoxicity toward breast cancer cells (MCF7 and MDA-MB-231, which were at par with that of CSNPs. Cell cycle analyses of MCF7 cells revealed a significant increase in sub-G1 cell population, indicating cytotoxicity of GSNPs. On the other hand, human peripheral blood lymphocytes showed significantly less cytotoxicity compared with MCF7 and MDA-MB-231 cells when treated with the same dose. Expression patterns of proteins suggested that GSNPs triggered caspase 9-dependent cell death in both cell lines. The Ames test showed that GSNPs were nonmutagenic in nature. Conclusion: GSNPs synthesized using Mentha arvensis may be considered as a promising anticancer agent in breast cancer therapy. They are less toxic and nonmutagenic and mediate caspase 9-dependent apoptosis in MCF7 and MDA-MB-231 cells. Keywords: nanoparticles, EDX, TEM, breast cancer cells, anticancer, nonmutagenic 

BETULINIC ACID WAS MORE CYTOTOXIC TOWARDS THE HUMAN BREAST CANCER CELL LINE MDA-MB-231 THAN THE HUMAN PROMYELOCYTIC LEUKAEMIA CELL LINE HL-60

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LATIFAH SAIFUL YAZAN

2009-01-01

Full Text Available Betulinic acid (BA is a pentacyclic triterpene found in several botanical sources that has been shown to cause apoptosis in a number of cell lines. This study was undertaken to determine the in vitro cytotoxic properties of BA towards the human mammary carcinoma cell line MDA-MB-231 and the human promyelocytic leukaemia cell line HL-60 and the mode of the induced cell death. The cytotoxicity and mode of cell death of BA were determined using the MTT assay and DNAfragmentation analysis, respectively. In our study, the compound was found to be cytotoxic to MDA-MB-231 and HL-60 cells with IC50 values of 58 μg/mL and 134 μg/mL, respectively. Cells treated with high concentrations of BA exhibited features characteristic of apoptosis such as blebbing, shrinking and a number of small cytoplasm body masses when viewed under an inverted light microscope after 24 h. The incidence of apoptosis in MDA-MB-231 was further confirmed bythe DNA fragmentation analysis, with the formation of DNA fragments of oligonucleosomal size (180-200 base pairs, giving a ladder-like pattern on agarose gel electrophoresis. BA was more cytotoxic towards MDA-MB-231 than HL-60 cells, and induced apoptosis in MDA-MB-231 cells.

La Arquitectura de Software en el Proceso de Desarrollo: Integrando MDA al Ciclo de Vida en Espiral

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Valeria S. Meaurio

2013-08-01

Full Text Available En la actualidad el desarrollo de software debe enfrentarse a una serie de problemas, por ejemplo, la rapidez con que el software debe estar disponible para su uso, el alto grado de evolución de los sistemas actuales y el nivel de complejidad de los mismos, entre otros. Contar con un modelo de la arquitectura en etapas tempranas se hace evidente, puesto que anticiparnos a la especificación detallada del sistema nos permite contar con un modelo de alto nivel de la alternativa de solución a los requerimientos planteados, que en sucesivos refinamientos conducirán al producto final. En vistas de estos problemas la propuesta de la OMG arquitectura dirigida por modelos (Model Driven Architecture - MDA propone la construcción de software como la trasformación sucesiva de modelos, desde un alto nivel de abstracción hasta el nivel de implementación en una plataforma concreta. El objetivo del presente trabajo propone aplicar el modelo MDA dentro del ciclo de vida en espiral propuesto por Bohem a fin de establecer el impacto de la arquitectura de software en las distintas etapas de este ciclo de vida y como MDA minimiza el riesgo.

Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.

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Marinello, Poliana Camila; da Silva, Thamara Nishida Xavier; Panis, Carolina; Neves, Amanda Fouto; Machado, Kaliana Larissa; Borges, Fernando Henrique; Guarnier, Flávia Alessandra; Bernardes, Sara Santos; de-Freitas-Junior, Júlio Cesar Madureira; Morgado-Díaz, José Andrés; Luiz, Rodrigo Cabral; Cecchini, Rubens; Cecchini, Alessandra Lourenço

2016-04-01

The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 μM) and experimental concentrations of metformin (1000 and 5000 μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.

Analysis of Protein–Protein Interactions in MCF-7 and MDA-MB-231 Cell Lines Using Phthalic Acid Chemical

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Shih-Shin Liang

2014-11-01

Full Text Available Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein–protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES. Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively.

Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

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Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

2013-05-10

Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by Targeting MDA5 and RIG-I

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Chunyuan Zhao

2017-11-01

Full Text Available Retinoic acid-inducible gene-I (RIG-I-like receptors (RLRs, including melanoma differentiation-associated gene 5 (MDA5 and RIG-I, are crucial for host recognition of non-self RNAs, especially viral RNA. Thus, the expression and activation of RLRs play fundamental roles in eliminating the invading RNA viruses and maintaining immune homeostasis. However, how RLR expression is tightly regulated remains to be further investigated. In this study, we identified a major histocompatibility complex (MHC-encoded gene, tripartite interaction motif 40 (TRIM40, as a suppressor of RLR signaling by directly targeting MDA5 and RIG-I. TRIM40 binds to MDA5 and RIG-I and promotes their K27- and K48-linked polyubiquitination via its E3 ligase activity, leading to their proteasomal degradation. TRIM40 deficiency enhances RLR-triggered signaling. Consequently, TRIM40 deficiency greatly enhances antiviral immune responses and decreases viral replication in vivo. Thus, we demonstrate that TRIM40 limits RLR-triggered innate activation, suggesting TRIM40 as a potential therapeutic target for the control of viral infection.

Mild and selective labeling of malondialdehyde with 2-Aminoacridone: assessment of urinary malondialdehyde levels.

NARCIS (Netherlands)

Giera, M.; Kloos, D.-P.; Raaphorst, A.; Mayboroda, O.A.; Deelder, A.M.; Lingeman, H.; Niessen, W.M.A.

2011-01-01

Malondialdehyde (MDA) has become a well-established biomarker for oxidative stress. The most commonly used way to determine urinary MDA levels is the thiobarbituric acid (TBA) assay, which suffers from several drawbacks. In this manuscript, we describe a novel derivatization strategy for the highly

Tobacco expressing pap1 increases the responses to par and uv-a by enhancing soluble sugars and flavonoids and elevating plant protections

International Nuclear Information System (INIS)

Sompornpailin, K.; Kanthang, S.

2015-01-01

Five lines of transgenic tobacco over-expressing Production of Anthocyanin Pigment 1 (PAP1) cDNA were analysis of metabolic response against the radiation and their protection of the plant under tissue culture condition. PAP1 transgenic and wild type (WT) plants were treated with the radiations of photosynthetically activate radiation (PAR) or PAR combined with UV-A. All lines of transgenic significantly increased in amounts of p-coumaric acid, naringenin apigenin more than WT under both treatments. Additional UV-A radiating to plant rose up kaempferol content in WT plant (1.5 times) and in PAP1 transgenics (1.8 times). These transgenic plants treated under both conditions had also increased anthocyanin substances (pelargonidin) with significant value after compared to WT. Content of total soluble sugar (TSS) was related to the content of total flavonoids in transgenic. PAR combined with UV-A had a lower induction of the electrolyte leakage percentage and malondialdehyde (MDA) level in the transgenic leaf tissue compared to WT tissue. The metabolic substance levels were considered on its protection of plant cells. In transgenic tissue, the enhancement of apigenin level strongly diminished the increase level of electrolyte leakage while the levels of TSS, p-coumaric acid and naringinin less affected. Moreover, the increase levels of kaempferol and pelargonidin associated with the decrease level of MDA, while the TSS level reversely responded. The PAP1 transgenic increased response of light by adaptation of their metabolites (TSS, p-coumaric acid and flavonoids) consequently enhance parameter indicating protections of the cell. (author)

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

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Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

2009-08-01

The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Interrelation of androgen receptor and miR-30a and miR-30a function in ER-, PR-, AR+ MDA-MB-453 breast cancer cells.

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Lyu, Shuhua; Liu, Han; Liu, Xia; Liu, Shan; Wang, Yahong; Yu, Qi; Niu, Yun

2017-10-01

The association between androgen-induced androgen receptor (AR) activating signal and microRNA (miR)-30a was investigated, as well as the function of miR-30a in estrogen receptor-negative (ER - ), progesterone receptor-negative (PR - ), and AR-positive (AR + ) MDA-MB-453 breast cancer cells. Androgen-induced AR activating signal upregulated the expression of AR, and downregulated the expression of miR-30a, b and c. Bioinformatics analysis indicated a putative miR-30a, b and c binding site in the 3'-untranslated region of AR mRNA. It was confirmed that the AR gene is a direct target of miR-30a, whereas AR does not target the miR-30a promoter, and AR activating signal may indirectly downregulate miR-30a through other cell signaling pathways. In this positive feedback mechanism AR is then upregulated through miR-30a. Overexpression of miR-30a inhibited cell proliferation, whereas inhibition of miR-30a expression by specific antisense oligonucleotides, increased cell growth. Previously, androgen-induced AR activating signal was demonstrated to inhibit cell proliferation in ER - , PR - and AR + MDA-MB-453 breast cancer cells, but AR activating signal downregulated the expression of miR-30a, relieving the inhibition of MDA-MB-453 cell growth. Therefore, in MDA-MB-453 breast cancer cells, miR-30a has two different functions regarding cell growth: Inhibition of cell proliferation through a positive feedback signaling pathway; and the relative promotion of cell proliferation through downregulation of miR-30a. Thus, the association between AR activating signal and microRNAs is complex, and microRNAs may possess different functions due to different signaling pathways. Although the results of the present study were obtained in one cell line, they contribute to subsequent studies on ER - , PR - and AR + breast cancer.

Study of Serum Malondialdehyde Level in Opioid and Methamphetamine Dependent Patients

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Khadije Najafi

2017-12-01

Full Text Available Opioid compound and methamphetamine are commonly used in drug abuse; these can disrupt the normal function of cellular and molecular systems, leading to several events such as oxidative stress, aging, apoptosis, and necrosis. Malondialdehyde (MDA is the most important biomarker for evaluation of oxidative stress and determination of lipid peroxidation. In this study, 42 drug abusers and 22 healthy persons participated as case and control groups, respectively. MDA in volunteer sera was determined by high-performance liquid chromatography (HPLC with fluorescence detection after pre-column derivatization using thiobarbituric acid. The analysis was performed on a ODS column by spectrofluorometer detection, operated at excitation of 515 nm and emission of 535 nm. A mixture of phosphate buffer (0.05 M, pH 6.8, containing potassium monobasic phosphate and methanol (60:40, v/v at a flow rate of 1 ml/min, was used as the mobile phase. The retention time of MDA-TBA was 3.2 min. Our findings showed that the MDA level increased in the opioid and methamphetamine abusers when compared to the control group (P<0.05; however, no significant difference was observed between the opioid and methamphetamine groups. A state of oxidative stress during biological processes leads to lipid peroxidation, DNA damage, biomolecule dysfunctions, and many other diseases. Since it is impossible to eradicate the drug addiction, we should reduce the side effects of drug abuse, such as oxidative stress, by intake of proper nutrition and antioxidants.

Effects of low-level exposure to xenobiotics present in paints on oxidative stress in workers.

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Moro, Angela M; Charão, Mariele; Brucker, Natália; Bulcão, Rachel; Freitas, Fernando; Guerreiro, Gilian; Baierle, Marília; Nascimento, Sabrina; Waechter, Fernanda; Hirakata, Vânia; Linden, Rafael; Thiesen, Flávia V; Garcia, Solange Cristina

2010-09-15

Paints are composed of an extensive variety of hazardous substances, such as organic solvents and heavy metals. Biomonitoring is an essential tool for assessing the risk to occupational health. Thus, this study analyzed the levels of biomarkers of exposure for toluene, xylene, styrene, ethylbenzene, and lead, as well as the oxidative stress biomarker alterations in painters of an industry. Lipid peroxidation biomarker (MDA), delta-aminolevulinate dehydratase (ALA-D), nonprotein thyol groups, superoxide dismutase and catalase (CAT) were analyzed in exposed and nonexposed subjects. We estimated which of the paint constituents have the greatest influence on the changes in the biomarkers of oxidative stress in this case of co-exposure. The results demonstrated that despite the fact that all the biomarkers of exposure were below the biological exposure limits, the MDA levels and antioxidant enzyme activities were increased, while nonprotein thyol groups and ALA-D levels were decreased in painters when compared with nonexposed subjects. After statistic test, toluene could be suggested as the principal factor responsible for increased lipid peroxidation and inhibition of ALA-D enzyme; however, further studies on the inhibition of ALA-D enzyme by toluene are necessary. Copyright 2010 Elsevier B.V. All rights reserved.

Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

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Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

2017-03-01

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies. Creative Commons Attribution License

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].

Science.gov (United States)

Yuan, Lei; Fan, Wen-Juan; Yang, Xu-Guang; Rao, Shu-Mei; Song, Jin-Ling; Song, Guo-Hua

2013-10-25

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

Elevated CO_2 levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem

International Nuclear Information System (INIS)

Yin, Ying; Hu, Zhengxue; Du, Wenchao; Ai, Fuxun; Ji, Rong; Gardea-Torresdey, Jorge L.; Guo, Hongyan

2017-01-01

Highlights: • Elevated CO_2 increased the Zn content in suspension by reducing pH value. • Elevated CO_2 led to higher Zn accumulation in fish tissues. • Elevated CO_2 also intensified the oxidative damage to fish induced by nZnO. - Abstract: Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO_2 levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO_2 to the ecosystem. Here we studied the toxicity of nZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400 ± 10 μL/L) or elevated (600 ± 10 μL/L) CO_2 for 30 days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO_2 increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of nZnO. Elevated CO_2 led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO_2 also intensified the oxidative damage to fish induced by nZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO_2 levels.

Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

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Youn Kyung Choi

2014-01-01

Full Text Available Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

Baseline geochemistry of soil and bedrock Tshirege Member of the Bandelier Tuff at MDA-P

International Nuclear Information System (INIS)

Warren, R.G.; McDonald, E.V.; Ryti, R.T.

1997-08-01

This report provides baseline geochemistry for soils (including fill), and for bedrock within three specific areas that are planned for use in the remediation of Material Disposal Area P (MDA-P) at Technical Area 16 (TA-16). The baseline chemistry includes leachable element concentrations for both soils and bedrock and total element concentrations for all soil samples and for two selected bedrock samples. MDA-P operated from the early 1950s to 1984 as a landfill for rubble and debris generated by the burning of high explosives (HE) at the TA-16 Burning Ground, HE-contaminated equipment and material, barium nitrate sand, building materials, and trash. The aim of this report is to establish causes for recognizable chemical differences between the background and baseline data sets. In many cases, the authors conclude that recognizable differences represent natural enrichments. In other cases, differences are best attributed to analytical problems. But most importantly, the comparison of background and baseline geochemistry demonstrates significant contamination for several elements not only at the two remedial sites near the TA-16 Burning Ground, but also within the entire region of the background study. This contamination is highly localized very near to the surface in soil and fill, and probably also in bedrock; consequently, upper tolerance limits (UTLs) calculated as upper 95% confidence limits of the 95th percentile are of little value and thus are not provided. This report instead provides basic statistical summaries and graphical comparisons for background and baseline samples to guide strategies for remediation of the three sites to be used in the restoration of MDA-P

THE USE OF MULTIPLE DISPLACEMENT AMPLIFICATION TO INCREASE THE DETECTION AND GENOTYPING OF TRYPANOSOMA SPECIES SAMPLES IMMOBILISED ON FTA FILTERS

Science.gov (United States)

MORRISON, LIAM J.; McCORMACK, GILLIAN; SWEENEY, LINDSAY; LIKEUFACK, ANNE C. L.; TRUC, PHILIPPE; TURNER, C. MICHAEL; TAIT, ANDY; MacLEOD, ANNETTE

2007-01-01

Whole genome amplification methods are a recently developed tool for amplifying DNA from limited template. We report its application in trypanosome infections, characterised by low parasitaemias. Multiple Displacement Amplification (MDA) amplifies DNA with a simple in vitro step, and was evaluated on mouse blood samples on FTA filter cards with known numbers of Trypanosoma brucei parasites. The data showed a twenty-fold increase in the number of PCRs possible per sample, using primers diagnostic for the multi-copy ribosomal ITS region or 177 bp repeats, and a twenty-fold increase in sensitivity over nested PCR against a single copy microsatellite. Using MDA for microsatellite genotyping caused allele dropout at low DNA concentrations, which was overcome by pooling multiple MDA reactions. The validity of using MDA was established with samples from Human African Trypanosomiasis patients. The use of MDA allows maximal use of finite DNA samples and may prove a valuable tool in studies where multiple reactions are necessary, such as population genetic analyses. PMID:17556624

The Effect of Histone Hyperacetylation on Viability of Basal-Like Breast Cancer Cells MDA-MB-231

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Aliasghar Rahimian

2017-06-01

Full Text Available Background The Basal-Like breast cancer, is always known for lack of expression of estrogen receptor (ER, progesterone receptor (PR and as well, absence of epidermal growth factor receptor 2 (HER2 gene amplification. Improper expression pattern of ER, PR, and Her2, makes Basal-Like breast tumors resistant to the current hormonal and anti HER2 treatments. In recent decades, several studies have been conducted to investigate the regulatory role of chemical modifications of core histones in gene expression. Their results have shown that histone acetylation is involved in regulation of cell survival. Acetylation of core histones is regulated by the epigenetic-modifying enzymes named Histone Deacetylases (HDACs. As a new approach to control the viability of breast tumor cells resistant to the hormonal and anti-HER2 treatments, we have targeted the HDACs. Using Trichostatin A (TSA as a known HDACs inhibitor, we have tried to hyperacetylate the core histones of MDA-MB-231 cells as an in vitro model of Basal-Like breast tumors. Then we have investigated the effect of histone hyperacetylation on viability of MDA-MB-231 cells. Methods MDA-MB-231 cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum (FBS and were incubated at 37°C, in a humidified incubator with 5% CO2 atmosphere. Then cells were treated with different concentrations of TSA including: 50, 100, 200, 400, 800 and 1000 nM or control (1% DMSO. After 24 and 48 hours, viability of cells was evaluated by MTT assay. Results After 24 and 48h exposure to different concentrations of TSA, MDA-MB-231 cells showed a maximum tolerable dose. At higher concentrations, TSA decreased the percentage of cell viability through a time-dose dependent manner. IC50 value for 48h treatment was 600 nM. Conclusions Our results indicate that HDACs inhibition and subsequently hyperacetylation of histones, leads to cytotoxic effects on breast tumor cells resistant to the current treatments. Following

Oxidative Stress and Genotoxicity of Long-Term Occupational Exposure to Low Levels of BTEX in Gas Station Workers

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Feng Xiong

2016-12-01

Full Text Available Atmospheric benzene, toluene, ethylbenzene, and xylenes (BTEX can lead to multiple health injuries. However, what remains uncertain is the effect of long-term exposure to low levels of BTEX. Thus, we determined the BTEX levels in the air from the refueling and office areas in gas stations. Then we collected workers’ (200 refueling vs. 52 office workers peripheral blood samples to analyze the serum total-superoxide dismutase (T-SOD, glutathione (GSH, malondialdehyde (MDA, and 8-hydroxydeoxyguanosine (8-OHdG levels. DNA damage was analyzed by the comet assay and micronucleus test in buccal epithelial cells. We found that the levels of BTEX in refueling areas were significantly higher than those in office areas (p < 0.001. The serum T-SOD and GSH of refueling workers were significantly lower than those in office workers (p < 0.001. By contrast, the serum MDA and 8-OHdG of refueling workers were significantly higher than those of office workers (p < 0.001, MDA; p = 0.025, 8-OHdG. Furthermore, tail and Olive tail moments in refueling workers were longer (p = 0.004, tail moment; p = 0.001, Olive tail moment, and the micronucleus rate was higher (p < 0.001 than those in office workers. Taken together, long-term exposure to low levels of BTEX may reduce the antioxidant ability and increase the risk of DNA damage in refueling workers of gas stations.

Estimation of malondialdehyde levels in serum and saliva of children affected with sickle cell anemia

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Sudhindra Baliga

2018-01-01

Full Text Available Background: Sickle cell anemia (SCA is an inherited disorder of hemoglobin synthesis characterized by deformed erythrocytes. Hemoglobin S present in sickle-shaped erythrocytes exhibits an enhanced rate of auto-oxidation compared with normal hemoglobin A. It produces more of reactive oxygen species (ROS which promotes oxidatively stressed environment. ROS degrade the membranes of sickle cell erythrocytes composed of polyunsaturated lipids and form malondialdehyde (MDA as a by-product. Aim: The aim of the study is to evaluate and compare the MDA levels of serum and saliva in SCA patients. Design: A total of 150 children aged 4–12 years were divided into two groups: Group A (n = 75 consisting of children suffering from SCA and Group B (n = 75 consisting of healthy children. Blood and saliva samples were collected aseptically from both the groups, and they were subjected to thiobarbituric acid assay. Absorbance was evaluated spectrophotometrically at 531 nm, and the values of concentration of MDA were derived. Results: The mean MDA levels in serum and saliva were 8.9825 ± 1.04 and 0.5152 ± 0.28, respectively, in Group A and they were found to be higher than mean MDA levels of serum (5.87 ± 0.92 and saliva (0.2929 ± 0.06 of Group B and the difference of their mean was found to be statistically significant. Conclusion: A significant correlation of the MDA was found in saliva and serum of the patients with SCA. This finding suggests that saliva can be effectively used as a noninvasive alternative for assessing the oxidative stress in patients with SCA.

Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

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Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

2016-01-01

Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

Elevated CO{sub 2} levels increase the toxicity of ZnO nanoparticles to goldfish (Carassius auratus) in a water-sediment ecosystem

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Yin, Ying; Hu, Zhengxue [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Du, Wenchao, E-mail: du@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Ai, Fuxun; Ji, Rong [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China); Gardea-Torresdey, Jorge L. [Department of Chemistry, The University of Texas at El Paso, El Paso, TX 79968 (United States); Environmental Science and Engineering PhD program, The University of Texas at El Paso, El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN), The University of Texas at El Paso, El Paso, TX 79968 (United States); Guo, Hongyan, E-mail: hyguo@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210046 (China)

2017-04-05

Highlights: • Elevated CO{sub 2} increased the Zn content in suspension by reducing pH value. • Elevated CO{sub 2} led to higher Zn accumulation in fish tissues. • Elevated CO{sub 2} also intensified the oxidative damage to fish induced by nZnO. - Abstract: Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO{sub 2} levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO{sub 2} to the ecosystem. Here we studied the toxicity of nZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400 ± 10 μL/L) or elevated (600 ± 10 μL/L) CO{sub 2} for 30 days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO{sub 2} increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of nZnO. Elevated CO{sub 2} led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO{sub 2} also intensified the oxidative damage to fish induced by nZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO{sub 2} levels.

Apoptotic potential of two Caryophyllaceae species in MCF-7 and MDA-MB-468 cell lines

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M. Mosaddegh

2018-01-01

Full Text Available Background and objectives: Plants have been used to treat diseases like cancer for many years and today the trend towards their use is increasing. One of the most effective mechanisms of plants against cancer is inducing apoptosis. Apoptosis is a programmed cell death which acts opposite to cell division. It starts in response to some stimuli. Despite the effectiveness of apoptosis inducing agents, their use has been limited due to side effects and resistance to these treatments; so, applying medicinal herbs due to their lower cost and toxicity has drawn attentions. Recent research at the Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences on two medicinal plants Acanthophyllum bracteatum and A. microcephalum has shown cytotoxic effects of these two species, but the mechanism of their toxicity has remained unknown; thus, the present study was designed to evaluate the apoptotic potential of Acanthophyllum bracteatum and A. microcephalum. Methods: In the present study, the cytotoxic effects of the methanol extract of Acanthophyllum bracteatum and A. microcephalum was evaluated against MCF-7 and MDA-MB-468 cells by MTT assay; furthermore, their apoptosis potential has been evaluated by annexin-V/propidium iodide assay and Hoechst 33258 staining in the same cell lines. Results: The methanol extract of A. microcephalum and A. bracteatum showed cytotoxic effects against MCF-7 and MDA-MB-468 cell lines with IC50 values of 64, 159 and 102, 250 μg/mL, respectively. The results of the apoptosis assays confirmed the potential of the two plants extracts to induce apoptosis in both cell lines while A. microcephalum demonstrated more considerable results. Conclusion: A. microcephalum could be a suitable choice for further breast cancer studies.

Association of Seminal Plasma Total Antioxidant Capacity and Malondialdehyde Levels With Sperm Parameters in Infertile Men With Varicocele

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Salimi

2016-05-01

Full Text Available Background Varicocele is one of the most common reasons for male infertility and could impair spermatogenesis through mechanisms that are not well known. Recently, oxidative stress has been introduced as a major reason for male infertility caused by varicocele. Objectives In the current study, we aimed to assess the TAC (total antioxidant capacity and MDA (malondialdehyde as stress oxidative markers in infertile men with varicocele and fertile men, and moreover, their correlation with sperm parameters. Patients and Methods This case control study was performed on 43 infertile men with varicocele and 46 men with proven fertility. The ferric reducing ability of plasma (FRAP and thiobarbituric acid (TBA reaction methods were used for seminal plasma TAC and MDA assay, respectively. Results Lower TAC levels (1.7 ± 0.2 vs. 1.3 ± 0.4 mmol/L, P = 0.0004 and higher MDA levels (2.5 ± 1.1 vs. 5.8 ± 1.9 mmol/L, P < 0.0001 were observed in infertile men with varicocele compared to fertile men. There was no correlation between TAC and MDA in fertile men (r = 0.02, P = 0.9, however, a negative correlation was found between TAC and MDA levels in varicocele infertile men (r = −0.44, P = 0.003. Moreover, a positive correlation was found between sperm count and sperm motility with TAC levels in varicocele infertile men (r = 0.4, P = 0.02 and r = 0.6, P < 0.0001, respectively. There was a correlation between sperm motility and TAC levels in fertile men (r = 0.5, P = 0.001, but other parameters did not correlate with TAC in this group. A negative correlation was shown between semen volume, sperm count, total sperm, sperm motility, and sperm morphology with MDA levels in varicocele infertile men (r = 0.3, P = 0.045; r = −0.4, P = 0.009; r = −0.5, P = 0.002; r = −0.5, P = 0.001 and r = −0.4, P = 0.008, respectively. There was no correlation between these parameters and MDA in fertile men. Conclusions Our findings indicated that oxidative stress could

Protective Effect of Curcumin Supplementation and Light Resistance Exercises on Superoxide Dismutase Enzyme Activity and Malondialdehyde Levels in a Severe Endurance Training Period in Male Wistar Rats

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A Gorzi

2017-07-01

Background and aim: Extreme endurance exercises lead to oxidative stress in athletes. Therefore, the purpose of this study was to investigate the effect of curcumin supplement supplementation and light resistance training on the activity of SOD and MDA levels of male Wistar rats during a 8-week endurance training. Methods: In the present experimental study, 36 male Wistar rats were randomly assigned into one of six control groups, curcumin, endurance training, exercise, after one week of information (age 9 weeks and weight 255.62 ± 19.69 grams. Endurance + resistance, endurance training + curcumin and endurance training + curcumin + resistance. Incremental endurance training (8 weeks, 5 sessions per week was performed on a special treadmill. Speed ​​and running time in the last week reached 35 m / min and 70 minutes. Resistance training (8 weeks, 2 sessions per week was performed on vertical ladder by closing the rat's weight to the tail. Rats received supplemental curcumin by intraperitoneal injection (8 weeks, 3 sessions per week, 30 mg / kg body weight. SOD activity of the muscle was measured using ELISA kits and serum MDA levels using Tobartic acid (TBARS method. Data were analyzed using one-way ANOVA (ANOVA.   Results: The antioxidant enzyme activity of SOD in the endometrial muscle of endurance group (1.08 ± 0.222 μg / ml was significantly lower than control group (22.2 ± 0.481 kg (P = 0.043, and SOD activity in the endurance + resistance group (1.87 ± 0.172, p = 0.44, endurance + curcumin (2.24 ± 0.222; P = 0.039, and endurance + curcumin + resistance (0.202 ± 0.15, p = 0.029 was significantly higher than endurance group. The levels of malondialdehyde in the endurance group (4.27 ± 0.438 nmol / ml protein were significantly higher in comparison with the control group (3.42 ± 0.350 (0.331 and Also, serum MDA levels in endurance + resistance groups (± 3.03 ± 0.342, p = 0.003, endurance + curcumin (p = 0.001, p <0.001, and endurance + curcumin

Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

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Anantha Koteswararao Kanugula

Full Text Available Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

Overexpression of the Maize Sulfite Oxidase Increases Sulfate and GSH Levels and Enhances Drought Tolerance in Transgenic Tobacco

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Zongliang Xia

2018-03-01

Full Text Available Sulfite oxidase (SO plays a pivotal role in sulfite metabolism. In our previous study, sulfite-oxidizing function of the SO from Zea mays (ZmSO was characterized. To date, the knowledge of ZmSO’s involvement in abiotic stress response is scarce. In this study, we aimed to investigate the role of ZmSO in drought stress. The transcript levels of ZmSO were relatively high in leaves and immature embryos of maize plants, and were up-regulated markedly by PEG-induced water stress. Overexpression of ZmSO improved drought tolerance in tobacco. ZmSO-overexpressing transgenic plants showed higher sulfate and glutathione (GSH levels but lower hydrogen peroxide (H2O2 and malondialdehyde (MDA contents under drought stress, indicating that ZmSO confers drought tolerance by enhancing GSH-dependent antioxidant system that scavenged ROS and reduced membrane injury. In addition, the transgenic plants exhibited more increased stomatal response than the wild-type (WT to water deficit. Interestingly, application of exogenous GSH effectively alleviated growth inhibition in both WT and transgenic plants under drought conditions. qPCR analysis revealed that the expression of several sulfur metabolism-related genes was significantly elevated in the ZmSO-overexpressing lines. Taken together, these results imply that ZmSO confers enhanced drought tolerance in transgenic tobacco plants possibly through affecting stomatal regulation, GSH-dependent antioxidant system, and sulfur metabolism-related gene expression. ZmSO could be exploited for developing drought-tolerant maize varieties in molecular breeding.

Overexpression of p65 attenuates celecoxib-induced cell death in MDA-MB-231 human breast cancer cell line

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Wang Ling

2013-02-01

Full Text Available Abstract Background Celecoxib is a selective cyclooxygenase (COX-2 inhibitor that has been reported to reduce the risk of breast cancer. In our previous study, celecoxib induced apoptosis and caused cell cycle arrest at the G0/G1 phase in the breast cancer cell line MDA-MB-231, and its effects were mediated by downregulation of NF-κB signaling. The NF-κB p65/RelA subunit may play a role in cell death through the activation of anti-apoptotic target genes including the inhibitor of apoptosis (IAP and Bcl-2 families, and inhibition of protein kinase B/Akt. The aim of the present study was to investigate p65 as the potential target of celecoxib treatment and determine whether p65 overexpression can override the inhibitory effect of celecoxib on NF-κB activity and affect cell survival. Methods The effects of p65 overexpression on celecoxib-inhibited NF-κB transcriptional activity were examined by western blotting, electrophoretic mobility shift assay (EMSA and luciferase reporter gene assay. Cell viability and cell death were evaluated by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazoliumbromide (MTT assay, and the levels of cleaved poly(ADP-ribose polymerase (PARP and caspase. Anti-apoptotic NF-κB target genes and cell cycle regulators were examined by western blotting to screen for the expression of target genes under direct regulation by p65. Results Overexpression of p65 increased NF-κB transcriptional activity and interfered with celecoxib-mediated apoptosis as assessed by MTT assay and caspase-3, caspase-9, and PARP expressions. Exogenously overexpressed p65 upregulated NF-κB-responsive genes, including anti-apoptotic genes such as survivin and XIAP, and the cell cycle regulatory gene cyclin D1. However, p65 overexpression did not affect celecoxib-induced p-Akt inactivation, suggesting that celecoxib might have separate molecular mechanisms for regulating Akt signaling independently of its inhibition of NF-κB transcriptional

Flavokawain A induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro.

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Nadiah Abu

Full Text Available The kava-kava plant (Piper methsyticum is traditionally known as the pacific elixir by the pacific islanders for its role in a wide range of biological activities. The extract of the roots of this plant contains a variety of interesting molecules including Flavokawain A and this molecule is known to have anti-cancer properties. Breast cancer is still one of the leading diagnosed cancers in women today. The metastatic process is also very pertinent in the progression of tumorigenesis.MCF-7 and MDA-MB231 cells were treated with several concentrations of FKA. The apoptotic analysis was done through the MTT assay, BrdU assay, Annexin V analysis, cell cycle analysis, JC-1 mitochondrial dye, AO/PI dual staining, caspase 8/9 fluorometric assay, quantitative real time PCR and western blot. For the metastatic assays, the in vitro scratch assay, trans-well migration/invasion assay, HUVEC tube formation assay, ex vivo rat aortic ring assay, quantitative real time PCR and western blot were employed.We have investigated the effects of FKA on the apoptotic and metastatic process in two breast cancer cell lines. FKA induces apoptosis in both MCF-7 and MDA-MB231 in a dose dependent manner through the intrinsic mitochondrial pathway. Additionally, FKA selectively induces a G2/M arrest in the cell cycle machinery of MDA-MB231 and G1 arrest in MCF-7. This suggests that FKA's anti-cancer activity is dependent on the p53 status. Moreover, FKA also halted the migration and invasion process in MDA-MB231. The similar effects can be seen in the inhibition of the angiogenesis process as well.FKA managed to induce apoptosis and inhibit the metastatic process in two breast cancer cell lines, in vitro. Overall, FKA may serve as a promising candidate in the search of a new anti-cancer drug especially in halting the metastatic process but further in vivo evidence is needed.

Spatiotemporal prediction of daily ambient ozone levels across China using random forest for human exposure assessment.

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Zhan, Yu; Luo, Yuzhou; Deng, Xunfei; Grieneisen, Michael L; Zhang, Minghua; Di, Baofeng

2018-02-01

In China, ozone pollution shows an increasing trend and becomes the primary air pollutant in warm seasons. Leveraging the air quality monitoring network, a random forest model is developed to predict the daily maximum 8-h average ozone concentrations ([O 3 ] MDA8 ) across China in 2015 for human exposure assessment. This model captures the observed spatiotemporal variations of [O 3 ] MDA8 by using the data of meteorology, elevation, and recent-year emission inventories (cross-validation R 2  = 0.69 and RMSE = 26 μg/m 3 ). Compared with chemical transport models that require a plenty of variables and expensive computation, the random forest model shows comparable or higher predictive performance based on only a handful of readily-available variables at much lower computational cost. The nationwide population-weighted [O 3 ] MDA8 is predicted to be 84 ± 23 μg/m 3 annually, with the highest seasonal mean in the summer (103 ± 8 μg/m 3 ). The summer [O 3 ] MDA8 is predicted to be the highest in North China (125 ± 17 μg/m 3 ). Approximately 58% of the population lives in areas with more than 100 nonattainment days ([O 3 ] MDA8 >100 μg/m 3 ), and 12% of the population are exposed to [O 3 ] MDA8 >160 μg/m 3 (WHO Interim Target 1) for more than 30 days. As the most populous zones in China, the Beijing-Tianjin Metro, Yangtze River Delta, Pearl River Delta, and Sichuan Basin are predicted to be at 154, 141, 124, and 98 nonattainment days, respectively. Effective controls of O 3 pollution are urgently needed for the highly-populated zones, especially the Beijing-Tianjin Metro with seasonal [O 3 ] MDA8 of 140 ± 29 μg/m 3 in summer. To the best of the authors' knowledge, this study is the first statistical modeling work of ambient O 3 for China at the national level. This timely and extensively validated [O 3 ] MDA8 dataset is valuable for refining epidemiological analyses on O 3 pollution in China. Copyright © 2017 Elsevier Ltd. All rights

Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

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Peterson, Sarah M; Concino, Michael F; Liaw, Lucy; Martini, Paolo GV; Iskenderian, Andrea; Cook, Lynette; Romashko, Alla; Tobin, Kristen; Jones, Michael; Norton, Angela; Gómez-Yafal, Alicia; Heartlein, Michael W

2010-01-01

Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular

Proficiency testing criteria for clearance level in solid waste gamma measurement in Taiwan

International Nuclear Information System (INIS)

Chen, Chun-Liang; Wang, Jeng-Jong; Chiu, Huang-Sheng

2013-01-01

To guarantee the measurement quality for clearance level in solid waste material, the Institute of Nuclear Energy Research (INER) established the criteria for proficiency testing of clearance level measurement. INER and the Taiwan Accreditation Foundation (TAF) organized the Technique Committee Meeting twice to discuss these criteria in 2011. The participating laboratories must completely conform to the ISO/IEC 17025, and they also must meet the requirements of the criteria. According to the criteria, the participating laboratories analyzed the minimum detectable amount (MDA) and that should be less than 20% of the clearance level (AMDA) given in the Atomic Energy Council's (AEC) “Regulations on Clearance Level for Radioactive Waste Management”. The testing results should conform to the deviation and traceability requirements. - Highlights: • The participating laboratories must completely conform to the ISO/IEC 17025 • The proficiency testing items were basically in two categories, box and barrel types • Analyzed the MDA and that should be less than 20% of the release level given in the AEC. • The are three limitations: MDA< AMDA, -0.25< Bi<+0.5, and En≤1.0 and uncertainty<20%

Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

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Qing-Rong Pan

2014-07-01

Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness.

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Ra, Song-Gyu; Choi, Youngju; Akazawa, Nobuhiko; Ohmori, Hajime; Maeda, Seiji

2016-06-01

There is a delayed increase in arterial stiffness after eccentric exercise that is possibly mediated by the concurrent delayed increase in circulating oxidative stress. Taurine has anti-oxidant action, and taurine supplementation may be able to attenuate the increase in oxidative stress after exercise. The purpose of the present study was to investigate whether taurine supplementation attenuates the delayed increase in arterial stiffness after eccentric exercise. In the present double-blind, randomized, and placebo-controlled trial, we divided 29 young, healthy men into 2 groups. Subjects received either 2.0 g of placebo (n = 14) or taurine (n = 15) 3 times per day for 14 days prior to the exercise, on the day of exercise, and the following 3 days. The exercise consisted of 2 sets of 20 maximal-effort eccentric repetitions with the nondominant arm only. On the morning of exercise and for 4 days thereafter, we measured serum malondialdehyde (MDA) and carotid-femoral pulse wave velocity (cfPWV) as indices of oxidative stress and arterial stiffness, respectively. On the third and fourth days after exercise, both MDA and cfPWV significantly increased in the placebo group. However, these elevations were significantly attenuated in the taurine group. The increase in MDA was associated with an increase in cfPWV from before exercise to 4 days after exercise (r = 0.597, p taurine group. Our results suggest that delayed increase in arterial stiffness after eccentric exercise was probably affected by the exercise-induced oxidative stress and was attenuated by the taurine supplementation.

Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.

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Inan, M; Bakar, E; Cerkezkayabekir, A; Sanal, F; Ulucam, E; Subaşı, C; Karaöz, E

2017-07-01

Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage. A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry. MDA was increased (Pcytokines interleukin-1β (IL1β), transforming growth factor-β1 (TGFβ1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (Pcytokines EP3 and IL1ra increased (poxygen radicals, suppression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential Ratios of Omega Fatty Acids (AA/EPA+DHA Modulate Growth, Lipid Peroxidation and Expression of Tumor Regulatory MARBPs in Breast Cancer Cell Lines MCF7 and MDA-MB-231.

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Prakash P Mansara

Full Text Available Omega 3 (n3 and Omega 6 (n6 polyunsaturated fatty acids (PUFAs have been reported to exhibit opposing roles in cancer progression. Our objective was to determine whether different ratios of n6/n3 (AA/EPA+DHA FAs could modulate the cell viability, lipid peroxidation, total cellular fatty acid composition and expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs in breast cancer cell lines and in non-cancerous, MCF10A cells. Low ratios of n6/n3 (1:2.5, 1:4, 1:5, 1:10 FA decreased the viability and growth of MDA-MB-231 and MCF7 significantly compared to the non-cancerous cells (MCF10A. Contrarily, higher n6/n3 FA (2.5:1, 4:1, 5:1, 10:1 decreased the survival of both the cancerous and non-cancerous cell types. Lower ratios of n6/n3 selectively induced LPO in the breast cancer cells whereas the higher ratios induced in both cancerous and non-cancerous cell types. Interestingly, compared to higher n6/n3 FA ratios, lower ratios increased the expression of tumor suppressor MARBP, SMAR1 and decreased the expression of tumor activator Cux/CDP in both breast cancer and non-cancerous, MCF10A cells. Low n6/n3 FAs significantly increased SMAR1 expression which resulted into activation of p21WAF1/CIP1 in MDA-MB-231 and MCF7, the increase being ratio dependent in MDA-MB-231. These results suggest that increased intake of n3 fatty acids in our diet could help both in the prevention as well as management of breast cancer.

Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells.

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Lee, Ming-Fen; Pan, Min-Hsiung; Chiou, Yi-Siou; Cheng, An-Chin; Huang, Han

2011-11-09

Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a subunit of the mammalian Mediator complex for transcription, was also identified as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial-derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas the underlying mechanism is unclear. Triple-negative breast cancers, often expressing epidermal growth factor (EGF) receptor (EGFR), are associated with metastasis and poor survival. The objective of this study is to compare the effect of resveratrol and pterostilbene and to investigate the role of MED28 in EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol, but not pterostlbene, suppressed EGF-mediated migration and expression of MED28 and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover, overexpression of MED28 increased migration, and the addition of EGF further enhanced migration. Our data indicate that resveratrol modulates the effect of MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3-kinase (PI3K) signaling pathway, in breast cancer cells.

Oxydative stress in rats caused by coal dust plus cigarette smoke

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Nia Kania

2016-02-01

Full Text Available Coal dust and cigarette smoke are pollutants found in coal mines that are capable of inducing oxidative stress, the effects of which on blood malondialdehyde (MDA level and serum superoxide dismutase (SOD level are still unknown. The purpose of the present study was to evaluate the effect of coal dust and cigarette smoke on levels of MDA and SOD in rats. An experimental study was done on Wistar male rats divided into the following groups: control (C, coal dust exposure (14 days (CDE, cigarette smoke exposure (14 days (CSE, coal dust exposure (7 days followed by cigarette smoke exposure (7 days (CDE+CSE, cigarette smoke exposure (7 days followed by coal dust exposure (7 days (CSE+CDE. All exposures increased MDA levels and decreased SOD activity significantly between groups (p=0.000. All exposure groups had significantly increased blood MDA levels, compared to the control group, although there was no difference between CSE + CDE and CDE + CSE. For SOD levels, all exposure groups had significantly decreased the SOD levels compared to control. But there were no significant differences between CSE vs CDE and CDE + CSE vs CSE + CDE. We conclude that exposure to cigarette smoke significantly increases blood MDA level and decreases serum SOD activity, which was not found in exposure to coal dust. Combined exposures also increase blood MDA level and decrease serum SOD activity significantly.

Oxydative stress in rats caused by coal dust plus cigarette smoke

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Nia Kania

2011-08-01

Full Text Available Coal dust and cigarette smoke are pollutants found in coal mines that are capable of inducing oxidative stress, the effects of which on blood malondialdehyde (MDA level and serum superoxide dismutase (SOD level are still unknown. The purpose of the present study was to evaluate the effect of coal dust and cigarette smoke on levels of MDA and SOD in rats. An experimental study was done on Wistar male rats divided into the following groups: control (C, coal dust exposure (14 days (CDE, cigarette smoke exposure (14 days (CSE, coal dust exposure (7 days followed by cigarette smoke exposure (7 days (CDE+CSE, cigarette smoke exposure (7 days followed by coal dust exposure (7 days (CSE+CDE. All exposures increased MDA levels and decreased SOD activity significantly between groups (p=0.000. All exposure groups had significantly increased blood MDA levels, compared to the control group, although there was no difference between CSE + CDE and CDE + CSE. For SOD levels, all exposure groups had significantly decreased the SOD levels compared to control. But there were no significant differences between CSE vs CDE and CDE + CSE vs CSE + CDE. We conclude that exposure to cigarette smoke significantly increases blood MDA level and decreases serum SOD activity, which was not found in exposure to coal dust. Combined exposures also increase blood MDA level and decrease serum SOD activity significantly.

Advanced oxidation protein products are increased in women with polycystic ovary syndrome: relationship with traditional and nontraditional cardiovascular risk factors in patients with polycystic ovary syndrome.

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Kaya, Cemil; Erkan, Aycan Fahri; Cengiz, S Dinçer; Dünder, Ilkkan; Demirel, Ozlem Erbaş; Bilgihan, Ayşe

2009-10-01

To determine whether or not plasma advanced oxidation protein products (AOPPs) are associated with known cardiovascular risk factors or carotid intima-media thickness (IMT) in patients with polycystic ovary syndrome (PCOS). A prospective, controlled study. University hospital. Forty-six women with PCOS and 46 age- and body mass index-matched healthy women. Carotid IMT was evaluated for both common carotid arteries. We measured serum levels of AOPP, homocysteine (Hcy), C-reactive protein (CRP), malonyldialdehyde (MDA), vitamin B(12), folate, lipid, and hormone profiles. The presence of insulin resistance was investigated by means of homeostasis model assessment (HOMA). Serum AOPP, fasting insulin, HOMA index, Hcy, MDA, CRP, and carotid IMT. The women with PCOS had significantly higher serum AOPP than control women. High AOPP was defined as equaling or exceeding the mean + 2 SD of the plasma AOPP in control subjects (56.2 pg/mLl). Carotid IMT, fasting insulin, HOMA index, Hcy, MDA, and CRP were significantly higher in PCOS patients with high AOPP than in those with normal AOPP. Fasting insulin, insulin resistance, and Hcy were independent determinants of plasma AOPP. Increased AOPP may contribute to the increased risk of atherosclerotic cardiovascular disease in women with PCOS.

Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis.

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Zhu, Xue; Wang, Ke; Zhang, Kai; Zhang, Ting; Yin, Yongxiang; Xu, Fei

2016-11-22

Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae , on the TNBC cell line MDA-MB-231. The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21 WAF1 , elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC.

Effect of lawsonia innermis (linn) leaves ethanolic extract on blood glucose and malondialdehyde level in alloxan-induced diabetic rats

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Indah Sari, Mutiara; Ilyas, Syafruddin; Widyawati, Tri; Anjelir Antika, Maya

2018-03-01

The case of diabetes mellitus (DM) tends to increase worldwide. DM triggers the oxidative stress condition that caused by the increasing of free radical. The present study was conducted to evaluate the effect of giving ethanolic extract of Lawsonia inermis (Linn) leaves to the glucose and malondialdehyde (MDA) level in alloxan-induced diabetic Wistar male rats. The powder of dry leaves of L.inermis was macerated in ethanol 96% to obtain ethanolic extract (LLEE).Thirty five of rats were divided into five groups, ie. K (normal and given 0.9% NaCl solution ), P1-P4 were induced using alloxan (120 mg/kg) intraperitoneally to get diabetic condition. Diabetic rats then were treated as follows: P1 (given 0.9% NaCl solution) P2 (LLEE (200 mg/kg BW), P3 (LLEE (400 mg/kg BW)), P4 ( LLEE (600 mg/kg BW)). All groups were treated for 28 days. The fasting blood glucose levels were measured at day 1, 7, 14, 21, 28 whereas MDA levels were measured at the end of treatment. The result showed that LLEE improved blood glucose level (BGLs) of alloxan-induced diabetic rats significantly (p 0.5). The study concluded that LLEE have antihyperglycemic properties.

Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

International Nuclear Information System (INIS)

Uma Suganya, K.S.; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

2016-01-01

Highlights: • Biosynthesis of stable and well dispersed predominantly spherical gold nanoparticles of size around ∼12.5 nm. • Anticancer assessment of gold nanoparticles on MDA-MB-231 and MCF-7 cell lines. • AuNPs were found non toxic to normal HMEC cells. • Flow cytometry results revealed significant arrest in cell proliferation in early G0/G1 to S phase. - Abstract: Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G_0/G_1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

Energy Technology Data Exchange (ETDEWEB)

Uma Suganya, K.S. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Govindaraju, K., E-mail: govindtu@gmail.com [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Ganesh Kumar, V. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Prabhu, D.; Arulvasu, C. [Department of Zoology, University of Madras, Guindy campus, Chennai 600 025 (India); Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India)

2016-05-15

Highlights: • Biosynthesis of stable and well dispersed predominantly spherical gold nanoparticles of size around ∼12.5 nm. • Anticancer assessment of gold nanoparticles on MDA-MB-231 and MCF-7 cell lines. • AuNPs were found non toxic to normal HMEC cells. • Flow cytometry results revealed significant arrest in cell proliferation in early G0/G1 to S phase. - Abstract: Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G{sub 0}/G{sub 1} to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

Selective regain of egfr gene copies in CD44+/CD24-/low breast cancer cellular model MDA-MB-468

International Nuclear Information System (INIS)

Agelopoulos, Konstantin; Buerger, Horst; Brandt, Burkhard; Greve, Burkhard; Schmidt, Hartmut; Pospisil, Heike; Kurtz, Stefan; Bartkowiak, Kai; Andreas, Antje; Wieczorek, Marek; Korsching, Eberhard

2010-01-01

Increased transcription of oncogenes like the epidermal growth factor receptor (EGFR) is frequently caused by amplification of the whole gene or at least of regulatory sequences. Aim of this study was to pinpoint mechanistic parameters occurring during egfr copy number gains leading to a stable EGFR overexpression and high sensitivity to extracellular signalling. A deeper understanding of those marker events might improve early diagnosis of cancer in suspect lesions, early detection of cancer progression and the prediction of egfr targeted therapies. The basal-like/stemness type breast cancer cell line subpopulation MDA-MB-468 CD44 high /CD24 -/low , carrying high egfr amplifications, was chosen as a model system in this study. Subclones of the heterogeneous cell line expressing low and high EGF receptor densities were isolated by cell sorting. Genomic profiling was carried out for these by means of SNP array profiling, qPCR and FISH. Cell cycle analysis was performed using the BrdU quenching technique. Low and high EGFR expressing MDA-MB-468 CD44 + /CD24 -/low subpopulations separated by cell sorting showed intermediate and high copy numbers of egfr, respectively. However, during cell culture an increase solely for egfr gene copy numbers in the intermediate subpopulation occurred. This shift was based on the formation of new cells which regained egfr gene copies. By two parametric cell cycle analysis clonal effects mediated through growth advantage of cells bearing higher egfr gene copy numbers could most likely be excluded for being the driving force. Subsequently, the detection of a fragile site distal to the egfr gene, sustaining uncapped telomere-less chromosomal ends, the ladder-like structure of the intrachromosomal egfr amplification and a broader range of egfr copy numbers support the assumption that dynamic chromosomal rearrangements, like breakage-fusion-bridge-cycles other than proliferation drive the gain of egfr copies. Progressive genome modulation

Correlation of Serum Levels of Vitronectin, Malondialdehyde and Hs-CRP With Disease Severity in Coronary Artery Disease

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Alireza Yaghoubi

2015-09-01

Conclusion: The association and correlation between VN, MDA and hs-CRP indicate their involvement in the atherosclerosis process that may lead to progression of CAD. Also, these findings suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and monitoring markers in CAD patients and as markers of disease severity.

Influence of gross saponins from tribulus terrestris L on SOD activity and MDA content for chronic high intraocular pressure in rabbit

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Nuo Li

2013-05-01

Full Text Available AIM:To observe influence of gross saponins from tribulus terrestris L(GSTTon SOD activity and MDA content for chronic high intraocular pressure in rabbit, and discusses the retina oxidative damage inhibition on chronic high intraocular pressure model of rabbit. METHODS:Totally 24 healthy New Zealand rabbits were randomly divided into 4 groups: normal control group(A group; high intraocular pressure model blank group(B group; high intraocular pressure model with GSTT treated group(C group; high intraocular pressure model with Erigeron brevicapas hand mass(EBHMtreated group(D group. High intraocular pressure model was induced by 20g/L methylcellulose injection into the anterior chamber in B group, C group and D group. D group was injected 5 mg/kg GSTT and C group was injected 4.5mg/kg EBHM and measured intraocular pressure with Schiotz tonometer every day for 4 weeks. The retina tissue superoxide dismutase(SODand maleic dialdehyde(MDAcontent were detected 28 days later. RESULTS: After glaucoma model of rabbit eyes were established, the intraocular pressure during observation period was maintained in 32-39mmHg; High intraocular pressure model blank group and normal control group, EBHM treatment group, GSTT treatment group were compared, the differences of retina MDA, SOD content had statistical significance(P0.05; EBHM treatment group, GSTT treatment group and normal control group were compared, the content of MDA in the retina was still slightly higher(P<0.05, the content of SOD slightly lower(P<0.05 CONCLUSION: GSTT can effectively improve the retina SOD activity of chronic high intraocular pressure in rabbit and reduce the content of MDA, which has a protective effect of persistent high intraocular retinal oxidative stress.

Oxidative Damage Does Not Occur in Striped Hamsters Raising Natural and Experimentally Increased Litter Size.

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Xiao-Ya Zhao

Full Text Available Life-history theory assumes that animals can balance the allocation of limited energy or resources to the competing demands of growth, reproduction and somatic maintenance, while consequently maximizing their fitness. However, somatic damage caused by oxidative stress in reproductive female animals is species-specific or is tissue dependent. In the present study, several markers of oxidative stress (hydrogen peroxide, H2O2 and malonadialdehyde, MDA and antioxidant (catalase, CAT and total antioxidant capacity, T-AOC were examined in striped hamsters during different stages of reproduction with experimentally manipulated litter size. Energy intake, resting metabolic rate (RMR, and mRNA expression of uncoupling protein 1 (UCP1 in brown adipose tissue (BAT and UCP3 in skeletal muscle were also examined. H2O2 and MDA levels did not change in BAT and liver, although they significantly decreased in skeletal muscle in the lactating hamsters compared to the non-reproductive group. However, H2O2 levels in the brain were significantly higher in lactating hamsters than non-reproductive controls. Experimentally increasing litter size did not cause oxidative stress in BAT, liver and skeletal muscle, but significantly elevated H2O2 levels in the brain. CAT activity of liver decreased, but CAT and T-AOC activity of BAT, skeletal muscle and the brain did not change in lactating hamsters compared to non-reproductive controls. Both antioxidants did not change with the experimentally increasing litter size. RMR significantly increased, but BAT UCP1 mRNA expression decreased with the experimentally increased litter size, suggesting that it was against simple positive links between metabolic rate, UCP1 expression and free radicals levels. It may suggest that the cost of reproduction has negligible effect on oxidative stress or even attenuates oxidative stress in some active tissues in an extensive range of animal species. But the increasing reproductive effort may

Regression analysis of γ-ray effect on sod activity and MDA content in four vegetable leaves

International Nuclear Information System (INIS)

Wang Zegang; Feng Min; Hu Jianwei; Gao Yue; Lv Haiyan; Luo Shishi; Zheng Haoxian; Ma Fei; Ge Cailin

2005-01-01

Dynamic effects of γ-ray on SOD, POD activities and MDA content in leaves of four vegetable varieties were studied. The results were quantitatively described by the method of curve fitting and establishing mathematical model. The parameters of the formula suggested that the four vegetable varieties' sensitivity to radiation appeared as following order: Basella rubra>Lactuca sativa>Lactuca sativa spp>Brassica Chinensis. (authors)

(−)-Xanthatin Selectively Induces GADD45γ and Stimulates Caspase-Independent Cell Death in Human Breast Cancer MDA-MB-231 Cells

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Takeda, Shuso; Matsuo, Kazumasa; Yaji, Kentaro; Okajima-Miyazaki, Shunsuke; Harada, Mari; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Shindo, Mitsuru; Omiecinski, Curtis J.; Aramaki, Hironori

2014-01-01

exo-Methylene lactone group-containing compounds, such as (−)-xanthatin, are present in a large variety of biologically active natural products, including extracts of Xanthium strumarium (Cocklebur). These substances are reported to possess diverse functional activities, exhibiting anti-inflammatory, antimalarial, and anticancer potential. In this study, we synthesized six structurally related xanthanolides containing exo-methylene lactone moieties, including (−)-xanthatin and (+)-8-epi-xanthatin, and examined the effects of these chemically defined substances on the highly aggressive and farnesyltransferase inhibitor (FTI)-resistant MDA-MB-231 cancer cell line. The results obtained demonstrate that (−)-xanthatin was a highly effective inhibitor of MDA-MB-231 cell growth, inducing caspase-independent cell death, and that these effects were independent of FTase inhibition. Further, our results show that among the GADD45 isoforms, GADD45γ was selectively induced by (−)-xanthatin and that GADD45γ-primed JNK and p38 signaling pathways are, at least in part, involved in mediating the growth inhibition and potential anticancer activities of this agent. Given that GADD45γ is becoming increasingly recognized for its tumor suppressor function, the results presented here suggest the novel possibility that (−)-xanthatin may have therapeutic value as a selective inducer of GADD45γ in human cancer cells, in particular in FTI-resistant aggressive breast cancers. PMID:21568272

Consumption of Oxidized Soybean Oil Increased Intestinal Oxidative Stress and Affected Intestinal Immune Variables in Yellow-feathered Broilers

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Fangfang Liang

2015-08-01

Full Text Available This study investigated the effect of oxidized soybean oil in the diet of young chickens on growth performance and intestinal oxidative stress, and indices of intestinal immune function. Corn-soybean-based diets containing 2% mixtures of fresh and oxidized soybean oil provided 6 levels (0.15, 1.01, 3.14, 4.95, 7.05, and 8.97 meqO2/kg of peroxide value (POV in the diets. Each dietary treatment, fed for 22 d, had 6 replicates, each containing 30 birds (n = 1,080. Increasing POV levels reduced average daily feed intake (ADFI of the broilers during d 1 to 10, body weight and average daily gain at d 22 but did not affect overall ADFI. Concentrations of malondialdehyde (MDA increased in plasma and jejunum as POV increased but total antioxidative capacity (T-AOC declined in plasma and jejunum. Catalase (CAT activity declined in plasma and jejunum as did plasma glutathione S-transferase (GST. Effects were apparent at POV exceeding 3.14 meqO2/kg for early ADFI and MDA in jejunum, and POV exceeding 1.01 meqO2/kg for CAT in plasma and jejunum, GST in plasma and T-AOC in jejunum. Relative jejunal abundance of nuclear factor kappa B (NF-κB P50 and NF-κB P65 increased as dietary POV increased. Increasing POV levels reduced the jejunal concentrations of secretory immunoglobulin A and cluster of differentiation (CD 4 and CD8 molecules with differences from controls apparent at dietary POV of 3.14 to 4.95 meqO2/kg. These findings indicated that growth performance, feed intake, and the local immune system of the small intestine were compromised by oxidative stress when young broilers were fed moderately oxidized soybean oil.

KIAA0100 Modulates Cancer Cell Aggression Behavior of MDA-MB-231 through Microtubule and Heat Shock Proteins

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Zhenyu Zhong

2018-06-01

Full Text Available The KIAA0100 gene was identified in the human immature myeloid cell line cDNA library. Recent studies have shown that its expression is elevated in breast cancer and associated with more aggressive cancer types as well as poor outcomes. However, its cellular and molecular function is yet to be understood. Here we show that silencing KIAA0100 by siRNA in the breast cancer cell line MDA-MB-231 significantly reduced the cancer cells’ aggressive behavior, including cell aggregation, reattachment, cell metastasis and invasion. Most importantly, silencing the expression of KIAA0100 particularly sensitized the quiescent cancer cells in suspension culture to anoikis. Immunoprecipitation, mass spectrometry and immunofluorescence analysis revealed that KIAA0100 may play multiple roles in the cancer cells, including stabilizing microtubule structure as a microtubule binding protein, and contributing to MDA-MB-231 cells Anoikis resistance by the interaction with stress protein HSPA1A. Our study also implies that the interaction between KIAA0100 and HSPA1A may be targeted for new drug development to specifically induce anoikis cell death in the cancer cell.

Activity test of various mangosteen (Garcinia mangostana pericarp extract fractions to decrease fasting blood cholesterol levels and lipid peroxidation activity in diabetic mice

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Saikhu Akhmad Husen

2017-01-01

Full Text Available The objectives of this study were to determine the effect of various fractions of mangosteen (Garcinia mangostana pericarp extract to the changes of the fasting blood cholesterol and serum malondialdehyde (MDA levels on diabetic mice (Mus musculus. Thirty 3-4 months old male mice strain BALB/c, weight 20-30 g were divided into six groups. The first group was KN as a non diabetic control group, KD as a diabetic control, KM as a group of diabetic mice treated with metformin, and NP, SP, and P as the treatment groups that were treated by using three different fractions from mangosteen pericarp extract, non polar, semi polar, and polar respectively. The induction of Diabetes mellitus was done by the injection of STZ, and the mice were given a high fat diet treatment to induce the hiperlipidemia condition using lard for three weeks. The blood cholesterol levels were measured in all groups before and after the injection of lard, and day 1, 7, and 14 of treatment as well. The serum MDA level as the indicator of lipid peroxidation were measured by using QuantiChrom TBARS Assay Kit (DTBA-100. The data of cholesterol levels were statistically analyzed by t-test, while the data of serum MDA levels were analyzed by variance analysis followed by Duncan test. The results showed that the polar fraction of mangosteen pericarp had effect to decrease the fasting blood cholesterol level in mice, however the non polar and semi polar fraction had no simmilar effect. All of the fractions has shown significant effect to decrease the serum MDA level in mice. Key words: cholesterol, diabetes mellitus, Garcinia mangostana, malondialdehyde (mda, obesity.

Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma.

Science.gov (United States)

Glas, Martin; Coch, Christoph; Trageser, Daniel; Dassler, Juliane; Simon, Matthias; Koch, Philipp; Mertens, Jerome; Quandel, Tamara; Gorris, Raphaela; Reinartz, Roman; Wieland, Anja; Von Lehe, Marec; Pusch, Annette; Roy, Kristin; Schlee, Martin; Neumann, Harald; Fimmers, Rolf; Herrlinger, Ulrich; Brüstle, Oliver; Hartmann, Gunther; Besch, Robert; Scheffler, Björn

2013-06-01

Cellular heterogeneity, for example, the intratumoral coexistence of cancer cells with and without stem cell characteristics, represents a potential root of therapeutic resistance and a significant challenge for modern drug development in glioblastoma (GBM). We propose here that activation of the innate immune system by stimulation of innate immune receptors involved in antiviral and antitumor responses can similarly target different malignant populations of glioma cells. We used short-term expanded patient-specific primary human GBM cells to study the stimulation of the cytosolic nucleic acid receptors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). Specifically, we analyzed cells from the tumor core versus "residual GBM cells" derived from the tumor resection margin as well as stem cell-enriched primary cultures versus specimens without stem cell properties. A portfolio of human, nontumor neural cells was used as a control for these studies. The expression of RIG-I and MDA5 could be induced in all of these cells. Receptor stimulation with their respective ligands, p(I:C) and 3pRNA, led to in vitro evidence for an effective activation of the innate immune system. Most intriguingly, all investigated cancer cell populations additionally responded with a pronounced induction of apoptotic signaling cascades revealing a second, direct mechanism of antitumor activity. By contrast, p(I:C) and 3pRNA induced only little toxicity in human nonmalignant neural cells. Granted that the challenge of effective central nervous system (CNS) delivery can be overcome, targeting of RIG-I and MDA5 could thus become a quintessential strategy to encounter heterogeneous cancers in the sophisticated environments of the brain. Copyright © 2013 AlphaMed Press.

MDA-image: an environment of networked desktop computers for teleradiology/pathology.

Science.gov (United States)

Moffitt, M E; Richli, W R; Carrasco, C H; Wallace, S; Zimmerman, S O; Ayala, A G; Benjamin, R S; Chee, S; Wood, P; Daniels, P

1991-04-01

MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.

PIEZO channel protein naturally expressed in human breast cancer cell MDA-MB-231 as probed by atomic force microscopy

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Weng, Yuanqi; Yan, Fei; Chen, Runkang; Qian, Ming; Ou, Yun; Xie, Shuhong; Zheng, Hairong; Li, Jiangyu

2018-05-01

Mechanical stimuli drives many physiological processes through mechanically activated channels, and the recent discovery of PIEZO channel has generated great interests in its mechanotransduction. Many previous researches investigated PIEZO proteins by transcribing them in cells that originally have no response to mechanical stimulation, or by forming PIEZO-combined complexes in vitro, and few studied PIEZO protein's natural characteristics in cells. In this study we show that MDA-MB-231, a malignant cell in human breast cancer cell line, expresses the mechanosensitive behavior of PIEZO in nature without extra treatment, and we report its characteristics in response to localized mechanical stimulation under an atomic force microscope, wherein a correlation between the force magnitude applied and the channel opening probability is observed. The results on PIEZO of MDA-MB-231 can help establish a basis of preventing and controlling of human breast cancer cell via mechanical forces.

Altered Antioxidant Status and Increased Lipid Per-Oxidation in Seminal Plasma of Tunisian Infertile Men

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Atig, Fatma; Raffa, Monia; Ali, Habib Ben; Abdelhamid, Kerkeni; Saad, Ali; Ajina, Mounir

2012-01-01

Human seminal plasma is a natural reservoir of antioxidants that protect spermatozoa from oxidative damages. There is evidence in literature supports the fact that impairments in seminal antioxidant and lipid per-oxidation status play important roles in the physiopathology of male infertility. Our present study forms the first one which was carried out in Tunisia. We evaluated the antioxidant status in the seminal plasma of 120 infertile men programmed to In Vitro Fertilization (IVF) for the first tentative. Patients were characterized by an idiopathic infertility. They were divided into three groups: normozoospermics who were considered as controls (n=40), asthenozoospermics (Astheno; n=45) and oligoasthenoteratozoospermics (OAT; n=35). Seminal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the levels of glutathione (GSH), zinc (Zn) and malondialdehyde (MDA) were measured. With the significant increase of the seminal activities of SOD and GPX in normozoospermics group, there were positive correlations observed between this enzymes and sperm quality. Also, significant elevated rates of seminal zinc and GSH were observed in control group, but there was contradictory associations reflecting the effects of these antioxidants on semen parameters. However, we noted significant increase of MDA levels in groups with abnormal seminogram. We showed negative associations between this per-oxidative marker and sperm parameters. These results obviously suggested that impairment on seminal antioxidants is an important risk factor for low sperm quality associated to idiopathic infertility and as a result can lead to poor IVF outcome. PMID:22211112

Correlation of Seminal Plasma Total Antioxidant Capacity and Malondialdehyde Levels With Sperm Parameters in Men With Idiopathic Infertility

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Fazeli

2016-01-01

Full Text Available Background Oxidative stress is the result of an imbalance between the production and scavenging of reactive oxygen species (ROS. Recently, oxidative stress has been introduced as a major cause of male infertility. Objectives The aim of the present study was to determine the correlation between total antioxidant capacity (TAC and malondialdehyde (MDA as markers of oxidative stress in relation to idiopathic male infertility and sperm parameters. Patients and Methods This case control study was conducted using 35 men with idiopathic infertility and 34 men with proven fertility. Seminal plasma TAC and MDA were measured by ferric reducing ability of plasma (FRAP and thiobarbituric acid (TBA reaction methods, respectively. Results Seminal TAC levels were significantly lower and seminal MDA levels were significantly higher in men with idiopathic infertility than in fertile men (P < 0.0001 and P = 0.004, respectively. A positive correlation was shown between sperm motility, sperm morphology, and TAC levels in men with idiopathic infertility (P = 0.002 and P = 0.002, respectively. In addition, there was a correlation between sperm motility and TAC levels in fertile men (P = 0.005. There was no correlation between sperm count and TAC levels in either men with idiopathic infertility or in fertile men. Negative correlations were observed between MDA levels and sperm motility, morphology, and sperm count only in men with idiopathic infertility (P = 0.003, P = 0.001, and P = 0.006, respectively. Conclusions Our results show that oxidative stress could play an important role in male infertility as well as in sperm motility and sperm morphology.

The influence of elevated levels of platelet-derived endothelial cell growth factor/thymidine phosphorylase on tumourigenicity, tumour growth, and oxygenation

International Nuclear Information System (INIS)

Griffiths, L.; Stratford, I.J.

1998-01-01

Purpose: Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels. Methods and Materials: MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation. Results: We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP. Conclusion: PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature

Hydrogen sulfide regulates the levels of key metabolites and antioxidant defense system to counteract oxidative stress in pepper (Capsicum annuum L.) plants exposed to high zinc regime.

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Kaya, Cengiz; Ashraf, Muhammad; Akram, Nudrat Aisha

2018-02-21

In the present experiment, we aimed to test the impact of hydrogen sulfide (H 2 S) on growth, key oxidant such as hydrogen peroxide, mineral elements, and antioxidative defense in Capia-type red sweet pepper (Capsicum annuum L.) plants subjected to high concentration of zinc (Zn). A factorial experiment was designed with two Zn levels (0.05 and 0.5 mM) and 0.2 mM sodium hydrosulfide (NaHS) as a donor of H 2 S supplied in combination plus nutrient solution through the root zone. High level of Zn led to reduce dry mass, chlorophyll pigments, fruit yield, leaf maximum fluorescence, and relative water content, but enhanced endogenous hydrogen peroxide (H 2 O 2 ), free proline, malondialdehyde (MDA), electrolyte leakage (EL), H 2 S, as well as the activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) enzymes. Exogenously applied NaHS significantly enhanced plant growth, fruit yield, water status, the levels of H 2 S and proline as well as the activities of different antioxidant enzymes, while it significantly suppressed EL, MDA, and H 2 O 2 contents in the pepper plants receiving low level Zn. NaHS application to the control plants did not significantly change all these parameters tested except the dry matter which increased significantly. High Zn regime led to increase intrinsic Zn levels in the leaves and roots, but it lowered leaf nitrogen (N), phosphorus (P), and iron (Fe) concentrations. However, NaHS reduces the Zn conc. and enhances Fe and N in leaf and root organs. It can be concluded that NaHS can mitigate the harmful effects of Zn on plant growth particularly by lowering the concentrations of H 2 O 2 , Zn, EL, and MDA, and enhancing the activities of enzymatic antioxidants and levels of essential nutrients in pepper plants.

Cytotoxic effects of chloroform and hydroalcoholic extracts of aerial parts of Cuscuta chinensis and Cuscuta epithymum on Hela, HT29 and MDA-MB-468 tumor cells.

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Jafarian, A; Ghannadi, A; Mohebi, B

2014-01-01

Previous studies have indicated that some species of Cuscuta possess anticancer activity on various cell lines. Due to the lack of detailed researches on the cytotoxic effects of Cuscuta chinensis and Cuscuta epithymum, the aim of the present study was to evaluate cytotoxic effects of chloroform and hydroalcoholic extracts of these plants on the human breast carcinoma cell line (MDA-MB-468), human colorectal adenocarcinoma cell line (HT29) and human uterine cervical carcinoma (Hela). Using maceration method, different extracts of aerial parts of C. chinensis and C. epithymum were prepared. Extraction was performed using chloroform and ethanol/water (70/30). Total phenolic contents of the extracts were determined according to the Folin-Ciocalteu method. Using MTT assay, the cytotoxic activity of the extracts against HT29, Hela and MDA-MB-468 tumor cells was evaluated. Extracts were considered cytotoxic when more than 50% reduction on cell survival was observed. The poly-phenolic content of the hydroalcoholic and chloroform extracts of C. chinensis and C. epithymum were 56.08 ± 4.11, 21.49 ± 2.00, 10.64 ± 0.86 and 4.81 ± 0.38, respectively. Our findings showed that the chloroform extracts of C. chinensis and C. epithyum significantly reduced the viability of Hela, HT-29 and MDA-MB-468 cells. Also, hydroalcoholic extracts of C. chinensis significantly decreased the viability of HT29, Hela and MDA-MB-468 cells. However, in the case of hydroalcoholic extracts of C. epithymum only significant decrease in the viability of MDA-MB-468 cells was observed (IC50 = 340 μg/ml). From these findings it can be concluded that C. chinensis and C. epithymum are good candidates for further study to find new possible cytotoxic agents.

Construction of expressing vectors including melanoma differentiation-associated gene-7 (mda-7 fused with the RGD sequences for better tumor targeting

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Mahboobeh Khodadad

2015-08-01

Conclusion: Theoretically RGD tagged mda-7 would be able to induce apoptosis with more specificity and stronger than the standard one, therefore, these new constructs may have the potential for further researches.

Niacin treatment increases plasma homocyst(e)ine levels.

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Garg, R; Malinow, M; Pettinger, M; Upson, B; Hunninghake, D

1999-12-01

Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

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García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

2011-06-01

Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Malondialdehyde in benign prostate hypertrophy: a useful marker?

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Rosaria Alba Merendino

2003-01-01

Full Text Available Benign prostate hypertrophy (BPH is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this end, 22 BPH patients and 22 healthy donors were enrolled. Data show an increase of MDA level in BPH patients and a positive correlation between PSA and MDA levels. In conclusion, we describe a previously unknown relationship between PSA and MDA as an index of inflammation and oxidative stress in BPH.

Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC-EI-MS after derivatization with perfluorooctanoyl chloride

DEFF Research Database (Denmark)

Johansen, Sys Stybe; Jornil, Jakob

2009-01-01

), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA or ecstasy). An intra-day precision of 3-6% RSD and an inter-day precision of 3-17% RSD were observed. Trueness was between 96 % and 106% for the target compounds. The limit of detection ranged from 0.07 to 0.14 ng...

Experimental studies on anti-oxidants reducing lipid peroxidation of irradiated mice

International Nuclear Information System (INIS)

Du Zeji; Liu Keliang; Su Liaoyuan

1993-08-01

The free radical plays an important role in the irradiation damage. The irradiation damage would be reduced if anti-oxidants is used, because anti-oxidants can scavenge free radicals and suppress lipid peroxidation. In the study, a fluoro-spectrophotometer was used to determine the changes of MDA levels in mice tissues and serum after irradiation and the protective effect of anti-oxidants of Vit E and DMSO on damage caused by free radicals. The results are as follows: (1) The highest MDA level was at 12 to 24 hours after irradiation dose of 3.0 Gy. (2) The MDA level is increasing with the increasing of irradiation dose. It means the MDA level can indicate the extent of irradiation damage. (3) Both Vit E and DMSO had a powerful effect on reducing MDA level, but the effect of DMSO was stronger than Vit E. The optimum doses of them were 0.25 mg/g body weight and 10 mg/g body weight respectively. (4) The best effect obtained was to use Vit E and DMSO simultaneously

Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis.

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Casoinic, F; Sampelean, D; Buzoianu, Anca D; Hancu, N; Baston, Dorina

2016-12-01

Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

Effect of electrolyzed reduced water on malondialdehyde levels and ...

African Journals Online (AJOL)

Purpose: To evaluate the effects of electrolyzed reduced water (ERW) on malondialdehyde (MDA) levels and neutrophil cells in Wistar rats suffering from aggressive periodontitis. Methods: Wistar rats (Rattus norvegicus) were infected with A. actinomycetemcomitans before being divided into a control group and a treatment ...

Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines - An Isobolographic Analysis.

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Anna Wawruszak

Full Text Available Histone deacetylase inhibitors (HDIs are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA, vorinostat, alone or in combination with cisplatin (CDDP on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic interaction was observed for the combination of CDDP with VPA in MDA-MB-231 "triple-negative" (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.

Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

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Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

2016-06-01

The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

Increased carboxyhemoglobin level during liver resection with inflow occlusion.

Science.gov (United States)

Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

2013-04-01

Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

Supplementation of xanthophylls increased antioxidant capacity and decreased lipid peroxidation in hens and chicks.

Science.gov (United States)

Gao, Yu-Yun; Xie, Qing-Mei; Ma, Jing-Yun; Zhang, Xiang-Bin; Zhu, Ji-Mei; Shu, Ding-Ming; Sun, Bao-Li; Jin, Ling; Bi, Ying-Zuo

2013-03-28

The present study investigated the effects of xanthophyll supplementation on production performance, antioxidant capacity (measured by glutathione peroxidase, superoxide dismutase (SOD), catalase, total antioxidant capacity (T-AOC), and reduced glutathione:oxidised glutathione ratio (GSH:GSSG)) and lipid peroxidation (measured by malondialdehyde (MDA)) in breeding hens and chicks. In Expt 1, 432 hens were fed diets supplemented with 0 (control group), 20 or 40 mg xanthophyll/kg diet. Blood samples were taken at 7, 14, 21, 28 and 35 d of the trial. Liver and jejunal mucosa were sampled at 35 d. Both xanthophyll groups improved serum SOD at 21 and 28 d, serum T-AOC at 21 d and liver T-AOC, and serum GSH:GSSG at 21, 28 and 35 d and liver GSH:GSSG. Xanthophylls also decreased serum MDA at 21 d in hens. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg in ovo xanthophyll/kg diet of hens were fed a diet containing either 0 or 40 mg xanthophyll/kg diet. Liver samples were collected at 0, 7, 14 and 21 d after hatching. Blood samples were also collected at 21 d. In ovo-deposited xanthophylls increased antioxidant capacity and decreased MDA in the liver mainly within 1 week after hatching. Maternal effects gradually vanished during 1-2 weeks after hatching. Dietary xanthophylls increased antioxidant capacity and decreased MDA in the liver and serum mainly from 2 weeks onwards. Data suggested that xanthophyll supplementation enhanced antioxidant capacity and reduced lipid peroxidation in different tissues of hens and chicks.

Serum Leptin levels do not correlate with disease activity in Rheumatoid Arthritis

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Sibel Yilmaz Oner

2015-01-01

Full Text Available Objectives Leptin, is a fat tissue hormone which effects energy expenditure , food intake , hematopoiesis, osteogenesis, angiogenesis, reproductive and immune systems. We aimed to determine serum leptin levels and investigate the association between disease activity and other parameters in RA patients. Methods Patients with RA (n=106 as the study group, healthy controls (n=52 and osteoarthritis (OA patients (n=37 as a control group were enrolled to the study. RA patients were categorized in four different groups according to DAS28 scores: remission ,low (LDA, moderate (MDA or high (HDA disease activity . Results No differences were present between the body mass indices of the three groups. Mean leptin levels in RA patients, OA group and healthy individuals were 25,60±13,41, 23,03±11,51 and 23,81±12,85 ng/ml, respectively and no significant difference was present between the groups. Nine of (8,5% RA patients were in remission, 16 (15,1% were in LDA, 40 (37,7% in MDA and 41 (38,7% were in HDA. Leptin levels did not correlate with DAS28 scores of RA patients (r=-0,12, p=0,11. Mean leptin levels in RA patients with remission was 32,65±7, 28 in LDA 23,94±10,94 in MDA 26,73±14,92 and in HDA 23,59±13,50 ng/ml (p=NS. No associations were observed between leptin levels and CRP, ESR, RF positivity and disease duration. Conclusions Our study revealed no correlation of disease activity and serum leptin levels. Therefore leptin does not seem to be an appropriate biomarker to monitorize inflammation in RA.

Effects of ω3 on Serum Level of Malondialdehyde and Homocysteine in Type 2 Diabetic Patients

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M Jalali

2008-01-01

Full Text Available ABSTRACT: Introduction & Objective: Diabetes is regarded as a serious condition for both the individual and the society. One of the most important mortality reasons in diabetic patients is atherosclerosis. Many epidemiological studies have shown that the total homocysteine concentration is a risk indicator for cardiovascular disease. Malondialdehyde (MDA also is a highly toxic by-product formed in part by lipid oxidation derived free radicals. Many studies have shown that its concentration increases considerably in diabetes mellitus. Epidemiological data indicate that the consumption of omega-3 unsaturated fatty acids (O3FA leads to a reduction in cardiovascular disorders may protect against metabolic diseases. In recent years, numerous researches on omega-3 fatty acids have been done but it cannot be used as a confident additive. So in order to evaluate and compare the effects of ω3 on malondialdehyde (as fat peroxidation indicator and homocysteine on diabetic type 2 patients, this research was carried out in Tehran University. Materials & Methods: A randomized double blind placebo controlled clinical trial was conducted on 81 type 2 diabetic patients, 45–85 years old with diabetes for at least 2 years.Diabetic patients were randomly assigned to one of the case or control groups, each subject received 3 capsules per day of omega-3 or placebo for a period of 2 months. 10 ml blood was collected from each subject at the beginning and at the end of a 2-month trial. Serum MDA was determined with Tiobarbituric acid for more sensitivity and homosystein was measured by Hitachi autoanalyzer with Enzymatic Cycling method. Nutrients intakes were estimated using 24 h dietary recall questionnaire at the beginning and at the end of the 2-month trial for 2 days and analyzed by FPп. T-test also was used to compare groups. Results: Copmaring the mean±S.D of BMI and food intake in both groups showed no significant differences. MDA level degreased 0.72 nmol

Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.

Science.gov (United States)

Zhang, Cathy; Yan, Zhengming; Arango, Maria E; Painter, Cory L; Anderes, Kenna

2009-01-01

Tumors grafted s.c. or under the mammary fat pad (MFP) rarely develop efficient metastasis. By applying bioluminescence imaging (BLI) technology, the MDA-MB-435-HAL-Luc subrenal capsule (SRC) model was compared with the MFP model for disease progression, metastatic potential, and response to therapy. The luciferase-expressing MDA-MB-435-HAL-Luc cell line was used in both MFP and SRC models. BLI technology allowed longitudinal assessment of disease progression and the therapeutic response to PD-0332991, Avastin, and docetaxel. Immunohistochemical analysis of Ki67 and CD31 staining in the primary tumors was compared in these models. Caliper measurement was used in the MFP model to validate the BLI quantification of primary tumors. The primary tumors in MDA-MB-435-HAL-Luc MFP and SRC models displayed comparable growth rates and vascularity. However, tumor-bearing mice in the SRC model developed lung metastases much earlier (4 weeks) than in the MFP model (>7 weeks), and the metastatic progression contributed significantly to the survival time. In the MFP model, BLI and caliper measurements were comparable for quantifying palpable tumors, but BLI offered an advantage for detecting the primary tumors that fell below a palpable threshold and for visualizing metastases. In the SRC model, BLI allowed longitudinal assessment of the antitumor and antimetastatic effects of PD-0332991, Avastin, and docetaxel, and the results correlated with the survival benefits of these agents. The MDA-MB-435-HAL-Luc SRC model and the MFP model displayed differences in disease progression. BLI is an innovative approach for developing animal models and creates opportunities for improving preclinical evaluations of anticancer agents.

Increased urinary 8-hydroxy-2'-deoxyguanosine levels in workers exposed to di-(2-ethylhexyl) phthalate in a waste plastic recycling site in China.

Science.gov (United States)

Wang, Qian; Wang, Li; Chen, Xi; Rao, Kai Min; Lu, Shao You; Ma, Sheng Tao; Jiang, Pu; Zheng, Dan; Xu, Shun Qing; Zheng, Hong Yan; Wang, Jian Shu; Yu, Zhi Qiang; Zhang, Rong; Tao, Yong; Yuan, Jing

2011-07-01

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in industrial and diverse consumer products. Animal studies indicate DEHP caused developmental, reproductive, and hepatic toxicities. However, human studies of the potential effects of DEHP are limited. The exposed site with a history of over 20 years of waste plastic recycling was located in Hunan Province, China. The reference site without known DEHP pollution source was about 50 km far away from the exposed site. In this study, 181 workers working in plastic waste recycling and 160 gender-age matched farmers were recruited. DEHP concentrations in water and cultivated soil samples, serum thyroid-stimulating hormone, malondialdehyde (MDA), superoxide dismutase (SOD), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and micronuclei frequency in human capillary blood lymphocytes were analyzed. Mean levels of DEHP were greater in environment at the recycling site than at reference site (industry wastewater for the exposed: 42.43 μg/l; well water: 14.20 vs. 0.79 μg/l, pond water: 135.68 vs. 0.37 μg/l, cultivated soil: 13.07 vs. 0.81 mg/kg, p history of working in waste plastic recycling was an independent risk factor for the increased urinary 8-OHdG levels in the male workers (p < 0.01). The occupational DEHP exposure might contribute to oxidative deoxyribonucleic acid damage in the male workers.

An investigation about correlations of the levels of sex hormones with lipid profile, malondialdehyde, superoxide dismutase and T lymphocyte subpopulations

International Nuclear Information System (INIS)

Wu Saizhu; Tan Jiayu; Wu Yingxing; Sun Fei; Rong Zhiyi; Zhou Zhongjiang

2004-01-01

Objective: To investigate the correlations of the levels of sex hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL)] and lipid profile, malondialdehyde (MDA), superoxide dismutase (SOD) and T lymphocyte subpopulations. Methods: Through epidemiological investigations in our country, the levels of sex hormones were measured by radio-immunological methods; lipid profile and apolipoprotein by automatic biochemistry analyses; T cell subsets by flow cytometry; and the MDA was evaluated by the thiobarbituric acid (TBA) test and SOD by the nitrite method modified by Oyanagui, respectively using spectrophotometry. Results: In the study women, the concentrations of serum FSH, LH increased significantly after menopause; PRL increased after menopause; compared with the control group in the study population, 17β-estradiol (E 2 ) and progesterone (P) in postmenopausal group reduced obviously, 17β-E 2 /P reduced significantly after menopause. Testosterone (T) increased significantly after menopause, but not did free testosterone (FT) . 17β-E 2 , P and the ratio of 17β-E 2 /P were negatively correlated with age, respectively by bivariate correlation analysis, and a positive relation between T and age was observed. After the age of 70 years, the level of total cholesterol (TC) increased obviously, so did that of triglyceride (TG) after menopause; high density lipoprotein cholesterol (HDL-C) decreased after menopause, but low density lipoprotein cholesterol (LDL-C) increased after 70, the ratios of HDL-C/TC and HDL-C/LDL-C all reduced after menopause; ApoA-I decreased after 70, but ApoB increased significantly after menopause, correspondingly, the ratio of ApoA-I/ApoB declined obviously. CD3 + and CD4 + didn't change until 60, but reduced after 60. Compared with that in the control group, CD8 + remained unchanged, CD4 + /CD8 + reduced greatly with aging, and both CD4 + and CD8 + presented a negative correlation with aging. The serum MDA

Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models.

Directory of Open Access Journals (Sweden)

Emma L Davis

2018-01-01

Full Text Available There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.

Malondialdehyde levels of frozen fish, chicken and turkey on sale in ...

African Journals Online (AJOL)

PRECIOUS

2009-12-01

Dec 1, 2009 ... Highest levels of MDA were obtained in oily fishes,. Trachurus trecae .... fish (or smoked fish) and game formed the major protein sources for ... Rey AI, Kerry JP, Lynch PB, Lopez-Bote CJ, Buckley DJ, Morrissey PA. (2001).

Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

Science.gov (United States)

Nishida, K; Ohta, Y; Ishiguro, I

1997-08-27

gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression.

Science.gov (United States)

Hooshmand, Somayeh; Ghaderi, Abbas; Yusoff, Khatijah; Thilakavathy, Karuppiah; Rosli, Rozita; Mojtahedi, Zahra

2014-01-01

The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα. The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

Phenolic Fractions from Muscadine Grape "Noble" Pomace can Inhibit Breast Cancer Cell MDA-MB-231 Better than those from European Grape "Cabernet Sauvignon" and Induce S-Phase Arrest and Apoptosis.

Science.gov (United States)

Luo, Jianming; Wei, Zheng; Zhang, Shengyu; Peng, Xichun; Huang, Yu; Zhang, Yali; Lu, Jiang

2017-05-01

Tons of grape pomace which still contained a rich amount of plant polyphenols, is discarded after winemaking. Plant polyphenols have multi-functional activities for human body. In this study, polyphenols of pomaces from Muscadinia rotundifolia "Noble" and Vitis vinifera "Cabernet Sauvignon" were extracted and fractionated, and then they were analyzed with LC-MS and the inhibitory effects on breast cancer cells were compared. The inhibition on MDA-MB-231 cells of fractions from "Noble" was further evaluated. The results showed that polyphenols from 2 grape pomaces could be separated into 3 fractions, and ellagic acid and/or ellagitannins were only detected in fractions from "Noble" pomace. All 3 fractions from "Noble" pomace inhibited MDA-MB-231 better than MCF-7. But fraction 2 from "Cabernet Sauvignon" inhibited MCF-7 better while fraction 1 and fraction 3 inhibited both 2 cells similarly. Moreover, the fractions from "Noble" pomace rather than "Cabernet Sauvignon" can inhibit MDA-MB-231 better. Finally, fractions from "Noble" pomace can induce S-phase arrest and apoptosis on MDA-MB-231. These findings suggested the extracts from grape pomace especially those from "Noble," are potential to be utilized as health beneficial products or even anti-breast cancer agents. © 2017 Institute of Food Technologists®.

Primary, Secondary Metabolites, H2O2, Malondialdehyde and Photosynthetic Responses of Orthosiphon stimaneus Benth. to Different Irradiance Levels

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Mohd Hafiz Ibrahim

2012-01-01

Full Text Available The resource availability hypothesis predicts an increase in the allocation to secondary metabolites when carbon gain is improved relative to nutrient availability, which normally occurs during periods of low irradiance. The present work was carried out to confirm this hypothesis by investigating the effects of decreasing irradiance on the production of plant secondary metabolites (flavonoids and phenolics in the herbal plant Orthosiphon stamineus, and to characterize this production by carbohydrate, H2O2, and malondialdehyde (MDA levels, net photosynthesis, leaf chlorophyll content and carbon to nitrogen ratio (C/N. Four levels of irradiance (225, 500, 625 and 900 µmol/m2/s were imposed onto two-week old seedlings for 12 weeks in a randomized complete block design experiment. Peak production of total flavonoids, phenolics, soluble sugar, starch and total non-structural carbohydrate ocurred under low irradiance of 225 µmol/m2/s, and decreased with increasing irradiance. The up-regulation of secondary metabolites could be explained by the concomitant increases in H2O2 and MDA activities under low irradiance. This condition also resulted in enhanced C/N ratio signifying a reduction in nitrogen levels, which had established significant negative correlations with net photosynthesis, total biomass and total chlorophyll content, indicating the possible existence of a trade-off between growth and secondary metabolism under low irradiance with reduced nitrogen content. The competition between total chlorophyll and secondary metabolites production, as exhibited by the negative correlation coefficient under low irradiance, also suggests a sign of gradual switch of investment from chlorophyll to polyphenols production.

Effects of thyroid dysfunction and radiation exposure on some biochemical aspects in rats

International Nuclear Information System (INIS)

Mansour, S.Z.

2005-01-01

Radiation exposure effect associated with altered thyroid gland activity was investigated in rats. The results obtained showed that hypothyroidism was associated with low blood levels of free thyroxine (FT4), free triiodothyronine (FT3), high levels of thyroid stimulating hormone (TSH), decreased blood malondialdehyde level (MDA), increased glutathione peroxidase (GSH-Px) activity and hypocalcemia were observed. Hyperthyroidism was accompanied with high blood FT4 and FT3, low TSH levels, increased MDA levels, decreased GSH-Px activity, hypercalcaemia, low albumin level and A/G ratio were recorded. Globulin and vitamin E levels were not affected by the changes of animal thyroid states. In hypothyroid irradiated rats, although significant amelioration was recorded in blood GSH-Px activity and MDA contents, compared to hypothyroid rats, irradiation exaggerated the changes in FT4, FT3, TSH levels and also increased globulin and decreased vitamin E. Irradiation of hyperthyroid rats ameliorated hormones and albumin levels as compared to hyperthyroid rats. Despite of a decrease in blood vitamin E, the changes in MDA levels, GSH-Px activity and Ca levels were nearly similar to those recorded for hyperthyroid rats. According to the data obtained in the present study, it could be concluded that symptoms of hypothyroidism could be intensified by exposure to radiation

Serum heme oxygenase-1 levels in patients with primary dysmenorrhea.

Science.gov (United States)

Aksoy, Ayse Nur; Laloglu, Esra; Ozkaya, Alev Lazoglu; Yilmaz, Emsal Pınar Topdagi

2017-04-01

Primary dysmenorrhea effects the life-quality of women negatively. The aim of this study was to evaluate heme oxygenase-1 (HO1) activity together with malondialdehyde (MDA) and nitric oxide (NO) levels in patients with primary dysmenorrhea. A total of 28 nulliparous women with the diagnosis of primary dysmenorrhea and 26 healthy controls were included in this study. On the first day of menstruation, all patients underwent ultrasound examination to exclude pelvic pathology and the visual analogue scale was applied to patients. Patient's visual analogue scale (VAS) scores, age, body mass index (BMI), menstrual cycle length (day), length of bleeding (day) were recorded. In the same day, fasting blood samples were taken from each patient for biochemical analysis. Serum MDA, NO and HO1 levels were found to be higher in women with primary dysmenorrhea compared to healthy controls (p = 0.012, p = 0.009, p dysmenorrhea. Antioxidant support might be helpful to reduce pain severity in primary dysmenorrhea.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

Science.gov (United States)

Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

2013-01-01

AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

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Orhan Ates

2013-10-01

Full Text Available AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP and plasma coenzyme Q10(CoQ10 concentration.METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50. The control group was consist of healthy individuals (n=50. Plasma CoQ10 and malondialdehyde (MDA levels were measured in both groups.RESULTS: Ubiquinone-10 (Coenzyme Q10 levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively.CONCLUSION:The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.

Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

DEFF Research Database (Denmark)

Kücükakin, Bülent; Kocak, Volkan; Lykkesfeldt, Jens

2011-01-01

of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. Study design and methods. Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35......, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6). Results. The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed...... significantly during the storage period (p oxidative and inflammatory stress during a storage period...

Malondialdehyde level and some enzymatic activities in subclinical ...

African Journals Online (AJOL)

The purpose of this study was to evaluate the changes occurring in milk malondialdehyde (MDA) level and some enzymatic activities as a result of subclinical mastitis (SCM) in dairy cows. A total of 124 milk samples were collected from 124 lactating cows from the same herd in the period between the 2nd week after calving ...

Dietary guanidinoacetic acid increases brain creatine levels in healthy men

DEFF Research Database (Denmark)

Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

2017-01-01

OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA......, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation......, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8...

Increased oxidative/nitrosative stress markers measured non- invasively in patients with high 2,3,7,8-tetrachloro-dibenzo-p-dioxin plasma level

Czech Academy of Sciences Publication Activity Database

Pelclová, D.; Navrátil, Tomáš; Fenclová, Z.; Vlčková, Š.; Kupka, K.; Urban, P.; Ridzoň, P.; Zikán, V.; Landová, L.; Syslová, K.; Kuzma, Marek; Kačer, P.

2011-01-01

Roč. 32, č. 1 (2011), s. 71-76 ISSN 0172-780X Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50200510 Keywords : dioxin * MDA * HNE Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.296, year: 2011

Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line.

Science.gov (United States)

Banerjee, Malabika; Chattopadhyay, Subrata; Choudhuri, Tathagata; Bera, Rammohan; Kumar, Sanjay; Chakraborty, Biswajit; Mukherjee, Samir Kumar

2016-04-16

Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration. Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide

Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

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Mennerich Detlev

2007-01-01

Full Text Available Abstract Background Stromelysin-3 (ST-3 is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. Methods The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Results Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. Conclusion These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated "early stage" breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour

Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

International Nuclear Information System (INIS)

Kasper, Grit; Lehmann, Kerstin E; Reule, Matthias; Tschirschmann, Miriam; Dankert, Niels; Stout-Weider, Karen; Lauster, Roland; Schrock, Evelin; Mennerich, Detlev; Duda, Georg N

2007-01-01

Stromelysin-3 (ST-3) is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated 'early stage' breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour fibroblasts leads to the stimulation of the IGF-1R pathway in

Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures

Science.gov (United States)

Tseroni, Maria; Baka, Agoritsa; Kapizioni, Christina; Snounou, Georges; Tsiodras, Sotirios; Charvalakou, Maria; Georgitsou, Maria; Panoutsakou, Maria; Psinaki, Ioanna; Tsoromokou, Maria; Karakitsos, George; Pervanidou, Danai; Vakali, Annita; Mouchtouri, Varvara; Georgakopoulou, Theano; Mamuris, Zissis; Papadopoulos, Nikos; Koliopoulos, George; Badieritakis, Evangelos; Diamantopoulos, Vasilis; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

2015-01-01

Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011–2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013–2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4–39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of

Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures.

Science.gov (United States)

Tseroni, Maria; Baka, Agoritsa; Kapizioni, Christina; Snounou, Georges; Tsiodras, Sotirios; Charvalakou, Maria; Georgitsou, Maria; Panoutsakou, Maria; Psinaki, Ioanna; Tsoromokou, Maria; Karakitsos, George; Pervanidou, Danai; Vakali, Annita; Mouchtouri, Varvara; Georgakopoulou, Theano; Mamuris, Zissis; Papadopoulos, Nikos; Koliopoulos, George; Badieritakis, Evangelos; Diamantopoulos, Vasilis; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

2015-11-01

Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011-2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013-2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4-39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of MDA can

Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women

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Sara Soleimani Rad

2015-07-01

Full Text Available Background: Infertility is defined as the inability to achieve the pregnancy within a year of unprotected intercourse. Infertility is a complex issue and different factors such as stress oxidative can be involved in this problem. So, any attempt to neutralize oxidative stress would be helpful in the treatment of infertility. Melatonin is a known scavenger of free radicals. Objective: The aim of our study was to evaluate the level of melatonin and its correlation with oxidative biomarkers in fertile and infertile women. Materials and Methods: The participants including fertile and infertile women were divided into two groups of 30 people. Blood sampling was performed and sera were collected. The level of Malondialdehyde (MDA, total antioxidant capacity (TAC and melatonin were detected. Data were analyzed using T-test and their correlation was assessed using Spearman test. Results: Serum melatonin from fertile women was higher than infertile women but the difference was not significant (p= 0.46. MDA level in fertile women was significantly lower than infertile women (p<0.001 and the level of TAC in fertile women was significantly higher than infertile women (p<0.001. Spearman test revealed a significant and direct correlation between melatonin and TAC in fertile and infertile women and a significant but reverse correlation between melatonin and MDA in infertile and fertile women. Conclusion: Differences in the level of oxidative stress biomarkers in fertile and infertile individuals have been reported. This study revealed a significant correlation between melatonin and oxidative stress biomarkers, concluding that melatonin level could be involved in infertility.

Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

Energy Technology Data Exchange (ETDEWEB)

Tsai, I-Lin [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Kuo, Tien-Chueh [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, Room 410 BL Building, No. 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Ho, Tsung-Jung [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Harn, Yeu-Chern [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Graduate Institute of Networking and Multimedia, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Wang, San-Yuan [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Fu, Wen-Mei [Department of Pharmacology, National Taiwan University, 11 F No. 1 Sec. 1, Ren-ai Rd., Taipei 10051, Taiwan (China); Kuo, Ching-Hua, E-mail: kuoch@ntu.edu.tw [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Tseng, Yufeng Jane, E-mail: kuoch@ntu.edu.tw [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, Room 410 BL Building, No. 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China)

2013-05-03

Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

International Nuclear Information System (INIS)

Tsai, I-Lin; Kuo, Tien-Chueh; Ho, Tsung-Jung; Harn, Yeu-Chern; Wang, San-Yuan; Fu, Wen-Mei; Kuo, Ching-Hua; Tseng, Yufeng Jane

2013-01-01

Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis

Lipid peroxidation and ascorbic acid levels in Nigeria children with ...

African Journals Online (AJOL)

This study was undertaken to establish data on the roles of lipid peroxidation and ascorbic acid in the pathology of malaria in Nigeria children. We measured the levels of malondialdehyde (MDA), a marker of lipid peroxidation and ascorbic acid in the plasma of 406 parasitaemic and 212 non-parasitaemic Nigerian children.

Influence of fatigue time and level on increases in postural sway.

Science.gov (United States)

Pline, Kevin M; Madigan, Michael L; Nussbaum, Maury A

2006-12-15

The purpose of this study was to investigate the influence of fatigue time and fatigue level on the increases in postural sway during quiet standing. Centre of pressure-based measures of postural sway were collected both before and after fatiguing participants using three different fatigue levels and two different fatigue times. Results showed increasing fatigue time increased sway velocity and sway area, and increasing fatigue level increased sway velocity. Fatigue time effects are important to consider when applying laboratory-based findings to the field given that the fatigue time can differ substantially between the two. Fatigue level effects imply a dose - response relationship between localized muscle fatigue and risk of falling that can have important implications in work/rest cycle scheduling for occupations at risk of injurious falls.

Diffuse radiation increases global ecosystem-level water-use efficiency

Science.gov (United States)

Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

2012-12-01

Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

Effect of radiation therapy on lipid peroxidation and total antioxidant capacity of blood and saliva in oral cancer patients

International Nuclear Information System (INIS)

Lobo, Aswin D.A.

2012-01-01

Radiation therapy is reported to induce oxidative stress in oral cancer patients. Saliva as a diagnostic tool has received increasing attention in recent years. Saliva analysis is proposed to be a noninvasive, sensitive tool for the evaluation of biological effects of radiation therapy in oral cancer. We aimed to assess the effect of radiation therapy on malondialdehyde, the marker of lipid peroxidation, and total antioxidant capacity in blood and saliva of oral cancer patients. We also aimed to assess the correlation between blood and saliva with respect to malonaldehyde (MDA) level and total antioxidant capacity (TAC). Thirty, clinically diagnosed oral cancer patients visiting the Oncology Department were the subjects. Thirty age- and sex-matched normal, healthy controls were included. Blood and saliva samples were collected from controls, and from oral cancer patients before and after radiation therapy. The samples were analyzed for MDA and TAC by standard spectrophotometric methods. Oral cancer patients showed significantly higher MDA level and lower TAC in blood and saliva when compared to controls. One week after radiation therapy, there was significant increase in MDA and decrease in TAC in oral cancer patients. After the completion of radiation therapy of six weeks, MDA level decreased and TAC increased, restoring the values near-to-controls. The pattern of change in MDA and TAC was similar between blood and saliva. There was significant correlation between blood and saliva with respect to MDA and TAC in oral cancer patients. Oral cancer patients showed increased oxidative stress and impaired antioxidant capacity. After radiation therapy of one week, oxidative stress increased further, and after six weeks of radiation therapy there was amelioration of antioxidant status. Saliva could be a sensitive and convenient laboratory tool for diagnosis of oral cancer and evaluation of biological effects of radiation therapy. (author)

Efeitos do butirato nos níveis de peroxidação lipídica em células da mucosa cólica sem trânsito fecal: estudo experimental em ratos Effects of butyrate on levels of lipid peroxidation in cells of the colonic mucosa without fecal stream: experimental study in rats

Directory of Open Access Journals (Sweden)

Thais Miguel do Monte Lameiro

2011-06-01

without fecal stream of animals irrigated with butyrate (p=0.006, but after four weeks were similar (p=0.08. In the colon without fecal stream irrigated with butyrate, MDA levels increased with the time (p=0.02, while in segments with fecal stream MDA not changed. (p=0.86. Butyrate reduces the levels of MDA in the colonic mucosa without fecal stream, after two weeks of derivation. However, the irrigation with the substance is not able to reduce the lipid peroxidation of mucosal cells with increasing time of intestinal exclusion.

Alteration of gene expression in MDA-MB-453 breast cancer cell line in response to continuous exposure to Trastuzumab.

Science.gov (United States)

Sharieh, Elham Abu; Awidi, Abdulla S; Ahram, Mamoun; Zihlif, Malek A

2016-01-10

Development of resistance against cancer therapeutic agents is a common problem in cancer management. Trastuzumab resistance is one of the challenges in management of HER-2-positive breast cancer patients resulting in breast cancer progression, metastasis, and patient poor outcome. The aim of this study is to determine the alteration in gene expression in response to Trastuzumab resistance after long-term exposure to Trastuzumab. The Trastuzumab-resistant MDA-MB-453 (MDA-MB-453/TR) cell line was developed by exposing cells to 10 μM Trastuzumab continuously for 6 months. Sensitivity toward Trastuzumab was tested using cell viability assays. The acquisition of an epithelial-to mesenchymal transition (EMT) phenotype was also observed in parallel with the development of resistance. Based on the real-time-based PCR array technology, several genes were altered affecting multiple networks. The most up-regulated genes were TGF-β1 and EGF, and IGFBP-3. These genes are known to have a critical role in Trastuzumab resistance in breast cancer cell lines and/or in the acquisition of EMT. They are also recognized for their role in cancer progression and metastasis. These alterations indicate that the development of Trastuzumab resistance is multifactorial and involves a development of a mesenchymal like phenotype. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of calcium electroporation in combination with metformin in vivo and correlation between viability and intracellular ATP level after calcium electroporation in vitro

DEFF Research Database (Denmark)

Frandsen, Stine Krog; Gehl, Julie

2017-01-01

cancer cell lines: Breast (MDA-MB231) and colon (HT29), and in normal human fibroblasts (HDF-n), as well as investigating viability in human bladder cancer cells (SW780) and human small cell lung cancer cells (H69) where we have previously published intracellular ATP levels. RESULTS: Calcium...... with calcium alone (pHDF-n, and MDA-MB231; p

Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

Science.gov (United States)

Kishimoto, Yoshimi; Taguchi, Chie; Saita, Emi; Suzuki-Sugihara, Norie; Nishiyama, Hiroshi; Wang, Wei; Masuda, Yasunobu; Kondo, Kazuo

2017-09-01

The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of different levels of catalase and superoxide dismutase in modified Beltsville extender on rooster post-thawed sperm quality.

Science.gov (United States)

Amini, Mahmood Reza; Kohram, Hamid; Zare-Shahaneh, Ahmad; Zhandi, Mahdi; Sharideh, Hossein; Nabi, Mohammad Mehdi

2015-06-01

Oxidative damage of sperm by means of reactive oxygen species generated by the cellular components of semen is one of the main reasons for decreased sperm motility and fertility during the freeze-thawing process. This study was conducted to determine the influence of catalase (CAT) and superoxide dismutase (SOD) on rooster sperm motility, viability and MDA level after freezing and thawing. Semen samples from 10 sexually-mature Ross 308 breeder roosters were collected and pooled, divided into nine equal parts and diluted with modified Beltsville extender containing no antioxidants (control), or supplemented with 50, 100, 200 and 300 μg/mL CAT, or 50, 100, 200 and 300 U/mL SOD. After thawing, sperm motility and motion parameters were assessed using a CASA system. Sperm viability and MDA level were assessed by eosin-nigrosin and MDA test, respectively. The results of this experiment showed that the extender supplemented with 100 and 200 μg CAT, and 50 U SOD had the highest sperm motility (Prooster semen. Copyright © 2015 Elsevier Inc. All rights reserved.

A study of oxidative stress in paucibacillary and multibacillary leprosy

Directory of Open Access Journals (Sweden)

Jyothi P

2008-01-01

Full Text Available Background: The study and assessment of oxidative stress plays a significant role in the arena of leprosy treatment. Once the presence of oxidative stress is proved, antioxidant supplements can be provided to reduce tissue injury and deformity. Aim: To study oxidative stress in paucibacillary (PB and multibacillary (MB leprosy and to compare it with that in a control group. Methods: Fifty-eight untreated leprosy patients (23 PB and 35 MB cases were studied and compared with 58 healthy controls. Superoxide dismutase (SOD level as a measure of antioxidant status; malondialdehyde (MDA level, an indicator of lipid peroxidation; and MDA/SOD ratio, an index of oxidative stress were estimated in the serum. Results: The SOD level was decreased in leprosy patients, especially in MB leprosy. The MDA level was increased in PB and MB leprosy. The MDA/SOD ratio was significantly elevated in MB patients. There was a steady increase in this ratio along the spectrum from tuberculoid to lepromatous leprosy (LL. Conclusion: There is increased oxidative stress in MB leprosy, especially in LL. This warrants antioxidant supplements to prevent tissue injury.

Endozepine-4 levels are increased in hepatic coma.

Science.gov (United States)

Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

2015-08-14

To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. Subjects with hepatic coma showed significant difference in endozepine-4 (P blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.

Dietary fiber and lipid peroxidation: effect of dietary fiber on levels of lipids and lipid peroxides in high fat diet.

Science.gov (United States)

Thampi, B S; Manoj, G; Leelamma, S; Menon, V P

1991-06-01

Effect of feeding coconut and blackgram fiber isolated as neutral detergent fiber (NDF) on the levels of lipids and lipid peroxides was studied in rats given a high fat diet. Concentration of cholesterol, free falty acid and phospholipids showed significant decrease in the serum, liver aorta and intestine of coconut and blackgram fiber groups. Concentration of malondialdehyde (MDA) and conjugated dienes was significantly decreased in liver and intestine of both fiber groups, while hydroperoxides showed significant increase in liver and heart of both the fiber groups. SOD and catalase activity was found to be increased in liver, intestine, heart proximal colon and distal colon of both the fiber groups. Serum ceruloplasmin levels showed a slight increase in animals fed coconut and blackgram fiber groups. Glutathione levels in liver, intestine proximal colon, distal colon and heart also showed a significant decrease in the animals of both the fiber groups.

Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

Directory of Open Access Journals (Sweden)

Yufeng Jane Tseng

2013-05-01

Full Text Available Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

Both experimental hypothyroidism and hyperthyroidism increase cardiac irisin levels in rats.

Science.gov (United States)

Atici, E; Menevse, E; Baltaci, A K; Mogulkoc, R

2018-01-01

Irisin is a newly discovered myokine and adipokine that increases total body energy expenditure. The aim of this study was to determine the effect of experimental hypothyroidism and hyperthyroidism on the levels of irisin in heart tissue in rats. The study was performed on the 40 male Sprague-Dawley rats. Experimental groups were designed as; Control, Hypothyroidism, Hypothyroidism+L-Thyroxine, Hyperthyroidism and Hyperthyroidism + PTU. Following 3 weeks experimental period, irisin levels were determined in heart tissues. Hypothyroidism group values of irisin were higher than in the control group, but lower than in the hyperthyroidism group. The hyperthyroidism group had the highest levels of cardiac irisin. The results of the study showed that the experimental hypothyroidism and hyperthyroidism increased the heart irisin levels, but the increase in the hyperthyroidism group was much higher than in the hypothyroidism group. However, treatment of hypothyroidism and hyperthyroidism corrected cardiac irisin levels (Fig. 1, Ref. 28).

Blood lipid peroxides and muscle damage increased following intensive resistance training of female weightlifters.

Science.gov (United States)

Liu, Jen-Fang; Chang, Wei-Yin; Chan, Kuei-Hui; Tsai, Wen-Yee; Lin, Chen-Li; Hsu, Mei-Chieh

2005-05-01

The aim of this study was to examine changes in muscle cell injury and antioxidant capacity of weightlifters following a 1-week intensive resistance-training regimen. Thirty-six female subjects participated in this study, and their ages ranged from 18 to 25 years. The sample group included 19 elite weightlifters with more than 3 years of weightlifting training experience, while the control group comprised 17 non-athletic individuals. Compared with non-athletes, weightlifters had significantly lower glutathione peroxidase activity and plasma vitamin C concentrations. Weightlifters also had significantly higher malondialdehyde + 4-hydroxy 2-(E)-nonenal (MDA+4-HNE) and thiobarbituric acid-reactive substance (TBARS) levels and creatine kinase (CK) activity. For weightlifters, the plasma vitamin E level and the activity of superoxide dismutase (SOD) decreased, and CK activity increased significantly (P weightlifters (P injury in female weightlifters. Furthermore, proper rest after intensive training was found to be important for recovery.

Effects of Water Level Increase on Phytoplankton Assemblages in a Drinking Water Reservoir

Directory of Open Access Journals (Sweden)

Yangdong Pan

2018-03-01

Full Text Available Excessive water level fluctuation may affect physico-chemical characteristics, and consequently ecosystem function, in lakes and reservoirs. In this study, we assessed the changes of phytoplankton assemblages in response to water level increase in Danjiangkou Reservoir, one of the largest drinking water reservoirs in Asia. The water level increased from a low of 137 m to 161 m in 2014 as a part of the South–North Water Diversion Project. Phytoplankton assemblages were sampled four times per year before, during and after the water level increase, at 10 sites. Environmental variables such as total nitrogen as well as phytoplankton biomass decreased after the water level increase. Non-metric multi-dimensional scaling analysis indicated that before the water level increase, phytoplankton assemblages showed distinct seasonal variation with diatom dominance in both early and late seasons while such seasonal variation was much less evident after the water level increase. Month and year (before and after explained 13% and 6% of variance in phytoplankton assemblages (PERMANOVA, p < 0.001 respectively, and phytoplankton assemblages were significantly different before and after the water level increase. Both chlorophytes and cyanobacteria became more abundant in 2015. Phytoplankton compositional change may largely reflect the environmental changes, such as hydrodynamics mediated by the water level increase.

Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

International Nuclear Information System (INIS)

Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

2014-01-01

Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells

Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

Energy Technology Data Exchange (ETDEWEB)

Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

2014-05-09

Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

Salt-tolerant rootstock increases yield of pepper under salinity through maintenance of photosynthetic performance and sinks strength.

Science.gov (United States)

Penella, Consuelo; Landi, Marco; Guidi, Lucia; Nebauer, Sergio G; Pellegrini, Elisa; San Bautista, Alberto; Remorini, Damiano; Nali, Cristina; López-Galarza, Salvador; Calatayud, Angeles

2016-04-01

The performance of a salt-tolerant pepper (Capsicum annuum L.) accession (A25) utilized as a rootstock was assessed in two experiments. In a first field experiment under natural salinity conditions, we observed a larger amount of marketable fruit (+75%) and lower Blossom-end Root incidence (-31%) in commercial pepper cultivar Adige (A) grafted onto A25 (A/A25) when compared with ungrafted plants. In order to understand this behavior a second greenhouse experiment was conducted to determine growth, mineral partitioning, gas exchange and chlorophyll a fluorescence parameters, antioxidant systems and proline content in A and A/A25 plants under salinity conditions (80 mM NaCl for 14 days). Salt stress induced significantly stunted growth of A plants (-40.6% of leaf dry weight) compared to the control conditions, while no alterations were observed in A/A25 at the end of the experiment. Accumulation of Na(+) and Cl(-) in leaves and roots was similar in either grafted or ungrafted plants. Despite the activation of protective mechanisms (increment of superoxide dismutase, catalase, ascorbate peroxidase activity and non-photochemical quenching), A plants showed severely reduced photosynthetic CO2 assimilation (-45.6% of AN390) and substantial buildup of malondialdehyde (MDA) by-product, suggesting the inability to counteract salt-triggered damage. In contrast, A/A25 plants, which had a constitutive enhanced root apparatus, were able to maintain the shoot and root growth under salinity conditions by supporting the maintained photosynthetic performance. No increases in catalase and ascorbate peroxidase activities were observed in response to salinity, and MDA levels increased only slightly; indicating that alleviation of oxidative stress did not occur in A/A25 plants. In these plants the increased proline levels could protect enzymatic stability from salt-triggered damage, preserving the photosynthetic performance. The results could indicate that salt stress was vanished by

Activity assay of mangosteen (Garcinia mangostana L.) pericarp extract for decreasing fasting blood cholesterol level and lipid peroxidation in type-2 diabetic mice

Science.gov (United States)

Husen, Saikhu Akhmad; Winarni, Dwi; Khaleyla, Firas; Kalqutny, Septian Hary; Ansori, Arif Nur Muhammad

2017-09-01

This study aimed to explore the activity of pericarp extract of mangosteen (Garcinia mangostana L.). Mangosteen pericarp contains various active compounds which are beneficial for human health. In-vivo antioxidant assay of pericarp extract was carried out using 3-4 month male mice of strain BALB/c weighed 30-40 g. The mice were divided into two groups: normal control (KN) group and STZ-induced diabetic group. STZ induction was performed using multiple low-dose method 30 mg/kg body weight treated daily for five consecutive days. Diabetic group was separated into two subgroups: diabetic control (KD), metformin control (KM), and crude extract treatment subgroups. The fasting blood glucose and the cholesterol level were measured before and after lard treatment, we also did it on the first, seventh, and fourteenth day of mangosteen pericarp crude extract treatment. The mice were treated with mangosteen pericarp crude extract for 14 days. The MDA level of the fasting blood serum was measured. The body weight and fasting blood cholesterol level before and after lard treatment were analyzed by t-test, whereas, the fasting blood cholesterol and the MDA level were analyzed using one-way variant analysis continued with Duncan test. The correlation between the increasing body weight and the fasting blood cholesterol level was determined by Pearson correlation test. The results of the study showed that the administration of mangosteen pericarp crude extract was able to reduce the fasting blood cholesterol and the malondialdehide level significantly.

Do levels of perceived stress increase with increasing age after age 65? A population-based study.

Science.gov (United States)

Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

2015-09-01

psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).

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Koutroumani, Nikolitsa; Partsalaki, Ioanna; Lamari, Fotini; Dettoraki, Athina; Gil, Andrea Paola Rojas; Karvela, Alexia; Kostopoulou, Eirini; Spiliotis, Bessie E

2013-01-01

Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.

Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in Renal Transplant Recipients

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Ghorbanihaghjo Amir

2005-05-01

Full Text Available Abstract Abstract Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR. The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from138.2 to 132.8 mmHg (p=0.001 and Malondialdehyde (MDA decreased from 2.4 to1.7 nmol/ml (p=0.009 by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03, triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008, MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001, systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001, diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001 and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03 by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed had no lowering effect on lipid level of serum. But Crushed garlic (chewed reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic.

Enhancement of viability of radiosensitive (PBMC and resistant (MDA-MB-231 clones in low-dose-rate cobalt-60 radiation therapy

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Patrícia Lima Falcão

2015-06-01

Full Text Available Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231 cells line and radiosensitive peripheral blood mononuclear cells (PBMC, as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

Comparison of inflammation and oxidative stress levels by the severity of obesity in prepubertal children

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Ni Luh Putu Surya Candra Eka Pertiwi

2018-01-01

Full Text Available Background Children with severe obesity are more likely to develop diabetes and cardiovascular diseases at a younger age. Inflammation and oxidative stress associated with childhood obesity may be important in the development of insulin resistance and atherosclerosis. Objective To compare levels of high-sensitivity C-reactive protein (hsCRP and malondialdehyde (MDA by the severity of obesity in prepubertal children aged 6 to 10 years. Methods We conducted a cross-sectional study at the Pediatric Nutrition and Metabolic Syndrome Clinic, Sanglah Hospital, Bali, from August to December 2015. Subjects were categorized into three body mass index (BMI groups, according to the 2000 Centers for Disease Control and Prevention growth chart: overweight (85th-94.9th percentile, obese (95th-98.9th percentile, or severely obese (≥ 99th percentile. Plasma MDA and serum hsCRP were analyzed in blood specimens obtained at enrollment. Data were analyzed by Kruskal-Wallis test, followed by Mann-Whitney U test for post-hoc comparison between groups. Results Subjects were 20 overweight children, 29 obese children, and 28 severely obese children. Levels of MDA were significantly higher in the severely obese [median 0.25 (IQR 0.1 μmol/L] than in obese subjects [median 0.19 (IQR 0.1 μmol/L; P=0.001], and than in overweight subjects [median 0.16 (IQR 0.1 μmol/L; P<0.0001]. Also, the severely obese children had significantly higher hsCRP levels compared to obese [median 3.2 (IQR 2.0 mg/L vs. 1.3 (1.6 mg/L, respectively; P<0.0001] and compared to overweight children [median 0.7 (IQR 0.6 mg/L; P<0.0001].     Conclusion Prepubertal children at the ≥ 99th percentile for BMI (severely obese are more likely to have significantly higher hsCRP and MDA compared to those in the obese and overweight groups.

Emotionally arousing pictures increase blood glucose levels and enhance recall.

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Blake, T M; Varnhagen, C K; Parent, M B

2001-05-01

Arousal enhances memory in human participants and this enhancing effect is likely due to the release of peripheral epinephrine. As epinephrine does not readily enter the brain, one way that peripheral epinephrine may enhance memory is by increasing circulating blood glucose levels. The present study investigated the possibility that emotionally arousing color pictures would improve memory and elevate blood glucose levels in human participants. Blood glucose levels were measured before, 15 min, and 30 min after male university students viewed 60 emotionally arousing or relatively neutral pictures. Participants viewed each picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and valence (pleasantness) of each picture. A free-recall memory test was given 30 min after the last picture was viewed. Although the emotionally arousing and neutral picture sets were given comparable valence ratings, participants who viewed the emotionally arousing pictures rated the pictures as being more arousing, recalled more pictures, and had higher blood glucose levels after viewing the pictures than did participants who viewed the neutral pictures. These findings indicate that emotionally arousing pictures increase blood glucose levels and enhance memory, and that this effect is not due to differences in the degree of pleasantness of the stimuli. These findings support the possibility that increases in circulating blood glucose levels in response to emotional arousal may be part of the biological mechanism that allows emotional arousal to enhance memory. Copyright 2001 Academic Press.

Efek Ekstrak Etanol Daun Premna cordifolia terhadap Malondialdehida Tikus yang Dipapar Asap Rokok

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Asri Adyttia

2014-08-01

Full Text Available Free radicals from cigarrete smoke cause lipid peroxidation that can be identified with increasing levels of Malondialdehida (MDA. Premna cordifolia leaves are known having antioxidant activity in in vitro study. This study aimed to know the effect of P. cordifolia leaves extract on the levels of MDA after exposure to cigarette smoke. The simplicia was extracted with maseration method using 70% ethanol. Twenty four male wistar rats were divided into six groups, i.e.: normal control, negative control, positive control which recieved cigarette smoke exposure and vitamin E (18mg/kg BW, as well as the other three groups which recieved cigarette smoke exposure and P. cordifolia leaves extract with doses of 200; 400; 600 mg/kg BW. All rats were treated for 14 days. MDA level was measured using Spectrophotometer UV-Vis at the wavelenght of 532,2 nm. MDA levels in the normal group was 0.0094±0.080 ppm; negative group was 13,733±2,829 ppm; positive group was 0,051±0,045 ppm; and doses of 200; 400; 600 mg/kg BW were 9,142±2,364; 0,120±0,019; 0,053±0,041 ppm, respectively. The MDA level was analyzed with the Kruskal-Wallis test and then Mann-Whitney test. The result showed that MDA levels of groups receiving P. cordifolia leaves extract were significantly (p>0,05 lower than negative control group. These results showed that P. cordifolia leaves extract could reduce the MDA level on the rats which recieved cigarette smoke exposure.

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

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Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

2016-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

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Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

2016-10-20

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2 H -furo[3,2- b ][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

IK channel activation increases tumor growth and induces differential behavioral responses in two breast epithelial cell lines.

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Thurber, Amy E; Nelson, Michaela; Frost, Crystal L; Levin, Michael; Brackenbury, William J; Kaplan, David L

2017-06-27

Many potassium channel families are over-expressed in cancer, but their mechanistic role in disease progression is poorly understood. Potassium channels modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and other voltage-sensitive signaling mechanisms, potentially acting as transcriptional regulators. This study investigated the differential response to over-expression and activation of a cancer-associated potassium channel, the intermediate conductance calcium-activated potassium channel (IK), on aggressive behaviors in mammary epithelial and breast cancer cell lines. IK was over-expressed in the highly metastatic breast cancer cell line MDA-MB-231 and the spontaneously immortalized breast epithelial cell line MCF-10A, and the effect on cancer-associated behaviors was assessed. IK over-expression increased primary tumor growth and metastasis of MDA-MB-231 in orthotopic xenografts, demonstrating for the first time in any cancer type that increased IK is sufficient to promote cancer aggression. The primary tumors had similar vascularization as determined by CD31 staining and similar histological characteristics. Interestingly, despite the increased in vivo growth and metastasis, neither IK over-expression nor activation with agonist had a significant effect on MDA-MB-231 proliferation, invasion, or migration in vitro. In contrast, IK decreased MCF-10A proliferation and invasion through Matrigel but had no effect on migration in a scratch-wound assay. We conclude that IK activity is sufficient to promote cell aggression in vivo. Our data provide novel evidence supporting IK and downstream signaling networks as potential targets for cancer therapies.

Increased plasma agmatine levels in patients with schizophrenia.

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Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

2013-08-01

Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p  0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lead-elevated activity of xanthine oxidase in lead-exposed workers

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Sławomir Kasperczyk

2013-04-01

Full Text Available Background: The aim of the present study was to explore the connection between lead toxicity and the activity of xanthine oxidase (XO. In addition, we indicated the uric acid (UA and creatinine levels and concentration of erythrocyte malondialdehyde (MDA to estimate oxidative stress intensity. Materials and Methods: The examined group consisted of 125 healthy male employees of zinc and lead works. The examined group was divided into tertiles according to blood lead levels. In the collected blood samples, concentrations of lead-exposure indices, UA, creatinine, and MDA as well as activity of XO were measured concomitantly. The control group consisted of 32 healthy male administrative workers who were exposed to lead only environmentally. Results: XO activity and MDA level were significantly elevated in all tertiles compared to the control group. Creatinine level was significantly elevated in the medium and high tertiles. However, the level of UA was significantly elevated in the high tertile, while in the low and medium tertile only a tendency toward higher values was observed. Conclusions: Occupational exposure to lead induces activity of XO. This induction may contribute to the observed simultaneously increased oxidative stress, measured as MDA level, and the increased level of UA. Med Pr 2013;64(2:175–180

Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

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Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

2016-03-16

Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. © 2016 The Authors.

Protective effect of serotonin on phospholipids and lipid peroxides contents in brain and liver of gamma irradiated rats

International Nuclear Information System (INIS)

Mohamed, M.A.; Saada, H.A.

1999-01-01

Treatment of normal rats with serotonin (2 mg/100 g body weight) produced no significant change in levels of phospholipids and lipid peroxides of the cerebral hemispheres and liver 1,3 and days after treatment. The content of lipid peroxides was measured as malondialdehyde (MDA). Whole body gamma-irradiation of rats at 8 Gy resulted in significant decrease in the level of phospholipids and significant increase in MDA level in cerebral hemispheres and lever. Changes were more pronounced in liver. Treatment with serotonin, 15 minutes before irradiation, had a pronounced protective effect against the radiation induced changes in the levels of phospholipids and MDA only in the liver through all the experimental period

Increased levels of metallothionein in placenta of smokers

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Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N.

2005-01-01

Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production

Identification of Novel Human Breast Carcinoma (MDA-MB-231 Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library

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Elena Lenci

2016-10-01

Full Text Available The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

Lithium chloride attenuates mitomycin C induced necrotic cell death in MDA-MB-231 breast cancer cells via HMGB1 and Bax signaling.

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Razmi, Mahdieh; Rabbani-Chadegani, Azra; Hashemi-Niasari, Fatemeh; Ghadam, Parinaz

2018-07-01

The clinical use of potent anticancer drug mitomycin C (MMC) has limited due to side effects and resistance of cancer cells. The aim of this study was to investigate whether lithium chloride (LiCl), as a mood stabilizer, can affect the sensitivity of MDA-MB-231 breast cancer cells to mitomycin C. The cells were exposed to various concentrations of mitomycin C alone and combined with LiCl and the viability determined by trypan blue and MTT assays. Proteins were analyzed by western blot and mRNA expression of HMGB1 MMP9 and Bcl-2 were analyzed by RT-PCR. Flow cytometry was used to determine the cell cycle arrest and percent of apoptotic and necrotic cells. Concentration of Bax assessed by ELISA. Exposure of the cells to mitomycin C revealed IC 50 value of 20 μM, whereas pretreatment of the cells with LiCl induced synergistic cytotoxicity and IC 50 value declined to 5 μM. LiCl combined with mitomycin C significantly down-regulated HMGB1, MMP9 and Bcl-2 gene expression but significantly increased the level of Bax protein. In addition, the content of HMGB1 in the nuclei decreased and pretreatment with LiCl reduced the content of HMGB1 release induced by MMC. LiCl increased mitomycin C-induced cell shrinkage and PARP fragmentation suggesting induction of apoptosis in these cells. LiCl prevented mitomycin C-induced necrosis and changed the cell death arrest at G2/M-phase. Taking all together, it is suggested that LiCl efficiently enhances mitomycin C-induced apoptosis and HMGB1, Bax and Bcl-2 expression may play a major role in this process, the findings that provide a new therapeutic strategy for LiCl in combination with mitomycin C. Copyright © 2018 Elsevier GmbH. All rights reserved.

The influence of royal jelly and human interferon-alpha (HuIFN-αN3) on proliferation, glutathione level and lipid peroxidation in human colorectal adenocarcinoma cells in vitro.

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Filipič, Bratko; Gradišnik, Lidija; Rihar, Klemen; Šooš, Eugen; Pereyra, Adriana; Potokar, Jana

2015-12-01

Among royal jelly's (RJ) various biological activities, its possible antitumour activity deserves particular attention. The purpose of this study was to investigate the influence of RJ, its bioactive component 10-hydroxy-2-decenoic acid (10- HDA), and human interferon-alpha (HuIFN-αN3) on the proliferation of human colorectal adenocarcinoma cells (CaCo- 2), and ascertain their effect on intracellular glutathione (GSH) level and lipid peroxidation. We studied the antiproliferative (AP) activity of RJ [(0.1 g/10 mL phosphate buffer saline (PBS)], HuIFN-αN3 (1000 I.U. mL⁻¹), 10-HDA at 100.0 μmol L⁻¹, and their different combinations, in the ratio 1:1, 1:2, and 2:1 on CaCo-2 cells. The GSH level was measured by glutathione assay. The lipid peroxidation was measured by malondialdehyde (MDA) assay. Single RJ had a low AP activity: 2.0 (0.5 mg mL⁻¹). HuIFN-αN3 had an AP activity of 2.5 (208.33 I.U. mL⁻¹), while 10-HDA had an AP activity of 1.5 (37.5 μmol mL⁻¹). The highest AP activity of 3.8 was obtained when RJ and HuIFN-αN3 were applied at the ratio 2:1. In that combination the level of GSH was 24.9±2.4 nmol g⁻³ of proteins (vs. 70.2±3.2 nmol g⁻³ in the control) and the level of MDA was 72.3±3.1 nmol g⁻³ (vs. 23.6±9.1 nmol g⁻³ in the control). It is generally assumed that 10-HDA, an important constituent of RJ, together with HuIFN-αN3, is responsible for the inhibition of CaCo-2 cells proliferation in vitro. In our study, however, RJ and HuIFN-αN3 applied at 2:1 decreased the level of GSH the most and significantly increased lipid peroxidation via MDA in CaCo-2 cells. Future studies should show whether these GSH- and MDA-related activities of RJ, HuIFN-αN3, 10-HDA, and their combinations may decrease the tumorigenicity index and tumorigenic potential of various tumour cells in vitro.

[Features of influence adenosine, AMP and hyperadrenalinemiya on the immune status, metabolic enzymes of purine nucleotides and the antioxidant defense system].

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Tapbergenov, S O; Sovetov, B S; Tapbergenov, A T

2016-11-01

Administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) increased blood levels of total leukocytes, lymphocytes, decreased T-cell suppressors, leukocyte migration inhibition reaction (LMIR) and NBT test, but increased the level of conjugated dienes (CD). Administration of AMPand adenosine increased levels of total leukocytes, lymphocytes, T- lymphocytes, T-helpers, decreased the level of malondialdehyde (MDA), LMIR, and T-cell suppressors. Sympathetic hyperactivation induced by administration of a large dose of adrenaline (4 mg/kg 60 min before analysis) was accompanied by an increase in heart and liver activities of glutathione peroxidase (GPx), catalase, AMP deaminase (AMPD), and adenosine deaminase (AD). Administration of AMP or adenosine caused a decrease in activities of glutathione reductase (GR), GPx, catalase, a decrease in the MDA level and an increase in activities of AMPD and AD in the heart. In the liver AMP and adenosine also caused a decrease in activities of glutathione reductase (GR), GPx, a decrease in the MDA level and an increase in activities of AMPD and AD. The data obtained suggest that administration of adrenaline, AMP, and adenosine influences activity of enzymes involved in purine nucleotide metabolism. However, in contrast to adrenaline, administration of AMP or adenosine does not provoke stress reaction.

Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

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K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

2016-05-01

Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells.

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Lou, Chenghua; Zhu, Zhihui; Zhao, Yaping; Zhu, Rui; Zhao, Huajun

2017-01-01

Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.

Effect of acute sup(60)Co-gamma-irradiation on the in vivo lipid peroxidation in experimental animals

International Nuclear Information System (INIS)

Ronai, Eva; Benkoe, Gy.

1984-01-01

The effect of sublethal (6.0 Gy) and LDsub(50/30) (9.0 Gy) doses of sup(60)Co-gamma-irradiation on malondialdehyde (MDA) level was studied in rats. The findings suggest that in the organs investigated (brain, liver, spleen, kidneys, testicles, stomach, small intestines) acute sup(60)Co gamma-irradiation increased the formation of MDA, the main product of lipid peroxidation, in a time-related manner to an extent characteristic of the organ investigated. Differences in the degree and temporal development of the changes allow some conclusions as to the radiosensitivity of individual organs. On this basis it can be assumed that the increase in MDA level caused by irradiation considerably contributes to the development of certain symptoms of radiation sickness. (author)

Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

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Graczyk, Halshka; Lewinski, Nastassja; Zhao, Jiayuan; Sauvain, Jean-Jacques; Suarez, Guillaume; Wild, Pascal; Danuser, Brigitta; Riediker, Michael

2016-06-10

Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is

Decreased total antioxidant levels and increased oxidative stress in ...

African Journals Online (AJOL)

21–25 ... Decreased total antioxidant levels and increased oxidative stress in South ... antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the .... glycation of proteins and the formation of advanced glycosylation.

Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage

Science.gov (United States)

2008-06-01

within the liposome samples using HPLC with electro-chemical detection. As we mentioned above, the liposome membrane is fairly stable physically, even...lipid peroxidation Vitamin E or flavonoids , while not influencing hepatic GSH depletion, did reduce MDA levels, suggesting a therapeutic potential.19 The... flavonoid .32 Inhalation exposure to HD depleted hepatic GSH levels, and increased hepatic and lung lipid peroxidation (as indirectly measured by MDA

Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer

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V Kenan Çelik

2017-09-01

Full Text Available In this study, it was aimed to investigate the relationship between diabetes and breast cancer and the detection of enzymes and ornithine levels in polyamine synthesis pathway in diabetes, breast cancer and diabetic breast cancer patients. Methods: Ornithine, arginine decarboxylase, ornithine decarboxylase and agmatinase levels have been measured in serum of all groups. Ornithine levels were measured spectrophotometrically. Arginine decarboxylase, ornithine decarboxylase and agmatinase levels were determined by ELISA kits. Results: Except for the diabetic group, the levels of enzymes in the polyamine synthesis pathway were increased in all and statistically significant (P < 0.05. The increase in the levels of agmatinase was very important among the enzymes (P < 0.001. Conclusions: Decreased levels of polyamine synthase enzymes in diabetes mellitus were found to be increased patients with breast cancer. Whether and how diabetes-based breast cancer development relates to increase activity of enzymes responsible for polyamine synthesis requires further mechanistic and prospective monitoring studies in larger patient cohorts.

Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals.

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Shashi Bala

Full Text Available Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

Epalrestat increases intracellular glutathione levels in Schwann cells through transcription regulation

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Keisuke Sato

2014-01-01

Full Text Available Epalrestat (EPS, approved in Japan, is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Here we report that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH, which is important for protection against oxidative injury, through transcription regulation. Treatment of Schwann cells with EPS caused a dramatic increase in intracellular GSH levels. EPS increased the mRNA levels of γ-glutamylcysteine synthetase (γ-GCS, the enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a key transcription factor that plays a central role in regulating the expression of γ-GCS. ELISA revealed that EPS increased nuclear Nrf2 levels. Knockdown of Nrf2 by siRNA suppressed the EPS-induced GSH biosynthesis. Furthermore, pretreatment with EPS reduced the cytotoxicity induced by H2O2, tert-butylhydroperoxide, 2,2'-azobis (2-amidinopropane dihydrochloride, and menadione, indicating that EPS plays a role in protecting against oxidative stress. This is the first study to show that EPS induces GSH biosynthesis via the activation of Nrf2. We suggest that EPS has new beneficial properties that may prevent the development and progression of disorders caused by oxidative stress.

N-acetylphytosphingosine enhances the radiosensitivity of tumor cells by increasing apoptosis

International Nuclear Information System (INIS)

Han, Y.; Kim, Y.; Yun, Y.; Jeon, S.; Kim, K.; Song, J.; Hong, S.H.; Park, C.

2005-01-01

Ceramides are well-known second messengers which mediate apoptosis, proliferation, differentiation in mammalian cells, but the physiological roles of phytosphingosines are poorly understood. We hypothesized that one of the phytosphingosine derivatives, N-acetylphytosphingosine (NAPS) can induce apoptosis in human leukemia Jurkat cell line and increase apoptosis in irradiated MDA-MB-231 cells. We first examined the effect of NAPS on apoptosis of Jurkat cells. NAPS had a more rapid and stronger apoptotic effect than C 2 -ceramide in Jurkat cells and significant increase of apoptosis was observed at 3 h after treatment. In contrast, the apoptosis induced by C2-ceramide was observed only after 16 h of treatment. NAPS induced apoptosis was mediated by caspase 3 and 8 activation and inhibited by z-VAD-fmk. Ceramide plays a pivotal role in radiation induced apoptosis. We postulated that exogenous treatment of NAPS sensitizes tumor cells to ionizing radiation, since NAPS might be used as a more effective alternative to C2-ceramide. As expected, NAPS decreased clonogenic survival of irradiated MDA-MB-231 cells dose dependently, and apoptosis of irradiated cells in the presence of NAPS was increased through the caspase activation. Taken together, NAPS is an effective apoptosis-inducing agent, which can be readily synthesized from yeast sources, and is a potent alternative to ceramide for the further study of ceramide associated signaling and the development of radiosensitizing agent. (orig.)

Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure

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Hale Maral Kir

2013-11-01

Full Text Available Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen and nitrogen species. Th e objective of this study was to investigate the eff ects of Neuropeptide Y on oxidative and nitrosative balance and brain-derived neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant drug in the hippocampus of Wistar rats. Th ree groups of seven rats were treated intraperitoneally as follows: group  (saline + saline  ml saline, group  (salin + Pentylenetetrazole  ml saline  min before Pentylenetetrazole; and group  (Neuropeptide Y + Pentylenetetrazole  μg/kg Neuropeptide Y  min before  mg/kg Pentylenetetrazole. After  h, the animals were euthanized by decapitation. Hippocampus were isolated to evaluate the malondialdehyde, glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three rat groups. Th e results of this study demonstrated that while intraperitoneally administered neuropeptide Y did not result in a statistically signifi cant diff erence in BDNF levels, its administration caused a statistically signifi cant decrease in malondialdehyde and nitric oxide levels and an increase in glutathione levels in rats with pentylenetetrazole-induced epileptic seizure. Neuropeptide Y were able to reduce nitroxidative damage induced by pentylenetetrazole in the hippocampus of Wistar rats.

Rhodamine B triggers ovarian toxicity through oxidative stress, decreases in the number of follicles, 17B-estradiol level, and thickness of endometrium

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Syiska Atik Maryanti

2014-06-01

Full Text Available Objective: The purpose of this study was to analyze the effects of exposure to rhodamine B on ovarian oxidative stress, ovarian follicles, hormone 17beta-estradiol and thickness of endometrium. Methods: A total of 28 female rats were divided into four groups consisting of control; groups treated with rhodamine B at doses of 4.5; 9, and 18 milligram/200 gram body weight. Rhodamine B was administered orally for 36 days with the probe. Analysis of MDA level was done spectrophotometrically. Analysis of the number of ovarian follicles and thickness of endometrium was done histopathologically by hematoxylin eosin staining. Analysis of 17-estradiol level was done by ELISA. Results: Rhodamine B administered in different doses in female rats can increase ovarian MDA levels significantly than the control (P 0.05. Administration of rhodamine B of the second and third doses in female rats can reduce the number of primary, secondary, and De Graaf follicles significantly compared to the control (P 0.05. Administration of rhodamine B of the second and third doses in female rats can reduce 17-estradiol level significantly compared to the control (P 0.05. The administration of rhodamine B could reduce thickness of endometrium significantly compared to the control (P 0.05. Conclusion: It was concluded that administration of rhodamine B triggered ovarian toxicity through oxidative stress, a decrease in the number of follicles, and decreased level of 17-estradiol which ultimately lowered the thickness of endometrium. [Cukurova Med J 2014; 39(3.000: 451-457

The protective effect of propolis on damage to lung and blood in rats by inhaled radioactive radon and its progeny

International Nuclear Information System (INIS)

Ding Jiansong; Nie Jihua; Tong Jian

2006-01-01

Twenty-eight male wistar rats were randomly divided into seven groups, i.e. the radon groups (3), the propolis+radon groups (3) and the control (1). The propolis+radon groups were fed intragastrically with propolis 0.2 g/kg, before exposing them, together with the radon groups, to radon and its progeny with the cumulative dose up to 30, 67 and 111 working level month (WLM), respectively. The levels of SOD (superoxide dismutase) and MDA (Malonic dialdehyde) in blood and lung tissue were determined. The SOD level of in blood and lung tissues of the radon groups decreased significantly and the MDA level increased. The MDA level in lung tissue of the 30 WLM propolis+radon group was significantly higher than the 30 WLM radon group. The SOD level in lung tissue of the 67 WLM propolis+radon group was significantly higher, but the MDA level was significantly lower, than the 67 WLM radon group. Both the SOD and MDA levels in blood and lung tissue of the 111 WLM propolis+radon group were significantly higher than the 111 WLM radon group. In conclusion, the inhalation of radon and its progeny can lead to persistent disturbance of the redox state in rats. Propolis show some protective effects on the redox damage under the experimental conditions. (authors)

Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

Science.gov (United States)

Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

2015-07-31

Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

OpenAIRE

Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

2017-01-01

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines...

Impact of placental Plasmodium falciparum malaria on the profile of some oxidative stress biomarkers in women living in Yaoundé, Cameroon.

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Rosette Megnekou

Full Text Available Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown.Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA, Nitric Oxide (NO, Superoxide dismutase (SOD, Catalase (CAT and Gluthatione (GSH in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays.Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively. The level of lipid peroxide product (MDA was significantly higher in the malaria infected (P = 0.0047 and anaemic (P = 0.024 women compared to their non-infected and non-anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024 but negatively with haemoglobin levels (P = 0.002. There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH.Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight. This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria

Non-Muscle Myosin II Isoforms Have Different Functions in Matrix Rearrangement by MDA-MB-231 Cells.

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Bridget Hindman

Full Text Available The role of a stiffening extra-cellular matrix (ECM in cancer progression is documented but poorly understood. Here we use a conditioning protocol to test the role of nonmuscle myosin II isoforms in cell mediated ECM arrangement using collagen constructs seeded with breast cancer cells expressing shRNA targeted to either the IIA or IIB heavy chain isoform. While there are several methods available to measure changes in the biophysical characteristics of the ECM, we wanted to use a method which allows for the measurement of global stiffness changes as well as a dynamic response from the sample over time. The conditioning protocol used allows the direct measurement of ECM stiffness. Using various treatments, it is possible to determine the contribution of various construct and cellular components to the overall construct stiffness. Using this assay, we show that both the IIA and IIB isoforms are necessary for efficient matrix remodeling by MDA-MB-231 breast cancer cells, as loss of either isoform changes the stiffness of the collagen constructs as measured using our conditioning protocol. Constructs containing only collagen had an elastic modulus of 0.40 Pascals (Pa, parental MDA-MB-231 constructs had an elastic modulus of 9.22 Pa, while IIA and IIB KD constructs had moduli of 3.42 and 7.20 Pa, respectively. We also calculated the cell and matrix contributions to the overall sample elastic modulus. Loss of either myosin isoform resulted in decreased cell stiffness, as well as a decrease in the stiffness of the cell-altered collagen matrices. While the total construct modulus for the IIB KD cells was lower than that of the parental cells, the IIB KD cell-altered matrices actually had a higher elastic modulus than the parental cell-altered matrices (4.73 versus 4.38 Pa. These results indicate that the IIA and IIB heavy chains play distinct and non-redundant roles in matrix remodeling.

HEALTH TECHNOLOGIES FOR INCREASING ADAPTIVE CAPABILITIESOF PREGNANT WOMEN

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T. S. Krivonogova

2014-01-01

trimester of pregnancy it were identified lower rates of lipid peroxidation compared with those observed during pregnancy in the usual way (control group, which corresponded to women's health indicators. At the same time in the third trimester of pregnancy it was found a significant increase in the concentration of vitamin E in the blood serum of women from the main group compared to the control group (p < 0.001.The complex of breathing exercises and aqua-gymnastics have a stimulating effect on metabolism, thereby it normalizes the level of antioxidant enzyme. During the breathing exercises process a direct correlation was revealed between the level of MDA and cortisol (r = 0.67 and between vitamin E and insulin (r = 0.61. These data allow suggesting the prospects for determining the concentration of MDA and vitamin E in the peripheral blood of pregnant women to determine the adaptive capability of the organism and the favorable course of pregnancy and childbirth.It is possible that the complex of adaptive respiratory and aqua-gymnastics performing by pregnant women promotes more intensive penetration of oxygen from the blood to tissue, which leads to better oxidation of the substrate and hence reduce the concentration of MDA in women of main group. Timely addition of breathing exercises complex during pregnancy, as well as aqua-gymnastics, promotes restoration of redox enzymatic processes in the tissues, leading to improved utilization of fetal oxygen; contributes to Verigo–Bohr strengthening effect, intensive penetration of oxygen from the blood into tissues, resulting in the release of carbon dioxide. Accumulated carbon dioxide promotes active oxygen transportation to the fetus and increases the adaptive capabilities of the organism.Thus, the experience of working with groups of pregnant women with somatic pathology and prenatal risk factors, allowed us to estimate the effectiveness of breathing exercises combined with aqua-gymnastics and develop a more

Status of Onchocerciasis transmission after more than a decade of mass drug administration for onchocerciasis and lymphatic filariasis elimination in central Nigeria: challenges in coordinating the stop MDA decision.

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Darin S Evans

2014-09-01

Full Text Available This study was undertaken in five onchocerciasis/lymphatic filariasis (LF co-endemic local government areas (LGAs in Plateau and Nasarawa, Nigeria. Annual MDA with ivermectin had been given for 17 years, 8 of which were in combination with albendazole. In 2008, assessments indicated that LF transmission was interrupted, but that the MDA had to continue due to the uncertain status of onchocerciasis transmission. Accordingly, assessments to determine if ivermectin MDA for onchocerciasis could be stopped were conducted in 2009.We evaluated nodule, microfilarial (mf skin snip, and antibody (IgG4 response to OV16 prevalence in adults and children in six sentinel sites where baseline data from the 1990s were available. We applied the 2001 WHO criteria for elimination of onchocerciasis that defined transmission interruption as an infection rate of <0.1% in children (using both skin snip and OV16 antibody and a rate of infective (L3 blackflies of <0.05%.Among adult residents in sentinel sites, mean mf prevalence decreased by 99.37% from the 1991-1993 baseline of 42.95% (64/149 to 0.27% (2/739 in 2009 (p<0.001. The OV16 seropositivity of 3.52% (26/739 among this same group was over ten times the mf rate. No mf or nodules were detected in 4,451 children in sentinel sites and 'spot check' villages, allowing the exclusion of 0.1% infection rate with 95% confidence. Seven OV16 seropositives were detected, yielding a seroprevalence of 0.16% (0.32% upper 95%CI. No infections were detected in PCR testing of 1,568 Simulium damnosum s.l. flies obtained from capture sites around the six sentinel sites.Interruption of transmission of onchocerciasis in these five LGAs is highly likely, although the number of flies caught was insufficient to exclude 0.05% with 95% confidence (upper CI 0.23%. We suggest that ivermectin MDA could be stopped in these LGAs if similar results are seen in neighboring districts.

Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

Energy Technology Data Exchange (ETDEWEB)

Kumar, Vijay [Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow (India); Kalita, Jayantee, E-mail: jayanteek@yahoo.com [Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow (India); Bora, Himangsu K. [National Laboratory Animal Centre, CSIR-Central Drug Research Institute, Lucknow (India); Misra, Usha K. [Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow (India)

2016-02-15

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the end of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO{sub 4} resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue

Potassium and zinc increase tolerance to salt stress in wheat (Triticum aestivum L.).

Science.gov (United States)

Jan, Amin Ullah; Hadi, Fazal; Midrarullah; Nawaz, Muhammad Asif; Rahman, Khaista

2017-07-01

Potassium and zinc are essential elements in plant growth and metabolism and plays a vital role in salt stress tolerance. To investigate the physiological mechanism of salt stress tolerance, a pot experiment was conducted. Potassium and zinc significantly minimize the oxidative stress and increase root, shoot and spike length in wheat varieties. Fresh and dry biomass were significantly increased by potassium followed by zinc as compared to control C. The photosynthetic pigment and osmolyte regulator (proline, total phenolic, and total carbohydrate) were significantly enhanced by potassium and zinc. Salt stress increases MDA content in wheat varieties while potassium and zinc counteract the adverse effect of salinity and significantly increased membrane stability index. Salt stress decreases the activities of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase) while the exogenous application of potassium and zinc significantly enhanced the activities of these enzymes. A significant positive correlation was found of spike length with proline (R 2  = 0.966 ∗∗∗ ), phenolic (R 2  = 0.741 ∗ ) and chlorophyll (R 2  = 0.853 ∗∗ ). The MDA content showed significant negative correlation (R 2  = 0.983 ∗∗∗ ) with MSI. It is concluded that potassium and zinc reduced toxic effect of salinity while its combine application showed synergetic effect and significantly enhanced salt tolerance. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics

Czech Academy of Sciences Publication Activity Database

Flodrová, Dana; Toporová, L.; Laštovičková, Markéta; Macejová, D.; Hunaková, L.; Brtko, J.; Bobálová, Janette

2017-01-01

Roč. 281, NOV (2017), s. 26-34 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GA15-15479S Grant - others:AV ČR(CZ) SAV-15-01 Program:Bilaterální spolupráce Institutional support: RVO:68081715 Keywords : breast cancer * MDA-MB-231 * biomarker * retinoids Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.858, year: 2016

Effects of dietary lipid levels on growth, body composition and antioxidants of clamworm (Perinereis aibuhitensis

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Fu Lv

2017-05-01

Full Text Available To determine the effects of dietary lipid levels on growth performance, body composition and antioxidant parameters of clamworm (Perinereis aibuhitensis, 1050 clamworms were fed diets with seven lipid levels (2.37%, 4.35%, 6.29%, 8.41%, 10.31%, 12.29% and 14.33%, named L2.37, L4.35, L6.29, L8.41, L10.31, L12.29 and L14.33, respectively for 10 weeks. Each diet was randomly assigned to triplicate groups of 50 clamworms. The results showed that the growth performance and protein efficiency ratio were significantly affected by the lipid levels. Clamworms fed L8.41 diet exhibited higher growth performance than others and the maximum specific growth rate can be possibly obtained when the diets were supplemented with 7.54% lipid level. The dietary lipid levels had significant influences on the whole body crude protein, crude lipid, moisture contents and ash profile of P. aibuhitensis. The eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA were also enhanced with increasing dietary lipid levels in whole body analyses. The contents of malonaldehyde (MDA and lipid peroxidation (LPO in clamworms increased significantly with increasing dietary lipid levels. Meanwhile, the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX and total autioxidative capacity (T-AOC tended to strengthen with dietary lipid levels increasing from 2.37% to 10.31% (except the GPX with 12.29% dietary lipid levels, and weaken with dietary lipid levels increasing from 10.31% to 14.33%. These results demonstrated that a proper dietary lipid level of 7.54%–10.31% could maintain solid growth performance and antioxidant capacity of juvenile P. aibuhitensis.

The effects of melatonin on the oxidants and antioxidants in the pancreatic tissue during the aging process

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Hakan Yüzüak

2014-12-01

Full Text Available Objective: To investigate the effect of melatonin on the levels of malondialdehyde (MDA, nitric oxide (NO and glutathione (GSH of pancreas tissues at young (4 months and middle-aged (14 months rats. Methods: Young and middle-age male Wistar albino rats were used in this experimental study. Rats were divided into two groups: melatonin applied; young rats , middle-aged rats and melatonin was not applied; young rats and middle-aged rats . Melatonin was administered at a dose of 10 mg/kg/day in 0.2 cc-% 1 ethanol-phosphate buffered saline (PBS solution via subcutan way for 7 days at 18:00 until surgery. In control group, 0.2 cc-%1 Ethanol-PBS was applied for 7 days at 18:00. At the end of seven days, MDA, NO levels which are indicators of oxidant stress and GSH were detected. Results: Although there were no significant difference between control and experiment group for the NO and MDA level of melatonin group of young rats, there were significantly difference in the GSH levels of pancreas tissues for melatonin levels. NO levels of the pancreas tissues were significantly reduced and GSH levels were significantly increased in the melatonin group of middle aged rats compared to the control group. The MDA levels of pancreas tissues were significantly increased in the middle aged control group compared to young control group. The MDA levels of pancreas tissues were not significantly different in melatonin group of middle-aged compared to control group. The NO and the GSH levels of the pancreas tissues were not significantly different between the control groups of young and middle aged rats. Conclusion: Aging may be related with an increase in free radicals and a reduction in the antioxidant capacity of the tissues and exogenous melatonin may play a protective role in aging by means of its action on free radicals. J Clin Exp Invest 2014; 5 (4: 583-588

Efficiency of fisheries is increasing at the ecosystem level

DEFF Research Database (Denmark)

Jacobsen, Nis Sand; Burgess, Matthew G; Andersen, Ken Haste

2017-01-01

examine the efficiency of North Sea and Baltic Sea fisheries with respect to economic rent and ecosystem impact, finding both to be inefficient but steadily improving. Our results suggest the following: (i) a broad and encouraging trend towards ecosystem-level efficiency of fisheries; (ii) that ecosystem......Managing fisheries presents trade-offs between objectives, for example yields, profits, minimizing ecosystem impact, that have to be weighed against one another. These trade-offs are compounded by interacting species and fisheries at the ecosystem level. Weighing objectives becomes increasingly...... regressing at least one other. We investigate the ecosystem-level efficiency of fisheries in five large marine ecosystems (LMEs) with respect to yield and an aggregate measure of ecosystem impact using a novel calibration of size-based ecosystem models. We estimate that fishing patterns in three LMEs (North...

Decreased total antioxidant levels and increased oxidative stress in ...

African Journals Online (AJOL)

Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) ...

Effect of Treasury Single Accounts (Tsa on the Performance of Ministries, Departments and Agencies (Mda in Nigeria

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Nkechi T. Ofor

2017-11-01

Full Text Available Purpose of the article: The policy on the Treasury Single Account (TSA was institutionalized to hedge financial loopholes, promote transparency and prevent mismanagement of government’s revenue by unifying all accounts of the government and preventing mismanagement of revenues by those agencies that generate revenue. This study however, examines the effect of the TSA policy on the performances of federal government MDAs in Nigeria. Methodology/methods: The study relied basically on primary data which was obtained through questionnaire designed and administered to 75 respondents drawn from the federal government ministries, departments, agencies and parastatals (MDA within Anambra metropolis in the eastern part of Nigeria. Analysis was based on the Wilcoxon sign test. Scientific aim: This study aims to empirically establish through available statistics the effect of implementing TSA on the performance of government ministries, departments and agencies in Nigeria. Findings: The result of this research indicate that the institutionalization of TSA has significantly affected and improved the performance of federal government MDAs at 5% level of significance which goes further to confirm that treasury single account is capable of blocking financial loopholes in revenue generation and promoting transparency and accountability. Conclusion: The study concludes by recommending that since the adoption of TSA has significantly improved the performance of federal government ministries, departments and agencies (MDAs in Nigeria, government should enforce the adoption of TSA and ensure that it is mandatory for all MDAs and parastatals in the country.

Oxidative stress responses in gills of tilapia (Oreochromis niloticus) at different salinities

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Handayani, Kiki Syaputri; Novianty, Zahra; Saputri, Miftahul Rohmah; Irawan, Bambang; Soegianto, Agoes

2017-08-01

The objective of present study is to evaluate the impact of different salinities on the levels of CAT, GSH and MDA of the gills of Nile tilapia (Oreochromis niloticus). Nile tilapia was treated by exposure to salinities concentration 0 ‰, 5 ‰ and 10 ‰. Research models were weakened and sacrificed, then took the left and right sides of the gills. The result of gills homogenity was centrifuged for supernatan, then supernatan was proceed with testing levels of CAT, GSH and MDA by ELISA assay methods. The levels of CAT in gills were significantly higher at 10 ‰ than at 5 ‰ and 0 ‰. The levels of GSH in gills were significantly higher at 0 ‰ than 5 ‰. The levels of GSH in gills at 5 ‰ and 10 ‰ salinities were not significantly different. The levels of MDA in gills at salinity 10 ‰ and 5 ‰ were higher than in control gills at 0 ‰ salinities. This occurs because the salinity of 10 ‰ salinity was optimal for live of fish tilapia. In conclusion, salinity impact the increasing of CAT, GSH, and MDA levels in gills of Nile tilapia.

Antioxidant tolerance of kidney after irradiation.

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Bukan, Neslihan; Güney, Yildiz; Hiçsönmez, Ayşe; Bilgihan, Ayşe

2003-03-01

Different doses of irradiation were performed in which group 1 (non-irradiated), group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body) were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in the whole kidney. The MDA content increased in animals irradiated with 8 and 15 Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when compared with control group. The activity of GSH-Px decreased significantly in group 2 and group 3 in comparison to controls. It may be concluded that a high dose of ionizing irradiation cause excessive oxidative stress in kidney.

Investigation of 3′-debenzoyl-3′-(3-([124I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo

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Sajjad, M.; Riaz, U.; Yao, R.; Bernacki, R.J.; Abouzied, M.; Erb, D.A.; Chaudhary, N.D.; Veith, J.M.; Georg, G.I.; Nabi, H.A.

2012-01-01

A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3′-debenzoyl-3′-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6 h post-injection. However, at 6 h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24 h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24 h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies. - Highlights: ► 3′-Debenzoyl-3′-(3-iodobenzoyl)paclitaxel cytotoxicity was comparable to paclitaxel. ► 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl)paclitaxel was synthesized. ► Uptake of the drug was higher in sensitive tumor compared to the resistant tumor. ► The Pgp-modulators had a positive effect on drug-sensitive tumor. ► The sensitive tumor was visible in images obtained using micoPET.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

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Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Influence of exogenous lactoferrin on the oxidant/antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro.

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Zalutskii, I V; Lukianova, N Y; Storchai, D M; Burlaka, A P; Shvets, Y V; Borikun, T V; Todor, I M; Lukashevich, V S; Rudnichenko, Y A; Chekhun, V F

2017-07-01

To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of "free" iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4-1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14-24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, "free" iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.

Increasing occurrence of multiple sclerosis in women correlates to hygiene level

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Wojciech Cendrowski

2014-12-01

Full Text Available Introduction: The increasing incidence of multiple sclerosis, particularly among women in Europe and North America, has a multifactorial aetiology. Method: The aim of the current study was to ascertain the relation between the hygiene level and occurrence of multiple sclerosis in women in Poland. The study was based on a large cohort of 14,200 multiple sclerosis individuals (male – 6,106, female – 8,094 who died in the years 1981–2010 in Poland. The female to male ratio (the F:M ratio in the multiple sclerosis group was calculated using the number of deaths per year. The rate of late mortality in infants (LMI per 1,000 live births yearly was used as a marker of the hygiene level. A correlation analysis was carried out between the rate of LMI and the F:M ratio in the multiple sclerosis cohort in the years 1981–2010. Demographic data were obtained from the Central Statistical Office in Warsaw. Results: The F:M ratio in the multiple sclerosis group evidently increased (range 1.08–1.79 in the years 1981–2010, showing increasing occurrence of multiple sclerosis in women (p < 0.0001. A significant, strong and inverse correlation was found between the marker of the hygiene level (LMI rate and the F:M ratio in the multiple sclerosis group over three decades: linear correlation coefficient by Pearson: r = –0.693, p < 0.0001. By contrast with this result, no correlation was established between the hygiene level marker and proportion of women to men in the general population on account of extremely low variance of the F:M ratio (0.000025. Conclusion: The improvement of the hygiene level showed association with the increasing occurrence of multiple sclerosis in women in the years 1981–2010. The higher the hygiene level was, the greater the occurrence of female multiple sclerosis in Poland.

Effects of epiphytic algae on biomass and physiology of Myriophyllum spicatum L. with the increase of nitrogen and phosphorus availability in the water body.

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Song, Yu-Zhi; Wang, Jin-Qi; Gao, Yong-Xia

2017-04-01

The disappearance of submerged vascular macrophytes in shallow eutrophic lakes is a common phenomenon in the world. To explore the mechanism of the decline in submerged macrophyte abundance due to the growth of epiphytic algae along a nutrient gradient in eutrophic water, a 2 × 3 factorial experiment was performed over 4 weeks with the submerged macrophyte (Myriophyllum spicatum L.) by determining the plant's biomass and some physiological indexes, such as chlorophyll (Chl) content, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity in the leaves of M. spicatum L. on days 7, 14, 21, and 28, which are based on three groups of nitrogen and phosphorus levels in the water body (N-P [mg L -1 ]: NP1 0.5-0.05, NP2 2.5-0.25, NP3 4.5-0.45) and two levels of epiphytic algae (the epiphytic algae group and the control group). Epiphytic algal biomass was also assayed. The results indicated that epiphytic algal biomass remarkably enhanced in the course of the experiment with elevated levels of nitrogen and phosphorus in the water. Under the same level of nutrient condition, plants' biomass accumulation and Chl content were higher in the control group than that in the epiphytic algae group, respectively, while MDA content and SOD activity in the former were lower than that in the latter. The influences of epiphytic algae on the biomass accumulation and Chl content and MDA content became greater and greater with elevated levels of nutrients. In general, in this experiment, water nutrients promoted the growth of both epiphytic algae and submerged plants, while the growth of epiphytic algae hindered submerged macrophytes' growth by reducing Chl content and promoting peroxidation of membrane lipids in plants.

The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

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Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

2017-07-25

Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

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Nicolas G. Azios

2005-02-01

Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

Oxidative stress in patients with essential hypertension: a comparison of dippers and non-dippers.

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Gönenç, Aymelek; Hacışevki, Aysun; Tavil, Yusuf; Çengel, Atiye; Torun, Meral

2013-03-01

Oxidative stress seems to play an important role in the pathophysiology of essential hypertension. We aimed to examine serum MDA, NO, 8-OHdG, ADMA, NT, CoQ10 and TAC as biomarkers of oxidative stress in dipper and non-dipper hypertensive patients. Eighteen dipper hypertensives, 20 non-dipper hypertensives and 22 healthy control subjects were included in the study. Clinical assessment and ambulatory blood pressure monitoring were performed in patients. Serum MDA, TAC and NO levels were measured by using spectrophotometric methods. CoQ10 levels were measured by HPLC method. 8-OHdG, ADMA and NT were quantitated by ELISA methods. MDA levels were significantly higher in dipper and non-dipper groups compared to controls (pstres compared with dipper hypertensive patients, which plays an important role in the development of cardiovascular diseases. Increased MDA and reduced TAC levels might be considered as prospective prognostic markers of the development of cardiovascular diseases in dipper and non-dipper hypertensive patients. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Controlling Taenia solium and soil transmitted helminths in a northern Lao PDR village: Impact of a triple dose albendazole regime.

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Ash, Amanda; Okello, Anna; Khamlome, Boualam; Inthavong, Phouth; Allen, John; Thompson, R C Andrew

2017-10-01

Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the

Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

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Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

2014-01-01

Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools

Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

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Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

2014-02-15

Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

Fly-ash-induced oxidative stress and tolerance in Prosopis juliflora L. grown on different amended substrates.

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Sinha, S; Rai, U N; Bhatt, K; Pandey, K; Gupta, A K

2005-03-01

Field experiments were conducted to study the impact of metal accumulation on malondialdehyde (MDA), cysteine and non-protein thiol (NPSH) contents in the plants of Prosopis juliflora grown on the fly ash (FA) amended with soil, blue green algae (BGA) biofertilizer, farm yard manure, press mud and Rhizobium inoculation. The analysis of data revealed that the level of MDA, cysteine and NPSH was higher in the roots of the plant than leaves, which was found positively correlated with metal accumulation. An increase of 361.14, 64.25 and 305.62% in MDA, cysteine and NPSH contents, respectively was observed after 45 days in the roots of the plants grown in 100% FA as compared to 100% garden soil (GS). The level of MDA, cysteine and NPSH was found less in the plants grown on various amendments of FA showing ameliorating effect on the toxicity induced due to the accumulation of metals. The decrease in MDA, cysteine and NPSH contents was higher in Rhizobium-inoculated plants as compared to uninoculated plants grown on 100% FA. The results showed a high tolerance potential of the plant, which is further increased by inoculating the plant with FA-tolerant Rhizobium showing feasibility of using P. julifilora in environmental monitoring of FA landfills.

Malondialdehyde suppresses cerebral function by breaking homeostasis between excitation and inhibition in turtle Trachemys scripta.

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Fangxu Li

Full Text Available The levels of malondialdehyde (MDA are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons.

Is there an oxidative stress in children with Helicobacter Pylori Infection?

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Arslan, D.; Kose, K.; Patiroglu, Tahir E.

2007-01-01

Objective was to investigate the status of oxidative stress in children with Helicobacter Pylori (HP) infection and their relationship with inflammatory parameters. At the Pediatric Gastroenterology Department of Erciyes University, Kayseri, Turkey, between January 2004 to August 2005, 39 children undergoing upper gastrointestinal endoscopy were investigated for malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in gastric tissue and erythrocytes and presence of HP infection by means of histology. There is an increase of the oxidative stress parameter, MDA, in gastric tissue, but not in erythrocytes in HP (+) and HP (-) patients. The antioxidant enzyme, SOD, levels both in gastric tissue and erythrocyte were not different between HP (+) and HP (-) patients. In 8 HP infected children after treatment with an anti-HP regimen, no change was observed except for tissue SOD activity which is increased after therapy. No correlation was observed between histological findings and tissue and erythrocyte MDA levels and SOD activities. Oxiadtive stress has some role in tissue damage in HP infection in children. (author)

Oxidative Stress and Modulatory effects of the root extract of Phlogacanthus tubiflorus on the activity of Glutathione-S-Transferase in Hydrogen Peroxide treated Lymphocyte

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Ramteke A

2012-04-01

Full Text Available Glutathione-S-transferase is one of the important enzyme systems that plays vital role in decomposition of lipid hydro-peroxides formed due to oxidative stress. In the present study GST activity increased in the lymphocytes treated with increasing concentration of H2O2, and decrease in the levels of GSH was observed. For similar treatment conditions LDH activity and MDA levels increased significantly leading to decrease in the cell viability. Treatment of lymphocytes with the root extract of Phlogacanthus tubiflorus (PTE resulted in dose dependent decline in the GST activity and rise in GSH levels. LDH activity and MDA levels also declined that led to the increase of cell viability. Lymphocytes pre-treated with the PTE followed by H2O2 (0.1 and 1% treatment, decline in the activity of GST and increase in GSH levels was observed. Also we have observed decline in the activity of LDH and MDA levels in the lymphocytes for both 0.1 and 1% of H2O2 though the magnitude of change was higher in the lymphocytes pre-treated with the PTE followed with 1% of H2O2 treatment. Significant increase in the cell viability for similar conditions was also observed. These findings suggest protective function of the root extracts might be through modulation of GST activity and levels of GSH and might find application in Chemomodulation in future.

Influence of Exposure to Fractionated Dose of Gamma Radiation and Antioxidants Supplementation to Mice on program cell death induction

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Hanafi, A.

2010-01-01

The previous studies reported that the tumor suppressor protein (P53) is not functioning correctly in most human cancers, and that it plays a crucial role in the prevention of tumor development. This study was designed to evaluate if exposure to fractionated dose of gamma radiation impair function of P53 by the administration of antioxidants. Group of control mice was used. Another groups treated with 3 mg/mouse/day of Antox drug which contains the three main antioxidant vitamins (A, C, and E) together with trace element selenium for 15 days. Another group subjected to 1 Gy of gamma radiation 5 times every other day either alone or combined with the Antox drug supplementation. Hepatic and renal functions were evaluated. Antioxidant markers (MDA and GSH) levels, histopathological changes and P53 expression were recorded in liver and kidney tissues. Animals treated with Antox showed some increase in liver transaminases, non significant changes in total protein and albumin levels, a non significant change in kidney function profiles, a non significant increase in MDA and a significant increase in GSH levels in liver and kidney tissues. However, the exposure of mice to fractionated dose of gamma radiation led to a significant increase in kidney function profiles, AST and ALT activity, a significant decrease in total protein and albumin level, a significant increase in MDA levels and a significant decrease in GSH levels in liver and kidney were observed. Exposure of experimental animals post treatment with Antox drug to fractionated dose of gamma radiation revealed a significant amelioration in liver and kidney function profiles, a highly significant decrease in MDA levels and a significant increase in GSH level in comparison with irradiated group. Histopathological changes in liver and kidney recorded the same alterations observed with the biochemical parameters. P53 expression negatively expressed in normal liver and kidney tissues. However, the exposure of mice to

The assessment of serum levels of malondialdehyde and total antioxidant capacity after the use of atorvastatin in patients with coronary artery stenosis

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Gholamreza Shahsavari

2015-02-01

significant reduction of plasma MDA levels as well as a significant enhancement of TAC in coronary artery stenosis patients with long time receiving atorvastatin contribute to the lowering oxidative stress in this patients.

Glömda Kriser : En studie av hur ideella organisationer marknadsför humanitära och miljömässiga risker och kriser som allmänheten tappat intresse för

OpenAIRE

Josephsen, Anna; Nilsson, Michael

2014-01-01

Hösten 2012 släppte organisationen Läkare Utan Gränser en rapport under titeln Kriserna Svenskarna Glömt. I denna uppmärksammas det faktum att det finns flera humanitära kriser i världen som allmänheten i Sverige inte känner till. Organisationen benämner dessa som “glömda kriser”. Anledningen till den låga kännedomen hos allmänheten är, enligt rapporten, en bristande mediebevakning av kriserna. Begreppet glömda kriser bygger till stor del på idén om att en kris eller en risk kan lida av ett o...

Efeito da berinjela sobre os lípides plasmáticos, a peroxidação lipídica e a reversão da disfunção endotelial na hipercolesterolemia experimental Effect of eggplant on plasma lipid levels, lipidic peroxidation and reversion of endothelial dysfunction in experimental hypercholesterolemia

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Paulo Afonso Ribeiro Jorge

1998-02-01

significantly increased in the LDL particles and in the arterial wall of H rabbits was reduced in the E group (p<0.05. Endothelium-dependent relaxation were significantly higher in the E group compared H group rabbits (p<0.05. CONCLUSION: In hypercholesterolemic rabbits egg plant juice significantly reduced weight, plasma cholesterol levels, aortic cholesterol content and the MDA concentrations in native-oxidized LDL and in the arterial wall and increased the endothelium-dependent relaxations.

Increased Blood-Reelin-Levels in First Episode Schizophrenia.

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Tobias Hornig

Full Text Available Reelin is an extracellular glycoprotein involved in several functions of brain development, synaptogenesis and dendritic proliferation. Numerous studies found perturbation in the reelin system and altered serum reelin levels in neuropsychiatric patients using the western blot procedure. In the international literature, this is the first study that made use of an enzyme-linked immunosorbent assay to analyze serum reelin protein concentration quantitatively.In order to study possible alterations in reelin blood levels in schizophrenia, we analyzed this signal in schizophrenic patients with a first episode hallucinatory and paranoid syndrome and control subjects in a pilot study design.We found increased blood reelin protein concentration in schizophrenic patients compared to healthy controls.Our findings point to a relevant role of reelin metabolism in the pathogenesis of schizophrenia.Reelin could be a biomarker for the course of disease or psychopharmacological treatment.We conclude that the reelin protein blood concentration might be a relevant signal with respect to the pathophysiology of schizophrenia.

The comparative effect of fasting with and without caloric restriction in Rat on oxidative stress parameters

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Nurina Tyagita

2016-09-01

Full Text Available Introduction: Fasting, like Islamic Ramadan Fasting, has been associated with health benefits. Islamic Ramadan fasting, a form of caloric restriction (CR or alternate day fasting that. Studies suggest a comparable effect of ADF and caloric restriction. Despite the fact that fasting can be considered as a form of dietary restriction, fasters tend to have difficulty to reduce their food intake during non-fasting period by overeating leading to the excessive calorie intake. To compare the effect of fasting with and without caloric restriction in Sprague Dawley rats. Methods: The rats were assigned to one of three groups: ADF with 70 % calorie intake (30% CR, ADF with 100 % calorie intake (0% CR, and ADF with 140 % calorie intake (excessive calorie intake and AL (fed ad libitum. All groups were subjected to 6 hour fasting per day (9 a.m. until 3 p.m. or 15 days. The plasma sample was taken for MDA level assessment. Urinary 8-oxodG levels were determined by using ELISA. Results: ADF with 30% calorie restriction (F70 group had the lowest MDA level. Measurement of 8-oxodG level showed that group F70 had the highest production of 8-oxodG. There was an inverse relationship between MDA level and 8-oxodG level meaning the lower MDA level, the lower 8-oxodG levels were produced. Conclusion: ADF fasting with 30% caloric restriction reduce the MDA level but increase 8-oxodG levels. This study suggest the beneficial effect of fasting requires decrease in overall caloric intake.

Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

Science.gov (United States)

Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

2015-01-01

Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

The Applications to Increase Drought Tolerance of Plants

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İlkay Yavaş

2016-01-01

Full Text Available Terminal drought is a major threat that adversely affects crop growth and metabolism, and limits the yield. Water stress causes many morphological, physiological and biochemical changes in plants. Plant height, root length, leaf area, fresh and dry biomass are reduced under drought stress. Besides, water stress causes the reduction of relative water content, the closure of stomata and decrease in photosynthesis and chlorophyll content. Antioxidant enzymes such as glutathione reductase (GR, superoxide dismutase (SOD, peroxidase (POD, ascorbat peroxidase (ASC, glutatiton (GSH, catalase (CAT enzyme activities, the indicator of oxidative stress malondialdehyde (MDA and proline levels also changes in drought conditions. Nutrient uptake by plants is prevented or restricted before grain development stage during drought conditions. Therefore the application of plant nutrients followed by micronutrient remobilization within plant is great importance. Osmoprotectants (cytokinin, mannitol, abscisic acid, proline, glycine betaine, polyamine etc. detoxify adverse effect of reactive oxygen species (ROS and alleviate drought stress. Exogenous plant growth promoting rhizobacteria (PGPR application encourage plant growth by colonizing the plant root and increase plants’ resistance to water stress. Besides, the farmers can use conservation tillage system in dry periods.

Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines

International Nuclear Information System (INIS)

Plummer, Howard K III; Yu, Qiang; Cakir, Yavuz; Schuller, Hildegard M

2004-01-01

Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling. Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting. Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta 2 -adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K + flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells. Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa.

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Cédric B Chesnais

2017-09-01

Full Text Available The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997 with the Alere Filariasis Test Strip (FTS, introduced in 2013 in 5 endemic study sites in Africa.The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire and in three sites that had received MDA (DRC and 2 sites in Liberia. Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings.Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings.This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance.

Benefits and costs of increased levels of corticosterone in seabird chicks

Science.gov (United States)

Kitaysky, A.S.; Kitaiskaia, E.V.; Piatt, John F.; Wingfield, J.C.

2003-01-01

Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. ?? 2003 Elsevier Science (USA). All rights reserved.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

International Nuclear Information System (INIS)

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E 2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G 0 /G 1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E 2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

Some positive effects of pine oil on brain tissue in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Demir, E.; Keser, S.; Yilmiz, O.

2016-01-01

Pine oil has antiseptic, expectorant and antioxidant properties and has been used for treatment of rheumatism, respiratory and urinary system and skin diseases. We aimed to determine protective effects of pine oil (PO) on the lipid-soluble vitamins, cholesterol, GSH, total protein, MDA, fatty acid levels of brain tissue of the streptozotocin-induced diabetic rats. Rats were randomly divided into three groups: Control (C), streptozotocin (STZ), streptozotocin+pine oil (PO) groups. Streptozotocin was injected intraperitoneally single dose (65 mg/kg) to the STZ and PO groups for inducing of diabetes. To the PO group 1 mg/kg dose pine oil was intraperitoneally injected every next day. While the GSH and total protein were significantly decreased in the Streptozotocin (STZ) group, their levels were protected in PO group. MDA level was significantly increased in STZ group, its level significantly decreased in the PO group. Our results showed that PO has a positive effect on the GSH, total protein, and MDA levels in the brain tissue of diabetic rats. The PO and STZ administrations were affected by levels of some important fatty acids. The decrease in the MDA level and observed protecting effects can be attributed to PO extract, because it contains some important phytochemical constituents. (author)

High Circulating Adrenaline Levels at Admission Predict Increased Mortality After Trauma

DEFF Research Database (Denmark)

Johansson, Pär Ingemar; Stensballe, Jakob; Rasmussen, Lars Simon

2012-01-01

partial thromboplastin time, international normalized ratio, hematology, biochemistry, circulating adrenaline and noradrenaline, 11 biomarkers of tissue and endothelial damage, glycocalyx degradation, natural anticoagulation and fibrinolysis (histone-complexed DNA fragments, high-mobility group box 1......:: The adrenaline level was increased in nonsurvivors (p = 0.026), it was independently associated with increased activated partial thromboplastin time (p = 0.034) and syndecan-1 (p = 0.007), a marker of glycocalyx degradation, and it correlated with biomarkers of tissue and endothelial damage (histone......-complexed DNA, high-mobility group box 1, soluble thrombomodulin) and hyperfibrinolysis (tissue-type plasminogen activator, d-dimer). Furthermore, nonsurvivors had higher syndecan-1, tissue factor pathway inhibitor, and d-dimer levels (all p adrenaline was independently associated with 30...

Antiperoxidative Activity of Tetracarpidium conophorum Leaf Extract in Reproductive Organs of Male Rats

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Seun Funmilola Akomolafe

2015-01-01

Full Text Available Tetracarpidium conophorum (Mull. Arg. Hutch. & Dalz is one of the many medicinal plants used in folklore as male fertility enhancers. This research was aimed at evaluating the anti-peroxidative activity of the leaves of this plant by determining their capacity to reduce malondialdehyde (MDA level in reproductive organs and accessory glands of rats. Adult male rats were administered orally with the aqueous leaf extract from T. conophorum at 50, 500 and 1000 mg/kg body weight for 21 consecutive days while clomiphene citrate (1.04 mg/kg body weight, a fertility drug was used as standard. The results of the study indicated that there was increase in relative organ weight, body weight, mean total food and water consumed by the treated groups. Testicular MDA level was highly significantly different from that of the control (p<0.0001 although a tentatively decreased MDA level was observed. However, MDA levels in the reproductive accessory glands, epididymis, seminal vesicle and prostate gland were insignificantly (p<0.05 lower than those of controls. The highest percentage decrease of MDA level (66.35, 42.68, 62.50 and 63.36% was observed at the highest concentration of the extract (1000 mg/kg in the testis, epididymis, seminal vesicle and prostate gland respectively. These values were two-fold greater than the values obtained for the standard drug. Interestingly, the treatment of rats with the extract significantly increased the activities of superoxide dismutase, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and the levels of GSH, vitamin C and total protein. Collectively, the results suggest that the extract from T. conophorum leaves had greater capacity to reduce lipid peroxidation in reproductive organs and accessory glands and thus, this plant may be useful in the treatment/management of reproductive cellular damage involving reactive oxygen species.

Ghrelin administered spinally increases the blood glucose level in mice.

Science.gov (United States)

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-04-01

Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level. Copyright © 2014 Elsevier Inc. All rights reserved.

Low Nourishment of Vitamin C Induces Glutathione Depletion and Oxidative Stress in Healthy Young Adults.

Science.gov (United States)

Waly, Mostafa I; Al-Attabi, Zahir; Guizani, Nejib

2015-09-01

The present study was conducted to assess the status of vitamin C among healthy young adults in relation to serum antioxidant parameters [glutathione (GSH), thiols, and total antioxidant capacity, (TAC)], and oxidative stress markers [malondialdehyde (MDA), and nitrites plus nitrates (NN)]. A prospective study included 200 young adults, and their dietary intake was assessed by using food diaries. Fasting plasma vitamin C, serum levels of GSH, thiols, TAC, MDA, and NN were measured using biochemical assays. It was observed that 38% of the enrolled subjects, n=76, had an adequate dietary intake of vitamin C (ADI group). Meanwhile, 62%, n=124, had a low dietary intake of vitamin C (LDI group) as compared to the recommended dietary allowances. The fasting plasma level of vitamin C was significantly higher in the ADI group as compared to the LDI group. Oxidative stress in the sera of the LDI group was evidenced by depletion of GSH, low thiols levels, impairment of TAC, an elevation of MDA, and increased NN. In the ADI group, positive correlations were found between plasma vitamin C and serum antioxidant parameters (GSH, thiols, and TAC). Meanwhile, the plasma vitamin C was negatively correlated with serum MDA and NN levels. This study reveals a significant increase of oxidative stress status and reduced antioxidant capacity in sera from healthy young adults with low intake of the dietary antioxidant, vitamin C.

Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

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Krystina eSorwell

2014-06-01

Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

Increasing Resilience Through Engagement In Sea Level Rise Community Science Initiatives.

Science.gov (United States)

Chilton, L. A.; Rindge, H.

2017-12-01

Science literate and engaged members of the public, including students, are critical to building climate resilient communities. USC Sea Grant facilitates programs that work to build and strengthen these connections. The Urban Tides Community Science Initiative (Urban Tides) and the Youth Exploring Sea Level Rise Science Program (YESS) engage communities across the boundaries of public engagement, K-12 education, and informal education. YESS is an experiential sea level rise education program that combines classroom learning, field investigations and public presentations. Students explore sea level rise using a new curricula, collect their own data on sea level rise, develop communication products, and present their findings to city governments, researchers, and others. Urban Tides engages community members, informal education centers, K-12 students, and local government leaders in a citizen science program photo- documenting extreme high tides, erosion and coastal flooding in Southern California. Images provide critical information to help calibrate scientific models used to identify locations vulnerable to damage from future sea level rise. These tools and information enable community leaders and local governments to set priorities, guidelines, and update policies as they plan strategies that will help the region adapt. The program includes a mobile app for data collection, an open database to view photos, a lesson plan, and community beach walks. Urban Tides has led to an increase in data and data-gathering capacity for regional scientists, an increase in public participation in science, and an increase in ocean and climate literacy among initiative participants. Both of these programs bring informed and diverse voices into the discussion of how to adapt and build climate resilient communities. USC Sea Grant will share impacts and lessons learned from these two unique programs.

Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

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Noeman Saad A

2011-08-01

Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset

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Lily Boo

2017-07-01

Full Text Available Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs, yet little is known about their phenotypic characteristics and microRNAs (miRNAs expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.

A Breast Cell Atlas: Organelle analysis of the MDA-MB-231 cell line by density-gradient fractionation using isotopic marking and label-free analysis

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Marianne Sandin

2015-09-01

Full Text Available Protein translocation between organelles in the cell is an important process that regulates many cellular functions. However, organelles can rarely be isolated to purity so several methods have been developed to analyse the fractions obtained by density gradient centrifugation. We present an analysis of the distribution of proteins amongst organelles in the human breast cell line, MDA-MB-231 using two approaches: an isotopic labelling and a label-free approach.

Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

International Nuclear Information System (INIS)

Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

2014-01-01

Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

Oxidative Role of Aflatoxin B1 on the Liver of Wheat Milling Workers

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Amal Saad-Hussein

2014-03-01

Full Text Available Aim: The study aimed to estimate oxidative role of aflatoxin B1 (AFB1 on the liver in wheat milling workers. Materials and Methods: Case-control study was conducted to compare between the levels of AFB1/albumin (AFB1/alb, liver enzymes (ALT, AST, GGT, and ALP, P53, MDA, GST, SOD, zinc and vitamin C in 35 wheat milling workers and 40 control subjects. Results: Statistical analysis revealed that ALT, AST, GGT, ALP, P53, MDA, GST and SOD in workers were significantly elevated compared to their controls. In the milling workers, there were significant correlations between MDA levels and the levels of AST, GGT, and P53, while, P53 was inversely correlated with GST and SOD activities. There were significant correlations between Zn levels and GGT, GST and SOD activities, between vitamin C and GST activities, and vitamin C inversely correlated with MDA. Conclusion: The present study concluded that the oxidative stress of AFB1 elevated the MDA and the liver enzymes in wheat milling workers. GST has a crucial role in the detoxification of aflatoxin and SOD as a scavenger antioxidant increased in the workers to overcome the oxidative toxic effects of AFB1 on the liver of the workers, and roles of Zn and vitamin C were significant in activation of these processes.

Low-dose carbon ion irradiation effects on DNA damage and oxidative stress in the mouse testis

Science.gov (United States)

Liu, Yang; Long, Jing; Zhang, Luwei; Zhang, Hong; Liu, Bin; Zhao, Weiping; Wu, Zhehua

2011-01-01

To investigate the effects of low-dose carbon ion irradiation on reproductive system of mice, the testes of outbred Kunming strain mice were whole-body irradiated with 0, 0.05, 0.1, 0.5 and 1 Gy, respectively. We measured DNA double-strand breaks (DNA DSBs) and oxidative stress parameters including malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and testis weight and sperm count at 12 h, 21 d and 35 d after irradiation in mouse testis. At 12 h postirradiation, a significant increase in DNA DSB level but no pronounced alterations in MDA content or SOD activity were observed in 0.5 and 1 Gy groups compared with the control group. At 21 d postirradiation, there was a significant reduction in sperm count and distinct enhancements of DSB level and MDA content in 0.5 and 1 Gy groups in comparison with control. At 35 d postirradiation, the levels of DNA DSBs and MDA, and SOD activity returned to the baseline except for the MDA content in 1 Gy (P sperm count were still observed in 0.5 (P sperm count. Furthermore, these data suggest that the deleterious effects may be chronic or delayed in reproductive system after whole-body exposure to acute high-dose carbon ions.

Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

International Nuclear Information System (INIS)

Pontillo, Carolina Andrea; Rojas, Paola; Chiappini, Florencia; Sequeira, Gonzalo; Cocca, Claudia; Crocci, Máximo; Colombo, Lucas; Lanari, Claudia

2013-01-01

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models

Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

Energy Technology Data Exchange (ETDEWEB)

Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Rojas, Paola, E-mail: parojas2010@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com [Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires (Argentina); Sequeira, Gonzalo, E-mail: chicon27_7@hotmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); Cocca, Claudia, E-mail: cm_cocca@hotmail.com [Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Crocci, Máximo, E-mail: info@crescenti.com.ar [Instituto de Inmunooncología Crescenti, Buenos Aires (Argentina); Colombo, Lucas, E-mail: lucascol2003@yahoo.com.ar [Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires,Argentina (Argentina); Lanari, Claudia, E-mail: lanari.claudia@gmail.com [Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires (Argentina); and others

2013-05-01

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.

Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

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D. Markovic

2013-12-01

Full Text Available Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

Labor Augmentation with Oxytocin Decreases Glutathione Level

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Naomi Schneid-Kofman

2009-01-01

Full Text Available Objective. To compare oxidative stress following spontaneous vaginal delivery with that induced by Oxytocin augmented delivery. Methods. 98 women recruited prior to labor. 57 delivered spontaneously, while 41 received Oxytocin for augmentation of labor. Complicated deliveries and high-risk pregnancies were excluded. Informed consent was documented. Arterial cord blood gases, levels of Hematocrit, Hemoglobin, and Bilirubin were studied. Glutathione (GSH concentration was measured by a spectroscopic method. Plasma and red blood cell (RBC levels of Malondialdehyde indicated lipid peroxidation. RBC uptake of phenol red denoted cell penetrability. SPSS data analysis was used. Results. Cord blood GSH was significantly lower in the Oxytocin group (2.3±0.55 mM versus 2.55±0.55 mM, =.01. No differences were found in plasma or RBC levels of MDA or in uptake of Phenol red between the groups. Conclusion. Lower GSH levels following Oxytocin augmentation indicate an oxidative stress, though selected measures of oxidative stress demonstrate no cell damage.

Effects of Vitamin C on Oxidative Stress in Erythrocytes Following Exposure to Radiofrequency Waves Generated by a BTS Antenna Model

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Gholam Ali Jelodar

2014-12-01

Full Text Available Background: Radiofrequency waves (RFW of electronic devices and wireless communication systems affect biological systems by changing free radicals, increase lipid peroxidation and changes of antioxidant activity thereby leading to oxidative stress. This study was conducted to evaluate the RFW-induced oxidative stress in the erythrocytes and the prophylactic effect of vitamin C on these cells by measuring antioxidant enzymes activity including: glutathione peroxidase (GPx, superoxide dismutase (SOD, catalase (CAT, and malondialdehyde (MDA. Materials and Methods: In this experimental study, 32 adult male Sprague-Dawley rats were randomly divided into 4 experimental groups and treated daily (4 h/day for 45 days as follows: sham, sham+vitamin C (200 mg/kg/day by nasogastric tube, RFW (exposed to 900 MHz RFW and RFW+ vitamin C group (received vitamin C in addition to exposure to RFW. At the end of the experiment blood sample was collected by heart puncture for measurement of antioxidant enzymes activity and MDA level. Results: The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p<0.05. In the treated group vitamin C improved antioxidant enzymes activity and improved MDA level compared to the test group (p<0.05. Conclusion: It can be concluded that RFW causes oxidative stress in erythrocytes, and vitamin C improves the antioxidant enzymes activity and decreases MDA.

The biochemical effects of occupational exposure to lead and cadmium on markers of oxidative stress and antioxidant enzymes activity in the blood of glazers in tile industry.

Science.gov (United States)

Hormozi, Maryam; Mirzaei, Ramazan; Nakhaee, Alireza; Izadi, Shahrokh; Dehghan Haghighi, Javid

2018-01-01

The aim of the present study was to evaluate the effects of occupational exposure to lead (Pb) and cadmium (Cd) on markers of oxidative stress in glazers in tile industries. Total antioxidant capacity (TAC), malondialdehyde (MDA), and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the blood of 80 subjects, including 40 glazers and 40 nonexposed subjects. Mean levels of blood Cd (8.90 ± 2.80 µg/L) and blood Pb (62.90 ± 38.10 µg/L) of glazers showed a significant increase compared with the control group. In the serum of glazers, the level of MDA was significantly higher and the level of TAC was significantly lower than the control group. We have noted a disturbance in the levels of antioxidants by a significant increase in the CAT activity and a significant decrease in the activities of SOD and GPx in the serum of glazers compared with the controls. Correlation analysis demonstrated that the serum MDA level and CAT activity were positively associated with the blood levels of Pb and Cd. Also, GPx and SOD were negatively correlated with blood Cd levels. The study clearly indicated that co-exposure to Cd and Pb can induce oxidative stress in glazers, resulting in increased lipid peroxidation and altered antioxidant enzymes.

The Information Content of Note Disclosures and MD&A Information in the Financial Report – A Study of Market Reactions in Denmark

DEFF Research Database (Denmark)

Thinggaard, Frank; Sønderby Jeppesen, Carsten; Madsen, Kasper

2015-01-01

The preparation of disclosures in the financial report constitutes a significant cost to most companies, but do the disclosures have information content to investors? This paper examines stock market reactions to the release of note disclosures and MD&A (management discussion and analysis......) information. The study is based on data from the Danish capital market in 2006-2009 because here it is largely possible to isolate the release of such information from other information in the financial report. The primary results suggest that for some companies, note disclosures and information in the MD...

Glutathione oxidation correlates with one-lung ventilation time and PO2/FiO2 ratio during pulmonary lobectomy.

Science.gov (United States)

García-de-la-Asunción, José; García-Del-Olmo, Eva; Galan, Genaro; Guijarro, Ricardo; Martí, Francisco; Badenes, Rafael; Perez-Griera, Jaume; Duca, Alejandro; Delgado, Carlos; Carbonell, Jose; Belda, Javier

2016-09-01

During lung lobectomy, the operated lung completely collapses with simultaneous hypoxic pulmonary vasoconstriction, followed by expansion and reperfusion. Here, we investigated glutathione oxidation and lipoperoxidation in patients undergoing lung lobectomy, during one-lung ventilation (OLV) and after resuming two-lung ventilation (TLV), and examined the relationship with OLV duration. We performed a single-centre, observational, prospective study in 32 patients undergoing lung lobectomy. Blood samples were collected at five time-points: T0, pre-operatively; T1, during OLV, 5 minutes before resuming TLV; and T2, T3, and T4, respectively, 5, 60, and 180 minutes after resuming TLV. Samples were tested for reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione redox potential, and malondialdehyde (MDA). GSSG and MDA blood levels increased at T1, and increased further at T2. OLV duration directly correlated with marker levels at T1 and T2. Blood levels of GSH and glutathione redox potential decreased at T1-T3. GSSG, oxidized glutathione/total glutathione ratio, and MDA levels were inversely correlated with arterial blood PO2/FiO2 at T1 and T2. During lung lobectomy and OLV, glutathione oxidation, and lipoperoxidation marker blood levels increase, with further increases after resuming TLV. Oxidative stress degree was directly correlated with OLV duration, and inversely correlated with arterial blood PO2/FiO2.

Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

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Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

2018-03-01

Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

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Vučeljić Marina

2006-01-01

Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

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Ganka Bekyarova

2017-04-01

Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

Myoclonic epilepsy with ragged-red fibers without increased lactate levels.

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Kimura, Shigemi; Ozasa, Shiro; Nakamura, Kyoko; Nomura, Keiko; Kosuge, Hirofumi

2009-07-01

Myoclonic epilepsy associated with ragged-red fibers is one of the mitochondrial encephalomyopathies. Pathogenic mitochondrial DNA mutations have been identified in the mitochondrial transfer RNA (tRNA)(Lys) at positions 8344 and 8356. Characteristics of myoclonic epilepsy associated with ragged-red fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance, lactic acidosis, and ragged-red fibers. The elevated lactate level is one of the most important symptoms needed to make a diagnosis of mitochondrial encephalomyopathy. In the present case, however, myoclonic epilepsy was associated with ragged-red fibers but without increased lactate levels. Therefore, myoclonic epilepsy associated with ragged-red fibers should be suspected in a patient who has myoclonic epilepsy that is difficult to control with antiepileptic medications and who has other symptoms of mitochondrial disease, such as mental retardation, even if the patient's lactate level is normal.

Increased plasma levels of soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1) in women by moderate exercise and increased plasma levels of VEGF in overweight/obese women

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Makey, Kristina L.; Patterson, Sharla G.; Robinson, James; Loftin, Mark; Waddell, Dwight E.; Miele, Lucio; Chinchar, Edmund; Huang, Min; Smith, Andrew D.; Weber, Mark; Gu, Jian-Wei

2012-01-01

The incidence of breast cancer is increasing worldwide, and this seems to be related to an increase in lifestyle risk factors, including physical inactivity, and overweight/obesity. We previously reported that exercise induced a circulating angiostatic phenotype characterized by increased sFlt-1 and endostatin and decreased unbound-VEGF in men. However, there is no data on women. The present study determines the following: 1) whether moderate exercise increased sFlt-1 and endostatin and decreased unbound-VEGF in the circulation of adult female volunteers; 2) whether overweight/obese women have a higher plasma level of unbound-VEGF than lean women. 72 African American and Caucasian adult women volunteers aged from 18–44 were enrolled into the exercise study. All the participants walked on a treadmill for 30 minutes at a moderate intensity (55–59% heart rate reserve), and oxygen consumption (VO2) was quantified by utilizing a metabolic cart. We had the blood samples before and immediately after exercise from 63 participants. ELISA assays (R&D Systems) showed that plasma levels of sFlt-1 were 67.8±3.7 pg/ml immediately after exercise (30 minutes), significantly higher than basal levels, 54.5±3.3 pg/ml, before exercise (P < 0.01; n=63). There was no significant difference in the % increase of sFlt-1 levels after exercise between African American and Caucasian (P=0.533) or between lean and overweight/obese women (P=0.892). There was no significant difference in plasma levels of unbound VEGF (35.28±5.47 vs. 35.23±4.96 pg/ml; P=0.99) or endostatin (111.12±5.48 vs. 115.45±7.15 ng/ml; P=0.63) before and after exercise. Basal plasma levels of unbound-VEGF in overweight/obese women were 52.26±9.6 pg/ml, significantly higher than basal levels of unbound-VEGF in lean women, 27.34±4.99 pg/ml (P < 0.05). The results support our hypothesis that exercise-induced plasma levels of sFlt-1 could be an important clinical biomarker to explore the mechanisms of exercise

Low level GAMMA0 spectrometry by beta-gamma coincidence

International Nuclear Information System (INIS)

Grigorescu, E.L.; Luca, A.; Razdolescu, A.C.; Ivan, C.

1999-01-01

Low level gamma spectrometry has a wide application, especially in environmental monitoring. Two variants, based on a beta-gamma coincidence technique, were studied. The equipment was composed of a beta detector and a Ge(Li) gamma detector (6% - relative efficiency), with the associated electronics. The gamma rays are recorded by the multichannel analyzer (4096 channels) only if the associated beta particles, which precede the gamma transitions, are registered in coincidence. Two types of beta detectors were used: plastic and liquid scintillators. In both cases, an external lead shield of 5 cm thick was used. The integral gamma background (50-1700 KeV) was reduced about 85 and 50 times, respectively. The corresponding MDA (Minimum Detectable Activity) values decreased about 1.5 and (3-7) times, respectively. The 2π sr plastic beta detector was placed on top the Ge(Li). The sample was inserted between the two detectors. The measurement time was 10 4 s. A 4π sr detector, built of the same material, was also studied, but it proved to be less advantageous because the background was reduced only 16 times; for a MDA reduction similar with that of the 2π sr variant, a longer measurement was needed (3.10 4 s). The other type of beta detector used, was a liquid scintillator. The dissolving of the samples in scintillator ensures a 4π sr measurement geometry. The vials with scintillator (10 ml volume) were placed on top the Ge(Li) and visualised by the photocathode of a phototube. This setup was surrounded by an enclosure which prevent the light penetration. The measurement time was 10 4 s. The only difficulty encountered in this low level measurement method is the accurate determination of the beta efficiency. A limitation is the possibility to measure only small mass samples. These variants are more simple and cheaper than others, previously studied. The advantage of the method is obvious when, instead of low MDA values, shorter measurement times are preferred. The

Reduction of cooking oil fume exposure following an engineering intervention in Chinese restaurants.

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Pan, Chih-Hong; Shih, Tung-Sheng; Chen, Chiou-Jong; Hsu, Jin-Huei; Wang, Shun-Chih; Huang, Chien-Ping; Kuo, Ching-Tang; Wu, Kuen-Yuh; Hu, Howard; Chan, Chang-Chuan

2011-01-01

A new engineering intervention measure, an embracing air curtain device (EACD), was used to increase the capture efficiency of cooker hoods and reduce cooking oil fume (COF) exposure in Chinese restaurants. An EACD was installed in six Chinese restaurants where the cooks complained of COF exposure. Before- and after-installation measurements were taken to compare changes in particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) in kitchen air, and changes in levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The association between PM and PAHs in air and 8-OHdG and MDA in urine was evaluated by linear mixed-effects regression analysis. Results showed that geometric mean kitchen air levels of PM(10), PM(2.5), PM(1.0) and total particulate PAHs were significantly reduced after the EACDs were introduced. Urinary levels of 8-OHdG and MDA in cooks were also significantly lower after EACD instalment. PM(2.5), PM(1.0) and benzo(a)pyrene (BaP) levels were positively associated with urinary 8-OHdG levels after adjusting for key personal covariates. Urinary MDA levels in cooks were also positively associated with BaP levels after adjusting for key personal covariates. This study demonstrates that the EACD is effective for reducing COF and oxidative stress levels in cooks working in Chinese kitchens.