The solar kettle-thermos flask (SK-TF) and solar vacuum tube oven

Energy Technology Data Exchange (ETDEWEB)

Yak, Alex Kee Koo [AkayConsult Enterprise, Johor Bahru (Malaysia)

2008-07-01

The Solar Kettle-Thermos Flask (SK-TF) and Solar Vacuum Tube Oven (SaVeTao): A Cost Effective, Sustainable and Renewable Water Pasteurization and Food Processing System For The Developing World. Based on the perfect solar thermal energy harvesting paradigm of maximum solar radiation absorption and minimum loss of stored converted solar thermal energy, Solar Vacuum Glass Tubes (SVGT) indefinitely delivers solar pasteurized safe drinking water, powered solely by free solar energy. The SVGT is the heart of the SK-TF. Being vacuum insulated, the SK-TF doubles up as a vacuum flask, delivering stored solar heated water in the morning before the Sun is up. With a high stagnation temperature of more than 200 C, the SK-TF can also be used for other heating purposes e.g. an oven or autoclave. Powered solely by free solar energy, the SK-TF and SaVeTaO could very well be the answer in providing safe solar pasteurized drinking water and cooking to the global poor and needy in a sustainable and renewable way. (orig.)

Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium.

Science.gov (United States)

Noble, Karen; Floyd, Rachel; Shmygol, Andre; Shmygol, Anatoly; Mobasheri, A; Wray, Susan

2010-01-01

Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels. 2009 Elsevier Ltd. All rights reserved.

[Roles of KLF5 in inhibition TNFα-induced SK-BR-3 breast cancer cell apoptosis].

Science.gov (United States)

Shi, Jianhong; Liu, Caiyun; Zhang, Anyi; Cui, Naipeng; Wang, Bing; Chen, Baoping; Ma, Zhenfeng

2014-07-08

To explore the expression levels and roles of Krüpple-like factor 5 (KLF5) in tumor necrosis factor α (TNFα)-induced SK-BR-3 breast cancer cells. SK-BR-3 breast cancer cells were stimulated by TNFα at different concentrations (0, 1, 5, 10, 20 µg/L) for specified durations (0, 6, 12, 24, 36 h). Western blot was performed to detect KLF5 protein levels. Then Western blot and quantitative real-time PCR (qRT-PCR) were used to detect the expression levels of apoptosis genes. Flow cytometry and qRT-PCR were used to observe the effects of exogenous KLF5 on TNFα-induced apoptosis of SK-BR-3 breast cancer cell. KLF5 expression levels significantly decreased in TNFα-stimulated SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Quantitative RT-PCR results showed that TNFα up-regulate apoptosis gene caspase 3, caspase 9 and bax expression levels and down-regulate bcl-1 level in SK-BR-3 cells. Adenovirus expression vectors of pAd-GFP and pAd-GFP-KLF5 were constructed and used to infect SK-BR-3 breast cancer cells. Over-expression of GFP-KLF5 inhibited apoptosis in TNFα-stimulated SK-BR-3 breast cancer cells. TNFα reduces KLF5 expression in SK-BR-3 breast cancer cells and KLF5 participates in TNFα-induced SK-BR-3 cell apoptosis.

Induction of cellular and molecular immunomodulatory pathways by vitamin A and Flavonoids

Science.gov (United States)

Patel, Sapna; Vajdy, Michael

2016-01-01

Introduction A detailed study of reports on the immunomodulatory properties of vitamin A and select flavonoids may pave the way for using these natural compounds or compounds with similar structures in novel drug and vaccine designs against infectious and autoimmune diseases and cancers. Areas Covered Intracellular transduction pathways, cellular differentiation and functional immunomodulatory responses have been reviewed. The reported studies encompass in vitro, in vivo preclinical and clinical studies that address the role of Vitamin A and select flavonoids in induction of innate and adaptive B and T cell responses, including TH1, TH2 and Treg. Expert Opinion While the immunomodulatory role of vitamin A, and related compounds, is well-established in many preclinical studies, its role in humans has begun to gain wider acceptance. In contrast, the role of flavonoids is mostly controversial in clinical trials, due to the diversity of the various classes of these compounds, and possibly due to the purity and the selected doses of the compounds. However, current preclinical and clinical studies warrant further detailed studies of these promising immuno-modulatory compounds. PMID:26185959

Pharmacokinetics of the vasopressin antagonist, SK and F 101926, a synthetic octapeptide, in the rat

International Nuclear Information System (INIS)

Lynn, R.K.; Straub, K.M.; Landvatter, S.W.; Garvie, C.T.

1986-01-01

SK and F 101926 is a synthetic analogue of vasopressin which antagonizes vasopressin induced antidiuresis. Radiolabeled SK and F 101926 ( 3 H-3,3-D-TYR) was administered i.v. as a single bolus to male Sprague Dawley rats. Serial plasma samples were analyzed for SK and F 101926 by HPLC/LSC. The plasma concentration time curve for SK and F 101926 displayed three disposition phases. However, 80% of the total area under the curve was represented in one phase which displayed a half-life (t 1/2) of 20 min. The total systematic clearance (Cl) and the steady state volume of distribution (Vdss) were 15 ml/min/kg and 450 ml/kg, respectively. The t 1/2, Cl and Vdss were identical following doses of 10 and 100 μg/kg. 3 H-SK and F 101926 accounted for > 80% of the plasma radiolabel 0-30 min after dosing. However, by 12 hr, 3 H-SK and F 101926 represented only 6% of the plasma radiolabel. Following oral administration of 3 H-SK and F 101926, < 5% of the administered radiolabel reached the systematic circulation; however, no parent compound was detectable in plasma. These studies demonstrate that although SK and F 101926 has a relatively low systematic clearance, it also displays a relatively small volume of distribution which together result in a moderate beta elimination half-life

Immunomodulatory, antiglycation and anti-ulcerative properties of ...

African Journals Online (AJOL)

useful drugs because of their wide functions [15]. Various disease conditions such as infections, organ transplant rejection, cancer, rheumatoid arthritis, and systemic lupus erythematosus are currently treated with immunomodulating agents. [16]. Many plants with immunomodulatory activities have been reported e.g. ...

Immunomodulatory effects of histone deacetylase inhibitors.

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Licciardi, P V; Ververis, K; Tang, M L; El-Osta, A; Karagiannis, T C

2013-05-01

Histone deacetylase inhibitors (HDACi) have emerged as a new generation of anticancer therapeutics. The classical broad-spectrum HDACi typically alter the cell cycle distribution and induce cell death, apoptosis and differentiation in malignant and transformed cells. This provides the basis for the clinical potential of HDACi in cancer therapy. Currently two compounds, suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza™) and depsipeptide (Romidepsin, Istodax™) have been approved for by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Apart from clinical application in oncology, HDACi have also been investigated as potential therapeutics for various pathologies including those of the central nervous system (such as Huntington's disease and multiple sclerosis), cardiac conditions (particularly hypertrophy), arthritis and malaria. Further, evidence is accumulating for potent immunomodulatory effects of classical HDACi which is the focus of this review. We review the antiinflammatory effects of HDACi and in particular findings implicating regulation of the innate and adaptive immune systems by HDAC enzymes. The recent findings highlighting the immunomodulatory function of HDAC11 which relates to balancing immune activation versus tolerance are also discussed.

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

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Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

Immunomodulatory Activity of Alcohol Extract of Terminalia chebula ...

African Journals Online (AJOL)

Erah

2011-01-02

Jan 2, 2011 ... Purpose: To investigate the immunomodulatory activity of the alcohol extract of Terminalia chebula Retz. (Combretaceae) ..... indicates a higher secretion of melatonin. (Mol. Wt. 248 ... especially the immune, nervous, and.

Immunomodulatory Potential of Patchouli Alcohol Isolated from ...

African Journals Online (AJOL)

Purpose: To isolate and purify patchouli alcohol (PA), a tricyclic sesquiterpene constituent of Pogostemon cablin, and investigate its immunomodulatory potential in Kunming mice. Methods: PA was prepared from an ethanol aqueous extract of P. cablin by silica gel column chromatography, and further purified by ...

Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

DEFF Research Database (Denmark)

Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

2014-01-01

(+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application

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Insausti CL

2014-03-01

Full Text Available Carmen L Insausti,1 Miguel Blanquer,1 Ana M García-Hernández,1 Gregorio Castellanos,2 José M Moraleda11Unidad de Trasplante Hematopoyético y Terapia Celular, 2Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Campus Mare Nostrum, Universidad de Murcia, El Palmar, Murcia, SpainAbstract: Epithelial and mesenchymal cells isolated from the amniotic membrane (AM possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.Keywords: epithelial cells, mesenchymal cells, cell therapy, immunomodulation

Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

DEFF Research Database (Denmark)

Follin, Bjarke; Juhl, Morten; Cohen, Smadar

2016-01-01

Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention...... for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs...... when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two-dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity...

Antitumor and immunomodulatory activity of Inonotus obliquus

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Staniszewska Justyna

2017-06-01

Full Text Available The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

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Samira Abbasi

2016-01-01

Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels

Characterization of CD4 and CD8 T Cell Responses in MuSK Myasthenia Gravis

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Yi, JS; Guidon, A; Sparks, S; Osborne, R; Juel, VC; Massey, JM; Sanders, DB; Weinhold, KJ; Guptill, JT

2014-01-01

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T-cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T-cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T-cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T-cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T-cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T-cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in Treg function or number. PMID:24378287

NEW MEAT PRODUCTS WITH IMMUNOMODULATORY EFFECT CREATION METHOD

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I. V. Kaltovich

2016-01-01

Full Text Available New meat products with immunomodulatory effect creation method reflecting differential characteristics of technological stages of manufacture of those types of meat products, including issues on the selection of primary and secondary raw materials, guidelines for development of formulations and production technologies, legislative requirements towards its labeling, etc, has been developed for the first time. A list of prospective meat raw materials for the manufacture of products with immunomodulatory effect was established: beef, pork, rabbit meat, broiler chicken meat, turkey, veal, ostrich meat, which have high content of protein (14,3– 21,7%, low content of fat (1,2–16,1%, excluding pork (33,3%, high levels of minimum amino-acid score (90,0–104,0%, protein quality indicator(0,91–1,64, essential amino acid index (1,16-1,25, coefficient of utility of amino acid content (0,72–0,86 and close to optimum fatty acid content, and also contain a great number of vitamins and minerals which play a significant role for immunity improvement. It was determined that the following functional ingredients are recommended to use: amino acids (valine, leucine, isoleucine, methionine, threonine, arginine, tryptophan, lysine, histidin, phenylalanyl, vitamins and provitamins (C,E, beta-carotene, B vitamins(Bc, B12, PP, etc., P(bioflavonoid complex, H, K, minerals (calcium, magnesium, iron, cuprum, zinc, manganese, selenium, polyunsaturated fatty acids omega-3 and omega-6, pseudo-vitamins (L-carnitin, coenzyme Q10, polysaccharides and peptides naturally occurring(squalen, B-Carotene, ginger, shiitake mushrooms, probiotics and prebiotics, glutathione, indole and lycopienes, bioflavonoids, L-arginine, N-acetylcysteine, gel from seaweed «Lamifaren». The use of the developed meat products with immunomodulatory effect creation method by process engineers of meat processing factories will allow them to form a single scientifically grounded approach during the

IMMUNO-MODULATORY PROPERTIES OF PREBIOTICS EXTRACTED FROM vernonia amygdalina.

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Im, Ezeonu; Ae, Asuquo; Bn, Ukwah; Po, Ukoha

2016-01-01

Vernonia amygdalina , commonly called bitter-leaf, is widely consumed in many parts of Africa, and Nigeria, in particular. The leaf extract has been reported to have antimicrobial, anti-plasmodial, anti-helminthic, as well as prebiotic properties, but its immuno-modulatory effects have not been well-studied, neither have the prebiotics been identified. This study evaluated the immuno-modulatory properties of the aqueous leaf extract and identified the prebiotic components. The immuno-modulatory potential was evaluated by monitoring the effects of oral administration of the extract on immunological, haematological and lipid profiles of Rattus norvegicus , while the prebiotic components were identified by thin layer chromatography (TLC), following liquid-liquid fractionation of the extract. Consumption of the extract caused significant increases in CD4+-, white blood cell-, total lymphocyte- and high density lipid (HDL) counts; decreases in low density lipid (LDL) and triglycerides and no significant effect on haemoglobin (Hb) and packed cell volume (PCV) in the blood of test animals. The water-soluble fraction of the extract contained most of the phyto-constituents of the extract and Thin Layer Chromatographic analysis of the fraction revealed the presence of fructo-oligosaccharide and galacto-oligosaccharide prebiotics. The results from this study have shown that the aqueous leaf extract of V. amygdalina has positive immune-modulatory and haematologic effects and contains some important prebiotic compounds.

Evaluation of immunomodulatory activity of " Shirishavaleha"-An Ayurvedic compound formulation in albino rats

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Shyamlal Singh Yadav

2011-01-01

Full Text Available The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth, i.e., Twak (Bark and Sara (Heartwood as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

Evaluation of immunomodulatory activity of "Shirishavaleha"-An Ayurvedic compound formulation in albino rats.

Science.gov (United States)

Yadav, Shyamlal Singh; Galib; Prajapati, P K; Ashok, B K; Ravishankar, B

2011-10-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

Infantile Onset Myasthenia Gravis with MuSK Antibodies

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J Gordon Millichap

2006-08-01

Full Text Available A late infantile case of myasthenia gravis (MG with anti-muscle-specific receptor tyrosine kinase (MuSK high antibody (Ab titer is reported from Kyushu University, Fukuoka; and Nagasaki University, Japan.

Immuno-modulatory properties of prebiotics extracted from Vernonia ...

African Journals Online (AJOL)

Methods: The immuno-modulatory potential was evaluated by monitoring the effects of oral administration of the extract on immunological, haematological and lipid profiles of Rattus norvegicus, while the prebiotic components were identified by thin layer chromatography (TLC), following liquid-liquid fractionation of the ...

Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

Science.gov (United States)

Soeiro, Vinicius C; Melo, Karoline R T; Alves, Monique G C F; Medeiros, Mayara J C; Grilo, Maria L P M; Almeida-Lima, Jailma; Pontes, Daniel L; Costa, Leandro S; Rocha, Hugo A O

2016-08-19

Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

Protective roles for potassium SK/KCa2 channels in microglia and neurons

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Amalia M Dolga

2012-11-01

Full Text Available New concepts on potassium channel function in neuroinflammation suggest that they regulate mechanisms of microglial activation, including intracellular calcium homeostasis, morphological alterations, pro-inflammatory cytokine release, antigen presentation, and phagocytosis. Although little is known about voltage independent potassium channels in microglia, special attention emerges on small (SK/KCNN1-3/KCa2 and intermediate (IK/KCNN4/KCa3.1-conductance calcium-activated potassium channels as regulators of microglial activation in the field of research on neuroinflammation and neurodegeneration. In particular, recent findings suggested that SK/KCa2 channels, by regulating calcium homeostasis, may elicit a dual mechanism of action with protective properties in neurons and inhibition of inflammatory responses in microglia. Thus, modulating SK/KCa2 channels and calcium signaling may provide novel therapeutic strategies in neurological disorders, where neuronal cell death and inflammatory responses concomitantly contribute to disease progression. Here, we review the particular role of SK/KCa2 channels for [Ca2+]i regulation in microglia and neurons, and we discuss the potential impact for further experimental approaches addressing novel therapeutic strategies in neurological diseases, where neuronal cell death and neuroinflammatory processes are prominent.

Development of immunotoxicity testing strategies for immunomodulatory drugs.

Science.gov (United States)

Kawabata, Thomas T; Evans, Ellen W

2012-01-01

The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.

Development of norepinephrine transporter reuptake inhibition assays using SK-N-BE(2C cells

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Ann M. Decker

2018-05-01

Full Text Available This report describes efforts to develop and validate novel norepinephrine transporter reuptake inhibition assays using human neuroblastoma SK-N-BE(2C cells in 24-well format. Before conducting the assays, the SK-N-BE(2C cells were first evaluated for their ability to uptake [3H]norepinephrine and were shown to have a saturable uptake with a KM value of 416 nM. Using this determined KM value, reuptake inhibition assays were then conducted with a variety of ligands including antidepressants, as well as piperazine and phenyltropane derivatives. The results obtained with the SK-N-BE(2C cells indicate that this model system can detect a range of ligand potencies, which compare well with other established transporter assays. Our data suggest that SK-N-BE(2C cells have potential utility to serve as another model system to detect norepinephrine reuptake inhibition activity.

S.K. De Datta receives Clifton Garvin Fellowship

OpenAIRE

Felker, Susan B.

2004-01-01

S.K. De Datta, of Blacksburg, associate provost for international affairs at Virginia Tech, received the university's Clifton Garvin Fellowship Award. The award was conferred by the Virginia Tech Board of Visitors at its quarterly meeting Monday, Nov. 8.

Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities.

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Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Sassi, Aicha; Abed, Besma; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

2016-06-01

The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.

Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells.

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Velagapudi, Ravikanth; Baco, Gina; Khela, Sunjeet; Okorji, Uchechukwu; Olajide, Olumayokun

2016-06-01

Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells. An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1β-stimulated SK-N-SH cells. Expression of COX-2, phospho-IκB, and phospho-IKK proteins was evaluated, while NF-κB reporter gene assay was carried out in TNFα-stimulated HEK293 cells to determine the effect of PWE on NF-κB transactivation. Levels of BACE-1 and Aβ in SK-N-SH cells stimulated with IL-1β were measured with an in cell ELISA. PWE (25-200 μg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1β. Phosphorylation of IκB and IKK was significantly (p pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1β-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease.

The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice.

Science.gov (United States)

Ayeka, Peter Amwoga; Bian, YuHong; Githaiga, Peter Mwitari; Zhao, Ying

2017-12-15

The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional Chinese medicine (TCM) has attracted great attention for its antitumor and immunomodulatory activities, the mechanism of action of its polysaccharides is still unclear. Here we report the immunomodulatory activity of licorice polysaccharides in vivo. The differential anticancer activities of licorice polysaccharides by tumorigenesis and immunomodulation was evaluated in vivo. Six weeks old, 120 CT-26 tumor bearing BALB/c mice, weighing 20 ± 2 g were used. They were randomly divided into six groups, three groups receiving high molecular weight (fraction A), low molecular weight (fraction B) polysaccharides and crude extract (fraction C); positive, negative and normal groups receiving cytoxin, saline and normal diet respectively. Weight of mice and tumors was determined and tumorigenicity assay calculated to determine the anticancer effects. Immunomodulatory potential was determined by immune organ indices, immune cell population and serum cytokine levels using immune organ weight and index, flow cytometry and cytokine/chemokine bead panel kit respectively. Licorice polysaccharides exhibited immunomodulatory activities in CT 26 tumor bearing BALB/c mice. The polysaccharides significantly suppressed tumor growth and increased immune organ index. Furthermore, the immunomodulatory effect was evident with activation of CD4 + and CD8 + immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels. In summary, licorice polysaccharide especially of low molecular weight exhibit anticancer and immunomodulatory activities by suppressing tumor growth and improving general health of mice. They also augment the thymus/spleen index and population of T lymphocytes

The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression.

Science.gov (United States)

Egloff, Sylvain; Vitali, Patrice; Tellier, Michael; Raffel, Raoul; Murphy, Shona; Kiss, Tamás

2017-04-03

The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P-TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII-specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII-specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII. © 2017 The Authors.

Pozytywizm, racjonalizm i... romantyzm Marii Skłodowskiej-Curie

Directory of Open Access Journals (Sweden)

Barbara Petelenz

2015-12-01

Full Text Available The International Year of Chemistry (2011, intertwined with commemoration of the Nobel Prize in Chemistry awarded in 1911 to Marie Skłodowska-Curie, made me to ask about the philosophical background of this outstanding woman. The first factor which I could see was the positivism, launched by August Comte in France and developed a few decades later by his Polish followers. Another factor which seemed to me important was the interplay between the emotional (romantic and intellectual (positivistic attitudes among the Poles in the 19th century. In her research, Marie Skłodowska-Curie used the positivistic, rationalistic method. This has led her (jointly with her husband Pierre Curie to elucidation of the radiation phenomena discovered by Henri Becquerel in 1896. The research initiated by the Curies (rewarded by the half of the Nobel Prize in Physics 1903 caused a subversion of the 19th century’s views on the structure of Matter. The way to such spectacular results must have been paved not only by the positivistic intellectual discipline but also by a dose of romantic enchantment. In the applicative terms, Marie Skłodowska-Curie became a pioneer of the evidence-based medicine. In moral terms, she represented a rare example of the practical altruism, inspired indirectly by Christianity, and directly by the Comte’s “religion of Humanity”.

Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL.

Science.gov (United States)

Bae, S I; Cheriyath, V; Jacobs, B S; Reu, F J; Borden, E C

2008-01-17

Human melanoma cell lines, SK-MEL-3 and SK-MEL-28, despite induction of the proapoptotic cytokine, Apo2L/TRAIL, did not undergo apoptosis in response to interferons (IFN-alpha2b or IFN-beta). Postulating that genes important for apoptosis induction by IFNs might be silenced by methylation, the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZAdC) was assessed. DR4 (TRAIL-R1) was identified as one of the genes reactivated by 5-AZAdC with a >3-fold increase in 8 of 10 melanoma cell lines. Pretreatment with 5-AZAdC sensitized SK-MEL-3 and SK-MEL-28 cells to apoptosis induced by IFN-alpha2b and IFN-beta; methylation-specific PCR and bisulfite sequencing confirmed demethylation of 5'CpG islands of DR4 and flow cytometry showed an increase in DR4 protein on the cell surface. In cells with reactivated DR4, neutralizing mAB to TRAIL reduced apoptosis in response to IFN-beta or Apo2L/TRAIL. To further confirm the role of DR4, it was expressed by retroviral vector in SK-MEL-3 and SK-MEL-28 cells with reversal of resistance to IFN-beta and Apo2L/TRAIL. Thus, reexpressing DR4 by 5-AZAdC or retroviral transfection in melanoma cell in which promoter methylation had suppressed its expression, potentiated apoptosis by IFN-alpha2b, IFN-beta and Apo2L/TRAIL. Reactivation of silenced proapoptotic genes by inhibitors of DNA methylation may enhance clinical response to IFNs or Apo2L/TRAIL.

Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

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Vuslat Yilmaz

Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK

Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea on human dendritic cells.

Science.gov (United States)

Santander, Sandra Paola; Hernández, John Fredy; Barreto, Claudia Cifuentes; Cifuentes B, Claudia; Masayuki, Aoki; M, Aoki; Moins-Teisserenc, Hélène; H, Moins-Teisserenc; Fiorentino, Susana

2012-01-01

Petiveria alliacea is a plant traditionally known for its anti-inflammatory and anti-tumor activities; however, the molecular and cellular mechanisms of its immunomodulatory properties are still unknown. Dendritic cells (DC) promote adaptive immune response by activating T lymphocytes, inducing an effector response or tolerance depending on the DC differentiation level. Herein, we evaluated the immunomodulatory activity of aqueous and organic plant fractions from P. alliacea using human monocyte-derived dendritic cells. The phenotype, cytokine secretion and gene expression were estimated after treatment with the plant fractions. We found that P. alliacea aqueous fraction induced morphological changes and co-stimulatory expression of CD86, indicating partial DC maturation. In addition, pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α were secreted. The fraction also increased NF-κB gene expression while down-regulating TGFβ gene expression. These results suggest that the aqueous fraction can induce partial DC activation, a situation that can be relevant in tolerance induction. It is important to state that the organic fraction by itself does not show any immunomodulatory activity. This study provides evidence for possible immunomodulatory activity of P. alliacea extracts which has been used in traditional medicine in Colombia.

Global features of the Alcanivorax borkumensis SK2 genome

DEFF Research Database (Denmark)

Reva, Oleg N.; Hallin, Peter Fischer; Willenbrock, Hanni

2008-01-01

The global feature of the completely sequenced Alcanivorax borkumensis SK2 type strain chromosome is its symmetry and homogeneity. The origin and terminus of replication are located opposite to each other in the chromosome and are discerned with high signal to noise ratios by maximal oligonucleot......The global feature of the completely sequenced Alcanivorax borkumensis SK2 type strain chromosome is its symmetry and homogeneity. The origin and terminus of replication are located opposite to each other in the chromosome and are discerned with high signal to noise ratios by maximal...... oligonucleotide usage biases on the leading and lagging strand. Genomic DNA structure is rather uniform throughout the chromosome with respect to intrinsic curvature, position preference or base stacking energy. The orthologs and paralogs of A. borkumensis genes with the highest sequence homology were found...

Influence of source batch Sk dispersion on dosimetry for prostate cancer treatment with permanent implants

DEFF Research Database (Denmark)

Nunez-Cumplido, Eduardo; Perez-Calatayud, J; Casares-Magaz, O

2015-01-01

PURPOSE: In clinical practice, specific air kerma strength (SK) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with (125)I and (103)Pd sources; in fact, commercial TPS provide only one SK input value for all implanted sources and the certified shipment...

[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].

Science.gov (United States)

Shi, Jianhong; Lü, Xinrui; Wang, Bing; Daudan, Lin; Yanan, Wang; Yuhui, Bu; Zhenfeng, Ma

2014-09-30

To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation. Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation. YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P BR-3 cells in a dose-dependent manner. A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.

Evaluation of immunomodulatory activity of “Shirishavaleha”–An Ayurvedic compound formulation in albino rats

Science.gov (United States)

Yadav, Shyamlal Singh; Galib; Prajapati, P. K.; Ashok, B. K.; Ravishankar, B.

2011-01-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity. PMID:22253509

Immunomodulatory activity of methanol extract of Adansonia digitata L

African Journals Online (AJOL)

Purpose: To evaluate the immune-modulatory activities of various plant parts Adansonia digitata L. using delayed-type hypersensitivity rat model. Methods: Defatted leaf, root bark and fruit pulp of A. digitata were extracted with methanol. Immunomodulatory activity of the methanol extracts (250 and 500 mg/kg) were ...

Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

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Jong Seok Lee

2014-01-01

Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

Science.gov (United States)

Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

2018-03-20

Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

The spatial distribution of rock landforms in the Pohořská Mountains (Pohořská hornatina), Czech Republic

Czech Academy of Sciences Publication Activity Database

Rypl, J.; Kirchner, Karel; Blažek, M.

2017-01-01

Roč. 57, č. 2 (2017), s. 45-55 ISSN 1581-6613 Institutional support: RVO:68145535 Keywords : geomorphology * rock landforms * lithology * Pohořská Mountains Subject RIV: DE - Earth Magnetism, Geodesy, Geography OBOR OECD: Physical geography Impact factor: 0.533, year: 2016 http://www.pf.jcu.cz/structure/departments/kge/upload/files/1184-13377-1-PB.pdf

Complete sequences of four plasmids of Lactococcus lactis subsp cremoris SK11 reveal extensive adaptation to the dairy environment

NARCIS (Netherlands)

Siezen, R.J.; Renckens, B.; Swam, van I.; Peters, S.; Kranenburg, van R.; Kleerebezem, M.; Vos, de W.M.

2005-01-01

Lactococcus lactis strains are known to carry plasmids encoding industrially important traits. L. lactis subsp. cremoris SK11 is widely used by the dairy industry in cheese making. Its complete plasmid complement was sequenced and found to contain the plasmids pSK11A (10,372 bp), pSK11B (13,332 bp),

Experimental analysis on frosting characteristic of SK-type finned refrigerating heat exchanger with large-diameter circular holes

International Nuclear Information System (INIS)

Fang, Zhao-song; Wang, Hou-hua; Zhang, Jie; Wu, Wei-wei

2014-01-01

This paper presents the construction of both a plane fin-and-tube heat exchanger and a SK-type fin-and-tube heat exchanger. Based on plane fin-and-tube heat exchanger, comparative industrial prototype experiments of SK-type fin-and-tube heat exchanger energy efficiency performance were carried out in the artificial climate chamber. Test results confirmed several findings: when the amount of the refrigerant charged is the same and face velocity u = 3.75 m s −1 , SK-type fin-and-tube heat exchanger refrigeration capacity increases by an average of 9.13%; energy consumption reduces by an average of 11.25%, coefficient of performance (COP) of heat exchanger increases by an average of 22.65% with continuous operation during the first 2 h. Also, when the operation time exceeds 2 h, the COP of both types of heat exchangers are both less than 0.6, illustrating that under frost conditions, the defrost interval should not be too long, otherwise energy consumption may sharply spike. - Highlights: •The large holes of SK-type induced the generation of turbulence flow. •The refrigeration capacity and COP of SK-type exceeds that of plane one. •The SK-type fin-and-tube heat exchanger is a new kind of heat transfer equipment. •The defrost interval should not exceed 2 h under frost conditions

Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds.

Science.gov (United States)

Tezuka, Hiroyuki; Imai, Shinjiro

2015-01-01

Inflammation is an immune response against both internal and external antigens in organisms, particularly in mammals, and includes both uncontrolled chronic and low-grade inflammations. Uncontrolled chronic inflammation often leads to severe diseases such as vascular disease, arthritis, cancer, diabete, allergy, and autoimmunity. On the other hand, low-grade inflammation is recognized as a relationship between obesity and risk of metabolic syndrome. Elevated production of pro-inflammatory cytokines and mediators is commonly observed in patients with uncontrolled or low-grade inflammation-associated diseases. Plants have been generated phytochemicals to overcome inflammations and infections through evolution. Phytochemicals belong to alkaloids, polyphenols, flavonoids, coumarins, and terpenoids. The consumption of soybeans plays a role in immune modulation through their components such as isoflavones, saponins, and anthocyanins. Recently, it was reported that the application of phytochemicals into patients with inflammatory diseases improves their symptoms. Therefore, it is important to identify novel phytochemicals with immunomodulatory activities. This review introduces and discusses recent advances and patents regarding soybean or processed soy food compounds which exhibit immunomodulatory activity in immune diseases, particularly allergy, by mediating the suppression of inflammatory pathways.

Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

Science.gov (United States)

Shi, Jian-Hong; Cui, Nai-Peng; Wang, Shuo; Zhao, Ming-Zhi; Wang, Bing; Wang, Ya-Nan; Chen, Bao-Ping

2016-01-01

Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

A Leishmania murine model to evaluate the immunomodulatory properties of Pythium insidiosum proteins

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Tatiana Maria Inêz-Ferreira

2017-03-01

Full Text Available Pythium insidiosum immunomodulatory vaccine (PiV has been tested in clinical and experimental pythiosis. Previous data showed that P. insidiosum immunogens have the ability to switch the Th2 immune response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c Leishmania infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential. Twenty-one days following challenge with L. major, large cutaneous granulomas developed in control mice, consistent with the expected Th2 response. In contrast, Leishmania-induced cutaneous lesions in PiV-immunized mice were minimal or absent. Flow cytometry analysis of spleen cells from mice immunized with PiV and subsequently challenged with L. major displayed more CD4+ and CD8+ cells than the control group. Moreover, spleen cells from mice that were immunized with PiV then challenged with L. major secreted high levels of IFN-γ, with a moderate IL-2, IL-4, and IL-10 mixed cytokine profile upon in vitro re-stimulation with PiV. Anti-P. insidiosum IgG1 in immunized animals was present at low titers suggesting a minor immunological role for this Ig isotype in this model. Our preliminary data showed that BALB/c mice challenged with L. major represent an attractive model in which to study PiV´s immunomodulatory properties.

Inhibition of SK4 Potassium Channels Suppresses Cell Proliferation, Migration and the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells.

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Panshi Zhang

Full Text Available Treatments for triple-negative breast cancer (TNBC are limited; intermediate-conductance calcium-activated potassium (SK4 channels are closely involved in tumor progression, but little is known about these channels in TNBC. We aimed to investigate whether SK4 channels affect TNBC. First, by immunohistochemistry (IHC and western blotting (WB, increased SK4 protein expression in breast tumor tissues was detected relative to that in non-tumor breast tissues, but there was no apparent expression difference between various subtypes of breast cancer (p>0.05. Next, functional SK4 channels were detected in the TNBC cell line MDA-MB-231 using WB, real-time PCR, immunofluorescence and patch-clamp recording. By employing SK4 specific siRNAs and blockers, including TRAM-34 and clotrimazole, in combination with an MTT assay, a colony-formation assay, flow cytometry and a cell motility assay, we found that the suppression of SK4 channels significantly inhibited cell proliferation and migration and promoted apoptosis in MDA-MB-231 cells (p<0.05. Further investigation revealed that treatment with epidermal growth factor (EGF/basic fibroblast growth factor (bFGF caused MDA-MB-231 cells to undergo the epithelial-mesenchymal transition (EMT and to show increased SK4 mRNA expression. In addition, the down-regulation of SK4 expression inhibited the EMT markers Vimentin and Snail1. Collectively, our findings suggest that SK4 channels are expressed in TNBC and are involved in the proliferation, apoptosis, migration and EMT processes of TNBC cells.

Branching fractions of Bplus → Ψ(2S)Kplus and BO → Ψ(2S)K*0 decays at CDF

International Nuclear Information System (INIS)

Warburton, A.

1996-07-01

This paper describes the observation of the decays B + → ψ(2S)K + and B 0 → ψ(2S)K * (892) 0 in 1.8 TeV pp collisions and presents measurements of the branching fractions Br(B + → ψ(2S)K + ) and Br(B 0 → ψ(2S)K * (892) 0 ) relative to Br(B + → J/ψK + ) and Br(B 0 → J/ψK * (892) 0 ), respectively. The ψ(2S) mesons are reconstructed in both the ψ(2S) → μ + μ - and ψ(2S) → J/ψπ + π - channels. The world average branching fractions for the J/ψ channels are used to extract the absolute branching fractions Br(B + → ψ(2S)K + ) = (6.8±1.0(stat.)±1.4(syst.))x10 -4 and Br(B 0 → ψ(2S)K * (892) 0 ) = (9.0±2.1(stat.)±2. 0(syst.))x10 -4 . 9 refs., 13 figs., 8 tabs

The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties.

Science.gov (United States)

Souza, Maria A; Carvalho, Fernanda C; Ruas, Luciana P; Ricci-Azevedo, Rafael; Roque-Barreira, Maria Cristina

2013-10-01

Advances in the glycobiology and immunology fields have provided many insights into the role of carbohydrate-protein interactions in the immune system. We aim to present a comprehensive review of the effects that some plant lectins exert as immunomodulatory agents, showing that they are able to positively modify the immune response to certain pathological conditions, such as cancer and infections. The present review comprises four main themes: (1) an overview of plant lectins that exert immunomodulatory effects and the mechanisms accounting for these activities; (2) general characteristics of the immunomodulatory lectin ArtinM from the seeds of Artocarpus heterophyllus; (3) activation of innate immunity cells by ArtinM and consequent induction of Th1 immunity; (4) resistance conferred by ArtinM administration in infections with intracellular pathogens, such as Leishmania (Leishmania) major, Leishmania (Leishmania) amazonensis, and Paracoccidioides brasiliensis. We believe that this review will be a valuable resource for more studies in this relatively neglected area of research, which has the potential to reveal carbohydrate targets for novel prophylactic and therapeutic strategies.

Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract.

Science.gov (United States)

Chandrashekar, Puthanapura M; Prashanth, Keelara V Harish; Venkatesh, Yeldur P

2011-02-01

Traditionally, garlic (Allium sativum) is known to be a significant immune booster. Aged garlic extract (AGE) possesses superior immunomodulatory effects than raw garlic; these effects are attributed to the transformed organosulfur compounds. AGE is also known to contain fructans; the amount of fructans in AGE represents a small fraction (0.22%) of the total fructans in raw garlic. In order to evaluate the biological activity of fructans present in AGE, both high molecular weight (>3.5 kDa; HF) and low molecular weight (immunomodulators such as zymosan and mannan. This study clearly demonstrates that garlic fructans also contribute to the immunomodulatory properties of AGE, and is the first such study on the biological effects of garlic fructans. Copyright © 2010 Elsevier Ltd. All rights reserved.

Group SkSP-R sampling plan for accelerated life tests

Indian Academy of Sciences (India)

Muhammad Aslam

2017-09-15

Sep 15, 2017 ... SkSP-R sampling; life test; Weibull distribution; producer's risk; ... designed a sampling plan under a time-truncated life test .... adjusted using an acceleration factor. ... where P is the probability of lot acceptance for a single.

Gene expression in SK-Mel-28 human melanoma cells treated with the snake venom jararhagin.

Science.gov (United States)

Klein, Anelise; Capitanio, Juliana Silva; Maria, Durvanei Augusto; Ruiz, Itamar Romano Garcia

2011-01-01

Alternative approaches to improve the treatment of advanced melanomas are highly needed. The disintegrin domain of metalloproteinases binds integrin receptors on tumor cells, blocking migration, invasion, and metastatization. Previous studies showed that jararhagin, from the Bothrops jararaca snake venom, induces changes in the morphology and viability of SK-Mel-28 human melanoma cells, and decreases the number of metastases in mice injected with pre-treated cells. The purpose of this study was to evaluate the molecular effects of jararhagin on SK-Mel-28 cells and fibroblasts, concerning the expression of integrins, cadherins, caspases, and TP53 genes. Sub-toxic doses of jararhagin were administered to confluent cells. RT-PCR was performed following extraction of total RNA. Jararhagin treatments induced similar morphological alterations in both normal and tumor cells, with higher IC50 values for fibroblasts. Integrin genes were downregulated in untreated cells, except for ITGA6a,b, ITGAv, and ITGB3 which were highly expressed in SK-Mel-28. The integrin expression profiles were not affected by the toxin. However, jararhagin 30ng/μl upregulated genes TP53, CDKN1A, CDKN2A, CASP3, CASP5, CASP6, CASP8, and E-CDH in SK-Mel-28, and genes ITGB6, ITGB7, CASP3, TP53, and CDKN1B in fibroblasts. Appropriate jararhagin concentration can have apoptotic and suppressant effects on SK-Mel-28 cells, rather than on fibroblasts, and can be used to develop potential anti-cancer drugs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Uncovering a Role for SK2 in Angelman Syndrome

Directory of Open Access Journals (Sweden)

Sofia B. Lizarraga

2015-07-01

Full Text Available Angelman syndrome is a severe neurodevelopmental disorder caused by mutations in UBE3A. Sun et al. (2015 report SK2 as a UBE3A substrate and provide insight into the molecular mechanisms that might underlie impaired neuronal function in individuals affected by Angelman syndrome.

Expression of the Small Conductance Ca(2+)-Activated Potassium Channel Subtype 3 (SK3) in Rat Uterus after Stimulation with 17β-Estradiol

DEFF Research Database (Denmark)

Rahbek, Mette; Nazemi, Sasan; Odum, Lars

2014-01-01

the expression of SK3 in the uterus of rats stimulated with 17β-estradiol and progesterone in order to get an in depth understanding of the rat uterine SK3. Using immunohistochemistry SK3 was localized to the glandular and luminal endometrial lamina epitheliali. Furthermore, a weak signal was observed...... in the myometrium. Using Western blot the protein level of SK3 was found to increase in uteri from animals treated with 17β-estradiol, an effect that was not reflected at the mRNA level. The levels of mRNA for SK3 were significantly lower in the uterus of 17β-estradiol-treated animals than in the uterus...... of ovariectomized animals. We conclude that the SK channels are present in the endometrial epithelium, and possibly also in the myometrium of the rat uterus. Furthermore, the hormonal effect on SK3 caused by 17β-estradiol includes divergent regulation at mRNA and protein levels....

Observation of the decay B¯s0→ψ(2SK+π−

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R. Aaij

2015-07-01

Full Text Available The decay B¯s0→ψ(2SK+π− is observed using a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. The branching fraction relative to the B0→ψ(2SK+π− decay mode is measured to beB(B¯s0→ψ(2SK+π−B(B0→ψ(2SK+π−=5.38±0.36(stat±0.22(syst±0.31(fs/fd%, where fs/fd indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a Bs0 or B0 meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K⁎(8920 meson is measured to be 0.645±0.049(stat±0.049(syst and its longitudinal polarisation fraction is 0.524±0.056(stat±0.029(syst. The relative branching fraction for this component is determined to be B(B¯s0→ψ(2SK⁎(8920B(B0→ψ(2SK⁎(8920=5.58±0.57(stat±0.40(syst±0.32(fs/fd%. In addition, the mass splitting between the Bs0 and B0 mesons is measured as M(Bs0−M(B0=87.45±0.44(stat±0.09(syst MeV/c2.

TaSK5, an abiotic stress-inducible GSK3/shaggy-like kinase from wheat, confers salt and drought tolerance in transgenic Arabidopsis.

Science.gov (United States)

Christov, Nikolai Kirilov; Christova, Petya Koeva; Kato, Hideki; Liu, Yuelin; Sasaki, Kentaro; Imai, Ryozo

2014-11-01

A novel cold-inducible GSK3/shaggy-like kinase, TaSK5, was isolated from winter wheat using a macroarray-based differential screening approach. TaSK5 showed high similarity to Arabidopsis subgroup I GSK3/shaggy-like kinases ASK-alpha, AtSK-gamma and ASK-epsilon. RNA gel blot analyses revealed TaSK5 induction by cold and NaCl treatments and to a lesser extent by drought treatment. TaSK5 functionally complemented the cold- and salt-sensitive phenotypes of a yeast GSK3/shaggy-like kinase mutant, △mck1. Transgenic Arabidopsis plants overexpressing TaSK5 cDNA showed enhanced tolerance to salt and drought stresses. By contrast, the tolerance of the transgenic plants to freezing stress was not altered. Microarray analysis revealed that a number of abiotic stress-inducible genes were constitutively induced in the transgenic Arabidopsis plants, suggesting that TaSK5 may function in a novel signal transduction pathway that appears to be unrelated to DREB1/CBF regulon and may involve crosstalk between abiotic and hormonal signals. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Comparison of Immunomodulatory Effects of Fresh Garlic and Black Garlic Polysaccharides on RAW 264.7 Macrophages.

Science.gov (United States)

Li, Min; Yan, Yi-Xi; Yu, Qing-Tao; Deng, Yong; Wu, Ding-Tao; Wang, Ying; Ge, Ya-Zhong; Li, Shao-Ping; Zhao, Jing

2017-03-01

Garlic has a long history to be used for medicine and food purposes. Black garlic, the fermented product of fresh garlic, is considered with better biological activities, such as antioxidant activity, and is developed as an increasingly popular functional food. Polysaccharides are the major components of fresh and black garlic, and immunomodulatory activity is one major pharmacological effect of polysaccharides. Therefore, chemical characteristics and immunomodulatory effects of polysaccharides from fresh and black garlic are investigated and compared in vitro for the 1st time, in order to reveal their molecular and pharmacological differences. It is demonstrated that the molecular weights of polysaccharides from the 2 sources and molar ratios of monosaccharides after acid hydrolysis are greatly variant. The effects of polysaccharides from 2 sources on RAW 264.7 macrophages functions, including promotion of phagocytosis, release of NO, and expressions of several immune-related cytokines (including interleukin [IL]-6, IL-10, tumor necrosis factor alpha, and interferon gamma), were different from each other. The results indicated that fresh garlic polysaccharide exhibited stronger immunomodulatory activities than that of black garlic. Moreover, it is revealed that fructan might be the bioactive component in garlic and it is indicated that during the fermentation treatment, fructan constituents of garlic has degraded, and basically no immunomodulatory effect can be found in black garlic polysaccharides. © 2017 Institute of Food Technologists®.

Immunomodulatory Effects of Kuseonwangdogo-Based Mixed Herbal Formula Extracts on a Cyclophosphamide-Induced Immunosuppression Mouse Model

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Joo Wan Kim

2018-01-01

Full Text Available Aim. Kuseonwangdogo is a traditional Korean immunomodulatory polyherbal prescription. However, there are no systemic findings on its complex immunomodulatory effects on in vivo models. In this study, we observed the immunomodulatory effects of Kuseonwangdogo-based mixed herbal formula aqueous extracts (MHFe on cyclophosphamide- (CPA- induced immunosuppression mouse model. Methods. In total, 60 male 6-week-old ICR mice (10 mice/group were selected based on body weight 24 h after the second CPA treatment and used in this experiment. Twelve hours after the end of the last (fourth oral administration of MHFe, the animals were sacrificed. Results. Following CPA treatment, a noticeable decrease in the body, thymus, spleen, and submandibular lymph node (LN weights; white blood cell, red blood cell, platelet number, hemoglobin, and hematocrit concentrations; serum interferon-γ levels; splenic tumor necrosis factor-α, interleukin- (IL- 1β, and IL-10 content; and peritoneal and splenic natural killer cell activities was observed. Depletion of lymphoid cells in the thymic cortex, splenic white pulp, and submandibular LN-related atrophic changes were also observed. However, these CPA-induced myelosuppressive signs were markedly and dose-dependently inhibited by the oral administration of 125, 250, and 500 mg/kg MHFe. Conclusion. MHFe can be a promising, potent immunomodulatory therapeutic agent for various immune disorders.

Technical Monitoring System for a New Part of Gdańsk Deepwater Container Terminal

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Miśkiewicz Mikołaj

2017-04-01

Full Text Available Development strategy for the port of Gdańsk assumes that , up to 2027, it will become the main transport centre in the Baltic Sea region. To this end , for many years work has been carried out to facilitate access to the port both by sea and land. One of the elements of extension of the port is the building of another terminal of Deepwater Container Terminal, Gdańsk. In this task, geotechnical operations aimed at appropriate preparation of subgrade for storage of containers and operation of cranes, have been especially important. Effectiveness of the assumed design solution of land-side girder for gantry crane has been verified by means of a technical monitoring system. This paper presents main elements of design the land-side girder of a new quay of the container terminal in Gdańsk, together with its computational analysis, as well as the results collected during a few months of observation, which have revealed real work of monitored elements.

Hvem sidder dér bag skærmen?

DEFF Research Database (Denmark)

Werlauff, Erik; Schaumburg-Müller, Peer

2009-01-01

Med udgangspunkt i nutidens daytrader, der sidder ´"bag skærmen" og foretager talrige daglige køb og salg af børsnoterede aktier mv., analyseres det i artiklen, hvornår en sådan lovlig daytrading udarter til strafbar kursmanipulation. Nogle daytradere har ment, at hvis en ikke-professionel invest...

Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

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Pia Rademann

2017-01-01

Full Text Available Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90 underwent cecal ligation and puncture (CLP and received SkQ1 (5 nmol/kg, MitoTEMPO (50 nmol/kg, or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments.

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells

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Parviz Mohammadi Ghalaei

2014-01-01

Full Text Available The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P<0.05. After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma.

Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

Science.gov (United States)

Salem, Mohamed Labib

2005-12-01

A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1

Immunomodulatory Effect of Rhaphidophora korthalsii on Natural Killer Cell Cytotoxicity

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Swee Keong Yeap

2012-01-01

Full Text Available The in vivo immunomodulatory effect of ethanolic extracts from leaves of Rhaphidophora korthalsii was determined via immune cell proliferation, T/NK cell phenotyping, and splenocyte cytotoxicity of BALB/c mice after 5 consecutive days of i.p. administration at various concentrations. Splenocyte proliferation index, cytotoxicity, peripheral blood T/NK cell population, and plasma cytokine (IL-2 and IFN-γ in mice were assessed on day 5 and day 15. High concentration of extract (350 μg/mice/day for 5 consecutive days was able to stimulate immune cell proliferation, peripheral blood NK cell population, IL-2, and IFN- γ cytokines, as well as splenocyte cytotoxicity against Yac-1 cell line. Unlike rIL-2 which degraded rapidly, the stimulatory effect from the extract managed to last until day 15. These results suggested the potential of this extract as an alternative immunostimulator, and they encourage further study on guided fractionation and purification to identify the active ingredients that contribute to this in vitro and in vivo immunomodulatory activity.

Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy

Science.gov (United States)

Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.

2014-01-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

Science.gov (United States)

Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

2014-08-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

[Effect of 3-bromopyruvate on mitochondrial membrane potential and apoptosis of human breast carcinoma SK-BR-3 cells].

Science.gov (United States)

Zhang, Yuanyuan; Liu, Zhe; Zhang, Qianwen; Chao, Zhenhua; Zhang, Pei; Xia, Fei; Jiang, Chenchen; Liu, Hao; Jiang, Zhiwen

2013-09-01

To study the effect of glycolysis inhibitor 3-bromopyruvate (3-BrPA) in inducing apoptosis of human breast carcinoma cells SK-BR-3 and the possible mechanism. MTT assay was used to detect the growth inhibition induced by 3-BrPA in breast cancer cells SK-BR-3. The apoptotic cells were detected by flow cytometry with propidium iodide (PI). ATP levels in the cells were detected by ATP assay kit, and DHE fluorescent probe technique was used to determine superoxide anion levels; the mitochondrial membrane potential was assessed using JC-1 staining assay. MTT assay showed that the proliferation of SK-BR-3 cells was inhibited by 3-BrPA in a time- and concentration-dependent manner. Exposure to 80, 160, and 320 µmol·L(-1) 3-BrPA for 24 h resulted in cell apoptosis rates of 6.7%, 22.3%, and 79.6%, respectively, and the intracellular ATP levels of SK-BR-3 cells treated with 80, 160, 320 µmol·L(-1) 3-BrPA for 5 h were 87.7%, 60.6%, and 23.7% of the control levels. 3-BrPA at 160 µmol·L(-1) increased reactive oxygen levels and lowered mitochondrial membrane potential of SK-BR-3 cells. 3-BrPA can inhibit cell proliferation, reduce the mitochondrial membrane potential and induce apoptosis in SK-BR-3 cells, the mechanism of which may involve a reduced ATP level by inhibiting glycolysis and increasing the reactive oxygen level in the cells.

Involvement of Transglutaminase-2 in α-MSH-Induced Melanogenesis in SK-MEL-2 Human Melanoma Cells.

Science.gov (United States)

Kim, Hyun Ji; Lee, Hye Ja; Park, Mi Kyung; Gang, Kyung Jin; Byun, Hyun Jung; Park, Jeong Ho; Kim, Mi Kyung; Kim, Soo Youl; Lee, Chang Hoon

2014-05-01

Skin hyperpigmentation is one of the most common skin disorders caused by abnormal melanogenesis. The mechanism and key factors at play are not fully understood. Previous reports have indicated that cystamine (CTM) inhibits melanin synthesis, though its molecular mechanism in melanogenesis remains unclear. In the present study, we investigated the effect of CTM on melanin production using ELISA reader and the expression of proteins involved in melanogenesis by Western blotting, and examined the involvement of transglutaminase-2 (Tgase-2) in SK-MEL-2 human melanoma cells by gene silencing. In the results, CTM dose-dependently suppressed melanin production and dendrite extension in α-MSH-induced melanogenesis of SK-MEL-2 human melanoma cells. CTM also suppressed α-MSH-induced chemotactic migration as well as the expressions of melanogenesis factors TRP-1, TRP-2 and MITF in α-MSH-treated SK-MEL-2 cells. Meanwhile, gene silencing of Tgase-2 suppressed dendrite extension and the expressions of TRP-1 and TRP-2 in α-MSH-treated SK-MEL-2 cells. Overall, these findings suggested that CTM suppresses α-MSH-induced melanogenesis via Tgase-2 inhibition and that therefore, Tgase-2 might be a new target in hyperpigmentation disorder therapy.

Parasitic helminths and HIV-1 infection: the effect of immunomodulatory antigens

NARCIS (Netherlands)

Mouser, E.E.I.M.

2016-01-01

In many regions of the world co-infection with parasitic helminths and HIV-1 is common. Both pathogens have major implications for the host immune system, helminths possess immunomodulatory properties whilst HIV-1 infects and kills immune cells. Currently very little is known regarding what effects

Production of prostate-specific antigen by a breast cancer cell line, Sk-Br-3

International Nuclear Information System (INIS)

Kamali Sarvestani, E.; Ghaderi, A.

2002-01-01

Prostate-specific antigen is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce prostate-specific antigen and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study prostate-specific antigen production in breast cancer and its association with prognostic factors such as progesterone receptor and c-erbB-2. For this purpose we investigated the ability of prostate-specific antigen production in five different cell lines, including two breast cancer cell lines, Sk-Br-3 and MDA-MB-453. The prostate-specific antigen in tissue culture supernatant and cytoplasm of the Sk-Br-3 cell line was detected by western blotting and immunoperoxidase, respectively. Furthermore, we found lower expression of c-erbB-2 in Sk-Br-3 than non-prostate-specific antigen producer breast cancer cell line, MDA-MB-453. Progesterone receptor was expressed by both prostate-specific antigen-positive and -negative cell lines and only the intensity of staining and the number of positive cells in Sk-Br-3 population was higher than MDA-MB-453. According to our findings prostate-specific antigen can be considered as a good prognostic factor in breast cancer and we suggest that these two cell lines are a good in vitro model to study the relationship of different breast cancer prognostic factors and their regulations

The Immunomodulatory Effects of Macrolides—A Systematic Review of the Underlying Mechanisms

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Petra Zimmermann

2018-03-01

Full Text Available BackgroundThe mechanisms underlying the non-antimicrobial immunomodulatory properties of macrolides are not well understood.ObjectivesTo systematically review the evidence for the immunomodulatory properties of macrolides in humans and to describe the underlying mechanism and extent of their influence on the innate and adaptive immune system.MethodsA systematic literature search was done in MEDLINE using the OVID interface from 1946 to December 2016 according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA. Original articles investigating the influence of four macrolides (azithromycin, clarithromycin, erythromycin, and roxithromycin on immunological markers in humans were included.ResultsWe identified 22 randomized, controlled trials, 16 prospective cohort studies, and 8 case–control studies investigating 47 different immunological markers (186 measurements in 1,834 participants. The most frequently reported outcomes were a decrease in the number of neutrophils, and the concentrations of neutrophil elastase, interleukin (IL-8, IL-6, IL-1beta, tumor necrosis factor (TNF-alpha, eosinophilic cationic protein, and matrix metalloproteinase 9. Inhibition of neutrophil function was reported more frequently than eosinophil function. A decrease in T helper (Th 2 cells cytokines (IL-4, IL-5, IL-6 was reported more frequently than a decrease in Th1 cytokines (IL-2, INF-gamma.ConclusionMacrolides influence a broad range of immunological mechanisms resulting in immunomodulatory effects. To optimize the treatment of chronic inflammatory diseases by macrolides, further studies are necessary, particularly comparing different macrolides and dose effect relationships.

Składniki mineralne w orzechach występujących w składzie „mieszanek studenckich” = Minerals in nuts which are components of „Trail Mix”

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Natalia Mikołajczak

2016-09-01

Wydział Nauki o Żywności, Uniwersytet Warmińsko-Mazurski w Olsztynie   Uniwersytet Warmińsko-Mazurski w Olsztynie, Katedra Przetwórstwa i Chemii Surowców Roślinnych Pl. Cieszyński 1, 10-726 Olsztyn e-mail: natalia.mikolajczak@uwm.edu.pl   Streszczenie   Wprowadzenie i cel pracy: Orzechy stanowią cenną grupę żywności pod względem wartości żywieniowej, dlatego też są jednym z głównych składników wykorzystywanych w produkcji mieszanek studenckich. Obecność orzechów w codziennej diecie konsumenta ma pozytywny wpływ na organizm poprzez redukcję poziomu cholesterolu we krwi, przeciwdziałanie nowotworom i cukrzycy czy również wspomaganie utraty masy ciała. Wszystkie te korzyści wynikają ze składu chemicznego orzechów i obecności w nich wielu wartościowych składników odżywczych, w szczególności składników mineralnych. Celem pracy był przegląd aktualnego piśmiennictwa na temat zawartości poszczególnych składników mineralnych w orzechach, będących składnikami tradycyjnych mieszanek studenckich, czyli laskowych, włoskich, arachidowych, nerkowcach oraz migdałach. Skrócony opis stanu wiedzy: Orzechy to cenne źródło składników mineralnych, zarówno mikro, jak i makroelementów. Przede wszystkim, orzechy laskowe, włoskie, arachidowe oraz migdały dostarczają znacznych ilości potasu, którego zawartość w 100 g surowca odnotowuje się na poziomie wyższym niż 500 mg. Z kolei zawartość fosforu obecna jest na zbliżonym poziomie jedynie w migdałach. Mikroelementy takie jak żelazo, miedź, cynk i mangan występują we wszystkich orzechach w ilości 5-10 mg/100 g. Podsumowanie: Zebrane dane literaturowe potwierdzają fakt, że analizowane rodzaje orzechów są cennym źródłem zarówno mikro, jak i makroelementów. Są one bogactwem potasu, fosforu, magnezu oraz wapnia. Ponadto, dostarczają także znacznych ilości żelaza, cynku oraz manganu.   Słowa kluczowe: składniki mineralne, orzechy laskowe, orzechy

Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

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Funda Karbek Akarca

2017-12-01

Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis

Optical spectroscopy of the blue supergiant Sk-69° 279 and its circumstellar shell with SALT

Science.gov (United States)

Gvaramadze, V. V.; Kniazev, A. Y.; Maryeva, O. V.; Berdnikov, L. N.

2018-02-01

We report the results of optical spectroscopy of the blue supergiant Sk-69° 279 and its circular shell in the Large Magellanic Cloud (LMC) with the Southern African Large Telescope (SALT). We classify Sk-69° 279 as an O9.2 Iaf star and analyse its spectrum by using the stellar atmosphere code CMFGEN, obtaining a stellar temperature of ≈30 kK, a luminosity of log (L*/ L⊙) = 5.54, a mass-loss rate of log (\\dot{M}/ M_{⊙} yr^{-1}) = -5.26, and a wind velocity of 800km s-1. We found also that Sk-69° 279 possesses an extended atmosphere with an effective temperature of ≈24 kK and that its surface helium and nitrogen abundances are enhanced, respectively, by factors of ≈2 and 20-30. This suggests that either Sk-69° 279 was initially a (single) fast-rotating ( ≳ 400 km s- 1) star, which only recently evolved off the main sequence, or that it is a product of close binary evolution. The long-slit spectroscopy of the shell around Sk-69° 279 revealed that its nitrogen abundance is enhanced by the same factor as the stellar atmosphere, which implies that the shell is composed mostly of the CNO processed material lost by the star. Our findings support previous propositions that some massive stars can produce compact circumstellar shells and, presumably, appear as luminous blue variables while they are still on the main sequence or have only recently left it.

Comparative Phosphoproteomics Reveals the Role of AmpC β-lactamase Phosphorylation in the Clinical Imipenem-resistant Strain Acinetobacter baumannii SK17*

Science.gov (United States)

Lai, Juo-Hsin; Yang, Jhih-Tian; Chern, Jeffy; Chen, Te-Li; Wu, Wan-Ling; Liao, Jiahn-Haur; Tsai, Shih-Feng; Liang, Suh-Yuen; Chou, Chi-Chi

2016-01-01

Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif S88VS90K of the AmpC β-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher β-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both β-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies. PMID:26499836

Fungal immunomodulatory proteins in the context of biomedicine.

Science.gov (United States)

Uribe-Echeverry, Paula Tatiana; Lopez-Gartner, German Ariel

2017-06-01

Fungi represent a large group of biodiverse microorganisms with potential applications ranging from industrial fields to the treatment for human diseases. A large number of pharmacologically active compounds including terpenoids, polysaccharides and proteins have been derived from these microorganisms. Fungal Immunomodulatory Proteins (FIPs) are a group of active compounds that are being considered for the treatment of asthma, allergy, autoimmune diseases and cancer. Here, we discuss the discovery, heterologous production bioactive mechanisms of action and their potential use in biomedicine.

Pääsküla raamatukogu / Maris Takk

Index Scriptorium Estoniae

Takk, Maris

2006-01-01

Pääsküla raamatukogu (Tallinn, Pärnu mnt. 480A) sisekujundus, mille eest sisekujundajad Katrin Kaevats ja Peeter Pere (AB Muru & Pere) pälvisid Eesti Sisearhitektide Liidu 2005. a. ühiskondliku interjööri preemia. Ehitaja: OÜ SCE Grupp. K. Kaevatsist, tema tähtsamad tööd. P. Perest, valik AB Muru & Pere projektidest. Ill.: kaks korruste plaani, 17 värv. vaadet, K. Kaevatsi ja P. Pere fotod

Calotropis procera extract induces apoptosis and cell cycle arrest at G2/M phase in human skin melanoma (SK-MEL-2) cells.

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Joshi, Aparna L; Roham, Pratiksha H; Mhaske, Rooth; Jadhav, Mahadev; Krishnadas, Kavitha; Kharat, Amol; Hardikar, Bhagyashree; Kharat, Kiran R

2015-01-01

Calotropis procera (family: Asclepiadaceae) contains cardiac glycosides which are cytotoxic to cancer cells. The extracts of C. procera have been reported to be cytotoxic to many cancer cell lines and this is the first report against the human skin melanoma cells (SK-MEL-2). The SK-MEL-2 cells treated with C. procera methanolic extract (CPME) were analysed for growth inhibition and apoptosis. The exposure of phosphatidylserine in apoptotic SK-MEL-2 was analysed by using the Annexin-V FITC flow cytometry method. In CPME-treated SK-MEL-2 cells, 19.6% of apoptotic and 58.3% dead cells were observed. The 15.97% and 15.85% of early apoptotic cells were found at 20 μg/mL of the ouabain and paclitaxel, respectively. Active caspases, nuclear degradation confirmed apoptotic SK-MEL-2 cells in time- and dose-dependent manner. The cell cycle analysis shows that CPME treated cells halt at G2/M phase. Significant cytotoxic activity of CPME against SK-MEL-2 may be attributed to its high cardenolide content.

Effect of SkQ1 Antioxidant on Structural and Functional Conditions of The Brain in PostResuscitation Period

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M. L. Lovat

2016-01-01

Full Text Available The aim was to assess the efficacy of mitochondriatargeted antioxidant SkQ1 in prevention of structural and functional abnormalities of brain postresuscitation after cardiac arrest.Materials and methods. Adult male Wistar rats (n=19 underwent cardiac arrest for 7 minutes followed by resuscitation. Nine rats were administered with 500 nmol/kg SkQ1 per os with water for 2 weeks (1 week before and 1 week after resuscitation. A control group consisted of shamoperated animals (n=10. At days 4—6 post operation locomotor activity and anxiety («elevated plus maze» test and sensorimotor function of limbs («beam walking» test were examined. Total numbers of neurons per 1 mm of their layer length in vulnerable neuronal populations (cerebellar Purkinje cells and piramidal neurons of hippocampus fields CA1 and CA4 were estimated by histological analysis of the specimens stained with cresyl violet on day 7 postresuscitation. To identify possible mechanisms of SkQ1 action, the immunohistochemical study of a glialderived neurotrophic factor (GDNF expression in piramidal neurons of hippocampus was performed by indirect peroxidaseantiperoxidase method and antiGDNF primary polyclonal antibodies.Results. Ischemiareperfusion resulted in neuronal loss in all studied brain areas followed by reduction in locomotor activity and development of sensorimotor deficit. SkQ1 prevented development of postresuscitative locomotor and sensorimotor irregularities, significantly reduced Purkinje cells loss, prevented death of piramidal neurons in hippocampal field CA4, but not in CA1. Data demonstrated, that iIn Purkinje cells from resuscitated rats treated with SkQ1 there was a significant increase in number of GDNFpositive neurons, which were more resistant to ischemia (transition of GDNFnegative cells toward the category of cells actively expressing this factor that promoted their survival postresuscitation.Conclusion. Data confirm the positive effects of SkQ1

Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses.

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Jacobs, Sandra A; Pinxteren, Jef; Roobrouck, Valerie D; Luyckx, Ariane; van't Hof, Wouter; Deans, Robert; Verfaillie, Catherine M; Waer, Mark; Billiau, An D; Van Gool, Stefaan W

2013-01-01

Multipotent adult progenitor cells (MAPCs) are bone marrow-derived nonhematopoietic stem cells with a broad differentiation potential and extensive expansion capacity. A comparative study between human mesenchymal stem cells (hMSCs) and human MAPCs (hMAPCs) has shown that hMAPCs have clearly distinct phenotypical and functional characteristics from hMSCs. In particular, hMAPCs express lower levels of MHC class I than hMSCs and cannot only differentiate into typical mesenchymal cell types but can also differentiate in vitro and in vivo into functional endothelial cells. The use of hMSCs as cellular immunomodulatory stem cell products gained much interest since their immunomodulatory capacities in vitro became evident over the last decade. Currently, the clinical grade stem cell product of hMAPCs is already used in clinical trials to prevent graft-versus-host disease (GVHD), as well as for the treatment of acute myocardial infarct, ischemic stroke, and Crohn's disease. Therefore, we studied the immune phenotype, immunogenicity, and immunosuppressive effect of hMAPCs in vitro. We demonstrated that hMAPCs are nonimmunogenic for T-cell proliferation and cytokine production. In addition, hMAPCs exert strong immunosuppressive effects on T-cell alloreactivity and on T-cell proliferation induced by mitogens and recall antigens. This immunomodulatory effect was not MHC restricted, which makes off-the-shelf use promising. The immunosuppressive effect of hMAPCs is partially mediated via soluble factors and dependent on indoleamine 2,3-dioxygenase (IDO) activity. At last, we isolated hMAPCs, the clinical grade stem cell product of hMAPCs, named MultiStem, and hMSCs from one single donor and observed that both the immunogenicity and the immunosuppressive capacities of all three stem cell products are comparable in vitro. In conclusion, hMAPCs have potent immunomodulatory properties in vitro and can serve as a valuable cell source for the clinical use of immunomodulatory cellular

Comparative Phosphoproteomics Reveals the Role of AmpC β-lactamase Phosphorylation in the Clinical Imipenem-resistant Strain Acinetobacter baumannii SK17.

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Lai, Juo-Hsin; Yang, Jhih-Tian; Chern, Jeffy; Chen, Te-Li; Wu, Wan-Ling; Liao, Jiahn-Haur; Tsai, Shih-Feng; Liang, Suh-Yuen; Chou, Chi-Chi; Wu, Shih-Hsiung

2016-01-01

Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif S(88)VS(90)K of the AmpC β-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher β-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both β-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

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Zhuo Chen

2014-01-01

Full Text Available Tanshinone IIA (Tan II A is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.

Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.).

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Saaby, Lasse; Jäger, Anna Katharina; Moesby, Lise; Hansen, Erik Wind; Christensen, Søren Brøgger

2011-02-01

A previously published systematic review and a metaanalysis have concluded that the consumption of standardized rose hip powder (Rosa canina L.) can reduce pain in osteoarthritis patients. Synovial inflammation has been suggested to play an important role in the pathogenesis of osteoarthritis and mainly to involve infiltration of the synovial membrane by macrophages. Therefore, the immunomodulatory effect of standardized rose hip powder of Rosa canina L. was investigated and active principles isolated using the Mono Mac 6 cell line as a model for human macrophages. Treatment of Mono Mac 6 cells with the residue of a crude dichloromethane extract of rose hip powder significantly and concentration dependently inhibited the lipopolysaccharide induced interleukin-6 release. Through bioassay-guided fractionation the immunomodulatory effect of the dichloromethane extract was correlated to a mixture of three triterpene acids; oleanolic acid, betulinic acid and ursolic acid (IC(50) 21 ± 6 µm). Further studies revealed that only oleanolic acid and ursolic acid, but not betulinic acid, could inhibit the lipopolysaccharide induced interleukin-6 release from Mono Mac 6 cells when tested separately. Combination of either oleanolic acid or ursolic acid with betulinic acid enhanced the immunomodulatory effect of the two triterpene acids. Copyright © 2010 John Wiley & Sons, Ltd.

Immunomodulatory potential of Anacyclus pyrethrum (L.) and Mucuna pruriens (L.) In male albino rats.

Science.gov (United States)

Yousaf, F; Shahid, M; Riaz, M; Atta, A; Fatima, H

2017-01-01

The present study was designed to investigate the immunomodulatory potential of Anacyclus pyrethrum roots and Mucuna pruriens seeds in male albino rats. The roots of A. pyrethrum and seeds of M. pruriens were extracted with methanolic solvent (70:30) and administered at dose concentrations of 50, 100 and 200 mg/Kg body weight to healthy male rats. The immune system of rats was suppressed by injecting carbon tetrachloride to animals in the toxic control group and test group animals. Cell-mediated immune response of animals was examined by performing neutrophil adhesion test and the humoral immune response was evaluated by determining serum immunoglobulin levels of the animals under study. The administration of methanolic extracts of A. pyrethrum roots and M. pruriens seeds significantly (p less than 0.05) increased the neutrophil adhesion to the nylon fiber. Increase in % neutrophil adhesion was observed in animals treated with 200 mg of each plant extract. Significant (p less than 0.05) improvement in immunoglobulin levels was recorded in the extract treated group animals, showing that the root extract of A. pyrethrum and seed extract of M. pruriens have immunomodulatory potential. We therefore conclude that the tested extracts can be used as immunomodulatory agents to stimulate the immune system.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

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Rodrigo Rezende Kitagawa

2011-12-01

Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

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Rodrigo Rezende Kitagawa

2011-08-01

Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation

OpenAIRE

Liu, Tao; Zhang, Yue; Shen, Zhongyang; Zou, Xunfeng; Chen, Xiaobo; Chen, Li; Wang, Yuliang

2016-01-01

Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immu...

Anti-MuSK-Positive Myasthenia Gravis in a Patient with Parkinsonism and Cognitive Impairment

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S. Lanfranconi

2011-01-01

Full Text Available Muscle-specific tyrosine kinase- (MuSK- antibodies-positive Myasthenia Gravis accounts for about one third of Seronegative Myasthenia Gravis and is clinically characterized by early onset of prominent bulbar, neck, shoulder girdle, and respiratory weakness. The response to medical therapy is generally poor. Here we report a case of late-onset MuSK-antibodies-positive Myasthenia Gravis presenting with signs of cognitive impairment and parkinsonism in addition to bulbar involvement and external ophthalmoplegia. The pattern of involvement of both peripheral and central nervous system dysfunction might suggest a common pathogenic mechanism, involving impaired cholinergic transmission.

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

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Abu-Rish Eman Y.

2017-12-01

Full Text Available Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH response to sheep red blood cell (SRBC antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense.

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Yang, Li-Chan; Lu, Ting-Jang; Hsieh, Chang-Chi; Lin, Wen-Chuan

2014-10-13

Dendrobium tosaense is a medicinal Dendrobium species widely used in traditional medicine. This study demonstrated some structural characterizations and immunomodulatory activity of the water-soluble polysaccharides derived from the stem of D. tosaense (DTP). DTP was fractioned using DEAE-650 M anion-exchange gel filtration chromatography, producing one neutral polysaccharide fraction (DTP-N), which was investigated for its structural characteristics, using HPAEC-PAD, HP-SEC, GC-MS, and NMR spectroscopy. DTP and DTP-N consisted of galactose, glucose, and mannose in ratios of 1:9.1:150.7 and 1:12.2:262.5, respectively. DTP-N comprised (1 → 4)Man as its main backbone, and its average molecular weight was 220 kDa. We also investigated the immunomodulatory effects of DTP administered orally to BALB/c mice for 3 weeks. DTP substantially boosted the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction in splenocytes. This is the first study to demonstrate the structural characteristics of an active polysaccharide derived from D. tosaense and its immunopharmacological effects in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma

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Urmeel H. Patel

2015-03-01

Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

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Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes

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Pushpa Ruwali

2018-01-01

Full Text Available Aim: Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD in chicken lymphocytes. Materials and Methods: Fresh aerial parts of A. indica Willd. (family: Asteraceae specimens were collected (altitude 1560 m, gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME. Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 107 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS and concanavalin A (Con A, respectively. Results: Maximum concentration of AME exhibiting 100% cell viability (MNCD was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 μg/ml dose of AME, resulted in significant (p<0.05 upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS and a significant (p<0.05 increase of 12.018% T cells proliferation in the presence of the mitogen (Con A, as compared to the control. Conclusion: The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

In vitro immunomodulatory potential of Artemisia indica Willd. in chicken lymphocytes.

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Ruwali, Pushpa; Ambwani, Tanuj Kumar; Gautam, Pankaj

2018-01-01

Evaluation of the in vitro immunomodulatory potential of Artemisia indica Willd. methanolic extract in chicken lymphocyte culture system through lymphocyte (B and T cells) proliferation assay, after standardizing the maximum non-cytotoxic dose (MNCD) in chicken lymphocytes. Fresh aerial parts of A. indica Willd. (family: Asteraceae) specimens were collected (altitude 1560 m), gotten authenticated, processed, dried, and Soxhlet extracted to yield methanolic extract (AME). Chicken splenocytes were isolated from spleens collected from healthy birds; lymphocytes were separated by density gradient centrifugation, percentage cell viability determined and final cell count adjusted to 10 7 cells/ml in RPMI-1640 medium. MNCD of AME in chicken lymphocytes was determined through 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide dye reduction assay. Immunomodulatory potential of AME was evaluated through lymphocytes proliferation or B and T cells blastogenesis assay in the presence of appropriate mitogens, namely, lipopolysaccharide (LPS) and concanavalin A (Con A), respectively. Maximum concentration of AME exhibiting 100% cell viability (MNCD) was 200 μg/ml and was selected for further in vitro analysis. The in vitro exposure of chicken lymphocytes to 200 µg/ml dose of AME, resulted in significant (p<0.05) upregulation of 11.76% in B cell proliferation in the presence of B cell mitogen (LPS) and a significant (p<0.05) increase of 12.018% T cells proliferation in the presence of the mitogen (Con A), as compared to the control. The significant upregulation in the proliferation of two major cell types modulating the immune system is an indication of the immunostimulatory potential of the plant. It would be worthwhile to further evaluate A. indica on relevant immunomodulatory aspects, especially the in vivo studies in a poultry system.

The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

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M. L. Perepechaeva

2014-01-01

Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

Immunomodulatory, Cytotoxicity, and Antioxidant Activities of Roots of Ziziphus mauritiana

OpenAIRE

Afzal, Samina; Batool, Murium; Ch, Bashir Ahmad; Ahmad, Ashfaq; Uzair, Muhammad; Afzal, Khurram

2017-01-01

Aims: The study is conducted to evaluate the immunomodulatory, cytotoxicity, and antioxidant potential of Ziziphus mauritiana (Rhamnaceae). Phytochemical analysis of Z. mauritiana revealed the presence of alkaloids, anthraquinone glycoside, cardiac glycoside, saponin, tannin, and flavonoids. Methodology: The cytotoxicity of the plant Z. mauritiana was evaluated by brine shrimp lethality test. Antioxidant parameters such as superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and ma...

Intestinal Immunomodulatory Cells (T Lymphocytes: A Bridge between Gut Microbiota and Diabetes

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Qingwei Li

2018-01-01

Full Text Available Diabetes mellitus (DM is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

Immunomodulatory Properties of Streptococcus and Veillonella Isolates from the Human Small Intestine Microbiota

NARCIS (Netherlands)

Bogert, van den B.; Meijerink, M.; Zoetendal, E.G.; Wells, J.M.; Kleerebezem, M.

2014-01-01

The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains

Production of coagulation factor VII in human cell lines Sk-Hep-1 and HKB-11.

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Corrêa de Freitas, Marcela Cristina; Bomfim, Aline de Sousa; Mizukami, Amanda; Picanço-Castro, Virgínia; Swiech, Kamilla; Covas, Dimas Tadeu

2017-09-01

Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX). Because of the post-translational modifications, rFVII needs to be produced in mammalian cell lines. In this study, for the first time, we have shown efficient rFVII production in HepG2, Sk-Hep-1, and HKB-11 cell lines. Experiments in static conditions for a period of 96 h showed that HepG2-FVII produced the highest amounts of rhFVII, with an average of 1843 ng/mL. Sk-hep-1-FVII cells reached a maximum protein production of 1432 ng/mL and HKB-11-FVII cells reached 1468 ng/mL. Sk-Hep-1-rFVII and HKB-11-rFVII were selected for the first step of scale-up. Over 10 days of spinner flask culture, HKB-11 and SK-Hep-1 cells showed a cumulative production of rFVII of 152 μg and 202.6 μg in 50 mL, respectively. Thus, these human cell lines can be used for an efficient production of recombinant FVII. With more investment in basic research, human cell lines can be optimized for the commercial production of different bio therapeutic proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Ocena przydatności kryteriów Williamsa w rozpoznawaniu atopowego zapalenia skóry w praktyce lekarza pediatry

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Zbigniew Samochocki

2009-09-01

Full Text Available O trudnościach w rozpoznawaniu AZS u dzieci świadczy stosowanie wielu różnych metod diagnostycznych. Jedną z nich są kryteria zaproponowane przez Williamsa iwsp. Celem pracy było określenie przydatności kryteriów Williamsa iwsp. wrozpoznawaniu AZS u dzieci poprzez ocenę porównawczą z kryteriami Hanifina iRajki. Badaniami objęto 166 pacjentów Poradni Dermatologicznej (67 chłopców i 99 dziewczynek w wieku od 4 do 15 lat (średnio 10,3 roku, którzy niezależnie od zmian skórnych zgłaszali świąd skóry. Poddano ich badaniu klinicznemu i procedurom zawartym w kryteriach Hanifina i Rajki. Dokonano analizy statystycznej wyników. U 108 dzieci rozpoznano AZS, a u 58 – świerzb, łojotokowe zapalenie skóry, zapalenie skóry z podrażnienia, łuszczycę, trądzik młodzieńczy oraz pokrzywkę. U wszystkich chorych naAZS wykazano suchość skóry. Zajęcie typowych okolic podawane wwywiadzie, początek zmian skórnych <2. roku życia, czynne zmiany w przegubach i osobnicze obciążenie atopią obserwowano odpowiednio u 96,3% (104/108, 71,3% (77/108, 67,6% (73/108 i 64,3% (70/108 pacjentów. Wszystkie te cechy występowały statystycznie istotnie częściej (p<0,001 wporównaniu z grupą dzieci, u których nie rozpoznano wyprysku atopowego. Stosując kryteria Williamsa i wsp., u 3/108 chorych wykazano fałszywie ujemne wyniki, a u 2/58 – fałszywie dodatnie. Czułość i swoistość tej metody badawczej wynosiła odpowiednio 97,2% i 96,6%. Wnioski: 1. Kryteria diagnostyczne Williamsa i wsp. są bardzo pomocne w praktyce lekarza pediatry w rozpoznawaniu AZS u dzieci powyżej 3. roku życia. 2. Suchość skóry i potwierdzenie wwywiadzie obecności zmian wypryskowych o typowej lokalizacji są najbardziej przydatne w rozpoznawaniu AZS u dzieci. 3. W przypadkach wątpliwych rozszerzenie granicy wieku wystąpienia pierwszych zmian skórnych z 2 do 5 lat zwiększa wykrywalność choroby.

Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway.

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Kwon, Soon-Jae; Lee, Ju-Hye; Moon, Kwang-Deog; Jeong, Il-Yun; Yee, Sung-Tae; Lee, Mi-Kyung; Seo, Kwon-Il

2014-11-01

Isoegomaketone (IK) is a major biologically active component of Perilla frutescens. In this study, we investigated the contribution of reactive oxygen species (ROS) to IK-induced apoptosis in human melanoma SK-MEL-2 cells. We found that IK inhibited the proliferation of SK-MEL-2 human melanoma cells in a dose-dependent manner. IK also induced sub-G1 DNA accumulation, formation of apoptotic bodies, nuclear condensation, and a DNA ladder in SK-MEL-2 cells. IK also induced activation of caspase-3 and -9, whereas caspase‑8 was unaffected. Further, N-acetyl-L-cysteine (NAC, ROS scavenger) treatment to SK-MEL-2 cells significantly reduced IK-induced cell death. Pretreatment of NAC to SK-MEL-2 cells followed by 100 µM IK reduced the protein levels of Bax and cytochrome c as well as PARP cleavage, whereas the protein level of Bcl-2 increased. Moreover, IK inhibited the phosphorylation of AKT/mTOR protein and cell proliferation induced by LY294002, a PI3K inhibitor. In conclusion, IK-induced ROS generation regulates cell growth inhibition and it induces apoptosis through caspase‑dependent and -independent pathways via modulation of PI3K/AKT signaling in SK-MEL-2 cells.

Immunomodulatory effects of the fungicide Mancozeb in agricultural workers

International Nuclear Information System (INIS)

Corsini, Emanuela; Birindelli, Sarah; Fustinoni, Silvia; De Paschale, Gioia; Mammone, Teresa; Visentin, Sara; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

2005-01-01

Available data suggest that ethylenebisdithiocarbamates (EBDCs) may have immunomodulatory effects. This study aimed to investigate the immunological profile of farmers exposed to Mancozeb, an EBDC fungicide, through the determination of several serum, cellular, and functional immune parameters. Twenty-six healthy subjects entered the study, 13 vineyards exposed to Mancozeb and 13 unexposed controls. Exposure was assessed through the determination of ethylentiourea (ETU) in urine. Complete and differential blood count, serum immunoglobulins, complement fractions, autoantibodies, lymphocyte subpopulations, proliferative response to mitogens, natural killer (NK) activity, and cytokine production were measured. Post-exposure samples showed ETU urine concentration significantly higher than pre-exposure and control groups. A significant increase in CD19+ cells, both percentage and absolute number, and a significant decrease in the percentage of CD25+ cells were found in post-exposure samples compared to controls. A statistically significant increase in the proliferative response to phorbol myristate acetate plus ionomycin (PMA + ionomycin) was observed in the post-exposure group compared to controls and baseline, while a significant reduction in LPS-induced TNF-α release in post-exposure samples was observed. Overall, our results suggest that low-level exposure to Mancozeb has slight immunomodulatory effects, and point out a method adequate to reveal immune-modifications in workers occupationally exposed to potential immunotoxic compounds, based on a whole blood assay

Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

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Parisa Lotfinegad

2014-03-01

Full Text Available Immunosuppressive ability of mesenchymal stem cells (MSCs, their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance.

Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

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Lotfinegad, Parisa; Shamsasenjan, karim; Movassaghpour, Aliakbar; Majidi, Jafar; Baradaran, Behzad

2014-01-01

Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance. PMID:24409403

Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

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Al-Oran, Sawsan Atallah; Hassuneh, Mona Rushdie; Al-Qaralleh, Haitham Naief; Rayyan, Walid Abu; Al-Thunibat, Osama Yosef; Mallah, Eyad; Abu-Rayyan, Ahmed; Salem, Shadi

2017-01-01

This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional), we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/106 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg. PMID:29204086

In vitro pyrogen test for toxic or immunomodulatory drugs

OpenAIRE

Daneshian, Mardas; Guenther, Armin; Wendel, Albrecht; Hartung, Thomas; Aulock, Sonja von

2006-01-01

Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After ri...

Genome-wide analysis of KAP1, the 7SK snRNP complex, and RNA polymerase II

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Ryan P. McNamara

2016-03-01

Full Text Available The transition of RNA polymerase II (Pol II from transcription initiation into productive elongation in eukaryotic cells is regulated by the P-TEFb kinase, which phosphorylates the C-terminal domain of paused Pol II at promoter-proximal regions. Our recent study found that P-TEFb (in an inhibited state bound to the 7SK snRNP complex interacts with the KAP1/TRIM28 transcriptional regulator, and that KAP1 and the 7SK snRNP co-occupy most gene promoters containing paused Pol II. Here we provide a detailed experimental description and analysis of the ChIP-seq datasets that have been deposited into Gene Expression Omnibus (GEO: GS72622, so that independent groups can replicate and expand upon these findings. We propose these datasets would provide valuable information for researchers studying mechanisms of transcriptional regulation including Pol II pausing and pause release. Keywords: P-TEFb/7SK snRNP, KAP1, RNA polymerase II, ChIP-seq, Transcription elongation

Identity of the immunomodulatory proteins from garlic (Allium sativum) with the major garlic lectins or agglutinins.

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Clement, Fatima; Pramod, Siddanakoppalu N; Venkatesh, Yeldur P

2010-03-01

Garlic (Allium sativum), an important medicinal spice, displays a plethora of biological effects including immunomodulation. Although some immunomodulatory proteins from garlic have been described, their identities are still unknown. The present study was envisaged to isolate immunomodulatory proteins from raw garlic, and examine their effects on certain cells of the immune system (lymphocytes, mast cells, and basophils) in relation to mitogenicity and hypersensitivity. Three protein components of approximately 13 kD (QR-1, QR-2, and QR-3 in the ratio 7:28:1) were separated by Q-Sepharose chromatography of 30 kD ultrafiltrate of raw garlic extract. All the 3 proteins exhibited mitogenic activity towards human peripheral blood lymphocytes, murine splenocytes and thymocytes. The mitogenicity of QR-2 was the highest among the three immunomodulatory proteins. QR-1 and QR-2 displayed hemagglutination and mannose-binding activities; QR-3 showed only mannose-binding activity. Immunoreactivity of rabbit anti-QR-1 and anti-QR-2 polyclonal antisera showed specificity for their respective antigens as well as mutual cross-reactivity; QR-3 was better recognized by anti-QR-2 (82%) than by anti-QR-1 (55%). QR-2 induced a 2-fold higher histamine release in vitro from leukocytes of atopic subjects compared to that of non-atopic subjects. In all functional studies, QR-2 was more potent compared to QR-1. Taken together, all these results indicate that the two major proteins QR-2 and QR-1 present in a ratio of 4:1 in raw garlic contribute to garlic's immunomodulatory activity, and their characteristics are markedly similar to the abundant Allium sativum agglutinins (ASA) I and II, respectively. Copyright 2010 Elsevier B.V. All rights reserved.

Use of Immunomodulatory Drugs at a Uveitis Clinic.

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Millán-Longo, Claudia; Peiteado, Diana; Schlincker, Armelle; Hidalgo, Ventura; Pieren, Amara; Balsa, Alejandro; de Miguel, Eugenio

2017-11-10

The treatment of noninfectious uveitis includes steroids and immunomodulatory drugs, the use of which has increased in the last few years, and the options have been enriched with the development of new treatments. However, clear therapeutic guidelines and protocols have not been developed. The purpose is to analyze the response to the drugs used and the characteristics of the patients treated at a multidisciplinary uveitis clinic. Observational and retrospective study of the patients attended to from January 2012 to December 2015. Infectious, posttraumatic and postoperative uveitis, as well as masquerade syndrome, were excluded. Two hundred six patients were included. Overall, 58.80% had uveitis without association of systemic disease, mostly idiopathic uveitis, and 35.65% had uveitis with systemic involvement, mainly related to spondyloarthritis. Uveitis without systemic association and anterior uveitis achieved disease control with local treatment more frequently than others (p=.002 and p treatment. Among those treated with immunomodulators, 53.26% needed a second drug and 31.52% needed a third drug. Women required immunomodulators more often than men (P=.042). Methotrexate was the most widely used immunomodulator. Posterior uveitis responded less favorably to the second immunomodulator than anterior uveitis (p=.006). Almost half of the patients needed an immunomodulatory drug and some of them required successive drug changes. Intermediate uveitis was the most treatment-refractory uveitis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The role of formyl peptide receptors for immunomodulatory activities of antimicrobial peptides and peptidomimetics

DEFF Research Database (Denmark)

Skovbakke, Sarah Line; Holdfeldt, André; Forsman, Huamei

2018-01-01

In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical trials. This paradox may be explained by the fact, that some of the intrinsic properties...... displaying analogous immunomodulatory activity profiles. Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis and by regulating other processes of innate immunity as well as promotion of resolution of inflammation. Several aspects of these effects...... are correlated to their expression of formyl peptide receptors (FPRs) that have been shown to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well...

A model of immunomodulatory for dengue infection mm

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Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

2018-03-01

An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner.

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Huang, Chang-Yu; Wu, Guang-Jer

2016-04-01

Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was caused by clonal variation, METCAM/MUC18-dosage effect, or the number of cells injected. Several G418-resistant clones of SK-BR-3, expressing different levels of METCAM/MUC18, were obtained for testing effects of human METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenicity) and in vivo tumorigenesis in female Balb/C athymic nude mice. Tumor sections were made for histology and immunohistochemistry analyses, and tumor lysates for Western blot analysis to determine the effects of human METCAM/MUC18 expression on levels of various downstream effectors. METCAM/MUC18 promoted in vitro motility, invasiveness, and in vitro tumorigenicity of SK-BR-3 cells in a dosage-specific manner. Overexpression of METCAM/MUC18 could promote in vivo tumorigenesis of SK-BR-3 cells even when one tenth of the previously used cell number (5 × 10(5)) was injected and in vivo tumorigenesis of SK-BR-3 cells was directly proportional to the dosage of the protein. The previously observed transient tumor suppression effect from the same clone was no longer observed. The downstream effector, such as phospho-AKT/AKT ratio, was elevated in the tumors. Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 10(6)-5 × 10(6)). METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway. Copyright © 2016. Published by Elsevier B.V.

Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells

International Nuclear Information System (INIS)

Tao, Yan-Fang; Wu, Dong; Wang, Na; Feng, Xing; Li, Yan-Hong; Ni, Jian; Wang, Jian; Pan, Jian; Lu, Jun; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Xuan; Peng, Liang; Cao, Lan; Xiao, Pei-Fang; Pang, Li

2012-01-01

Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. YM155, a novel molecular targeted agent, suppresses survivin, which is overexpressed in many tumor types. The aim of this study was to determine the antitumor activity of YM155 in SK-NEP-1 cells. SK-NEP-1 cell growth in vitro and in vivo was assessed by MTT and nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometric analysis was used to detect apoptosis in cell culture. Then gene expression profile of tumor cells treated with YM155 was analyzed with real-time PCR arrays. We then analyzed the expression data with MEV (Multi Experiment View) cluster software. Datasets representing genes with altered expression profile derived from cluster analyses were imported into the Ingenuity Pathway Analysis tool. YM155 treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner. Annexin V assay, cell cycle, and activation of caspase-3 demonstrates that YM155 induced apoptosis in SK-NEP-1 cells. YM155 significantly inhibited growth of SK-NEP-1 xenografts (YM155 5 mg/kg: 1.45 ± 0.77 cm 3 ; YM155 10 mg/kg: 0.95 ± 0.55 cm 3 ) compared to DMSO group (DMSO: 3.70 ± 2.4 cm 3 ) or PBS group cells (PBS: 3.78 ± 2.20 cm 3 , ANOVA P < 0.01). YM155 treatment decreased weight of tumors (YM155 5 mg/kg: 1.05 ± 0.24 g; YM155 10 mg/kg: 0.72 ± 0.17 g) compared to DMSO group (DMSO: 2.06 ± 0.38 g) or PBS group cells (PBS: 2.36 ± 0.43 g, ANOVA P < 0.01). Real-time PCR array analysis showed between Test group and control group there are 32 genes significantly up-regulated and 54 genes were significantly down-regulated after YM155 treatment. Ingenuity pathway analysis (IPA) showed cell death was the highest rated network with 65 focus molecules and the significance score of 44. The IPA analysis also groups the differentially expressed genes into biological mechanisms that are related to cell

RuvBL2 Is Involved in Histone Deacetylase Inhibitor PCI-24781-Induced Cell Death in SK-N-DZ Neuroblastoma Cells

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Zhan, Qinglei; Tsai, Sauna; Lu, Yonghai; Wang, Chunmei; Kwan, Yiuwa; Ngai, Saiming

2013-01-01

Neuroblastoma is the second most common solid tumor diagnosed during infancy. The survival rate among children with high-risk neuroblastoma is less than 40%, highlighting the urgent needs for new treatment strategies. PCI-24781 is a novel hydroxamic acid-based histone deacetylase (HDAC) inhibitor that has high efficacy and safety for cancer treatment. However, the underlying mechanisms of PCI-24781 are not clearly elucidated in neuroblastoma cells. In the present study, we demonstrated that PCI-24781 treatment significantly inhibited tumor growth at very low doses in neuroblastoma cells SK-N-DZ, not in normal cell line HS-68. However, PCI-24781 caused the accumulation of acetylated histone H3 both in SK-N-DZ and HS-68 cell line. Treatment of SK-N-DZ with PCI-24781 also induced cell cycle arrest in G2/M phase and activated apoptosis signaling pathways via the up-regulation of DR4, p21, p53 and caspase 3. Further proteomic analysis revealed differential protein expression profiles between non-treated and PCI-24781 treated SK-N-DZ cells. Totally 42 differentially expressed proteins were identified by MALDI-TOF MS system. Western blotting confirmed the expression level of five candidate proteins including prohibitin, hHR23a, RuvBL2, TRAP1 and PDCD6IP. Selective knockdown of RuvBL2 rescued cells from PCI-24781-induced cell death, implying that RuvBL2 might play an important role in anti-tumor activity of PCI-24781 in SK-N-DZ cells. The present results provide a new insight into the potential mechanism of PCI-24781 in SK-N-DZ cell line. PMID:23977108

The tetraindole SK228 reverses the epithelial-to-mesenchymal transition of breast cancer cells by up-regulating members of the miR-200 family.

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Chie-Hong Wang

Full Text Available The results of recent studies have shown that metastasis, the most common malignancy and primary cause of mortality promoted by breast cancer in women, is associated with the epithelial-to-mesenchymal transition (EMT. The results of the current study show that SK228, a novel indole containing substance, exhibits anti-cancer activity. In addition, the effects of SK228 on the regulation of EMT in breast cancer cells as well as the underlying mechanism have been explored. SK228 was observed to induce a fibroblastoid to epithelial-like change in the appearance of various breast cancer cell lines and to suppress the migration and invasion of these cancer cells in vitro. Moreover, expression of E-cadherin was found to increase following SK228 treatment whereas ZEB1 expression was repressed. Expression of other major EMT inducers, including ZEB2, Slug and Twist1, is also repressed by SK228 as a consequence of up-regulation of members of the miR-200 family, especially miR-200c. The results of animal studies demonstrate that SK228 treatment leads to effective suppression of breast cancer growth and metastasis in vivo. The observations made in this investigation show that SK228 reverses the EMT process in breast cancer cells via an effect on the miR-200c/ZEB1/E-cadherin signalling pathway. In addition, the results of a detailed analysis of the in vivo anti-cancer activities of SK228, carried out using a breast cancer xenograft animal model, show that this substance is a potential chemotherapeutic agent for the treatment of breast cancer.

Polyploidization on SK-N-MC human neuroblastoma cells infected with herpes simplex virus 1.

Science.gov (United States)

Karalyan, Zaven; Izmailyan, Roza; Karalova, Elena; Abroyan, Liana; Hakobyan, Lina; Avetisyan, Aida; Semerjyan, Zara

2016-01-01

Polyploidization is one of the most dramatic changes occurring within cell genome owing to various reasons including under many viral infections. We examined the impact of herpes simplex virus-1 (HSV-1) on SK-N-MC human neuroblastoma cell line. The infected cells were followed from 6 hours up to 96 hours post infection (hpi). A large number of polyploid cells with giant nuclei was observed under the influence of HSV-1 at 24 hpi with the DNA content of 32c to 64c or more, in comparison with control SK-N-MC cells that were characterized by relatively moderate values of ploidy, i.e. 8с to 16с (where 1c is the haploid amount of nuclear DNA found in normal diploid populations in G0/G1). After 48-96 hpi, the population of polyploid cells with giant nuclei decreased to the benchmark level. The SK-NMC cells infected with HSV-1 for 24 hours were stained with gallocyanine and monitored for cytological features. The infected cells underwent virus induced cellcell and nuclei fusion with the formation of dense nuclei syncytium. The metabolic activity of HSV-1 infected cells was higher in both nuclei and nucleoli when compared to control cells.

In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).

Science.gov (United States)

Majdalawieh, Amin F; Carr, Ronald I

2010-04-01

Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

Science.gov (United States)

Gueguinou, M; Crottès, D; Chantôme, A; Rapetti-Mauss, R; Potier-Cartereau, M; Clarysse, L; Girault, A; Fourbon, Y; Jézéquel, P; Guérin-Charbonnel, C; Fromont, G; Martin, P; Pellissier, B; Schiappa, R; Chamorey, E; Mignen, O; Uguen, A; Borgese, F; Vandier, C; Soriani, O

2017-06-22

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca 2+ -activated K + channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca 2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca 2+ homeostasis in epithelial cancers.

Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol.

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Klopčič, Ivana; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

2018-05-16

A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

Calcium-dependent stoichiometries of the KCa2.2 (SK) intracellular domain/calmodulin complex in solution.

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Halling, D Brent; Kenrick, Sophia A; Riggs, Austen F; Aldrich, Richard W

2014-02-01

Ca(2+) activates SK Ca(2+)-activated K(+) channels through the protein Ca(2+) sensor, calmodulin (CaM). To understand how SK channels operate, it is necessary to determine how Ca(2+) regulates CaM binding to its target on SK. Tagless, recombinant SK peptide (SKp), was purified for binding studies with CaM at low and high Ca(2+) concentrations. Composition gradient multi-angle light scattering accurately measures the molar mass, stoichiometry, and affinity of protein complexes. In 2 mM Ca(2+), SKp and CaM bind with three different stoichiometries that depend on the molar ratio of SKp:CaM in solution. These complexes include 28 kD 1SKp/1CaM, 39 kD 2SKp/1CaM, and 44 kD 1SKp/2CaM. A 2SKp/2CaM complex, observed in prior crystallographic studies, is absent. At sedimentation coefficient is smaller for a 1SKp:1CaM solution than it is for either 2SKp:1CaM or 1SKp:2CaM. At low Ca(2+) and at >100 µM protein concentrations, a molar excess of SKp over CaM causes aggregation. Aggregation is not observed in Ca(2+) or with CaM in molar excess. In low Ca(2+) both 1SKp:1CaM and 1SKp:2CaM solutions have similar sedimentation coefficients, which is consistent with the absence of a 1SKp/2CaM complex in low Ca(2+). These results suggest that complexes with stoichiometries other than 2SKp/2CaM are important in gating.

Antioxidant, immunomodulatory and antiproliferative effects of gelatin hydrolysate from unicorn leatherjacket skin.

Science.gov (United States)

Karnjanapratum, Supatra; O'Callaghan, Yvonne C; Benjakul, Soottawat; O'Brien, Nora

2016-07-01

The in vitro cellular bioactivities including, antioxidant, immunomodulatory and antiproliferative effects of a gelatin hydrolysate (GH) prepared from unicorn leatherjacket skin, using partially purified glycyl endopeptidase, were investigated in order to optimize the use of fish skin waste products as functional food ingredients. GH under the tested concentrations (750-1500 µg mL(-1) ) protected against H2 O2 -induced DNA damage in U937 cells. GH also protected against the H2 O2 -induced reduction in cellular antioxidant enzyme activities, superoxide dismutase and catalase, in HepG2 cells. GH demonstrated immunomodulatory potential by reducing pro-inflammatory cytokine (interleukin-6 (IL-6) and IL-1β) production and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Cell proliferation in human colon cancer (Caco-2) cells was significantly reduced in a dose-dependent manner following incubation with GH. These results indicate that GH has several bioactivities which support its potential as a promising functional food ingredient with various health benefits. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells.

Science.gov (United States)

Zeng, Guofang; Liu, Jie; Chen, Hege; Liu, Bin; Zhang, Qingyu; Li, Mingyi; Zhu, Runzhi

2014-06-01

Dihydromyricetin (DHM) exhibits multiple pharmacological activities; however, the role of DHM in anti-melanoma activities and the underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on cell proliferation, cell cycle distribution and apoptosis in the human melanoma SK-MEL-28 cell line, and to explore the related mechanisms. The effect of DHM on cell proliferation was investigated by MTT assay, and cell cycle distribution was determined by flow cytometry. TUNEL assay was used to evaluate DHM-mediated apoptosis, and western blotting was applied to examine expression levels of p53, p21, Cdc25A, Cdc2, P-Cdc2, Bax, IKK-α, NF-κB p65, p38 and P-p38 proteins. The results revealed that DHM suppressed cell proliferation of SK-MEL-28 cells in a concentration- and time-dependent manner, and caused cell cycle arrest at the G1/S phase. DHM increased the production of p53 and p21 proteins and downregulated the production of Cdc25A, Cdc2 and P-Cdc2 proteins, which induced cell cycle arrest. Additionally, DHM significantly induced the apoptosis of SK-MEL-28 cells, and enhanced the expression levels of Bax proteins and decreased the protein levels of IKK-α, NF-κB (p65) and P-p38. The results suggest that DHM may be a novel and effective candidate agent to inhibit the growth of melanoma.

$K^{0}_{s}-K^{0}_{s}$ correlations in pp collisions at $\\sqrt{s}=7 TeV$ from the LHC ALICE experiment

CERN Document Server

Abelev, Betty; Adamova, Dagmar; Adare, Andrew Marshall; Aggarwal, Madan; Aglieri Rinella, Gianluca; Agocs, Andras Gabor; Agostinelli, Andrea; Aguilar Salazar, Saul; Ahammed, Zubayer; Ahmad, Arshad; Ahmad, Nazeer; Ahn, Sang Un; Akindinov, Alexander; Aleksandrov, Dmitry; Alessandro, Bruno; Alfaro Molina, Jose Ruben; Alici, Andrea; Alkin, Anton; Almaraz Avina, Erick Jonathan; Alme, Johan; Alt, Torsten; Altini, Valerio; Altinpinar, Sedat; Altsybeev, Igor; Andrei, Cristian; Andronic, Anton; Anguelov, Venelin; Anielski, Jonas; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Aphecetche, Laurent Bernard; Appelshauser, Harald; Arbor, Nicolas; Arcelli, Silvia; Armesto, Nestor; Arnaldi, Roberta; Aronsson, Tomas Robert; Arsene, Ionut Cristian; Arslandok, Mesut; Augustinus, Andre; Averbeck, Ralf Peter; Awes, Terry; Aysto, Juha Heikki; Azmi, Mohd Danish; Bach, Matthias Jakob; Badala, Angela; Baek, Yong Wook; Bailhache, Raphaelle Marie; Bala, Renu; Baldini Ferroli, Rinaldo; Baldisseri, Alberto; 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de Rooij, Raoul Stefan; Delagrange, Hugues; Deloff, Andrzej; Demanov, Vyacheslav; Denes, Ervin; Deppman, Airton; Di Bari, Domenico; Di Giglio, Carmelo; Di Liberto, Sergio; Di Mauro, Antonio; Di Nezza, Pasquale; Diaz Corchero, Miguel Angel; Dietel, Thomas; Divia, Roberto; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Dobrowolski, Tadeusz Antoni; Dominguez, Isabel; Donigus, Benjamin; Dordic, Olja; Driga, Olga; Dubey, Anand Kumar; Ducroux, Laurent; Dupieux, Pascal; Dutta Majumdar, AK; Dutta Majumdar, Mihir Ranjan; Elia, Domenico; Emschermann, David Philip; Engel, Heiko; Erdal, Hege Austrheim; Espagnon, Bruno; Estienne, Magali Danielle; Esumi, Shinichi; Evans, David; Eyyubova, Gyulnara; Fabris, Daniela; Faivre, Julien; Falchieri, Davide; Fantoni, Alessandra; Fasel, Markus; Fedunov, Anatoly; Fehlker, Dominik; Feldkamp, Linus; Felea, Daniel; Fenton-Olsen, Bo; Feofilov, Grigory; Fernandez Tellez, Arturo; Ferretti, Alessandro; Ferretti, Roberta; Figiel, Jan; Figueredo, Marcel; Filchagin, Sergey; 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Klay, Jennifer Lynn; Klein, Jochen; Klein-Bosing, Christian; Kluge, Alexander; Knichel, Michael Linus; Knospe, Anders Garritt; Koch, Kathrin; Kohler, Markus; Kolojvari, Anatoly; Kondratiev, Valery; Kondratyeva, Natalia; Konevskih, Artem; Korneev, Andrey; Kour, Ravjeet; Kowalski, Marek; Kox, Serge; Koyithatta Meethaleveedu, Greeshma; Kral, Jiri; Kralik, Ivan; Kramer, Frederick; Kraus, Ingrid Christine; Krawutschke, Tobias; Krelina, Michal; Kretz, Matthias; Krivda, Marian; Krizek, Filip; Krus, Miroslav; Kryshen, Evgeny; Krzewicki, Mikolaj; Kucheriaev, Yury; Kuhn, Christian Claude; Kuijer, Paul; Kulakov, Igor; Kumar, Jitendra; Kurashvili, Podist; Kurepin, A; Kurepin, AB; Kuryakin, Alexey; Kushpil, Svetlana; Kushpil, Vasily; Kweon, Min Jung; Kwon, Youngil; La Pointe, Sarah Louise; La Rocca, Paola; Ladron de Guevara, Pedro; Lakomov, Igor; Langoy, Rune; Lara, Camilo Ernesto; Lardeux, Antoine Xavier; Lazzeroni, Cristina; Le Bornec, Yves; Lea, Ramona; Lechman, Mateusz; Lee, Graham Richard; Lee, Ki Sang; 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Suire, Christophe Pierre; Sukhorukov, Mikhail; Sultanov, Rishat; Sumbera, Michal; Susa, Tatjana; Szanto de Toledo, Alejandro; Szarka, Imrich; Szczepankiewicz, Adam; Szostak, Artur Krzysztof; Szymanski, Maciej; Takahashi, Jun; Tapia Takaki, Daniel Jesus; Tarazona Martinez, Alfonso; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terrevoli, Cristina; Thader, Jochen Mathias; Thomas, Deepa; Tieulent, Raphael Noel; Timmins, Anthony; Toia, Alberica; Torii, Hisayuki; Tosello, Flavio; Trzaska, Wladyslaw Henryk; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ulery, Jason Glyndwr; Ullaland, Kjetil; Ulrich, Jochen; Uras, Antonio; Urban, Jozef; Urciuoli, Guido Marie; Usai, Gianluca; Vajzer, Michal; Vala, Martin; Valencia Palomo, Lizardo; Vallero, Sara; van der Kolk, Naomi; van Leeuwen, Marco; Vande Vyvre, Pierre; Vannucci, Luigi; Vargas, Aurora Diozcora; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vechernin, Vladimir; Veldhoen, Misha; Venaruzzo, Massimo; Vercellin, Ermanno; Vergara, Sergio; Vernet, Renaud; Verweij, Marta; Vickovic, Linda; Viesti, Giuseppe; Vikhlyantsev, Oleg; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Vinogradov, Alexander; Vinogradov, Leonid; Vinogradov, Yury; Virgili, Tiziano; Viyogi, Yogendra; Vodopianov, Alexander; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; von Haller, Barthelemy; Vranic, Danilo; Øvrebekk, Gaute; Vrlakova, Janka; Vulpescu, Bogdan; Vyushin, Alexey; Wagner, Boris; Wagner, Vladimir; Wan, Renzhuo; Wang, Dong; Wang, Mengliang; Wang, Yifei; Wang, Yaping; Watanabe, Kengo; Weber, Michael; Wessels, Johannes; Westerhoff, Uwe; Wiechula, Jens; Wikne, Jon; Wilde, Martin Rudolf; Wilk, Alexander; Wilk, Grzegorz Andrzej; Williams, Crispin; Windelband, Bernd Stefan; Xaplanteris Karampatsos, Leonidas; Yaldo, Chris G; Yamaguchi, Yorito; Yang, Hongyan; Yang, Shiming; Yasnopolsky, Stanislav; Yi, JunGyu; Yin, Zhongbao; Yoo, In-Kwon; Yoon, Jongik; Yu, Weilin; Yuan, Xianbao; Yushmanov, Igor; Zach, Cenek; Zampolli, Chiara; Zaporozhets, Sergey; Zarochentsev, Andrey; Zavada, Petr; Zaviyalov, Nikolai; Zbroszczyk, Hanna Paulina; Zelnicek, Pierre; Zgura, Sorin Ion; Zhalov, Mikhail; Zhang, Haitao; Zhang, Xiaoming; Zhou, Daicui; Zhou, Fengchu; Zhou, You; Zhu, Jianhui; Zhu, Xiangrong; Zichichi, Antonino; Zimmermann, Alice; Zinovjev, Gennady; Zoccarato, Yannick Denis; Zynovyev, Mykhaylo; Zyzak, Maksym

2013-07-16

Identical neutral kaon pair correlations are measured in $\\sqrt{s}$=7 TeV pp collisions in the ALICE experiment. One-dimensional K$^{0}_{s}$-K$^{0}_{s}$ correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the $a_0/f_0$ resonance. K$^{0}_{s}$-K$^{0}_{s}$ correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, $m_T$, as seen in pion-pion correlations in the pp system and in heavy-ion collisions. Transverse mass scaling is observed between the K$^{0}_{s}$-K$^{0}_{s}$ and pion-pion radii. Also, the first observation is made of the decay of the $f_{2}'$(1525) meson into the K$^{0}_{s}$-K$^{0}_{s}$ channel in pp collisions.

Intra-annual distribution of Temora longicornis biomass in the Gulf of Gdańsk (the southern Baltic Sea – numerical simulations

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Lidia Dzierzbicka-Głowacka

2017-11-01

Full Text Available A population model of the copepod Temora longicornis coupled with the ecosystem model 3D CEMBS (Coupled Ecosystem Model of the Baltic Sea was used to determine the intra-annual distribution of the species biomass in the Gdańsk Basin (the southern Baltic Sea. The population model for T. longicornis consists of twelve equations for twelve state variables, six for mass and six for abundance, i.e. two state variables for each of the six model stages of the development: eggs (Egg, non-feeding stage (N1, subsequent nauplii stages (N2–N6, two copepodite stages (C1–C3 and C4–C5 and adults (C6. The empirical validation of the population model was based on in situ data collected in 2010 and 2011 in the Gdańsk Deep and the western part of the Gulf of Gdańsk. The highest values of the model biomass occurred in the period of high water temperatures – in June 2010 and July 2011 in the Gulf of Gdańsk (ca 5200 mg wet weight (w.w. m–2 and 6300 mg w.w. m–2, and for almost the whole summer in the Gdańsk Deep (24 500 mg w.w. m–2 and 27 800 mg w.w. m–2. Temora longicornis produced 4 to 5 generations per year in the Gulf of Gdańsk and Gdańsk Deep, respectively. The population model was satisfactorily verified and the calculated results were consistent with the in situ data. Despite some differences between the field and model data, the developed population model of T. longicornis is the first model for this species in the Baltic Sea and, even though it needs further improvement, it can be a useful tool for determining the population dynamics of the species and ecological relationships in the environment.

The Making of the Gdańsk Metropolitan Region. Local Discourses of Identities, Powers, and Hopes

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Czepczyński Mariusz

2014-12-01

Full Text Available The process of metropolitanisation of the Gdańsk area is facilitated by public discourse involving local and regional politicians, media, and inhabitants. The discussion is based upon historical narrations, but also local ambitions, hopes and emotions, as well as infrastructural projects and investment attractiveness. Foucault suggests that modern power is a dispersed set of micro-practices, many of which operate through the normalising gaze of surveillance regimes. Gdańsk metropolitan cooperation, competition and encounters make the core of the paper; local and regional unifying initiatives and processes are accompanied by examples of separatism, identity conflicts, and political disagreements

Chronic ethanol exposure induces SK-N-SH cell apoptosis by increasing N-methyl-D-aspartic acid receptor expression and intracellular calcium.

Science.gov (United States)

Wang, Hongbo; Wang, Xiaolong; Li, Yan; Yu, Hao; Wang, Changliang; Feng, Chunmei; Xu, Guohui; Chen, Jiajun; You, Jiabin; Wang, Pengfei; Wu, Xu; Zhao, Rui; Zhang, Guohua

2018-04-01

It has been identified that chronic ethanol exposure damages the nervous system, particularly neurons. There is scientific evidence suggesting that neuronal loss caused by chronic ethanol exposure has an association with neuron apoptosis and intracellular calcium oscillation is one of the primary inducers of apoptosis. Therefore, the present study aimed to investigate the inductive effects of intracellular calcium oscillation on apoptosis in SK-N-SH human neuroblastoma cells and the protective effects of the N-methyl-D-aspartic acid receptor (NMDAR) antagonist, memantine, on SK-N-SH cell apoptosis caused by chronic ethanol exposure. SK-N-SH cells were treated with 100 mM ethanol and memantine (4 µM) for 2 days. Protein expression of NR1 was downregulated by RNA interference (RNAi). Apoptosis was detected by Annexin V/propidium iodide (PI) double-staining and flow cytometry and cell viability was detected using an MTS kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration and the levels of NR1 and caspase-3 were detected using western blotting. NR1 mRNA levels were also detected using qPCR. It was found that chronic ethanol exposure reduced neuronal cell viability and caused apoptosis of SK-N-SH cells, and the extent of damage in SK-N-SH cells was associated with ethanol exposure concentration and time. In addition, chronic ethanol exposure increased the concentration of intracellular calcium in SK-N-SH cells by inducing the expression of NMDAR, resulting in apoptosis, and memantine treatment reduced ethanol-induced cell apoptosis. The results of the present study indicate that the application of memantine may provide a novel strategy for the treatment of alcoholic dementia.

A novel subtilase with NaCl-activated and oxidant-stable activity from Virgibacillus sp. SK37

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Yamabhai Montarop

2011-06-01

Full Text Available Abstract Background Microbial proteases are one of the most commercially valuable enzymes, of which the largest market share has been taken by subtilases or alkaline proteases of the Bacillus species. Despite a large amount of information on microbial proteases, a search for novel proteases with unique properties is still of interest for both basic and applied aspects of this highly complex class of enzymes. Oxidant stable proteases (OSPs have been shown to have a wide application in the detergent and bleaching industries and recently have become one of the most attractive enzymes in various biotechnological applications. Results A gene encoding a novel member of the subtilase superfamily was isolated from Virgibacillus sp. SK37, a protease-producing bacterium isolated from Thai fish sauce fermentation. The gene was cloned by an activity-based screening of a genomic DNA expression library on Luria-Bertani (LB agar plates containing 1 mM IPTG and 3% skim milk. Of the 100,000 clones screened, all six isolated positive clones comprised one overlapping open reading frame of 45% identity to the aprX gene from Bacillus species. This gene, designated aprX-sk37 was cloned into pET21d(+ and over-expressed in E. coli BL21(DE3. The enzyme product, designated AprX-SK37, was purified by an immobilized metal ion affinity chromatography to apparent homogeneity and characterized. The AprX-SK37 enzyme showed optimal catalytic conditions at pH 9.5 and 55°C, based on the azocasein assay containing 5 mM CaCl2. Maximum catalytic activity was found at 1 M NaCl with residual activity of 30% at 3 M NaCl. Thermal stability of the enzyme was also enhanced by 1 M NaCl. The enzyme was absolutely calcium-dependent, with optimal concentration of CaCl2 at 15 mM. Inhibitory effects by phenylmethanesulfonyl fluoride and ethylenediaminetetraacetic acid indicated that this enzyme is a metal-dependent serine protease. The enzyme activity was sensitive towards reducing agents

Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells

NARCIS (Netherlands)

M. Roemeling-Van Rhijn (Marieke); F.K.F. Mensah (Fane ); S.S. Korevaar (Sander); M.J.C. Leijs (Maarten J.C.); G.J.V.M. van Osch (Gerjo); J.N.M. IJzermans (Jan); M.G.H. Betjes (Michiel); C.C. Baan (Carla); W. Weimar (Willem); M.J. Hoogduijn (Martin)

2013-01-01

textabstractAdipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

OpenAIRE

Heyes, Richard; Iarocci, Andrew; Tchoukalova, Yourka; Lott, David G.

2016-01-01

This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human popul...

Sweet whey as a raw material for the dietary supplements obtaining with immunomodulatory effect

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G. Didukh

2017-06-01

Full Text Available This article presents the results of the study of literary sources to prove the viability of the idea of using sweet whey to deep its fractionation, and to obtain biologically active proteins with immunomodulatory effect. We demonstrated methods for fractionation of milk whey (membrane and chromatographic, as well as the technological scheme of concentration of sweet whey. We introduced the composition of sweet whey and protein content of immunomodulatory action. Modern methods of processing whey, which include, basically, only the process of dehydration and concentration of whey and its use in the complete component composition, which limits its use for food purposes are shown. The necessity of processing of secondary resources in a catastrophic ecological situation on the planet and full use of the composite processing of raw materials for food purposes, and also shows properties of proteins immunomodulating actions which are part of the whey are grounded.

Reflection seismic studies over the end-glacial Burträsk fault, Skellefteå, Sweden

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C. Juhlin

2011-01-01

Full Text Available Reflection seismic data were acquired along a ca. 22 km long profile over the end-glacial Burträsk fault with a nominal receiver and source spacing of 20 m. A steeply dipping reflection can be correlated to the Burträsk fault, indicating that the fault dips at about 55° to the southeast near the surface. The reflection from the fault is rather poorly imaged, probably due to a lateral offset in the fault of about 1 km at this location and the crookedness of the seismic profile in the vicinity of the fault. A more pronounced steeply dipping reflection is observed about 4 km southeast of the Burträsk fault. Based on its correlation with a topographic low at the surface this reflection is interpreted to originate from a fracture zone. There are no signs of large displacements along this zone as the glacial ice receded, but earthquakes could be associated with it today. Other reflections on the processed seismic section may originate from changes in lithological variations in the supra-crustal rocks or from intrusions of more mafic rock. Constraints on the fault geometry provided by the reflection seismic data will help determine what stresses were required to activate the fault when the major rupture along it occurred ca. 9500 years ago.

Preventive and therapeutic effects of SkQ1-containing Visomitin eye drops against light-induced retinal degeneration.

Science.gov (United States)

Novikova, Yu P; Gancharova, O S; Eichler, O V; Philippov, P P; Grigoryan, E N

2014-10-01

The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.

Anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology

OpenAIRE

Swetalina Pradhan; Bhushan Madke; Poonam Kabra; Adarsh Lata Singh

2016-01-01

Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. ...

Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

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Mariana P. Miranda-Hernández

2015-01-01

Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

Comparison of the Immunomodulatory Properties of Root and Leaves of Arctium Lappa (Burdock in Vitro

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Hasan Namdar Ahmadabad

2017-10-01

Full Text Available Background: The roots and leaves of Arctium lappa (burdock have been used for different therapeutic purposes, especially for diseases linked to chronic inflammation. Objectives: The present study was designed to evaluate and compare the immunomodulatory activities of root extract of burdock and leaves extract of burdock in vitro. Methods: In this experimental study, PHA- or LPS-stimulated splenocytes were treated with different concentrations of root or leaves extract of burdock and proliferation of splenocytes measured by MTT assay. The levels of IFN-γ and IL4 in the supernatants of PHA-stimulated splenocytes determined using ELISA. We also studied the effects of root and leaves extract of burdock on Nitric Oxide production by LPS-stimulated macrophages using the Griess reagent. The data were analyzed by one-way ANOVA followed by Tukey’s post-test using GraphPad Prism software, version 5.0. Results: Our findings showed that both root and leaves extract of burdock have suppressive effects on LPS-stimulated splenocytes proliferation, IL-4 secretion from PHA-stimulated splenocytes, and NO production from LPS-stimulated macrophage and stimulatory effects on PHA-stimulated splenocytes proliferation, and IFN-γ secretion from PHA-stimulated splenocytes. Although both root and leaves extract of burdock had similar immunomodulatory effects in vitro, stronger immunomodulatory effects seen in root extract of burdock. Conclusions: According to our results, we suggest that root of burdock is better option than leaves of burdock in modulation immune responses and inflammations.

Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

Science.gov (United States)

Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

2017-08-16

NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

Science.gov (United States)

Morton, Laura Dill; Spindeldreher, Sebastian; Kiessling, Andrea; Allenspach, Roy; Hey, Adam; Muller, Patrick Y; Frings, Werner; Sims, Jennifer

2010-01-01

Most therapeutic monoclonal antibodies (mAbs) licensed for human use or in clinical development are indicated for treatment of patients with cancer and inflammatory/autoimmune disease and as such, are designed to directly interact with the immune system. A major hurdle for the development and early clinical investigation of many of these immunomodulatory mAbs is their inherent risk for adverse immune-mediated drug reactions in humans such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the immunopharmacology of a mAb in humans and animals is required to both anticipate the clinical risk of adverse immunotoxicological events and to select a safe starting dose for first-in-human (FIH) clinical studies. This review summarizes the most common adverse immunotoxicological events occurring in humans with immunomodulatory mAbs and outlines non-clinical strategies to define their immunopharmacology and assess their immunotoxic potential, as well as reduce the risk of immunotoxicity through rational mAb design. Tests to assess the relative risk of mAb candidates for cytokine release syndrome, innate immune system (dendritic cell) activation and immunogenicity in humans are also described. The importance of selecting a relevant and sensitive toxicity species for human safety assessment in which the immunopharmacology of the mAb is similar to that expected in humans is highlighted, as is the importance of understanding the limitations of the species selected for human safety assessment and supplementation of in vivo safety assessment with appropriate in vitro human assays. A tiered approach to assess effects on immune status, immune function and risk of infection and cancer, governed by the mechanism of action and structural features of the mAb, is described. Finally, the use of immunopharmacology and immunotoxicity data in determining a minimum anticipated biologic effect Level (MABEL) and in the selection of safe human

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

Science.gov (United States)

Owen, David; Töpf, Ana; Preethish-Kumar, Veeramani; Lorenzoni, Paulo José; Vroling, Bas; Scola, Rosana Herminia; Dias-Tosta, Elza; Geraldo, Argemiro; Polavarapu, Kiran; Nashi, Saraswati; Cox, Daniel; Evangelista, Teresinha; Dawson, John; Thompson, Rachel; Senderek, Jan; Laurie, Steven; Beltran, Sergi; Gut, Marta; Gut, Ivo; Nalini, Atchayaram; Lochmüller, Hanns

2018-04-28

Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS. © 2018 Wiley Periodicals, Inc.

Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

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Belén Climent

Full Text Available Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals.In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR compared to Lean Zucker Rats (LZR. Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer.Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.

Antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from Sterculia villosa.

Science.gov (United States)

Das, Antu; Jawed, Junaid Jibran; Das, Manash C; Sandhu, Padmani; De, Utpal C; Dinda, Biswanath; Akhter, Yusuf; Bhattacharjee, Surajit

2017-10-01

Visceral leishmaniasis (VL) is one of the most severe forms of leishmaniasis, caused by the protozoan parasite Leishmania donovani. Nowadays there is a growing interest in the therapeutic use of natural products to treat parasitic diseases. Sterculia villosa is an ethnomedicinally important plant. A triterpenoid was isolated from this plant and was screened for its antileishmanial and immunomodulatory activities in vitro and in vivo. Biochemical colour test and spectroscopic data confirmed that the isolated pure compound was lupeol. Lupeol exhibited significant antileishmanial activity, with IC 50 values of 65 ± 0.41 µg/mL and 15 ± 0.45 µg/mL against promastigote and amastigote forms, respectively. Lupeol caused maximum cytoplasmic membrane damage of L. donovani promastigote at its IC 50 dose. It is well known that during infection the Leishmania parasite exerts its pathogenicity in the host by suppressing nitric oxide (NO) production and inhibiting pro-inflammatory responses. It was observed that lupeol induces NO generation in L. donovani-infected macrophages, followed by upregulation of pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. Lupeol was also found to reduce the hepatic and splenic parasite burden through upregulation of the pro-inflammatory response in L. donovani-infected BALB/c mice. Strong binding affinity of lupeol was observed for four major potential drug targets, namely pteridine reductase 1, adenine phosphoribosyltransferase, lipophosphoglycan biosynthetic protein and glycoprotein 63 of L. donovani, which also supported its antileishmanial and immunomodulatory activities. Therefore, the present study highlights the antileishmanial and immunomodulatory activities of lupeol in an in vitro and in vivo model of VL. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Antibacterial, Antiproliferative, and Immunomodulatory Activity of Silver Nanoparticles Synthesized with Fucans from the Alga Dictyota mertensii

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Marília Medeiros Fernandes-Negreiros

2017-12-01

Full Text Available In this study, we aimed to synthesize silver nanoparticles containing fucans from Dictyota mertensii (Martius Kützing using an environmentally friendly method and to characterize their structure as well as antiproliferative, immunomodulatory, and antibacterial effects. Fucan-coated silver nanoparticles (FN were characterized by Fourier-transform infrared analysis, dynamic light scattering, zeta potential, atomic force microscopy, energy dispersive X-ray spectroscopy, and inductively coupled plasma emission spectrometry. They were evaluated for their effect on cell viability, minimum inhibitory bactericidal concentration, and release of nitric oxide and cytokines. The FN were successfully synthesized using an environmentally friendly method. They were size-stable for 16 months, of a spherical shape, negative charge (−19.1 mV, and an average size of 103.3 ± 43 nm. They were able to inhibit the proliferation of the melanoma tumor cell line B16F10 (60%. In addition, they had immunomodulatory properties: they caused an up to 7000-fold increase in the release of nitric oxide and cytokines (IL-10; IL-6 and TNF-α up to 7000 times. In addition, the FN showed inhibitory effect on Gram-positive and -negative bacteria, with MIC values of 50 µg/mL. Overall, the data showed that FN are nanoparticles with the potential to be used as antitumor, immunomodulatory, and antibacterial agents.

Identification of Bioactive Agents and Immunomodulatory Factors from Seashells of the Persian Gulf

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Arezoo Najafi

2010-09-01

Full Text Available Background: Research in marine pharmacology will promise new bioactive agents. The marine bioenvironment is the unique resource for bioactive agents that could not be found in terrestrial organisms. Methods: A total of known 611 seashells species in the Persian Gulf were investigated for synonymy in OBIS database. Then, all the species, including their synonymy were searched in PubMed database to find their isolated bioactive agents. Results: From 611 known seashells in the Persian Gulf, 172 genera/species had bioactive compounds. Bioactive agents were isolated and purified for 16 genera/ species. The crude or purified extracts from these seashells had immunomodulatory effects (6 seashells, anti-toxicologic effects (4 seashells, analgesic (1 seashell, cardiotonic and vasoactive agents (2 seashells, hypolipidemic agents (4 seashells, anti-osteoporotic and osteoblastic agents (2 seashells and anti-dermatitis effect (1 seashell. Conclusion: The known seashells from the Persian Gulf have bioactive and immunomodulatory compounds and increase in the efforts to isolate these agents will promise a treasure for novel anti-infective agents.

The immunomodulatory effects of laparoscopic surgery.

LENUS (Irish Health Repository)

Corrigan, Mark

2012-02-03

Laparoscopic alternatives to conventional surgical procedures confer many advantages to patients including reduced postoperative pain, shortened convalescence and, perhaps, improved disease-related outcomes. The diminished degree of immune dysfunction apparent with these techniques may underpin these beneficial aspects. However, minimal access is accompanied by various ancillary anesthetic and mechanical associations (including the induction of a carbon dioxide pneumoperitoneum), which must be considered in addition to reduced tissue trauma when attempting to correlate cause with effect. Furthermore, the opportunity to establish causation between the immunomodulatory aspects of laparoscopy and subsequent clinical outcome by prospective, randomized study is difficult because of the rapid incorporation of minimal access techniques into clinical practice. Therefore, experimental in vitro and in vivo studies must be used to complement the limitations of clinical studies in this area. Although the initial investigations into the immunological effects of laparoscopy are encouraging, many of the intricacies associated with this approach still await elaboration.

Býčí skála Cave, Czech Republic: Radiocarbon dates of rock paintings

Czech Academy of Sciences Publication Activity Database

Svoboda, Jiří; van der Plicht, H.; Balák, I.

2005-01-01

Roč. 43, - (2005), s. 7-9 ISSN 1022-3282 Institutional research plan: CEZ:AV0Z80010507 Keywords : Býčí skála Czech Republic * rock art * radiocarbon dating Subject RIV: AC - Archeology, Anthropology, Ethnology

L-Glutamine in vitro Modulates some Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells.

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Dos Santos, Guilherme Galvão; Hastreiter, Araceli Aparecida; Sartori, Talita; Borelli, Primavera; Fock, Ricardo Ambrósio

2017-08-01

Glutamine (GLUT) is a nonessential amino acid that can become conditionally essential under stress conditions, being able to act in the modulation of the immune responses. Mesenchymal stem cells (MSCs) are known to their capability in the modulation of immune responses through cell-cell contact and by the secretion of soluble factors. Considering that GLUT is an immunonutrient and little is known about the influence of GLUT on the capability of MSCs to modulate immune cells, this work aims to investigate how variations in GLUT concentrations in vitro could affect some immunomodulatory properties of MSCs. In order to evaluate the effects of GLUT on MSCs immunomodulatory properties, cell proliferation rates, the expression of NFκB and STAT-3, and the production of IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. Based on our findings, GLUT at high doses (10 mM) augmented the proliferation of MSCs and modulated immune responses by decreasing levels of pro-inflammatory cytokines, such as IL-1β and IL-6, and by increasing levels of anti-inflammatory cytokines IL-10 and TGF-β. In addition, MSCs cultured in higher GLUT concentrations (10 mM) expressed lower levels of NF-κB and higher levels of STAT-3. Furthermore, conditioned media from MSCs cultured at higher GLUT concentrations (10 mM) reduced lymphocyte and macrophage proliferation, increased IL-10 production by both cells types, and decreased IFN-γ production by lymphocytes. Overall, this study showed that 10 mM of GLUT is able to modify immunomodulatory properties of MSCs.

Isolation and Characterization of Exopolysaccharide with Immunomodulatory Activity from Fermentation Broth of Morchella Conica

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Chao-an Su

2013-01-01

Full Text Available Background and the purpose of this study: Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. In vitro and in vivo studies suggest that certain polysaccharides affect immune system function. Morchella conica (M. conica is a species of rare edible mushroom whose multiple medicinal functions have been proven. Thus, the objective of this study is to isolate and characterize of exopolysaccharide from submerged mycelial culture of M. conica, and to evaluate its immunomodulatory activity.MethodsA water-soluble Morchella conica Polysaccharides (MCP were extracted and isolated from the fermentation broth of M. conica through a combination of DEAE-cellulose and Sephacryl S-300 HR chromatograph. NMR and IR spectroscopy has played a developing role in identification of polysaccharide with different structure and composition from fungal and plant sources, as well as complex glycosaminoglycans of animal origin. Thus, NMR and IR spectroscopy were used to analyze the chemical structure and composition of the isolated polysaccharide. Moreover, the polysaccharide was tested for its immunomodulatory activity at different concentrations using in vitro model.ResultsThe results showed that MCP may significantly modulate nitric oxide production in macrophages, and promote splenocytes proliferation. Analysis from HPLC, infrared spectra and nuclear magnetic resonance spectroscopy showed that MCP was a homogeneous mannan with an average molecular weight of approximately 81.2 kDa. The glycosidic bond links is [rightwards arrow]6-alpha-D-Man p-(1[rightwards arrow].ConclusionThe results suggested that the extracted MCP may modulate nitric oxide production in macrophages and promote splenocytes proliferation, and it may act as a potent immunomodulatory agent.

Therapeutic Potential of HDPs as Immunomodulatory Agents

DEFF Research Database (Denmark)

Jenssen, Håvard; Hancock, Robert E.W.

2010-01-01

One of the most significant advances in medical history is the discovery and development of antibiotics, which in the middle of last century was flourishing and appeared to be the ultimate solution to the treatment of life-threatening human bacterial diseases. However, lately there has been a huge...... decline in the rate of discovery of new antimicrobial intervention strategies in parallel with an increasing incidence of multidrug-resistant pathogens; if these circumstances do not change we will continue to approach the end of the antibiotic era. Facing this dark future, scientists are considering new...... strategies for intervention tailored around the appropriate (selective) stimulation of the host’s immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One recent player in such an immunomodulatory strategy is the naturally occurring host...

Phytochemical, chromatographic and spectroscopic investigation of Carum copticum seeds and their potential as immunomodulatory agents.

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Sonar, Pankaj K; Singh, Ranjit; Saraf, Shailendra K

2016-01-01

Carum copticum seeds have been prescribed in the traditional system of medicine for the treatment of immune disorders, such as asthma and rheumatism. The objective of this study was to determine immunomodulatory effects of the alcoholic extract and isolated compounds in Swiss albino mice. Seeds of C. copticum were extracted with 95% v/v alcohol. The immunomodulatory activity of the crude extract was evaluated at the doses of 100, 300, and 500 mg/kg body weight of mice, administered in mice once daily (orally) for 25 days. Volatile oil of C. copticum was isolated by steam distillation and was characterized by GLC and HPLC. Bio-assay-guided fractionation and isolation were carried out and the isolated compounds were characterized and subjected to immunomodulatory activity studies. The n-hexane fraction yielded p-cymene, carvacrol, and α-pinene. The LD50 value of the crude extract was found to be 4500 mg/kg and the values reported for p-cymene, carvacrol, and α-pinene in the literature were 4750, 810, and 3700 mg/kg, respectively. The oral administration of crude extract, n-hexane fraction (HEF), and isolated oils at the dose of 500, 150, and 50 mg/kg body weight, respectively, showed a significant increase in the HA titers, DTH-response, and phagocytosis. The stimulatory effect observed, on humoral and cellular immunity, was compared with the standard (levamisole treated) and control groups. The results obtained in the study endorse the traditional use of the seeds of C. copticum and the isolated constituents act as immunostimulants.

[N-methyl-D-aspartate receptor antibody encephalitis: value of immunomodulatory therapy].

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Le Moigno, L; Ternant, D; Paintaud, G; Thibault, G; Cloarec, S; Tardieu, M; Lagrue, E; Castelnau, P

2014-06-01

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology. We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool. Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides

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van Dijk, Albert; van Eldik, Mandy; Veldhuizen, Edwin J. A.; Tjeerdsma-van Bokhoven, Hanne L. M.; de Zoete, Marcel R.; Bikker, Floris J.; Haagsman, Henk P.

2016-01-01

Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives. PMID:26848845

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.

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Albert van Dijk

Full Text Available Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11 we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS. N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives.

Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

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Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

2016-01-15

Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

The 5K70SK automatically tuned, high power, S-band klystron

Science.gov (United States)

Goldfinger, A.

1977-01-01

Primary objectives include delivery of 44 5K70SK klystron amplifier tubes and 26 remote tuner assemblies with spare parts kits. Results of a reliability demonstration on a klystron test cavity are discussed, along with reliability tests performed on a remote tuning unit. Production problems and one design modification are reported and discussed. Results of PAT and DVT are included.

Immunomodulatory response of mice splenocytes induced by RcaL, a lectin isolated from cobia fish (Rachycentron canadum) serum.

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Coriolano, Marília Cavalcanti; Silva, Cynarha Daysy Cardoso da; Melo, Cristiane Moutinho Lagos de; Bezerra, Ranilson de Souza; Santos, Athiê Jorge Guerra; Pereira, Valéria Rêgo Alves; Coelho, Luana Cassandra Breitenbach Barroso

2012-11-01

This work reports the isolation of a serum lectin from cobia fish (Rachycentron canadum) named RcaL. Immunomodulatory activity on mice splenocyte experimental cultures through cytotoxic assays and cytokine production were also performed. RcaL was obtained through precipitation with ammonium sulphate and affinity chromatography on a Concanavalin A-Sepharose 4B column. The ammonium sulphate fraction F3 showed the highest specific hemagglutinating activity and was applied to affinity chromatography. The lectin was eluted with methyl-α-D-mannopyranoside. RcaL showed highest affinity for methyl-α-D-mannopyranoside and D-mannose; eluted fractions of RcaL agglutinated rabbit erythrocytes (titre, 128(-1)) retained 66 % of chromatographed lectin activity, and the obtained purification factor was 1.14. Under reducing conditions, a polypeptide band of 19.2 kDa was revealed in sodium dodecyl sulphate polyacrylamide gel electrophoresis (PAGE). PAGE confirmed RcaL as an acidic protein revealed in a single band. Cytotoxic and immunomodulatory assays with RcaL in mice splenocyte cultures showed that the lectin was not cytotoxic and induced higher interferon gamma and nitric oxide production in splenocyte cultures. Purified RcaL induced preferential Th1 response, suggesting that it acts as an immunomodulatory compound.

In vivo screening of five phytochemicals/extracts and a fungal immunomodulatory protein against colibacillosis in broilers

NARCIS (Netherlands)

Peek, H.W.; Halkes, S.B.A.; Tomassen, M.M.M.; Mes, J.J.; Landman, W.J.M.

2013-01-01

Five phytochemicals/extracts (an extract from Echinacea purpurea, a ß-glucan-rich extract from Shiitake, betaine [Betain™], curcumin from Curcuma longa [turmeric] powder, carvacrol and also a recombinant fungal immunomodulatory protein [FIP] from Ganoderma lucidum) cloned and expressed in

Food truck som ett nytt fenomen i Skåne

OpenAIRE

Fromell, Hilda; Winter, Regina

2016-01-01

Food truck is a mobile restaurant business which originates from the United States, and can now be seen also in Sweden. There are specific guidelines regarding the food that are served from the food trucks rolling the streets of Skåne from 2013. For example the food should be ecological, which is in keeping with the other municipal goals regarding food and meal. The concept is communicated and marketed through social media, which makes it possible to effectively reach many people. Four food t...

Immunomodulatory Properties of Carvone Inhalation and Its Effects on Contextual Fear Memory in Mice

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Lasarte-Cia, Aritz; Lozano, Teresa; Pérez-González, Marta; Gorraiz, Marta; Iribarren, Kristina; Hervás-Stubbs, Sandra; Sarobe, Pablo; Rabal, Obdulia; Cuadrado-Tejedor, Mar; García-Osta, Ana; Casares, Noelia; Lasarte, Juan José

2018-01-01

A complex network of interactions exists between the immune, the olfactory, and the central nervous system (CNS). Inhalation of different fragrances can affect immunological reactions in response to an antigen but also may have effects on the CNS and cognitive activity. We performed an exploratory study of the immunomodulatory ability of a series of compounds representing each of the 10 odor categories or clusters described previously. We evaluated the impact of each particular odor on the immune response after immunization with the model antigen ovalbumin in combination with the TLR3 agonist poly I:C. We found that some odors behave as immunostimulatory agents, whereas others might be considered as potential immunosuppressant odors. Interestingly, the immunomodulatory capacity was, in some cases, strain-specific. In particular, one of the fragrances, carvone, was found to be immunostimulatory in BALB/c mice and immunosuppressive in C57BL/6J mice, facilitating or impairing viral clearance, respectively, in a model of a viral infection with a recombinant adenovirus. Importantly, inhalation of the odor improved the memory capacity in BALB/c mice in a fear-conditioning test, while it impaired this same capacity in C57BL/6J mice. The improvement in memory capacity in BALB/c was associated with higher CD3+ T cell infiltration into the hippocampus and increased local expression of mRNA coding for IL-1β, TNF-α, and IL-6 cytokines. In contrast, the memory impairment in C57BL/6 was associated with a reduction in CD3 numbers and an increase in IFN-γ. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals. These results highlight the potential of studying odors as therapeutic agents for CNS-related diseases. PMID:29422905

Evaluation of the immunomodulatory and DNA protective activities of the shoots of Cynodon dactylon.

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Mangathayaru, K; Umadevi, M; Reddy, C Umamaheswara

2009-05-04

Fresh juice of Cyanodon dactylon known as 'durva' grass is employed in India as a rejuvenator and for wound healing. To validate the traditional use of the herb through evaluation of DNA protective activity in vitro and immunomodulatory activity in vivo. Fresh juice of the grass was prepared as indicated for use in traditional medicine and standardized for solid content. Its total phenol content was estimated by Folin-Ciocalteau method. Freshly prepared juice was investigated for its effect on doxorubicin-induced DNA damage in vitro. Its immunomodulatory activity was tested on balb/c mice by the humoral antibody response which was determined by haemagglutination antibody titer and spleen cell assay. Fresh juice of Cyanodon dactylon of 1.46% (w/w) solid content had a phenolic content of 47+/-0.33 mg/kg GAE. At doses equivalent to 50, 100 and 200mg total solids/kg body weight the juice protected human DNA against doxorubicin-induced DNA damage as demonstrated in DNA spectral studies, where the ratio of absorbance of DNA at 260 and 280 nm in samples pretreated with the juice was 1.66, 1.53 and 1.63 respectively, while it was 1.37 for DNA treated with doxorubicin only. This indicates nucleic acid purity in the Cynodon dactylon treated samples. Oral administration of the juice at 250 and 500 mg/kg in balb/c mice increased humoral antibody response upon antigen challenge, as evidenced by a dose-dependent, statistically significant increase in antibody titer in the haemagglutination antibody assay and plaque forming cell assay. The present report demonstrated the DNA protective activity and immunomodulatory property of the fresh juice of Cynodon dactylon validating the traditional use of the herb as a 'rasayana' in ayurvedic system of medicine.

Immunomodulatory properties of fermented soy and dairy milks prepared with lactic acid bacteria.

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Wagar, L E; Champagne, C P; Buckley, N D; Raymond, Y; Green-Johnson, J M

2009-10-01

Fermented soy and dairy milk preparations provide a means for delivering lactic acid bacteria and their fermentation products into the diet. Our aims were to test immunomodulatory bioactivity of fermented soy beverage (SB) and dairy milk blend (MB) preparations on human intestinal epithelial cells (IEC) and to determine the impact of freezing medium on culture survival prior to bioactivity analyses. Fermented SB and MB were prepared using pure or mixed cultures of Streptococcus thermophilus ST5, Bifidobacterium longum R0175, and Lactobacillus helveticus R0052. Immunomodulatory bioactivity was assessed by testing selected SB and MB ferments on tumor necrosis factor alpha (TNFalpha)-treated IEC and measuring effects on Interleukin-8 (IL-8) production. Impact of timing of ferment administration relative to this pro-inflammatory challenge was investigated. The most pronounced reductions in IEC IL-8 production were observed when IEC were treated with either SB or MB ferment preparations prior to TNFalpha challenge. These results indicate that freezing-stable MB and SB ferments prepared with selected strains can modulate IEC IL-8 production in vitro, and suggest that yogurt-like fermented soy formulations could provide a functional food alternative to milk-based fermented products.

Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity

NARCIS (Netherlands)

Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone|info:eu-repo/dai/nl/311474683; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin

Assessment of immunomodulatory activity of aqueous extract of Calamus rotang

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Amit Gupta

2017-04-01

Full Text Available Objective: There are a number of medicinal plant products which has been used to treat various immunological diseases. Out of these medicinal plants, Calamus rotang has shown several medicinal properties including anti-viral, anti-diabetic, anti-inflammatory effects. Normally, the roots of C. rotang are used in various ailments to cure piles, burning sensation, cough, leprosy and bleeding disorder and also it was used in the treatment of inflammation. In the present study, our group were investigated the immunomodulatory activity of aqueous extract of C. rotang root in human whole blood and peripheral blood mononuclear cells (PBMC using hepatitis B vaccine (HBsAg as an antigen. Materials and Methods: Variable doses of root aqueous extract (0.5 – 30 mg/ml, 100 µl was administered to human whole blood and PBMC using hepatitis B vaccine containing surface antigen (HBsAg; 20 µg/ml, 10 µl as specific antigen in order to estimate the total blood counts in human whole blood and nitric oxide production and CD14 FITC surface marker from human PBMC. Results: Overall, the results showed that roots aqueous extract of C. rotang showed remarkable increase in the number of blood counts in human whole blood at lower doses (0.5 mg/ml. In addition, root aqueous extract of C. rotang also showed the same pattern in case of nitric oxide production and estimation of CD14 FITC surface marker in human PBMC. Conclusion: Altogether, the results suggest that root aqueous extract of C. rotang showed immunomodulatory activity.

SCREENING OF PHYTOCHEMICALS AND IMMUNOMODULATORY POTENTIAL OF A MEDICINAL PLANT, CINNAMOMUM TAMALA

OpenAIRE

P. Jeyasree* and P. Dasarathan

2012-01-01

Cinnamomum tamala is found in tropical and sub-tropical Himalayas and in some other places. Phytochemical screening of the plant extracts were done to screen their active constituents. Antimicrobial activity of this plant extract was investigated by Kirby-Bayer methodology against four pathogenic organisms: K. Pneumonae,E. coli, S. aureus, and P.aeroginosa. The plant Butanol extract showed inhibitory activity against all the tested organisms and it has enhanced immunomodulatory activity also....

BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways.

Science.gov (United States)

Ren, Wei; Liu, Yuehong; Wan, Shaoheng; Fei, Chang; Wang, Wei; Chen, Yingying; Zhang, Zhihui; Wang, Ting; Wang, Jinshu; Zhou, Lan; Weng, Yaguang; He, Tongchuan; Zhang, Yan

2014-01-01

Bone morphogenetic protein 9 (BMP9), a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-regulated expression. Results indicated that exogenously expressed BMP9 inhibited the proliferation and metastasis of SK-BR-3 cells while decreased endogenous BMP9 expression in SK-BR-3 cells promoted the proliferation and migration of breast cancer cells in vitro and in vivo. In SK-BR-3 cells with BMP9 over-expression, the phosphorylation of HER2, ERK1/2 and AKT was markedly suppressed and the HER2 expression decreased at both mRNA and protein levels, while opposite results were observed in SK-BR-3 cells with BMP9 knock down. When the phosphorylation of ERK1/2 and PI3K/AKT was inhibited by PD98059 and LY294002, respectively, the decreased proliferation and invasion induced by BMP9 knock down were eliminated. These findings suggest that BMP9 can inhibit the proliferation and metastasis of SK-BR-3 cells via inactivating ERK1/2 and PI3K/AKT signaling pathways. Thus, BMP9 may serve as a useful agent in the treatment of HER-2 positive breast cancer.

A dehydrin-dehydrin interaction: the case of SK3 from Opuntia streptacantha

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Itzell eHernandez

2014-10-01

Full Text Available Dehydrins belongs to a large group of highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA proteins. It is well know that dehydrins are intrinsically disordered plant proteins that accumulate during the late stages of embryogenesis and in response to abiotic stresses; however, the molecular mechanisms by which their functions are carried out are still unclear. We have previously reported that transgenic Arabidopsis plants overexpressing an Opuntia streptacantha SK3 dehydrin (OpsDHN1 show enhanced tolerance to freezing stress. Herein, we show using a split-ubiquitin yeast two-hybrid system that OpsDHN1 dimerizes. We found that the deletion of regions containing K-segments and the histidine-rich region in the OpsDHN1 protein affects dimer formation. Not surprisingly, in silico protein sequence analysis suggests that OpsDHN1 is an intrinsically disordered protein, an observation that was confirmed by circular dichroism and gel filtration of the recombinantly expressed protein. The addition of zinc triggered the association of recombinantly expressed OpsDHN1 protein, likely through its histidine-rich motif. These data brings new insights about the molecular mechanism of the OpsDHN1 SK3-dehydrin

PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

International Nuclear Information System (INIS)

Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R.; Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D.; Huang, K.; Urata, Y.; Mulchaey, J. S.

2013-01-01

We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 × 10 3 km s –1 ) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt ∼ 9-23 days and shows an NUV-NIR spectral energy distribution with temperature ∼> 17 × 10 3 K and a peak magnitude of M z = –18.88 ± 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M ☉ ) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208–042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits (Σ Hα ∼ –3 M ☉ yr –1 kpc –2 ). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts

Science.gov (United States)

Wang, Qi; Clarkson, Christina; Graham, Melanie; Donahue, Robert; Hering, Bernhard J.; Verfaillie, Catherine M.; Bansal-Pakala, Pratima; O'Brien, Timothy D.

2015-01-01

Background Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported. Methods We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. Results and Conclusions Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable. PMID:24825538

Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

Directory of Open Access Journals (Sweden)

Anton M Markovets

Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

Novel immunomodulatory effects of adiponectin on dendritic cell functions.

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Tsang, Julia Yuen Shan; Li, Daxu; Ho, Derek; Peng, Jiao; Xu, Aimin; Lamb, Jonathan; Chen, Yan; Tam, Paul Kwong Hang

2011-05-01

Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

Immunomodulatory dietary polysaccharides: a systematic review of the literature

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Nelson Erika D

2010-11-01

Full Text Available Abstract Background A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides. Methods Studies were identified by conducting PubMed and Google Scholar electronic searches and through reviews of polysaccharide article bibliographies. Only articles published in English were included in this review. Two researchers reviewed data on study design, control, sample size, results, and nature of outcome measures. Subsequent searches were conducted to gather information about polysaccharide safety, structure and composition, and disposition. Results We found 62 publications reporting statistically significant effects of orally ingested glucans, pectins, heteroglycans, glucomannans, fucoidans, galactomannans, arabinogalactans and mixed polysaccharide products in rodents. Fifteen controlled human studies reported that oral glucans, arabinogalactans, heteroglycans, and fucoidans exerted significant effects. Although some studies investigated anti-inflammatory effects, most studies investigated the ability of oral polysaccharides to stimulate the immune system. These studies, as well as safety and toxicity studies, suggest that these polysaccharide products appear to be largely well-tolerated. Conclusions Taken as a whole, the oral polysaccharide literature is highly heterogenous and is not sufficient to support broad product structure/function generalizations. Numerous dietary polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in numerous animal tissues, including the blood, GI tract and spleen. Glucan extracts from the Trametes versicolor

Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis.

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Velazquez-Villoria, D; Macia-Badia, C; Segura-García, A; Pastor Idoate, S; Arcos-Algaba, G; Velez-Escola, L; García-Arumí, J

2017-06-01

To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. Interferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Analysis of antimicrobial and immunomodulatory substances produced by heterofermentative Lactobacillus reuteri.

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Greifová, Gabriela; Májeková, Hyacinta; Greif, Gabriel; Body, Patrik; Greifová, Maria; Dubničková, Martina

2017-11-01

Antimicrobial and immunomodulatory potential of various Lactobacillus reuteri strains is closely connected to their metabolite production profile under given cultivation conditions. We determined the in vitro production of antimicrobial substances such as organic acids, ethanol, and reuterin by four strains of L. reuteri (L. reuteri E, L. reuteri KO5, L. reuteri CCM 3625, and L. reuteri ATCC 55730). All studied L. reuteri strains showed the ability to produce lactic acid, acetic acid, and ethanol with concominant consumption of glucose and together with phenyllactic acid-a potent antifungal compound-with concominant consumption of phenylalanine. The reuterin production from glycerol was confirmed for all analyzed lactobacilli strains except L. reuteri CCM 3625. Production of organic acids, ethanol, and reuterin is significantly involved in antimicrobial activity of lactobacilli which was determined using the dual-culture overlay diffusion method against six indicator bacteria and five indicator moulds. In comparison to the referential L. reuteri ATCC 55730, the highest inhibition potential was observed against Escherichia coli CCM 3988 and Pseudomonas aeruginosa CCM 3955. Among analyzed indicators of moulds, the growth of Alternaria alternata CCM F-128 was the most inhibited by all four analyzed L. reuteri strains. Finally, the immunomodulatory potential of analyzed lactobacilli were proven by the determination of the in vitro production of biogenic amines histamine and tyramine. L. reuteri CCM 3625 was able to produce tyramine, and L. reuteri E and L. reuteri KO5 were able to produce histamine under given cultivation conditions.

Immunomodulatory effects of intravenous bis-1 f(ab')(2) administration in renal-cell cancer-patients

NARCIS (Netherlands)

Janssen, R. A. J.; Kroesen, B. J.; Mesander, G.; Sleijfer, D. T.; The, T. Hauw; Mulder, N. H.; de Leij, L

We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

Constant envelope OFDM scheme for 6PolSK-QPSK

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Li, Yupeng; Ding, Ding

2018-03-01

A constant envelope OFDM scheme with phase modulator (PM-CE-OFDM) for 6PolSK-QPSK modulation was demonstrated. Performance under large fiber launch power is measured to check its advantages in counteracting fiber nonlinear impairments. In our simulation, PM-CE-OFDM, RF-assisted constant envelope OFDM (RF-CE-OFDM) and conventional OFDM (Con-OFDM) are transmitted through 80 km standard single mode fiber (SSMF) single channel and WDM system. Simulation results confirm that PM-CE-OFDM has best performance in resisting fiber nonlinearity. In addition, benefiting from the simple system structure, the complexity and cost of PM-CE-OFDM system could be reduced effectively.

Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

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Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-01-01

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121

Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

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Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-02-03

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.

Býčí skála: prvé datování skalních maleb

Czech Academy of Sciences Publication Activity Database

Svoboda, Jiří; Plicht van der, J.; Balák, I.

2005-01-01

Roč. 84, - (2005), s. 574-575 ISSN 0042-4544 Institutional research plan: CEZ:AV0Z80010507 Keywords : Býčí skála * rock art * radiocarbon dating Subject RIV: AC - Archeology, Anthropology, Ethnology

An evolutionary perspective on the immunomodulatory role of hydrogen sulphide.

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Rivers-Auty, J

2015-11-01

Most preclinical studies on endogenous hydrogen sulphide signalling have given little consideration to the fact that the human body contains more bacterial cells than human cells, and that evolution provides the context for all biology. Whether hydrogen sulphide is pro or anti-inflammatory is heavily debated within the literature, yet researchers have not fully considered that invasive bacteria produce hydrogen sulphide, often at levels far above the endogenous levels of the host. Here I argue that if hydrogen sulphide is an endogenous signalling molecule with immunomodulatory functions, then it must have evolved in the presence of virulent bacteria which produce hydrogen sulphide. This context leads to two competing theories about the evolution of endogenous hydrogen sulphide signalling. The detectable emission theory proposes that bacteria produce hydrogen sulphide as part of normal metabolism and hosts which evolved to detect and respond to this hydrogen sulphide would gain a selective survival advantage. This predicts that the endogenous production of hydrogen sulphide is a mechanism which amplifies the bacterial hydrogen sulphide signal. The opposing protective agent theory predicts that bacterial hydrogen sulphide is an effective defence against the bactericidal mechanisms of the host's immune response. In this case, endogenous hydrogen sulphide production is either at inconsequential levels to alter the immune response, or is involved in the inflammation resolution process. Evidence suggests that the direct interactions of hydrogen sulphide with the bactericidal mechanisms of the innate immune system are most congruent with the protective agent theory. Therefore, I argue that if hydrogen sulphide is an immunomodulatory endogenous signalling molecule its effects are most likely anti-inflammatory. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs: An Achievement of Significant Morphological, Numerical and Functional Recovery.

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Tetsuro Tamaki

Full Text Available Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34 and CD34-/45-/29+ (Sk-DN/29+ cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells were also observed. A significant tetanic tension recovery (over 90% of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon and functional (80% vs. 60% in tetanus recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks of recovery was observed in both groups with the expression of key factors (mRNA and protein levels, suggesting the paracrine effects to angiogenesis. These results suggested that the

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

Science.gov (United States)

Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

Immunomodulatory factors in cervicovaginal secretions from pregnant and non-pregnant women: A cross-sectional study

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Stek Alice

2011-09-01

Full Text Available Abstract Background Pregnant women are at an increased risk for HIV infection due to unknown biological causes. Given the strong effect of sex-hormones on the expression of immunomuodulatory factors, the central role of mucosal immunity in HIV pathogenesis and the lack of previous studies, we here tested for differences in immunomuodulatory factors in cervico-vaginal secretions between pregnant and non-pregnant women. Methods We compared concentrations of 39 immunomodulatory factors in cervicovaginal lavages (CVL from 21 pregnant women to those of 24 non-pregnant healthy women from the US. We used Bonferroni correction to correct for multiple testing and linear regression modeling to adjust for possible confounding by plasma cytokine concentration, cervical ectopy, total protein concentration, and other possible confounders. Cervical ectopy was determined by planimetry. Concentration of immunomodulatory factors were measured by a multiplex assay, protein concentration by the Bradford Method. Results Twenty six (66% of the 39 measured immunomodulatory factors were detectable in at least half of the CVL samples included in the study. Pregnant women had threefold lower CVL concentration of CCL22 (geometric mean: 29.6 pg/ml versus 89.7 pg/ml, p = 0.0011 than non-pregnant women. CVL CCL22 concentration additionally correlated negatively with gestational age (Spearman correlation coefficient [RS]: -0.49, p = 0.0006. These associations remained significant when corrected for multiple testing. CCL22 concentration in CVL was positively correlated with age and negatively correlated with time since last coitus and the size of cervical ectopy. However, none of these associations could explain the difference of CCL22 concentration between pregnant and non-pregnant women in this study, which remained significant in adjusted analysis. Conclusions In this study population, pregnancy is associated with reduced concentrations of CCL22 in cervicovaginal secretions

Trehalolipid biosurfactants from nonpathogenic Rhodococcus actinobacteria with diverse immunomodulatory activities.

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Kuyukina, Maria S; Ivshina, Irena B; Baeva, Tatiana A; Kochina, Olesia A; Gein, Sergey V; Chereshnev, Valery A

2015-12-25

Actinobacteria of the genus Rhodococcus produce trehalolipid biosurfactants with versatile biochemical properties and low toxicity. In recent years, these biosurfactants are increasingly studied as possible biomedical agents with expressed immunological activities. Applications of trehalolipids from Rhodococcus, predominantly cell-bound, in biomedicine are also attractive because their cost drawback could be less significant for high-value products. The review summarizes recent findings in immunomodulatory activities of trehalolipid biosurfactants from nonpathogenic Rhodococcus and related actinobacteria and compares their biomedical potential with well-known immunomodifying properties of trehalose dimycolates from Mycobacterium tuberculosis. Molecular mechanisms of trehalolipid interactions with immunocompetent cells are also discussed. Copyright © 2015. Published by Elsevier B.V.

In vitro characterization of PlySK1249, a novel phage lysin, and assessment of its antibacterial activity in a mouse model of Streptococcus agalactiae bacteremia.

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Oechslin, Frank; Daraspe, Jean; Giddey, Marlyse; Moreillon, Philippe; Resch, Grégory

2013-12-01

Beta-hemolytic Streptococcus agalactiae is the leading cause of bacteremia and invasive infections. These diseases are treated with β-lactams or macrolides, but the emergence of less susceptible and even fully resistant strains is a cause for concern. New bacteriophage lysins could be promising alternatives against such organisms. They hydrolyze the bacterial peptidoglycan at the end of the phage cycle, in order to release the phage progeny. By using a bioinformatic approach to screen several beta-hemolytic streptococci, a gene coding for a lysin was identified on a prophage carried by Streptococcus dysgalactiae subsp. equisimilis SK1249. The gene product, named PlySK1249, harbored an original three-domain structure with a central cell wall-binding domain surrounded by an N-terminal amidase and a C-terminal CHAP domain. Purified PlySK1249 was highly lytic and bactericidal for S. dysgalactiae (2-log10 CFU/ml decrease within 15 min). Moreover, it also efficiently killed S. agalactiae (1.5-log10 CFU/ml decrease within 15 min) but not several streptococcal commensal species. We further investigated the activity of PlySK1249 in a mouse model of S. agalactiae bacteremia. Eighty percent of the animals (n = 10) challenged intraperitoneally with 10(6) CFU of S. agalactiae died within 72 h, whereas repeated injections of PlySK1249 (45 mg/kg 3 times within 24 h) significantly protected the mice (P S. dysgalactiae, demonstrated high cross-lytic activity against S. agalactiae both in vitro and in vivo. These encouraging results indicated that PlySK1249 might represent a good candidate to be developed as a new enzybiotic for the treatment of systemic S. agalactiae infections.

Immunomodulatory Activities of a Fungal Protein Extracted from Hericium erinaceus through Regulating the Gut Microbiota

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Chen Diling

2017-06-01

Full Text Available A single-band protein (HEP3 was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities.

Immunomodulatory Activities of a Fungal Protein Extracted from Hericium erinaceus through Regulating the Gut Microbiota.

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Diling, Chen; Chaoqun, Zheng; Jian, Yang; Jian, Li; Jiyan, Su; Yizhen, Xie; Guoxiao, Lai

2017-01-01

A single-band protein (HEP3) was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities.

Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri.

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Risco, Ester; Ghia, Felipe; Vila, Roser; Iglesias, José; Alvarez, Elida; Cañigueral, Salvador

2003-09-01

The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.

PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

Energy Technology Data Exchange (ETDEWEB)

Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D. [Astrophysics Research Centre, School of Maths and Physics, Queens University, Belfast BT7 1NN (United Kingdom); Huang, K. [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Mulchaey, J. S., E-mail: nsanders@cfa.harvard.edu [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); and others

2013-05-20

We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 Multiplication-Sign 10{sup 3} km s{sup -1}) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt {approx} 9-23 days and shows an NUV-NIR spectral energy distribution with temperature {approx}> 17 Multiplication-Sign 10{sup 3} K and a peak magnitude of M{sub z} = -18.88 {+-} 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M{sub Sun }) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208-042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits ({Sigma}{sub H{alpha}} {approx}< 2 Multiplication-Sign 10{sup -3} M{sub Sun} yr{sup -1} kpc{sup -2}). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

The immunomodulatory protein RH36 is relating to blood-feeding success and oviposition in hard ticks.

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Wang, Fangfang; Lu, Xiaojuan; Guo, Fengxun; Gong, Haiyan; Zhang, Houshuang; Zhou, Yongzhi; Cao, Jie; Zhou, Jinlin

2017-06-15

An immunomodulatory protein designated RH36 was identified in the tick Rhipicephalus haemaphysaloides. The cDNA sequence of RH36 has 844bp and encodes a deduced protein with a predicted molecular weight of 24kDa. Bioinformatics analysis indicated that RH36 presented a degree of similarity of 34.36% with the immunomodulatory protein p36 from the tick Dermacentor andersoni. The recombinant RH36 (rRH36) expressed in Sf9 insect cells suppressed the T-lymphocyte mitogen-driven in vitro proliferation of splenocytes and the expression of several cytokines such as IL-2, IL-12, and TNF-α. Furthermore, the proliferation of splenocytes isolated from rRH36-inoculated mice was significantly lower than that in control mice, suggesting that rRH36 could directly suppress immune responses in vivo. In addition, microarray analysis of splenocytes indicated that the expression of several immunomodulatory genes was downregulated by rRH36. The silencing of the RH36 gene by RNAi led to a 37.5% decrease in the tick attachment rate 24h after placement into the rabbit ears, whereas vaccination with RH36 caused a 53.06% decrease in the tick engorgement rate. Unexpectedly, RNAi induced a significant decrease in the oviposition rate, ovary weight at day 12 after engorgement, and egg-hatching rate. The effects of RH36 on blood feeding and oviposition were further confirmed by vaccination tests using the recombinant protein. These results indicate that RH36 is a novel member of immunosuppressant proteins and affects tick blood feeding and oviposition. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

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Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

2012-01-01

The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

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Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

2017-01-01

Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

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Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

2016-01-01

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

Physicochemical Characterization of Polysaccharides with Macrophage Immunomodulatory Activities Isolated from Red Ginseng (Panax ginseng C. A. Meyer

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Liang Zheng

2017-01-01

Full Text Available In this study, four polysaccharide fractions designated as RGP1, RGP2, RGP3, and RGP4 were isolated from red ginseng by DEAE-52 cellulose chromatography, and their macrophage immunomodulatory activities were investigated. The results revealed that the proliferation, NO production, and neutral red phagocytosis of RAW 264.7 macrophage cells in groups treated with RGP1 and RGP2 in vitro were increased significantly compared to RGP3 and RGP4. In addition, the level of TNF-α in RAW 264.7 cells was significantly increased in RGP1 and RGP2 groups. All the results consistently indicated that polysaccharide fractions RGP1 and RGP2 had strong macrophage immunomodulatory activities. Furthermore, RGP1 and RGP2 were purified by Sephadex G-100 column and RGP2 was further fractionated into a homogeneous fraction RGP2-1, with the molecular weight of 2.16 × 104 Da. The analysis of monosaccharide composition revealed that RGP1 was composed of arabinose, glucose, and galactose with a relative molecular ratio of 0.02 : 0.88 : 0.10. RGP2-1 was composed of rhamnose, arabinose, glucose, and galactose with a relative molecular ratio of 0.02 : 0.10 : 0.77 : 0.11. These results provided evidences that the neutral polysaccharide fractions RGP1 and RGP2 possessed significant immunomodulatory activity and could be explored as a promising natural immunomodulating agent applied in functional foods or medicines.

Differential immunomodulatory responses to nine polycyclic aromatic hydrocarbons applied by passive dosing

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Oostingh, Gertie J.; Smith, Kilian E. C.; Tischler, Ulrike

2015-01-01

Studying the effects of hydrophobic chemicals using in vitro cell based methods is hindered by the difficulty in bringing and keeping these chemicals in solution. Their effective concentrations are often lower than their nominal concentrations. Passive dosing is one approach that provides defined...... and stable dissolved concentrations during in vitro testing, and was applied to control and maintain freely dissolved concentrations of polycyclic aromatic hydrocarbons (PAHs) at levels up to their aqueous solubility limit. The immunomodulatory effects of 9 different PAHs at aqueous solubility on human...

Nekonvenční metody zpracování nožířských materiálů

OpenAIRE

Bražina, Jakub

2017-01-01

Tato práce se zaobírá problematikou nekonvenčních nožířských materiálu a jejich následnou aplikaci pro výrobu a zpracování loveckého nože. V rešeršní části je čtenáři přiblížena nožířská problematika, kde jsou uvedeny základní konstrukční charakteristiky a potřebné vlastnosti nože. V další části práce jsou popsány různé kovové i nekovové materiály, jejich vlastnosti, případné zpracování a výroba. Dále se práce zabývá problematikou povrchové ochrany těchto nožířských materiálu. Práce se také z...

Distribution and fate of polycyclic aromatic hydrocarbons (PAHs in recent sediments from the Gulf of Gdańsk (SE Baltic

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Ludwik Lubecki

2010-12-01

Full Text Available Polycyclic aromatic hydrocarbons (PAHs were determined in recent (0-10 cm sediments from the Gulf of Gdańsk during 2003-07 andcorrelated with environmental parameters. Located in the south-eastern part of the Baltic and receiving the waters of the River Wisła(Vistula, this area of negligible tides and strong anthropogenic stress, highly eutrophic as a consequence, is an exceptionalmodel basin for studying the fate of hydrophobic organic contaminants introduced to the sea. Environmental conditions determine thedistribution and composition patterns of parent PAHs in Gulf of Gdańsk sediments. PAHs were associated mainly with fine particlesediments, rich in organic carbon, with hypoxia/anoxia near the bottom. The highest PAH contents were found in the Gdańsk Deep(ca 110 m, where the mean concentration of Σ12PAHs was ~3600 ng g-1, and no distinct temporal trend was observed.Lighter PAHs were found to be depleted in deeper regions. It was estimated that the Wisła discharges ~50% of the total PAH load deposited in recent Gulf sediments.

Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

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Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))

1991-01-01

The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

Under the glacier, the groundwater - the case of Skálafell area, Iceland

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Vincent, Aude; Hart, Jane

2017-04-01

The research addressing glaciers evolution under climate change is well developed, and is now looking not only at their mass balance, but also at the associated subsurface hydrology and downstream hydrology. However, the groundwater component is rarely considered, even though it will be required to forecast the evolution of water resources and of water linked hazards under climate change. The few available studies demonstrate the existence of sub-or pro-glacial aquifers. Some of them suggest strong coupling between rivers and the aquifer, observe the flooding due to water table rising following enhanced glacier melting, or expect stronger recharge in the future due to glacier melting. The present study is the first step of a wider project, GlacAq, aiming at filling this knowledge gap, by characterizing the particular hydrogeology encountered under and downstream of glaciers of alpine type, i.e. sub-, pro- and periglacial hydrogeology, and its sensibility to climate change, in order to provide operational management directions. Skálafell glacier area (Iceland) has been chosen as it has already been followed for climatic, glaciological, and surface hydrology data (Hart et al. (2015), Young et al. (2015)). The present work will use those data, as well as topographic and surface data from the National Land Survey of Iceland, and geological data, to run a comprehensive numerical modelling. The work conducted on the Skálafell site will lead both to the achievement of an operational understanding of a poorly known underground system, and to the anticipation of its hydrodynamic response to climate change. The foreseen mechanisms include an enhanced sub-glacial aquifer recharge, intense surface water bodies-aquifer exchanges, and the aquifer discharge either through springs, or to an offshore system. Those offshore stocks are being increasingly recognised, but their origins are still only guessed at. Skálafell site allows the exploration of the potential role of the

Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

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Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

2012-09-18

The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

DEFF Research Database (Denmark)

Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

2011-01-01

• To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri......• To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced...

Agaricus blazei Murill - immunomodulatory properties and health benefits

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Biedron R

2012-11-01

Full Text Available AbstractThe Agaricus blazei Murill (AbM, also known as Agaricus brasiliensis L. due to its origin in Brazilian rain forest, is an edible mushroom of the Basidiomycetes family, which also comprises medicinal mushrooms such as Hericium erinaceus and Grifola frondosa. AbM has been used in traditional medicine locally and also recently as a health food worldwide. Since it has been found to possess immunomodulatory properties, its biological and health-related effects, as well as its isolated active ingredients e.g. beta-glucans, have been examined by scientists. Otherinvestigations have been performed with mixed mushroom products, such as AndoSanTM, which contains mostly AbM, but also the two other mushrooms above. AbM-related benefits reviewed here include effects against cancer, infections, inflammation, allergy/ asthma and diabetes. Effects of AndoSanTMand other AbM-based extracts have been compared in a bacterial sepsis model.

Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

DEFF Research Database (Denmark)

Strøbaek, Dorte; Teuber, Lene; Jørgensen, Tino D

2004-01-01

We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated...

Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus.

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Mesaik, M Ahmed; Murad, Shahnaz; Khan, Khalid Mohammed; Tareen, Rasool Bakhsh; Ahmed, Aqeel; Choudhary, Muhammad Iqbal

2009-11-01

Casticin (1), a flavonoid isolated from the aerial parts of Vitex agnus-castus, was found to be a potent immunomodulatory and cytotoxic compound. The activity was tested in vitro for chemiluminescence, chemotaxis, T-cell proliferation and cytotoxicity. Casticin (1) exhibited a significant inhibitory effect on monocyte oxidative burst in a dose dependent manner. It was found to have a significant suppressive effect on the chemotaxic action at higher concentrations on fMLP (10(-8) m) stimulated neutrophils. It also showed a potent suppressive effect on PHA stimulated T-cell (PMBC).

Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines of Scutellaria barbata D. Don in Lewis-Bearing C57BL/6 Mice

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Tao Gong

2015-01-01

Full Text Available Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB, an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41±5.44%, 33.56±4.85%, and 27.57±4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer.

The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells.

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Dos Santos, Guilherme Galvão; Batool, Shafqat; Hastreiter, Araceli; Sartori, Talita; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

2017-08-01

Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles

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Karin Pachler

2017-07-01

Full Text Available The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies.

RNA sequence analyses of r-Moj-DM treated cells: TXNIP is required to induce apoptosis of SK-Mel-28.

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McBride, Terri D; Andrew, U; Ly, Nicko; Soto, Julio G

2016-10-01

RNA sequencing of untreated and r-Moj-DM treated SK-Mel-28 cells was performed after 6 h, to begin unraveling the apoptotic pathway induced by r-Moj-DM. Bioinformatic analyses of RNA sequencing data yielded 40 genes that were differentially expressed. Nine genes were upregulated and 31 were downregulated. qRT-PCR was used to validate differential expression of 13 genes with known survival or apoptotic-inducing activities. Expression of BNiP3, IGFBP3, PTPSF, Prune 2, TGF-ß, and TXNIP were compared from cells treated with r-Moj-DN (a strong apoptotic inducer) or r-Moj-DA (a non-apoptotic inducer) for 1 h, 2 h, 4 h, and 6 h after treatment. Our results demonstrate that significant differences in expression are only detected after 4 h of treatment. In addition, expression of TXNIP (an apoptotic inducer) remains elevated at 4 h and 6 h only in r-Moj-DN treated cells. Based on the consistency of elevated TXNIP expression, we further studied TXNIP as a novel target of disintegrin activation. Confocal microscopy of anti-TXNIP stained SK-Mel-28 cells suggests nuclear localization of TXNIP after r-Moj-DM treatment. A stable TXNIP knockdown SK-Mel-28 cell line was produced to test TXNIP' role in the apoptotic induction by r-Moj-DM. High cell viability (74.3% ±9.1) was obtained after r-Moj-DM treatment of TXNIP knocked down SK-Mel-28 cells, compared to 34% ±0.187 for untransduced cells. These results suggest that TXNIP is required early in the apoptotic-inducing pathway resulting from r-Moj-DM binding to the αv integrin subunit. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experience of Using Immunomodulatory Therapy in Comprehensive Treatment of Chronic Tonsillitis in Children

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Yu.V. Marushko

2015-02-01

Full Text Available Immunomodulatory therapy is an important part of treating patients with chronic tonsillitis caused by β-hemolytic streptococcus group A, on the background of antibiotic therapy it allows us to achieve a more effective elimination of the pathogen. Administration of Imupret in the comprehensive treatment for exacerbation of chronic tonsillitis of streptococcal origin leads to the rapid disappearance of clinical manifestations of the disease, high frequency of pathogen elimination, reduces the incidence of chronic tonsillitis exa­cerbations.

Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

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Wim Adriaensen

2018-01-01

Full Text Available Patients with visceral leishmaniasis (VL–human immunodeficiency virus (HIV coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

Science.gov (United States)

Adriaensen, Wim; Dorlo, Thomas P. C.; Vanham, Guido; Kestens, Luc; Kaye, Paul M.; van Griensven, Johan

2018-01-01

Patients with visceral leishmaniasis (VL)–human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients. PMID:29375567

The mojastin mutant Moj-DM induces apoptosis of the human melanoma SK-Mel-28, but not the mutant Moj-NN nor the non-mutated recombinant Moj-WN.

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Seoane, Agustin I; Tran, Victoria L; Sanchez, Elda E; White, Stephanie A; Choi, Jason L; Gaytán, Brandon; Chavez, Natalie; Reyes, Steven R; Ramos, Carla J; Tran, Luan H; Lucena, Sara E; Sugarek, Maria; Perez, John C; Mandal, Stephanie A; Ghorab, Shervin; Rodriguez-Acosta, Alexis; Fung, Branden K; Soto, Julio G

2010-09-01

In this study, three recombinant mojastin peptides (Moj-WN, Moj-NN, and Moj-DM) were produced and compared functionally. Recombinant Moj peptides were purified as GST-fusions. GST-Moj-WN and GST-Moj-NN inhibited ADP-induced platelet aggregation in platelet rich plasma. The GST-Moj-WN had an IC(50) of 160nM, while the GST-Moj-NN had an IC(50) of 493nM. The GST-Moj-DM did not inhibit platelet aggregation. All three GST-Moj peptides inhibited SK-Mel-28 cell adhesion to fibronectin. The GST-Moj-WN inhibited the binding of SK-Mel-28 cells to fibronectin with an IC(50) of 11nM, followed by the GST-Moj-NN (IC(50) of 28nM), and the GST-Moj-DM (IC(50) of 46nM). The GST-Moj peptides' ability to induce apoptosis on SK-Mel-28 cells was determined using Annexin-V-FITC and nuclear fragmentation assays. Cells were incubated with 5muM GST-Moj peptides for 24h. At 5microM GST-Moj-DM peptide, 13.56%+/-2.08 of treated SK-Mel-28 cells were in early apoptosis. The GST-Moj-DM peptide also caused nuclear fragmentation as determined by fluorescent microscopy and Hoechst staining. The GST-Moj-WN and GST-Moj-NN peptides failed to induce apoptosis. We characterized the SK-Mel-28 integrin expression, as the first step in determining r-Moj binding specificity. Our results indicate that SK-Mel-28 cells express alphavbeta3, alphav, alpha6, beta1, and beta3 integrin receptors. Published by Elsevier Ltd.

Pro-inflammatory cytokines derived from West Nile virus (WNV-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

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Nerurkar Vivek R

2010-10-01

Full Text Available Abstract Background WNV-associated encephalitis (WNVE is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. Methods A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. Results WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. Conclusion Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV

Characterization and immunomodulatory effects of glucans from Pleurotus albidus, a promising species of mushroom for farming and biomass production.

Science.gov (United States)

Castro-Alves, Victor Costa; Gomes, Daniel; Menolli, Nelson; Sforça, Maurício Luís; Nascimento, João Roberto Oliveira do

2017-02-01

Polysaccharides from a number of mushroom species are recognized as functional food ingredients with potential health benefits, including immunomodulatory effects. In this study, polysaccharides extracted from the basidiome with cold water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo- (MyEX) and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a promising species for farming and biomass production, were analyzed for their chemical composition and structure and immunomodulatory effects on macrophages. Compositional (HPAEC-PAD and HPSEC-RID/MWD) and structural (FT-IR, 1D- and 2D-NMR) analyses identified BaCW and MyEX as β-(1,6)-branched β-(1,3)-glucans, BaHW and MyEN as α-(1,3)-(1,2)-branched α-(1,6)-glucans, and BaHA as a mixture of α-(1,6)- and β-(1,3)-glucans. BaCW and MyEX stimulated the production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO), but not interleukin-6 (IL-6), and decreased phagocytosis of zymosan particles. In contrast, BaHW and MyEN induced TNF-α, NO and IL-6 production, and increased zymosan phagocytosis, while BaHA displayed intermediary effects in comparison the other polysaccharides. In conclusion, the basidiome and the submerged culture of P. albidus are sources of easily extractable α- and β-glucans with potential immunomodulatory effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic)

Science.gov (United States)

Foroutan-Rad, Masoud; Tappeh, Khosrow Hazrati; Khademvatan, Shahram

2015-01-01

Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms “Allium sativum,” “Garlic,” “Allicin,” “Ajoene,” “Leishmania,” “in vitro,” “in vivo,” and “clinical trial,” alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis. PMID:26721553

Sjuksköterskor och skötares upplevelser av möten i psykiatrisk öppenvård : En intervjustudie

OpenAIRE

Bäckman, Jenny; Nyman, Nyman

2016-01-01

Syftet med studien var att undersöka sjuksköterskors och skötares upplevelser av möten med patienter i psykiatrisk öppenvård.   Bakgrund – I psykiatrisk öppenvård möter sjuksköterskor och skötare många olika människor med individuella behov. Sedan tidigare forskning har det framkommit att patienters känsla av trygghet uppkommer genom faktorer som personalens inställning och empati. Relationen mellan personal och patient är viktig för patientens känsla av att bli tagen på allvar samt att bli b...

Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.

Science.gov (United States)

Mori, Shuuichi; Motohashi, Norio; Takashima, Rumi; Kishi, Masahiko; Nishimune, Hiroshi; Shigemoto, Kazuhiro

2017-11-01

Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathogenicity of anti-LRP4 Abs in MG patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The cytotoxicity of a 2-chloroethylnitrosourea analog of sarcosinamide in the SK-MG-1 human glioma cell line as a possible indicator for transport

Energy Technology Data Exchange (ETDEWEB)

Skalski, V.; Feindel, W.; Panasci, L.C. (Lady Davis Institute for Medical Research, Montreal, Quebec (Canada))

1989-07-01

The cytotoxicities of a new sarcosinamide analog of chloroethylnitrosourea (SarCNU) and of BCNU were examined in the glioma cell line SK-MG-1 in the presence or absence of excess concentrations of amino acids and sarcosinamide. The cytotoxicity of SarCNU, but not of BCNU, was significantly reduced in the presence of excess sarcosinamide. The stability of SarCNU was not significantly altered by increasing concentrations of sarcosinamide. In order to investigate the possibility that sarcosinamide inhibits the uptake of SarCNU, the transport of tritiated sarcosinamide was examined in SK-MG-1 cells. The uptake of 3H-sarcosinamide was inhibited by excess, unlabelled sarcosinamide and SarCNU but not by BCNU, glycine or sarcosine. These results suggest the existence of a carrier-mediated transport for sarcosinamide which can accomodate SarCNU in SK-MG-1 cells.

Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network

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Wei Shu

2012-09-01

Full Text Available Abstract Background The Arabidopsis microRNA156 (miR156 regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. Results In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated SPL15 (SPL15m largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro

[Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

Science.gov (United States)

Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

2015-01-20

Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Hasseldam, Henrik; Hansen, C S; Johansen, F F

2013-01-01

hygiene standards that exist in the western world, with reduced exposure to various pathogens, including parasites, as a consequence. Parasites are known to employ various immunomodulatory and anti-inflammatory strategies, which enable them to evade destruction by the immune system. This is most likely...... one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune...

Dílna kultury zvoncovitých pohárů na zpracování rohovce typu Stránská skála (Brno, katastrální území Slatina)

Czech Academy of Sciences Publication Activity Database

Šebela, Lubomír; Škrdla, Petr; Přichystal, A.; Kopacz, J.

2016-01-01

Roč. 1, č. 1 (2016), s. 119-128 ISSN 2453-8612 Institutional support: RVO:68081758 Keywords : Moravia (East part of Czech Republic) * Stránská skála (Brno, cadastral territory of Slatina) * Bell Beaker culture * workshop * chert of the Stránská skála type Subject RIV: AC - Archeology, Anthropology, Ethnology https://fphil.uniba.sk/fileadmin/fif/katedry_pracoviska/karch/MusArch/1_1/119-128.pdf

SkQ1 Ophthalmic Solution for Dry Eye Treatment: Results of a Phase 2 Safety and Efficacy Clinical Study in the Environment and During Challenge in the Controlled Adverse Environment Model.

Science.gov (United States)

Petrov, Anton; Perekhvatova, Natalia; Skulachev, Maxim; Stein, Linda; Ousler, George

2016-01-01

This Phase 2 clinical trial assessed the efficacy and safety of the novel antioxidative, renewable compound SkQ1 for topical treatment of dry eye signs and symptoms. In a single-center, randomized, double-masked, placebo-controlled, 29-day study, 91 subjects with mild to moderate dry eye instilled the study drug twice daily and recorded dry eye symptoms daily. Subjects were randomized 1:1:1 into one of three ophthalmic solution treatment groups: SkQ1 1.55 µg/mL, SkQ1 0.155 µg/mL, or 0.0 µg/mL (placebo). Subjects were exposed to a controlled adverse environment chamber at 3 of the 4 study visits (Day -7, Day 1, and Day 29). Investigator assessments occurred at all study visits. SkQ1 was safe and efficacious in treating dry eye signs and symptoms. Statistically significant improvements with SkQ1 compared to placebo occurred for the dry eye signs of corneal fluorescein staining and lissamine green staining in the central region and lid margin redness, and for the dry eye symptoms of ocular discomfort, dryness, and grittiness. In addition, SkQ1 demonstrated greater efficacy compared to placebo, although the differences were not statistically significant, for corneal fluorescein staining in other regions and/or time points (total staining score, central region, corneal sum score, and temporal region), lissamine green staining for the central and nasal regions, and blink rate scores. This Phase 2 study indicated that SkQ1 is safe and efficacious for the treatment of dry eye signs and symptoms and supported previous study results. Clinicaltrials.gov identifier: NCT02121301. Miotech S.A.

Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

OpenAIRE

Lotfinegad, Parisa; Shamsasenjan, karim; Movassaghpour, Aliakbar; Majidi, Jafar; Baradaran, Behzad

2013-01-01

Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs ...

Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin

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Kuo Y

2017-04-01

Full Text Available Yung-Chih Kuo, Chien-Wei Tsao Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China Abstract: A drug delivery system of quercetin (QU-encapsulated liposomes (LS grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf was developed to permeate the blood–brain barrier (BBB and rescue degenerated neurons, acting as an Alzheimer’s disease (AD pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS was used to traverse human brain microvascular endothelial cells (HBMECs regulated by human astrocytes (HAs and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications. Keywords: Alzheimer’s disease, blood–brain barrier, β-amyloid, drug targeting, neurodegeneration, pharmacotherapy

Immunomodulatory Activity of Ganoderma atrum Polysaccharide on Purified T Lymphocytes through Ca2+/CaN and Mitogen-Activated Protein Kinase Pathway Based on RNA Sequencing.

Science.gov (United States)

Xiang, Quan-Dan; Yu, Qiang; Wang, Hui; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

2017-07-05

Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes and further elucidate the underlying mechanism based on RNA sequencing (RNA-seq). Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ, and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes. KEGG pathway analysis identified 20 significant canonical pathways and seven biological functions. Furthermore, PSG-1 elevated intracellular Ca 2+ concentration and calcineurin (CaN) activity and raised the p-ERK, p-JNK, and p-p38 expression levels. T lymphocytes proliferation and the production of IL-2, IFN-γ, and IL-12 were decreased by the inhibitors of calcium channel and mitogen-activated protein kinases (MAPKs). These results indicated that PSG-1 possesses immunomodulatory activity on purified T lymphocytes, in which Ca 2+ /CaN and MAPK pathways play essential roles.

Confirming a Role for α9nAChRs and SK Potassium Channels in Type II Hair Cells of the Turtle Posterior Crista

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Xiaorong Xu Parks

2017-11-01

Full Text Available In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum. Sharp-electrode recordings have inferred that efferent-mediated inhibition of bouton afferents requires the sequential activation of alpha9-containing nicotinic ACh receptors (α9*nAChRs and small-conductance, calcium-dependent potassium channels (SK in type II hair cells. Gradations in the strength of efferent-mediated inhibition across the crista likely reflect variations in α9*nAChRs and/or SK activation in type II hair cells from those different regions. However, in turtle cristae, neither inference has been confirmed with direct recordings from type II hair cells. To address these gaps, we performed whole-cell, patch-clamp recordings from type II hair cells within a split-epithelial preparation of the turtle posterior crista. Here, we can easily visualize and record hair cells while maintaining their native location within the neuroepithelium. Consistent with α9*nAChR/SK activation, ACh-sensitive currents in type II hair cells were inward at hyperpolarizing potentials but reversed near −90 mV to produce outward currents that typically peaked around −20 mV. ACh-sensitive currents were largest in torus hair cells but absent from hair cells near the planum. In current clamp recordings under zero-current conditions, ACh robustly hyperpolarized type II hair cells. ACh

Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

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Marcio A. R. Araujo

2011-09-01

Full Text Available Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters, terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an anti-inflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

Immunomodulatory activity of Lactobacillus plantarum KLDS1.0318 in cyclophosphamide-treated mice

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Yueyue Meng

2018-03-01

Full Text Available Background: Probiotics in fermented foods have attracted considerable attention lately as treatment options for immune diseases, the incidence of which has been increasing throughout the world. Objective: The objective of the present study was to investigate the immunomodulatory activity of Lactobacillus plantarum (L. plantarum KLDS1.0318 in cyclophosphamide-treated mice. Design: To investigate the immune-enhancing effects of L. plantarum KLDS1.0318, we used a immunosuppressive model. Ninety female six-week-old BALB/c mice were randomly divided into six groups: normal control (NC group, model control (MC group, immunosuppression plus L. plantarum KLDS1.0318 groups with three different doses (KLDS1.0318-L, KLDS1.0318-M, and KLDS1.0318-H, and plus levamisole hydrochloride as positive control (PC group. Results and discussions: Results showed that the thymus and spleen indexes of the four treatment groups were significantly higher than those of the MC group (2.01±0.16 ( p < 0.05. The capacity of lymphocyte proliferation, the activity of natural killer (NK cell and macrophages phagocytosis were significantly increased ( p < 0.05 in four treatment groups as compared with the MC group (0.327±0.022, 62.29±0.8, 0.087±0.008, respectively. The levels of relative immune factors (IL-2, IL-6, and IFN-γ showed similar patterns ( p < 0.05. Conclusions: This study suggested that orally administered L.plantarum KLDS1.0318 may effectively accelerate the recovery of immunosuppressive mice caused by cyclophosphamide (CTX. The immunomodulatory activity of the srtain recommended that L. plantarum KLDS1.0318 could be used as a powerful medicinal treatment against immunosuppression.

Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro

International Nuclear Information System (INIS)

Yang, Min; Zhang, Rui; Yan, Ming; Ye, Zhengxu; Liang, Wei; Luo, Zhuojing

2010-01-01

Dye exclusion is a valuable technique to isolate cancer stem cells (CSCs) based on an ability of stem cell to efflux fluorescent DNA-binding dye, especially for tumors without unique surface markers. It has been proven that side population (SP) cells that exclude Hoechst 33342 dye are enriched with stem-like cells in several cancer cell lines. In this study, we isolated and characterized SP cells from human Ewing's sarcoma cell line SK-ES-1 in vitro. SP cells were detected in SK-ES-1 and comprised 1.2% of total cell population. Only SP cells had the capacity to regenerate both SP and non-SP cells. The proliferation rates were similar between SP and non-SP cells. However, the clonogenicity and invasiveness of SP cells were significantly higher than that of non-SP cells. Further characterization of this SP phenotype presented other properties. SP cells exhibited increased multi-drug resistance and the ATP binding cassette protein (ABC) transporters were up-regulated in SP population. These findings suggest that SP cells derived from Ewing's sarcoma play the critical role in tumor metastasis and recurrence and might be an ideal target for clinical therapy.

DJ1 Expression Downregulates in Neuroblastoma Cells (SK-N-MC Chronically Exposed to HIV-1 and Cocaine.

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Upal eRoy

2015-07-01

Full Text Available Background: HIV-associated neurological disorder (HAND has long been recognized as a consequence of Human Immunodeficiency Virus (HIV infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease in regulating dopamine transmission and reactive oxygen species (ROS production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder.Methods: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC. Gene expression and protein analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry.Results: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine.Conclusion: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1and/or cocaine indicating oxidative stress level of dopamine neurons.

Variability of morphological conditions of the Vistula river channel in the section Czerwińsk-Kępa Polska

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Popek Zbigniew

2015-03-01

Full Text Available Variability of morphological conditions of the Vistula river channel in the section Czerwińsk-Kępa Polska. The paper presents an assessment of morphological changes that occurred in the Vistula river channel in selected section of about 33 km long, located in the middle of the Vistula river course between Czerwińsk and Kępa Polska (km 576–609. Based on the analysis of archival material from 1972–2009, a characteristics of river channel changes, taking primarily into account the horizontal layout (shape in the plan, was obtained. An attempt was made to estimate the trends and rate of transformation of the following parameters in the river channel: width, length, and position of the riverbanks, abundance and size of islands and fluvial deposits, as well as their percentage in the total area of the main river channel and the floodplain area between levees.

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

OpenAIRE

Arancibia, Sergio; Espinoza, Cecilia; Salazar, Fabián; Del Campo, Miguel; Tampe, Ricardo; Zhong, Ta-Ying; De Ioannes, Pablo; Moltedo, Bruno; Ferreira, Jorge; Lavelle, Ed C.; Manubens, Augusto; De Ioannes, Alfredo E.; Becker, María Inés

2014-01-01

PUBLISHED Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropo...

The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review.

Science.gov (United States)

Baraya, Yushau Shuaibu; Wong, Kah Keng; Yaacob, Nik Soriani

2017-01-01

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dispersant Application during SG Wet Layup at SK Unit 1

Energy Technology Data Exchange (ETDEWEB)

Kwon, Hyukchul; Lee, Dooho; Sung, Kibang [KHNP Central Institute, Daejeon (Korea, Republic of)

2014-05-15

The corrosion products in the feedwater are deposited onto the steam generators (SGs) despite the effort to control them within limit of impurity. This deposit is one of causes for occurrence of SCC (Stress Corrosion Cracking), water level fluctuation and further corrosion of SGs. To minimize corrosion and remove deposit, the nuclear power plants apply high pH to the secondary system and SG chemical cleaning, respectively. But these methods can be costly and carry risks of extended outages or incomplete cleaning. Another method is an on-line dispersant application. The role of dispersant is to make deposit suspended in the SGs. Then, the suspended deposit is discharged to the blowdown system. The iron removal is increased in the blowdown system during the dispersant application. Additional significant benefit in the form of reduced corrosion product transport may be obtained through applying dispersant in the SGs wet lay operational mode. This method helps to reduce the total SGs loading without affecting critical outage activities and with minimal additional effort on the part of the utilities. This study provides the results of the dispersant application trial during the SG wet layup at SK Unit 1. As the PAA concentrations were increased, the corrosion rates of Alloy 690 and SA 106 Gr.B were increased. The corrosion rate of Alloy 690 was 2 times less than that of SA 106 Gr.B at 100 ppm of PAA based on the electrochemical experimental. There were no significant feasibility problems with application of PAA during the SG wet layup. The reasonable estimation of the additional mass removed by the presence of PAA during SGs wet layup is 460 g. The iron removal depended on PAA concentration injected based on the comparative results of the SK Unit 1 and TMI-1. It is expected that injection of PAA into the SG result in a significant decrease in the amount of iron transported to the SGs during the startup.

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

Science.gov (United States)

Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

2010-01-01

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn. Seeds

Directory of Open Access Journals (Sweden)

Yafeng Zheng

2016-11-01

Full Text Available Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg treatment (50.79%. The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01, while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.

Inclusive K0SK0S resonance production in ep collisions at HERA

CERN Document Server

AUTHOR|(CDS)2076592; Magill, S.; Musgrave, B.; Nicholass, D.; Repond, J.; Yoshida, R.; Mattingly, M.C.K.; Antonioli, P.; Bari, G.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Cindolo, F.; Corradi, M.; Iacobucci, G.; Margotti, A.; Nania, R.; Polini, A.; Antonelli, S.; Basile, M.; Bindi, M.; Cifarelli, L.; Contin, A.; De Pasquale, S.; Sartorelli, G.; Zichichi, A.; Bartsch, D.; Brock, I.; Hartmann, H.; Hilger, E.; Jakob, H.P.; Jungst, M.; Nuncio-Quiroz, A.E.; Paul, E.; Samson, U.; Schonberg, V.; Shehzadi, R.; Wlasenko, M.; Brook, N.H.; Heath, G.P.; Morris, J.D.; Capua, M.; Fazio, S.; Mastroberardino, A.; Schioppa, M.; Susinno, G.; Tassi, E.; Kim, J.Y.; Ibrahim, Z.A.; Kamaluddin, B.; Wan Abdullah, W.A.T.; Ning, Y.; Ren, Z.; Sciulli, F.; Chwastowski, J.; Eskreys, A.; Figiel, J.; Galas, A.; Gil, M.; Olkiewicz, K.; Stopa, P.; Zawiejski, L.; Adamczyk, L.; Bold, T.; Grabowska-Bold, I.; Kisielewska, D.; Lukasik, J.; Przybycien, M.; Suszycki, L.; Kotanski, A.; Slominski, W.; Behrens, U.; Blohm, C.; Bonato, A.; Borras, K.; Ciesielski, R.; Coppola, N.; Fang, S.; Fourletova, J.; Geiser, A.; Gottlicher, P.; Grebenyuk, J.; Gregor, I.; Haas, T.; Hain, W.; Huttmann, A.; Januschek, F.; Kahle, B.; Katkov, I.I.; Klein, U.; Kotz, U.; Kowalski, H.; Lobodzinska, E.; Lohr, B.; Mankel, R.; Melzer-Pellmann, I.A.; Miglioranzi, S.; Montanari, A.; Namsoo, T.; Notz, D.; Parenti, A.; Rinaldi, L.; Roloff, P.; Rubinsky, I.; Santamarta, R.; Schneekloth, U.; Spiridonov, A.; Szuba, D.; Szuba, J.; Theedt, T.; Wolf, G.; Wrona, K.; Yagues Molina, A.G.; Youngman, C.; Zeuner, W.; Drugakov, V.; Lohmann, W.; Schlenstedt, S.; Barbagli, G.; Gallo, E.; Pelfer, P.G.; Bamberger, A.; Dobur, D.; Karstens, F.; Vlasov, N.N.; Bussey, P.J.; Doyle, A.T.; Dunne, W.; Forrest, M.; Rosin, M.; Saxon, D.H.; Skillicorn, I.O.; Gialas, I.; Papageorgiu, K.; Holm, U.; Klanner, R.; Lohrmann, E.; Schleper, P.; Schorner-Sadenius, T.; Sztuk, J.; Stadie, H.; Turcato, M.; Foudas, C.; Fry, C.; Long, K.R.; Tapper, A.D.; Matsumoto, T.; Nagano, K.; Tokushuku, K.; Yamada, S.; Yamazaki, Y.; Barakbaev, A.N.; Boos, E.G.; Pokrovskiy, N.S.; Zhautykov, B.O.; Aushev, V.; Borodin, M.; Kadenko, I.; Kozulia, A.; Libov, V.; Lisovyi, M.; Lontkovskyi, D.; Makarenko, I.; Sorokin, Iu.; Verbytskyi, A.; Volynets, O.; Son, D.; de Favereau, J.; Piotrzkowski, K.; Barreiro, F.; Glasman, C.; Jimenez, M.; Labarga, L.; del Peso, J.; Ron, E.; Soares, M.; Terron, J.; Zambrana, M.; Corriveau, F.; Liu, C.; Schwartz, J.; Walsh, R.; Zhou, C.; Tsurugai, T.; Antonov, A.; Dolgoshein, B.A.; Gladkov, D.; Sosnovtsev, V.; Stifutkin, A.; Suchkov, S.; Dementiev, R.K.; Ermolov, P.F.; Gladilin, L.K.; Golubkov, Yu.A.; Khein, L.A.; Korzhavina, I.A.; Kuzmin, V.A.; Levchenko, B.B.; Lukina, O.Yu.; Proskuryakov, A.S.; Shcheglova, L.M.; Zotkin, D.S.; Abt, I.; Caldwell, A.; Kollar, D.; Reisert, B.; Schmidke, W.B.; Grigorescu, G.; Keramidas, A.; Koffeman, E.; Kooijman, P.; Pellegrino, A.; Tiecke, H.; Vazquez Acosta, Monica Luisa; Wiggers, L.; Brummer, N.; Bylsma, B.; Durkin, L.S.; Lee, A.; Ling, T.Y.; Allfrey, Philip Daniel; Bell, M.A.; Cooper-Sarkar, A.M.; Devenish, R.C.E.; Ferrando, J.; Foster, B.; Korcsak-Gorzo, K.; Oliver, K.; Robertson, A.; Uribe-Estrada, C.; Walczak, R.; Bertolin, A.; Dal Corso, F.; Dusini, S.; Longhin, A.; Stanco, L.; Bellan, P.; Brugnera, R.; Carlin, R.; Garfagnini, A.; Limentani, S.; Oh, B.Y.; Raval, A.; Ukleja, J.; Whitmore, J.J.; Iga, Y.; D'Agostini, G.; Marini, G.; Nigro, A.; Cole, J.E.; Hart, J.C.; Abramowicz, H.; Ingbir, R.; Kananov, S.; Levy, A.; Stern, A.; Kuze, M.; Maeda, J.; Hori, R.; Kagawa, S.; Okazaki, N.; Shimizu, S.; Tawara, T.; Hamatsu, R.; Kaji, H.; Kitamura, S.; Ota, O.; Ri, Y.D.; Costa, M.; Ferrero, M.I.; Monaco, V.; Sacchi, R.; Solano, A.; Arneodo, M.; Ruspa, M.; Fourletov, S.; Martin, J.F.; Stewart, T.P.; Boutle, S.K.; Butterworth, J.M.; Gwenlan, C.; Jones, T.W.; Loizides, J.H.; Wing, M.; Brzozowska, B.; Ciborowski, J.; Grzelak, G.; Kulinski, P.; Luzniak, P.; Malka, J.; Nowak, R.J.; Pawlak, J.M.; Tymieniecka, T.; Ukleja, A.; zarnecki, A.F.; Adamus, M.; Plucinski, P.; Eisenberg, Y.; Hochman, D.; Karshon, U.; Brownson, E.; Danielson, T.; Everett, A.; Kcira, D.; Reeder, D.D.; Ryan, P.; Savin, A.A.; Smith, W.H.; Wolfe, H.; Bhadra, S.; Catterall, C.D.; Cui, Y.; Hartner, G.; Menary, S.; Noor, U.; Standage, J.; Whyte, J.

2008-01-01

Inclusive K0SK0S production in ep collisions at HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb-1. Enhancements in the mass spectrum were observed and are attributed to the production of f2(1270)/a02(1320), f'2(1525) and f0(1710). The f0(1710) state was observed with a statistical significance of 5 standard deviations. Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

Science.gov (United States)

Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

2018-05-01

An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations

[Prevalence of the Diabetic Retinopathy and Genetic Factors Significance in the Development of Diabetic Retinopathy in Patients with Diabetes Mellitus type I and II in Slovakia (DIARET SK study). Overview of Actual Findings and Design of the Epidemiological DIARET SK Study].

Science.gov (United States)

Krásnik, V; Štefaničková, J; Fabková, J; Bucková, D; Helbich, M

2015-09-01

Diabetic retinopathy (DR) is the second most common microvascular complication and the most common cause of blindness in patients with diabetes mellitus (DM). Despite the ongoing research, the findings of diabetic retinopathy epidemiological and risk factors are, until now, not consistent. More finding may be revealed by epidemiological studies, consistently mapping DR epidemiology under the current possibilities of investigations and treatment of the DM. DIARET SK Study, with 5 000 enrolled patients with diabetes mellitus in the Slovak Republic, is, until now, the largest epidemiological study to set the prevalence of diabetic retinopathy. The primary aim is to establish the prevalence of diabetic retinopathy in patients with diabetes mellitus type I and II, according to the duration of the disease. The secondary aim is to establish prevalence of the different stages of the DR and diabetic macular edema (DME) and analysis of the risk factors influence. Included are patients with DM type I and II regardless to the ocular complications history and the period of DM duration. Each enrolled patient has both complex diabetic and ophthalmic examinations.Projects to establish DR prevalence: Tens of projects concerned with diabetic retinopathy epidemiology with different approaches to establish the prevalence and with different patients population. Results from different studies vary significantly (from 12.3 % to 66.9 %). The results depend on the design of the study and the patients recruitment, used examination methods, specific patients population with regard to the geography, prevalence of risk factors, period of diabetes duration, glycated hemoglobin (HbA1C) level, blood pressure, and is higher in type I diabetic patients. The most accurate results are from population epidemiological studies with well-controlled patient recruitment and uniform complex examination that are similar to the DIARET SK study. The DIARET SK study represents the largest epidemiological study

Immunomodulatory effect of exo-polysaccharides from submerged cultured Cordyceps sinensis: enhancement of cytokine synthesis, CD11b expression, and phagocytosis.

Science.gov (United States)

Kuo, Mei-Chun; Chang, Chien-Yu; Cheng, Tso-Lin; Wu, Ming-Jiuan

2007-06-01

Cordyceps sinensis is widely used as a traditional medicine for treatment of a wide variety of diseases or to maintain health. The immunomodulatory activity of polysaccharides prepared from submerged cultured C. sinensis BCRC36421 was investigated in human peripheral blood. Results demonstrated that Fr. A (exo-polysaccharides, 0.025 approximately 0.1 mg/ml) induced the production of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10 dose-dependently. Fr. A, as low as 0.025 mg/ml, could significantly augment surface expression of CD11b in monocytes and polymorphonuclear neutrophils. Functional assay revealed that Fr. A (0.05 mg/ml) also elevated phagocytosis in monocytes and PMN. On the other hand, Fr. B (intracellular polysaccharides) only moderately induced TNF-alpha release, CD11b expression, and phagocytosis at the same concentrations. Our results indicate that the immunomodulatory components of submerged cultured C. sinensis mainly reside in the culture filtrate.

Neuroprotective effects of corn silk maysin via inhibition of H2O2-induced apoptotic cell death in SK-N-MC cells.

Science.gov (United States)

Choi, Doo Jin; Kim, Sun-Lim; Choi, Ji Won; Park, Yong Il

2014-07-25

Neuroprotective effects of maysin, which is a flavone glycoside that was isolated from the corn silk (CS, Zea mays L.) of a Korean hybrid corn Kwangpyeongok, against oxidative stress (H2O2)-induced apoptotic cell death of human neuroblastoma SK-N-MC cells were investigated. Maysin cytotoxicity was determined by measuring cell viability using MTT and lactate dehydrogenase (LDH) assays. Intracellular reactive oxygen species (ROS) were measured using a 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by a TUNEL assay. Antioxidant enzyme mRNA levels were determined by real-time PCR. The cleavage of poly (ADP-ribose) polymerase (PARP) was measured by western blotting. Maysin pretreatment reduced the cytotoxic effect of H2O2 on SK-N-MC cells, as shown by the increase in cell viability and by reduced LDH release. Maysin pretreatment also dose-dependently reduced the intracellular ROS level and inhibited PARP cleavage. In addition, DNA damage and H2O2-induced apoptotic cell death were significantly attenuated by maysin pretreatment. Moreover, maysin pretreatment (5-50 μg/ml) for 2h significantly and dose-dependently increased the mRNA levels of antioxidant enzymes (CAT, GPx-1, SOD-1, SOD-2 and HO-1) in H2O2 (200 μM)-insulted cells. These results suggest that CS maysin has neuroprotective effects against oxidative stress (H2O2)-induced apoptotic death of human brain SK-N-MC cells through its antioxidative action. This report is the first regarding neuroprotective health benefits of corn silk maysin by its anti-apoptotic action and by triggering the expression of intracellular antioxidant enzyme systems in SK-N-MC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

MiRNA-135a regulates the expression of small conductance calcium-activated potassium (SK3) channels in epilepsy-like conditions

NARCIS (Netherlands)

Honrath, Birgit; Norwood, Braxton; Tanrioever, Gaye; Kuter, Katarzyna; Henshall, David C; Aksel-Aksoy, Ayla; Schratt, Gerhard; Pasterkamp, Jeroen; Dencher, Norbert A.; Nieweg, Katja; Culmsee, Carsten; Dolga, Amalia Mihalea

2017-01-01

Background Excessive and hypersynchronous neuronal discharges are key characteristics in the pathophysiology of neurological disorders such as epilepsy. Owing to their ability of regulating neuronal excitability, small conductance calcium-activated potassium (SK) channels have been implicated in

Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic): A Review.

Science.gov (United States)

Foroutan-Rad, Masoud; Tappeh, Khosrow Hazrati; Khademvatan, Shahram

2017-01-01

Leishmaniasis is caused by an obligate intracellular protozoa belonging to Leishmania genus. The current drugs for treatment of leishmaniasis possess many disadvantages; therefore, researchers are continuously looking for the more effective and safer drugs. The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. All relevant databases were searched using the terms "Allium sativum," "Garlic," "Allicin," "Ajoene," "Leishmania," "in vitro," "in vivo," and "clinical trial," alone or in combination from 5 English databases (Web of Science, PubMed, Science Direct, Scopus, Google Scholar) and 3 Persian databases (Scientific Information Database, Iran Medex, and Magiran) from 1990 to 2014. In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis. © The Author(s) 2015.

Andrographolide promotes vincristine-induced SK-NEP-1 tumor cell death via PI3K-AKT-p53 signaling pathway

Science.gov (United States)

Zhang, Mingsheng; Xue, Enda; Shao, Wei

2016-01-01

Background Nephroblastoma (Wilms’ tumor [WT]) is the most common malignant renal cancer in children. Although the outcome of WT has significantly improved as a result of the combination of surgery, chemotherapy, and radiotherapy; in some cases WT results in severe complications. Thus, novel strategies that would decrease treatment burden are required. The aim of the current study was to investigate the synergistic antitumor effect of andrographolide (AND) in combination with vincristine (VCR) on WT cells. Methods Cell Counting Kit-8 assay was used to investigate the synergistic antiproliferation effect of AND and/or VCR on SK-NEP-1 cells in vitro. Meanwhile, SK-NEP-1 xenografts were used to detect the antitumor effect in vivo. Apoptosis and autophagy were then detected by Annexin V, monodansylcadaverine staining. Finally, the underlying signaling transduction was determined with Western blotting. Results The combination of AND with VCR significantly suppressed SK-NEP-1 cell proliferation in vitro and inhibited xenograft tumor growth in vivo, compared with AND or VCR treatment alone. In addition, the synergistic antitumor effect of AND on the cells was due to an increased apoptosis, not autophagy. Moreover, PI3K-AKT-p53 signaling pathway was involved in the process of combination treatment, which was confirmed when a selective AKT activator was applied. Conclusion The combination of AND with VCR has a strong synergistic antitumor effect on WT via PI3K-AKT-p53 signaling pathway, thereby representing a potential treatment for WT in the near future. PMID:27729773

A Parametric Study on the Immunomodulatory Effects of Electroacupuncture in DNP-KLH Immunized Mice

Directory of Open Access Journals (Sweden)

Sun Kwang Kim

2011-01-01

Full Text Available This study was conducted to compare the effects of low frequency electroacupuncture (EA and high frequency EA at acupoint ST36 on the production of IgE and Th1/Th2 cytokines in BALB/c mice that had been immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH, as well as to investigate the difference in the immunomodulatory effects exerted by EA stimulations at acupoint ST36 and at a non-acupoint (tail. Female BALB/c mice were divided into seven groups: normal (no treatments, IM (immunization only, ST36-PA (IM + plain acupuncture at ST36, ST36-LEA (IM + low frequency (1 Hz EA at ST36, ST36-HEA (IM + high frequency (120 Hz EA at ST36, NA-LEA (IM + low frequency (1 Hz EA at non-acupoint and NA-HEA (IM + high frequency (120 Hz EA at non-acupoint. EA stimulation was performed daily for two weeks, and total IgE, DNP-KLH specific IgE, IL-4 and IFN-γ levels were measured at the end of the experiment. The results of this study showed that the IgE and IL-4 levels were significantly suppressed in the ST36-LEA and ST36-HEA groups, but not in the NA-LEA and NA-HEA groups. However, there was little difference in the immunomodulatory effects observed in the ST36-LEA and ST36-HEA groups. Taken together, these results suggest that EA stimulation-induced immunomodulation is not frequency dependent, but that it is acupoint specific.

Vypravěčské strategie v povídkách Raymonda Carvera

OpenAIRE

SELNER, Ondřej

2016-01-01

The thesis Vypravěčské strategie v povídkách Raymonda Carvera deals with the literary concept of a narrator. It's results - typologically different narrators and their characterizations - are based on reading and analysis of all published Carver's short stories. The thesis is divided into two main parts - into the theoretical part in which we briefly introduce the development and fundamental concepts of narrator in the literary theory (e.g. in concepts of F. K. Stanzel, K. Friedmann, G. Genet...

Grasshoppers (Orthoptera: Caelifera and crickets (Orthoptera: Ensifera from slopes of Macošská stráň and Vilémovická stráň (Moravský kras Protected landscape area, Czech Republic

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Jana Niedobová

2011-01-01

Full Text Available In 2008 we found 21 species of grasshoppers and crickets on Macošská stráň slope and 18 species on Vilémovická stráň slope. Both slopes are located in the northern part of the Moravský kras Protected landscape area and have xerothermic character. Both slopes are influenced by pasture management. For the most comprehensive picture of Orthoptera we used a standard method (sweeping of vegetation and nonstandard methods (pitfall traps and Möricke yellow cups. Termophilous species of Orthoptera on Macošská stráň (47% were dominating. On Vilémovická stráň mezophilous species (46% were dominating. The most common species were Stenobothrus lineatus (Panzer, 1796 on Macošská stráň slope and Chorthippus parallelus (Zetterstedt, 1821, Stenobothrus lineatus, Chorthippus bigutulus (Linné, 1758 and Chorthippus dorsatus (Zetterstedt, 1821 on Vilémovická stráň slope. Rare species of this assemblage were Stenobothrus nigromaculatus (Herrich-Schaffer, 1840 which was on Macošská stráň slope only and Tetrix bipunctata (Linnaeus, 1758 which has much bigger abundances also on Macošská stráň slope.

Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

DEFF Research Database (Denmark)

Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

2011-01-01

• To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri...

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.

Science.gov (United States)

Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

2017-10-01

To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

Mesenchymal stromal cells express GARP/LRRC32 on their surface: effects on their biology and immunomodulatory capacity.

Science.gov (United States)

Carrillo-Galvez, Ana Belén; Cobo, Marién; Cuevas-Ocaña, Sara; Gutiérrez-Guerrero, Alejandra; Sánchez-Gilabert, Almudena; Bongarzone, Pierpaolo; García-Pérez, Angélica; Muñoz, Pilar; Benabdellah, Karim; Toscano, Miguel G; Martín, Francisco; Anderson, Per

2015-01-01

Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine involved in MSC migration, differentiation, and immunomodulation. Recently, glycoprotein A repetitions predominant (GARP) was shown to bind latency-associated peptide (LAP)/TGF-β1 to the cell surface of activated Foxp3(+) regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF-β1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF-β1 and reduced their proliferative capacity in a TGF-β1-independent manner. Importantly, we showed that GARP expression on MSCs contributed to their ability to inhibit T-cell responses in vitro. In summary, we have found that GARP is an essential molecule for MSC biology, regulating their immunomodulatory and proliferative activities. We envision GARP as a new target for improving the therapeutic efficacy of MSCs and also as a novel MSC marker. © 2014 AlphaMed Press.

Immunomodulatory effects of herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mice with lung cancer.

Science.gov (United States)

Zhou, Xing; Liu, Zijing; Long, Tingting; Zhou, Lijng; Bao, Yixi

2018-01-01

This study is to investigate the immunomodulatory effects of the herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mouse models of immunosuppression and lung cancer. Immune parameters were recorded for these model mice. Peripheral white blood cells (WBC) were detected with the automatic blood cell analyzer. Spleen and thymus indices, and tumor inhibition ratio were obtained. Percentage of peripheral blood CD4 + and CD8 + T lymphocytes were detected by flow cytometry. Serum levels of Th1 (IL-2, TNF, and IFN-γ), Th2 (IL-4, IL-6, and IL-10), and Th17 (IL-17A) were detected with the BD cytometric bead array (CBA) mouseTh1/Th2/Th17 cytokine kit. Compared with the NS group, the PSP and APS herbal formula significantly improved the WBC, thymus index, spleen index, CD4 + /CD8 + ratio, TNF, IFN-γ, IL-2, andIL-17Ainimmunosuppressivemice and lung cancer mice (PAPS herbal formula group (PAPS herbal formula group induced comparable tumor inhibiting effect with the AMD group (23.3% and 24.1%, respectively). The PSP+APS herbal formula have immunomodulatory effects and anti-tumor activity in mice with of lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunomodulatory effect of Mesenchymal Stem Cells on B cells

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Marcella eFranquesa

2012-07-01

Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

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Milo, Ron

2015-04-01

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

In vitro pyrogen test for toxic or immunomodulatory drugs.

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Daneshian, Mardas; Guenther, Armin; Wendel, Albrecht; Hartung, Thomas; von Aulock, Sonja

2006-06-30

Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After rinsing, the beads are incubated with human whole blood and the release of the endogenous pyrogen interleukin-1beta is measured as a marker of pyrogenic activity. Intentional contaminations with lipopolysaccharide were retrieved from the chemotherapeutic agents paclitaxel, cisplatin and liposomal daunorubicin, the antibiotic gentamicin, the antifungal agent liposomal amphotericin B, and the corticosteroid prednisolone at lower dilutions than in the standard in vitro pyrogen test. This represents a promising new approach for the detection of pyrogenic contamination in drugs or in drugs containing interfering additives and should lead to improved safety levels.

In vivo immunomodulatory effects of the methanolic leaf extract of Gymnema sylvestre in Swiss albino mice

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Ahirwal Laxmi

2015-01-01

Full Text Available In the present study we performed a comparative phytochemical analysis of the immunomodulating activities of the methanol leaf extract of Gymnema sylvestre (MLEGS in Swiss albino mice. The phytochemical screening conducted on MLEGS revealed the presence of several phytoconstituents, including saponins, alkaloids, glycosides, phenols, tannins, and flavonoids. Immunomodulatory activities were determined by hemagglutination antibody (HA titer and delayed-type hypersensitivity (DTH tests for determining specific and non-specific immune responses. Flow cytometric techniques were performed for the estimation of B lymphocytes (CD3 and CD19 and Th2 cytokines (IL-2, IFN-γ and IL-4. The response produced by oral administration of MLEGS elicited a significant reduction in a dose-related manner in the primary and secondary antibody response and DTH response. The response produced by oral administration of MLEGS elicited significant reduction in a dose-related manner in the primary and secondary antibody and DTH responses, with maximum reduction observed at 200 mg/kg-body wt. The maximal reductions in the production of CD3, CD19, IL-2, IFN-γ and IL-4 were 31.59, 32.12, 29.51, 32.45 and 33.53%, respectively, at 200 mg/kg body weight. This study demonstrates that G. sylvestre exerts immunosuppressive effects on the components of the immune system of mice, and points to its significant immunomodulatory potential.

Immunomodulatory effects of royal jelly on aorta CD3, CD68 and eNOS expression in hypercholesterolaemic rats

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Amal Attia El-Morsy Ibrahim

2014-08-01

RJ administration (300 mg/kg/day with CH, produced a counteractive effect, represented in recompense of biochemical alteration, CD4 and CD8 expression. RJ intake also amended the histological picture. The immunohistochemical picture revealed a decrease in CD3, CD86 and eNOS in the aortic tissue. These findings attributed to the significant immunomodulatory effect of RJ remedy suppress deleterious effects of hypercholesterolaemia.

Effect of ultrasonic extraction conditions on antioxidative and immunomodulatory activities of a Ganoderma lucidum polysaccharide originated from fermented soybean curd residue.

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Shi, Min; Yang, Yingnan; Hu, Xuansheng; Zhang, Zhenya

2014-07-15

A crude Ganoderma lucidum polysaccharide (GLPL) was extracted from fermented soybean curd residue by ultrasonic assisted extraction. The optimal extraction conditions were 30 min at 80 °C with 80 W and water to solid ratio of 10, and with this method 115.47 ± 2.95 mg/g of GLPL yield was obtained. Additionally, the antioxidant and immunomodulatory activities of GLPL were investigated. The results showed that GLPL exhibited strong antioxidant effects, which included scavenging activities against DPPH radicals, hydrogen oxide and ABTS radicals with IC50 values of 0.23, 0.48 and 0.69 mg/mL, respectively. For immunomodulatory activities, GLPL was shown to strongly stimulate the proliferation of macrophages (158.02 ± 13.12%), the production of nitric oxide and phagocytosis (21.16 ± 1.65 μM), and, at 40.00 μg/mL, protected macrophage from Doxorubicin (DOX) (0.16 ± 0.003). Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism.

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Alazami, Anas M; Al-Owain, Mohammad; Alzahrani, Fatema; Shuaib, Taghreed; Al-Shamrani, Hussain; Al-Falki, Yahya H; Al-Qahtani, Saleh M; Alsheddi, Tarfa; Colak, Dilek; Alkuraya, Fowzan S

2012-10-01

Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype. © 2012 Wiley Periodicals, Inc.

Immunomodulatory effect of vitamin K2: Implications for bone health.

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Myneni, V D; Mezey, E

2018-03-01

In women with postmenopausal osteoporosis, vitamin K2 appears to decrease the incidence of hip, vertebral, and non-vertebral fractures. Women with postmenopausal osteoporosis have more circulating activated T cells compared with healthy postmenopausal and premenopausal women, but the effects of vitamin K2 on T cells have not been studied. In this study, we have looked at T-cell suppression by vitamin K2. Peripheral blood mononuclear cells (PBMCs) from three healthy donors were used. The PBMCs were stimulated with the mitogens phytohemagglutinin and concanavalin A, and T-cell proliferation was analyzed using flow cytometry based on carboxyfluorescein succinimidyl ester (CSFE) dye dilution. Vitamin K2 (60 and 100 μM) inhibited T-cell proliferation. Vitamin K1 at the same concentrations did not inhibit T-cell proliferation. Vitamin K2 has immunomodulatory activities. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Immunomodulatory Role of Stem Cell from Human Exfoliated Deciduous Teeth on Periodontal Regeneration.

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Gao, Xianling; Shen, Zongshan; Guan, Meiliang; Huang, Qiting; Chen, Lingling; Qin, Wei; Ge, Xiaohu; Chen, Haijia; Xiao, Yin; Lin, Zhengmei

2018-03-20

Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multi-dose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophages conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for approximately 7 days in periodontal tissues with little tissue diffusion. Then, multi-dose SHEDs delivery was applied to treat periodontitis at 7-day intervals. Results showed that muti-dose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHEDs administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest (CEJ-ABC). Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2

First report on intersex in invasive round goby Neogobius melanostomus from the Baltic Sea (Gulf of Gdańsk, Poland

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Tatiana Guellard

2015-01-01

Full Text Available This study is the first to report the presence of intersex in invasive round goby Neogobius melanostomus inhabiting the Baltic Sea. The discovery was made in the area of two harbours of the Gulf of Gdańsk (Poland. Macro- and microscopic male gonad analysis revealed the presence of female gametes in testes (testis-ova of single specimens. In addition, a female-like urogenital papilla was observed in one of the intersex fish. These findings might be due to the exposure to estrogenic endocrine disrupting compounds (EDCs however the occurrence of single intersex individuals as a baseline level in investigated population is also possible. In the future, more comprehensive research in the other areas of the Gulf of Gdańsk needs to be carried out in order to determine the extent and to better understand the cause of the observed phenomenon.

Effect of arthritic synovial fluids on the expression of immunomodulatory factors by mesenchymal stem cells: an explorative in-vitro study

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Maarten J.C. Leijs

2012-08-01

Full Text Available Background: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs can have immunomodulatory effect by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. Materials & Methods: MSCs were cultured in medium with SF of six osteoarthritis (OA or six rheumatoid arthritis (RA donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1 and indoleamine 2,3-dioxygenase (IDO were analysed. L-kynurenine concentration in conditioned medium (CM by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analysed. Results: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA induced significantly higher expression of IDO than SF(control, although no difference in IDO activity of the MSCs could be shown with a L-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control.Discussion: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.

Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties.

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Aravind, S R; Krishnan, Lissy K

2016-05-01

Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates

Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares

DEFF Research Database (Denmark)

Christoffersen, Mette; Woodward, Elizabeth; Bojesen, Anders Miki

2012-01-01

endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study...... inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory...

The Chinese Cretaceous Continental Scientific Drilling Project in the Songliao Basin, NE China: Organic-rich source rock evaluation with geophysical logs from Borehole SK-2

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Zhang, X.; Zou, C.

2017-12-01

The Cretaceous strata have been recognized as an important target of oil or gas exploration in the Songliao Basin, northeast China. The second borehole (SK-2) of the Chinese Cretaceous Continental Scientific Drilling Project in the Songliao Basin (CCSD-SK) is the first one to drill through the Cretaceous continental strata in the frame of ICDP. It was designed not only to solve multiple scientific problems (including the Cretaceous paleoenvironment and paleoclimate, as well as deep resources exploration of the Songliao Basin), but also to expect to achieve new breakthroughs in oil and gas exploration. Based on the project, various geophysical log data (including gamma, sonic, resistivity, density etc.) and core samples have been collected from Borehole SK-2. We do research on organic-rich source rocks estimation using various geophysical log data. Firstly, we comprehensively analyzed organic-rich source rocks' geophysical log response characteristics. Then, source rock's identification methods were constructed to identify organic-rich source rocks with geophysical logs. The main identification methods include cross-plot, multiple overlap and Decision Tree method. Finally, the technique and the CARBOLOG method were applied to evaluate total organic carbon (TOC) content from geophysical logs which provide continuous vertical profile estimations (Passey, 1990; Carpentier et al., 1991). The results show that source rocks are widely distributed in Borehole SK-2, over a large depth strata (985 5700m), including Nenjiang, Qingshankou, Denglouku, Yingcheng, Shahezi Formations. The organic-rich source rocks with higher TOC content occur in the Qingshankou (1647 1650m), Denglouku (2534 2887m) and Shahezi (3367 5697m) Formations. The highest TOC content in these formations can reach 10.31%, 6.58%, 12.79% respectively. The bed thickness of organic-rich source rocks in the these formations are totally up to 7.88m, 74.34m, 276.60m respectively. These organic-rich rocks in the

Immunomodulatory effects of hydroxyethylated Hericium erinaceus polysaccharide on macrophages RAW264.7.

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Ren, Zhe; Qin, Tao; Qiu, Fuan; Song, Yulong; Lin, Dandan; Ma, Yufang; Li, Jian; Huang, Yifan

2017-12-01

Hericium erinaceus polysaccharide (HEP) has been shown to possess a variety of biological activities. In present study, HEP was successfully modified to obtain its hydroxyethylated derivative hHEP. Its potential immunomodulatory activities on RAW264.7 macrophages were investigated. Results showed that the hHEP were significantly stronger than that of the corresponding unmodified polysaccharide, HEP. Meanwhile, the NO, IL-6 and TNF-α production activities of macrophages were enhanced in the RAW264.7 macrophages by stimulation of hHEP. In addition, the hHEP increase significantly higher iNOS expression than HEP. These results indicated that the hydroxyethylated derivative hHEP could enhance the activation of peritoneal macrophages, and hydroxyethylation modification can enhance the immunomodulation function of HEP. Copyright © 2017 Elsevier B.V. All rights reserved.

Pääsküla sõjaväeobjekti jääkreostus ning piirkonna edasise kasutamise perspektiivid / Triin Uudeväli, Anto Raukas

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Uudeväli, Triin

2004-01-01

Pääskülas asunud NL-i raketijuhtimisekeskuse ja sideväeosa poolt tekitatud keskkonnareostuse hindamisest, likvideerimisest ning ettepanekutest territooriumi edasiseks kasutamiseks. Kaart. Skeem. Fotod

The Immunomodulatory Effect of Acupoint Application for Childhood Asthma: A Systematic Review and Meta-Analysis

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Xiao Cun Yang

2015-01-01

Full Text Available Objective. To evaluate the evidence on the immunomodulatory effect of acupoint application for childhood asthma. Methods. Five electronic databases through October 2014 were searched. The risk of bias in eligible studies was assessed using the Cochrane Collaboration tool. Standardised mean difference (SMD and 95% confidence intervals (CI of random-effects model were calculated. And heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results. Six studies were included in our review. The aggregated results suggested that acupoint application showed the beneficial effect for childhood asthma in improving IgA (SMD, −0.83; 95% CI −1.14 to −0.52; P<0.00001, IgE (SMD, −0.52; 95% CI −0.76 to −0.29; P<0.001, IgG (SMD, −1.17; 95% CI −1.61 to −0.74; P<0.0001, IL-4 (SMD, −0.57; 95% CI −0.91 to −0.23; P=0.0009, and IFN-γ (SMD, −0.38; 95% CI −0.71 to −0.04; P=0.03 but not IgM (SMD, −0.40; 95% CI −0.98 to 0.18; P=0.18. And the effective dose of acupoint application may be 2–6 hours/time and a total of 3 times within 4 weeks. Conclusions. This review showed the positive evidence that acupoint application had the favorable immunomodulatory effect for childhood asthma. However, more studies with long follow-up are warrant to confirm the current findings.

Functional characterization of six aspartate (D) recombinant mojastin mutants (r-Moj): A second aspartate amino acid carboxyl to the RGD in r-Moj-D_ peptides is not sufficient to induce apoptosis of SK-Mel-28 cells.

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Ramos, Carla J; Gutierrez, Daniel A; Aranda, Ana S; Koshlaychuk, Melissa A; Carrillo, David A; Medrano, Rafael; McBride, Terri D; U, Andrew; Medina, Stephanie M; Lombardo, Melissa C; Lucena, Sara E; Sanchez, Elda E; Soto, Julio G

2016-08-01

Disintegrins are small peptides produced in viper venom that act as integrin antagonists. When bound to integrins, disintegrins induce altered cellular behaviors, such as apoptotic induction. Disintegrins with RGDDL or RGDDM motifs induce apoptosis of normal and cancer cells. We hypothesized that a second aspartate (D) carboxyl to the RGD is sufficient to induce apoptosis. Five recombinant mojastin D mutants were produced by site-directed mutagenesis (r-Moj-DA, r-Moj-DG, r-Moj-DL, r-Moj-DN, and r-Moj-DV). Stable αv integrin knockdown and shRNA scrambled control SK-Mel-28 cell lines were produced to test a second hypothesis: r-Moj-D_ peptides bind to αv integrin. Only r-Moj-DL, r-Moj-DM, and r-Moj-DN induced apoptosis of SK-Mel-28 cells (at 29.4%, 25.6%, and 36.2%, respectively). Apoptotic induction was significantly reduced in SK-Mel-28 cells with a stable αv integrin knockdown (to 2%, 17%, and 2%, respectively), but not in SK-Mel-28 cells with a stable scrambled shRNA. All six r-Moj-D_ peptides inhibited cell proliferation; ranging from 49.56% (r-Moj-DN) to 75.6% (r-Moj-DA). Cell proliferation inhibition by r-Moj-D_ peptides was significantly reduced in SK-Mel-28 cells with a stable αv integrin knockdown. All six r-Moj-D_ peptides inhibited SK-Mel-28 cell migration at high levels (69%-100%). As a consequence, rac-1 mRNA expression levels were significantly reduced as early as 1 h after treatment, suggesting that rac-1 is involved in the cell migration activity of SK-Mel-28. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of vinegar–egg on growth inhibition, differentiation human leukemic U937 cells and its immunomodulatory activity

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Shiu-Yu Wang

2018-04-01

Full Text Available Vinegar and eggs have rich nutrients. In this study, the mixed form of both derived products, vinegar–egg solution and its products (vinegar–egg concentrate and vinegar–egg condensate were chosen for an assessment of their biological activity. To further our understanding regarding the anticancer and immunomodulatory effects of vinegar–egg, we investigated its effects on the proliferation and differentiation of U937 cells. Vinegar–egg was treated using spray drying, freeze drying and vacuum concentration and used to stimulate human mononuclear cells. The conditioned media obtained from these cultures by filtration were used to treat U937 cells. Three conditioned media inhibited U937 cell growth by 22.1–67.25% more effectively than PHA-treated control (22.53%. CD11b and CD14 expression on the treated U937 cells were 29.1–45.4% and 31.6–47.2%, respectively. High levels of cytokines IL-1β, IFN-γ and TNF-α were detected in the three conditioned media. Vinegar–egg stimulates human mononuclear cells to secrete cytokines, which inhibit the growth of U937 cells and induce their differentiation. Keywords: Cytokines, Differentiation, Immunomodulatory activity, Leukemic U937 cells, Vinegar–egg

Andrographolide promotes vincristine-induced SK-NEP-1 tumor cell death via PI3K-AKT-p53 signaling pathway

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Zhang M

2016-09-01

Full Text Available Mingsheng Zhang, Enda Xue, Wei Shao Department of Pediatric Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong Province, People’s Republic of China Background: Nephroblastoma (Wilms’ tumor [WT] is the most common malignant renal cancer in children. Although the outcome of WT has significantly improved as a result of the combination of surgery, chemotherapy, and radiotherapy; in some cases WT results in severe complications. Thus, novel strategies that would decrease treatment burden are required. The aim of the current study was to investigate the synergistic antitumor effect of andrographolide (AND in combination with vincristine (VCR on WT cells.Methods: Cell Counting Kit-8 assay was used to investigate the synergistic antiproliferation effect of AND and/or VCR on SK-NEP-1 cells in vitro. Meanwhile, SK-NEP-1 xenografts were used to detect the antitumor effect in vivo. Apoptosis and autophagy were then detected by Annexin V, monodansylcadaverine staining. Finally, the underlying signaling transduction was determined with Western blotting.Results: The combination of AND with VCR significantly suppressed SK-NEP-1 cell proliferation in vitro and inhibited xenograft tumor growth in vivo, compared with AND or VCR treatment alone. In addition, the synergistic antitumor effect of AND on the cells was due to an increased apoptosis, not autophagy. Moreover, PI3K-AKT-p53 signaling pathway was involved in the process of combination treatment, which was confirmed when a selective AKT activator was applied.Conclusion: The combination of AND with VCR has a strong synergistic antitumor effect on WT via PI3K-AKT-p53 signaling pathway, thereby representing a potential treatment for WT in the near future. Keywords: andrographolide, vincristine, p53, drug combination

The immunomodulatory effects of titanium dioxide and silver nanoparticles.

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Lappas, Courtney M

2015-11-01

Due to their characteristic physical, chemical and optical properties, titanium dioxide and silver nanoparticles are attractive tools for use in a wide range of applications. The use of nanoparticles for biological applications is, however, dependent upon their biocompatibility with living cells. Because of the importance of inflammation as a modulator of human health, the safe and efficacious in vivo use of titanium dioxide and silver nanoparticles is inherently linked to a favorable interaction with immune system cells. However, both titanium dioxide and silver nanoparticles have demonstrated potential to exert immunomodulatory and immunotoxic effects. Titanium dioxide and silver nanoparticles are readily internalized by immune system cells, may accumulate in peripheral lymphoid organs, and can influence multiple manifestations of immune cell activity. Although the factors influencing the biocompatibility of titanium dioxide and silver nanoparticles with immune system cells have not been fully elucidated, nanoparticle core composition, size, concentration and the duration of cell exposure seem to be important. Because titanium dioxide and silver nanoparticles are widely utilized in pharmaceutical, commercial and industrial products, it is vital that their effects on human health and immune system function be more thoroughly evaluated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wytrzymałość na ścinanie odpadów komunalnych a stateczność skarp składowisk

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Tymoteusz Zydroń

2015-12-01

Full Text Available W pierwszej części pracy dokonano analizy literatury tematycznej dotyczącej parametrów charakteryzujących wytrzymałość na ścinanie odpadów komunalnych. Wykazała ona, że odpady komunalne charakteryzują się bardzo zróżnicowanymi warto­ściami kąta tarcia wewnętrznego i spójności, które zależą m.in. od ich struktury, stopnia rozkładu, metody badań, w tym zakresu odkształceń. Wpływ tych czynników na wytrzyma­łość na ścinanie odpadów jest często niejednoznaczny, co powoduje, że dobór parametrów wytrzymałościowych dla prognozowania stateczności składowisk jest zadaniem złożonym. W drugiej części pracy dokonano obliczeń stateczności skarpy kwatery składowiska od­ padów komunalnych w Chełmku, wykorzystując wartości parametrów wytrzymałościowych przyjętych z przedmiotowej literatury. Wykazano, że tradycyjna metoda obliczeń stateczności skarpy składowiska, z zastosowaniem uśrednionych parametrów wytrzyma­łościowych odpadów, dała wysoką wartość współczynnika stateczności, natomiast analiza probabilistyczna wykazała, że bezpieczeństwo konstrukcji można uznać jako sytuujące się pomiędzy słabym, a przeciętnym.

Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection

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Yi Jin

2013-01-01

Full Text Available The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR. These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.

Purification, characterization and immunomodulatory activity of polysaccharides from stem lettuce.

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Nie, Chenzhipeng; Zhu, Peilei; Ma, Shuping; Wang, Mingchun; Hu, Youdong

2018-05-15

Stem lettuce has a long history of cultivation in China and possesses high nutritional and medicinal value. In our previous studies, extraction optimization, characterization, and bioactivities of stem lettuce polysaccharides (SLP) were investigated. In this study, SLP were further separated into two purified polysaccharides, SLP-1 and SLP-2, by anion exchange chromatography followed by size exclusion chromatography. SLP-1, with a molecular weight of 90 KDa, was mainly composed of galacturonic acid, galactose and arabinose in a molar ratio of 17.6:41.7:33.9. SLP-2, with a molecular weight of 44 KDa, was mainly composed of mannose, galacturonic acid, galactose and arabinose in a molar ratio of 11.5:69.5:9.3:8.2. In addition, both purified polysaccharides contain sulphate radicals, have triple helical structures and can promote macrophage proliferation without cytotoxicity. SLP-2 was better able to stimulate phagocytic and nitric oxide production than SLP-1. The results suggest that polysaccharides from stem lettuce could be explored as immunomodulatory agents in the field of pharmaceuticals and functional foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

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Valérie Rodrigues

2018-01-01

Full Text Available The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86 and by measuring the production of nitric oxide (NO and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein. We also characterized an intriguing ubiquitination complex that could be involved in

Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

Science.gov (United States)

Rodrigues, Valérie; Fernandez, Bernard; Vercoutere, Arthur; Chamayou, Léo; Andersen, Alexandre; Vigy, Oana; Demettre, Edith; Seveno, Martial; Aprelon, Rosalie; Giraud-Girard, Ken; Stachurski, Frédéric; Loire, Etienne; Vachiéry, Nathalie; Holzmuller, Philippe

2018-01-01

The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva

A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

International Nuclear Information System (INIS)

Altenburg, Jeffrey D; Bieberich, Andrew A; Terry, Colin; Harvey, Kevin A; VanHorn, Justin F; Xu, Zhidong; Jo Davisson, V; Siddiqui, Rafat A

2011-01-01

Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED 50 . Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER - PR - Her2 + ) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes

Cytotoxic and Immunomodulatory Potential Activity of Physalis peruviana Fruit Extracts on Cervical Cancer (HeLa) and Fibroblast (L929) Cells.

Science.gov (United States)

Mier-Giraldo, Helen; Díaz-Barrera, Luis Eduardo; Delgado-Murcia, Lucy Gabriela; Valero-Valdivieso, Manuel Fernando; Cáez-Ramírez, Gabriela

2017-10-01

It was purposed to evaluate the biological potential of ethanol and isopropanol crude extracts of ripe Physalis peruviana fruits. Cytotoxic and immunomodulatory effects of the expression of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 (MCP-1) were evaluated on human cervical cancer (HeLa) and murine fibroblast (L929) cells. The composition was evaluated by high-performance liquid chromatography diode-array detection and high-performance liquid chromatography ultraviolet/visible detection. The presence of ursolic acid and rosmarinic acid was found in both solvents. However, gallic acid, quercetin, and epicatechin were higher in isopropanol extracts ( P < .05). The results indicated a relationship among the total polyphenol content, antioxidant activity, and cytotoxic activity that was dependent on the solvent used. Isopropanol extracts presented a half-maximal inhibition concentration value (IC 50 ) of 60.48 ± 3.8 μg/mL for HeLa cells and 66.62 ± 2.67 μg/mL for L929 fibroblasts. The extracts reduced the release of interleukin-6, interleukin-8, and MCP-1 in a dose-dependent manner. Extracts showed anticancer and immunomodulatory potential for new complementary pharmaceutical products development.

Characterization of Two Homogalacturonan Pectins with Immunomodulatory Activity from Green Tea

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Huijun Wang

2014-06-01

Full Text Available Two natural homogalacturonan (HG pectins (MW ca. 20 kDa were isolated from green tea based on their immunomodulatory activity. The crude tea polysaccharides (TPS1 and TPS2 were obtained from green tea leaves by hot water extraction and followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water soluble polysaccharides (TPS1-2a and TPS1-2b were obtained from TPS1 after purification with gel permeation, which gave a higher phagocytic effect than TPS2. A combination of composition, methylation and configuration analyses, as well as NMR (nuclear magnetic resonance spectroscopy revealed that TPS1-2a and TPS1-2b were homogalacturonan (HG pectins consisting of a backbone of 1,4-linked α-d-galacturonic acid (GalA residues with 28.4% and 26.1% of carboxyl groups as methyl ester, respectively. The immunological assay results demonstrated that TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing activity in HL-60 cells.

Design, Synthesis, and Biological Evaluation of γ-Aminopropyl Silatrane-Acyclovir Hybrids with Immunomodulatory Effects.

Science.gov (United States)

Ye, Faqing; Song, Xiaoqin; Liu, Jianmin; Xu, Xuemei; Wang, Yuewu; Hu, Lichuan; Wang, Yi; Liang, Guang; Guo, Ping; Xie, Zixin

2015-10-01

Several derivatives of γ-aminopropyl silatrane containing acyclovir in their molecular structure were synthesized and evaluated for their immunomodulatory and antiviral activities. The structures of all these derivatives were confirmed by mass spectra, IR, and (1) H NMR. Based on WST-1 assay in vitro, these compounds could stimulate proliferation of splenic lymphocytes at certain concentrations. Furthermore, compound 3d could also potentiate the expression of IFN-γ, IL-2, CD4(+) , CD8(+) , and CD4(+) /CD8(+) in vivo. Our results show that these derivatives possess antiviral activity against herpes simplex viruses with a similar potency to acyclovir without a cellular immune response. © 2015 John Wiley & Sons A/S.

On the nature of capture centers in irradiated ceramics SK-1

International Nuclear Information System (INIS)

Ashurov, M.Kh.; Gasanov, E.M.; Kim, Gen Chan; Nuritdinov, I.; Saidahmedov, Kh.

2006-01-01

Full text: Along with other methods, for detection of radiation defects, the luminescent methods are widely used. One of such methods is the thermo-stimulated luminescence (TSL) method. By using this method, information on nature and energy depth (E c ) of capture centers can be obtained. In this work, the influence of high dose γ--irradiation on magnesial ceramics SK-1 was studied by the TL method. The samples were irradiated with ' 60 Co source, and the γ-irradiation dose varied between 10 4 and 10 10 R. The TL curves were measured in the temperature ranges from 80 to 700 K. As a result of irradiation the samples acquired brown colour. After γ-irradiation one can see the peak with maximum of 220 K and the peaks with 428, 548 and 658 K in the low-temperature ( 300 K) regions of the TL curves, respectively. To determine the nature of capture centers the samples were annealed in the air-conditions environment. Annealing conditions do not lead to changes in intensities of the existing TL peaks. After heat treatment in air the increase in intensity of 220, 428 and 548 K of TLS peaks can be observed, whereas in 10-hour treatment the saturation can be observed. Besides, the TL peaks at 353-363 K appears. Consequent restoring annealing decreases intensities of 220, 428 and 548 K and leads to disappearing peaks at 353-363 K. The energy depth values E c calculated by the Uhrbach formula E c =T, K/500 occurred to be : 0,44 eV; 0,86 eV and 1,096 eV for 220, 428 and 548 K, respectively. Besides, at annealing the increase of reflection characteristics of ceramics samples within 300-700 nm in observed, whereas the reflection intensities fall for the samples undergone the annealing. The analysis of the experimental results demonstrated that 220, 428 and 548 K peaks and additional absorption in the region of 300-700 nm are conditioned by V-centers. Possible mechanisms of CC formation and improvement of explanation characteristics of SK-1 ceramics in the ionization fields are

The effect of VMP35 supplement ingredients encapsulated in a novel Phospholipid Prodosome SK713 SLP nutrient delivery technology on properties of live human blood.

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Kenneth Blum

2015-09-01

Full Text Available Background: In North America digestive malfunction in terms of disintegration, dissolution, and absorption of food and nutrients, is a widespread malady. Malabsorption is also an exacerbating factor in most chronic degenerative diseases that might benefit from dietary supplementation. The purpose of this experiment was to determine, as shown by changes in properties of live blood, whether, a novel soy-lecithin-phospholipid-nutrient encapsulation technology could promote rapid bioavailability and bioactivity of a VMP35 nutraceutical formulation encapsulated within its clustoidal multilamellar Soy Lecithin Phospholipid (SLP liquid SK713 SLP structures. Method: Changes in peripheral blood smears from 38 subjects were measured utilizing peripheral live blood cell imaging (LBCI with phase contrast microscopy. Results: Compared to baseline and control, consistently and reproducibly, the SK713 SLP technology effected positive changes in the blood as demonstrated by observable morphological, hematological and rheological changes five minutes from intake and sustained for at least 30 minutes post intake. Conclusions: These results showed that the SK713 SLP system makes an important contribution by increasing the potential benefits of dietary supplementation to those patients with compromised digestive processes. We encourage additional research on this novel delivery system believing that it has potential impact on future therapy.

Ulcer: An Antioxidative Trail Weaved with Immunomodulatory Effect

Directory of Open Access Journals (Sweden)

Ananya Chatterjee

2011-01-01

Full Text Available Amla (Phyllanthus emblica L., apart from its food value, can be used as a gastroprotective agent in non steroidal anti-inflammatory drug (NSAID-induced gastropathy. It has been suggested that the antioxidative property of amla is the key to its therapeutic effect. Hence, on the basis of in vitro antioxidative potential, the ethanolic extract of amla (eAE was selected for in vivo study in NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated mice, with healing effect observed at 60 mg/kg and an adverse effect at 120 mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro-oxidant shift and immunomodulatory property could be the major cause for its biphasic effect, as evident from the total antioxidant status, thiol concentration, lipid peroxidation, protein carbonyl content followed by mucin content, PGE2 synthesis and cytokine status. Further, Buthionine sulfoxamine (BSO pretreatment established the potential impact of antioxidative property in the healing action of eAE. However, eAE efficiently reduced pro-inflammatory cytokine (TNF- and IL-1 levels and appreciably upregulate anti-inflammatory cytokine (IL-10 concentration. In conclusion, gastric ulcer healing induced by eAE was driven in a dose-specific manner through the harmonization of the antioxidative property and modulation of anti-inflammatory cytokine level.

MIBG causes oxidative stress and up-regulation of anti-oxidant enzymes in the human neuroblastoma cell line SK-N-BE(2c)

NARCIS (Netherlands)

Cornelissen, J.; van Kuilenburg, A. B.; Voûte, P. A.; van Gennip, A. H.

1997-01-01

We report the effects of meta-iodobenzylguanidine (MIBG), a neuroblastoma-seeking agent, on cell proliferation and several oxidative stress-related parameters in the human neuroblastoma cell line SK-N-BE(2c). MIBG inhibited the proliferation of this cell line in micromolar concentrations.

Immunomodulatory activity of dioscorin, the storage protein of yam (Dioscorea alata cv. Tainong No. 1) tuber.

Science.gov (United States)

Liu, Yen-Wenn; Shang, Huey-Fang; Wang, Chung-Kwe; Hsu, Feng-Lin; Hou, Wen-Chi

2007-11-01

The purified dioscorin from yam (Dioscorea alata L. cv. Tainong 1) tuber was previously reported (Hsu et al., 2002. J. Agric. Food Chem., 50, 6109-6113). In this report, we evaluated its immunomodulatory ability in vitro in the presence of polymyxin B (50 microg/ml) to eliminate lipopolysaccharide (LPS) contamination. Dioscorin (5-100 microg/ml) was able to stimulate nitric oxide production (expressed as nitrite concentrations) in RAW264.7 cells. The stimulation index on the phagocytosis of RAW264.7 cells against E. coli and the oxidative burst (determined by the intensity of rhodamine fluorescence) of RAW264.7 cells were both enhanced by different concentrations of dioscorin (5-100 microg/ml). The cytokine production, including IL-6, TNF-alpha, and IL-1beta in dioscorin-treated RAW264.7 cells or human monocytes, was measured in the cultured medium. Dioscorin (5-100 microg/ml) was found able to induce IL-6, TNF-alpha, and IL-1beta production in RAW264.7 cells and human monocytes. To evaluate the effects of dioscorin on the proliferation of spleen cells from BALB/c mice, phytohemagglutinin (PHA, 2 microg/ml) alone or PHA mixed with different concentrations of dioscorin (10, 25, and 50 microg/ml) was used to treat spleen cells for 24h. The stimulated proliferation index of splenic cells ranged from 1.38- to 1.48-fold of PHA alone for PHA mixed with different concentrations of dioscorin (10, 25, and 50 microg/ml). We suggest that the tuber storage protein of yam dioscorin functions as an immunomodulatory substance.

German register for detection of late sequelae after radiotherapy for children and adolescents (RiSK): present status and first results

International Nuclear Information System (INIS)

Boelling, T.; Schuck, A.; Willich, N.; Pape, H.; Ruebe, C.; Meyer, F.M.; Martini, C.; Timmermann, B.; Asadpour, B.; Kortmann, R.D.; Beck, J.D.; Langer, T.; Paulides, M.

2007-01-01

Undoubtedly, radiotherapy is an important treatment strategy for many malignancies in paediatric oncology. However, sufficient data about late side effects do not exist. There is a lack of information about radiation dose-effect relationships in view of late side effects in childhood and adolescence. Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Therefore the German Group of Paediatric Radiation Oncology (APRO) established the ''Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK)''. Aim of this prospective multicentric register study is to evaluate irradiation dose effect relationships of organs and part of organs with respect to late effects. The feasibility of RiSK has already been shown and first results have recently been published. The characterization of late effects after cancer therapy in childhood is of rising interest. In Germany, several study groups like the ''Late Effects Surveillance System'' (LESS) or the working group ''Quality of life'' examine different aspects of late effects. In the United States of America, the ''Childhood Cancer Survivor Study'' has been established to characterize retrospectively the health status of 5-year-survivors of childhood cancer. In these studies, more than 12,000 patients were evaluated by questionnaires regarding their health status. For radiotherapy, this study is not able to give detailed information about late side effects due to rare data about radiation doses and organ dose levels. To our knowledge, ''RiSK'' is the only multicentric study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. (orig.)

A numerical investigation of phytoplankton and Pseudocalanus elongatus dynamics in the spring bloom time in the Gdańsk Gulf

Science.gov (United States)

Dzierzbicka-Głowacka, Lidia

2005-01-01

A nutrient-phytoplankton-zooplankton-detritus (1D-NPZD) `phytoplankton {Phyt} and Pseudocalanus elongatus {Zoop} dynamics in the spring bloom time in the Gdańsk Gulf. The 1D-NPZD model consists of three coupled, partial second-order differential equations of the diffusion type for phytoplankton {Phyt}, zooplankton {Zoop}, nutrients {Nutr} and one ordinary first-order differential equation for benthic detritus pool {Detr}, together with initial and boundary conditions. In this model, the {Zoop} is presented by only one species of copepod ( P. elongatus) and {Zoop} is composed of six cohorts of copepods with weights ( Wi) and numbers ( Zi); where Zoop= limit∑i=16W iZ i. The calculations were made for 90 days (March, April, May) for two stations at Gdańsk Gulf with a vertical space step of 0.5m and a time step of 900 s. The flow field and water temperature used as the inputs in the biological model 1D-NPZD were reproduced by the prognostic numerical simulation technique using hydrographic climatological data. The results of the numerical investigations described here were compared with the mean observed values of surface chlorophyll- a and depth integrated P. elongatus biomass for 10 years, 1980-1990. The slight differences between the calculated and mean observed values of surface chlorophyll- a and zooplankton biomass are ca. 10-60 mg C m -3 and ca. 5-23 mg C m -2, respectively, depending on the location of the hydrographic station. The 1D-NPZD model with a high-resolution zooplankton module for P. elongatus can be used to describe the temporal patterns for phytoplankton biomass and P. elongatus in the centre of the Gdańsk Gulf.

German register for detection of late sequelae after radiotherapy for children and adolescents (RiSK): present status and first results

Energy Technology Data Exchange (ETDEWEB)

Boelling, T.; Schuck, A.; Willich, N. [Dept. of Radiotherapy of the Univ. Hospital Muenster (Germany); Pape, H. [Dept. of Radiotherapy of the Univ. Hospital Duesseldorf (Germany); Ruebe, C. [Dept. of Radiotherapy of the Univ. Saarland, Homburg/Saar (Germany); Meyer, F.M. [Dept. of Radiotherapy of the Clinic of Augsburg (Germany); Martini, C. [Dept. of Radiotherapy of the Univ. Hospitals Freiburg (Germany); Timmermann, B. [Paul Scherrer Inst., Villigen (Switzerland); Asadpour, B. [Dept. of Radiotherapy of the Univ. Hospital Aachen (Germany); Kortmann, R.D. [Dept. of Radiotherapy of the Univ. Hospital Leipzig (Germany); Beck, J.D.; Langer, T.; Paulides, M. [LESS Center, Univ. Children' s Hospital Erlangen (Germany)

2007-12-15

Undoubtedly, radiotherapy is an important treatment strategy for many malignancies in paediatric oncology. However, sufficient data about late side effects do not exist. There is a lack of information about radiation dose-effect relationships in view of late side effects in childhood and adolescence. Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Many of these analyses are limited due to little information about organ dose levels and older radiation techniques in some cases. Therefore the German Group of Paediatric Radiation Oncology (APRO) established the 'Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK)'. Aim of this prospective multicentric register study is to evaluate irradiation dose effect relationships of organs and part of organs with respect to late effects. The feasibility of RiSK has already been shown and first results have recently been published. The characterization of late effects after cancer therapy in childhood is of rising interest. In Germany, several study groups like the 'Late Effects Surveillance System' (LESS) or the working group 'Quality of life' examine different aspects of late effects. In the United States of America, the 'Childhood Cancer Survivor Study' has been established to characterize retrospectively the health status of 5-year-survivors of childhood cancer. In these studies, more than 12,000 patients were evaluated by questionnaires regarding their health status. For radiotherapy, this study is not able to give detailed information about late side effects due to rare data about radiation doses and organ dose levels. To our knowledge, 'RiSK' is the only multicentric study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. (orig.)

Elementary analysis and energetic potential of the municipal sewage sludges from the Gdańsk and Kościerzyna WWTPs

Science.gov (United States)

Ostojski, Arkadiusz

2018-01-01

This paper aims to present municipal sewage sludge (MSS) elementary analysis and energetic potential based on measurement of heat of combustion (higher heating value HHV) and calculation of calorific values (lower heating value LHV). The analysis takes into the consideration water content in sewage sludge, at different utilization stages, in wastewater treatment plants in Gdańsk Wschód and Kościerzyna - Pomeranian Voivodeship. The study yielded the following results (in % dry matter): ash 19÷31 %, C - 31÷36 %, H - 5÷6 %, N - 4÷6 %, O - 28÷32 %, S - 1 %. Calorific value of stabilized sludges in Gdańsk was on average 13.8÷15 MJ/kg. In case of sludges not undergoing digestion from Kościerzyna WWTP, the calorific value was at the level of 17.5 MJ/kg. Thus, sewage sludges are good energy carriers. High water content though is the problem, as it lowers the useful effect of heat. There is no alternative for thermal sewage sludge neutralization, which is in conformity with valid Polish National Waste Management Plan (KPGO 2022).

Macrovipecetin, a C-type lectin from Macrovipera lebetina venom, inhibits proliferation migration and invasion of SK-MEL-28 human melanoma cells and enhances their sensitivity to cisplatin.

Science.gov (United States)

Hammouda, Manel B; Riahi-Chebbi, Ichrak; Souid, Soumaya; Othman, Houcemeddine; Aloui, Zohra; Srairi-Abid, Najet; Karoui, Habib; Gasmi, Ammar; Magnenat, Edith M; Wells, Timothy N C; Clemetson, Kenneth J; Rodríguez-López, José Neptuno; Essafi-Benkhadir, Khadija

2018-03-01

The resistance of melanoma cells to cisplatin restricts its clinical use. Therefore, the search for novel tumor inhibitors and effective combination treatments that sensitize tumor cells to this drug are still needed. We purified macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina snake venom and investigated its anti-tumoral effect on its own or combined with cisplatin, in human melanoma cells. Biochemical characterization, in vitro cells assays such as viability, apoptosis, adhesion, migration, invasion, Western blotting and in silico analysis were used in this study. Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin. Interestingly, when combined with the drug, macrovipecetin enhanced the sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased expression of the apoptosis inducing factor (AIF) and activation of ERK 1/2 , p38, AKT and NF-κB. Moreover, macrovipecetin alone or combined with cisplatin induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl-2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the function and expression of αvβ3 integrin along with regulating E-cadherin, vimentin, β-catenin, c-Src and RhoA expression. In silico study suggested that only the α chain of macrovipecetin interacts with a region overlapping the RGD motif binding site on this integrin. We validated the antitumor effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28 cells. The presented work proposes the potential use of macrovipecetin and cisplatin in combination as an effective anti-melanoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Analýza a návrh online marketingovej stratégie spoločnosti AQT.sk

OpenAIRE

Múdry, Daniel

2017-01-01

The diploma thesis deals with the online marketing strategy and online activities of the company AQT.sk. The aim of the thesis is to analyze this strategy, individual tools and activities that the company uses and to propose further steps to improve the performance and efficiency of online marketing as a component of the communication mix. Theoretical part briefly describes the development of online marketing and at the same time presents in detail individual online marketing tools and their ...

TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

DEFF Research Database (Denmark)

Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel

2013-01-01

affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab...... and lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level...... to trastuzumab and lapatinib....

Kit-negative fibroblast-like cells expressing SK3, a Ca2+-activated K+ channel, in the gut musculature in health and disease

DEFF Research Database (Denmark)

Vanderwinden, Jean-Marie; Rumessen, Jüri J; de Kerchove d'Exaerde, Alban

2002-01-01

The apamin-sensitive component of the inhibitory response of the gastrointestinal musculature involves the small conductance Ca(2+)-activated K(+) channel SK3. Kit-immunoreactive (ir) interstitial cells of Cajal appear to be involved in nitrergic inhibition while the role of the recently describe...

Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology.

Science.gov (United States)

Sheng, Xiaotong; Yan, Jingmin; Meng, Yue; Kang, Yuying; Han, Zhen; Tai, Guihua; Zhou, Yifa; Cheng, Hairong

2017-03-22

This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.

Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo

International Nuclear Information System (INIS)

Bertrand, Yanick; Demeule, Michel; Michaud-Levesque, Jonathan; Beliveau, Richard

2007-01-01

The expression of melanotransferrin (MTf), a membrane-bound glycoprotein highly expressed in melanomas, is correlated with tumor vascularization and progression, suggesting a proinvasive function associated with MTf in malignant tumors. To test this hypothesis, we silenced MTf in human melanoma SK-MEL-28 cells using small interfering RNA (siRNA) and examined the plasmin activity and invasiveness of MTf-silenced melanoma. In vitro, the siRNA-mediated MTf knockdown inhibited by 58% the cell surface activation of plasminogen into plasmin. In addition, decreased expression of MTf in melanoma cells reduced cell migration. In vivo, we used a nude mice invasion model in which tissue factor (TF) induces vascular [ 125 I]-fibrin deposition following injection. Using this metastasis model, the invasive potential of MTf-silenced cells into the lungs was reduced by fivefold. Altogether, these findings strongly suggest that MTf overexpression in melanoma cells contributes to tumor progession by stimulating plasmin generation as well as cell migration and invasion

The first recorded bloom of Pseudochattonella farcimen (Dictyochophyceae, Heterokonta, (Riisberg I., 2008 in the Gulf of Gdańsk

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Maria Łotocka

2009-03-01

Full Text Available In April 2001 a local bloom of the heterokont phytoflagellate Pseudochattonella farcimen (Riisberg I., 2008 (initially named Chattonella aff. verruculosa was observed for the first time in the southern part of the Gulf of Gdańsk.The species occurred in high cell densities: the count was 11.5 × 106 cells dm-3 and the biomass 927.5 µgC dm-3.

Um siðferðis- og skapgerðarmenntun: á óformlegt nám erindi inn í skóla?

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Pálsdóttir, Kolbrún Þ.

2017-01-01

Þessi grein varpar ljósi á siðferðis- og skapgerðarmenntun innan skóla og stöðu slíkrar menntunar á Íslandi. Margt bendir til þess að þó að fræðimenn hafi á síðustu árum varpað ljósi á mikilvægi þess að efla siðferðilega dómgreind nemenda, sem og félags- og tilfinningaþroska þeirra, verði sá þáttur skólastarfsins iðulega útundan. Innleiðingu á lífsleikni sem námsgrein í grunn- og framhaldsskóla má skoða sem einn þátt í þeirri viðleitni að efla siðferðismenntun og heildstæða sýn...

Chemical composition and immunomodulatory effects of enzymatic protein hydrolysates from common carp (Cyprinus carpio) egg.

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Chalamaiah, M; Hemalatha, R; Jyothirmayi, T; Diwan, Prakash V; Bhaskarachary, K; Vajreswari, A; Ramesh Kumar, R; Dinesh Kumar, B

2015-02-01

The aim of this study was to prepare protein hydrolysates from underutilized common carp (Cyprinus carpio) egg and to investigate their immunomodulatory effects in vivo. Common carp (Cyprinus carpio) egg (roe) was hydrolysed by pepsin, trypsin, and Alcalase. Chemical composition (proximate, amino acid, mineral and fatty acid compositions) and molecular mass distribution of the three hydrolysates were determined. The carp egg protein hydrolysates (CEPHs) were evaluated for their immunomodulatory effects in BALB/c mice. CEPHs (0.25, 0.5 and 1 g/kg body weight) were orally administered daily to female BALB/c mice (4-6 wk, 18-20 g) for a period of 45 d. After 45 d, mice were sacrificed and different tissues were collected for the immunologic investigations. The three hydrolysates contained high protein content (64%-73%) with all essential amino acids, and good proportion of ω-3 fatty acids, especially docosahexaenoic acid. Molecular mass analysis of hydrolysates confirmed the conversion of large-molecular-weight roe proteins into peptides of different sizes (5-90 kDa). The three hydrolysates significantly enhanced the proliferation of spleen lymphocytes. Pepsin hydrolysate (0.5 g/kg body weight) significantly increased the splenic natural killer cell cytotoxicity, mucosal immunity (secretory immunoglobulin A) in the gut and level of serum immunoglobulin A. Whereas Alcalase hydrolysate induced significant increases in the percentages of CD4+ and CD8+ cells in spleen. The results demonstrate that CEPHs are able to improve the immune system and further reveal that different CEPHs may exert differential influences on the immune function. These results indicate that CEPHs could be useful for several applications in the health food, pharmaceutical, and nutraceutical industries. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunomodulatory nutraceuticals with potential clinical use for dogs and cats

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Leandro Zaine

2014-09-01

Full Text Available The use of nutraceuticals in veterinary medicine is growing and is assumed that they could aid in clinical treatment. This review aims to describe some nutraceuticals that act on the immunity of dogs and cats and show the possible benefits as an adjuvant treatment for some diseases. The action of some yeast derivates as immunomodulators, especially the beta-glucan fraction, was already proved to occur in dogs and cats, being beneficial as an adjuvant therapy in many clinical conditions. Omega-3 polyunsatured fatty acids, possibly the mostly used nutraceuticals, can improve the condition in some diseases, such as hypertension, renal, cardiac, gastrointestinal and autoimmune diseases, arthritis and cancer. Vitamin E has antioxidant and immunomodulatory action and can aid in the treatment of dermatologic and hepatobiliar conditions. The use of carotenoids, which have similar action to vitamin E, can be of interest for being potent antioxidants and might be helpful for enhancing immune response against microorganisms and also act preventing tumors. Despite it are still needed clinical trials to better understand the real benefits of nutraceuticals supplementation in each specific disease, the comprehension of the mechanisms by which they act indicates they are promising for clinical use.

Polska w oczach guwernera Skórzewskich, czyli zapiski księdza Pocharda z lat 1792–1833 w zbiorach Biblioteki Uniwersyteckiej w Poznaniu

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Renata Wilgosiewicz-Skutecka

2011-01-01

Full Text Available W zbiorach rękopisów przechowywanych w Bibliotece Uniwersyteckiej w Poznaniu znajdują się trzy tomy wspomnień Claude’a Antoine’a Pocharda – francuskiego księdza, żyjącego w czasach rewolucji francuskiej, należącego do prêtres réfractaires i w roku 1792 zmuszonego do opuszczenia ojczyzny. W latach 1792–1796 pozostawał on na emigracji w Szwajcarii, później przyjął posadę guwernera synów Józefa Skórzewskiego, starosty gnieźnieńskiego, i Heleny z Lipskich Skórzewskiej. Zapiski księdza Pocharda prowadzone w latach 1792–1833 dotyczą obu tych okresów. Ich lektura daje możliwość śledzenia losów duchownego w trudnych czasach rewolucyjnych, a także zagłębienia się w relacje naocznego świadka wydarzeń z życia rodzinnego Skórzewskich, wydarzeń ukazanych w szerszym kontekście historycznym – polskim i europejskim. Artykuł jest wprowadzeniem do badania tych rękopisów jako wielowątkowego materiału mogącego zainteresować zarówno literaturoznawców, jak i historyków, pozwalającego weryfikować wiedzę i stawiać hipotezy dotyczące dziejów jednego z najznamienitszych rodów wielkopolskich.

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

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Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

2015-04-01

To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

Recombinant rubistatin (r-Rub), an MVD disintegrin, inhibits cell migration and proliferation, and is a strong apoptotic inducer of the human melanoma cell line SK-Mel-28.

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Carey, Clayton M; Bueno, Raymund; Gutierrez, Daniel A; Petro, Christopher; Lucena, Sara E; Sanchez, Elda E; Soto, Julio G

2012-02-01

Disintegrins are low molecular weight peptides isolated from viper venom. These peptides bind to integrin receptors using a conserved binding motif sequence containing an RGD or similar motif. As a consequence, disintegrins can inhibit platelet aggregation and inhibit cell migration, proliferation, and initiate apoptosis in cancer cell lines. Rubistatin is a MVD disintegrin cloned from a Crotalus ruber ruber venom gland. The biological activity of MVD disintegrins is poorly understood. Recombinant rubistatin (r-Rub) was cloned into a pET32b plasmid and expressed in reductase-deficient Escherichia coli. Expression was induced with IPTG and the resulting fusion peptide was affinity purified, followed by thrombin cleavage, and removal of vector coded sequences. r-Rub peptide inhibited ADP-induced platelet aggregation by 54% ± 6.38 in whole blood. We assessed the ability of r-Rub to initiate apoptosis in three human cancer cell lines. Cultures of SK-Mel-28, HeLA, and T24 cells were grown for 24 h with 2.5 μM r-Rub followed by Hoechst staining. Chromatin fragmentation was observed in treated SK-Mel-28, but not in T24 or HeLA cells. A TUNEL assay revealed that 51.55% ± 5.28 of SK-Mel-28 cells were apoptotic after 18 h of treatment with 3.5 μM of r-Rub. Cell migration and proliferation assays were performed in order to further characterize the biological effects of r-Rub on SK-Mel-28 cells. At 3 μM, r-Rub inhibited cell migration by 44.4% ± 0.5, while at 3.5 μM it was able to inhibit cell proliferation by 83% ± 6.0. Copyright © 2011 Elsevier Ltd. All rights reserved.

Immunomodulatory effect of APS and PSP is mediated by Ca2+-cAMP and TLR4/NF-κB signaling pathway in macrophage.

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Wang, Zhixue; Liu, Zijing; Zhou, Lijng; Long, Tingting; Zhou, Xing; Bao, Yixi

2017-01-01

This study is to investigate the role of second messengers and TLR4/NF-κB signaling pathway in the immunomodulatory activities of Astragalus polysaccharide (APS) and Polysaccharopeptide (PSP) in macrophages. RAW 264.7 macrophage cells were treated with APS, PSP, lipopolysaccharide (LPS), or NiCl 2 . Power-spectral method was used to detect protein kinase C (PKC) and Griess reaction to detect nitric oxide (NO). ELISA was conducted to detect cyclic adenosine monophosphate (cAMP), diglycerides (DAG), inositol 1, 4, 5-triphosphate (IP3), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Confocal laser scanning microscopy was performed to detect calcium level. qRT-PCR and Western blot was used to detect mRNA and protein expression of NF-κB. APS and PSP significantly increased the concentrations of intracellular second messengers (NO, cAMP, DAG, IP3, Ca 2+ ) and the activity of PKC in macrophages (pAPS and PSP (pAPS and PSP mediated immunomodulatory activities in macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunomodulatory Effectiveness of Aqueous Obat Pahit Extract of Lingga Malay Ethnic on White Rats (Rattus novergicus

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Fitmawati Fitmawati

2017-12-01

Full Text Available Obat pahit has been generally known and believed by Lingga Malay society as anti-aging agent. However, the study of Obat pahit is not scientifically proven. This research was aimed to prove immunomodulatory ability of Obat pahit potion from Lingga, Riau Archipelago. This study used white rats as an animal modelling, and Staphylococcus aureus as bacteria tester. The rats had been treated with aqueous Obat pahit extract from three TMPs on dose scales of 0.09, 0.18 and 0.27 mL/200g of body weight through oral administration for 7 days. Furthermore, on the 8th days, the experiment animals were injected by the preparation of bacteria tester through intraperitoneal administration in the amount of 0.5 mL/200 gram of body weigth and subsequently incubated for 1 hour after the injection. There were 2 observed parameters on this study, i.e efectivity and capacity of phagocytosis by leukocytes. The observation of leukocytes-phagocytocis activity was carried out by making a smear preparat samples of peritoneum fluid from rats. After the observation under microscope on a magnification of 100 times. The result was obtained the Obat pahit from Kalan PMT swere more effective on dose 2, while from SP4 and Linau TMPs were much more effective on dose 1. It is therefore, using these data of the results, the advanced doses scale of this Obat pahit would not be necessary. Obat pahit potion from Malay Lingga Malay Ethnic could become raw materials of immunomodulatory herbal medicine based on traditional knowledge. It also potentially as a standardized herbal.

Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.

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Chorfa, Areski; Bétemps, Dominique; Morignat, Eric; Lazizzera, Corinne; Hogeveen, Kevin; Andrieu, Thibault; Baron, Thierry

2013-06-01

Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. In particular, a relationship between Parkinson's disease and occupational exposure to pesticides has been repeatedly suggested. Our objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate) using Western blot and flow cytometry. These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. We found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. The observed differences in the propensities of pesticides to increase α-syn levels are in agreement with numerous reports that indicate a potential role of exposure to certain pesticides in the development of Parkinson's disease. Our data support the hypothesis that pesticides can trigger some molecular events involved in this disease and also in malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.

Ex vivo immunomodulatory effect of ethanolic extract of propolis during Celiac Disease: involvement of nitric oxide pathway.

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Medjeber, Oussama; Touri, Kahina; Rafa, Hayet; Djeraba, Zineb; Belkhelfa, Mourad; Boutaleb, Amira Fatima; Arroul-Lammali, Amina; Belguendouz, Houda; Touil-Boukoffa, Chafia

2018-03-07

Celiac Disease (CeD) is a chronic immune-mediated enteropathy, in which dietary gluten induces an inflammatory reaction, predominantly in the duodenum. Propolis is a resinous hive product, collected by honeybees from various plant sources. Propolis is well-known for its anti-inflammatory, anti-oxidant and immunomodulatory effects, due to its major compounds, polyphenols and flavonoids. The aim of our study was to assess the ex vivo effect of ethanolic extract of propolis (EEP) upon the activity and expression of iNOS, along with IFN-γ and IL-10 production in Algerian Celiac patients. In this context, PBMCs isolated from peripheral blood of Celiac patients and healthy controls were cultured with different concentrations of EEP. NO production was measured using the Griess method, whereas quantitation of IFN-γ and IL-10 levels was performed by ELISA. Inducible nitric oxide synthase (iNOS) expression, NFκB and pSTAT-3 activity were analyzed by immunofluorescence assay. Our results showed that PBMCs from Celiac patients produced high levels of NO and IFN-γ compared with healthy controls (HC). Interestingly, EEP reduced significantly, NO and IFN-γ levels and significantly increased IL-10 levels at a concentration of 50 µg/mL. Importantly, EEP downmodulated the iNOS expression as well as the activity of NFκB and pSTAT-3 transcription factors. Altogether, our results highlight the immunomodulatory effect of propolis on NO pathway and on pro-inflammatory cytokines. Therefore, we suggest that propolis may constitute a potential candidate to modulate inflammation during Celiac Disease and has a potential therapeutic value.

Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

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Mezei Z

2012-10-01

Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

Impact of image segmentation on high-content screening data quality for SK-BR-3 cells

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Li Yizheng

2007-09-01

Full Text Available Abstract Background High content screening (HCS is a powerful method for the exploration of cellular signalling and morphology that is rapidly being adopted in cancer research. HCS uses automated microscopy to collect images of cultured cells. The images are subjected to segmentation algorithms to identify cellular structures and quantitate their morphology, for hundreds to millions of individual cells. However, image analysis may be imperfect, especially for "HCS-unfriendly" cell lines whose morphology is not well handled by current image segmentation algorithms. We asked if segmentation errors were common for a clinically relevant cell line, if such errors had measurable effects on the data, and if HCS data could be improved by automated identification of well-segmented cells. Results Cases of poor cell body segmentation occurred frequently for the SK-BR-3 cell line. We trained classifiers to identify SK-BR-3 cells that were well segmented. On an independent test set created by human review of cell images, our optimal support-vector machine classifier identified well-segmented cells with 81% accuracy. The dose responses of morphological features were measurably different in well- and poorly-segmented populations. Elimination of the poorly-segmented cell population increased the purity of DNA content distributions, while appropriately retaining biological heterogeneity, and simultaneously increasing our ability to resolve specific morphological changes in perturbed cells. Conclusion Image segmentation has a measurable impact on HCS data. The application of a multivariate shape-based filter to identify well-segmented cells improved HCS data quality for an HCS-unfriendly cell line, and could be a valuable post-processing step for some HCS datasets.

Effectiveness of the immunomodulatory extract of Kalanchoe pinnata against murine visceral leishmaniasis.

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Gomes, D C O; Muzitano, M F; Costa, S S; Rossi-Bergmann, B

2010-04-01

Previously, we described the protective action of the immunomodulatory extract of Kalanchoe pinnata (Kp) in murine and human cutaneous leishmaniasis. In the present study, we investigated the effectiveness of Kp against visceral leishmaniasis, using the BALB/c mouse model of infection with Leishmania chagasi. Mice receiving oral daily doses of Kp (400 mg/kg) for 30 days displayed significantly reduced hepatic and splenic parasite burden, when compared with untreated animals. Protectiveness was accompanied by a reduction in parasite-specific IgG serum levels, and impaired capacity of spleen cells to produce IL-4, but not IFN-gamma and nitric oxide upon antigen recall in vitro. The reference drug Pentostam (72 mg/kg) given by the intra-peritoneal route on alternate days produced an anti-leishmanial effect similar to oral Kp. Our findings show that the oral efficacy of Kp, seen previously in murine cutaneous leishmaniasis, extends also to visceral leishmaniasis caused by L. chagasi, a difficult to treat and lethal disease of man.

Rola pielęgniarki w opiece nad pacjentem z atopowym zapaleniem skóry = Nurse’s role in taking care of a patient with atopic dermatitis

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Karolina Filipska

2016-01-01

3Wydział Kultury Fizycznej, Zdrowia i Turystyki, Uniwersytet Kazimierza Wielkiego w Bydgoszczy   Słowa kluczowe: atopowe zapalenie skóry, psychologiczne aspekty chorób, świąd, rola pielęgniarki. Keywords: atopic dermatitis, psychological aspects of diseases, itching, nurse’s role.   Streszczenie Wstęp. Atopowe zapalenie skóry (AZS, ang. atopic dermatitis jest chorobą alergiczną o przewlekłym i nawracającym przebiegu. Toczący się proces chorobowy dotyczy naskórka i skóry właściwej. AZS to najpowszechniej występująca przewlekła choroba zapalna dzieci, której patogeneza nie jest do końca poznana. Uznaje się, że na rozwój choroby składają się czynniki genetyczne, immunologiczne, oraz środowiskowe. Cel. Przedstawienie roli pielęgniarki w opiece nad pacjentem z atopowym zapaleniem skóry. Materiał i metody. Dokonano przeglądu 43 doniesień naukowych – artykuły badawcze i poglądowe oraz literatura współczesna - obejmujących swą tematyką rolę pielęgniarki w opiece nad pacjentem z atopowym zapaleniem skóry. Posługując się słowami kluczowymi: atopowe zapalenie skóry, psychologiczne aspekty chorób, świąd rola pielęgniarki przeszukano bazy bibliograficzne  Ebsco, ScienceDirect, SpringerLink, Medline. Wyniki. Zadania pielęgnacyjno-opiekuńcze wynikają z poszczególnych symptomów AZS. Wśród założeń opieki pielęgniarskiej wymienia się: zmniejszenie świądu i suchości skóry;  zminimalizowanie zaburzeń sennych; obniżenie ryzyka wtórych nadkażeń bakteryjnych, wirusowych lub grzybiczych; oraz kompleksowa edukacja chorego i jego rodziny w celu szybszej rekonwalescencji i wydłużenia okresów remisji. Wnioski. AZS wpływa negatywnie na domenę fizyczną, psychiczną i społeczną chorego. Ze względu na swoją przewlekłość oraz szerokie roz­powszechnienie należy do jednego z największych wyzwań zarówno dla pielęgniarki jak i całego zespołu terapeutycznego. Skuteczne leczenie dermatologiczne, w

Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gda?sk in Poland

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Bory?o, Alicja; Skwarzec, Bogdan; Roma?czyk, Grzegorz; Siebert, Janusz

2013-01-01

The determination of polonium 210Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gda?sk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. 210Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body...

Elementary analysis and energetic potential of the municipal sewage sludges from the Gdańsk and Kościerzyna WWTPs

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Ostojski Arkadiusz

2018-01-01

Full Text Available This paper aims to present municipal sewage sludge (MSS elementary analysis and energetic potential based on measurement of heat of combustion (higher heating value HHV and calculation of calorific values (lower heating value LHV. The analysis takes into the consideration water content in sewage sludge, at different utilization stages, in wastewater treatment plants in Gdańsk Wschód and Kościerzyna – Pomeranian Voivodeship. The study yielded the following results (in % dry matter: ash 19÷31 %, C - 31÷36 %, H - 5÷6 %, N - 4÷6 %, O - 28÷32 %, S – 1 %. Calorific value of stabilized sludges in Gdańsk was on average 13.8÷15 MJ/kg. In case of sludges not undergoing digestion from Kościerzyna WWTP, the calorific value was at the level of 17.5 MJ/kg. Thus, sewage sludges are good energy carriers. High water content though is the problem, as it lowers the useful effect of heat. There is no alternative for thermal sewage sludge neutralization, which is in conformity with valid Polish National Waste Management Plan (KPGO 2022.

The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways

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Wan-Ling Chuang

2016-04-01

Full Text Available Ursolic acid (UA is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis.

Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8

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2014-01-01

Background Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. Methods T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe+2/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. Conclusions The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa. PMID:24969238

A High Molecular-Mass Anoxybacillus sp. SK3-4 Amylopullulanase: Characterization and Its Relationship in Carbohydrate Utilization

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Kian Mau Goh

2013-05-01

Full Text Available An amylopullulanase of the thermophilic Anoxybacillus sp. SK3-4 (ApuASK was purified to homogeneity and characterized. Though amylopullulanases larger than 200 kDa are rare, the molecular mass of purified ApuASK appears to be approximately 225 kDa, on both SDS-PAGE analyses and native-PAGE analyses. ApuASK was stable between pH 6.0 and pH 8.0 and exhibited optimal activity at pH 7.5. The optimal temperature for ApuASK enzyme activity was 60 °C, and it retained 54% of its total activity for 240 min at 65 °C. ApuASK reacts with pullulan, starch, glycogen, and dextrin, yielding glucose, maltose, and maltotriose. Interestingly, most of the previously described amylopullulanases are unable to produce glucose and maltose from these substrates. Thus, ApuASK is a novel, high molecular-mass amylopullulanase able to produce glucose, maltose, and maltotriose from pullulan and starch. Based on whole genome sequencing data, ApuASK appeared to be the largest protein present in Anoxybacillus sp. SK3-4. The α-amylase catalytic domain present in all of the amylase superfamily members is present in ApuASK, located between the cyclodextrin (CD-pullulan-degrading N-terminus and the α-amylase catalytic C-terminus (amyC domains. In addition, the existence of a S-layer homology (SLH domain indicates that ApuASK might function as a cell-anchoring enzyme and be important for carbohydrate utilization in a streaming hot spring.

Synthesis of carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium derivatives as new potential PET SK{sub Ca} channel imaging agents

Energy Technology Data Exchange (ETDEWEB)

Gao Mingzhang; Wang Min [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

2008-02-15

Small conductance Ca{sup 2+}-activated K{sup +} (SK{sub Ca}) channels play an important role in many functions such as neuronal communication and behavioral plasticity, secretion, and cell proliferation. SK{sub Ca} channel modulation is associated with various brain, heart, and cancer diseases. N-methyl-laudanosine and its structurally related derivatives, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums, are reversible and selective SK{sub Ca} channel blockers. Carbon-11 labeled N-methyl-laudanosine and its tetrahydroisoquinolinium derivatives may serve as new probes for positron emission tomography (PET) to image SK{sub Ca} channels in the brain, heart, and cancer. The key intermediates, substituted isoquinolines (3a-c), were synthesized using a modification of the Pomeranz-Fritsch procedure. The precursors, substituted 1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines (8a-c), and their corresponding reference standards, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums (9a-c), were synthesized from compounds 3a-c with 3,4-dimethoxybenzyl chloride (2) in multiple steps with moderate to excellent chemical yields. The precursor 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3, 4-tetrahydroisoquinoline (10) was commercially available, and the methylation of compound 10 with methyl iodide provided N-methyl-laudanosine (11). The target quaternary ammonium tracers, carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums ([{sup 11}C]9a-c and [{sup 11}C]11), were prepared by N-[{sup 11}C]methylation of the tertiary amine precursors (8a-c and 10) with [{sup 11}C]methyl triflate and isolated by a simplified solid-phase extraction (SPE) purification using a SiO{sub 2} or cation-exchange CM Sep-Pak cartridge in 40-65% radiochemical yields.

Discovery of the target for immunomodulatory drugs (IMiDs).

Science.gov (United States)

Ito, Takumi; Ando, Hideki; Handa, Hiroshi

2016-05-01

Half a century ago, the sedative thalidomide caused a serious drug disaster because of its teratogenicity and was withdrawn from the market. However, thalidomide, which has returned to the market, is now used for the treatment of leprosy and multiple myeloma (MM) under strict control. The mechanism of thalidomide action had been a long-standing question. We developed a new affinity bead technology and identified cereblon (CRBN) as a thalidomide-binding protein. We found that CRBN functions as a substrate receptor of an E3 cullin-Ring ligase complex 4 (CRL4) and is a primary target of thalidomide teratogenicity. Recently, new thalidomide derivatives, called immunomodulatory drugs (IMiDs), have been developed by Celgene. Among them, lenalidomide (Len) and pomalidomide (Pom) were shown to exert strong therapeutic effects against MM. It was found that Len and Pom both bind CRBN-CRL4 and recruit neomorphic substrates (Ikaros and Aiolos). More recently it was reported that casein kinase 1a (Ck1a) was identified as a substrate for CRBN-CRL4 in the presence of Len, but not Pom. Ck1a breakdown explains why Len is specifically effective for myelodysplastic syndrome with 5q deletion. It is now proposed that binding of IMiDs to CRBN appears to alter the substrate specificity of CRBN-CRL4. In this review, we introduce recent findings on IMiDs.

Antimicrobial and immunomodulatory activities of PR-39 derived peptides.

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Edwin J A Veldhuizen

Full Text Available The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.

Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

Science.gov (United States)

Veldhuizen, Edwin J. A.; Schneider, Viktoria A. F.; Agustiandari, Herfita; van Dijk, Albert; Tjeerdsma-van Bokhoven, Johanna L. M.; Bikker, Floris J.; Haagsman, Henk P.

2014-01-01

The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics. PMID:24755622

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM.

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Patrícia Kellen Martins Oliveira Brito

Full Text Available Toll-like receptors (TLR contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c. ArtinM (0.5 μg in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval with ArtinM (0.5, 1.0, 2.5, or 5.0 μg, LPS (positive control, or PBS (negative control and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg. Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

Science.gov (United States)

Oliveira Brito, Patrícia Kellen Martins; Gonçalves, Thiago Eleutério; Fernandes, Fabrício Freitas; Miguel, Camila Botelho; Rodrigues, Wellington Francisco; Lazo Chica, Javier Emílio; Roque-Barreira, Maria Cristina

2017-01-01

Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice. PMID:29084277

Seed oil composition of Acacia nilotica (L. Delile from Iran / Skład oleju z nasion Acacia nilotica (L. Delile rosnącej w Iranie

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Abbasian Karim

2016-03-01

Full Text Available Wstęp: Acacia nilotica (L. Delile należy do rodziny Fabaceae, podrodziny Mimosoideae; otrzymuje się z niej gumę arabską. W południowym Iranie są spożywane pieczone młode strąki i nasiona tej rośliny Cel: Badano skład oleju z dojrzałych nasion A. nilotica zebranych z naturalnych stanowisk na południu Iranu w celu określenia jego przydatności do spożycia przez ludzi i zwierzęta. Metody: Wyekstrahowany olej analizowano metodą chromatografii gazowej sprzężonej ze spektrometrią mas (GC/MS. Wyniki: Zawartość oleju w jadalnych nasionach wynosiła 3.4% (v/w świeżej masy. Olej zawierał rzadko spotykany fitosterol, sześć kwasów tłuszczowych, dziewięć węgolwodorów i jeden diterpenoid; związki te stanowiły łącznie około 83.5% oleju. Głównymi składnikami oleju były: fitosterol, 26-ethylcholesta-5,25(Z-dien-3.β-ol (20.8% oraz nasycone i nienasycone kwasy tłuszczowe. Zawartość pozostałych składników nie przekroczyła 5%. Wniosek: Olej z nasion omawianego gatunku może być nowym naturalnym środkiem odżywczym dla ludzi.

Supplier evaluation system of the wood processing enterprise in the region of the CZ, SK, HU and AT

OpenAIRE

Muselíková, Vladislava

2015-01-01

The Bachelor thesis Supplier evaluation system of the wood processing enterprise in the region of the CR, the SK, HU and AT deals with the analysis of the current supplier evaluation system in IKEA Industry company in Malacky. The theoretical part is based on literature review and contains a description of the purchasing process and methodology for selection and evaluation of suppliers. The practical part is devoted to the analysis of the Supplier Classification in IKEA. The main output of th...

The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

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Cosette M. Rivera-Cruz

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3

International Nuclear Information System (INIS)

Alper, O.; Yamaguchi, K.; Hitomi, J.; Honda, S.; Matsushima, T.; Abe, K.

1990-01-01

The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein

Analysis of CPolSK-based FSO system working in space-to-ground channel

Science.gov (United States)

Su, Yuwei; Sato, Takuro

2018-03-01

In this article, the transmission performance of a circle polarization shift keying (CPolSK)-based free space optical (FSO) system working in space-to-ground channel is analyzed. Formulas describing the optical polarization distortion caused by the atmospheric turbulence and the communication qualities in terms of signal-to-noise-ratio (SNR), bit-error-ratio (BER) and outage probability of the proposed system are derived. Based on the Stokes parameters data measured by a Japanese optical communication satellite, we evaluate the space-to-ground FSO link and simulate the system performance under a varying regime of turbulence strength. The proposed system provides a more efficient way to compensate scintillation effects in a comparison with the on-off-keying (OOK)-based FSO system. These results are useful to the designing and evaluating of a deep space FSO communication system.

The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs).

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Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohamad Ali; Jalili, Ali; Rahmani, Mohammad Reza

2017-11-01

Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-β1, FOX P 3 , IFN-γ, CXCL12 and β-actin mRNA expression. UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-β1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis.

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García-Hernández, M; Castro-Corona, M A; Segoviano-Ramírez, J C; Brattig, N W; Medina-De la Garza, C E

2014-11-01

We tested whether diethylcarbamazine (DEC) or ivermectin (IVM), both antiparasitic drugs with reported immunomodulatory properties, were able to affect the immune system to potentiate host defense mechanisms and protect against actinomycetoma in a mouse model. Male BALB/c mice of 10-12 weeks of age were injected with either Nocardia brasiliensis or saline solution. Recorded were the effects of a treatment by DEC (6 mg/kg per os daily for one week) or IVM (200 μg/kg subcutaneously on days 1 and 3) on (i) the development of mycetoma lesion, (ii) the expression of reactive oxygen intermediates (ROI) by phagocytes, (iii) the proliferation index of lymphocytes and (iv) antibody production of IgG and IgM. After an initial lesion in all mice, DEC inhibited a full development and progression of actinomycetoma resulting in a reduced lesion size (p brasiliensis antigens and concanavalin A in DEC-treated group was higher than in non-treated group at day 21 and 28 postinfection (p brasiliensis leading to retrogression of the mycetoma and increasing cellular immune responses. Our findings may indicate a potential use of DEC as a putative adjuvant in infectious disease or vaccination. Copyright © 2014 Elsevier B.V. All rights reserved.

[Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

Science.gov (United States)

Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

2016-05-01

Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in Hypercholesterolemic Rats.

Science.gov (United States)

Nisar, Jaweria; Mustafa, Imtiaz; Anwar, Haseeb; Sohail, Muhammad Umar; Hussain, Ghulam; Ullah, Muhammad Irfan; Faisal, Muhammad Naeem; Bukhari, Shazia Anwer; Basit, Abdul

2017-01-01

Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

Anti-herpes simplex virus 1 and immunomodulatory activities of a poly-γ- glutamic acid from Bacillus horneckiae strain APA of shallow vent origin.

Science.gov (United States)

Marino-Merlo, Francesca; Papaianni, Emanuela; Maugeri, Teresa L; Zammuto, Vincenzo; Spanò, Antonio; Nicolaus, Barbara; Poli, Annarita; Di Donato, Paola; Mosca, Claudia; Mastino, Antonio; Gugliandolo, Concetta

2017-10-01

Herpes simplex virus type 1 (HSV-1) is responsible of common and widespread viral infections in humans through the world, and of rare, but extremely severe, clinical syndromes in the central nervous system. The emergence of resistant strains to drugs actually in use encourages the searching for novel antiviral compounds, including those of natural origin. In this study, the recently described poly-γ-glutamic acid (γ-PGA-APA), produced by the marine thermotolerant Bacillus horneckiae strain APA, and previously shown to possess biological and antiviral activity, was evaluated for its anti-HSV-1 and immunomodulatory properties. The biopolymer hindered the HSV-1 infection in the very early phase of virus replication. In addition, the γ-PGA-APA was shown to exert low cytotoxicity and noticeable immunomodulatory activities towards TNF-α and IL-1β gene expression. Moreover, the capacity to positively modulate the transcriptional activity of the cytokine genes was paired with increased level of activation of the transcription factor NF-kB by γ-PGA-APA. Overall, as non-cytotoxic biopolymer able to contribute in the antiviral defense against HSV-1, γ-PGA-APA could lead to the development of novel natural drugs for alternative therapies.

Immunomodulatory constituents of human milk change in response to infant bronchiolitis.

Science.gov (United States)

Bryan, Dani-Louise; Hart, Prue H; Forsyth, Kevin D; Gibson, Robert A

2007-09-01

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2

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Dorothy I. Wallace

2016-01-01

Full Text Available Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, as in vitro spheroids or in vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2 and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model of in vitro tumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M as well as quiescent (Q and necrotic (N cells. Monolayer treatment data for 15-deoxy-PGJ2 is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.

n Vitro Immunomodulatory Effect of R10 Fraction of Garlic on Viability and Production of TNF-? in CD8+ T Cells

OpenAIRE

T. Ghazanfari; H. Rashidi; Sh. Jalaei; P. Alijani

2014-01-01

Introduction & Objective: -cells, especially CD8+ T lymphocytes are the most important cells in anti-tumor response. Previously R10 fraction of garlic extract was reported as an immuno-modulator which induced an effective cellular immunity and Th1 responses. In this study the in vitro immunomodulatory effect of R10 on CD8+ T cells viability and production of TNF-? were evaluated. Materials & Methods: In this experimental study, using monoclonal antibodies attached to magnetic beads with isola...

Immunomodulatory activity of extracts from Cordia superba Cham. and Cordia rufescens A. DC. (Boraginaceae), plant species native from Brazilian Semi-arid

OpenAIRE

Costa,José Fernando Oliveira; David,Juceni P. L.; David,Jorge M.; Giulietti,Ana M.; Queiroz,Luciano P.; Santos,Ricardo R.; Soares,Milena Botelho P.

2008-01-01

The family Boraginaceae is widely distributed in Brazil and in the Northeastern region some species are popularly used to treat symptoms of rheumatism, painful menstruation and dyspepsia. In this work we studied Cordia superba Cham. and C. rufescens A. DC., native from Brazilian Semi-arid region, in order to investigate their immunomodulatory activity. Six extracts were prepared from aerial parts of C. superba and C. rufescens. The cytotoxicity was evaluated using splenocytes from BALB/c mice...

Immunomodulatory activities and antioxidant properties of polysaccharides from Monascus-fermented products in vitro.

Science.gov (United States)

Tseng, Kuo-Chuan; Fang, Tony J; Chiang, Shen-Shih; Liu, Chin-Feng; Wu, Cheng-Lun; Pan, Tzu-Ming

2012-05-01

Monascus-fermented products have featured in Chinese cuisine for thousands of years and are widely used as food colourants and dietary materials in many Asian countries. Rice and dioscorea fermented with Monascus purpureus NTU 568 have health-promoting attributes in vitro and in vivo. The aim of this study was to investigate the immunomodulatory and antioxidant effects of polysaccharides from red mould rice (RMRP) and red mould dioscorea (RMDP) in Raw 264.7 cells. The results showed the antioxidant capabilities (including scavenging, chelating, inhibition of lipid peroxidation, and reducing power) of RMRP and RMDP at a concentration of 10 mg mL(-1). RMRP and RMDP also stimulated cell proliferation, nitric oxide production, phagocytosis and cytokine production (including IL1-β, IL-6 and TNF-α) in Raw 264.7 cells. These findings demonstrate that RMRP and RMDP have antioxidant and immunomodulation potential to be developed as novel dietary supplements. Copyright © 2011 Society of Chemical Industry.

Structural analyses and immunomodulatory properties of fructo-oligosaccharides from onion (Allium cepa).

Science.gov (United States)

Kumar, V Prasanna; Prashanth, K V Harish; Venkatesh, Y P

2015-03-06

Onion (Allium cepa) is an immune-boosting food rich in fructans. The major aim of this study is to characterize and investigate the immunomodulatory properties of onion fructo-oligosaccharides (FOS). FOS was isolated from onion bulbs by hot 80% ethanol extraction (yield: ∼4.5 g/100 g fw) followed by gel permeation chromatography. NMR of onion FOS revealed unusual β-D-Glc terminal residue at the non-reducing end. TLC and ESI-MS analyses showed that onion FOS ranged from trisaccharides to hexasaccharides. Onion FOS (50 μg/mL) significantly increased (∼3-fold) the proliferation of mouse splenocytes/thymocytes vs. control. Further, onion FOS enhanced (∼2.5-fold) the production of nitric oxide by peritoneal exudates cells (PECs) from Wistar rats; intracellular free radicals production and phagocytic activity of isolated murine PECs were also augmented. Our structural and in vitro results indicate that onion FOS comprising of tri- to hexasaccharide units belongs to inulin-type fructans, and possess immunostimulatory activities towards murine lymphocytes and macrophages. Copyright © 2014 Elsevier Ltd. All rights reserved.

Upper Campanian-Maastrichtian chronostratigraphy of the Skælskør-1 core, Denmark

DEFF Research Database (Denmark)

Thibault, Nicolas Rudolph; Anderskouv, Kresten; Bjerager, Morten

2015-01-01

The lithostratigraphy, calcareous nannofossil biostratigraphy, carbon- and oxygen-isotope stratigraphy and gamma-ray profile are presented for the Skælskør-1 core, eastern Denmark. The correlation of carbon isotopes to Gubbio (Italy) and ODP Site 762C (Indian Ocean) provides...... the chronostratigrahical framework of the core through a tie to magnetostratigraphy. Two new carbon-isotope excursions are defined for the uppermost Maastrichtian of the core and prove useful for long-distance correlation. Twenty stratigraphic tie-points are used for correlation of the upper Campanian......-Maastrichtian interval by combining carbon-isotope and gamma-ray variations. Significant dissimilarities in the gamma-ray profiles of the Danish Basin cores preclude the sole use of this tool for basin-scale correlations. Bulk oxygen-isotopes and semi-quantitative abundance changes in the warm-water calcareous...

‘Close to the city centre, close to the university’. Are there symptoms of studentification in Gdańsk, Poland?

OpenAIRE

Grabkowska Maja; Frankowski Jan

2016-01-01

Students are increasingly recognised as important actors of urban change in contemporary cities. The article presents an analysis of incipient studentification processes in Gdańsk. Its general aim is to reveal patterns of students’ presence and activity which translate into spatial and socio-economic transformations of a post-socialist city at the level of neighbourhoods. The study consists of a survey on students’ residential behaviour, complemented by field and desk research. According to t...

Etteheited räsivad pidu / Henri Reeder, Ly Rääsk, Heli Jürgenson ... [jt.] ; intervjueerinud Anneli Aasmäe

Index Scriptorium Estoniae

2009-01-01

Küsimustele tänavusele üldlaulu- ja üldtantsupeole minekust ja peo repertuaari raskusest vastavad Aruküla noortekoori laulja Henri Reeder, Äksi segakoori dirigent Ly Rääsk, üldlaulupeo segakooride liigijuht Heli Jürgenson, Laulu- ja Tantsupeo SA muusikatoimetaja Ave Sopp, Laulu- ja Tantsupeo SA tantsutoimetaja Kadri Tiis , Lüganuse segakoori dirigent Priit-Andres Pärtna ja kolme tantsurühma juhendaja Vändrast Kädi Pärnoja

Urbánno-rurálně rozdiely voličského správania v Česku a na Slovensku

Czech Academy of Sciences Publication Activity Database

Kostelecký, Tomáš; Krivý, V.

2015-01-01

Roč. 47, č. 4 (2015), s. 390-413 ISSN 0049-1225 R&D Projects: GA ČR(CZ) GAP408/12/1442 Institutional support: RVO:68378025 Keywords : voting behaviour * aggregated data * Czech and Slovak society Subject RIV: AO - Sociology , Demography Impact factor: 0.275, year: 2015 https://www.sav.sk/journals/uploads/08190954Krivy%20-%20Kostelecky%20OK.pdf

Immunomodulatory activity of extracts from Cordia superba Cham. and Cordia rufescens A. DC. (Boraginaceae, plant species native from Brazilian Semi-arid

Directory of Open Access Journals (Sweden)

José Fernando Oliveira Costa

Full Text Available The family Boraginaceae is widely distributed in Brazil and in the Northeastern region some species are popularly used to treat symptoms of rheumatism, painful menstruation and dyspepsia. In this work we studied Cordia superba Cham. and C. rufescens A. DC., native from Brazilian Semi-arid region, in order to investigate their immunomodulatory activity. Six extracts were prepared from aerial parts of C. superba and C. rufescens. The cytotoxicity was evaluated using splenocytes from BALB/c mice. The immunomodulatory activity was determined by in vitro assays using activated mouse macrophages and lymphocytes. Peritoneal macrophages obtained from BALB/c mice were stimulated with IFN-gamma and LPS in the presence/absence of the samples. The NO production was measured indirectly through Griess method. Three samples inhibited the production of nitric oxide in values near 50% at a concentration of 100 µg/mL. To evaluate the effects of the extracts on lymphocytes, splenocytes from BALB/c mice were incubated with the samples and concanavalin A. Proliferation inhibition was determined by analysis of ³H-thymidine uptake. Samples from the two species had a strong inhibitory activity on lymphocyte proliferation and IL-2 production. Two chloroform extracts prepared from aerial parts of C. rufescens had the lowest IC50 values (7.6 and 11.0 µg/mL.

Apple cider vinegar boosted immunomodulatory and health promoting effects of Lactobacillus casei in common carp (Cyprinus carpio).

Science.gov (United States)

Safari, Roghieh; Hoseinifar, Seyed Hossein; Nejadmoghadam, Shabnam; Khalili, Mohsen

2017-08-01

The present study was performed to investigate the immunomodulatory and health promoting effects of combined or singular administration of apple cider vinegar (ACV) and Lactobacillus casei in common carp (Cyprinus carpio) diet. An 8-week feeding trial was designed with following treatments: Control (basal diet), Pro (contains 10 7  CFU g -1 L. casei), LACV (contains 1% ACV), HACV (contains 2% ACV), Pro + LACV (contains 10 7  CFU g -1 L. casei plus 1% ACV) and Pro + HACV (contains 10 7  CFU g -1 L. casei plus 2% ACV). Evaluation of skin mucus revealed notable increase of total Ig level and lysozyme activity in Pro + LACV and Pro + HACV treatments compared other groups (P < 0.05). Similarly, serum total Ig and lysozyme activity in HACV, Pro + LACV and Pro + HACV fed carps was remarkably higher than other groups (P < 0.05). However, regarding serum alternative complement (ACH50) activity significant difference was observed just between Pro + HACV and control treatment (P < 0.05). The highest expression of immune related (LYZ, TNF-alpha, IL1b, IL8) and antioxidant enzymes genes (GSR, GST) were observed in carps fed Pro + HACV and Pro + LACV. The expression of GH gene expression in Pro, LACV and HACV treatments was significantly higher than those in control group (P < 0.05). The highest expression level of GH and IGF1 was observed in fish fed combined Pro and ACV (P < 0.05). These results indicated that co-administration of ACV boosted immunomodulatory and health promoting effects of L. casei and can be considered as a promising immunostimulants in early stage of common carp culture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure

International Nuclear Information System (INIS)

Corsini, Emanuela; Codeca, Ilaria; Mangiaratti, Simona; Birindelli, Sarah; Minoia, Claudio; Turci, Roberta; Viviani, Barbara; Facchi, Alessandra; Vitelli, Nora; Lucchi, Laura; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

2007-01-01

Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG 1 and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-α production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity

Protective Effects of Streblus asper Leaf Extract on H2O2-Induced ROS in SK-N-SH Cells and MPTP-Induced Parkinson’s Disease-Like Symptoms in C57BL/6 Mouse

Directory of Open Access Journals (Sweden)

Kanathip Singsai

2015-01-01

Full Text Available This study investigated the effects of Streblus asper leaf extract (SA on reactive oxygen species (ROS in SK-N-SH cell culture and on motor functions and behaviors in MPTP-treated C57BL/6 mice. SK-N-SH cell viability after incubation with SA for 24 h was measured by MTT assay. Intracellular ROS levels of SK-N-SH cells were quantified after pretreatment with SA (0, 200, 600, and 1000 µg/mL in the presence of H2O2 (300 µM. Male C57BL/6 mice were force-fed with water or 200 mg/kg/day SA for 32 days. Intraperitoneal injection of MPTP was used to induce Parkinson’s disease-like symptoms. Catalepsy, beam balance ability, olfactory discrimination, social recognition, and spontaneous locomotor activity were assessed on days 19, 21, 23, 26, and 32, respectively. In cell culture, SA at 200, 600, and 1000 µg/mL significantly decreased ROS levels in H2O2-treated SK-N-SH cells. MPTP-treated C57BL/6 mice showed a significant change in all parameters tested when compared to the control group. Pretreatment and concurrent treatment with 200 mg/kg/day SA could antagonize the motor and cognitive function deficits induced by MPTP. The results show that SA possesses anti-Parkinson effects in MPTP-treated C57BL/6 mice and that reduction in ROS levels might be one of the mechanisms.

Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation

Czech Academy of Sciences Publication Activity Database

Ježek, J.; Engstová, Hana; Ježek, Petr

2017-01-01

Roč. 1858, č. 9 (2017), s. 750-762 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GA17-01813S Institutional support: RVO:67985823 Keywords : mitochondria-targeted antioxidant SkQ1 * mitochondrial Complex I superoxide formation * mitochondrial Complex III superoxide formation * HepG2 cell s * NAD(P)H fluorescence lifetime imaging microscopy Subject RIV: ED - Physiology OBOR OECD: Cell biology Impact factor: 4.932, year: 2016

[The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors (AtR!Sk) - A Pioneering Approach of Outpatient Early Detection and Intervention of Borderline Personality Disorder].

Science.gov (United States)

Kaess, Michael; Ghinea, Denisa; Fischer-Waldschmidt, Gloria; Resch, Franz

2017-07-01

The Outpatient Clinic for Adolescent Risk-taking and Self-harm behaviors (AtR!Sk) - A Pioneering Approach of Outpatient Early Detection and Intervention of Borderline Personality Disorder Self-harm and risk-taking behaviors are frequently occurring problems in adolescents' everyday life and commonly challenge the present child and adolescent health-care system. Those behaviors are typical features of borderline-personality disorder (BPD), a severe mental disorder that is associated with immense psychological strain, increased risk of mortality and poor psychosocial functioning. Despite controversy in the past, recent evidence shows that BPD is a valid and reliable diagnosis in adolescence. Consequently, specified and effective intervention programs for this age group are necessary. Instead, present health-care services for children and adolescents in Germany are usually characterized by long waiting periods for specialized outpatient treatments and unnecessary expanses of unnecessary long inpatient stays. Alternatively, and in order to prevent serious long-term consequences, new concepts - integrated in an ambulatory setting and close to patients' daily routines - should focus on early detection and treatment of adolescents at-risk presenting with borderline personality features. The specialist outpatient clinic AtR!Sk at the University Hospital Heidelberg ensures a low-threshold initial contact service, comprehensive and accurate diagnosis of BPD features, and rapidly "tailored" therapy for young people presenting with any types of risk-taking and self-harm behavior. AtR!Sk - as a pioneering approach in south Germany - provides evidence-based early detection and intervention for adolescent BPD.

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

Science.gov (United States)

Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

2016-09-01

Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. Copyright © 2016. Published by Elsevier Ltd.

In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis.

Science.gov (United States)

Li, Z; Kang, H; You, Q; Ossa, F; Mead, P; Quinton, M; Karrow, N A

2018-04-11

The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor β, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Niewirusowy transfer genów do komórek skóry – wybrane metody = Non-viral gene transfer into skin cells – selected methods

Directory of Open Access Journals (Sweden)

Ewelina Wędrowska

2016-01-01

3Department of Pathobiochemistry and Clinical Chemistry, Nicolaus Copernicus University Collegium Medicum, Bydgoszcz, Poland       Streszczenie   Wprowadzenie: Skóra jako największy i najłatwiej dostępny narząd stanowi atrakcyjny cel dla terapii genowej, która od wielu lat budzi ogromne nadzieje środowiska naukowego. Jednakże, próby terapii przeprowadzone z wykorzystaniem wektorów wirusowych wykazały szereg wad i ograniczeń m.in. obserwowano indukcję odpowiedzi immunologicznej, losową integrację transgenu z genomem gospodarza i/lub niską wydajność jego ekspresji. Dlatego, wciąż poszukuje się alternatywnych, skuteczniejszych i jednocześnie bezpieczniejszych metod transferu genów. Atrakcyjnej alternatywy upatruje się w metodach niewirusowych. Cel pracy: Przedstawienie wybranych metod niewirusowego transferu genów wykorzystywanych w terapii genowej chorób skóry. Skrócony opis stanu wiedzy: Terapia genowa chorób skóry obejmuje wykorzystanie wektorów plazmidowych jako nośnika genów terapeutycznych, a także metod ich dostarczania do komórek takich jak: elektroporacja, mikroiniekcja, sonikacja, wykorzystanie nośników lipidowych i polimerów kationowych. Podsumowanie: Niewirusowe metody transferu genów oferują pewne zalety włączając niską toksyczność, brak infekcyjności oraz łatwość i niskie koszty produkcji w porównaniu z technikami wirusowymi. Niewirusowe metody wydają się być obiecującym narzędziem terapii genowej chorób skóry w szczególności nowotworów tego narządu.   Słowa kluczowe: plazmid, transfer genów, skóra, wirus, terapia genowa.     Summary Introduction: Skin, the largest and most accessible organ of the human body is considered as an ideal gene therapy target. However, various types of viral vectors used in classical gene therapy have a number of disadvantages, such as possibility of immune response induction, random integration of inserts into the host genome or low expression efficiency

Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State.

Science.gov (United States)

Belkacemi, Abdenour; Ramassamy, Charles

2016-01-01

In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by-products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox-sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-β-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5μM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-κB and Nrf2, the proteins γ-GCS and GSK3β, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-β toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention.

A standardized crisis management model for self-harming and suicidal individuals with three or more diagnostic criteria of borderline personality disorder: The Brief Admission Skåne randomized controlled trial protocol (BASRCT).

Science.gov (United States)

Liljedahl, Sophie I; Helleman, Marjolein; Daukantaité, Daiva; Westrin, Åsa; Westling, Sofie

2017-06-15

Brief Admission is a crisis and risk management strategy in which self-harming and suicidal individuals with three or more diagnostic criteria of borderline personality disorder self-admit to hospital at times of increasing risk when other efforts to stay safe are failing. Standardized in the current randomized controlled trial, the intensity of Brief Admission Skåne is implemented in durations of three days, with a maximum frequency of three times a month. Brief Admission is integrated into existing treatment plans in advance of crises to prevent reliance on general psychiatric admissions for risk management, as these may be lengthy, unstructured, and of uncertain therapeutic value. The overall objective of the Brief Admission Skåne randomized controlled trial is to determine if Brief Admission can replace general psychiatric admission for self-harming and suicidal individuals with complex mental illness at times of escalating risk. Other objectives of the study are to evaluate whether Brief Admission increases daily functioning and enhances coping, reduces psychiatric symptoms including frequency and severity of self-harm and suicidal behaviours. A final objective is to determine if Brief Admission is an effective crisis management model for this population. Participants are randomized at an individual level to either Brief Admission Skåne plus Treatment as Usual or Treatment As Usual. Based on a priori power analyses, N = 124 participants will be recruited to the study. Data collection is in progress, and will continue until June 2018. All participant data are single-blinded and will be handled with intention-to-treat analysis. Based on the combined clinical experience of our international research group, the Brief Admission Skåne randomized controlled trial upon which the current protocol is based represents the first initiative to standardize, implement and evaluate Brief Admission amongst self-harming and suicidal individuals, including those with

In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection.

Science.gov (United States)

Haghani, Amin; Mehrbod, Parvaneh; Safi, Nikoo; Aminuddin, Nur Ain; Bahadoran, Azadeh; Omar, Abdul Rahman; Ideris, Aini

2016-06-05

For centuries, Edible Bird Nest (EBN) has been used in treatment of variety of respiratory diseases such as flu and cough as a Chinese natural medicine. This natural remedy showed the potential to inhibit influenza A virus (IAV). However, little is known about the mechanism of this process and also the evaluation of this product in an animal model. Hence, the current study was designed to elucidate the antiviral and immunomodulatory effects of EBN against IAV strain A/Puerto Rico/8/1934 (H1N1). First, influenza infected MDCK cells treated with EBNs from two locations of Malaysia (Teluk Intan and Gua Madai) that prepared with different enzymatic preparations were analyzed by RT-qPCR and ELISA for detection of viral and cytokines genes. The sialic acid composition of these EBNs was evaluated by H-NMR. Subsequently, after toxicity evaluation of EBN from Teluk Intan, antiviral and immunomodulatory effects of this natural product was evaluated in BALB/c mice by analysis of the viral NA gene and cytokine expressions in the first week of the infection. EBN showed high neuraminidase inhibitory properties in both in vitro and in vivo, which was as effective as Oseltamivir phosphate. In addition, EBN decreased NS1 copy number (p<0.05) of the virus along with high immunomodulatory effects against IAV. Some of the immune changes during treatment of IAV with EBN included significant increase in IFNγ, TNFα, NFκB, IL2, some proinflammatory cytokines like IL1β, IL6, and cytokines with regulatory properties like IL10, IL27, IL12, CCL2 and IL4 depends on the stage of the infection. EBNs from two locations contained different composition of sialic acid and thymol derivatives, which gave them different antiviral properties. EBN from Gua Madai that contained more acetylated sialic acid (Neu2,4,7,8,9 Ac6) showed higher antiviral activity. The findings of this study support the antiviral activity of EBN against influenza virus and validate the traditional usage of this natural remedy

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides.

Science.gov (United States)

Stenberg, Lena; Stößel, Maria; Ronchi, Giulia; Geuna, Stefano; Yin, Yaobin; Mommert, Susanne; Mårtensson, Lisa; Metzen, Jennifer; Grothe, Claudia; Dahlin, Lars B; Haastert-Talini, Kirsten

2017-07-18

Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. No considerable differences appear for the delayed nerve regeneration

Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

DEFF Research Database (Denmark)

Sölétormos, G; Fogh, J M; Sehested-Hansen, B

1997-01-01

A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (hGH...

Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and associated inflammatory cytokines in rats with experimental autoimmune uveitis.

Science.gov (United States)

Tang, Kai; Guo, Dadong; Zhang, Lian; Guo, Junguo; Zheng, Fengming; Si, Junkang; Bi, Hongsheng

2016-09-01

Longdan Xiegan Tang (LXT) is a mixture of herbal extracts commonly used in traditional Chinese medicine that may exert immunomodulatory effects for the treatment of autoimmune diseases. However, the detailed mechanisms that mediate the actions of LXT are unclear. The present study induced an experimental autoimmune uveitis (EAU) model in Lewis rats via injection of IRBP1177‑1191 emulsion. The model was used to investigate the effects of LXT on EAU rats and assess the efficacy of LXT by measuring clinical manifestations and histopathological changes caused by EAU. Additionally, alterations in the ratio of CD4+/CD8+‑T cells were determined by flow cytometry, and the expression of interferon (IFN)‑γ, interleukin (IL)‑17, IL‑10 and tumor necrosis factor (TNF)‑α were measured using reverse transcription‑quantitative polymerase chain reaction and enzyme‑linked immunosorbent assay analysis. The results of the present study demonstrate that LXT can efficiently alleviate the symptoms of EAU, inhibit the differentiation of uveitogenic CD4+ T cells and reduce the expression of proinflammatory cytokines, including IFN‑γ, IL‑17 and TNF‑α. Furthermore, LXT promotes the production of IL‑10 and accelerates the recovery of EAU, indicating that the immunomodulatory effects of LXT may potentially be used for the treatment of uveitis.

10Be exposure age chronology of the last glaciation of the Roháčská Valley in the Western Tatra Mountains, central Europe

Science.gov (United States)

Engel, Zbyněk; Mentlík, Pavel; Braucher, Régis; Křížek, Marek; Pluháčková, Markéta; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Keddadouche, Karim; Aster Team; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Keddadouche, Karim

2017-09-01

10Be exposure ages from moraines and bedrock sites in the Roháčská Valley provide chronology of the last glaciation in the largest valley of the Western Tatra Mts., the Western Carpathians. The minimum apparent exposure age of 19.4 ± 2.1 ka obtained for the oldest sampled boulder and the mean age of 18.0 ± 0.8 ka calculated for the terminal moraine indicate that the oldest preserved moraine was probably deposited at the time of the global Last Glacial Maximum (LGM). The age of this moraine coincides with the termination of the maximum glacier expansion in other central European ranges, including the adjacent High Tatra Mts. and the Alps. The equilibrium line altitude (ELA) of the LGM glacier in the Roháčská Valley, estimated at 1400-1410 m a.s.l., was 50-80 m lower than in the eastern part of the range, indicating a positive ELA gradient from west to east among the north-facing glaciers in the Tatra Mts. Lateglacial glacier expansion occurred no later than 13.4 ± 0.5 ka and 11.9 ± 0.5 ka, as indicated by the mean exposure ages calculated for re-advance moraines. This timing is consistent with the exposure age chronology of the last Lateglacial re-advance in the High Tatra Mts., Alps and lower mountain ranges in central Europe. The ELA in the Roháčská Valley estimated at 1690-1770 m a.s.l. in this period was located 130-300 m lower than in the north-facing valleys in the High Tatra Mts. 10Be exposure ages obtained for a rock glacier constrains the timing of this landform stabilization in the Salatínska Valley and provides the first chronological evidence for the Lateglacial activity of rock glaciers in the Carpathians.

Developments in damage assessment by Marie Skłodowska-Curie TRUSS ITN project

Science.gov (United States)

González, A.

2017-05-01

The growth of cities, the impacts of climate change and the massive cost of providing new infrastructure provide the impetus for TRUSS (Training in Reducing Uncertainty in Structural Safety), a €3.7 million Marie Skłodowska-Curie Action Innovative Training Network project funded by EU’s Horizon 2020 programme, which aims to maximize the potential of infrastructure that already exists (http://trussitn.eu). For that purpose, TRUSS brings together an international, inter-sectoral and multidisciplinary collaboration between five academic and eleven industry institutions from five European countries. The project covers rail and road infrastructure, buildings and energy and marine infrastructure. This paper reports progress in fields such as advanced sensor-based structural health monitoring solutions - unmanned aerial vehicles, optical backscatter reflectometry, monitoring sensors mounted on vehicles, … - and innovative algorithms for structural designs and short- and long-term assessments of buildings, bridges, pavements, ships, ship unloaders, nuclear components and wind turbine towers that will support infrastructure operators and owners in managing their assets.

Evaluation of Antioxidant, Immunomodulatory, and Cytotoxic Action of Fractions from Eugenia uniflora L. and Eugenia malaccensis L.: Correlation with Polyphenol and Flavanoid Content

OpenAIRE

Figueir?a, Evellyne de Oliveira; Nascimento da Silva, Lu?s Cl?udio; de Melo, Cristiane Moutinho Lagos; Neves, Juliana Kelle de Andrade Lemoine; da Silva, Nic?cio Henrique; Pereira, Val?ria R?go Alves; Correia, Maria Tereza dos Santos

2013-01-01

An increasing number of biological activities presented by medicinal plants has been investigated over the years, and they are used in the search for new substances with lower side effects. Eugenia uniflora L. and Eugenia malaccensis L. (Myrtaceae) have many folk uses in various countries. This current study was designed to quantify the polyphenols and flavonoids contents and evaluate the immunomodulatory, antioxidant, and cytotoxic potentials of fractions from E. uniflora L. and E. malaccens...

Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon.

Science.gov (United States)

Valenzuela, Beatriz; Rodríguez, Felipe E; Modak, Brenda; Imarai, Mónica

2018-03-01

In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

Survival, Intestinal Mucosa Adhesion, and Immunomodulatory Potential of Lactobacillus plantarum Strains.

Science.gov (United States)

Santarmaki, Valentini; Kourkoutas, Yiannis; Zoumpopoulou, Georgia; Mavrogonatou, Eleni; Kiourtzidis, Mikis; Chorianopoulos, Nikos; Tassou, Chrysoula; Tsakalidou, Effie; Simopoulos, Constantinos; Ypsilantis, Petros

2017-09-01

Survival during transit through the gastrointestinal track, intestinal mucosa adhesion, and a potential immunomodulatory effect of Lactobacillus plantarum strains 2035 and ACA-DC 2640 were investigated in a rat model. According to microbiological and multiplex PCR analysis, both strains were detected in feces 24 h after either single-dose or daily administration for 7 days. Intestinal mucosa adhesion of L. plantarum 2035 was noted in the large intestine at 24 h after single-dose administration, while it was not detected at 48 h. Daily dosing, prolonged detection of the strain up to 48 h post-administration, and expanded adhesion to the small intestine. Adhesion of L. plantarum ACA-DC 2640 to the intestinal mucosa after single-dose administration was prolonged and more extended compared to L. plantarum 2035. Daily dosing increased both the levels and the rate of positive cultures of the strains compared to those of the single-dose scheme. In addition, both strains increased total IgG while decreased IgM and IgA serum levels. In conclusion, L. plantarum 2035 and L. plantarum ACA-DC 2640 survived transit through the gastrointestinal track, exhibited transient distinct adhesion to the intestinal mucosa and modulated the systemic immune response.

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

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Richard Heyes

2016-01-01

Full Text Available This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs in promoting vascularized composite allotransplant (VCA tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.

Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

Science.gov (United States)

Özek, Gulmira; Schepetkin, Igor A; Utegenova, Gulzhakhan A; Kirpotina, Liliya N; Andrei, Spencer R; Özek, Temel; Başer, Kemal Hüsnü Can; Abidkulova, Karime T; Kushnarenko, Svetlana V; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

2017-06-01

Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were ( E )-propenyl sec -butyl disulfide (15.7-39.4%) and ( Z )-propenyl sec -butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca 2+ ] i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca 2+ ] i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca 2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be ( Z )-propenyl sec -butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs. © Society for Leukocyte Biology.

Finančná analýza podniku Choceňská mlékárna, s.r.o.

OpenAIRE

Zigo, Michal

2011-01-01

The bachelor thesis assesses a financial position of the company Choceňská mlékárna, s.r.o. with the help of financial analysis tools such as horizontal and vertical analyses, parallel and pyramidal system of financial ratios, creditworthy and bankruptcy models, and economic value added in the horizon of five years. Theoretical-methodological part describes the financial analysis as a tool for an assessment of the financial position of the company and it further defines the evaluation apparat...

High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.

Science.gov (United States)

Cho, Doo-Yeoun; Bae, Soo Hyeon; Shon, Ji-Hong; Bae, Soo Kyung

2013-03-01

A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

Science.gov (United States)

Warrender-Sparkes, Matthew; Spelman, Tim; Izquierdo, Guillermo; Trojano, Maria; Lugaresi, Alessandra; Grand'Maison, François; Havrdova, Eva; Horakova, Dana; Boz, Cavit; Oreja-Guevara, Celia; Alroughani, Raed; Iuliano, Gerardo; Duquette, Pierre; Girard, Marc; Terzi, Murat; Hupperts, Raymond; Grammond, Pierre; Petersen, Thor; Fernandez-Bolaños, Ricardo; Fiol, Marcela; Pucci, Eugenio; Lechner-Scott, Jeannette; Verheul, Freek; Cristiano, Edgardo; Van Pesch, Vincent; Petkovska-Boskova, Tatjana; Moore, Fraser; Kister, Ilya; Bergamaschi, Roberto; Saladino, Maria Laura; Slee, Mark; Barnett, Michael; Amato, Maria Pia; Shaw, Cameron; Shuey, Neil; Young, Carolyn; Gray, Orla; Kappos, Ludwig; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija

2016-04-01

We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, ptreatment compared with other therapies (ptreatment discontinuation. Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications. © The Author(s), 2015.

The Immunomodulatory Effect of You-Gui-Wan on Dermatogoides-pteronyssinus-Induced Asthma

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Li-Jen Lin

2012-01-01

Full Text Available The traditional Chinese medicine You-Gui-Wan (YGW contains ten species of medicinal plants and has been used to improve health in remissive states of asthma for hundreds of years in Asia. However, little is known about the immunomodulatory mechanisms in vivo. Therefore, this study investigated the pathologic and immunologic responses to YGW in mice that had been repeatedly exposed to Dermatogoides-pteronyssinus (Der p. YGW reduced Der-p-induced airway hyperresponsiveness and total IgE in serum. It also inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in serum and changed the Th2-bios in BALF by upregulating IL-12. Results of the collagen assay and histopathologic examination showed that YGW reduced airway remodeling in the lung. In addition, after YGW treatment there was a relative decrease in mRNA expression of TGF-β1, IL-13, eotaxin, RANTES, and MCP-1 in lung in the YGW group. The results of EMSA and immunohistochemistry revealed that YGW inhibited NF-κB expression in epithelial lung cells. YGW exerts its regulative effects in chronic allergic asthmatic mice via its anti-inflammatory activity and by inhibiting the progression of airway remodeling.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

International Nuclear Information System (INIS)

Rödel, Franz; Frey, Benjamin; Manda, Katrin; Hildebrandt, Guido; Hehlgans, Stephanie; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Gaipl, Udo S.; Rödel, Claus

2012-01-01

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rödel, Franz [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Frey, Benjamin [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Manda, Katrin; Hildebrandt, Guido [Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock (Germany); Hehlgans, Stephanie [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Keilholz, Ludwig [Department of Radiotherapy, Clinical Center Bayreuth, Bayreuth (Germany); Seegenschmiedt, M. Heinrich [Strahlenzentrum Hamburg Medizinisches Versorgungszentrum, Hamburg (Germany); Gaipl, Udo S. [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Rödel, Claus, E-mail: franz.roedel@kgu.de [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany)

2012-09-25

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Mechanizmy regulacji odpowiedzi immunologicznej w zwierzęcym modelu alergicznego kontaktowego zapalenia skóry [Mechanisms involved in the regulation of immune response in animal model of allergic contact dermatitis

Directory of Open Access Journals (Sweden)

Anna Strzępa

2014-09-01

Full Text Available Streszczenie Alergiczne kontaktowe zapalenie skóry jest klasycznym przykładem późnej reakcji nadwrażliwości typu IV, którą mediują limfocyty efektorowe CD4+ Th1. Rozwój alergicznego kontaktowego zapalenia skóry (ACD jest następstwem ekspozycji na działanie małocząsteczkowych substancji (hapteny. Obecnie ACD jest jedną z najczęstszych chorób zawodowych. Występowanie alergii kontaktowej na co najmniej jeden czynnik w krajach Europy Zachodniej i Ameryki Północnej dochodzi do 19,5% dla różnych grup wiekowych. Klasyczna egzematyczna postać ACD manifestuje się jako rumień, naciek, nadmierne rogowacenie, obrzęk i pęcherze, którym towarzyszy świąd. Modelem zwierzęcym ACD jest reakcja nadwrażliwości kontaktowej (CS. Składa się ona z dwóch następujących po sobie etapów: indukcja (faza aferentna i wywołanie (faza eferentna. W trakcie pierwszego kontaktu z haptenem powstają swoiste limfocyty efektorowe (Tef, które są rekrutowane do miejsca ponownej ekspozycji na hapten. W tym artykule przedstawiono mechanizmy immunologiczne leżące u podstaw ACD, opierając się na modelu CS.

Use of solar parabolic cookers (SK-14) in Nepal

Energy Technology Data Exchange (ETDEWEB)

Shrestha, S. [Asia Network for Small Scale Bioresources, Kathmandu (Nepal)

2000-07-01

Solar Cooker is a device that uses only sunlight to cook food and pasteurise water. Solar cooker can be used along with other cooking devices to save cost, fuel and the time spent in gathering fuelwood. Solar cooking enables individual families to do without commercially sold fuel and help save money. In Nepal, supply of energy is one of the major problems for both urban and rural households. Increase in population, high migration, expensive fuel bills, environmental degradation, and unsafe drinking water have resulted in the keen interest from people of Nepal in the use of solar energy. The increasing number of tourists and trekkers are now one of the major sources of income and many people are engaged in running hotels, lodges, and restaurants. This has also increased the fuel demand. This paper highlights the current energy situation of Nepal, the technical details of solar parabolic cooker (SK-14), its uses throughout Nepal, strategies adopted by various organisations for its promotion. A lot of effort have been made by various organisations, educational, governmental and health related institutions in order to introduce solar cooking programs in villages of Nepal. The parameters, which have influenced the adoption of this technology in Nepal are also mentioned. Various awareness programs and the government subsidy program are playing considerable role in dissemination of such technologies. The promotion activities with the objective of mass awareness have long term effect and sustainable rather than instant business. Continued efforts to create awareness, development of models as well as proper promotion and dissemination are required. (au)

Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics.

Science.gov (United States)

Drago, Lorenzo; De Vecchi, Elena; Gabrieli, Arianna; De Grandi, Roberta; Toscano, Marco

2015-07-01

The aim of this study was to evaluate probiotic characteristics of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their immunomodulatory activity in asthmatic subjects. Subjects affected by allergic asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth compatibility by a broth compatibility assay. To study the antimicrobial activity of probiotic strains, an agar diffusion assay was performed. Finally, cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and BR03 was determined by means of specific quantitative enzyme-linked immunosorbent assay (ELISA). The growth of some clinical pathogens were slightly inhibited by LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed promising probiotic properties and beneficial immunomodulatory activity that are increased when the 2 strains are used in combination in the same formulation.

Preparation of Ginsenoside Rg3 and Protection against H2O2-Induced Oxidative Stress in Human Neuroblastoma SK-N-SH Cells

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Gang Li

2014-01-01

Full Text Available The aim of this study is to evaluate the protection of ginsenoside Rg3 against oxidative stress in human neuroblastoma SK-N-SH cells. 20(R-ginsenoside Rg3 (20(R-Rg3 and 20(S-ginsenoside Rg3 (20(S-Rg3 were prepared by the method of chemical degradation and column chromatography, and the structure of the two compounds was characterized by 1H-NMR and 13C-NMR spectroscopy. MTT assay and LDH leakage assay were used to determine the cell viability and the oxidative stress cellular model was established by means of H2O2 (600 μM for 4 h. We also investigated the changes of intracellular MDA content, SOD activity, and ROS formation after the treatment of ginsenoside Rg3 for 20 h. The results indicated that both 20 (R-Rg3 and 20 (S-Rg3 had obvious protection against H2O2-induced oxidative stress in SK-N-SH cells. Moreover, 20(R-Rg3 exhibited better antioxidant activity than 20(S-Rg3 in vitro. These findings are expected to provide some implication for further research and application of ginsenoside Rg3 in neuroprotection.

Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database.

Science.gov (United States)

Zhong, Zhangfeng; Liu, Li-Juan; Dong, Zhi-Qiang; Lu, Lihua; Wang, Modi; Leung, Chung-Hang; Ma, Dik-Lung; Wang, Yitao

2015-06-30

We report herein the identification of an immunomodulatory natural product-like compound as a direct inhibitor of TLR1-TLR2 heterodimerization. Compound suppressed TNF-α and IL-6 secretion in Pam3CSK4-induced macrophages. Moreover, compound inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-κB. Molecular docking revealed that compound bound to the interface region of TLR1-TLR2 by forming two hydrogen bonds with residues lining the binding site. To our knowledge, compound has been only the second inhibitor overall of TLR1-TLR2 heterodimerization reported to date.

Immunomodulatory interplay of the microbiome and therapy of rheumatic diseases.

Science.gov (United States)

Ostrov, Barbara E; Amsterdam, Daniel

2017-11-01

Modulation of the immune system by microbes, especially from the gastrointestinal tract, is increasingly considered a key factor in the onset, course and outcome of rheumatic diseases. The interplay of the microbiome, along with genetic predisposition and environmental exposure, is thought to be an important trigger for rheumatic diseases. Improved identification of the relationship of disease-specific genetic alterations and rheumatic diseases has potential diagnostic and therapeutic applications. Treatment of rheumatic disorders is influenced by microbial actions but this interplay can be challenging due to variable and unpredictable responses to therapies. Expanded knowledge of the microbiome now allows clinicians to more precisely select ideal medication regimens and to predict response to and toxicity from drugs. Rheumatic diseases and associated therapies were among the earliest microbiome interactions investigated, yet it is notable that current research is focused on clinical and immunological associations but, in comparison, a limited number of studies regarding the microbiome's impact on treatment for rheumatic diseases have been published. In the coming years, further knowledge of immunomodulating interactions between the microbiome and the immune system will aid our understanding of autoimmunity and will be increasingly important in selection of therapeutic agents for patients with autoimmune and rheumatic diseases. In this review, recent literature regarding the bidirectional immunomodulatory effects of the microbiome with rheumatic diseases and current understanding and gaps regarding the drug-microbiome interface in the management of these disorders is presented.

Immunomodulatory activity and partial characterisation of polysaccharides from Momordica charantia.

Science.gov (United States)

Deng, Yuan-Yuan; Yi, Yang; Zhang, Li-Fang; Zhang, Rui-Fen; Zhang, Yan; Wei, Zhen-Cheng; Tang, Xiao-Jun; Zhang, Ming-Wei

2014-08-29

Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant's polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP) fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg-·d⁻¹ of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy)-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55×10⁴ Da and 4.41×10⁵ Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants.

Immunomodulatory Activity and Partial Characterisation of Polysaccharides from Momordica charantia

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Yuan-Yuan Deng

2014-08-01

Full Text Available Momordica charantia Linn. is used as an edible and medicinal vegetable in sub-tropical areas. Until now, studies on its composition and related activities have been confined to compounds of low molecular mass, and no data have been reported concerning the plant’s polysaccharides. In this work, a crude polysaccharide of M. charantia (MCP fruit was isolated by hot water extraction and then purified using DEAE-52 cellulose anion-exchange chromatography to produce two main fractions MCP1 and MCP2. The immunomodulatory effects and physicochemical characteristics of these fractions were investigated in vitro and in vivo. The results showed that intragastric administration of 150 or 300 mg·kg−·d−1 of MCP significantly increased the carbolic particle clearance index, serum haemolysin production, spleen index, thymus index and NK cell cytotoxicity to normal control levels in cyclophosphamide (Cy-induced immunosuppressed mice. Both MCP1 and MCP2 effectively stimulated normal and concanavalin A-induced splenic lymphocyte proliferation in vitro at various doses. The average molecular weights of MCP1 and MCP2, which were measured using high-performance gel permeation chromatography, were 8.55 × 104 Da and 4.41 × 105 Da, respectively. Both fractions exhibited characteristic polysaccharide bands in their Fourier transform infrared spectrum. MCP1 is mainly composed of glucose and galactose, and MCP2 is mainly composed of glucose, mannose and galactose. The results indicate that MCP and its fractions have good potential as immunotherapeutic adjuvants.

Felicjan Sławoj-Składkowski (1885-1962): The only known doctor-soldier-politician with an outdoor-wooden-toilet named after him.

Science.gov (United States)

Ohry, Avi

2017-05-01

Felicjan Sławoj-Składkowski was a Polish physician, General and politician who served as Polish Minister of Internal Affairs and was the last Prime Minister of Poland before the Second World War. The lack of basic sanitation in many of Poland's villages caused him to issue a decree that every household in Poland must have a latrine in working order. Wooden sheds were built in the backyards, subsequently named 'sławojkis'.

Analysis and Risk Evaluation on the Case of Alteration, Revitalization and Conversion of a Historic Building in Gdańsk

Science.gov (United States)

Grzyl, Beata; Kristowski, Adam; Miszewska-Urbańska, Emilia

2017-10-01

Each investment plan, including the one concerning a building, is exposed to the consequences of various types of threats taking place. Therefore, in the case of some large-scale, atypical and complicated building ventures, some actions included in the procedure of risk management should be taken (identifications, analysis, measurements, control and supervision of the risk). This will allow for the risk to be eliminated or limited. While preparing a building venture, an investor does not possess full information about the course of events on each stage of investment completion. The identification of the above-mentioned unknowns, subjecting them to quantification and specifying the method of dealing with them, allows an investor to increase the effectiveness of the intended plan. The enterprise discussed in this article and analyzed in the context of risk, concerns alteration, revitalization and conversion for office purposes of two buildings located in Gdańsk at 1 and 2 Lastadia Street. These buildings are situated on the area of historical urban layout of Gdańsk, in the northern-eastern part of Stare Przedmieście District (Old Suburb), about 800 meters south from Dlugi Targ Street and 200 meters west from The Old Motława River. The investor is “Gdańskie Melioracje Ltd.”, a limited liability company, which belongs to the Council of Gdańsk. In order to increase the effectiveness of the intended investment venture, while organizing the investment process, the investor commissioned preparation of an analysis and risk evaluation connected with the above-mentioned intention. Based on an on-site visit, the opinions of experts, who have been involved in the process of the preparation of the investment, studies of the available monographies about the technical condition of the buildings at 1 and 2 Lastadia Street and their own experiences, the authors identified 54 types of relevant risks, which have been systematized into 10 subject groups (among others

Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line.

Science.gov (United States)

Doggui, Sihem; Sahni, Jasjeet Kaur; Arseneault, Madeleine; Dao, Lé; Ramassamy, Charles

2012-01-01

Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-β activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease.

Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells.

Science.gov (United States)

Garofalo, Tina; Ferri, Alberto; Sorice, Maurizio; Azmoon, Pardis; Grasso, Maria; Mattei, Vincenzo; Capozzi, Antonella; Manganelli, Valeria; Misasi, Roberta

2018-04-01

Since stressing conditions induce a relocalization of endogenous human neuroglobin (NGB) to mitochondria, this research is aimed to evaluate the protective role of NGB overexpression against neurotoxic stimuli, through mitochondrial lipid raft-associated complexes. To this purpose, we built a neuronal model of oxidative stress by the use of human dopaminergic neuroblastoma cells, SK-N-BE2, stably overexpressing NGB by transfection and treated with 1-methyl-4-phenylpyridinium ion (MPP+). We preliminary observed the redistribution of NGB to mitochondria following MPP+ treatment. The analysis of mitochondrial raft-like microdomains revealed that, following MPP+ treatment, NGB translocated to raft fractions (Triton X-100-insoluble), where it interacts with ganglioside GD3. Interestingly, the administration of agents capable of perturbating microdomain before MPP+ treatment, significantly affected viability in SK-N-BE2-NGB cells. The overexpression of NGB was able to abrogate the mitochondrial injuries on complex IV activity or mitochondrial morphology induced by MPP+ administration. The protective action of NGB on mitochondria only takes place if the mitochondrial lipid(s) rafts-like microdomains are intact, indeed NGB fails to protect complex IV activity when purified mitochondria were treated with the lipid rafts disruptor methyl-β-cyclodextrin. Thus, our unique in vitro model of stably transfected cells overexpressing endogenous NGB allowed us to suggest that the role in neuroprotection played by NGB is reliable only through interaction with mitochondrial lipid raft-associated complexes. Copyright © 2018 Elsevier Inc. All rights reserved.

Psychologiczne aspekty chorób alergicznych: trudności dorosłych pacjentów z astmą oskrzelową i atopowym zapaleniem skóry

Directory of Open Access Journals (Sweden)

Paulina Albińska

2014-12-01

Full Text Available Celem pracy jest zaprezentowanie przeglądu badań na temat psychologicznego funkcjonowania dorosłych cierpiących na choroby alergiczne. Artykuł koncentruje się na dorosłych ze względu na istnienie małej liczby prac naukowych dotyczących zmiany manifestacji symptomów u pacjentów z wyżej wymienionymi chorobami, która może być traktowana jako pierwsze i ostatnie stadium marszu alergicznego, ponieważ jego objawowa manifestacja u dzieci zwykle przybiera postać atopowego zapalenia skóry, podczas gdy u dorosłych jest znana jako astma oskrzelowa. Analiza odpowiada na pytanie, czy wspólnej, alergiczno-zapalnej etiologii tych schorzeń odpowiadają podobieństwa doświadczanych trudności psychologicznych. Omówienie odwołuje się do polskiej i zagranicznej literatury przedmiotu i uwzględnia kluczowe aspekty chorób psychosomatycznych – astmy i atopowego zapalenia skóry – czyli trudności ze snem, depresję, lęk, inne zaburzenia afektywne, zaburzenia zachowania i trudności poznawcze. Współwystępowanie zaburzeń psychicznych i somatycznych u chorych na alergię to niepodważalny dowód integralności somy i psyche, co rzadko dostrzegają osoby odpowiedzialne za system opieki zdrowotnej. Ignorują one tym samym ważny element procesu diagnostyczno-terapeutycznego, istotny dla wyzdrowienia pacjentów z astmą i atopowym zapaleniem skóry.

Observations of the anisotropy in the cosmic microwave background by the FIRS, SK93, and MSAM-I experiments

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Kowitt, Matt; Cheng, Ed; Silverberg, Bob; Ganga, Ken; Page, Lyman; Jarosik, Norm; Netterfield, Barth; Wilkinson, Dave; Meyer, Stephan; Inman, Casey;

Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes

DEFF Research Database (Denmark)

Boje, Alex; Moesby, Lise; Timm, Michael

2012-01-01

The sex hormones are known to affect innate immunity in humans. In this study we evaluated the immunomodulatory effects of testosterone in a model system comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed the results in human granulocytes and monocytes. Results showed...... that testosterone at pharmacological doses reduced the production of interleukin-8 and reactive oxygen species from differentiated HL-60 cells in a concentration dependent manner without affecting phagocytosis. The cells were stimulated with zymosan, lipopolysaccharide, or Bacillus subtilis. At the highest...... concentration of testosterone (120 µM), interleukin-8 secretion was reduced 42-80%, and production of reactive oxygen species was reduced 32-46%. Flutamide, an antagonist of the classical intracellular androgen receptor, was unable to antagonize the immunosuppressive effect of testosterone. We further...

Antineoplastic and immunomodulatory effect of polyphenolic components of Achyranthes aspera (PCA) extract on urethane induced lung cancer in vivo.

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Narayan, Chandradeo; Kumar, Arvind

2014-01-01

Polyphenolic compounds of Achyranthes aspera (PCA) extract is evaluated for anti-cancerous and cytokine based immunomodulatory effects. The PCA extract contains known components of phenolic acid and flavonoids such as mixture of quinic acid, chlorogenic acid, kaempferol, quercetin and chrysin along with many unknown components. PCA has been orally feed to urethane (ethyl carbamate) primed lung cancerous mice at a dosage of 100 mg/kg body weight for 30 consecutive days. 100 mg powder of A. aspera contains 2.4 mg phenolic acid and 1.1 mg flavonoid (2:1 ratio). Enhanced activities and expression of antioxidant enzymes GST, GR, CAT, SOD, while down regulated expression and activation of LDH enzymes in PCA feed urethane primed lung cancerous tissues as compared to PCA non-feed urethane primed lung cancerous tissues were observed. PCA feed urethane primed lung tissues showed down regulated expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α along with TFs, NF-κB and Stat3 while the expression of pro-apoptotic proteins Bax and p53 were enhanced in PCA feed urethane primed lung tissues. FTIR and CD spectroscopy data revealed that PCA resisted the urethane mediated conformational changes of DNA which is evident by the shift in guanine and thymine bands in FTIR from 1,708 to 1,711 cm(-1) and 1,675 to 1,671 cm(-1), respectively in PCA feed urethane primed lung cancerous tissues DNA in comparison to urethane primed lung cancerous tissues DNA. The present study suggests that PCA components have synergistic anti-cancerous and cytokine based immunomodulatory role and DNA conformation restoring effects. However, more research is required to show the effects of each component separately and in combination for effective therapeutic use to cure and prevent lung cancer including other cancers.

Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro.

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Prasanna, Vaddi K; Venkatesh, Yeldur P

2015-06-01

Onion (Allium cepa), a bulb crop of economic importance, is known to have many health benefits. The major objective of the present study is to address the immunomodulatory properties of onion lectin (A. cepa agglutinin; ACA). ACA was purified from onion extract by D-mannose-agarose chromatography (yield: ~1 mg/kg). ACA is non-glycosylated and showed a molecular mass of ~12 kDa under reducing/non-reducing SDS-PAGE; glutaraldehyde cross-linking indicated that ACA is a non-covalent tetramer of ~12 kDa subunits. Its N-terminal sequence (RNVLLNNEGL; UniProt KB Accn. C0HJM8) showed 70-90% homology to mannose-specific Allium agglutinins. ACA showed specific hemagglutination activity of 8200 units/mg and is stable in the pH range 6-10 and up to 45° C. The immunomodulatory activity of ACA was assessed using the macrophage cell line, RAW264.7 and rat peritoneal macrophages; at 0.1 μg/well, it showed a significant increase (6-8-fold vs. control) in the production of nitric oxide at 24h, and significantly stimulated (2-4-fold vs. control) the production of pro-inflammatory cytokines (TNF-α and IL-12) at 24h. ACA (0.1 μg/well) enhanced the proliferation of murine thymocytes by ~4 fold (vs. control) at 24h; however, ACA does not proliferate B cell-enriched rat splenocytes. Further, it significantly elevated the expression levels of cytokines (IFN-γ and IL-2) over the control in murine thymocytes. Taken together, purified ACA induces a Th1-type immune response in vitro. Though present in low amounts, ACA may contribute to the immune-boosting potential of the popular spice onion since considerable amounts are consumed on a daily basis universally. Copyright © 2015 Elsevier B.V. All rights reserved.

A comparative study on immunomodulatory activity of polysaccharides from two official species of Ganoderma (Lingzhi).

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Meng, Lan-Zhen; Xie, Jing; Lv, Guang-Ping; Hu, De-Jun; Zhao, Jing; Duan, Jin-Ao; Li, Shao-Ping

2014-01-01

Two Ganoderma species, G. lucidum and G. sinense, are listed as Lingzhi in Chinese Pharmacopoeia and they are considered to have the same therapeutic effects. Polysaccharides were the main immunomodulatory and anticancer components in Ganoderma. In this study, the chemical characters and the effects of polysaccharides from G. lucidum (GLPS) and G. sinense (GSPS) on macrophage functions were investigated and compared. Chemical studies showed that GLPS and GSPS were different, displaying various molecular weight distribution and ratio of monosaccharide components. In vitro pharmacological studies showed that both GLPS and GSPS had potent effects on macrophage functions, such as promoting macrophage phagocytosis, increasing their release of nitric oxide and cytokines interleukin (IL)-1α, IL-6, IL-10, and tumor necrosis factor-α. Generally, GLPS was more powerful than GSPS. This study is helpful to elucidate the active components and pharmacological variation between the 2 Ganoderma species. The structure-activity relationship of polysaccharides from Ganoderma needs further study.

Liquefied Natural Gas Storage of Variable Composition / Magazynowanie Skroplonego Gazu Ziemnego O Zmiennym Składzie

Science.gov (United States)

Łaciak, Mariusz

2015-03-01

Thanks to the increasing diversification of LNG supply sources, being a result of the growing number of LNG liquefaction installations over the World, increase of short-term trade contracts and general trend to globally liberalize gas markets, reception terminals have to cope with the broad range of qualitatively diversified LNG deliveries from various sources. Different LNG deliveries potentially have different density caused by different gas composition. Although the LNG composition depends on LNG source, it mainly consists of methane, ethane, propane, butane and trace nitrogen. When a new supply of LNG is transported to the tank, the LNG composition and temperature in the tank can be different from LNG as delivered. This may lead to the liquid stratification in the tank, and consequently the rollover. As a result, LNG rapidly evaporates and the pressure in the tank increases. More and more restrictive safety regulations require fuller understanding of the formation and evolution of layers. The paper is focused on the analysis of liquid stratification in the tank which may take place when storing LNG, and which process leads to the rapid evaporation of considerable quantities of LNG. The aim was to attempt modeling of the process of liquid stratification in an LNG tank. The paper is closed with the results of modelling. Dzięki rosnącej dywersyfikacji źródeł dostaw LNG, spowodowanej zwiększającą się liczbą instalacji skraplania gazu na całym świecie, wzrostem ilości kontraktów krótkoterminowych w handlu i ogólnej tendencji do globalnej liberalizacja rynków gazu, terminale do odbioru muszą radzić sobie z coraz większą gamą różnych jakościowo dostaw LNG z różnych źródeł. Różne dostawy LNG mają potencjalnie inną gęstość dzięki różnym składom gazu. Chociaż kompozycja LNG zależy od źródła, to przede wszystkim składa się z metanu, etanu, propanu, butanu i w śladowych ilościach z azotu. Gdy nowa dostawa LNG jest

Zircon and baddeleyite from the economic ultramafic-mafic Noril'sk-1 intrusion (Russia): Hf-isotope constraints on source composition

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Malitch, K. N.; Belousova, E. A.; Badanina, I. Yu.; Griffin, W. L.

2012-04-01

The ultramafic-mafic Noril'sk-1 intrusion in the northwestern part of the Siberian Craton (Russia) represents one of three known Noril'sk-type, ore-bearing intrusions, which host one of the world's major economic sulphide platinum-group-element (PGE)-Cu-Ni deposits. Zircon and baddeleyite dated previously both by SHRIMP (i.e. 248.0 ± 3.7 Ma, Campbell et al. 1992) and ID-TIMS (251.1 ± 3.6 Ma, Kamo et al. 1996) have been restricted to one lithology (e.g. leucogabbro) of the Noril'sk-1 intrusion. To better constrain the age of igneous event and sources involved in its generation our multi-technique study utilized ten rock samples characteristic of unmineralized and mineralized lithologies. The rocks investigated comprise (from top to bottom) gabbro-diorite (sample N1-1), leucogabbro (N1-3), olivine-free gabbro (N1-2 and N1-4), olivine-bearing gabbro (N1-5), olivine gabbro (N1-6), plagiowehrlite and plagiodunite (N1-7), taxitic-textured rocks comprising melanotroctolite, olivine gabbro with relics of ultramafic rocks (N1-8, N1-9) and contact fine-grained gabbro (N1-10). Sulphide PGE-Cu-Ni ores occur in ultramafic (N1-7) and taxitic-textured rocks (N1-8 and N1-9), which have thickness of about 17 m, whereas the low-sulphide horizon of about 1 m thick occurs in the upper part of intrusion (N1-3). In situ U-Pb analyses of zircon from these rocks, combined with detailed study of crystal morphology and internal structure, identify four zircon populations (Malitch et al. 2012). The U-Pb ages of baddeleyite and the defined zircon populations cover a significant time span, from Late Paleozoic to Early Mesozoic (e.g., 290 ± 2.8; 261.3 ± 1.6; 245.7 ± 1.1; 236.5 ± 1.8 and 226.7 ± 0.9 Ma). The established distribution of U-Pb ages implies that crystallization of baddeleyite and zircon corresponds to several stages of protracted evolution of ultramafic-mafic magmas at deep-seated staging chambers and/or probably characterizes interaction of distinct magmas during formation

Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

Science.gov (United States)

Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

2017-01-01

Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

Structural characterization and immunomodulatory activity of a pectic polysaccharide (CALB-4) from Fructus aurantii.

Science.gov (United States)

Shu, Zunpeng; Yang, Yanni; Xing, Na; Wang, Yi; Wang, Qiuhong; Kuang, Haixue

2018-02-01

A purified polysaccharide, designated CALB-4, was acquired from Fructus aurantii that is the traditional edible/medicina plant in China. The present study was performed to characterize the CALB-4 and to evaluate its immunomodulatory activities on human peripheral blood mononuclear cells (PBMCs). The structure of CALB-4 was characterized by partial acid hydrolysis, periodate oxidation, Smith degradation, and methylation analysis combined with gas chromatography-mass spectrometry (GC-MS), Infrared Spectroscopy (IR) and scanning electron microscopy (SEM). The results indicated that CALB-4 was elucidated as a pectic polysaccharide and its main chain is composed of Man, Gal UA and Gal, interspersed with Ara, Rha, Man and Gal. Furthermore, immunological tests showed that CALB-4 exhibits the immunoenhancement effects. The mechanism for this action might be attributed to the increase of the cytoplasmic concentration of pro-IL-1 via the up-regulation of several mitogen-activated protein kinases (MAPKs) and the nuclear translocation of p65. This study clarified that CALB-4 could be as an efficacious biological response modifier in immunotherapy. Copyright © 2018. Published by Elsevier B.V.

Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma

International Nuclear Information System (INIS)

Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

2015-01-01

Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities

Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma.

Science.gov (United States)

Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

2015-05-15

Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities.

Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice

Directory of Open Access Journals (Sweden)

R.N.M. Guerra

2003-09-01

Full Text Available Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties. In Brazilian folk medicine, the aqueous extract of A. tenella Colla is used for its anti-inflammatory activity. The present study investigated the immunomodulatory property of A. tenella extract by evaluating the antibody production in male albino Swiss mice weighing 20-25 g (10 per group. The animals received standard laboratory diet and water ad libitum. The effect of A. tenella extract (5 and 50 mg/kg, ip was evaluated in mice immunized with sheep red blood cells (SRBC 10%, ip as T-dependent antigen, or in mice stimulated with mitogens (10 µg, Escherichia coli lipopolysaccharide, LPS, ip. The same doses (5 and 50 mg/kg, ip of A. tenella extract were also tested for antitumor activity, using the Ehrlich ascites carcinoma as model. The results showed that 50 mg/kg A. tenella extract ip significantly enhanced IgM (64% and IgG2a (50% antibody production in mice treated with LPS mitogen. The same dose had no effect on IgM-specific response, whereas the 5 mg/kg treatment caused a statiscally significant reduction of anti-SRBC IgM-specific antibodies (82%. The aqueous extract of A. tenella (50 mg/kg increased the life span (from 16 ± 1 to 25 ± 1 days and decreased the number of viable tumor cells (59% in mice with Ehrlich ascites carcinoma. The present findings are significant for the development of alternative, inexpensive and perhaps even safer strategies for cancer treatment.

Inhibitions of mTORC1 and 4EBP-1 are key events orchestrated by Rottlerin in SK-Mel-28 cell killing.

Science.gov (United States)

Daveri, E; Maellaro, E; Valacchi, G; Ietta, F; Muscettola, M; Maioli, E

2016-09-28

Earlier studies demonstrated that Rottlerin exerts a time- and dose-dependent antiproliferative effect on SK-Mel-28 melanoma cells during 24 h of treatment, but cytotoxicity due to cell death began only after a 48 h exposure. In the current study, in order to identify the type of cell death in this cell line, which is notoriously refractory to most anticancer therapies, and to clarify the underlying mechanisms of this delayed outcome, we searched for apoptotic, necrotic/necroptotic and autophagic traits in Rottlerin-exposed cells. Although SK-Mel-28 cells are both apoptosis and autophagy competent, Western blotting analysis, caspase activity assay, nuclear imaging and the effects of autophagy, apoptosis and necroptosis inhibitors, indicated that Rottlerin cytotoxicity was due to none of the aforementioned death mechanisms. Nevertheless, in growth arrested cells, the death did occur after a prolonged treatment and most likely ensued from the observed blockage of protein synthesis that reached levels expected to be incompatible with cell survival. From a mechanistic point of view, we ascribed this effect to the documented inhibition of mTORC1 activity; mTORC1 inhibition on the one hand led to a not deadly, rather protective autophagic response but, on the other hand caused a near complete arrest of protein synthesis. Interestingly, no cytotoxicity was found towards normal skin fibroblasts, which only resulted mildly growth arrested by the drug. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Process optimization and photostability of silymarin nanostructured lipid carriers: effect on UV-irradiated rat skin and SK-MEL 2 cell line.

Science.gov (United States)

Singh, Pooja; Singh, Mahendra; Kanoujia, Jovita; Arya, Malti; Saraf, Shailendra K; Saraf, Shubhini A

2016-10-01

The objective of the present work was to formulate a novel stable delivery system which would not only overcome the solubility issue of silymarin, but also help to increase the therapeutic value by better permeation, anticancer action and reduced toxicity. This was envisaged through the recent developments in nanotechnology, combined with the activity of the phytoconstituent silymarin. A 2(3) full factorial design based on three independent variables was used for process optimization of nanostructured lipid carriers (NLC). Developed formulations were evaluated on the basis of particle size, morphology, in vitro drug release, photostability and cell line studies. Optimized silymarin-NLC was incorporated into carbopol gel and further assessed for rheological parameters. Stable behaviour in presence of light was proven by photostability testing of formulation. Permeability parameters were significantly higher in NLC as compared to marketed phytosome formulation. The NLC based gel described in this study showed faster onset, and prolonged activity up to 24 h and better action against edema as compared to marketed formulation. In case of anticancer activity of silymarin-NLC against SK-MEL 2 cell lines, silymarin-NLC proved to possess anticancer activity in a dose-dependent manner (10-80 μM) and induced apoptosis at 80 μM in SK-MEL 2 cancer cells. This work documents for the first time that silymarin can be formulated into nanostructured lipoidal carrier system for enhanced permeation, greater stability as well as anticancer activity for skin.

[Comparison of the immunomodulatory effects of spore polysaccharides and broken spore polysaccharides isolated from Ganoderma lucidum on murine splenic lymphocytes and peritoneal macrophages in vitro].

Science.gov (United States)

Wang, Peng-yun; Wang, Sai-zhen; Lin, Shu-qian; Lin, Zhi-bin

2005-12-18

To compare the immunomodulatory effects of spore polysaccharides (Gl-SP) and broken spore polysaccharides (Gl-BSP) isolated from Ganoderma lucidum(Leyss et Fr.) Karst. on murine splenic lymphocytes and peritoneal macrophages in vitro. Mixed lymphocyte culture reaction (MLR), lymphocyte proliferation in the presence or absence of mitogen, and the cytotoxic activity of splenic natural killer (NK) cells were detected with MTT assay in vitro. The percentage of phagocytosis of neutral red (NR) by mouse peritoneal macrophages was detected by colorimetric assay. Splenic T-lymphocyte subpopulations were measured with flow cytometry(FCM). IL-2, IFN-gamma and TNF-alpha in the culture supernatants were detected by ELISA and biological assay. Nitric oxide (NO) production was examined by Griess reaction. At the concentration range of 0.2-12.8 mg/L, Gl-SP and Gl-BSP were shown to increase lymphocyte proliferation in the presence or absence of mitogen, enhance NK cytotoxic activity, augment the production of TNF-alpha and NO in Gl-SP- or Gl-BSP-activated macrophages, as well the percentage of phagocytosis of NR by macrophages in vitro. Both Gl-SP and Gl-BSP could promote MLR, however, at the dose of 12.8 mg/L, Gl-BSP showed higher activity than Gl-SP in the proliferation of lymphocytes. These two kinds of polysaccharide could significantly increase the secretion of IL-2 and IFN-gamma in doublejway MLR at the concentrations of 0.2-12.8 mg/L, but Gl-BSP had stronger effects than Gl-SP at the same concentrations. Both Gl-SP and Gl-BSP could increase the ratio of T-lymphocyte subpopulations in double-way MLR. At the concentrations of 0.2-12.8 mg/L or 3.2-12.8 mg/L, Gl-BSP demonstrated more significant activity in increasing the percentage of the CD4(+) or CD8(+) subset than Gl-SP. At the concentrations of 0.2-0.8 mg/L, the ratio of the CD4(+) and CD8(+) subset in the Gl-BSP treated group was higher than that of the Gl-SP treated group. Gl-SP and Gl-BSP have similar immunomodulatory

The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells

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Sekiya, M.; Frohlich, E.D.; Cole, F.E. (Alton Ochsner Medical Foundation, New Orleans, LA (USA))

1991-01-01

In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation. In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products.

Science.gov (United States)

Cornara, Laura; Biagi, Marco; Xiao, Jianbo; Burlando, Bruno

2017-01-01

Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

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Laura Cornara

2017-06-01

Full Text Available Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs, and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA, with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

Immunomodulatory and Physical Effects of Oil Composition in Vaccine Adjuvant Emulsions

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Fox, Christopher B.; Baldwin, Susan L.; Duthie, Malcolm S.; Reed, Steven G.; Vedvick, Thomas S.

2011-01-01

Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60 °C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60 °C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants. PMID:21906648

Bacterial infections in cynomolgus monkeys given small molecule immunomodulatory antagonists.

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Price, Karen D

2010-01-01

Opportunistic infections (OIs) during the course of non-clinical toxicity studies can serve as a clinical indicator of immunosuppression. In monkeys, severity may be magnified since the possibility for fecal-oral and cage-to-cage transmission of bacteria exists, reserve capacity is low, and clinical signs of infection are not easily detected until the infectious process is well underway. This review summarizes a case study presented at the HESI-ILSI ITC-Sponsored workshop on Naturally Occurring Infections in Non-human Primates and Immunotoxicity Implications. It gives an overview on the impact of bacterial infections in monkeys on the development and regulatory assessment of three closely-related representative small molecule immunomodulatory (anti-inflammatory) drug candidates all inhibiting the same drug target. The infections, which sometimes progressed to bacteremia and death, originally manifested in the skin, upper respiratory tract, gastrointestinal tract, and less frequently as soft tissue abscesses. Infections were sporadic and not observed in all studies despite coverage of equivalent or higher systemic exposures or longer durations of treatment. To address concerns regarding inconsistency in the presentation and type of findings and their potential relationship to infection, steps were taken to identify causative agents (via culture, microscopy), implement various intervention and treatment regimens (supportive care, antibiotics, drug holiday), demonstrate reversibility of clinical and immune effects, and study major immune components/mechanisms affected (cytokine/stress protein profiling, immune cell phenotyping, and humoral/innate immune cell function tests). Appropriate diagnosis and characterization of the infection was critical to discrimination of these findings as a secondary pharmacologic effect rather than a direct drug-related target organ effect, and also guided clinical protocol design and regulatory acceptance.

Genomic diversity and immunomodulatory activity of Lactobacillus plantarum isolated from dairy products.

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Zago, M; Scaltriti, E; Bonvini, B; Fornasari, M E; Penna, G; Massimiliano, L; Carminati, D; Rescigno, M; Giraffa, G

2017-08-24

In this study, we aimed to investigate some functional characteristics and the immunomodulatory properties of three strains of Lactobacillus plantarum of dairy origin which, in a previous screening, showed to be candidate probiotics. Genome sequencing and comparative genomics, which confirmed the presence of genes involved in folate and riboflavin production and in the immune response of dendritic cells (DCs), prompted us to investigate the ability of the three strains to accumulate the two vitamins and their immunomodulation properties. The ability of the three strains to release antioxidant components in milk was also investigated. Small amounts of folate and riboflavin were produced by the three strains, while they showed a good antioxidant capacity in milk with FRAP method. The immune response experiments well correlated with the presence of candidate genes influencing in DCs cytokine response to L. plantarum. Specifically, the amounts of secreted cytokins by DCs after stimulation with cells of Lp790, Lp813 and Lp998 resulted pro-inflammatory whereas stimulation with culture supernatants (postbiotics) inhibited the release of interleukin (IL)-12p70 and increased the release of the anti-inflammatory IL-10 cytokine. This study adds further evidence on the importance of L. plantarum in human health. Understanding how probiotics (or postbiotics) work in preclinical models can allow a rational choice of the different strains for clinical and/or commercial use.

Wpływ regularnej aktywności fizycznej na skład ciała i ciśnienie tętnicze dzieci ze szkoły sportowej

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Małgorzata Stańczyk

2013-06-01

Full Text Available Wstęp: Trening fizyczny uważany jest za czynnik wpływający na parametry antropometryczne i ciśnienie tęt‑ nicze. Twierdzi się, że osoby regularnie ćwiczące mają lepsze wskaźniki składu ciała oraz niższe wartości ciśnienia tętniczego krwi w porównaniu z osobami nieuprawiającymi sportu. Cel: Ocena wpływu regularnej rocznej aktywności fizycznej prowadzonej w szkole sportowej na skład ciała oraz wartości ciśnienia tętnicze‑ go u dzieci 14-letnich (II klasa gimnazjum. Materiał i metodyka: W badaniu wzięło udział 25 dzieci z gim‑ nazjum sportowego. Dzieci badano dwukrotnie w odstępie 12 miesięcy. Analizie poddano zmianę parame‑ trów antropometrycznych, składu ciała metodą impedancji bioelektrycznej oraz wartości ciśnienia krwi. Wyniki: W całej grupie zaobserwowano wzrost wartości centylowych ciśnienia skurczowego krwi (p < 0,05, przede wszystkim u chłopców. W zakresie ciśnienia rozkurczowego nie zanotowano istotnych różnic. Skład ciała zmienił się niekorzystnie u wszystkich badanych – wzrósł udział tłuszczu (13% vs 20%, p < 0,05, a przy‑ rost masy tłuszczowej był wyższy u dziewczynek (6% vs 3%, p < 0,05. Centyl BMI istotnie statystycznie wzrósł w grupie dziewczynek (37 vs 49, p < 0,05, u chłopców nie uległ zmianie. Wnioski: Aktywność fizyczna proponowana przez szkołę sportową nie poprawia stanu odżywienia 13–14-letnich dziewcząt i chłopców, u których obserwuje się istotne zwiększenie w organizmie zawartości tkanki tłuszczowej. Szkolna aktywność fizyczna nie powoduje obniżenia ciśnienia tętniczego wśród młodzieży w wieku 13–14 lat w odniesieniu do norm wiekowych. W zakresie ciśnienia skurczowego w grupie chłopców zaobserwowano nawet wyższe wartości centylowe.

Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

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Stephanie H. Shirley

2012-01-01

Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression.

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Valenzuela, Beatriz; Imarai, Mónica; Torres, René; Modak, Brenda

2013-12-01

Fish farming crops are constantly exposed to infectious diseases due to intensive production conditions under which microorganisms develop and spread easily, resulting in severe economic losses. The massive use of antibiotics to control these diseases has lead to the accumulation of residues and the development of drug resistance. Consequently, it is urgent to develop new pharmacological tools to stimulate protective immune responses in salmonids to combat infectious diseases. We evaluated the immunostimulant activity of terpenoid derivatives isolated from species of the Heliotropium genus, which had previously shown antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and in vivo in Atlantic salmon. For the evaluation, we studied the effect of this compound in the expression of various cytokines. The results showed that Filifolinone increases the levels of expression of pro-inflammatory and anti-inflammatory cytokines. This suggests that Filifolinone is a potential alternative immunomodulator for veterinary purposes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells.

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Hossain, Md Motarab; Banik, Naren L; Ray, Swapan K

2012-08-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

Stržový systém v Bosonožském hájku – jedinečný geomorfologický fenomén západně od Brna

Czech Academy of Sciences Publication Activity Database

Kirchner, Karel; Münster, P.; Máčka, Z.

2011-01-01

Roč. 18, č. 2 (2011), s. 32-35 ISSN 1212-6209 Institutional research plan: CEZ:AV0Z30860518 Keywords : gully networks * loess * Bosonožský hájek area * Brno region Subject RIV: DE - Earth Magnetism, Geodesy, Geography

Finanční analýza podniku Drůbežářský závod Klatovy a.s.

OpenAIRE

Kohoutová, Kateřina

2010-01-01

This bachelor thesis deals with the financial analysis of Drůbežářský závod Klatovy a.s. during the period 2005-2009. The goal of the thesis is to evaluate the economic situation of the corporation and find out its competitive strength. A part of the project is the methodology which qualifies concepts and indicators and creates bases for the practical part. In the practical part of the project horizontal and vertical analysis of balance sheet and profit and loss statement with comments are pe...

Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gdańsk in Poland.

Science.gov (United States)

Boryło, Alicja; Skwarzec, Bogdan; Romańczyk, Grzegorz; Siebert, Janusz

The determination of polonium 210 Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdańsk with ischaemic heart disease ( morbus ischaemicus cordis , MIC ). The polonium concentrations in analyzed human blood samples are very differentiated. 210 Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of 210 Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers.

Dextrans produced by lactic acid bacteria exhibit antiviral and immunomodulatory activity against salmonid viruses.

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Nácher-Vázquez, Montserrat; Ballesteros, Natalia; Canales, Ángeles; Rodríguez Saint-Jean, Sylvia; Pérez-Prieto, Sara Isabel; Prieto, Alicia; Aznar, Rosa; López, Paloma

2015-06-25

Viral infections in the aquaculture of salmonids can lead to high mortality and substantial economic losses. Thus, there is industrial interest in new molecules active against these viruses. Here we describe the production, purification, and the physicochemical and structural characterization of high molecular weight dextrans synthesized by Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10. The purified dextrans, and commercial dextrans with molecular weights ranging from 10 to 2000kDa, were assayed in infected BF-2 and EPC fish cell-line monolayers for antiviral activity. Only T2000 and dextrans from MN1 and RTF10 had significant antiviral activity. This was similar to results obtained against infectious pancreatic necrosis virus. However the dextran from MN1 showed ten-fold higher activity against hematopoietic necrosis virus than T2000. In vivo assays using the MN1 polymer confirmed the in vitro results and revealed immunomodulatory activity. These results together with the high levels of dextran production (2gL(-1)) by Lb. sakei MN1, indicate the compounds potential utility as an antiviral agent in aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

The interaction between the light source dose and caspase-dependent and -independent apoptosis in human SK-MEL-3 skin cancer cells following photodynamic therapy with zinc phthalocyanine: A comparative study.

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Doustvandi, Mohammad Amin; Mohammadnejad, Fateme; Mansoori, Behzad; Mohammadi, Ali; Navaeipour, Farzaneh; Baradaran, Behzad; Tajalli, Habib

2017-11-01

The aim of this study is to determine the behavior of relative expression of Bcl-2, caspase-8, caspase-9, and caspase-3 genes of/in SK-MEL-3 cancer cells and explore molecular mechanisms responsible for the apoptosis response during an in vitro photodynamic therapy (PDT) with Zinc Phthalocyanine (ZnPc) using different doses of the light source. In this study, firstly the cytotoxic effects of ZnPc-PDT on SK-MEL-3 cells were evaluated. By irradiating the laser, ZnPc induced a significant amount of apoptosis on SK-MEL-3 cells in three IC 50 s including 0.064±0.01, 0.043±0.01, and 0.036±0.01μg/mL at the doses of 8, 16, and 24J/cm 2 , respectively. Moreover, flow cytometry and QRT-PCR experiments were done. The high percentage of apoptotic cells was seen in the early apoptosis stage. The expression of Bcl-2 and caspase-8 genes at all doses of laser experienced an obvious reduction in comparison to the control group. On the other hand, although the expression of caspase-9 and caspase-3 genes remains almost constant at 8J/cm 2 , but they faced an increment at 16 and 24J/cm 2 doses. These data reveal caspase-dependent apoptosis in high and caspase-independent apoptosis in low doses of laser. Based on the results of present work, it can be suggested that the dose of the light source is a key factor in induction of caspase-dependent and caspase-independent apoptosis pathways following PDT. Copyright © 2017. Published by Elsevier B.V.

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study.

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Julio Plaza-Diaz

Full Text Available We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers' feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.ClinicalTrials.gov NCT01479543.

Biochanin A induces anticancer effects in SK-Mel-28 human malignant melanoma cells via induction of apoptosis, inhibition of cell invasion and modulation of NF-κB and MAPK signaling pathways.

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Xiao, Peng; Zheng, Bowen; Sun, Jiaming; Yang, Jia

2017-11-01

The present study aimed to investigate the antitumor activity of Biochanin A in SK-Mel-28 human malignant melanoma cells. An MTT assay was used to study the cytotoxic effects of Biochanin A. In vitro wound healing and invasion assays were used to investigate the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/propidium iodide was used to study effects on cell morphology and apoptosis. Nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) protein expression levels were determined by western blot analysis. The results indicated that Biochanin A significantly inhibited the growth of SK-Mel-28 cells in a dose and time dependent manner. Treatment of the cells with Biochanin A induced apoptosis in a dose dependent manner. Additionally, Biochanin A led to inhibition of cell migration and invasion in a dose-dependent manner and upregulated the expression of key proteins in the NF-κB and MAPK signaling pathways.

Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

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Keith A Russell

Full Text Available Mesenchymal stromal cells (MSC hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies.We hypothesized that canine adipose tissue (AT and bone marrow (BM MSC (derived from the same dogs will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1 proliferation rate, 2 cell surface marker expression, 3 DNA methylation levels, 4 potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5 immunomodulatory potency in vitro.1 AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days for passage (P 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21. 2 Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3 Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4 Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-β3-based induction medium. 5 Immunomodulatory capacity was equal regardless of cell source when tested in

Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties

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Marzaioli V

2014-06-01

Full Text Available Viviana Marzaioli,1 Juan Antonio Aguilar-Pimente,1,2 Ingrid Weichenmeier,1 Georg Luxenhofer,3 Martin Wiemann,4 Robert Landsiedel,5 Wendel Wohlleben,5 Stefanie Eiden,6 Martin Mempel,7 Heidrun Behrendt,1 Carsten Schmidt-Weber,1 Jan Gutermuth,1,8 Francesca Alessandrini1 1Center of Allergy and Environment (ZAUM, Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL, Munich, Germany; 2Department of Dermatology and Allergy Biederstein, Technische Universität München (TUM and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany, 3Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany; 4IBE R&D gGmbH, Münster, Germany; 5BASF, Ludwigshafen, Germany; 6Bayer Technology Services, Leverkusen, Germany; 7Department of Dermatology, Venereology and Allergology, Universitätsmedizin Göttingen (UMG, Göttingen, Germany; 8Department of Dermatology, Vrije Universiteit Brussel, Brussels, Belgium Background: Silica (SiO2 nanoparticles (NPs are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. Objective: To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. Methods: Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 µg over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 µg/mouse, and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. Results: Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo

Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-Bakir

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Joanna Tokarska-Bakir

2012-12-01

Full Text Available Between overabundance and scarcity. Joanna Tokarska-Bakir in an interview with Irena Grudzińska Gross This conversation with Irena Grudzińska-Gross starts a series of interviews in “Studia Litteraria et Historica”, which motto is the title of the essay of Jan Stanisław Bystroń “On subjects I was advised not to pursue”. Among these subjects that Irena Grudzińska-Gross names are: war, family history, women.  Grudzińska-Gross tells also about the reactions to “Złote Żniwa” - a book that she wrote together with Jan Tomasz Gross, and about academic work of people of Eastern Europe living in the United States. One part of the interview concerns also a “collective hypnosis”, that Americans underwent after the 9/11 World Trade Center Attack and the price, that Susan Sontag had to pay for being critical about American militarism.   Między brakiem a nadmiarem. Z Ireną Grudzińską-Gross rozmawia Joanna Tokarska-Bakir Rozmowa z Ireną Grudzińską-Gross otwiera cykl wywiadów “Studia Litteraria et Historica”, których mottem jest tytuł eseju Jana Stanisława Bystronia: “Tematy, które mi odradzano”. Wśród “odradzanych” tematów, które wymienia Irena Grudzińska-Gross są między innymi: wojna, historia rodzinna, kobiety. Grudzińska-Gross opowiada także o reakcjach na książkę “Złote żniwa”, którą napisała wraz z Janem Tomaszem Grossem oraz o pracy akademickiej osób z Europy Wschodniej w Stanach Zjednoczonych. Część rozmowy dotyczy także “zbiorowej hipnozy”, której ulegli mieszkańcy USA po ataku 11 września 2001 na World Trade Center i ceny, jaką musiała zapłacić Susan Sontag za krytykę amerykańskiego militaryzmu.

Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N- BE2 and SH-SY5Y cells

Science.gov (United States)

Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

2012-01-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (−)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in expression of NFP, NSE, and e-cadherin and also decreases in expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro network

Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model.

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Lagos, Leidy; Tandberg, Julia I; Becker, María Inés; Winther-Larsen, Hanne C

2017-08-01

The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolecules with strong immunogenic and immunomodulatory properties. Due to these characteristics, hemocyanin from Concholepas concholepas (CCH) has been biochemically characterized and evaluated as vaccine adjuvant in mice and humans. Francisellosis is a chronic granulomatous disease, which can result in high mortality depending on the host. The disease is caused by the facultative intracellular Gram-negative bacteria Francisella noatunensis, which remains an unsolved problem for the aquaculture, as no efficient vaccines are available. The aim of the present work was to investigate the immunoregulatory properties of CCH against francisellosis in an experimental zebrafish model. When immunized with CCH, zebrafish were protected from subsequent challenge with a lethal dose of Francisella noatunensis subsp. orientalis. Subsequently the mRNA expression levels of several immune-related genes were studied, including mhcii, il12a, tnfα and ifng1-1. Taken together, the data report the immunoregulatory properties of CCH and its potential use as a vaccine adjuvant for aquaculture. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134.

Science.gov (United States)

Kamarehei, Maryam; Yazdanparast, Razieh

2014-10-01

The brain in Alzheimer's disease is under increased oxidative stress, and this may have a role in the pathogenesis and neural death in this disorder. It has been verified that numerous signaling pathways involved in neurodegenerative disorders are activated in response to reactive oxygen species (ROS). EUK134, a synthetic salen-manganese antioxidant complex, has been found to possess many interesting pharmacological activities awaiting exploration. The present study is to characterize the role of Notch signaling in apoptotic cell death of SK-N-MC cells. The cells were treated with hydrogen peroxide (H2O2) or menadione to induce oxidative stress. The free-radical scavenging capabilities of EUK134 were studied through the MTT assay, glutathione peroxidase (GPx) enzyme activity assay, and glutathione (GSH) Levels. The extents of lipid peroxidation, protein carbonyl formation, and intracellular ROS levels, as markers of oxidative stress, were also studied. Our results showed that H2O2/menadione reduced GSH levels and GPx activity. However, EUK134 protected cells against ROS-induced cell death by down-regulation of lipid peroxidation and protein carbonyl formation as well as restoration of antioxidant enzymes activity. ROS induced apoptosis and increased NICD and HES1 expression. Inhibition of NICD production proved that Notch signaling is involved in apoptosis through p53 activation. Moreover, H2O2/menadione led to Numb protein down-regulation which upon EUK134 pretreatment, its level increased and subsequently prevented Notch pathway activation. We indicated that EUK134 can be a promising candidate in designing natural-based drugs for ROS-induced neurodegenerative diseases. Collectively, ROS activated Notch signaling in SK-N-MC cells leading to cell apoptosis.

The Skælskør structure in eastern Denmark – wrench-related anticline or primary Late Cretaceous sea-floor topography?

DEFF Research Database (Denmark)

Surlyk, Finn; Boldreel, Lars Ole; Lykke-Andersen, Holger

2010-01-01

seismic studies of the Chalk Group in Øresund and Kattegat have shown that similar highs actually represent topographic highs on the Late Cretaceous – Danian seafloor formed by strong contourparallel bottom currents. Reflection seismic data collected over the Skælskør structure in order to test...... the Ringkøbing Fyn High into the Danish Basin. The elevated position is maintained due to reduced subsidence as compared with the Danish Basin north of the high. The hypothesis of wrench tectonics as origin can be refuted. The seismic data show that the upper part of the Chalk Group is characterised by irregular...

IMMUNOMODULATORY ACTION OF MYELOPIDUM UNDER ITS INCLUSION IN COMPLEX THERAPY OF PATIENTS WITH PENETRATING OCULAR INJURIES

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T. V. Gavrilova

2008-01-01

Full Text Available Abstract. Examination of immunomodulatory actions and clinical efficiency of myelopidum when included into complex therapy that was carried out in 24 male patients with severe (stage 3 penetrating eye injury in the course of trauma treatment. The levels of C-reactive protein, lactoferrin, interleukin (IL-1β, IL-6, and activity of complement system were measured in peripheral blood, and concentrations of lactoferrin and IL-8 were determined in tears. An increase in lactoferrin, C-reactive protein, IL-1β, IL-8, and C5 complement component levels was detected during early post-traumatic period, as compared with data from the control group. As compared to effects of steroid and non-steroid anti-inflammatory drugs included into standard therapy, treatment with myelopidum has led to a more favorable clinical course of traumatic process, and resulted into more pronounced anti-inflammatory effect that was manifested by decrease in lactoferrin and C-reactive protein levels, reduction of IL-1β concentration, and C5 complement component activity. (Med. Immunol., 2008, vol. 10, N 2-3, pp 239-244.

Antibody constant region peptides can display immunomodulatory activity through activation of the Dectin-1 signalling pathway.

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Elena Gabrielli

Full Text Available We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc of human IgG(1, is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules.

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice.

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Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

2014-01-01

Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4(+) T and CD8(+) T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

Ultraviolet Radiation and the Slug Transcription Factor Induce Pro inflammatory and Immunomodulatory Mediator Expression in Melanocytes

International Nuclear Information System (INIS)

Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.

2012-01-01

Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

Antioxidant and immunomodulatory properties of polysaccharides from Allanblackia floribunda Oliv stem bark and Chromolaena odorata (L.) King and H.E. Robins leaves.

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Boudjeko, Thaddée; Megnekou, Rosette; Woguia, Alice Louise; Kegne, Francine Mediesse; Ngomoyogoli, Judith Emery Kanemoto; Tchapoum, Christiane Danielle Nounga; Koum, Olga

2015-12-09

Many plant polysaccharides have shown high antioxidant and immunostimulating properties and can be explored as novel molecules with biological properties that can potentially improve immune function. The objective of this work was to characterize soluble and cell wall polysaccharides isolated from the stem bark of Allanblackia floribunda and Chromolaena odorata leaves and to evaluate their antioxidant and immunomodulatory properties. Three polysaccharide fractions: soluble polysaccharides (PoS), pectins (Pec) and hemicelluloses (Hem) were extracted from A. floribunda stem bark and C. odorata leaves. These samples were analysed for their proteins, phenolic compounds and total sugar contents. The monosaccharide composition was determined by gas chromatography and arabinogalactan proteins content in PoS was evaluated by rocket electrophoresis. The in vitro antioxidant activities were evaluated by 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-bis-3-éthylbenzylthiazoline-6-sulphonic acid (ABTS) radical scavenging assays and ferrous ions chelating activity. Immunomodulatory activities were performed on the peripheral blood mononuclear cells (PBMCs) using proliferation and enzyme linked immunospot (ELISPOT) method to determine the production of an interferon-gamma. The characterization of the various fractions showed varied metabolites in each plant. In PoS fractions, Ara and Gal were the major monosaccharides found, indicating that arabinogalactans are the primary macromolecules. Hem fractions contained predominantly Xyl and GalA for A. floribunda and Xyl (upto 80 %) for and C. odorata. A. floribunda Hem fraction and C. odorata PoS fraction showed significant DPPH and ABTS radical scavenging activities and immunostimulatory activity via stimulation of PBMC and production of IFN-γ in a dose-dependent manner. The results obtained from this study support the ethnomedicinal use of the stem bark of A. floribunda and leaves of C. odorata. Further research is

Selection of optimal therapy for neuroblastoma: a study of the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model

International Nuclear Information System (INIS)

Topalian, S.L.; Ziegler, M.M.

1987-01-01

Human neuroblastoma is an immunogenic tumor for which therapy directed in an immunologic context may offer some advantage over conventional treatment. This study examines the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. In vivo studies of primary tumor growth characteristics after treatment demonstrated no superiority of either therapeutic modality in control of local tumor or prolongation of host survival. However, irradiated hosts showed an increased ability to reject a secondary tumor challenge, compared to their surgical counterparts. That this phenomenon may be immune-related is suggested by in vitro studies of T lymphocyte function utilizing mixed lymphocyte-tumor cell cultures and PHA lymphoblastogenesis

Unusual immuno-modulatory triterpene-caffeates in the skins of russeted varieties of apples and pears.

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Andre, Christelle M; Larsen, Lesley; Burgess, Elaine J; Jensen, Dwayne J; Cooney, Janine M; Evers, Danièle; Zhang, Jingli; Perry, Nigel B; Laing, William A

2013-03-20

Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent.

Science.gov (United States)

Ilan, Yaron; Elstein, Deborah; Zimran, Ari

2009-10-01

Gaucher disease (GD) is caused by the reduced activity of a lysosomal enzyme, glucocerebrosidase, leading to the accumulation of glucocerebroside (GC). The relatively high prevalence of this disease within an ethnic group is believed to reflect a selective advantage. Treatment with enzyme replacement therapy (ERT) is safe and effective in ameliorating the primary symptoms of the disease, yet there have been reports that some patients on ERT have developed type 2 diabetes or metabolic syndrome, malignancies and central nervous system disorders. A series of animal studies suggest that these complications may be related to the reduction of GC levels by the enzyme administered. GC has been shown to have an immunomodulatory effect through the promotion of dendritic cells, natural killer T cells, and regulatory T cells. The break down of GC to ceramide can underline part of these findings. Clinical trials suggested a beneficial effect of GC in type 2 diabetes or nonalcoholic steatohepatitis. This review of the data from animal models and humans proposes that the increased level of GC may provide an evolutionary advantage for patients with GD. Indirectly, these data support treating symptomatic patients with mild/moderate GD with low-dose ERT and re-evaluating the use of ERT in asymptomatic patients.

Intrinsic Immunomodulatory Effects of Low-Digestible Carbohydrates Selectively Extend Their Anti-Inflammatory Prebiotic Potentials

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Jérôme Breton

2015-01-01

Full Text Available The beneficial effects of carbohydrate-derived fibers are mainly attributed to modulation of the microbiota, increased colonic fermentation, and the production of short-chain fatty acids. We studied the direct immune responses to alimentary fibers in in vitro and in vivo models. Firstly, we evaluated the immunomodulation induced by nine different types of low-digestible fibers on human peripheral blood mononuclear cells. None of the fibers tested induced cytokine production in baseline conditions. However, only one from all fibers almost completely inhibited the production of anti- and proinflammatory cytokines induced by bacteria. Secondly, the impact of short- (five days and long-term (three weeks oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic acid colitis model in mice. The immunosuppressive fiber significantly reduced levels of inflammatory markers over both treatment periods, whereas a nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms of the observed fermentation products and colonic microbiota after three weeks of treatment, suggesting that the anti-inflammatory action was not related to prebiotic properties. Hence, we observed a direct effect of a specific fiber on the murine immune system. This intrinsic, fiber-dependent immunomodulatory potential may extend prebiotic-mediated protection in inflammatory bowel disease.

Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.

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Bandeira, Ana Carla Balthar; da Silva, Talita Prato; de Araujo, Glaucy Rodrigues; Araujo, Carolina Morais; da Silva, Rafaella Cecília; Lima, Wanderson Geraldo; Bezerra, Frank Silva; Costa, Daniela Caldeira

2017-02-01

Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep-1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP-2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Postavení OPEC v mezinárodních hospodářských vztazích

OpenAIRE

Košteková, Eva

2008-01-01

Bakalárska práca sa týka Organizácie krajín vyvážajúcich ropu.Cieľom práce je zhodnotiť postavenie OPEC od jeho vzniku, charakterizovať význam tejto organizácie a popísať zapojenie OPEC vo svetovej ekonomike.V prvej časti práce je základná charakteristika OPEC. Druhá časť práce skúma vývoj postavenia OPEC od jeho vzniku v roku 1960 do roku 2000 so zameraním na ropné šoky. Tretia časť práce sa zaoberá postavením OPEC v treťom miléniu, vzťahmi s EÚ a obnoviteľnými zdrojmi energie....

Hydraulic conditions of water flow in seminatural fish pass, A case study of the Skórka barrage on the Głomia river

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Mateusz Hämmerling

2017-06-01

Full Text Available The article presents results of a field study of the fish pass located within the Skórka barrage on the Głomia river. The aim of the study was to identify water flow conditions in particular chambers of the fish pass. On the basis of results of the field study, the hydraulic conditions of water flow through the fish pass were determined and referred to the optimum performance parameters of the construction. The results obtained make a basis for discussion of possible problems related to construction and operation of the fish passes resembling „close to nature” structures.

Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum

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Peng-Yun eWang

2012-07-01

Full Text Available The antitumor activity of Gl-BSP, a polysaccharide isolated from boiling water extract of the broken-spores of Ganoderma lucidum (Leyss ex Fr Karst. and its possible mechanism were investigated in vivo and in vitro. It was showed that Gl-BSP (50, 100, 200 mg/kg exhibited antitumor effect against Sarcoma 180 (S180 in BALB/c mice. The Gl-BSP was not cytotoxicity in S180 cells and PG cells (human lung carcinoma cell in vitro. However, Gl-BSP-treated serum potently inhibited S180 cells and PG cells proliferation in vitro. Moreover, Gl-BSP could promote the splenic lymphocyte proliferation induced by Con A or LPS, enhance nature killer cell (NK cell cytotoxic activity, augment the percentage of neutral red (NR phagocytosis by macrophages, and increase the percentage of the CD4+ or CD8+ subset in S180-bearing BALB/c mice. The level of IFN-γ, TNF-α and NO of serum apparently was increased by Gl-BSP. Gl-BSP also showed immunomodulatory activities in tumor-bearing mice. Furthermore，It was proved that neutralization with anti-TNF-α and/or anti-IFN-γ significantly diminished growth inhibition induced by Gl-BSP –treated serum in S180 or PG cells. Blocking effect was noted in the combination of anti-TNF-α and anti-IFN-γ. These observations suggest that the antitumor activity of Gl-BSP may mainly relate to the activation of the immune response of the host organism by the stimulation of NK cells, T cells, and macrophages.

3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells.

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Estévez-Sarmiento, Francisco; Said, Mercedes; Brouard, Ignacio; León, Francisco; García, Celina; Quintana, José; Estévez, Francisco

2017-11-01

Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G 2 -M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death. Copyright © 2017 Elsevier Ltd. All rights reserved.

Jón Ólafsson (ed., Lýðræðistilraunir. Ísland í hruni og endurreisn [Democratic experiments. Iceland in collapse and renaissance] (Reykjavík: Háskólaútgáfan, 2014

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Guðmundur Heiðar Frímannsson

2015-03-01

Full Text Available Review of the following book: Jón Ólafsson (ed., Lýðræðistilraunir. Ísland í hruni og endurreisn [Democratic experiments. Iceland in collapse and renaissance], (Reykjavík: Háskólaútgáfan, 2014

Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

International Nuclear Information System (INIS)

Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

2012-01-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (−)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response

Science.gov (United States)

Wang, Wei; Wang, Jing; Dong, Sheng-fu; Liu, Chun-hong; Italiani, Paola; Sun, Shu-hui; Xu, Jing; Boraschi, Diana; Ma, Shi-ping; Qu, Di

2010-01-01

Aim: To investigate the immunomodulatory effects of andrographolide on both innate and adaptive immune responses. Methods: Andrographolide (10 μg/mL in vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface antigen expression was evaluated by flow cytometry, whereas phosphorylation level of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg specific IL-4-producing splenocyte was enumerated by ELISPOT. Results: Andrographolide treatment in vitro attenuated either LPS or IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody production and the number of IL-4-producing splenocytes were reduced by in vivo administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and AKT were observed in macrophages treated with andrographolide. Conclusion: Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signaling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization. PMID:20139902

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines.

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Amanda L Patchett

Full Text Available The survival of the Tasmanian devil (Sarcophilus harrisii is threatened by devil facial tumour disease (DFTD. This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7 signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms. Here we investigate the potential of imiquimod as a DFTD therapy through analysis of treated DFTD cell lines and Tasmanian devil fibroblasts. WST-8 proliferation assays and annexin V apoptosis assays were performed to monitor apoptosis, and changes to the expression of pro- and anti-apoptotic genes were analysed using qRT-PCR. Our results show that DFTD cell lines, but not Tasmanian devil fibroblasts, are sensitive to imiquimod-induced apoptosis in a time and concentration dependent manner. Induction of apoptosis was accompanied by down-regulation of the anti-apoptotic BCL2 and BCLXL genes, and up-regulation of the pro-apoptotic BIM gene. Continuous imiquimod treatment was required for these effects to occur. These results demonstrate that imiquimod can deregulate DFTD cell growth and survival in direct and targeted manner. In vivo, this may increase DFTD vulnerability to imiquimod-induced TLR7-mediated immune responses. Our findings have improved the current knowledge of imiquimod action in tumour cells for application to both DFTD and human cancer therapy.

The immunomodulatory effects of shark cartilage on the mouse and human immune system

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ali Sheikhian

2007-01-01

Materials and methods: In an experimental study, the effects of different doses of shark cartilage on humoral (antibody titer immune response against sheep red blood cells (SRBC, were measured in mouse. In addition, we evaluated the modulatory effects of the shark cartilage on the natural killer (NK activity of the peritoneal cells of mouse against a tumor cell line called K562, according to the standard methods. The proliferative response of the human peripheral blood mononuclear cells was measured under the influence of shark cartilage. Results: Pure shark cartilage enhanced antibody response against SRBC in vivo. The hemagglutination titer which was 1/147 in the control group (injected with hen cartilage, increased to 1/1355 in the test group. The optimal dose was 100 mg/ml. both type of cartilage had blastogenic effect on peripheral blood mononuclear cells (the blastogenic index was 6.7 and 4.9 for impure shark cartilage and hen cartilage, respectively. NK activity was inhibited completely by pure shark cartilage (the amount of the killing activity of the effector peritoneal cells for the control and test groups against target cells was 25.9% and 5.5% respectively. Conclusion: Shark cartilage has a potent immunomodulatory effect on the specific immune mechanisms and some inhibitory effects on the innate immune mechanisms such as NC activity. Since the specific immunity has a more pivotal role against tumor formation, shark cartilage can be used as a cancer immunotherapeutic.

Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions

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Elisa Wirthgen

2018-01-01

Full Text Available Tryptophan metabolites are known to participate in the regulation of many cells of the immune system and are involved in various immune-mediated diseases and disorders. Kynurenic acid (KYNA is a product of one branch of the kynurenine pathway of tryptophan metabolism. The influence of KYNA on important neurophysiological and neuropathological processes has been comprehensively documented. In recent years, the link of KYNA to the immune system, inflammation, and cancer has become more apparent. Given this connection, the anti-inflammatory and immunosuppressive functions of KYNA are of particular interest. These characteristics might allow KYNA to act as a “double-edged sword.” The metabolite contributes to both the resolution of inflammation and the establishment of an immunosuppressive environment, which, for instance, allows for tumor immune escape. Our review provides a comprehensive update of the significant biological functions of KYNA and focuses on its immunomodulatory properties by signaling via G-protein-coupled receptor 35 (GPR35- and aryl hydrocarbon receptor-mediated pathways. Furthermore, we discuss the role of KYNA–GPR35 interaction and microbiota associated KYNA metabolism for gut homeostasis.

Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

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Teixeira, Marcus Zulian

2016-11-01

Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Thermal treatment of luteolin-7-O-β-glucoside improves its immunomodulatory and antioxidant potencies.

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Maatouk, Mouna; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaaban, Hind; Abed, Besma; Iaonnou, Irina; Ghedira, Kamel; Ghoul, Mohamed; Ghedira, Leila Chekir

2017-11-01

Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing-prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-β-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.

Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum.

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Lee, Jung-Woo; Shin, Jung-Gul; Kim, Eun Hee; Kang, Hae Eun; Yim, In Been; Kim, Ji Yeon; Joo, Hong-Gu; Woo, Hee Jong

2004-03-01

The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.

Antiplasmodial, antioxidant and immunomodulatory activities of ethanol extract of Vernonia amygdalina del. Leaf in Swiss mice

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Ehimwenma Omoregie

2016-03-01

Full Text Available Objective: Vernonia amygdalina (V.  amygdalina leaf is locally employed in the Southern region of Nigeria in the treatment of malari a infection. This study evaluated the in vivo antiplasmodial, antioxidant and immunomodulatory effect of ethanol extract of V.  amygdalina leaf. Materials and Methods: The active principles of the dried leaf were extracted with ethanol. For quality validation, chemical finger-print of the extract was performed through high performance thin layer chromatography (HPTLC. The extract was assessed for antiplasmodial activity by the standard four-day suppressive test on Plasmodium berghei (ANKA infected male Swiss mice (six weeks old placed into five groups of six animals each. Result: The absorption spectra from the HPTLC revealed several peaks suggesting presence of some bioactive compounds. Results from the in vivo study showed that the ethanol extract of the plant leaf was significantly active against P. berghei in a dose-dependent manner with the minimum and maximum activity observed in the mice treated orally with 100mg/kg (% inhibition of 23.7% and 1000 mg/kg (% inhibition of 82.3 % of the extract, respectively, on day four of the study. There was also a dose-dependent decrease (p

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM on Streptozotocin-Induced Diabetic Mice

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Jong-Jin Kim

2014-01-01

Full Text Available HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.. In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4+ T and CD8+ T, which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

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Frederick Wasinski

2014-01-01

Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

Associations between cognitive abilities and life satisfaction in the oldest-old. Results from the longitudinal population study Good Aging in Skåne

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Enkvist Å

2013-07-01

Full Text Available Åsa Enkvist, Henrik Ekström, Sölve Elmståhl Department of Health Sciences, Division of Geriatric Medicine, Lund University, Skåne University Hospital, Malmö, Sweden Introduction: Studies on the associations between cognitive abilities and life satisfaction (LS in the oldest-old are few. The aim of this study was to explore whether abilities in six different cognitive domains could predict LS in the oldest-old 3 years later. Methods: The study population consisted of 681 individuals aged 78–98 years, drawn from the longitudinal population study “Good Aging in Skåne,” which is part of a national survey (The Swedish National Study on Aging and Care. Scores on 13 cognitive tests were related to scores on Neugartens’ LS index A (LSI-A 3 years later. The cognitive tests were added into six different cognitive domains. A multiple regression analysis was constructed for each cognitive domain separately, with scores on the LSI-A as the dependent variable. The model was adjusted stepwise for sex, age, education, functional capacity, and depressive mood. Results: Significant correlations were found between digit cancellation, word recall, verbal fluency (VF A, VF animals, VF occupations, and mental rotations at baseline, as well as LSI-A at follow-up. The domains of spatial abilities (B = 0.453, P = 0.014 and processing speed (B = 0.118, P = 0.020 remained significantly associated with LSI-A 3 years later after adjustment. Conclusion: The cognitive domains of spatial abilities and processing speed predicted LS 3 years later in the oldest-old. Clinical implications are discussed. Keywords: oldest-old, life satisfaction, longitudinal, crystallized and fluid intelligence, cognition

Heat shock protein 90 inhibitor enhances apoptosis by inhibiting the AKT pathway in thermal-stimulated SK-MEL-2 human melanoma cell line.

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Shin, Min Kyung; Jeong, Ki-Heon; Choi, Hyeongwon; Ahn, Hye-Jin; Lee, Mu-Hyoung

2018-02-08

Heat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence. We evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions. SK-MEL-2 cells were stimulated at 43 °C for 1 h and treated with 0, 0.1 and 1 μM 17-DMAG. We evaluated the cell viability using MTT and apoptosis with HSP 90 inhibitor. We studied the protein expression of AKT, phospho-AKT, ERK, phospho-ERK, MAPK, and phospho-MAPK, caspase 3,7,9, and anti-poly (ADP-ribose) polymerase. 17-DMAG significantly inhibited the proliferation of the SK-MEL-2 cells at 37 °C (0.1 μM: 44.47% and 1 μM: 61.23%) and 43 °C (0.1 μM: 49.21% and 1 μM: 63.60%), suggesting synergism between thermal stimulation and 17-DMAG. 17-DMAG treatment increased the frequency of apoptotic cell populations to 2.17% (0.1 μM) and 3.05% (1 μM) in 37 °C controls, and 4.40% (0.1 μM) and 4.97% (1 μM) in the group stimulated at 43 °C. AKT phosphorylation were activated by thermal stimulation and inhibited by 17-DMAG. Hsp90 inhibitor treatment may be clinically applicable to enhance the apoptosis of melanoma cells in hyperthermic condition. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cells via regulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway.

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Bhardwaj, Jyoti; Chaudhary, Narendra; Seo, Hyo-Jin; Kim, Min-Yong; Shin, Tai-Sun; Kim, Jong-Deog

2014-06-01

The anti-cancer activity of saponins and phenolic compounds present in green tea was previously reported. However, the immunomodulatory and adjuvanticity activity of tea saponin has never been studied. In this study, we investigated the immunomodulatory effect of tea saponin in T-lymphocytes and EL4 cells via regulation of cytokine response and mitogen-activated protein kinases (MAPK) signaling pathway. Quantitative analysis of mRNA expression level of cytokines were performed by reverse transcription polymerase chain reaction following stimulation with tea saponin, ovalbumin (OVA) alone or tea saponin in combination with OVA. Tea saponin inhibited the proliferation of EL4 cells measured in a dose-dependent manner. No cytotoxicity effect of tea saponin was detected in T-lymphocytes; rather, tea saponin enhanced the proliferation of T-lymphocytes. Tea saponin with OVA increased the expression of interleukin (IL)-1, IL-2, IL-12, interferon-γ and tumor necrosis factor (TNF)-α and decreased the expression level of IL-10 and IL-8 in T-lymphocytes. Furthermore, tea saponin, in the presence of OVA, downregulated the MAPK signaling pathway via inhibition of IL-4, IL-8 and nuclear factor kappaB (NF-κB) in EL4 cells. Th1 cytokines enhancer and Th2 cytokines and NF-κB inhibitor, tea saponin can markedly inhibit the proliferation and invasiveness of T-lymphoma (EL4) cells, possibly due to TNF-α- and NF-κB-mediated regulation of MAPK signaling pathway.

Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

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Hossain, Md. Motarab [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States); Banik, Naren L. [Department of Neurosciences, Medical University of South Carolina, Charleston, SC (United States); Ray, Swapan K., E-mail: swapan.ray@uscmed.sc.edu [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States)

2012-08-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-{kappa}B), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.

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Urvashi Bhan

Full Text Available Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA, has emerged as a leading cause of post influenza pneumonia.Linezolid (LZD prevents acute lung injury in murine model of post influenza bacterial pneumonia.Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3 vs. 2.3×10(4, p < 0.01, which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.

Estragole and methyl-eugenol-free extract of Artemisia dracunculus possesses immunomodulatory effects

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Seyyed Meysam Abtahi Froushani

2016-08-01

Full Text Available Objective: Some evidence suggests that chronic uptake of estragole and methyl-eugenol, found in the essential oil of Artemisia dracunculus (tarragon, may be associated with an increased risk of hepato-carcinogenicity. The present study was conducted to investigate the immumodulatory and anti-inflammatory potentials of estragole and methyl-eugenol free extract of tarragon. Materials and Methods: Aqueous, hydroalcoholic, methanol and hexane extracts of dried and milled tarragon was prepared and analyzed by GC-MS. The estragole and methyl-eugenol free extract was characterized and used for evaluation of immunity in NMRI mice after challenging with sheep red blood cells. Results: It was shown that the aqueous extract of tarragon was free from potentially harmful estragole or methyl-eugenol. Moreover, the immunomodulatory effect of the aqueous extract of tarragon (100 mg/kg for 21 consecutive days was investigated. The extract significantly increased the level of anti-sheep red blood cells (SRBC (antibody and simultaneously decreased the level of cellular immunity in the treatment group. Moreover, tarragon caused a significant reduction in the production of pro-inflammatory IL-17 and IFN-γ in parallel with a reduction in the ratio of INF-γ to Il-10 or IL-17 to IL-10 in the splenocytes. In addition, the levels of the respiratory burst and nitric oxide production in peritoneal macrophages were significantly decreased. Additionally, the phagocytosis potential of macrophages was significantly increased in treated mice. Conclusion: These data showed that the aqueous extract of tarragon may be used as a natural source to modulate the immune system, because it can inhibit pro-inflammatory cytokines and induce anti-inflammatory macrophages.

Performance Analysis of Heterodyne-Detected OCDMA Systems Using PolSK Modulation over a Free-Space Optical Turbulence Channel

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Fan Bai

2015-10-01

Full Text Available This paper presents a novel model of heterodyne-detected optical code-division multiple-access (OCDMA systems employing polarization shift keying (PolSK modulation over a free-space optical (FSO turbulence channel. In this article, a new transceiver configuration and detailed analytical model for the proposed system are provided and discussed, taking into consideration the potential of heterodyne detection on mitigating the impact of turbulence-induced irradiance fluctuation on the performance of the proposed system under the gamma-gamma turbulence channel. Furthermore, we derived the closed-form expressions for the system error probability and outage probability, respectively. We determine the advantages of the proposed modeling by performing a comparison with a direct detection scheme obtained from an evaluation of link performance under the same environment conditions. The presented work also shows the most significant impact factor that degrades the performance of the proposed system and indicates that the proposed approach offers an optimum link performance compared to conventional cases.

Zasady prezentacji składników pozostałego wyniku całościowego – praktykasprawozdawcza spółek należących do WIG 30 oraz DAX w latach 2012–2013 

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Jacek Gad

2015-04-01

Full Text Available Celem artykułu jest wskazanie wpływu nowelizacji MSR 1 z roku 2012 na prezentację składników pozostałego wyniku całościowego przez spółki należące do indeksów WIG 30 oraz DAX. Część teoretyczną artykułu opracowano z wykorzystaniem studiów literatury krajowej i zagranicznej. Część empiryczną opracowano na podstawie informacji prezentowanych w raportach rocznych spółek z warszawskiego indeksu WIG 30 oraz niemieckiego indeksu DAX. Na przestrzeni lat 2012–2013 zmieniła się forma prezentacji składników pozostałego wyniku całościowego. Dotyczy to zarówno spółek z indeksu WIG 30, jak i DAX. Zidentyfikowano cztery główne warianty prezentacji składników pozostałego wyniku całościowego. Zdaniem autora kolejne warianty charakteryzują się rosnącą przejrzystością informacyjną sprawozdania z pozostałego wyniku całościowego. Praktyka sprawozdawcza spółek z indeksu DAX wyprzedza praktykę sprawozdawczą spółek z indeksu WIG 30. Do analizy uzyskanych wyników wykorzystano następujące statystyki opisowe: średnią arytmetyczną, odchylenie standardowe, medianę, percentyle. W ramach badania wykorzystano także wskaźnik podobieństwa struktur.

IMMUNO-MODULATORY EFFECT OF INACTIVATED EIMERIA TENELLA VACCINE AND LIVE IMPPORTED COCCIDIAL VACCINE ON NEWCASTLE DISEASE VIRUS VACCINA TED BROILER CHICKS

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Muhammad Akram Muneer, Haji Ahmad Hashmi, Masood Rabbani, Zahid Munir Chaudhry and Ali M. Bahrami

2001-01-01

Full Text Available A total of 160 one-day-old broiler chicks were used to evaluate the immunomodulatory effects of an inactivated Eimeria tenella vaccine and a live polyvalent imported antiococcidial vaccine (Coccivac. This study indicated that both of these vaccines did not adversely affect the development of serum antibody against Newcastle disease virus (NDV and the chicks vaccinated with either of the anticoccidial vaccines resisted the virulent NDV challenge. A study of the lymphoid organs such as bursa of fabricuis: thymus and spleen from the experimental chicks indicated that those organs were comparable with those from the chicks not vaccinated with these coccidial vaccines. The overall findings of this study indicate that anticoccidial vaccines do not have any effects on the immune functions of the vaccinates. In fact these vaccines prevented the occurrence of clinical coccidiosis in the vaccinates.

[Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń] / Dennis Hormuth

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Hormuth, Dennis

2013-01-01

Arvustus : Roman Czaja. Die Anfänge preussischer Hansestädte im Lichte der historischen und archäologischen quellen : Danzig/Gdańsk, Elbing/Elbląg, Thorn/Toruń. In: Stadtgründung und Stadterweiterung. Beiträge von Archäologie und Stadtgeschichtsforschung. (=Beiträge zur Geschichte der Städte Mitteleuropas XXII). LInz, 2011. S. 59-74

Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.

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Ohno, Kinji; Ohkawara, Bisei; Ito, Mikako

2017-10-01

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.

Antiproliferative effects of Plumbago rosea and its purified constituent plumbagin on SK-MEL 28 melanoma cell lines.

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Anuf, Alexander Ronaldo; Ramachandran, Rajesh; Krishnasamy, Rajaram; Gandhi, P S Sudhakar; Periyasamy, Sureshkumar

2014-10-01

Plumbago rosea is used in traditional systems of medicine for the preparation of formulations used for treating inflammations, cough, bronchitis, and gastrointestinal disorders, and also in conjunction with cancer chemotherapy. In the present study, the cytotoxic and anti-proliferative effects of plumbagin, and the ethanolic root extract of P. rosea (ETPR) was evaluated on SK-MEL 28 melanoma cell lines and human lymphocytes. MTT and apoptotic assays were used for the evaluation of cytotoxic and anti-proliferative effects, respectively. In addition, the effect of Plumbagin and ETPR in down regulation of BCL-2 expression is investigated using RT-PCR analysis. Both plumbagin and ETPR dose-dependently decreased the cell viability more potently in melanoma cell lines. P. rosea extract demonstrated significant synergy in inhibiting BCL-2 expression than plumbagin. Moreover plumbagin showed more toxicity in human lymphocytes. Plumbagin has anti-cancer potential, but the side effects limits its use; yet plumbagin, in combination with other ingredients in Plumbago rosea extract, displays significant synergy leading to a stronger anticancer effect with significantly less toxicity.

Volcanic history and petrography of the Pliocene Etrüsk Stratovolcano, E Turkey

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Oyan, Vural; Keskin, Mehmet; Lebedev, Vladimir; Sharkov, Evgenii; Lustrino, Michele; Mattioli, Michele

2010-05-01

The Pliocene Etrusk volcano, with its 3100 m elevation and ~500 km2 area, is one of the major centers of the collision-related volcanism in E Anatolia. It is located in the northeast of Lake Van, sitting almost on the culmination of the "Lake Van dome" structure forming the vertex of the eastern Turkish high plateau (Sengor et al., 2008). A ~5-km-wide horseshoe-shaped caldera, open to the south, is located in the center of the volcano. Apart from two trace element analyses and two K/Ar dates, there are virtually no data available in the literature on this major eruption center. Our study intends to fill this gap with a detailed petrographical, geochemical and geochronological study. Our new K/Ar age determinations indicate that the main volcanic edifice of the Etrusk volcano was formed in period between 4.3 and 3.9 Ma, with the eruption of several intermediate to acid lavas from a central vent. This phase ended up with the formation of a small collapse caldera that produced pyroclastic material emplaced on the earlier lavas. The final impulse of the volcano activity from the Etrusk volcanic center was the eruption of a post-caldera rhyolitic lava flow from the southern flank of the volcano (~3.8-3.7 Ma). After about 2.7 Myr of magmatic quiescence, during the Quaternary time between ~1 and 0.43 Ma, basalts erupted from the SW flank of the Etrusk volcano. They were generated predominantly from a ~N-S extending fissure, as well as from a scoria cone (Karniyarik hill) and a maar-shaped volcanic center (i.e. Düzgeyikçukuru). Edifice-forming products of the Etrüsk stratovolcano are represented by sanidine-plagioclase-biotite-clinopyroxene-phyric trachytes and plagioclase-clinopyroxene-orthopyroxene-phyric trachyandesites containing sporadic olivine phenocrysts. K-feldspar is the most abundant mineral phase in trachitic lavas of the Etrüsk volcanic system. Post caldera lavas, on the other hand, have relatively more evolved compositions ranging from trachydacite to

Definitive Endoderm Formation from Plucked Human Hair-Derived Induced Pluripotent Stem Cells and SK Channel Regulation

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Anett Illing

2013-01-01

Full Text Available Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs generated from plucked human hair keratinocytes have been exploited in vitro to recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny.

‘Close to the city centre, close to the university’. Are there symptoms of studentification in Gdańsk, Poland?

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Grabkowska Maja

2016-06-01

Full Text Available Students are increasingly recognised as important actors of urban change in contemporary cities. The article presents an analysis of incipient studentification processes in Gdańsk. Its general aim is to reveal patterns of students’ presence and activity which translate into spatial and socio-economic transformations of a post-socialist city at the level of neighbourhoods. The study consists of a survey on students’ residential behaviour, complemented by field and desk research. According to the results, due to the fact that Polish students’ housing and lifestyle choices are limited by their low purchasing power, student-dedicated services have a rather negative impact on the quality of urban space. Furthermore, under these conditions studentification may not be regarded as a stimulus to the gentrification process, which is rather driven by hipsters and affluent foreign students.

Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants.

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Daoudi, Abdeljlil; Aarab, Lotfi; Abdel-Sattar, Essam

2013-04-01

Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments. A large number of plants in Morocco were used in folk medicine to treat immune-related disorders. The objective of this study is to evaluate the immunomodulatory activity of protein extracts (PEs) of 14 Moroccan medicinal plants. This activity was tested on the proliferation of immune cells. The prepared total and PEs of the plant samples were tested using MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay on the splenocytes with or without stimulation by concanavalin-A (Con-A), a mitogenic agent used as positive control. The results of this study indicated different activity spectra. Three groups of activities were observed. The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity. The second group that showed a significant immunostimulatory activity was represented by Aristolochia longa, Datura stramonium, Marrubium vulgare, Sinapis nigra, Delphynium staphysagria, Lepidium sativum, Ammi visnaga and Tetraclinis articulata. The rest of the plant extracts did not alter the proliferation induced by Con-A. This result was more important for the PE than for the total extract. In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use. The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy.

Immunomodulatory Effects of Deokgu Thermomineral Water Balneotherapy on Oxazolone-Induced Atopic Dermatitis Murine Model.

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Lee, Young Bok; Kim, Su Jin; Park, Sae Mi; Lee, Kyung Ho; Han, Hyung Jin; Yu, Dong Soo; Woo, So Youn; Yun, Seong Taek; Hamm, Se-Yeong; Kim, Hong Jig; Kim, Jin-Wou

2016-04-01

Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4(+) Foxp3(+) regulatory T cells in thermomineral balneotherapy compared with distilled water bath. Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.

Microgramma vacciniifolia (Polypodiaceae) fronds contain a multifunctional lectin with immunomodulatory properties on human cells.

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de Siqueira Patriota, Leydianne Leite; Procópio, Thamara Figueiredo; de Santana Brito, Jéssica; Sebag, Virginie; de Oliveira, Ana Patrícia Silva; de Araújo Soares, Ana Karine; Moreira, Leyllane Rafael; de Albuquerque Lima, Thâmarah; Soares, Tatiana; da Silva, Túlio Diego; Paiva, Patrícia Maria Guedes; de Lorena, Virgínia Maria Barros; de Melo, Cristiane Moutinho Lagos; de Albuquerque, Lidiane Pereira; Napoleão, Thiago Henrique

2017-10-01

In this study, we report the purification and characterization of a multifunctional lectin (MvFL) from Microgramma vacciniifolia fronds as well as its immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). MvFL (pI 4.51; 54kDa) is a glycoprotein able to inhibit trypsin activity and that has sequence similarities (32% coverage) with a plant RNA-binding protein. Hemagglutinating activity of MvFL was not altered by heating at 100°C for 30min, but was reduced in alkaline pH (8.0 and 9.0). Fluorimetric analyses showed that this lectin did not undergo marked conformational changes when heated. However, the MvFL conformation changed depending on the pH. MvFL at 6.25-25μg/mL was not cytotoxic to lymphocytes present among PBMCs. The PBMCs incubated for 24h with the lectin (12.5μg/mL) showed increased TNF-α, IFN-γ, IL-6, IL-10, and nitric oxide production. MvFL also stimulated T lymphocytes from PBMCs to differentiate into CD8 + cells. The activation (indicated by CD28 expression) of these cells was also stimulated. In conclusion, MvFL is a heat-stable and multifunctional protein, with both lectin and trypsin inhibitor activities, and capable of inducing predominantly a Th1 response in human PBMCs as well as activation and differentiation of T lymphocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant Arthritis.

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Wang, Yang; Han, Chen-Chen; Cui, Dongqian; Luo, Ting-Ting; Li, Yifan; Zhang, Yuwen; Ma, Yang; Wei, Wei

2018-06-01

Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti-inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA) rats, but the role of the spleen function is still unclear. The aim of this study was to research how CP-25 regulated spleen function of AA rats. Male Sprague-Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29 after immunization. The spleen histopathological changes were analyzed by hematoxylin-eosin staining. G protein-coupled receptor kinases (GRKs) and prostaglandin receptor subtypes (EPs) were screened by Western blot and immunohistochemistry. The co-expression of GRK2 and EP2 as well as GRK2 and EP4 was measured by immunofluorescence and co-immunoprecipitation. The expression of GRK2 and EP4 in splenic T cells was further detected by immunofluorescence. CP-25 was found to relieve the secondary paw swelling, attenuate histopathologic changes, and downregulate GRK2, EP2 and EP4 expression in AA rats. Additionally, CP-25 not only downregulated the co-expression of GRK2 and EP4 but also downregulated GRK2, EP4 expression in splenic T cells of AA rats. From these results, we can infer that CP-25 play an anti-inflammatory and immune function by affecting the function of the splenic T cells.

Cultural Identity of Citizens of Gdańsk from an Ethnolinguistic Perspective on the Basis of Chosen Texts of the Free City of Danzig

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Izabela Olszewska

2015-06-01

Full Text Available Cultural Identity of Citizens of Gdańsk from an Ethnolinguistic Perspective on the Basis of Chosen Texts of the Free City of Danzig As a consequence of the First World War and in the wake of the Treaty of Versailles the Free City of Danzig was established. The image of Danzig identity was created, first of all, by the following ethnic groups: German, Polish and Jewish. Was the Free City of Danzig multicultural or was it German with Polish and Jewish minorities? Did those nationalities live beside each other, did they together, as citizens of Danzig, create a common reality? Is it possible to talk about a uniform culture/identity of Danzig? The aim of this article is an analysis of linguistic image of the world of the citizens of the Free City of Danzig, which has been carried out on the basis of characteristics of the image of relations and cultural differences in the interpretation of Polish community. Yet, the whole image of identity consists of a mosaic of smaller interpretations which, only after being reduced to the lowest common denominator, may give the holistic image of Danzig identity as an image of a common multiple subjectivity. Mutual perception of nationalities inhabiting the area of the Free City of Danzig is the starting point for the discussion on their identity and an attempt to answer the question: did the citizens of Danzig see themselves as one community – exactly the one of Danzig? The analysed research material consists of chosen texts of the local press (in Polish and occasionally in German concerning socio-cultural and political and informative issues. The Polish "Gazeta Gdańska" had been published since 1891 as the first Polish Danzig newspaper in Polish. Its first aim was to integrate Polish circles and to defend the rights of the Polish. "Danziger Neuesten Nachrichten", published since 1894, was the biggest Danzig conservative newspaper in German which influenced public opinion. In the analysis of the linguistic

Evaluation of antitumor, immunomodulatory and free radical scavenging effects of a new herbal prescription seaweed complex preparation

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Liu, Xin; Shao, Changlun; Kong, Wenwen; Fang, Yuchun; Wang, Changyun

2013-09-01

Seaweed Complex Preparation (SCP) is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little information is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on splenocyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell (CRBC) method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antitumor effects of SCP might be achieved by improving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.

Joint Polish–Finnish sampling of surface waters around the phosphogypsum waste stacks in Gdańsk and Police from 1 to 3 July 2013 – Results of the expedition

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Räike, Antti; Koskela, Jarkko; Knuuttila, Seppo; Lehtoranta, Jouni; Pitkänen, Heikki; Risto, Maarit; Vuorinen, Jyrki

2015-01-01

The report describes the results of the joint Polish–Finnish sampling expedition aimed at estimating the possible effects of the two Polish phosphogypsum stacks located in Wislinka (Gdańsk) and Police on the loading of the Baltic Sea and the nearby watercourses. The joint expedition was based on the agreement between the Polish and Finnish Ministers of the Environment in June 2013. The results indicate a clear effect of the phosphogypsum stack on phosphate and total phosphorus concentratio...

Trudności terapeutyczne u pacjenta z ciężką postacią młodzieńczego zapalenia skórno-mięśniowego powikłanego uogólnioną wapnicą

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Joanna Szymańska-Kałuża

2011-08-01

Full Text Available Młodzieńcze zapalenie skórno-mięśniowe (MZSM to najczęstszaidiopatyczna miopatia zapalna wieku dziecięcego. Do charakterystycznychobjawów tej choroby należą: osłabienie mięśni, głównieobręczy barkowej lub biodrowej, oraz zmiany skórne w postaciobrzęku twarzy, heliotropowego zabarwienia powiek, zmian plamisto-rumieniowych na twarzy i klatce piersiowej. W badaniachlaboratoryjnych typowe dla MZSM są podwyższone wskaźnikiostrej fazy, wysoka aktywność enzymów mięśniowych (aminotransferaz,kinazy kreatynowej oraz dehydrogenazy mleczanowej,a także czasami obecność przeciwciał anty-Jo1. Badanie elektromiograficznewykazuje cechy pierwotnego uszkodzenia mięśni,a w obrazie histopatologicznym wycinka skórno-mięśniowegoodnotowuje się nacieki zapalne. U dzieci często obserwowane sątakże ogniska zwapnień w tkankach miękkich, prowadzące doatrofii mięśni i przykurczów stawowych.Leczeniem I rzutu u pacjentów z MZSM są glikokortykosteroidy,w przypadku nieskuteczności tej terapii stosuje się leki immunosupresyjnelub leki biologiczne, w tym immunoglobuliny.W pracy przedstawiono przypadek pacjenta z ciężkim przebiegiemMZSM powikłanego wapnicą, z uwzględnieniem objawów klinicznychi możliwości leczenia. Omówiono również trudności w doborzenajskuteczniejszej farmakoterapii dla tego pacjenta. U chorego– obecnie 14-letniego chłopca – występowały uogólnione zmianyskórne oraz bardzo gwałtownie narastające liczne złogi soli wapniaw skórze, tkance podskórnej, powięziach i mięśniach, które pojawiły się po 3 latach od wystąpienia pierwszych objawów chorobowych(ryc. 1–8. U chłopca z powodu wybitnie ciężkiego przebieguchoroby prowadzono agresywną konwencjonalną terapię(glikokortykosteroidy, metotreksat, cyklosporyna, pamidronian,która nie przynosiła zadowalających rezultatów i poprawy stanuklinicznego. Na podstawie doniesień z piśmiennictwa światowegopodjęto próbę leczenia

Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

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Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

2017-06-01

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Structure characterization of a novel polysaccharide from Hericium erinaceus fruiting bodies and its immunomodulatory activities.

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Wu, Fangfang; Zhou, Chunhui; Zhou, Dandan; Ou, Shiyi; Zhang, Xiaoai; Huang, Huihua

2018-01-24

A novel polysaccharide fraction (HEP-S) was extracted and isolated from the fruiting bodies of Hericium erinaceus. Structural characterization revealed that HEP-S had an average molecular weight of 1.83 × 10 4 Da and consisted of rhamnose, fucose, mannose, glucose and galactose at a molar ratio of 1.47 : 0.93 : 1.36 : 8.68 : 4.08. Periodate oxidation-Smith degradation and NMR analysis showed that the main linkage types of HEP-S were composed of (1→)-α-d-Glc, (1→3,4)-α-d-Glc, (1→6)-α-d-Gal, (1→3,4)-β-d-Man, (1→3,6)-α-Rha and (1→2)-β-l-Fuc. The immunomodulatory assay indicated that HEP-S could significantly enhance the pinocytic and phagocytic capacity and promote the secretion of nitric oxide and pro-inflammatory cytokines by activating the corresponding mRNA and protein expression in RAW 264.7 cells involving a toll-like receptor 2 membrane receptor. Besides, HEP-S was also found to improve the adaptive immune function by enhancing T and B lymphocyte proliferation and increasing the interleukin-2, interleukin-4 and interferon-γ secretion in spleen lymphocytes. These results suggested that HEP-S could be used as a potential immunoregulatory agent in functional foods.

Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

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Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

2017-11-13

During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

High-Yield Production in Escherichia coli of Fungal Immunomodulatory Protein Isolated from Flammulina velutipes and Its Bioactivity Assay in Vivo

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Shenkui Liu

2013-01-01

Full Text Available A fungal immunomodulatory protein isolated from Flammulina velutipes (FIP-fve has structural similarity to the variable region of the immunoglobulin heavy chain. In the present study, the recombinant bioactive FIP-fve protein with a His-tag in N-terminal of recombinant protein was expressed in transetta (DE3 at a high level under the optimized culturing conditions of 0.2 mM IPTG and 28 °C. The efficiency of the purification was improved with additional ultrasonication to the process of lysozyme lysis. The yield of the bioactive FIP-fve protein with 97.1% purity reached 29.1 mg/L with a large quantity for industrial applications. Enzyme-linked immunosorbent assay showed a maximum increase in interleukin-2 (IL-2 and gamma interferon (IFN-γ for the mice serum group of 5 mg/kg body mass (p < 0.01 with three doses of His-FIP-fve. However, the production of IL-4 had no apparent difference compared to the control.

The N- and C-terminal carbohydrate recognition domains of Haemonchus contortus galectin bind to distinct receptors of goat PBMC and contribute differently to its immunomodulatory functions in host-parasite interactions.

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Lu, MingMin; Tian, XiaoWei; Yang, XinChao; Yuan, Cheng; Ehsan, Muhammad; Liu, XinChao; Yan, RuoFeng; Xu, LiXin; Song, XiaoKai; Li, XiangRui

2017-09-05

Hco-gal-m is a tandem-repeat galectin isolated from the adult worm of Haemonchus contortus. A growing body of studies have demonstrated that Hco-gal-m could exert its immunomodulatory effects on host peripheral blood mononuclear cells (PBMC) to facilitate the immune evasion. Our previous work revealed that C-terminal and N-terminal carbohydrate recognition domains (CRD) of Hco-gal-m had different sugar binding abilities. However, whether different domains of Hco-gal-m account differently for its multiple immunomodulatory functions in the host-parasite interaction remains to be elucidated. We found that the N-terminal CRD of Hco-gal-m (MNh) and the C-terminal CRD (MCh) could bind to goat peripheral blood mononuclear cells by distinct receptors: transmembrane protein 63A (TMEM63A) was a binding receptor of MNh, while transmembrane protein 147 (TMEM147) was a binding receptor of MCh. In addition, MCh was much more potent than MNh in inhibiting cell proliferation and inducing apoptosis, while MNh was much more effective in inhibiting NO production. Moreover, MNh could suppress the transcription of interferon-γ (IFN-γ), but MCh not. Our data suggested that these two CRDs of Hco-gal-m bind to distinct receptors and contributed differently to its ability to downregulate host immune response. These results will improve our understanding of galectins from parasitic nematodes contributing to the mechanism of parasitic immune evasion and continue to illustrate the diverse range of biological activities attributable to the galectin family.

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

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Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

2005-11-30

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

TRAIL Activates a Caspase 9/7-Dependent Pathway in Caspase 8/10-Defective SK-N-SH Neuroblastoma Cells with Two Functional End Points: Induction of Apoptosis and PGE2 Release

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Giorgio Zauli

2003-09-01

Full Text Available Most neuroblastoma cell lines do not express apical caspases 8 and 10, which play a key role in mediating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL cytotoxicity in a variety of malignant cell types. In this study, we demonstrated that TRAIL induced a moderate but significant increase of apoptosis in the caspase 8/10-deficient SK-N-SH neuroblastoma cell line, through activation of a novel caspase 9/7 pathway. Concomitant to the induction of apoptosis, TRAIL also promoted a significant increase of prostaglandin E2 (PGE2 release by SKN-SH cells. Moreover, coadministration of TRAIL plus indomethacin, a pharmacological inhibitor of cyclooxygenase (COX, showed an additive effect on SKN-SH cell death. In spite of the ability of TRAIL to promote the phosphorylation of both ERKi/2 and p38/MAPK, which have been involved in the control of COX expression/activity, neither PD98059 nor SB203580, pharmacological inhibitors of the ERKi/2 and p38/MAPK pathways, respectively, affected either PGE2 production or apoptosis induced by TRAIL. Finally, both induction of apoptosis and PGE2 release were completely abrogated by the broad caspase inhibitor z-VAD4mk, suggesting that both biologic end points were regulated in SK-N-SH cells through a caspase 9/7-dependent pathway.

Immunomodulatory and antioxidant protective effect of Sarcocornia perennis L. (swampfire) in lead intoxicated rat.

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Gargouri, Manel; Hamed, Houda; Akrouti, Amel; Christian, Magné; Ksouri, Riadh; El Feki, Abdelfattah

2017-11-01

Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6 g/L lead acetate (via drinking water) or a combination of both. At the end of the three-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication-induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin-10 (IL-10) and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased. S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.

Expression, purification, and analysis of three recombinant ECD disintegrins (r-colombistatins) from P-III class snake venom metalloproteinases affecting platelet aggregation and SK-MEL-28 cell adhesion.

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Suntravat, Montamas; Helmke, Thomas J; Atphaisit, Chairat; Cuevas, Esteban; Lucena, Sara E; Uzcátegui, Nestor L; Sánchez, Elda E; Rodriguez-Acosta, Alexis

2016-11-01

Crotalid venoms are rich sources of components that affect the hemostatic system. Snake venom metalloproteinases are zinc-dependent enzymes responsible for hemorrhage that also interfere with hemostasis. The disintegrin domain is a part of snake venom metalloproteinases, which involves the binding of integrin receptors. Integrins play an essential role in cancer survival and invasion, and they have been major targets for drug development and design. Both native and recombinant disintegrins have been widely investigated for their anti-cancer activities in biological systems as well as in vitro and in vivo systems. Here, three new cDNAs encoding ECD disintegrin-like domains of metalloproteinase precursor sequences obtained from a Venezuelan mapanare (Bothrops colombiensis) venom gland cDNA library have been cloned. Three different N- and C-terminal truncated ECD disintegrin-like domains of metalloproteinases named colombistatins 2, 3, and 4 were amplified by PCR, cloned into a pGEX-4T-1 vector, expressed in Escherichia coli BL21, and tested for inhibition of platelet aggregation and inhibition of adhesion of human skin melanoma (SK-Mel-28) cancer cell lines on collagen I. Purified recombinant colombistatins 2, 3, and 4 were able to inhibit ristocetin- and collagen-induced platelet aggregation. r-Colombistatins 2 showed the most potent inhibiting SK-Mel-28 cancer cells adhesion to collagen. These results suggest that colombistatins may have utility in the development of therapeutic tools in the treatment of melanoma cancers and also thrombotic diseases. Copyright © 2016. Published by Elsevier Ltd.