Current Issue : July - September Volume : 2016 Issue Number : 3 Articles : 4 Articles
Background: Dendritic cells (DCs) rendered suppressive by treatment with mitomycin C and loaded with the\nautoantigen myelin basic protein demonstrated earlier their ability to prevent experimental autoimmune encephalomyelitis\n(EAE), the animal model for multiple sclerosis (MS). This provides an approach for prophylactic vaccination\nagainst autoimmune diseases. For clinical application such DCs are difficult to generate and autoantigens hold the risk\nof exacerbating the disease.\nMethods: We replaced DCs by peripheral mononuclear cells and myelin autoantigens by glatiramer acetate (Copaxone\n�®), a drug approved for the treatment of MS. Spleen cells were loaded with Copaxone�®, incubated with mitomycin\nC (MICCop) and injected into mice after the first bout of relapsing-remitting EAE. Immunosuppression mediated by\nMICCop was investigated in vivo by daily assessment of clinical signs of paralysis and in in vitro restimulation assays of\nperipheral immune cells. Cytokine profiling was performed by enzyme-linked immunosorbent assay (ELISA). Migration\nof MICCop cells after injection was examined by biodistribution analysis of 111Indium-labelled MICCop. The number\nand inhibitory activity of CD4+CD25+FoxP3+ regulatory T cells were analysed by histology, flow cytometry and in vitro\nmixed lymphocyte cultures. In order to assess the specificity of MICCop-induced suppression, treated EAE mice were\nchallenged with the control protein ovalbumin. Humoral and cellular immune responses were then determined by\nELISA and in vitro antigen restimulation assay.\nResults: MICCop cells were able to inhibit the harmful autoreactive T-cell response and prevented mice from further\nrelapses without affecting general immune responses. Administered MICCop migrated to various organs leading to an\nincreased infiltration of the spleen and the central nervous system with CD4+CD25+FoxP3+ cells displaying a suppressive\ncytokine profile and inhibiting T-cell responses.\nConclusion: We describe a clinically applicable cell therapeutic approach for controlling relapses in autoimmune\nencephalomyelitis by specifically silencing the deleterious autoimmune response....
This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from\na Sarawak local rice variety (local name: ââ?¬Å?BJLNââ?¬Â) and a commercial rice variety, ââ?¬Å?MR219,ââ?¬Â on oxidative stress in rat H9c2(2-\n1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2),\nrespectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were\nselected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dosedependent\ncytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the\ndose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of\ninduction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating\nthese activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly\nupregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This\npreliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via\nupregulation in enzymatic activities and expression levels of CAT....
Background: Sepsis is a debilitating systemic disease and described as a severe and irregular systemic\ninflammatory reaction syndrome (SIRS) against infection. We employed CLP (Cecal Ligation and Puncture) model in\nrats to investigate anti-inflammatory and antioxidant effects of phloretin, as a natural antioxidant agent, and its\nprotective effect on liver tissue damage caused by sepsis.\nMethods: Male Wistar albino rats were randomly divided into three groups: sham group, CLP induced sepsis group\nand phloretin treated CLP group. Sepsis was induced by CLP method. 50 mmol/kg Phloretin was administered\nintraperitoneally in two equal doses immediately after surgery.\nResults: It was observed that blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-�±) levels were\ndramatically increased in the CLP induced sepsis group (43.88 �± 1.905 mg/dl, 37.63 �± 1.92, respectively) when\ncompared to the sham group. Moreover, tissue Glutathione (GSH) and liver nuclear factor �¸B (NF-�¸B p65)\ntranscription factor values were higher in CLP induced sepsis group. This elevation was considerably reduced in the\nphloretin treated CLP group. No significant differences were observed in serum creatinine and creatinine\nphosphokinase levels.\nConclusions: The present study suggested that phloretin, as a natural protective agent, act against tissue damages\nintroduced following the experimental sepsis induced model, likely caused by free oxygen radicals....
Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However,\nthe effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods.The neural-crest derived PC12 cells were\ncultured for 72 h in the HG (75mM) or control (25mM) groups.We used NMR-based metabolomics to examine both intracellular\nand extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may\nbe due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other\nenergy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of\nglutamate from the branched-chain amino acids (isoleucine and valine)may be enhanced under HG. Increased levels of intracellular\nalanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in\nintracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism.\nConclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic\nchanges, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group\nmetabolism....
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