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The role of resveratrol (RV), a natural polyphenol, is well documented, although its role on neurogenesis is still controversial and poorly understood. Therefore, to decipher the cellular insights of RV on neurogenesis, we investigated the potential effects of the compound on the survival, proliferation, and neuronal differentiation of human cord blood-derived mesenchymal stem cells (hCBMSCs). For neuronal differentiation, purified and characterized hCBMSCs were exposed to biological safe doses of RV (10 μM) alone and in combination with nerve growth factor (NGF-50 ng). The cells exposed only to NGF (50 ng/mL) served as positive control for neuronal differentiation. The genes showing significant involvement in the process of neuronal differentiation were further funneled down at transcriptional and translational level. It was observed that RV promotes PKA-mediated neuronal differentiation in hCBMSCs by inducing canonical pathway. The studies with pharmacological inhibitors also confirmed that PKA significantly induces β-catenin expression via GSK3β induction and stimulates CREB phosphorylation and pERK1/2 induction. Besides that, the studies also revealed that RV additionally possesses the binding sites for molecules other than PKA and GSK3β, with which it interacts. The present study therefore highlights the positive impact of RV over the survival, proliferation, and neuronal differentiation in hCBMSCs via PKA-mediated induction of GSK3β, β catenin, CREB, and ERK1/2. [ABSTRACT FROM AUTHOR]

Sepsis remains as a leading cause of death in critically ill patients. Unfortunately, there have been very few successful specific therapeutic agents that can significantly reduce the attributable mortality and morbidity of sepsis. Developing novel therapeutic strategies to improve outcomes of sepsis remains an important focus of ongoing research in the field of critical care medicine. Apoptosis has recently been identified as an important mechanism of cell death and evidence suggests that prevention of cell apoptosis can improve survival in animal models of sepsis and endotoxaemia. In this review article, we summarise the critical role of apoptosis of the immune cells in the pathophysiology of sepsis and propose that blocking cell-signaling pathways leading to apoptosis may present a promising specific therapy for sepsis. Various methods to inhibit apoptosis including the cell surface Fas receptor pathway inhibitors, caspase inhibitors, over-expression of anti-apoptotic genes and small interfering ribonucleic acid therapy are discussed. [ABSTRACT FROM AUTHOR]

The increased inhaled application of titanium dioxide nanoparticles (TiO2 NPs) increases the potential pulmonary health risks. The present investigations were carried out to study the TiO2 NPs-induced apoptosis, oxidative stress and genotoxicity in the human lung cancer cell line, A549, a widely used cell system for pulmonary toxicity studies. Tetrazolium bromide salt and lactate dehydrogenase release assays were used to study the cytotoxicity. The genotoxicity studies were carried out using cytokinesis block micronucleus assay. Apoptosis was confirmed by the formation of apoptotic bodies and altered expression (messenger RNA (mRNA) and protein) of markers such as P53, P21, Bax, Bcl2 and cleaved caspase-3. Cells exposed to TiO2 NPs (10 and 50 μg/ml) for 6–24 h shows significant induction in oxidative stress, that is, the production of reactive oxygen species and malondialdehyde and decrease in the activity of catalase and glutathione. TiO2 NPs exposure also induces the formation of apoptotic bodies and micronucleus as marker of genotoxicity. A significant up-regulation in the expression of apoptosis markers such as P53, P21 and cleaved caspase-3 was observed, while the levels were down-regulated for Bcl2 at both mRNA and protein levels. TiO2 NPs exposure could not pose significant effects on Bax expression. Data indicate that nano-TiO2 induces oxidative stress, genotoxicity and apoptosis in human lung cancer cell line, A549. Our result also identifies the mechanisms involved in TiO2 NP-induced changes in A549 cells. Perhaps, reporting for the first time, the association of TiO2 NPs-induced genotoxicity and apoptosis at transcriptional and translational level in the human lung cancer cell line, A549 cells. [ABSTRACT FROM PUBLISHER]

The present investigations were aimed to identify the possible association between genetic polymorphism in interleukin-6 (IL-6) G-174C gene, which confers susceptibility to metabolic syndrome, and serum level of resistin in North Indian women. The study population comprised 370 unrelated Indian women (192 having abdominal obesity and 178 controls). Polymorphism in genotype (CC+GC) of IL-6 G-174C gene was determined using a combination of polymerase chain reaction (PCR) and sequence-specific primer with restriction fragment length polymorphism (RFLP) technology. Insulin resistance (IR) and serum resistin level were also analyzed along with metabolic risk factors. Of 192 abdominal obese women, 147 (76.56%) were found to have mutant CC+GC (p = 0.001) genotype and allele frequency (p = 0.001), which was significantly higher 45 (23.44%) than non-obese and their respective wild type. The mutant genotype (CC+GC) of IL-6 gene was found to be associated significantly with high triglyceride (p = 0.025) and resistin level (p < 0.001), when compared with respective wild genotype (GG) in obese women. Non-obese women with no signs of metabolic risk factors were found to have significantly low level of serum resistin and IR in comparison to obese women having genetic polymorphism for IL-6 G-174C gene. Study suggests that IL-6 G-174C gene is one among the susceptibility loci for metabolic syndrome in North Indian women. Genotype for this polymorphism may prove informative for prediction of genetic risk for metabolic syndrome. Further, high level of serum resistin molecules may be targeted to correlate with metabolic syndrome risk factors and could be used as early prediction marker. [ABSTRACT FROM PUBLISHER]

Pharmacological potential of curcumin was assessed in PC12 cells against hydrogen peroxide (H2 O2) exposure. In MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays, 24-hour exposure of H2O2 (0.5 mM and above) was found to be cytotoxic. A significant (p < 0.001) increase in percentage cell viability was recorded in PC12 cells pretreated with curcumin (25, 50 and 100 µg/mL) for 24 hours prior to H2O2 (0.5 and 1 mM) exposure for 24 hours. Co-exposure to H2O2 and curcumin was also found effective. However, a therapeutic treatment of curcumin for 24 hours after H2O 2 exposure to the cells was found ineffective. Differential response of PC12-H2O2 model to curcumin in MTT and LDH assays suggests the utility of these endpoints to sort the drug candidates to study their antioxidant potential. [ABSTRACT FROM PUBLISHER]