Int J Med Sci
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Hypercholesterolemia is a major risk factor for several cardiovascular and metabolic diseases as it triggers oxidative and pro-inflammatory cascades. Baicalein (BL) is a natural flavone with multiple therapeutic properties. The present study aimed to evaluate the potential protective effect of BL supplementation in hypercholesterolaemic rats. ⋯ Histological alterations induced by cholesterol overload in cardiac, hepatic, and renal tissues were ameliorated by BL supplementation. Our results show that the BL treatments (25 and 50 mg/kg/day) to HCD fed rats improved all the altered parameters. These results demonstrate that BL treatment improves cardiac, renal and hepatic dysfunctions in hypercholesterolaemic rats by activation of cellular antioxidant enzymes and/or suppression of inflammatory cytokines.
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Oxidative stress has been linked to senescence and tumorigenesis via modulation of the cell cycle. Using a hydrogen peroxide (H2O2)-induced oxidative stress-induced premature senescence (OSIPS) model previously reported by our group, this study aimed to investigate the effects of oxidative stress on microRNA (miRNA) expression in relation to the G1-to-S-phase (G1/S) transition of the cell cycle and cell proliferation. On global miRNA analysis of the OSIPS cells, twelve significantly up- or down-regulated miRNAs were identified, the target genes of which are frequently associated with cancers. ⋯ However, under oxidative stress, E2F1 expression was down-regulated, consistent with hampered G1/S transition and suppressed DNA synthesis and cell proliferation. To explain the observed E2F1 down-regulation under oxidative stress, a scheme is proposed which includes miR-20b-5p/miR-106a-5p-dependent regulation, miRNA-E2F1 autoregulatory feedback and E2F1 response to repair oxidative stress-induced DNA damages. The oxidative stress-modulated expression of miR-17 miRNAs and E2F1 may be used to develop strategies to retard or reverse MSC senescence in culture, or senescence in general.
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Aims: Dexmedetomidine (Dex) as a highly selective α2-adrenoceptor agonist, was widely used anesthetic in perioperative settings, whether Dex induces cardiac hypertrophy during perioperative administration is unknown. Methods: The effects of Dex on cardiac hypertrophy were explored using the transverse aortic constriction model and neonatal rat cardiomyocytes. Results: We reported that Dex induces cardiomyocyte hypertrophy with activated ERK, AKT, PKC and inactivated AMPK in both wild-type mice and primary cultured rat cardiomyocytes. ⋯ However, suppression of mitochondrial coupling efficiency and membrane potential by FCCP blocks Dex induced AMPK inactivation as well as ERK, AKT, and PKC activation. All of these effects are blocked by the α2-adrenoceptor antagonist atipamezole. Conclusion: The present study demonstrates Dex preconditioning induces cardiac hypertrophy that protects against heart failure through mitochondria-AMPK pathway in perioperative settings.
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Aspirin has been used as anti-inflammatory and anti-aggregate for decades but the precise mechanism(s) of action after the presence of the toxic peptide Aβ1-42 in cultured astrocytes remains poorly resolved. Here we use low-doses of aspirin (10-7 M) in astrocytes in primary culture in presence or absence of Aβ1-42 toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ1-42 peptide presence in aspirin treated cells. ⋯ Aspirin inhibited COX-2 and iNOS without changes in COX-1 expression, increasing anti-oxidant protein (Cu/Zn-SOD and Mn-SOD) expression in presence or absence of Aβ1-42. Taken together, our results show that aspirin, at low doses increases cell viability by decreasing inflammation and oxidative stress, preventing the deleterious effects of the Aβ1-42 peptide on astrocytes in primary culture. The use of low doses of aspirin may be more suitable for Alzheimer's disease.
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Background: Illustrating the pathogenesis of hepatocellular carcinoma (HCC) pathogenesis as well as identifying specific biomarkers are of great significance. Methods: The original CEL files were obtain from Gene Expression Omnibus, then affymetrix package was used to preprocess the CEL files, the function of DEGs were investigated by multiple bioinformatics approach. Finally, typical HCC cell lines and tissue samples were using to validate the role of CDC6 in vitro. ⋯ Furthermore, we recognized that miR-215-5p, could directly bind to the 3'UTR of CDC6. In addition, CDC6 promoted proliferation via regulation of G1 phase checkpoint and was negative regulated by miR-215-5p to involve in the proliferation of HCC. Conclusion: Our study suggested that CDC6 served as a potential therapeutic target for HCC.