Hyperglycemia-induced inflammation and apoptosis have important roles in the pathogenesis of diabetic cardiomyopathy. We recently found that a novel curcumin derivative, C66, is able to reduce the high glucose (HG)-induced inflammatory response. This study was designed to investigate the protective effects on diabetic cardiomyopathy and its underlying mechanisms. Pretreatment with C66 significantly reduced HG-induced overexpression of inflammatory cytokines via inactivation of nuclear factor-κB in both H9c2 cells and neonatal cardiomyocytes. Furthermore, we showed that the inhibition of Jun NH2-terminal kinase (JNK) phosphorylation contributed to the protection of C66 from inflammation and cell apoptosis, which was validated by the use of SP600125 and dominant-negative JNK. The molecular docking and kinase activity assay confirmed direct binding of C66 to and inhibition of JNK. In mice with type 1 diabetes, the administration of C66 or SP600125 at 5 mg/kg significantly decreased the levels of plasma and cardiac tumor necrosis factor-α, accompanied by decreasing cardiac apoptosis, and, finally, improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. Thus, this work demonstrated the therapeutic potential of the JNK-targeting compound C66 for the treatment of diabetic cardiomyopathy. Importantly, we indicated a critical role of JNK in diabetic heart injury, and suggested that JNK inhibition may be a feasible strategy for treating diabetic cardiomyopathy.
Ribosomes, which are important sites for the synthesis of proteins related to expression and transmission of genetic information in humans, have a complex structure and diverse functions. They consist of a variety of ribosomal proteins (RPs), ribosomal RNAs (rRNAs) and small nucleolar RNAs. Owing to the involvement of ribosomes in many important biological processes of cells, their major components, rRNAs and RPs, have an important role in human diseases, including the initiation and evolvement of malignancies. However, the main mechanisms underlying the involvement of ribosomes in cancer remain unclear. This review describes the crucial role of ribosomes in various common malignant tumors; in particular, it examines the effects of RPs, including S6, the receptor for activated C-kinase and RPS15A, on the development and progression of hepatocellular carcinoma.
Objective To estimate a stillbirth rate at 24 or more gestational weeks in 2015-2016 and to explore potentially preventable causes in China. Design A multi-centre cross-sectional study. Setting Ninety-six hospitals distributed in 24 (of 34) provinces in China. Population A total of 75 132 births at 24 completed weeks of gestation or more. Methods COX Proportional Hazard Models were performed to examine risk factors for antepartum and intrapartum stillbirths. Population attributable risk percentage was calculated for major risk factors. Correspondence analysis was used to explore regionspecific risk factors for stillbirths. Main outcome measures Stillbirth rate and risk factors for stillbirth. Results A total of 75 132 births including 949 stillbirths were used for the final analysis, giving a weighted stillbirth rate of 13.2 per *These authors contributed equally to the work and should be considered as first authors. † The complete list of participating institutions and principle investigators are provided in the Acknowledgements.
Oral verrucous carcinoma (OVC) is a verrucous variant of oral cavity squamous carcinoma (OSCC). The expression of miRNA from OVC and OSCC including their matched normal oral mucosa tissues was profiled through the Affymetrix GeneChip miRNA Arrays. TargetScan and miRanda databases were used to predict the target gene of miRNA-195. The quantitative real-time PCR was applied to validate the expression of miRNA-195. The expression of CDK6 was investigated by the quantitative real-time PCR and immunohistochemistry. In this study, a total of 23 and 35 differentially expressed miRNAs were identified in OVC and OSCC, respectively. Moreover, 44 miRNAs were differentially expressed between OSCC and OVC. In addition, miRNA-195 was significantly decreased in both OVC and OSCC compared to normal oral mucosa. Target gene prediction demonstrated that CDK6 was a potential target gene of miRNA-195. In the quantitative real-time PCR, miR-195 was decreased in OVC and OSCC, which was consistent with the result of miRNA chip analysis. CDK6 was increased in OVC and OSCC, which was opposite to the expression of miRNA-195. In conclusion, miRNA-195 could be the potential diagnosis biomarker and therapy target of OVC.
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