Abbreviations: AICAR, 5-amino-4-imidazolecarboxamide ribonucleotide; AMPK, AMP-activated protein kinase; GLUT4, glucose transporter 4; MEF2, myocyte enhancer factor 2
AbstractChronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. ) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKα subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFα levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKα1 and α2, the protein levels of total-and phospho-AMPKα in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKα and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFα level. Taken together, chronic ethanol exposure decreases the expression of AMPKα and MEF2, and is associated with GLUT4 decline in rat myocardium.
Evidence about the clinical effects of entecavir (ETV) for patients with hepatitis B decompensated cirrhosis remain controversial. Therefore, we perform this meta-analysis to assess the treatment outcomes of ETV in participants with hepatitis B decompensated cirrhosis. Relevant studies were identified by searching databases until the March 2016. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). GRADEprofiler3.6 was used to evaluate the quality of the evidence. A total of 26 studies (involving 2040 patients) were included. The quality of the evidence was classified from very low to high by the GRADED approach for all included RCTs. Meta-analysis showed that patients were more likely to experience HBV-DNA loss (RR:1.85, 95%CIs: 1.41 to 2.43, P < 0.0001 at 48 weeks), have normalized alanine aminotransferase levels (ALT) (P = 0.003 at 24 weeks, P = 0.02 at 48 weeks), and have a low mortality rate at 24 weeks (P = 0.003) when treated with ETV. There was no significant different between ETV and the control groups at the total mortality (P = 0.06) and HBeAg seroconversion (P = 0.14). In conclusion, ETV could be the first line therapy for patients with HBV related decompensated cirrhosis, because ETV could reduce the early mortality and move HBV DNA load down.
As preliminarily estimated from the results of the study, TRAILis negatively correlated with drug-resistant genes. It is possible that TRAIL increases the apoptosis and growth inhibition of chemotherapy drug tumor cells by reducing the expression of drug-resistant genes MDR1, LRP and GST-Tt, thereby participating in the reversion of the multidrug resistance of gastric cancer
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