Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats

AIM: To investigate whether ezetimibe ameliorates hepatic steatosis and induces autophagy in a rat model of obesity and type 2 diabetes. METHODS: Male age-matched lean control LETO and obese and diabetic OLETF rats were administered either PBS or ezetimibe(10 mg/kg per day) via stomach gavage for 20 wk. Changes in weight gain and energy intake were regularly monitored. Blood and liver tissue were harvested after overnight fasting at the end of study. Histological assessment was performed in liver tissue. The concentrations of glucose, insulin, triglycerides(TG), free fatty acids(FFA), and total cholesterol(TC) in blood and TG, FFA, and TG in livertissue were measured. m RNA and protein abundance involved in autophagy was analyzed in the liver. To investigate the effect of ezetimibe on autophagy and reduction in hepatic fat accumulation, human Huh7 hepatocytes were incubated with ezetimibe(10 μmol/L) together with or without palmitic acid(PA, 0.5 mmol/L, 24 h). Transmission electron microscopy(TEM) was employed to demonstrate effect of ezetimibe on autophagy formation. Autophagic flux was measured with bafilomycin A1, an inhibitor of autophagy and following immunoblotting for autophagy-related protein expression.RESULTS: In the OLETF rats that received ezetimibe(10 mg/kg per day), liver weight were significantly decreased by 20% compared to OLETF control rats without changes in food intake and body weight(P < 0.05). Lipid parameters including TG, FFA, and TC in liver tissue of ezetimibe-administrated OLETF rats were dramatically decreased at least by 30% compared to OLETF controls(P < 0.01). The serum glucose, insulin, HOMA-IR, and lipid profiles were also improved by ezetimibe(P < 0.05). In addition, autophagy-related m RNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3(LC3) were significantly increased in the liver in rats that received ezetimibe(P < 0.05). Likewise, for hepatocytes cultured in vitro, ezetimibe treatment significantly decreased PA-induced fat accumulation and increased PA-reduced m RNA and protein expression involved in autophagy(P < 0.05). Ezetimibe-increased autophagosomes was observed in TEM analysis. Immunoblotting analysis of autophagy formation with an inhibitor of autophagy demonstrated that ezetimibe-increased autophagy resulted from increased autophagic flux. CONCLUSION: The present study demonstrates that ezetimibe-mediated improvement in hepatic steatosis might involve the induction of autophagy.

α-Vitamin E derivative, RRR-α-tocopheryloxybutyric acid inhibits the proliferation of prostate cancer cells

Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

不需二段硫化的密封垫用丙烯酸酯橡胶

1、前言聚丙烯酸酯弹性体系耐油、耐热、耐臭氧类橡胶,广泛用作汽年发动机的密封垫、密封件、O 形圈及胶管。丙烯酸酯橡胶的耐油性与氟橡胶不相上下,特别是在含有腐蚀性添加剂的发动机油中,除氟橡胶和硅橡胶外,与大多数其它橡胶相比,丙烯酸酯橡胶具有更好的耐热性。就成本一效果而言,它在这一类别的橡胶中是最好的橡胶之一。