G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Relationship of the total length of coronary stent and patients’postoperative quality of life / 局解手术学杂志

Objective To analyze the relationship of the total length of coronary stent and patients’postoperative quality of life. Methods A number of 280 patients who were diagnosed as coronary artery by coronary angiography and successfully completed PCI surgery in our hospital from April 2012 to March 2013 were retrospectively collected.And they were divided into 3 groups according to the total length of the coronary stent,namely:group Ⅰ (68 cases,length of the coronary stent were less than 36 mm),group Ⅱ (156 cases,length of the coronary stent were 36 ~72 mm),and group Ⅲ (56 cases,length of the coronary stent were more than 72 mm).The prognosis and quality of life of patients of the 3 groups were compared.Results There was no significant difference in terms of in-stent restenosis,angina recurrence and target vessel revascularization rates among the 3 groups within 6 months after PCI surgery (P >0.05).But the incidence rate of adverse cardiac events of the 3 groups were significant different,and group Ⅲ were significantly higher than group Ⅱ,group Ⅱwas significantly high-er than in group Ⅰ (P 0.05).Conclusion Although the total length of coronary stent and patients’postoperative quality of life were of no correlation,it is still recommend to make assessment of vascular lesions carefully before surgery.For patients with stable disease,it is recommend to take conservative medication treatment.Make stent implan-tation only when it’s necessary and the length of coronary stent should be strictly controlled so as to reduce the incidence of adverse cardiac events.