ABSTRACT
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.
ABSTRACT
Objective To evaluate the perioperative rehabilitation treatment effects of the patients receiving minimally invasive hip replacement under the guidance of fast-track rehabilitation surgery concept. Methods Seventy-two pa-tients with femoral head aseptic necrosis and femoral neck fractures treated in our hospital were selected and divided into the FTS nursing group and the traditional nursing group according to the hospital admission time, with 36 patients in each group. The traditional nursing group followed the traditional clinical pathway and the FTS group followed the clinical pathway with FTS run through artificial hip replacement for the purpose of treatment and optimized nursing. The nursing and treatment effects of the two groups were analyzed retrospectively. Results The FTS group had better nursing satisfaction than the traditional nursing group (P<0.05), and shorter hospital stay and lower hospitalization cost than the traditional group (P<0.05). In terms of postoperative long-term rehabilitation effect, the two groups were not significantly different in the ADL scores in the 3rd and 6th month(t=-1.467, P=0.147;t=-1.599, P=0.114), but in terms of postoperative short-term rehabilitation effect, the FTS group had higher ADL scores than the traditional nursing group in the 2nd week and 1st month, with statistically significant differences (t=-2.307, P=0.024; t=-2.451, P=0.017). Conclusion In the clinical pathway of artificial hip replacement, the application of fast-track rehabilitation concept can effectively prevent the occurrence of complications, shorten hospital stay, reduce hospitalization cost, improve nursing satisfaction, accelerate functional recovery of the patients receiving artificial hip replacement and improve the quality of life.