The Gut Microbiome and Ferroptosis in MAFLD

Metabolic-associated fatty liver disease(MAFLD)is a new disease definition,and is proposed to replace the previous name,nonalcoholic fatty liver disease(NAFLD).Globally,MAFLD/NAFLD is the most common liver disease,with an incidence rate ranging from 6%to 35%in adult populations.The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance(IR),and the genetic susceptibility to acquired metabolic stress-associated liver injury.Similarly,the gut microbiota in MAFLD/NAFLD is being revaluated by scientists,as the gut and liver influence each other via the gut-liver axis.Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation.Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD,and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD.This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis.It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.

Expression of integrin in hepatic fibrosis and intervention of resveratrol

The aim of this study was to explore the expression of integrin-β1 in different stages of hepaticfibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepaticfibrosis.Hepaticfibrosis models of male Sprague Dawley(SD)rats were created and intragastric administration of resveratrol was given in low(40 mg/kg),middle(120 mg/kg)and high(200 mg/kg)dose groups.The expression of integrin-β1,transforming growth factor-β(TGF-β)and tissue inhibitor of metalloproteinase-1(TIMP-1)in different stages of hepaticfibrosis was detected by using RT-PCR.The expression of hexadecenoic acid(HA)and precollagen III(pc III)was assayed by radioimmunoassay.The expression of integrin-β1,TGF-βand TIMP-1 was determined in each group.Liver function and pathological sections of each group in different stages of hepaticfibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses.The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepaticfibrosis,but it was increased in other groups.The expression levels of integrin-β1 in the model control group(0.878±0.03,P<0.01)and low dose group(0.855±0.04,P<0.01)were higher than other groups,but there was no difference between model control group and low dose group(P>0.05).The expression levels of integrin-β1 and TGF-βin middle dose group and high dose group were higher than other groups(P<0.01).The expression levels of integrin-β1 and TGF-βin model control group and low dose group were lower than the normal control group(P<0.01).The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups(P<0.01).The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group(P<0.01).The expression of integrin-β1 existed in all stages of hepaticfibrosis of SD rats,and it was increased with the development of hepaticfibrosis.The expression of TGF-βand TIMP-1 was consistent with that of integrin-β1 in different stages of hepaticfibrosis.Resveratrol could improve the degree of hepaticfibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.