microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation.

Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA-143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir-143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1-mediated miRNA-143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA-143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA-143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.

Dietary Copper Plays an Important Role in Maintaining Intestinal Barrier Integrity During Alcohol-Induced Liver Disease Through Regulation of the Intestinal HIF-1α Signaling Pathway and Oxidative Stress.

Impaired intestinal barrier function and oxidative stress injury play critical roles in the pathogenesis of alcoholic liver disease (ALD), and recent investigations have revealed a role for dietary copper in the liver and intestinal barrier function. Therefore, the current study investigates the mechanisms and role of dietary copper in alcohol induced liver diseases. C57BL/6 mice were used to create an alcoholic liver disease model with a Lieber-DeCarli diet containing 5% alcohol and were fed with different concentrations of dietary copper of adequate (6 ppm, CuA), marginal (1.5 ppm, CuM), or supplemental (20 ppm, CuS) amounts. Caco-2 cells were also exposed to ethanol and different concentrations of copper. Damages of the liver and intestine were evaluated by transaminases, histology staining, and protein and mRNA level, as well as cell proliferation, oxidative stress, and mitochondrial membrane potential. In animal experiments, the results indicate that an alcohol diet causes liver injury and disruption of intestinal barrier function as well as decreasing the expression of genes such as HIF-1α, occludin, SOD1, and GPX1. Supplemental dietary copper can revert these changes except for SOD1, but marginal dietary copper can worsen these changes. The in vitro cell experiments showed that proper copper supplementation can promote cell growth and reduce reactive oxygen species (ROS) production. In conclusion, supplemental dietary copper has beneficial effects on alcohol-induced intestine and liver injury, and marginal dietary copper shows detrimental effects on these parameters.

Characteristics of Liver Functions in Patients With COVID-19 and Construction of a Prognostic Evaluation Decision Model Based on Liver Functions.

A number of studies have suggested that coronavirus disease 2019 (COVID-19) can cause liver damage. However, clinical features and outcome of COVID-19 in patients with liver injury remain to be further investigated. In this study, the clinical data of 265 COVID-19 patients admitted to seven tertiary hospitals were collected. Based on a threshold for transaminase or total bilirubin levels at two times the normal upper limit, patients were divided into mild or moderate/severe liver injury groups. Among the 265 patients, 183 patients showed liver injury within 48 hours of admission. Aspartate aminotransferase levels were predominantly elevated in the liver injury group, but albumin levels were reduced. Moreover, fibrinogen and D-dimer were significantly increased. Furthermore, 68% of the patients with moderate/severe liver injury had one or more underlying diseases. Almost half of these patients developed acute respiratory distress syndrome (44%) and secondary infections (46%). These patients showed increased interleukin-6 and interleukin-10 levels and a decrease in PaO2 and the oxygenation index. In addition, levels of alanine aminotransferase, aspartate aminotransferase, and albumin were correlated with the oxygenation index, D-dimer and lymphocyte counts. Furthermore, a novel prognostic assessment model based on liver function was established, which accuracy reached 88% and was able to accurately assess the prognosis of COVID-19 patients.