Because of self‐renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow‐derived mesenchymal stem cells (BM‐MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM‐MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM‐MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600‐ to 7000‐fold), transforming growth factor, and procollagen‐α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM‐MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow‐derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.
Hepatic stellate cell (HSC) activation via the autophagy pathway is a critical factor in liver fibrogenesis. This study tests the hypothesis that chloroquine (CQ) treatment can prevent autophagy and HSC activation in vitro and in vivo in bile-duct-ligated (BDL) mice. Sham-operated and BDL mice were treated with either PBS or CQ in two 60 mg/kg doses the day (D) before and after surgery. On day 2 (2D), HSCs were isolated, and their biological activities were evaluated by measuring intracellular lipid content, α-sma/collagen, and expression of autophagy lc3, sqstm1/p62 markers. The treatment efficacy on liver function was evaluated with serum albumin, transaminases (AST/ALT), and hepatic histology. Primary HSCs were treated in vitro for 24 h with CQ at 0, 2.5, 5, 10, 30, and 50 µM. Autophagy and HSC activation were assessed after 2D of treatment. CQ treatment improved serum AST/ALT, albumin, and bile duct proliferation in 2D BDL mice. This is associated with a suppression of HSC activation, shown by higher HSC lipid content and collagen I staining, along with the blockage of HSC autophagy indicated by an increase in p62 level and reduction in lc3 staining. CQ 5 µM inhibited autophagy in primary HSCs in vitro by increasing p62 and lc3 accumulation, thereby suppressing their in vitro activation. The autophagy inhibitor CQ reduced HSC activation in vitro and in vivo. CQ improved liver function and reduced liver injury in BDL mice.
28 October 2021 in Journal of Gastroenterology and Hepatology
Autophagy is a physiological process that is ubiquitous and essential to the disposal or recycling of damaged cellular organelles and misfolded proteins to maintain organ homeostasis and survival. Its importance in the regulation of liver function in normal and pathological conditions is increasingly recognized. This review summarizes how autophagy regulates epithelial cell- and non-epithelial cell-specific function in the liver and how it differentially participates in hepatic homeostasis, hepatic injury response to stress-induced liver damage such as cholestasis, sepsis, non-alcoholic and alcohol-associated liver disease, viral hepatitis, hepatic fibrosis, hepatocellular and cholangiocellular carcinoma, and aging. Autophagy-based interventional studies for liver diseases that are currently registered in clinicatrials.gov are summarized. Given the broad and multidirectional autophagy response in the liver, a more refined understanding of the liver cell-specific autophagy activities in a context-dependent manner is necessary.
The aim was to study the actual situation of subjective fatigue among the Vietnamese workers in factories with newly imported technology. A cross-sectional study concerning working conditions and the fatigue complaints of 389 workers who are employed in 10 Vietnamese factories with newly imported technology, was conducted from August to September 1994. About 60% of the workers were satisfied with their current working conditions. Regarding occupational risks at the workplace, heat, dust and noise were identified as the three most dangerous risks. About 46% of the workers complained about the incompatibility of the machines and equipment they were using, which are too large for Vietnamese workers. One third of all workers felt that the work pace is too rapid. Seventeen percent of the workers considered their working conditions monotonous. Finally, among 150 female workers under 40 years old, 45 workers (30.0%) complained of irregularity of menstruation. Generally these problems were more common among workers in textile factories. The prevalence rate of subjective fatigue complaints was significantly increased after work in all 30 items. The fatigue level were substantially high among workers in textile factories. Female workers in this sector had a high prevalence rate of irregularity of menstruation. There were many problems observed in the Vietnamese factories with newly imported technology. Special consideration is required to improve the working conditions of female workers in the textile industry. Both the Vietnamese government and donor countries have to give special attention to the transfer of worker-friendly technology to Vietnam, in order to achieve sound economic development.