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Background: Alcohol‐associated hepatic fibrosis is a widespread liver disease with no effective treatment. Recent studies have indicated that interleukin‐22 (IL‐22) can ameliorate alcohol‐associated liver disease. However, the mechanism underlying the role of IL‐22 in alcohol‐associated hepatic fibrosis remains unclear. Therefore, we investigated the effect of IL‐22 in a mouse model of alcohol‐associated hepatic fibrosis and its underlying mechanisms. Methods: Alcohol‐associated hepatic fibrosis was induced by feeding male C57BL/6J mice with a Lieber‐DeCarli liquid diet containing 4% ethyl alcohol for 8 weeks and injecting them with 5% tetrachloromethane (CCl4) intraperitoneally for the last 4 weeks. During the last 4 weeks, IL‐22 was also administered. We investigated the role of IL‐22 in autophagy and the PI3K/AKT/mTOR signaling pathway using a 3‐methyladenine intraperitoneal injection in the mice treated with IL‐22. The effects of IL‐22 on alcohol‐associated hepatic fibrosis, autophagy‐related gene expression, and PI3K/AKT/mTOR activity were assessed using histopathology, biochemical analysis, transmission electron microscopy, quantitative real‐time PCR, immunohistochemistry, and western blotting. Results: Mice treated with ethanol and CCl4 displayed distinct liver injuries, including hepatocyte necrosis, inflammatory cell infiltration, and hepatic fibrosis, which were substantially attenuated by IL‐22 treatment. In addition, we found that IL‐22 regulated the expression of autophagy‐related genes and inhibited the PI3K/AKT/mTOR pathway, as evidenced by the reduction in p‐PI3K, p‐AKT, and p‐mTOR expression after IL‐22 treatment. Conclusions: IL‐22 exerts a marked protective effect against alcohol‐associated hepatic fibrosis. Its effect may be partly related to the alteration of autophagy‐related gene expression and inhibition of the PI3K/AKT/mTOR pathway in the liver. [ABSTRACT FROM AUTHOR]

Background. Human Schlafen 5 (SLFN5) is reported to inhibit or promote the proliferation of several specific types of cancer cells by our lab and other researchers. We are curious about its implications in lung adenocarcinoma (LUAC), a malignant tumor with a high incidence rate and high mortality. Method. Lentiviral stable transfections of SLFN5-specific shRNA for knockdown and SLFN5 full-length coding sequence for overexpression were performed in LUAC cell for proliferation analysis in vitro and in vivo in nude mice. Clinical LUAC samples were collected for immunohistochemical analysis of SLFN5 protein levels. Results. We found that knockdown of endogenous SLFN5 upregulates cancer cell proliferation while inhibiting apoptosis. Besides, SLFN5 inhibition on proliferation was also observed in a nude mouse xenograft model. In contrast, overexpression of exogenous SLFN5 inhibited cell proliferation in vitro and in vivo and promoted apoptosis. As to the signaling pathway, we found phosphatase and tensin homolog on chromosome 10 (PTEN) was positively regulated by SLFN5, while its downstream signaling pathway AKT/mammalian target of rapamycin (mTOR) was inhibited. Moreover, compared with adjacent normal tissues, SLFN5 protein levels were markedly decreased in lung adenocarcinoma tissues. In conclusion, these suggest that human SLFN5 plays inhibitory roles in LUAC progression through the PTEN/PI3K/AKT/mTOR pathway, providing a potential target for developing drugs for lung cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Objective. By observing the needle-knife of KOA rabbit morphology, knee joint cartilage p-FAK, p-PI3K, Aggrecan gene, and protein expression, to study the effect of needle-knife to promote cartilage cell synthesis metabolism mechanism. Method. 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model-inhibitors (MP), needle-knife group (D), needle-knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT-PCR and Western Blot were used to test each animal cartilage p-FAK, p-PI3K, and Aggrecan gene and protein expression level. Results. Compared with N group, p-FAK and p-PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p-FAK, p-PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p-FAK, p-PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). Conclusion. Needle-knife therapy can promote the repairment of cartilage cells by activating FAK-PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism. [ABSTRACT FROM AUTHOR]