The assembly of [Mo2O2S2]2+ based on polydentate phosphonate templates and their proton conductivity.

The assembly of [Mo2O2S2]2+ units depends on the configuration of polydentate phosphonic acid templates, leading to novel topologies with enhanced nuclearity and complexity. The variation of the assembled structures also gives rise to distinct proton-conducting properties.

Interleukin-22 alleviates alcohol-associated hepatic fibrosis, inhibits autophagy, and suppresses the PI3K/AKT/mTOR pathway in mice.

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.

[Inhibitory effect of lentivirus-mediated hTERTp-TK combined with hTERTp-tumstatin on human hepatocarcinoma HepG2 cells].

OBJECTIVE: To observe targeted expression of recombinant lentivirus-mediated (Lv)-hTERTp-TK and Lv-hTERTp-tumstatin in HepG2 cells, and explore the inhibitory effect of their combination on HepG2 cells both in vitro and in vivo. METHODS: Lv-hTERTp-TK and Lv-hTERTptumstatin were used to infect HepG2 and L02 cells at different MOIs. Transfection efficiency was observed by fluorescence microscopy. Expression of TK and tumstatin mRNA was detected by reverse-transcriptase PCR. Proliferation and apoptosis were detected by MTT and flow cytometry, respectively. The HepG2 cells were examined by real time-PCR and western blotting to determine expression level of bcl-2 and VEGF mRNA and protein.A murine hepatocellular carcinoma model was established by injecting 1 * 10(7) HepG2 cells into 30 BALB/c nude mice. The modeled mice were randomly divided into a control group, mock group, Lv-hTERTp-tumstatin group, Lv-hTERTp-TK group, and combination group for four weeks of injections at regular intervals of PBS, Lv-hTERTp-null, Lv-hTERTp-tumstatin, Lv-hTERTp-TK, and Lv-hTERTp-tumstatin plus Lv-hTERTp-TK, respectively.Changes in tumor volume and weight, and cell morphology of tumor and major organs, were assessed by hematoxylin-eosin staining.Microvascular density of tumor tissue and cell apoptosis were assessed by immunohistochemical and TUNEL staining, respectively. RESULTS: The Lv-infected HepG2 cells, and not the Lv-infected L02 cells, expressed TK and tumstatin. Lv-hTERTp-TK and Lv-hTERTp-tumstatin, alone or in combination, inhibited proliferation and increased apoptosis of the HepG2 cells, but the combination was more effective than either alone (P less than 0.05). None of the treatments affected proliferation or apoptosis of the L02 cells (P more than 0.05). The combination also led to a greater reduction of bcl-2 and VEGF than either alone (all, P less than 0.05). Tumor growth was significantly inhibited by the combination (P less than 0.05). In vivo, the combination treatment induced the greatest amount of apoptosis of the HepG2 cells. Cell morphology of major organs such as liver, spleen and kidney were similar to the control group. The combination also produced the most significant effect on tumor microvascular density (P less than 0.05) and the highest apoptosis index (P less than 0.05). CONCLUSION: The HTERT promoter can induce targeted expression of TK and tumstatin in HepG2 cells. Lv-hTERTp-TK combined with Lv-hTERTp-tumstatin can significantly inhibit proliferation and induce apoptosis of human HepG2 cells in vitro and in vivo, which may be related to down-regulation ofbcl-2 and VEGF.