Protective effect of fu-qi granule on carbon tetrachloride-induced liver fibrosis in rats

AIM： To investigate the effcacy of fu-qi granule （FQG） on carbon tetrachloride （CCl4） induced liver fbrosis in rats and the underlying mechanisms. METHODS： Sixty rats were randomly divided into six groups： normal control group, CCl4 induced liver fbrosis group, AnluoHuaxianWan group and three treatment groups of FQG. Treatment of rats with intraperitoneal injection of carbon tetrachloride solution at 0.3 mL per 100 g body weigh twice a week for 8 wk. The normal control group the rats were given the media （olive oil） at the same time. In the frst 2 wk, rats were raised with feedstuff （80% corn meal, 20% lard, 0.5% cholesterol）. Serum samples were collected for alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein assay and typical histopathological changes was observed in Hematoxylin-eosin staining sections. Smooth muscle alpha actin （α-SMA） was analyzed with immunohistochemistry. Mammalian target of rapamycin （mTOR） and hypoxia-inducible factor-1 （HIF-1α） expressions were detected by Western blot-ting. Tissue inhibitor of matrix metalloproteinases-1 （TIMP-1） and matrix metalloproteinases-9 （MMP-9） were measured with semi-quantitative reverse transcriptase-polymerase chain reaction.RESULTS： FQG significantly reduced the serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and increased the serum contents of albumin, total protein in rats with liver fibrosis. Moreover, FQG promoted extracellular matrix degradation by increasing MMP-9 and inhibiting TIMP-1 and α-SMA. mTOR and HIF-1α expression in liver significantly decreased in the rats treated with FQG. CONCLUSION： The results indicated that FQG signi-fcantly reverse fbrosis induced by CCl4, which should be developed as a new and promising preparation for the prevention of liver fbrosis.

Heat stress inhibits proliferation, promotes growth, and induces apoptosis in cultured Lantang swine skeletal muscle satellite cells

Proliferation suppression and apoptosis are the prominent characteristics induced by heat stress（HS） in cells, whereas the effects of HS on cell growth（mass accumulation） are unknown. In this study, Lantang swine（an indigenous breed of China） skeletal muscle satellite cells（SCs） were pre-cultured at 37 °C for 24 h. The HS group was subjected to HS at 41 °C, while the control group was maintained at 37 °C. Heat shock protein 70（HSP70） expression and SC size are significantly increased（P〈0.05） by HS, but cell proliferation is suppressed（P〈0.05） and apoptosis is induced（P〈0.05）. HS led to a lower percentage of SCs in the G0/G1 phase（P〈0.05） together with a higher percentage of SCs in the S phase（P〈0.05）. However, the percentage of SCs in the G2/M phase was decreased（P〈0.05） at 48 h but then increased（P〈0.05） at 72 h with HS. In addition, the phosphorylation ratios of protein kinase b（Akt）, ribosomal protein S6 kinase（S6K）, and ribosomal protein S6 were increased（P〈0.05） by HS. Nevertheless, the phosphorylation ratios of the 4E binding protein 1 and the eukaryotic initiation factor-4E were indistinguishable（P〉0.05） from those of the control group. The phosphorylation ratio of the mammalian target of rapamycin（m TOR）（Ser^2448） increased（P〈0.05） within 48 h, and apparent differences were abrogated at 72 h（P〉0.05）. Moreover, cleaved caspase-3 expression was increased at 72 h（P〈0.05）. These findings indicate that HS induces apoptosis and disrupts cell cycle distribution to decrease the number of cells. Additionally, HS can promote SC growth via an activated Akt/m TOR/S6 K signaling pathway.

FXYD6： a novel therapeutic target toward hepatocellular carcinoma

FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na＋/K＋-ATP- ase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma （HCC） and enhances the migration and prolif- eration of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na＋IK＋-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.