Acyl-CoA thioesterase 12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis.

Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma (HCC). A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine(DEN)/carbon tetrachloride (CCl4) administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis (NASH). Relative to controls, Acot12-/- mice exhibited accelerated liver tumor formation that was characterized by the hepatic accumulation of glycerolipids, including lysophosphatidic acid (LPA), and that was associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity. In Acot12-/- mice, restoration of hepatic Acot12 expression inhibited hepatocarcinogenesis and YAP activation, as did knockdown of hepatic YAP expression. Excess LPA produced due to deletion of Acot12 signaled through LPA receptors (LPARs) coupled to Gα12/13 subunits to suppress YAP phosphorylation, thereby promoting its nuclear localization and transcriptional activity. These findings identify a protective role for Acot12 in suppressing hepatocarcinogenesis by limiting biosynthesis of glycerolipids including LPA, which preserves Hippo signaling.

Effect of purity of tea polysaccharides on its antioxidant and hypoglycemic activities.

The effects of purity of tea polysaccharides (TPS) on its five antioxidant activities and hypoglycemic activities in vitro were studied. The results showed that the higher the purity of TPS, the lower the antioxidant capacity. The purity of FTPSI is the highest (sugar content 80.72%), but its antioxidant activities were lower than those of Fujian tea polysaccharides (FTPS) and FTPSII. The antioxidant activity of tea polysaccharide is related to its protein and polyphenol content (Pearson r > .90). The protective effect of Zhejiang tea polysaccharides and FTPS on human umbilical vein endothelial cells (HUVEC) was better than that of its purified fractions. The inhibition rates of FTPSII (5 and 2 mg/ml) on α-glucosidase (32.76%) and α-amylase (-11.93%) were higher than those of FTPS and FTPSII. Purification does not change the basic structure of TPS. This study has certain reference value for the study of the antioxidant activities of TPS. Meanwhile, TPS can be used as a potential resource with hypoglycemic function. PRACTICAL APPLICATIONS: A large number of studies have shown that TPS have antioxidant activity. However, several studies considered that the antioxidant activity of TPS mainly comes from the residues of tea polyphenols. Therefore, the in vitro and cell antioxidant activities of TPS were studied in this paper. We believe that both glycoprotein and tea polyphenol are antioxidants of tea, and tea polysaccharide perform preferable effect on hypoglycemic. HUVEC cell model and four in vitro antioxidant test methods were used to study the antioxidant activities of TPS, and two enzyme inhibition activities were used to study the hypoglycemic effect of TPS, in order to provide a theoretical basis for the study of biological activity of TPS.

Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation.

Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.