Structure, function, and mechanism of the TNFAIP8 (TIPE) family of proteins in cancer and inflammation

The multiple roles of the tumor necrosis factor(TNF)-α-inducible protein 8(TNFAIP8),also named TIPE family of proteins have been shown in tumor and inflammation progression and regulation of cellular autophagy and apoptosis.In this review,we found that the TIPE family showed highly homologous sequences and conserved functional domains,such as the death effector domain(DED)-like domain but displayed different roles and mechanisms in different biological activities.For example,while TIPE is primarily associated with tumor progression and antitumor drug resistance,TIPE1 suppresses tumor progression in most instances.TIPE2 has multiple roles in tumor progression regulation,and antitumor drug resistance.Moreover,TIPE2 was also involved in inflammatory response regulation,tumor typing,and staging.A few studies reported that TIPE3 was engaged in tumor development by activating the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.The structure,function,and mechanism of the TIPE family in cancer and inflammation have been summarized in this review.This might serve as a reference for further research on the TIPE family and shed new light on the crosstalk among antitumor responses,inflammation,and immunology.

Effect of Hirudin on farnesol X receptor pathway during acute intrahepatic cholestasis

Objective:The purpose of this study is to explore the effect of Hirudin on the farnesoid X receptor(FXR)pathway during acute intrahepatic cholestasis in vivo and in vitro.Method:In vivo,sixty male Sprague-Dawley rats were randomly divided into six groups:regular group,model group,ursodeoxycholic acid(UDCA)group(60 mg/kg),hirudin treatment group(84 u/kg),hirudin treatment group(63 u/kg)and hirudin treatment group(42 u/kg).The male Sprague-Dawley rats of UDCA group were intragastrically administered with a corresponding concentration of 0.005 mL/g body weight for seven days,once a day;and the hirudin treatment group was injected subcutaneously with different concentrations of Hirudin for seven days,once a day;Except for the normal group,other groups of rats were given 100 mg/kg ANIT by gavage on the 5th day.The model was administered by gavage once a day for three days.In vitro,(Z)-Guggulsterone was used to stimulate the L02 cells(0.05μmol/ml),with or without different concentrations of Hirudin(2,4 and 8 u/ml)for 24 h.The liver tissue was examined by HE microscope and the pathological state of the rat liver was observed;FXR,Small heterodimeric chaperone receptor(SHP),uridine diphosphate glucuronide transfer 2B4(UGT2B4),bile salt output pump(BSEP)mRNA and protein expressions were tested by real-time fluorescent quantitative PCR and Western blot test.And immunohistochemistry(IHC)was used to analyze the expression of FXR.Results:Compared with the model group,the hirudin group can improve liver tissue damage,and promote FXR,SHP,BSEP and UGT2B4 proteins and mRNA expression in vivo and in vitro.Conclusion:Hirudin can alleviate intrahepatic cholestasis,reduce liver tissue damage.Hirudin can up-regulate the expression of FXR gene,promote the up-regulation of SHP,BSEP and UGT2B4 genes,and inhibit the cholestasis pathway to protect liver cells.The study may provide an effective drug for clinical treatment of intrahepatic cholestasis.