Objective To observe the effect of Sirt1 on the phosphorylation of Tau protein in neuroblastoma SK-N-SH cell line.Methods We cultured SK-N-SH cells in vitro with adenovirus packaging of Sirt1 and SirtM (Sirt mutant),and then observed the expression of Sirt1 under an inverted fluorescence microscope.The expressions of Sirt1and SirtM were detected by Western blot;t-Tau protein and phosphorylation of Tau protein were detected by Western blot,Real-time PCR,immunohistochemistry and immunofluorescence;and the effect of Sirt1 on SK-N-SH apoptosis was investigated by flow cytometry.Results The t-Tau protein level and its phosphorylation were significantly decreased in Sirt1 and SirtM groups compared with those in control group,and Sirt1 group showed more significantly decreased ser404,thr231 phosphorylation of tau protein and the mRNA level of Tau.Flow cytometry showed that Sirt1 could significantly reduce the apoptosis of SK-N-SH cells compared with the control group.Conclusion Sirt1 can decrease the phosphorylation of Tau protein and reduce the apoptosis of SK-N-SH,which provides an important laboratory basis for studies on Tau protein disease and other neurodegenerative diseases.

Objective The study aims to investigate the associationbetweencholesterol 7α-hydroxylase (CYP7A1) gene polymorphism and different clinical outcomes after Hepatitis B virus (HBV)infection in Fujian Han population and lay a foundation for understanding the mechanisms of genesis anddevelopment of HBV-related diseases.Methods Case-control study was conducted.586 patients of HBVpersistent infection without antiviral therapy and 225 HBV rehabilitation patients (35-55 years old) werecollected from May 2015 to June 2016 in the Liverish Center of First Clinical College of Fujian MedicalUniversity.The group of HBV persistent infection without antiviral therapy included 246 patients with chronichepatitis B, 177 patients with hepatitis B-related cirrhosis, and 163 patients with hepatitis B-related liver cancer.The rs3824260, rs4738687and rs8192871 loci of CYP7A1 gene were detected by improved multipleligase detection reaction (iMLDR).Logistic regression analysis and chi-square test were used to analyze thegenotyping results.Results Three SNPs ( single nucleotide polymorphisms ) of CYP7A1 gene wereselected and compared between HBV persistent infection group and HBV rehabilitation group and betweenchronic hepatitis B subgroup, liver cirrhosis subgroup and liver cancer subgroup.After adjustment for factorsincluding age andgender, there was no significant difference in the distribution of rs3824260 genotype amongthe groups(χ2 =1.565,P =0.459), however,the frequency of allele C in HBV rehabilitation group wassignificantly higher than in HBV persistent in fectiongroup for men (χ2 =4.365,P =0.037), whereas thefrequency of rs3824260 CC and CT was more likely to be observed in liver cancer group than in non -livercancer group (chronic hepatitis B subgroup and liver cirrhosis subgroup ) for women (χ2 =5.768,P =0.012;χ2 =10.130,P =0.001).The frequency of rs4738687 GG genotype was more likely to be observed innon-liver cancer group than in liver cancer group (χ2 =4.403,P =0.041;χ2 =6.940,P =0.009).Theresults of gender stratification showed that there were significant differences in the distribution of rs 4738687among the HBV persistent infection groups for men (χ2 =10.697,P =0.030), however, there was nosignificant difference in the distribution of rs4738687 among the HBV persistent infection groups for women(χ2 =4.627,P =0.329), and there was no significant difference in the distribution of genotype frequencyand allele frequency among all groups(χ2 =0.489,P =0.792).There was no significant difference after sexstratification either (χ2 =1.282, P =0.526;χ2 =1.565,P =0.465) .Conclusions These findingssuggested that CYP7A1 gene polymorphism was related todifferent clinical outcomes in Fujian Hanpopulation.The rs3824260 mutation had a certain gender preference and the mutation allele was detected ina higher proportion in male patients.Male HBV patients with rs3824260 C allele had more chance ofswitching to rehabilitation.The rs4738687 was likely to be related to the occurrence of liver cancer in FujianHan population, and GG genotype may delay the occurrence and development of liver cancer especially in themale group.The rs8192871 was not found to be related to the different clinical outcomes of HBV infection.