A mutual regulatory loop between transcription factor Yin Yang 1 and hepatitis B virus replication influences chronic hepatitis B.

Hepatitis B virus (HBV) infections pose a major threat to human health. HBV can upregulate the expression of the transcription factor Yin Yang 1 (YY1) in in vitro cytological experiments, suggesting an association between YY1 and HBV infection. However, data on YY1 expression in chronic hepatitis B (CHB) patients are lacking. In this study, we aimed to assess the correlation between YY1 expression and HBV infection. We detected serum YY1 levels in 420 patients with chronic HBV infection, 30 patients with chronic hepatitis C virus infection, and 32 healthy controls using an enzyme-linked immunosorbent assay. The correlation between YY1 levels and clinical parameters was analyzed. Meanwhile, the changes of YY1 before and after interferon or entecavir treatment were analyzed. YY1 levels in the liver tissues were detected using immunofluorescence staining. The expression of YY1 in HBV-expressing cells was detected through western blotting. Meanwhile, we explored the effects of YY1 on HBV replication and gene expression. We found that YY1 was highly expressed in the serum and liver tissues of CHB patients. Serum YY1 levels positively correlated with HBV DNA and hepatitis B surface antigen (HBsAg). Additionally, HBV DNA levels increased but HBsAg levels decreased after HBV-expressing cells overexpress YY1. In conclusion, our study demonstrates that YY1 plays an important role in HBV replication and gene expression, providing a potential target for the treatment of CHB.

Linking distinct conformations of nicotinamide adenine dinucleotide with protein fold/function.

Nicotinamide adenine dinucleotide (NAD or NADP) are essential cofactor/substrate for enzymes that catalyze redox or nonredox reactions. Because several enzymes involved in NAD(P) metabolism have been implicated in a wide array of diseases, there is great interest in designing inhibitors/activators of these NAD(P)-dependent enzymes based on their structures. Hence, we have elucidated the various distinct enzyme-bound NAD(P) conformations and their correlation with the respective protein fold and function using hierarchical clustering methods. Torsion angles distinguishing enzyme-bound NAD versus NADP conformations and NAD(P) conformations bound to redox versus nonredox enzymes were identified. Although an unusually small χ(N) in diphtheria toxin-bound NAD(+) had been postulated to strain the N-glycosidic bond, thus facilitating catalysis, toxin-bound NAD(+) molecules with χ(N) varying from 0 to 60° were found to exhibit similar C(1D)-N(1N) bond cleavage barriers in water. The findings herein provide useful guidelines in the design of inhibitors/activators of NAD(P)-dependent enzymes that are therapeutic targets.