TRIM25 inhibits HBV replication by promoting HBx degradation and the RIG-I-mediated pgRNA recognition / 中华医学杂志(英文版)

BACKGROUND@#The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25.@*METHODS@#The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay.@*RESULTS@#We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process.@*CONCLUSIONS@#The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.

Clinical observation of Wumeiwan combined with triple therapy for treatment of chronic atrophic gastritis / 国际中医中药杂志

Objective@#To explore clinical efficacy and safety of Wumeiwan combined with triple therapy for treatment of chronic atrophic gastritis (CAG).@*Methods@#According to the random indicator method, 113 patients with CAG were divided into control group (n=56) and treatment group (n=57). Patients of control group were treated with triple therapy, while treatment groupwere treated Wumeiwan combined with triple therapy. The two groups were treated for 3 months. Clinical effect was evaluated after treatment. The helicobacter pylori (Hp) conversion to negative of the two groups was compared and recorded. The Hp overcast conditions of the two groups were compared. The serum TNF-α, IL-6, IL-8 and peripheral blood CD3+, CD4+, CD8+, CD4+/CD8+ of the two groups before and after treatment were compared. The adverse reactions of the two groups during the treatment were compared.@*Results@#Total effective rate of treatment group was 94.7% (54/57), which was significantly higher than the control group 82.14% (46/56), and the difference was statistically significant (χ2=4.401, P=0.036). Hp overcast rate of treatment group was 88.2% (45/51), which was significantly higher than the control group 48.0%(24/50), and the difference was statistically significant (χ2=18.883, P=0.000). After treatment, the serum TNF-α (1.43 ± 0.17 mg/L vs. 1.97 ± 0.22 mg/L, t=14.615), IL-6 (30.79 ± 3.65 ng/L vs. 41.13 ± 4.10 ng/L, t=14.166), IL-8 (7.52 ± 1.32 ng/L vs. 9.60 ± 1.77 ng/L, t=7.090) in the treatment group were lower than those in the control group (P<0.05). After treatment, the peripheral blood CD3+ (75.12% ± 16.44% vs. 67.33% ± 14.37%, t=2.680), CD4+ (39.02% ± 11.41% vs. 33.49% ± 10.61%, t=2.667), CD4+/CD8+ (1.58 ± 0.35 vs. 1.19 ± 0.32, t=6.179) in the treatment group were higher than those in the control group (P<0.05), the peripheral blood CD8+ (24.75% ± 9.69% vs. 28.12% ± 11.29%, t=1.704) in the treatment group were higher than those in the control group (P<0.05). There was no significantly difference of the adverse reaction rates of the two groups during treatment (χ2=0.134, P=0.714).@*Conclusions@#The Wumeiwan combined with triple therapy for treatment of CAG has a good efficacy and low adverse reactions, has serious anti-inflammatory effects, can improve the body immunity, and it was worthy clinical application.