The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV). We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95%) and low cytotoxicity (66% to 77%). Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy)-phenol (compound 1) and 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol (compound 2), which are classified as polybrominated diphenyl ethers (PBDEs), were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs.

Children with JDM express antibodies to autoantigens in endothelial cells. The clinical and pathological significance of such autoantibodies require further investigation.

Background There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods The clinical charts of 233 patients with CRPC treated with enzalutamide were reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were divided into a reduced dose group and a standard dose group, and the prostate specific antigen (PSA) response and the incidence of AEs were compared. Results 190 patients with CRPC initiated with standard dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between the standard and the reduced dose group. In the PSM cohort, the PSA response rate was significantly lower in the reduced dose group than in the standard dose group (-66.3% and -87.4%, p = 0.02). The incidence rates of AEs were not statistically different between the groups (22.6% and 34.4%, respectively, p = 0.24). Conclusion Initiating treatment with a reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed poorer PSA response rate. There is no clear rationale for treating with a reduced initial dose of enzalutamide to reduce the incidence of AEs.

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