RESUMO
Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.
RESUMO
We previously showed that hepatitis B virus (HBV) X protein (HBx) could promote the trimethylation of histone H3 lysine 9 (H3K9me3) to repress tumor suppressor genes in hepatocellular carcinoma (HCC). In this work, we analyze 23,148 human promoters using ChIP-chip to determine the effects of HBx on H3K9me3 enrichments in hepatoma cells with transfection of HBx-expressing plasmid. Immunohistochemistry for HBx and H3K9me3 was performed in 21 cases of HBV-associated HCC tissues. We identified that H3K9me3 immunoreactivity was significantly correlated with HBx staining in HCC tissues. ChIP-chip data indicated that HBx remarkably altered promoter enrichments of H3K9me3 in hepatoma cells. We identified 25 gene promoters, whose H3K9me3 enrichments are significantly altered in hepatoma cells transfected HBx-expressing plasmid, including 19 gaining H3K9m3, and six losing this mark. Most of these genes have not been previously reported in HCC, and BTBD17, MIR6089, ZNF205-AS1 and ZP1 have not previously been linked to cancer; only two genes (DAB2IP and ZNF185) have been reported in HCC. Genomic analyses suggested that genes with the differential H3K9me3 enrichments function in diverse cellular pathways and many are involved in cancer development and progression.