Chromatin-regulatory genes served as potential therapeutic targets for patients with urothelial bladder carcinoma.

Urothelial bladder carcinoma is the ninth most common cancer in the world, with an estimated 150,000 deaths per year. Two comprehensive analysis based on The Cancer Genome Atlas urothelial bladder carcinoma reported that chromatin modifier gene mutations were common in bladder cancer. We aimed to find how the mutations and transcriptional profiles of the genes involving in chromatin modification affected the prognosis of patients. The data were retrieved from the Genomic Data Commons data portal and the gene list in pathway Chromatin Modifying Enzymes were obtained from Reactome. The expression levels and mutational profiles of the genes involving in the chromatin were utilized altogether to construct a fusion patient similarity network by similarity network fusion. The genes that were differentially expressed in one clustered group or two were identified. Fifty chromatin-regulating genes had nonsilent mutations in at least 10 patients. KMT2D, KDM6A, CREBBP, ARID1A, and ARID2 had enriched inactivating mutations. Among 399 cases where both the single-nucleotide polymorphism information and the messenger RNA expression profiles were available, 326, 23, and 50 patients were clustered into Groups 1, 2, and 3, respectively. The survival analysis suggested that the patients in these three groups had a different prognosis. Thity-one genes were identified as differentially expressed in any group. The Gene Ontology term enrichment showed that the differentially expressed genes were enriched in the immune response especially in the complement activation. Altogether, chromatin-regulatory genes were key in bladder cancer and can serve, with the differentially expressed genes, as potential therapeutic targets.

Chemical constituents from Spiraea salicifolia / 中草药

Objective: To investigate the chemical constituents from the ethanol extract of Spiraea salicifolia. Methods: The compounds were isolated and purified by chromatography on silica gel, ODS, and preparative HPLC methods. Their structures were elucidated on the basis of chemical and spectral data. Results: Twelve compounds were isolated and identified as 7S,8R-3,5- dimethoxy-4',7-epoxy-8,5'-neolignan-3',4,9,9'-tetraol (1, salicifoneoliganol), 3β-acetylursolic acid methyl ester (2), 3β-acetyloleanolic acid methyl ester (3), lupeol (4), β-amyrin (5), (7R,8S)-5-methoxydiyhdrodehydroconiferyl alcohol (6), 8-hydroxy-7'-epipinoresinol (7), 8-hydroxypinoresinol (8), fraxiresinol (9), (+)-africannal (10), (+)-lyoniresinol (11), and 5-methoxy-(+)-isolariciresinol (12). Conclusion: Compound 1 is a new lignan named salicifoneoliganol. Compounds 6 and 7 are isolated from the plants of Spiraea L. for the first time, and compounds 4, 5, and 8-12 are firstly obtained from this plant. Compounds 2 and 3 are artifacts of isolation from ursolic acid and loleanolic acid.