RESUMO
AIM: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation. PATIENTS & METHODS: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery. RESULTS: AA show higher expression of genes associated with immune response and inflammation. CONCLUSION: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D3 supplementation.
Assuntos
Negro ou Afro-Americano/genética , Próstata/fisiologia , Neoplasias da Próstata/genética , Análise de Sistemas , Transcriptoma/genética , População Branca/genética , Idoso , Colecalciferol/administração & dosagem , Estudos de Coortes , Suplementos Nutricionais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/efeitos dos fármacos , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Transcriptoma/efeitos dos fármacosRESUMO
The Deepwater Horizon (DWH) oil spill contaminated the spawning habitats for numerous commercially and ecologically important fishes. Exposure to the water accommodated fraction (WAF) of oil from the spill has been shown to cause cardiac toxicity during early developmental stages across fishes. To better understand the molecular events and explore new pathways responsible for toxicity, RNA sequencing was performed in conjunction with physiological and morphological assessments to analyze the time-course (24, 48, and 96 h post fertilization (hpf)) of transcriptional and developmental responses in embryos/larvae of mahi-mahi exposed to WAF of weathered (slick) and source DWH oils. Slick oil exposure induced more pronounced changes in gene expression over time than source oil exposure. Predominant transcriptomic responses included alteration of EIF2 signaling, steroid biosynthesis, ribosome biogenesis and activation of the cytochrome P450 pathway. At 96 hpf, slick oil exposure resulted in significant perturbations in eye development and peripheral nervous system, suggesting novel targets in addition to the heart may be involved in the developmental toxicity of DHW oil. Comparisons of changes of cardiac genes with phenotypic responses were consistent with reduced heart rate and increased pericardial edema in larvae exposed to slick oil but not source oil.