Inflammatory bowel disease

This article reviews the etiology, clinical characteristics, and treatment of inflammatory bowel disease (IBD) and associated psychological sequelae in children and adolescents with this lifelong disease. Pediatric-onset IBD, consisting of Crohn's disease and ulcerative colitis, has significant medical morbidity and in many young persons is also associated with psychological and psychosocial challenges. Depression and anxiety are particularly prevalent and have a multifaceted etiology, including IBD-related factors such as cytokines and steroids used to treat IBD and psychosocial stress. A growing number of empirically supported interventions, such as cognitive behavioral therapy, hypnosis, and educational resources, help youth and their parents cope with IBD as well as the psychological and psychosocial sequelae. While there is convincing evidence that such interventions can help improve anxiety, depression, and health-related quality of life, their effects on IBD severity and course await further study.     

Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Epigenetic therapy induced by dietary components has become a strong interest in the field of cancer prevention. Olive oil, a potent dietary chemopreventive agent, control colon cancer, however, its role in epigenetic therapy remains unclear. Thus, we aimed to investigate the effect of olive oil in a preclinical model of colon cancer by targeting genetic and epigenetic mechanisms. DMH was used to induce colon cancer in rats; while olive oil was given to separate group of rats along with DMH treatment. Tumor burden and incidence in DMH and DMH + olive oil-treated rats was observed by macroscopic examination and histoarchitectural studies. Potent anti-inflammatory, anti-angiogenic and pro-apoptotic activity of olive oil was explored by gene expression and immunohistochemical studies. The effect of olive oil on epigenetic alterations was examined by detecting promoter methylation with MS-HRM and dysregulation of miRNA by TaqMan MicroRNA Assay. We observed that olive oil administration lowered tumor incidence and inhibited the development of tumors in DMH-treated rats. Olive oil markedly decreased the expression of inflammatory and angiogenic markers and restored the expression of pro-apoptotic markers in DMH-treated rats. Furthermore, the inverse relationship between gene expression and DNA methylation, deviant miRNA pattern and miRNA silencing mediated by aberrant DNA methylation was also seen in DMH-treated rats, which was potentially reversible upon olive oil treatment. Our study concludes that olive oil may play a role in the epigenetic therapy by altering NF-κB and apoptotic pathways via targeting noncoding RNAs and methylation machinery that affecting epigenome to prevent colon carcinogenesis.     

Indole-3-carbinol induces apoptosis in AGS cancer cells via mitochondrial pathway

Indole-3-carbinol is produced from the cruciferous vegetables and broadly investigated for their various biological effects in in-vitro and in-vivo aspects. However, the anticancer activity of I3C and its molecular mechanisms have not been investigated in human adeno gastro carcinoma (AGS) cells. In our study of AGS cells, nuclear condensation was observed by 4′,6-diamidino-2-phenylindole (DAPI) staining, cell death was confirmed by a cell viability assay, and fragmented DNA was observed at the IC₅₀ dose by a DNA fragmentation assay. Apoptosis was evaluated by the qPCR technique. Treatment of the AGS cells with I3C at different concentrations has drastically decreased cell proliferation and differentiation. By releasing cytochrome-c from mitochondria in the intrinsic pathway, I3C prevents the multiplication of AGS cells and initiates apoptosis. The WST-1 assay result showed that I3C treatment against AGS cells had considerably reduced the viability of the cells. Furthermore, RT-qPCR showed the fold change among the expressed proteins compared with reference gene β-actin. Molecular docking revealed that I3C showed a strong binding affinity for the apoptotic protein 3DCY. The results show the caspase group of proteins contribute to the core of apoptotic machinery. I3C and its metabolites target a variety of components of cell-cycle control via distinct signaling pathways in light of the rapid development of tumors and oncogenesis. The translational significance of I3C and its metabolites in cancer is highlighted by their wide range of antitumor activity and low toxicity. Furthermore, the novel prodrug I3C, which has overlapping underlying mechanisms, could encourage new strategies to decrease oncogenesis.