Flavonoids and the gastrointestinal tract: Local and systemic effects.

The gastrointestinal (GI) tract plays a central role in the absorption, distribution, metabolism, and excretion of flavonoids, which ultimately define the health effects of these bioactives. These aspects are modulated by the interactions of flavonoids with other dietary components, environmental factors, the host, and the GI microbiota. Flavonoid can target molecules in the luminal content, the different GI tract cell types, and the microbiota. Importantly, flavonoid actions at the GI tract can have an impact systemically, e.g. on glucose homeostasis, lipid and energy metabolism, or cardiovascular risk factors. The beneficial actions of flavonoids at the GI include their capacity to: i) protect the intestinal epithelium against pharmacological insults and food toxins; ii) modulate the activity of enzymes involved in lipid and carbohydrate absorption; iii) maintain the intestinal barrier integrity; iv) modulate the secretion of gut hormones; v) modulate the GI tract immune system; vi) exert potential anti-colorectal cancer activity; and vii) shape microbiota composition and function. Further understanding of the mechanisms mediating the effects of flavonoids on the intestine (and its microbiota) is of critical importance given the relevance of the GI tract on sustaining overall health and of the widespread recommendations of increasing the intake of plant bioactives.

Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common malignant tumour in young males. Although aberrant DNA methylation is implicated in the pathophysiology of many cancers, only a limited number of genes are known to be epigenetically changed in TGCT. This report documents the genome-wide analysis of differential methylation in an in vitro model culture system. Interesting genes were validated in TGCT patient samples. METHODS: In this study, we used methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to identify differentially methylated regions (DMRs). RESULTS: We identified 35 208 DMRs. However, only a small number of DMRs mapped to promoters. A genome-wide analysis of gene expression revealed a group of differentially expressed genes that were regulated by DNA methylation. We identified several candidate genes, including APOLD1, PCDH10 and RGAG1, which were dysregulated in TGCT patient samples. Surprisingly, APOLD1 had previously been mapped to the TGCT susceptibility locus at 12p13.1, suggesting that it may be important in TGCT pathogenesis. We also observed aberrant methylation in the loci of some non-coding RNAs (ncRNAs). One of the ncRNAs, hsa-mir-199a, was downregulated in TGCT patient samples, and also in our in vitro model culture system. CONCLUSION: This report is the first application of MeDIP-chip for identifying epigenetically regulated genes and ncRNAs in TGCT. We also demonstrated the function of intergenic and intronic DMRs in the regulation of ncRNAs.