Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells

Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l) and high (4.5 g/l) glucose cell culture condition. Malondialdehyde (MDA) as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS) was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1) and the DNA methyltransferase 1 (DNMT1) as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.Copyright © 2018 Katja Zappe et a

MicroRNAs Responsible for Inflammation in Obesity

Background: In recent years, more and more evidence has accumulated to elucidate the modulating roles of microRNA in immune and inflammatory system. We conducted a novel positional omics integration study to identify microRNAs that could shed further light on the possible links between microRNAs, adipose tissue immunity/inflammation and obesity. Methods: In contrast to previous methodologies employed for integration of heterogeneous OMIC data, we based the integration on genomic positions of alterations in human disease and employed an additional weighing step. A data search for various types of studies on obesity (genome-wide association, meta-analysis, transcriptomic, proteomic studies and epigenetic studies) was conducted to establish the initial data set. Results and discussion: The analysis identified 19 high scoring microRNAs (miR-146, miR-378, miR-143, miR-145, miR-194, miR-1273, miR-190, miR-561, miR-151, miR-215, miR-196, miR-328, miR-208, miR-3155A, miR-933, miR-4685, miR-640, miR-4659, and miR-877). Five (miR-146, miR-378, miR-143, miR-145, and miR-194), which may be directly linked to adipose tissue inflammation or obesity-related diseases, eight other microRNAs (miR-1273, miR-190, miR-561, miR-151, miR-215, miR-196, miR-328, and miR-208) have been identified to play a role in cancer and myocardial infarction, where obesity is a defined risk factor. Conclusion: In this study, we applied a new method of positional integrational analysis of different OMIC-layers and utilized an additional validation step through weighing. Our study yields a number of plausible microRNAs that provide an interesting basis for further research to elucidate underlying mechanisms of obesity. Our detection of common microRNAs which are also related with an increased risk for inflammations, cardiovascular problems and type 2 diabetes, irrespectively of gender and age may provide a path for understanding the inherited or acquired impact of microRNAs on human health and wellbeing.© The author

The Relevance of Epigenetic Biomarkers for Breast Cancer and Obesity for Personalised Treatment in Public Healthcare: A Systematic Review

Background: Personalised medicine has gained attention as a result of the advances of genomic research in the last decade. This includes the rise in epigenetic research, which focuses on the environmental influences on the genome and examines biomarkers that might be useful for cancer therapy. This study investigates the epigenetic biomarkers for breast cancer and its risk factor, obesity, and evaluates their relevance for global public health. Methods: A systematic search of articles published from 2005 to May 2015 was performed in PubMed for epigenetic breast cancer marker. An additional literature search was carried out on the epigenetic markers of obesity. Results: The search resulted in 84 articles on breast cancer, which demonstrate the various applications of epigenetic markers for breast cancer diagnostics, prognostics and treatment. Particularly, non-invasive blood-based diagnostic biomarkers and epigenetic therapy could improve the health outcomes of cancer patients using a personalised approach. The 14 obesity-related articles highlight the epigenetic link of disease and risk factors and emphasise the relevance of nutritional influences. Conclusions: Although epigenetics offers many opportunities, new discoveries have to be confirmed first in clinical settings to ensure advantages over traditional methods. Furthermore, before personalised epigenetic therapy can be applied in public health it is crucial to ensure a fair implementation in both high and low-income settings globally