Gene regulatory network reveals oxidative stress as the underlying molecular mechanism of type 2 diabetes and hypertension

<p>Abstract</p> <p>Background</p> <p>The prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.</p> <p>Methods</p> <p>The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.</p> <p>Results</p> <p>By analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.</p> <p>Conclusion</p> <p>The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.</p

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Effect of deep Southwestern Subtropical Atlantic Ocean circulation on the biogeochemistry of mercury during the last two glacial/interglacial cycles

During glacial/interglacial cycles, changes in the strength of the Atlantic Meridional Overturning Circulation (AMOC) modified the intermediate and deep-water mass proportions and high latitude productivity in the Atlantic Ocean. These factors influence the distribution and geochemical partitioning of trace metals in the ocean. Mercury is a redox and productivity-sensitive trace metal, making it a potential proxy of paleoenvironmental changes. Therefore, this work examines the effect of Atlantic Ocean circulation changes during the last two glacial/interglacial cycles on the biogeochemistry of Hg. For this, a high-resolution record of the total Hg concentration was determined in core GL-1090 collected from the Southwestern Subtropical Atlantic that represents the last 185 thousand years. During the reported glacial/interglacial cycles, Hg showed a distinct trend throughout Marine Isotope Stages with higher concentrations during periods of enhanced penetration of northern component water into the southwestern Atlantic. This is supported by the similarity of mercury variability with benthic foraminifera δ13C, suggesting a strong influence of deep ocean circulation on the availability and accumulation of this metal in deep-sea sediments. Mercury geochemistry and particle scavenging were correlated with organic matter (OM) input at the core site. We also noted that mercury responded to redox variation in sediment after Termination II, which can be explained by the increase in deep ocean ventilation due to AMOC strengthening. This hypothesis was confirmed by the antiphase behavior of Hg and Total Organic Carbon when compared with Mn/Al ratios and CaCO3. Our work, therefore, allows for a better understanding of the processes leading to long-term mercury removal to sediments