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Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (KATP) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of KATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the KATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein–protein interactions, Kir6.2 function, and case-control studies. [ABSTRACT FROM AUTHOR]

Hepatic antioxidant enzymes as oxidative stress biomarkers were investigated and correlated with the identified dominant gut microbial phyla. The results showed that while the antioxidant enzymes, Superoxide Dismutase (SOD), and Catalase (CAT) levels were reduced in the polluted PO site, significant elevation (*P ≥ 0.05) was observed at the clean reference CR site indicating negative correlation to pollution stress. On the other hand, among five significant bacterial genera, Lactobacillus and Vagococcus showed a positive relationship to the oxidative pollution stress between PO and CR sites. Diversity and bacterial richness had been observed in the PO site compared to the CR site. As a result, 429,346 sequences were obtained from the pooling of 20 samples identified into 10 phyla and 79 genera in which Firmicutes was dominant in both PO and CR sites. The number of common OTUs was 221 for both CR and PO samples. The results revealed that under the stressed environmental state, the homo-lactic Vagococcus genus is dominant over the hetero-lactic Lactobacillus, which uses less energy in the derived process. [ABSTRACT FROM AUTHOR]