miR-146a-5p/TXNIP axis attenuates intestinal ischemia-reperfusion injury by inhibiting autophagy via the PRKAA/mTOR signaling pathway.

Autophagy is being increasingly recognized as an important regulator of intestinal ischemia-reperfusion(I/R)injury, but its exact role is still debated. Emerging evidence suggests that miR-146a-5p is involved in the initiation and development of I/R injury, but its role in intestinal I/R injury remains unclear. The present study generated an intestinal I/R mouse model and an oxygen glucose deprivation/reoxygenation (OGD/R) Caco-2 cell model and found that autophagy was increased and contributed to the intestinal injury and cell death induced by I/R and OGD/R. In addition, in both I/R and OGD/R models, the miR-146a-5p expression level was decreased and accompanied by an increase in TXNIP expression. By transfecting cells with an miR-146a-5p inhibitor or mimic, we observed that miR-146a-5p inhibits autophagy during OGD/R by targeting TXNIP; this was confirmed by the dual luciferase reporter gene assay. Additionally, through overexpression and knockdown cell lines, we established that TXNIP regulates autophagy during intestinal I/R via the PRKAA/mTOR pathway. The interaction between TXNIP and p-PRKAA was verified by immunofluorescence co-localization and immunoprecipitation assays. Moreover, we confirmed that TXNIP is indispensable for miR-146a-5p-mediated cell protection. Finally, we observed that miR-146a-5p overexpression inhibits autophagy and attenuates intestinal I/R injury via the PRKAA/mTOR pathway by targeting TXNIP in vivo. In conclusion, this study highlights the role of miR-146a-5p in regulating autophagy by targeting TXNIP, suggesting that miR-146a-5p may be a novel drug target for intestinal I/R therapy.

Comparison of One-Year Survival After Acute Coronary Syndrome in Patients ≥75 Years of Age With Versus Without Living With Spouse.

Patients with acute coronary syndrome (ACS) face high postevent mortality. This study aims to evaluate the impact of living without spouse on 1-year mortality of ACS patients. This retrospective study enrolled a total of 600 consecutive patients (≥75 years of age) with ACS hospitalized in our hospital between January 2013 and December 2016. Patients' clinical characteristics, laboratory values, hospital course, demographic characteristics, and angiographic data were collected. Patients were divided into 2 groups according to living with (n = 396) or without (n = 204) spouse. Patients living without spouse were older (79 [77,82] vs 77 [76,80], p <0.001), more frequently female (54.9% vs 31.8%, p <0.001), less smokers (23.5% vs 38.9%, p <0.001), lower left ventricular ejection fraction value (52.1±10.7% vs 54.4±9.8%, p = 0.021) compared with patients living with spouse. In addition, compared to patients living with spouse, patients living without spouse were less likely to get percutaneous coronary intervention (41.2% vs 54.0%, p = 0.003) during hospitalization and had higher 1-year mortality post-ACS (22.1% vs 13.4%, p = 0.006). Multivariate logistic regression analysis showed that living without spouse remained an independent risk factor for 1-year mortality after ACS in patients ≥75 years (odds ratio 2.350, 95% confidence interval 1.245 to 4.434, p = 0.008), after adjusted with age, gender, heart rate, systolic blood pressure, left ventricular ejection fraction value at baseline, hemoglobin, white blood cell, alanine aminotransferase, albumin, creatinine, brain natriuretic peptide, type of ACS, severe heart failure at admission, percutaneous coronary intervention treatment, ß blocker, diuretics application during hospital. In conclusion, living without spouse is an independent risk factor for 1-year all-cause mortality in ACS patients ≥75 years.

Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B 12 intakes.

We assessed the association between dietary intake of folate and the MTHFR genotype with breast cancer in a Chinese population, with additional analysis of the interactions of gene polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12. A case-control study was performed, and 535 patients with newly diagnosed breast cancer and 673 controls were enrolled into this study. The MTHFR 667TT genotype (odds ratio (OR) = 1.82, 95 % confidence interval (CI) = 1.24-2.97) and T allele (OR 0= 1.48, 95 % CI = 1.15-1.78) were correlated with a moderately significant increased risk of breast cancer when compared with the CC genotype. Individuals carrying the MTR 2756GG genotype (OR = 1.66, 95 % CI = 1.16-2.56) and G allele (OR = 1.42, 95 % CI = 1.26-1.81) had a higher risk of breast cancer when compared with subjects with the AA genotype. The MTHFR 667 T allele and MTR 2756 G allele were associated with a higher risk of breast cancer in individuals with low folate intake, vitamin B6, and vitamin B12, but the association disappeared among subjects with moderate and high intake of folate, vitamin B6, and vitamin B12. This case-control study found that the MTHFR C677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B6, and vitamin B12 intakes influence these associations.