ABSTRACT
Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10-4), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10-4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.
ABSTRACT
Myocardial infarction, one of the main factors that threatens human health, leads to cardiac cell death. Myocardial cells suffer ischemia and hypoxia for a long period of time, which can lead to irreversible cell death or apoptosis and cardiac dysfunction. MicroRNAs (miRs) have been reported to play an important role in a wide range of biological processes in cardiac myocytes, which respond to inflammation and oxidative stress. The aim of the present study was to investigate the effect of miR-370 on oxidative stress and apoptosis of cardiac myocytes in ischemic H9C2 cells induced by hydrogen peroxide (H2O2). H9C2 cells were cultured and treated with different concentrations of H2O2 solution. Then, cells were transfected with miR-370 mimic or negative control (NC) mimic, small interfering (si)-RNA-Forkhead box O1 (FOXO1) and NC siRNA. A Cell Counting Kit-8 and flow cytometry assay were conducted to detect cell viability and cell apoptosis. The expression of oxidative stress associated factors were detected by ELISA. The levels of miR-370 and FOXO1 were examined using western blotting and reverse transcription-quantitative PCR. A luciferase reporter gene assay was performed to verify whether FOXO1 was a target gene of miR-370. The results revealed that miR-370 expression was downregulated and FOXO1 expression was increased in H9C2 cells induced by H2O2. Additionally, FOXO1 was proven to be a target of miR-370. The ELISA and flow cytometry assay revealed that miR-370 overexpression and FOXO1 silencing reversed H2O2-induced oxidative stress and apoptosis. The results indicated that miR-370 could inhibit the oxidative stress and apoptosis of H9C2 cells induced by H2O2 by targeting FOXO1. Therefore, miR-370 may be a new therapeutic target for ischemic heart disease.
