Adipose-Derived Stem Cells-Derived Exosomes with High Amounts of Circ_0001747 Alleviate Hypoxia/Reoxygenation-Induced Injury in Myocardial Cells by Targeting MiR-199b-3p/MCL1 Axis.

Recent studies demonstrated that circular RNAs play important roles in exosome-mediated cardio-protective effects after acute myocardial infarction (AMI). A previous study reported that circ_0001747 level is down-regulated in mouse hypoxia/reoxygenation (H/R) injury model. However, its biological role and working mechanism in AMI remain largely unknown.Exosomes were isolated from the culture supernatant of adipose-derived stem cells (ADSCs) using an ExoQuick precipitation kit. We treated mouse myocardial cells HL-1 with H/R to explore the role of exosomal circ_0001747 in AMI pathology. Cell viability, proliferation, apoptosis, and inflammation were analyzed by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and enzyme-linked immunosorbent assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to confirm the interaction between microRNA-199b-3p (miR-199b-3p) and circ_0001747 or MCL1 apoptosis regulator, BCL2 family member (MCL1).H/R-induced HL-1 dysfunction was attenuated by the incubation of exosomes derived from ADSCs, especially the exosomes with high amounts of circ_0001747. Circ_0001747 directly targeted miR-199b-3p in HL-1 cells. miR-199b-3p overexpression partly overturned exosomal circ_0001747-mediated protective effects in H/R-induced HL-1 cells. MCL1 was a direct target of miR-199b-3p in HL-1 cells. miR-199b-3p silencing alleviated H/R-induced damage in HL-1 cells partly by up-regulating MCL1. Circ_0001747 can elevate the messenger RNA and protein levels of MCL1 by sequestering miR-199b-3p.Overall, these results indicated that ADSCs-derived exosomes with high amounts of circ_0001747 attenuated H/R-induced HL-1 dysfunction partly by targeting miR-199b-3p/MCL1 signaling.

Associations between cold spells of different time types and coronary heart disease severity.

Limited evidence showed the association between cold spells and the severity of coronary heart disease (CHD). This study was to investigate the association between cold spells with their different time types and CHD severity. We collected data on CHD patients admitted to the Zhongnan Hospital, Wuhan, China from 2016 to 2021. CHD severity was quantified using the SYNTAX score and transformed into a binomial variable. Daily mean, maximum and minimum temperature were collected during the study period. We first used daily mean temperature to find the optimum definition among multiple thresholds and durations. The daily maximum and minimum temperatures were used to define different types of cold spells (daytime, nighttime and compound) based on the optimum definition. Annual cold spell days were included to assess individual exposure to cold spells. Logistic regression models were performed to fit the association between cold spell days and CHD severity stratified by different tertiles of PM2.5 and NDVI. In this study, 1937 CHD patients were included. The cold spell defined as at least four consecutive days with daily mean temperature below the 5th percentile exhibited the optimum model. We found that a 4-day increase in cold spell days was associated with more severe CHD (OR = 1.170, 95% CI: 1.074, 1.282). Such an association was more pronounced under higher levels of PM2.5 by OR = 1.270 (1.086, 1.494) and lower levels of greenness by OR = 1.240 (1.044, 1.476). Compared with daytime and compound cold spells, nighttime cold spells showed the strongest association with CHD severity by OR = 1.141 (1.026, 1.269). This study showed that exposure to cold spells was positively associated with CHD severity, especially the nighttime cold spells. The association between cold spells and CHD severity was more significant in high levels of PM2.5 and low levels of greenness.

DNA sensors to assess the effect of VKORC1 and CYP2C9 gene polymorphisms on warfarin dose requirement in Chinese patients with atrial fibrillation.

The optimal dose of warfarin depends on polymorphisms in the VKORC1 (the vitamin K epoxide reductase complex subunit (1) and CYP2C9 (cytochrome P450 2C9) genes. To minimize the risk of adverse reactions, warfarin dosages should be adjusted according to results from rapid and simple monitoring methods. However, there are few pharmacogenetic-guided warfarin dosing algorithms that are based on large cohorts from the Chinese population, especially patients with atrial fibrillation. This study aimed to validate a pharmacogenetic-guided warfarin dosing algorithm based on results from a new rapid electrochemical detection method used in a multicenter study. Three SNPs (CYP2C9 *2, *3 and VKORC1 c.-1639G > A) were genotyped by electrochemical detection using a sandwich-type format that included a 3' short thiol capture probe and a 5' ferrocene-labeled signal probe. A total of 1285 samples from four clinical hospitals were evaluated. Concordance rates between the results from the electrochemical DNA biosensor and the sequencing test were 99.8%. The results for gene distribution showed that most Chinese patients had higher warfarin susceptibility because mutant-type and heterozygotes were present in the majority of subjects (99.4%) at locus c.-1639G > A. When the International Warfarin Pharmacogenetics Consortium algorithm was used to estimate therapeutic dosages for 362 patients with AF and the values were compared with their actual dosages, the results revealed that 56.9% were similar to actual dosages (within the 20% range). A novel electrochemical detection method of CYP2C9 *2, *3and VKORC1 c.-1639G > A alleles was evaluated. The warfarin dosing algorithm based on data gathered from a large patient cohort can facilitate the reasonable and effective use of warfarin in Chinese patients with AF.