Ergothioneine improves myocardial remodeling and heart function after acute myocardial infarction via S-glutathionylation through the NF-ĸB dependent Wnt5a-sFlt-1 pathway.

Myocardial infarction (MI) remains the leading cause of cardiovascular death worldwide. Studies have shown that soluble fms-like tyrosine kinase-1 (sFlt-1) has a harmful effect on the heart after MI. However, ergothioneine (ERG) has been shown to have protective effects in rats with preeclampsia by reducing circulating levels of sFlt-1. In this study, we aimed to investigate the mechanism by which ERG protects the heart after MI in rats. Our results indicate that treatment with 10 mg/kg ERG for 7 days can improve cardiac function as determined by echocardiography. Additionally, ERG can reduce the size of the damaged area, prevent heart remodeling, fibrosis, and reduce cardiomyocyte death after MI. To explain the mechanism behind the cardioprotective effects of ERG, we conducted several experiments. We observed a significant reduction in the expression of monocyte chemoattractant protein-1 (MCP-1), p65, and p-p65 proteins in heart tissues of ERG-treated rats compared to the control group. ELISA results also showed that ERG significantly reduced plasma levels of sFlt-1. Using Glutaredoxin-1 (GLRX) and CD31 immunofluorescence, we found that GLRX was expressed in clusters in the myocardial tissue surrounding the coronary artery, and ERG can reduce the expression of GLRX caused by MI. In vitro experiments using a human coronary artery endothelial cell (HCAEC) hypoxia model confirmed that ERG can reduce the expression of sFlt-1, GLRX, and Wnt5a. These findings suggest that ERG protects the heart from MI damage by reducing s-glutathionylation through the NF-ĸB-dependent Wnt5a-sFlt-1 pathway.

Genome-wide identification and expression analysis of the bZIP transcription factor family genes in response to abiotic stress in Nicotiana tabacum L.

BACKGROUND: The basic leucine zipper (bZIP) transcription factor (TF) is one of the largest families of transcription factors (TFs). It is widely distributed and highly conserved in animals, plants, and microorganisms. Previous studies have shown that the bZIP TF family is involved in plant growth, development, and stress responses. The bZIP family has been studied in many plants; however, there is little research on the bZIP gene family in tobacco. RESULTS: In this study, 77 bZIPs were identified in tobacco and named NtbZIP01 through to NtbZIP77. These 77 genes were then divided into eleven subfamilies according to their homology with Arabidopsis thaliana. NtbZIPs were unevenly distributed across twenty-two tobacco chromosomes, and we found sixteen pairs of segmental duplication. We further studied the collinearity between these genes and related genes of six other species. Quantitative real-time polymerase chain reaction analysis identified that expression patterns of bZIPs differed, including in different organs and under various abiotic stresses. NtbZIP49 might be important in the development of flowers and fruits; NtbZIP18 might be an important regulator in abiotic stress. CONCLUSIONS: In this study, the structures and functions of the bZIP family in tobacco were systematically explored. Many bZIPs may play vital roles in the regulation of organ development, growth, and responses to abiotic stresses. This research has great significance for the functional characterisation of the tobacco bZIP family and our understanding of the bZIP family in higher plants.

Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

Objective: Randomized controlled trials (RCTs) evaluating the influence of remote ischemic preconditioning (RIPC) on acute kidney injury (AKI) after cardiac surgery showed inconsistent results. We performed a meta-analysis to evaluate the efficacy of RIPC on AKI after cardiac surgery. Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Meta-regression and subgroup analyses were used to determine the source of heterogeneity. Results: Twenty-two RCTs with 5,389 patients who received cardiac surgery -2,702 patients in the RIPC group and 2,687 patients in the control group-were included. Moderate heterogeneity was detected (p for Cochrane's Q test = 0.03, I 2 = 40%). Pooled results showed that RIPC significantly reduced the incidence of AKI compared with control [odds ratio (OR): 0.76, 95% confidence intervals (CI): 0.61-0.94, p = 0.01]. Results limited to on-pump surgery (OR: 0.78, 95% CI: 0.64-0.95, p = 0.01) or studies with acute RIPC (OR: 0.78, 95% CI: 0.63-0.97, p = 0.03) showed consistent results. Meta-regression and subgroup analyses indicated that study characteristics, including study design, country, age, gender, diabetic status, surgery type, use of propofol or volatile anesthetics, cross-clamp time, RIPC protocol, definition of AKI, and sample size did not significantly affect the outcome of AKI. Results of stratified analysis showed that RIPC significantly reduced the risk of mild-to-moderate AKI that did not require renal replacement therapy (RRT, OR: 0.76, 95% CI: 0.60-0.96, p = 0.02) but did not significantly reduce the risk of severe AKI that required RRT in patients after cardiac surgery (OR: 0.73, 95% CI: 0.50-1.07, p = 0.11). Conclusions: Current evidence supports RIPC as an effective strategy to prevent AKI after cardiac surgery, which seems to be mainly driven by the reduced mild-to-moderate AKI events that did not require RRT. Efforts are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the outcome.

Exchange proteins directly activated by cAMP mediate cardiac repolarization and arrhythmogenesis during chronic heart failure.

Most sudden cardiac death in chronic heart failure (CHF) is caused by malignant ventricular arrhythmia (VA); however, the molecular mechanism remains unclear. This study aims to explore the effect of exchange proteins directly activated by cAMP (Epac) on VA in CHF and the potential molecular mechanism. Transaortic constriction was performed to prepare CHF guinea pigs. Epac activation model was obtained with 8-pCPT administration. Programmed electrical stimulation (PES) was performed to detect effective refractory period (ERP) or induce VA. Isolated adult cardiomyocytes were treated with 8-pCPT and (or) the Epac inhibitor. Cellular electrophysiology was examined by whole-cell patch clamp. With Epac activation, corrected QT duration was lengthened by 12.6%. The 8-pCPT increased action potential duration (APD) (APD50: 236.9 ± 18.07 ms vs. 328.8 ± 11.27 ms, p < 0.05; APD90: 264.6 ± 18.22 ms vs. 388.6 ± 6.47 ms, p < 0.05) and decreased rapid delayed rectifier potassium (IKr) current (tail current density: 1.1 ± 0.08 pA/pF vs. 0.7 ± 0.03 pA/pF, p < 0.05). PES induced more malignant arrhythmias in the 8-pCPT group than in the control group (3/4 vs. 0/8, p < 0.05). The selective Epac1 inhibitor CE3F4 rescued the drop in IKr after 8-pCPT stimulation (tail current density: 0.5 ± 0.02 pA/pF vs. 0.6 ± 0.03 pA/pF, p < 0.05). In conclusion, Epac1 regulates IKr, APD, and ERP in guinea pigs, which could contribute to the proarrhythmic effect of Epac1 in CHF.

ß-Arrestin2 regulates the rapid component of delayed rectifier K+ currents and cardiac action potential of guinea pig cardiomyocytes after adrenergic stimulation.

A decrease in the rapid component of delayed rectifier potassium current (IKr) during chronic heart failure (CHF) prolongs action potential (AP), and plays a key role in the pathogenesis of ventricular arrhythmias. ß-Arrestin2 has been shown to restore the inotropic reserve of ß-adrenergic regulation, but little or nothing is known about its effect on intrinsic channel. This study investigated the role of ß-arrestin2 in the regulation of cardiac hERG/IKr potassium channel and AP during chronic adrenergic stimulation. Single left ventricular myocytes were isolated from guinea pig heart, and were transfected with adenovirus encoding ß-arrestin2, or ß-arrestin2 siRNA or an empty adenovirus. Cell cultures containing 10 nM isoproterenol, 1 nM phenylephrine or vehicle alone (control medium) were electro-physiologically examined after 48 h of incubation. Action potential duration at 50 and 90 % of repolarization (APD50 and APD90) were measured using whole-cell patch-clamp recording. Sustained adrenergic stimulation significantly reduced the density of the IKr current (p < 0.001). ß-Arrestin2 expression in cell cultures treated with isoproterenol or phenylephrine was significantly downregulated after adrenergic stimulation (p < 0.001). Overexpression of ß-arrestin2 significantly attenuated isoproterenol or phenylephrine-induced reduction in IKr current. It also prevented the phenylephrine-induced prolongation of AP (p < 0.05 for APD50 and p < 0.001 for APD90), but did not significantly affect AP profile after exposure of the cardiomyocytes to isoproterenol (p > 0.05). Therefore, Increased levels of ß-Arrestin2 weaken dysregulation of IKr current and prevent excessive AP prolongation, making it an effective anti-arrhythmic strategy.