Context Ferroptosis was described as an important contributor to the myocardial ischaemia/reperfusion (MIR) injury, and britanin (Bri) was reported to exert antitumor and anti-inflammatory activities. Objective Our study explores the effect and mechanism of Bri on MIR damage. Materials and methods The rat model of MIR was established by ligation of the left anterior descending coronary artery. Male Sprague–Dawley (SD) rats were divided into three groups: sham group ( n = 6), MIR group ( n = 6) and MIR + Bri group ( n = 6; 50 mg/kg). Rats were intragastrically pre-treated with Bri or normal saline once daily for 3 days. To further verify the role and mechanism of Bri, H9C2 cells were subjected to hypoxia plus reoxygenation (H/R) to induce the in vitro model of MIR. Results Compared with MIR rats, Bri significantly decreased infarct area (22.50% vs. 38.67%), myocardial apoptosis (23.00% vs. 41.5%), creatine phosphokinase (0.57 U/mL vs. 0.76 U/mL), and lactate dehydrogenase levels (3.18 U/mL vs. 5.17 U/mL), concomitant with alleviation of ferroptosis. Mechanistically, Bri treatment induced the activation of the adenosine monophosphate activated protein kinase (AMPK)/glycogen synthase kinase 3β (GSK3β)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in vivo . In addition, the AMPK/GSK3β/Nrf2 pathway participated in the regulation of glutathione peroxidase 4 (GPX4) expression, and silencing of Nrf2 attenuated the effect of Bri on H/R-induced cell injury. Discussion and conclusions Bri protected against ferroptosis-mediated MIR damage by upregulating GPX4 through activation of the AMPK/GSK3β/Nrf2 signalling, suggesting that Bri might become a novel therapeutic agent for MIR.
Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown.Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin’s efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3.5 Software and STATA version 15.1 Software.Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04–0.66), patient thrombosis (I2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37–0.93), in-circuit thrombosis/interventions (I2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24–0.68), and in-hospital mortality (I2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46–0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46–1.62), 30-day mortality (I2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41–1.68), and ECMO duration in adults (I2 = 41%, p = 0.75, mean difference (MD) = −3.19, 95% CI: −23.01–16.63) and children (I2 = 76%, p = 0.65, MD = 40.33, 95% CI:−135.45–216.12).Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.
Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.
Purpose: Myocardial contraction fraction (MCF) of cardiac magnetic resonance (CMR) was used to evaluate myocardial function in patients with hypertrophic cardiomyopathy (HCM), which may represent a proxy marker of disease severity in HCM. Materials and Methods: A total of 60 HCM patients and 20 healthy controls were examined with CMR. MCF was calculated by dividing left ventricular stroke volume by left ventricular myocardial volume. The difference in MCF between late gadolinium enhancement (LGE)-positive and LGE-negative patients were compared. The differences in MCF were compared among patients with stages Ⅱ, Ⅲ, and Ⅳ of HCM. Logistic regression analysis was used to detect independent discriminants of more severe HCM. Receiver operating characteristic analysis differentiated HCM with different clinical stages. Results: Compared with controls (110.67±20.40%, P<0.001), values for MCF were significantly reduced in HCM (61.40±15.60%). The MCF reduction in LGE detected by CMR was more significant than in HCM patients without LGE (53.15±10.67% vs. 76.72±11.04%, P<0.001). Patients with stage IV of HCM had the lowest MCF (45.36±10.97%, P<0.05 vs. stage II and III). Lower MCF remains an independent discriminator for more severe HCM (Stage Ⅱ vs. Stage Ⅲ, odds ratio: 0.85; Stage Ⅲ vs. Stage Ⅳ, odds ratio: 0.88, all P<0.05). The optimal cutoff value for detecting more severe HCM is MCF under 66.40% (Stage Ⅱ vs. Stage Ⅲ, P<0.05) and 44.75% (Stage Ⅲ vs. Stage Ⅳ, P<0.05). Conclusion: MCF may be a useful and simple tool to evaluate myocardial function in patients with HCM and provide an indicator of disease severity in individuals with HCM.
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