The Kv4 potassium channel modulator NS5806 attenuates cardiac hypertrophy in vivo and in vitro.

The compound NS5806 is a Kv4 channel modulator. This study investigated the chronic effects of NS5806 on cardiac hypertrophy induced by transverse aortic constriction (TAC) in mice in vivo and on neonatal rat ventricular cardiomyocyte hypertrophy induced by endothelin-1 (ET-1) in vitro. Four weeks after TAC, NS5806 was administered by gavage for 4 weeks.

Phosphoproteomics reveals a novel mechanism underlying the proarrhythmic effects of nilotinib, vandetanib, and mobocertinib.

The use of tyrosine kinase inhibitors (TKIs) has resulted in significant occurrence of arrhythmias. However, the precise mechanism of the proarrhythmic effect is not fully understood. In this study, we found that nilotinib (NIL), vandetanib (VAN), and mobocertinib (MOB) induced the development of "cellrhythmia" (arrhythmia-like events) in a concentration-dependent manner in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Transcriptomics coupled with proteomics reveals osimertinib-induced myocardial mitochondrial dysfunction.

Osimertinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for cancer treatment, can cause significant cardiac toxicity. However, the specific mechanism of osimertinib-induced cardiotoxicity is not fully understood. In this study, we administered osimertinib to mice and neonatal rat ventricular myocytes (NRVMs).

Healing of the Torn Anterior Horn of Rabbit Medial Meniscus to Bone after Transtibial Pull-Out Repair and Autologous Platelet-Rich Plasma Gel Injection.

Objectives: The transtibial pull-out repair (TP) is a relatively new method for treating meniscal root tear; however, the clinical evaluation of its healing effect remains controversial. Due to ethical constraints and limitations of imaging techniques in humans, here we dynamically observe the healing effects of TP and TP with platelet-rich plasma gel (PRG) at the histological level using an animal model.

Methods: Platelet-rich plasma (PRP) and PRG of rabbits were prepared.

Pharmacological suppression of Nedd4-2 rescues the reduction of Kv11.1 channels in pathological cardiac hypertrophy.

The human gene (hERG) encodes the pore-forming subunit (Kv11.1), conducting a rapidly delayed rectifier K current ( ). Reduction of in pathological cardiac hypertrophy (pCH) contributes to increased susceptibility to arrhythmias.

Downregulation of hERG channel expression by tyrosine kinase inhibitors nilotinib and vandetanib predominantly contributes to arrhythmogenesis.

Cardiotoxicity by tyrosine kinase inhibitors remains an important concern. Nilotinib and vandetanib clinically carry high proarrhythmic risk and the exact mechanism underlying arrhythmogenesis is not fully understood. In this study, we investigated the effects of nilotinib and vandetanib on the abundance of human ether-á-go-go-related gene (hERG) K channel and assessed the potential role of acute hERG blockage versus chronic effects in arrhythmogenesis.

Inhibitory G-protein-mediated modulation of slow delayed rectifier potassium channels contributes to increased susceptibility to arrhythmogenesis in aging heart.

Background: Slow delayed rectifier potassium current (I) is an important component of repolarization reserve during sympathetic nerve excitement. However, little is known about age-related functional changes of I and its involvement in age-dependent arrhythmogenesis.

Objective: The purpose of this study was to investigate age-related alteration of the I response to β-adrenergic receptor (βAR) activation.

Auxiliary subunits control biophysical properties and response to compound NS5806 of the Kv4 potassium channel complex.

Kv4 pore-forming subunits co-assemble with β-subunits including KChIP2 and DPP6 and the resultant complexes conduct cardiac transient outward K current (I). Compound NS5806 has been shown to potentate I in canine cardiomyocytes; however, its effects on I in other species yet to be determined. We found that NS5806 inhibited native I in a concentration-dependent manner (0.

Transcriptome analysis reveals new microRNAs-mediated pathway involved in anther development in male sterile wheat.

Background: 337S is a novel bi-pole-photo-thermo-sensitive genic male sterile line in wheat, and sensitive to both long day length/high temperature and short day length/low temperature condition. Although the regulatory function of MicroRNAs (miRNAs) in reproductive development has been increasingly studied, their roles in pre-meiotic and meiotic cells formation of plants have not been clearly explored. Here, we explored the roles of miRNAs in regulating male sterility of 337S at short day length/low temperature condition.

Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension: A Meta-analysis of Randomized Controlled Trials.

Background: Previous meta-analyses of pulmonary arterial hypertension (PAH)-specific therapy for PAH pooled PAH-specific combination therapy and monotherapy. This flaw may threaten the authenticity of their findings.

Methods: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials that evaluated any PAH-specific medications in the treatment of PAH.

Combinations of Histone Modifications for Pattern Genes.

Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories (four kinds of pattern genes and non-pattern genes) in coding regions.

[Role of calcineurin in down-regulation of left ventricular transmural voltage- dependent K(+) currents in mice with heart failure].

The aim of the present study was to investigate the role of calcineurin in the down-regulation of left ventricular transmural voltage-dependent K(+) currents in heart failure. Transverse aorta was banded by using microsurgical techniques to create mouse heart failure model. Sham-operated (Sham) or aorta banded (Band) mice were randomized to receive calcineurin inhibitor cyclosporine A (CsA) or vehicle.

Compound ICA-105574 prevents arrhythmias induced by cardiac delayed repolarization.

Impaired ventricular repolarization can lead to long QT syndrome (LQT), a proarrhythmic disease with high risk of developing lethal ventricular tachyarrhythmias. The compound ICA-105574 is a recently developed hERG activator and it enhances IKr current with very high potency by removing the channel inactivation. The present study was designed to investigate antiarrhythmic properties of ICA-105574.

[Effect of increased posterior tibial slope or partial posterior cruciate ligament release on knee kinematics of total knee arthroplasty].

Objective: To compare the effects of increased posterior tibial slope or partial posterior cruciate ligament (PCL) release on knee kinematics of total knee arthroplasty (TKA).

Methods: Anteroposterior laxity, rotational laxity, varus and valgus laxity and maximum flexion angle were evaluated in 6 normal cadaver knees and the knees after TKA at flexion 0 degrees , 30 degrees , 60 degrees , 90 degrees and 120 degrees . Then the femoral prosthesis was shifted 5 mm posteriorly to simulate the tightly implanted knee.

[Transmural L-type calcium current in a pressure-overloaded mouse model with heart failure].

Transmural electrical heterogeneity plays an important role in the normal dispersion of repolarizaion and propagation of excitation in the heart. The amplification of transmural electrical heterogeneity contributes to the genesis of arrhythmias in cardiac hypertrophy and failure. We established a mouse model with cardiac failure by aortic banding and investigated the possible contribution of L-type calcium current (I(Ca-L)) to transmural electrical heterogeneity in both normal and failing hearts.

Electrophysiologic effects of adenosine triphosphate on rabbit sinoatrial node pacemaker cells via P1 receptors.

Aim: To study the electrophysiologic effects of adenosine triphosphate (ATP) on rabbit sinoatrial node pacemaker cells and the receptors related with the action of ATP.

Methods: Intracellular microelectrode method was used to record the parameters of action potential (AP) in the rabbit sinoatrial nodes.

Results: ATP (0.