Identification and Functional Investigation of as a Novel Gene Underpinning Familial Atrial Fibrillation.

Atrial fibrillation (AF) signifies the most prevalent supraventricular arrhythmia in humans and may lead to cerebral stroke, cardiac failure, and even premature demise. Aggregating strong evidence points to genetic components as a cornerstone in the etiopathogenesis of familial AF. However, the genetic determinants for AF in most patients remain elusive.

Discovery of as a new gene underpinning congenital heart defects.

Objective: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in -knockout animals. The objective of this retrospective study was to identify a new mutation responsible for CHD and characterize the functional effect of the identified CHD-causing mutation.

Somatic mutation contributes to tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital heart pathology and causes infant morbidity and mortality worldwide. GATA-binding protein 4 (GATA4) serves as a pivotal transcriptional factor for embryonic cardiogenesis and germline mutations are causally linked to TOF. However, the effects of somatic mutations on the pathogenesis of TOF remain to be ascertained.

Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.

Type 2 diabetes mellitus (T2DM) patients exhibit greater susceptibility to vascular calcification (VC), which has a higher risk of death and disability. However, there is no specific drug for VC therapy. NLRP3 inflammasome activation as a hallmark event of medial calcification leads to arterial stiffness, causing vasoconstrictive dysfunction in T2DM.

Discovery of as a Novel Gene Underlying Atrial Fibrillation.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite.

Discovery of (Cx45) as a New Gene Underlying Congenital Heart Disease and Arrhythmias.

As the most prevalent type of birth malformation, congenital heart disease (CHD) gives rise to substantial mortality and morbidity as well as a socioeconomic burden. Although aggregating investigations highlight the genetic basis for CHD, the genetic determinants underpinning CHD remain largely obscure. In this research, a Chinese family suffering from autosomal dominant CHD (atrial septal defect) and arrhythmias was enrolled.

Increased gestational palmitic acid predisposes offspring to congenital heart disease.

Identification of the causes for congenital heart disease (CHD) is a prerequisite for precise prevention and personalized treatment of CHD. Zhao et al. show increased that gestational serum palmitic acid (PA) predisposes offspring to CHD by perturbating the MARS/K-Hcy/GATA4 signaling pathway.

A novel GJA5 variant associated with increased risk of essential hypertension.

Objectives: Gap junction protein alpha 5 (GJA5), also termed connexin 40 (Cx40), exerts a pivotal role in the mediation of vascular wall tone and two closely-linked polymorphisms in the promoter (-44G>A and +71A>G) have been associated with enhanced susceptibility to essential hypertension (EH) in men. The present investigation aimed to ascertain whether a novel common polymorphism within the upstream regulatory region of (transcript 1B), -26A>G (rs10465885), confers an increased risk of EH.

Methods: For this investigation, 380 unrelated patients with EH and 396 unrelated normotensive individuals employed as control persons were enrolled from the Chinese Han-ethnicity population, and their genotypes and plasma renin concentrations were determined by Sanger sequencing and an automated chemiluminescent immunoassay, respectively.

mA demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3.

The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (mA) plays an essential role in numerous biological processes. However, the roles of mA and mA demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear.

VEZF1 loss-of-function mutation underlying familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM), characteristic of left ventricular or biventricular dilation with systolic dysfunction, is the most common form of cardiomyopathy, and a leading cause of heart failure and sudden cardiac death. Aggregating evidence highlights the underlying genetic basis of DCM, and mutations in over 100 genes have been causally linked to DCM. Nevertheless, due to pronounced genetic heterogeneity, the genetic defects underpinning DCM in most cases remain obscure.

SMAD4 loss-of-function mutation predisposes to congenital heart disease.

Congenital heart disease (CHD) represents the most frequent developmental deformity in human beings and accounts for substantial morbidity and mortality worldwide. Accumulating investigations underscore the strong inherited basis of CHD, and pathogenic variations in >100 genes have been related to CHD. Nevertheless, the heritable defects underpinning CHD remain elusive in most cases, mainly because of the pronounced genetic heterogeneity.

KLF13 Loss-of-Function Mutations Underlying Familial Dilated Cardiomyopathy.

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases.

Atrial Fibrillation: Focus on Myocardial Connexins and Gap Junctions.

Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia worldwide and contributes to substantial morbidity, mortality and socioeconomic burden. Aggregating evidence highlights the strong genetic basis of AF. In addition to chromosomal abnormalities, pathogenic mutations in over 50 genes have been causally linked to AF, of which the majority encode ion channels, cardiac structural proteins, transcription factors and gap junction channels.

SOX7 loss-of-function variation as a cause of familial congenital heart disease.

Introduction: As the most frequent type of birth defect in humans, congenital heart disease (CHD) leads to a large amount of morbidity and mortality as well as a tremendous socioeconomic burden. Accumulating studies have convincingly substantiated the pivotal roles of genetic defects in the occurrence of familial CHD, and deleterious variations in a great number of genes have been reported to cause various types of CHD. However, owing to pronounced genetic heterogeneity, the hereditary components underpinning CHD remain obscure in most cases.

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus.

Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood.

A novel mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve.

Recently, mutations in the Kruppel-like factor 13 () gene encoding a Kruppel-like transcription factor have been reported to cause congenital heart disease (CHD). However, due to pronounced genetic heterogeneity, the mutational spectrum of in other cohorts of cases suffering from distinct types of CHD remain to be ascertained. In the present investigation, by Sanger sequencing of in 316 unrelated cases affected by different forms of CHD, a new mutation in heterozygous status, NM_015995.

SMAD1 Loss-of-Function Variant Responsible for Congenital Heart Disease.

As the most common form of developmental malformation affecting the heart and endothoracic great vessels, congenital heart disease (CHD) confers substantial morbidity and mortality as well as socioeconomic burden on humans globally. Aggregating convincing evidence highlights the genetic origin of CHD, and damaging variations in over 100 genes have been implicated with CHD. Nevertheless, the genetic basis underpinning CHD remains largely elusive.

PRRX1 Loss-of-Function Mutations Underlying Familial Atrial Fibrillation.

Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive.

Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells.

The tumor suppressor p53 is usually inactivated by somatic mutations in malignant neoplasms, and its reactivation represents an attractive therapeutic strategy for cancers. Here, we reported that a new quinolone compound RYL-687 significantly inhibited non-small cell lung cancer (NSCLC) cells which express wild type (wt) p53, in contract to its much weaker cytotoxicity on cells with mutant p53. RYL-687 upregulated p53 in cells with wt but not mutant p53, and ectopic expression of wt p53 significantly enhanced the anti-NSCLC activity of this compound.

SOX17 Loss-of-Function Mutation Underlying Familial Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) refers to a rare, progressive disorder that is characterized by occlusive pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure, right-sided heart failure, and eventual death. Emerging evidence from genetic investigations of pediatric-onset PAH highlights the strong genetic basis underpinning PAH, and deleterious variants in multiple genes have been found to cause PAH. Nevertheless, PAH is of substantial genetic heterogeneity, and the genetic defects underlying PAH in the overwhelming majority of cases remain elusive.

KLF15 Loss-of-Function Mutation Underlying Atrial Fibrillation as well as Ventricular Arrhythmias and Cardiomyopathy.

Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia and substantially increases the risks of cerebral stroke, heart failure and death. Accumulating evidence has convincingly demonstrated the strong genetic basis of AF, and an increasing number of pathogenic variations in over 50 genes have been causally linked to AF. Nevertheless, AF is of pronounced genetic heterogeneity, and the genetic determinants underpinning AF in most patients remain obscure.

SOX17 loss-of-function variation underlying familial congenital heart disease.

As the most prevalent form of human birth defect, congenital heart disease (CHD) contributes to substantial morbidity, mortality and socioeconomic burden worldwide. Aggregating evidence has convincingly demonstrated that genetic defects exert a pivotal role in the pathogenesis of CHD, and causative mutations in multiple genes have been causally linked to CHD. Nevertheless, CHD is of pronounced genetic heterogeneity, and the genetic components underpinning CHD in the overwhelming majority of patients remain obscure.