Gata4

Background: Current treatment methods are not successful in restoring the lost cardiomyocytes after injury. Stem cell-based strategies have attracted much attention in this regard. Smoking, as a strong cardiovascular risk factor, not only affects the cardiac cells adversely but also deteriorates the function of stem cells. Since mesenchymal stem cells (MSCs) are one of the popular candidates in cardiovascular disease (CVD) clinical trials, we investigated the impact of nicotine on the regenerative properties (viability and cardiac differentiation) of these cells...

Heart failure is a serious medical condition with a poor prognosis. Current treatments can only help manage the symptoms and slow the progression of heart failure. However, there is currently no cure to prevent and reverse cardiac remodeling. Transcription factors are in a central role in various cellular processes, and in the heart, GATA4 and NKX2-5 transcription factors mediate hypertrophic responses and remodeling. We have identified compounds that modulate the synergistic interaction of GATA4 and NKX2-5 and shown that the most promising compound (1, 3i-1000) is cardioprotective in vitro and in vivo...

Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5 hmC) in the human brain...

ATR-X (alpha thalassemia, mental retardation, X-linked) syndrome features genital and testicular abnormalities including atypical genitalia and small testes with few seminiferous tubules. Our mouse model recapitulated the testicular defects when Atrx was deleted in Sertoli cells (Sc Atrx KO) which displayed G2/M arrest and apoptosis. Here, we investigated the mechanisms underlying these defects. In control mice, Sertoli cells contain a single novel "GATA4 PML nuclear body (NB)" that contained the transcription factor GATA4, ATRX, DAXX, HP1α, and PH3 and co-localized with the Y chromosome short arm (Yp)...

Enhanced interferon α (IFNα) production has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We previously reported IFNα production by monocytes upon activation of the stimulator of IFN genes (STING) pathway was enhanced in patients with SLE. We investigated the mechanism of enhanced IFNα production in SLE monocytes. Monocytes enriched from the peripheral blood of SLE patients and healthy controls (HC) were stimulated with 2'3'-cyclic GAMP (2'3'-cGAMP), a ligand of STING...

OBJECTIVE: To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. METHODS: Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group...

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 μg/L, 1 μg/L, and 2 μg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development...

The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F1 rats. However, the mechanism driving hypergonadotropism in F1 rats exposed to Cr(VI) prenatally remains an enigma. Therefore, we hypothesized that 'Prenatal Cr(VI) exposure may disrupt steroid hormones-mediated negative feedback regulation of the hypothalamic GnRH, and its receptor in the pituitary of F1 rats, leading to hypergonadotropism...

Direct conversion of cardiac fibroblasts (CFs) to cardiomyocytes (CMs) in vivo to regenerate heart tissue is an attractive approach. After myocardial infarction (MI), heart repair proceeds with an inflammation stage initiated by monocytes infiltration of the infarct zone establishing an immune microenvironment. However, whether and how the MI microenvironment influences the reprogramming of CFs remains unclear. Here, we found that in comparison with cardiac fibroblasts (CFs) cultured in vitro, CFs that transplanted into infarct region of MI mouse models resisted to cardiac reprogramming...

Stem cells have gained attention as a promising therapeutic approach for damaged myocardium, and there have been efforts to develop a protocol for regenerating cardiomyocytes (CMs). Certain cells have showed a greater aptitude for yielding beating CMs, such as induced pluripotent stem cells, embryonic stem cells, adipose-derived stromal vascular fraction cells and extended pluripotent stem cells. The approach for generating CMs from stem cells differs across studies, although there is evidence that Wnt signaling, chemical additives, electrical stimulation, co-culture, biomaterials and transcription factors triggers CM differentiation...

INTRODUCTION: Hyperglycemia may be a stumbling block for delivery of regenerative benefits of mesenchymal stem cells (MSCs) to diabetic patients with cardiovascular diseases. Our study aims to assess the viability and cardiac differentiation potential of MSCs after being exposed to diabetic glucose concentration. METHODS: MSCs were extracted from rat bone marrow. Cells were characterized based on morphology, differentiation potential, and expression of mesenchymal specific markers...

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis...

Familial dilated cardiomyopathy (DCM) is among the leading indications for heart transplantation. DCM alters the transcriptomic profile. The alteration or activation/silencing of physiologically operating transcripts may explain the onset and progression of this pathological state. The mediator complex (MED) plays a fundamental role in the transcription process. The aim of this study is to investigate the MED subunits, which are altered in DCM, to identify target crossroads genes. RNA sequencing allowed us to identify specific MED subunits that are altered during familial DCM, transforming into human myocardial samples...

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo...

Studies have shown that genetic factors play an important role in CHD's development. The mutations in GATA4 and CITED2 genes result in the failure of the heart to develop normally, thereby leading to septal defects. The present study investigated the underlying molecular aetiology of patients with cardiac septation defects from Xinjiang. We investigated variants of the GATA4 and CITED2 gene coding regions in 172 patients with cardiac septation defects by sequencing. Healthy controls (n = 200) were included...

CONTEXT: In the last decade Sanger method of DNA sequencing has been replaced by next generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). OBJECTIVE: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) versus 2013-2022 (NGS). METHODS: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM+c...

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10-15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4 , TBX5 , NKX2-5 , BMP4 , and CRELD1 genes in patients with syndromic and isolated CHDs...

UNLABELLED: Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community...

3-bromine carbazole (3-BCZ) represents a group of emerging aromatic disinfection byproducts (DBP) detected in drinking water; however, limited information is available regarding its potential cardiotoxicity. To assess its impacts, zebrafish embryos were exposed to 0, 0.06, 0.14, 0.29, 0.58, 1.44 or 2.88 mg/L of 3-BCZ for 120 h post fertilization (hpf). Our results revealed that ≥1.44 mg/L 3-BCZ exposure induced a higher incidence of heart malformation and an elevated pericardial area in zebrafish larvae; it also decreased the number of cardiac muscle cells and thins the walls of the ventricle and atrium while increasing cardiac output and impeding cardiac looping...

PURPOSE: The objective of this study was to clarify the phenotypic characteristics of monogenic diabetes abnormalities in Thai children with autoantibody-negative insulin. PATIENTS AND METHODS: Two hundred and thirty-one Thai type 1 diabetes (T1D) patients out of 300 participants with recent-onset diabetes were analyzed for GAD65 and IA2 pancreatic autoantibodies. A total of 30 individuals with T1D patients with negative autoantibody were screened for 32 monogenic diabetes genes by whole-exome sequencing (WES)...