STZ-induced gestational diabetes exposure alters PTEN/AKT/mTOR-mediated autophagy signaling pathway leading to increase the risk of neonatal hypoxic-ischemic encephalopathy.

Exposure to gestational diabetes mellitus (GDM) during pregnancy has significant consequences for the unborn baby and newborn infant. However, whether and how GDM exposure induces the development of neonatal brain hypoxia/ischemia-sensitive phenotype and the underlying molecular mechanisms remain unclear. In this study, we used a late GDM rat model induced by administration of streptozotocin (STZ) on gestational day 12 and investigated its effects of GDM on neonatal brain development.

Smoked, smokeless, and poly-tobacco use during pregnancy in relation to infant mortality in Cambodia: Findings from a nationwide sample.

Introduction: Maternal cigarette smoking during pregnancy is an established risk factor for adverse maternal, fetal, and infant outcomes. In contrast, maternal smokeless tobacco use (i.e.

In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway.

Background: In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood.

STZ-induced gestational diabetes exposure alters PTEN/AKT/mTOR-mediated autophagy signaling pathway leading to increase the risk of neonatal hypoxic-ischemic encephalopathy.

Exposure to gestational diabetes mellitus (GDM) during pregnancy has significant consequences for the unborn baby and newborn infant. However, whether and how GDM exposure induces the development of neonatal brain hypoxia/ischemia-sensitive phenotype and the underlying molecular mechanisms remain unclear. In this study, we used a late GDM rat model induced by administration of streptozotocin (STZ) on gestational day 12 and investigated its effects of GDM on neonatal brain development.

Prenatal Nicotine Exposure Raises Male Blood Pressure via FTO-Mediated NOX2/ROS Signaling.

Background: Cigarette smoking/nicotine exposure in pregnancy shows an increased risk of hypertension in offspring, but the mechanisms are unclear. This study tested the hypothesis that m6A RNA hypomethylation epigenetically regulates vascular NOX (NADPH oxidase) and reactive oxygen species production, contributing to the fetal programming of a hypertensive phenotype in nicotine-exposed offspring.

Methods: Pregnant rats were exposed to episodic chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21, and experiments were performed in 6-month-old adult offspring.

MicroRNA-210 Downregulates TET2 (Ten-Eleven Translocation Methylcytosine Dioxygenase 2) and Contributes to Neuroinflammation in Ischemic Stroke of Adult Mice.

Background: Stroke is a leading cause of morbidity and mortality worldwide. Neuroinflammation plays a key role in acute brain injury of ischemic stroke. MicroRNA-210 (miR210) is the master hypoxamir and regulates microglial activation and inflammation in a variety of diseases.

Single-nucleus chromatin accessibility and RNA sequencing reveal impaired brain development in prenatally e-cigarette exposed neonatal rats.

Although emerging evidence reveals that vaping alters the function of the central nervous system, the effects of maternal vaping on offspring brain development remain elusive. Using a well-established exposure model, we performed single-nucleus ATAC-seq (snATAC-seq) and RNA sequencing (snRNA-seq) on prenatally e-cigarette-exposed rat brains. We found that maternal vaping distorted neuronal lineage differentiation in the neonatal brain by promoting excitatory neurons and inhibiting lateral ganglionic eminence-derived inhibitory neuronal differentiation.

The Regulatory Role of H19/miR-181a/ATG5 Signaling in Perinatal Nicotine Exposure-Induced Development of Neonatal Brain Hypoxic-Ischemic Sensitive Phenotype.

Nicotine exposure either from maternal cigarette smoking or e-cigarette vaping is one of the most common risk factors for neurodevelopmental disease in offspring. Previous studies revealed that perinatal nicotine exposure programs a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE) in postnatal life, yet the underlying mechanisms remain undetermined. The goal of the present study was to determine the regulatory role of H19/miR-181a/ATG5 signaling in perinatal nicotine exposure-induced development of neonatal brain hypoxic-ischemic sensitive phenotype.

Inhibition of DNA methylation in newborns reprograms ischemia-sensitive biomarkers resulting in development of a heart ischemia-sensitive phenotype late in life.

Adverse environmental stress exposure at critical perinatal stages can alter cardiovascular development, which could persist into adulthood and develop a cardiovascular dysfunctional phenotype late in life. However, the underlying molecular mechanisms remain largely unknown. The present study provided a direct evidence that DNA methylation is a key epigenetic mechanism contributing to the developmental origins of adult cardiovascular disease.

Fetal e-cigarette exposure programs a neonatal brain hypoxic-ischemic sensitive phenotype via altering DNA methylation patterns and autophagy signaling pathway.

Maternal e-cigarette (e-cig) exposure is a pressing perinatal health concern. Emerging evidence reveals its potential adverse impacts on brain development in offspring, yet the underlying mechanisms are poorly understood. The present study tested the hypothesis that fetal e-cig exposure induces an aberrant DNA methylation profile in the developing brain, leading to alteration of autophagic flux signaling and programming of a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE).

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs.

The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020.

E-Cigarettes and Cardiopulmonary Health.

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated.

Early Detection of Coronary Artery Disease by Micro-RNA Analysis in Asymptomatic Patients Stratified by Coronary CT Angiography.

Early detection of asymptomatic coronary artery disease (CAD) is essential but underdeveloped. The aim of this study was to assess micro-RNA (miRNA) expression profiles in patients with or without CAD as selected by coronary CT angiography (CTA) and stratified by risk of CAD as determined by Framingham Risk Score (FRS). In this pilot study, patients were divided into two groups based on the presence or absence of CAD.

Reprogramming of miR-181a/DNA methylation patterns contribute to the maternal nicotine exposure-induced fetal programming of cardiac ischemia-sensitive phenotype in postnatal life.

E-cigarette and other novel electronic nicotine delivery systems (ENDS) have recently entered the market at a rapid pace. The community desperately needs answers about the health effects of ENDS. The present study tested the hypothesis that perinatal nicotine exposure (PNE) causes a gender-dependent increase in vulnerability of the heart to ischemia-reperfusion (I/R) injury and cardiac dysfunction in male rat offspring reprogramming of the miRNA-181a (miR-181a)-mediated signaling pathway and that miR-181a antisense could rescue this phenotype.

Gestational Hypoxia Inhibits Pregnancy-Induced Upregulation of Ca Sparks and Spontaneous Transient Outward Currents in Uterine Arteries Via Heightened Endoplasmic Reticulum/Oxidative Stress.

Hypoxia during pregnancy profoundly affects uterine vascular adaptation and increases the risk of pregnancy complications, including preeclampsia and fetal intrauterine growth restriction. We recently demonstrated that increases in Ca sparks and spontaneous transient outward currents (STOCs) played an essential role in pregnancy-induced uterine vascular adaptation. In the present study, we hypothesize that gestational hypoxia suppresses Ca sparks/STOCs coupling leading to increased uterine vascular tone via enhanced endoplasmic reticulum (ER)/oxidative stress.

Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy.

Aims: Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy.

Methods And Results: Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study.

Inhibition of Autophagy Signaling via 3-methyladenine Rescued Nicotine-Mediated Cardiac Pathological Effects and Heart Dysfunctions.

Cigarette smoking is a well-established risk factor for myocardial infarction and sudden cardiac death. The deleterious effects are mainly due to nicotine, but the mechanisms involved and theranostics remain unclear. Thus, we tested the hypothesis that nicotine exposure increases the heart sensitivity to ischemia/reperfusion injury and dysfunction, which can be rescued by autophagy inhibitor.

Perinatal nicotine exposure alters Akt/GSK-3β/mTOR/autophagy signaling, leading to development of hypoxic-ischemic-sensitive phenotype in rat neonatal brain.

Maternal cigarette smoking is a major perinatal insult that contributes to an increased risk of cardiovascular and neurodevelopmental diseases in offspring. Our previous studies revealed that perinatal nicotine exposure reprograms a sensitive phenotype in neonatal hypoxic-ischemic encephalopathy (HIE), yet the underlying molecular mechanisms remain largely elusive. The present study tested the hypothesis that perinatal nicotine exposure impacts autophagy signaling in the developing brain, resulting in enhanced susceptibility to neonatal HIE.

Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life.

The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model.

Impact of moderate- and high-intensity exercise on the endothelial ultrastructure and function in mesenteric arteries from hypertensive rats.

Oxidative stress (OS) influences vascular function and structure in spontaneously hypertensive rats (SHRs). It is also responsible for the decreased nitric oxide (NO) bioavailability that influences endothelial vasodilation. The effects of high-intensity exercise on endothelial function and ultrastructure in hypertension remain unknown.

Epigenetic down-regulation of BK channel by miR-181a contributes to the fetal and neonatal nicotine-mediated exaggerated coronary vascular tone in adult life.

Background: Fetal origin of adult cardiovascular disease is one of the most pressing public concerns and economic problem in modern life. Maternal cigarette smoking/nicotine abuse increases the risk of cardiovascular disease in offspring. However, the underlying mechanisms and theranostics remain unclear.

Pregnancy Increases Ca Sparks/Spontaneous Transient Outward Currents and Reduces Uterine Arterial Myogenic Tone.

Spontaneous transient outward currents (STOCs) at physiological membrane potentials of vascular smooth muscle cells fundamentally regulate vascular myogenic tone and blood flow in an organ. We hypothesize that heightened STOCs play a key role in uterine vascular adaptation to pregnancy. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep.

Paternal hyperglycemia induces transgenerational inheritance of susceptibility to hepatic steatosis in rats involving altered methylation on Pparα promoter.

Objective: Diabetes exerts adverse effects on the initiation or progression of diabetes and metabolic syndrome in the next generation. In past studies, limited attention has been given to the fathers' role in shaping the metabolic landscape of offspring. Our study was designed to investigate how paternal hyperglycemia exerts an intergenerational effect in mammals as well as the underlying mechanisms.

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice.

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice.