Ferrostatin-1 improves acute sepsis-induced cardiomyopathy via inhibiting neutrophil infiltration through impaired chemokine axis.

Introduction: Sepsis-induced cardiomyopathy is a common complication of sepsis and is associated with higher mortality. To date, effective diagnostic and management strategies are still lacking. Recent studies suggest that ferroptosis plays a critical role in sepsis-induced cardiomyopathy and ferroptosis inhibitor Ferrostatin-1 (Fer-1) improved cardiac dysfunction and survival in lipopolysaccharide (LPS) induced endotoxemia.

NINJ1 regulates plasma membrane fragility under mechanical tension.

Plasma membrane integrity is vital not only for cell survival but also nearly all aspects of cell functioning1. Mechanical stress can cause plasma membrane damage2, but it is not known whether there are large molecules (proteins) that control plasma membrane integrity. Here we constructed a 384-well cellular stretch system that delivers precise, reproducible mechanical strain to adherent cells.

G protein-coupled receptor GPR68 inhibits lymphocyte infiltration and contributes to gender-dependent melanoma growth.

Introduction: Melanoma is a common and aggressive type of skin cancer with rising incidence rate globally. Gender is one of the determining factors, and overall males have a higher risk of developing melanoma as well as worse prognosis. Emerging evidence show that GPR68, a G protein-coupled receptor that is sensitive to acid and mechanical stimulations for cellular microenvironment, plays an important role in tumor biology.

Drug Discovery for Adult Cardiomyocyte Regeneration: Opportunities and Challenges.

Cardiovascular disease is a major contributor to human mortality and morbidity. The cardiac tissue undergoes fibrotic healing after injury because of the limited regenerative capacity of adult mammalian cardiomyocyte (CM). Extensive research has been performed to identify therapeutic targets for CM regeneration, as the success of promoting adult human CM regeneration to repair the injured heart is considered the Holy Grail in the field.

The epigallocatechin gallate derivative Y6 reduces the cardiotoxicity and enhances the efficacy of daunorubicin against human hepatocellular carcinoma by inhibiting carbonyl reductase 1 expression.

Ethnopharmacological Relevance: Green tea is the most ancient and popular beverage worldwide and its main constituent epigallocatechin-3-gallate (EGCG) has a potential role in the management of cancer through the modulation of cell signaling pathways. However, EGCG is frangible to oxidation and exhibits low lipid solubility and bioavailability, and we synthesized a derivative of EGCG in an attempt to overcome these limitations.

Aim Of The Study: The anthracycline antibiotic daunorubicin (DNR) is a potent anticancer agent.

The epigallocatechin gallate derivative Y inhibits human hepatocellular carcinoma by inhibiting angiogenesis in MAPK/ERK1/2 and PI3K/AKT/ HIF-1α/VEGF dependent pathways.

Ethnopharmacological Relevance: Hypervascularity has been considered as one of the major features of many solid tumors. Green tea is one of the commonly drink resources in China, and its active component, Epigallocatechin gallate (EGCG), exhibits antiangiogenic activities in various experimental tumor models. However, EGCG has many shortages, e.

GPR68 Senses Flow and Is Essential for Vascular Physiology.

Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis.

Loss of β-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice.

Cardiac fibrosis is characterized by excessive extracellular matrix deposition that contributes to compromised cardiac function and potentially heart failure. Cardiac pressure overload resulting from trans-aortic constriction in mice leads to cardiac fibrosis and increased Wnt/β-catenin signaling in cardiac fibroblasts. Here, we conditionally induce β-catenin loss of function in resident cardiac fibroblasts using Tcf21 or in activated cardiac fibroblasts using periostin (Postn) .

Effect of Y6, an epigallocatechin gallate derivative, on reversing doxorubicin drug resistance in human hepatocellular carcinoma cells.

Cancer cells can acquire resistance to a wide variety of diverse and unrelated drugs, this phenomenon is termed multidrug resistance (MDR). Multidrug resistance has been an obstacle to the success of cancer chemotherapy. The present study investigated the reversal effect of Y6, a new compound obtained by chemically modifying the structure of epigallocatechin-3-gallate (EGCG) extracted from green tea.

Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction.

Background: Adult mammalian cardiomyocytes (CMs) have the potential to proliferate, but this is not sufficient to generate adequate CMs after myocardial infarction (MI). The transcription factor Tbx20 is required for CM proliferation during development and adult CM homeostasis. The ability of Tbx20 overexpression (Tbx20(OE)) to promote adult CM proliferation and to improve cardiac function after MI was examined.

Epicardium-derived fibroblasts in heart development and disease.

The majority of cardiac fibroblasts in a mature mammalian heart are derived from the epicardium during prenatal development and reactivate developmental programs during the progression of fibrotic disease. In addition, epicardial activation, proliferation, and fibrosis occur with ischemic, but not hypertensive injury. Here we review cellular and molecular mechanisms that control epicardium-derived cell lineages during development and disease with a focus on cardiac fibroblasts.

Cardiac-specific overexpression of human stem cell factor promotes epicardial activation and arteriogenesis after myocardial infarction.

Background: The adult epicardium is a potential source of cardiac progenitors after myocardial infarction (MI). We tested the hypothesis that cardiomyocyte-specific overexpression of membrane-associated human stem cell factor (hSCF) enhances epicardial activation, epicardium-derived cells (EPDCs) production, and myocardial arteriogenesis post MI.

Methods And Results: Wild-type and the inducible cardiac-specific hSCF transgenic (hSCF/tetracycline transactivator) mice were subjected to MI.

Three-dimensional imaging of the mouse heart and vasculature using micro-CT and whole-body perfusion of iodine or phosphotungstic acid.

Recent studies have investigated histological staining compounds as micro-computed tomography (micro-CT) contrast agents, delivered by soaking tissue specimens in stain and relying on passive diffusion for agent uptake. This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels.

Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.

Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT.

Cardiomyocyte-specific overexpression of human stem cell factor protects against myocardial ischemia and reperfusion injury.

Background: Cardiomyocyte-specific overexpression of human membrane-associated stem cell factor (hSCF) improves cardiac function post-myocardial infarction. However, whether hSCF overexpression protects the heart from ischemia and reperfusion (I/R) injury is unknown. We aimed to investigate the effects of cardiomyocyte-specific overexpression of hSCF on cardiac injury after acute myocardial I/R and related cellular and molecular signaling mechanisms.

Nitric oxide synthase-3 deficiency results in hypoplastic coronary arteries and postnatal myocardial infarction.

Aims: Hypoplastic coronary artery disease is a rare congenital abnormality that is associated with sudden cardiac death. However, molecular mechanisms responsible for this disease are not clear. The aim of the present study was to assess the role of nitric oxide synthase-3 (NOS3) in the pathogenesis of hypoplastic coronary arteries.

Rapid microcomputed tomography suggests cardiac enlargement occurs during conductance catheter measurements in mice.

Conductance catheters (CC) represent an established method of determining cardiac function in mice; however, the potentially detrimental effects a catheter may have on the mouse heart have never been evaluated. The present study takes advantage of rapid three-dimensional (3D) microcomputed tomography (CT) to compare simultaneously acquired micro-CT and CC measurements of left ventricular (LV) volumes in healthy and infarcted mice and to determine changes in LV volume and function associated with CC insertion. LV volumes were measured in C57BL/6 mice (10 healthy, 10 infarcted, 2% isoflurane anesthesia) using a 1.

Combination of donor splenocyte transfusion with blockade of γc signal synergizes to inhibit alloreactive T-cell proliferation and induces apoptosis.

Background: The common γ chain (γc) plays a critical role in regulating proliferation, differentiation, and apoptosis of peripheral T-cells. It was previously confirmed that blocking the γc signal can successfully induce transplant tolerance in a murine model. Here we investigated the potential mechanism.

North American ginseng protects the heart from ischemia and reperfusion injury via upregulation of endothelial nitric oxide synthase.

Emerging evidence suggests ginseng has therapeutic potential in cardiovascular disease. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) in the cardioprotective effects of ginseng during myocardial ischemia and reperfusion (I/R). Treatment with ginseng extract significantly increased Akt phosphorylation and eNOS protein levels in cultured neonatal cardiomyocytes.

The renal stanniocalcin-1 gene is differentially regulated by hypertonicity and hypovolemia in the rat.

Stanniocalcin-1 (STC-1) is made by kidney collecting duct cells for autocrine and paracrine targeting of nephron cell mitochondria. Here, the ligand stimulates respiratory uncoupling and calcium uniport activity. However, the underlying purpose of these actions and how the renal gene is regulated are poorly understood.

NOX2 deficiency protects against streptozotocin-induced beta-cell destruction and development of diabetes in mice.

Objective: The role of NOX2-containing NADPH oxidase in the development of diabetes is not fully understood. We hypothesized that NOX2 deficiency decreases reactive oxygen species (ROS) production and immune response and protects against streptozotocin (STZ)-induced β-cell destruction and development of diabetes in mice.

Research Design And Methods: Five groups of mice--wild-type (WT), NOX2(-/-), WT treated with apocynin, and WT adoptively transferred with NOX2(-/-) or WT splenocytes--were treated with multiple-low-dose STZ.

Neuronal nitric oxide synthase protects against myocardial infarction-induced ventricular arrhythmia and mortality in mice.

Background: Neuronal nitric oxide synthase (nNOS) is expressed in cardiomyocytes and plays a role in regulating cardiac function and Ca2+ homeostasis. However, the role of nNOS in cardiac electrophysiology after myocardial infarction (MI) is unclear. We hypothesized that nNOS deficiency increases ventricular arrhythmia and mortality after MI.

Cardiomyocyte-specific overexpression of human stem cell factor improves cardiac function and survival after myocardial infarction in mice.

Background: Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overexpression of the membrane-associated isoform of human SCF (hSCF) on cardiac function after MI.

Endothelial nitric oxide synthase promotes bone marrow stromal cell migration to the ischemic myocardium via upregulation of stromal cell-derived factor-1alpha.

The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) in the host myocardium on bone marrow mesenchymal stromal cells (MSC) migration to the ischemic myocardium and whether stromal cell-derived factor-1alpha (SDF-1alpha) contributes to eNOS-mediated MSC migration. MSCs and coronary microvascular endothelial cells were isolated from adult wild-type (WT) mouse bone marrow and hearts, respectively. Cultured neonatal cardiomyocytes from WT, eNOS(-/-), and eNOS overexpressing transgenic (Tg) mice were subjected to anoxia and reoxygenation (A/R), and the conditioned medium was used as a chemoattractant for in vitro transendothelial migration assay.

Erythropoietin protects the heart from ventricular arrhythmia during ischemia and reperfusion via neuronal nitric-oxide synthase.

Erythropoietin (EPO) is a potent cardioprotective agent in models of myocardial ischemia and reperfusion (I/R). It has been suggested recently that EPO may also reduce ventricular arrhythmia after I/R. The present study investigated the role of neuronal nitric oxide synthase (nNOS) on the antiarrhythmic effects of EPO.