A5008126022- RNA modifications and cancer
- RNA Research and Splicing
- Diabetes Treatment and Management
- Cardiac Fibrosis and Remodeling
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Cardiomyopathy and Myosin Studies
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Congenital heart defects research
- Diet and metabolism studies
- SARS-CoV-2 and COVID-19 Research
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Epigenetics and DNA Methylation
- Neuropeptides and Animal Physiology
- Adipokines, Inflammation, and Metabolic Diseases
- Medical Malpractice and Liability Issues
- Cardiac Ischemia and Reperfusion
University of Colorado Anschutz Medical Campus
2020-2024
University Hospitals of Derby and Burton NHS Foundation Trust
2024
Royal Derby Hospital
2024
Emory University Hospital
2024
Maastricht University
2018-2023
University of New Brunswick
2022-2023
Royal College of Physicians
2020-2023
University of Birmingham
2014-2023
Thomas Jefferson University
2023
University of Colorado Denver
2021-2022
Interstitial fibrosis is an important component of diastolic, and systolic, dysfunction in heart failure (HF) depends on activation differentiation fibroblasts into myofibroblasts (MyoFb). Recent clinical evidence suggests that late-stage HF, not reversible. The study aims to examine the degree cardiac MyoFb end-stage HF potential for their phenotypic reversibility. Fibroblasts were isolated from left ventricle explanted hearts transplant recipients (ischemic dilated cardiomyopathy), nonused...
Doxorubicin is a highly effective cancer treatment whose use severely limited by dose-dependent cardiotoxicity. It well established that doxorubicin increases reactive oxygen species (ROS) production. In this study, we investigated contributions to cardiotoxicity from Nox2 NADPH oxidase, an important ROS source in cardiac cells, which known modulate several key processes underlying the myocardial response injury. Nox2-deficient mice (Nox2-/-) and wild-type (WT) controls were injected with...
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function often a precursor heart failure. In contrast, physiologically induced hypertrophy adaptive, resulting improved function. The processes that selectively induce these states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 H3K27me3, which involved stable cellular differentiation, specifically cardiomyocytes from...
Pharmacological inhibition of AQP1 prevents H 2 O transport and hypertrophy cardiac myocytes.
In addition to its' established metabolic and cardioprotective effects, glucagon-like peptide-1 (GLP-1) reduces post-infarction heart failure via preferential actions on the extracellular matrix (ECM). Here, we investigated whether GLP-1 mimetic, exendin-4, modulates cardiac remodelling in experimental diabetes by specifically targeting inflammatory/ECM pathways, which are characteristically dysregulated this setting. Adult mice were subjected streptozotocin (STZ) infused with...
Glucagon-like peptide-1 (GLP-1) is an insulin-releasing hormone clinically exploited for glycaemic control in diabetes, which also confers acute cardioprotection and benefits experimental/clinical heart failure. We specifically investigated the role of GLP-1 mimetic, exendin-4, post-myocardial infarction (MI) remodelling, a key contributor to Adult female normoglycaemic mice underwent coronary artery ligation/sham surgery prior infusion with exendin-4/vehicle 4 weeks. Metabolic parameters...
G-protein coupled receptor (GPCR) mediated activation of the MAPK signalling cascade is a key pathway in induction hypertrophic remodelling heart - response to pathological cues including hypertension and myocardial infarction. While levels pro-hypertrophic hormone agonists GPCRs increase during periods greater workload enhance cardiac output, hypertrophy does not necessarily result. Here we investigated relationship between duration exposure GPCR agonist endothelin-1 (ET-1) neonatal rat...
The Joint Advisory Group on Gastrointestinal (GI) Endoscopy (JAG) biennial census provides a unique view of UK endoscopy. 2021 was conducted to understand the impact ongoing pressures, highlighted in previous census, as well COVID-19.The sent all JAG-registered services April 2021. Data were analysed across domains activity, waiting time targets, workforce, COVID-19, safety, GI bleeding, anaesthetic support, equipment and decontamination. Statistical methods used determine associations...
N-myristoylation on glycine is an irreversible modification that has long been recognized to govern protein localization and function. In contrast, the biological roles of lysine myristoylation remain ill-defined. We demonstrate cytoplasmic scaffolding protein, gravin-α/A kinase-anchoring 12, myristoylated two residues embedded in its carboxyl-terminal kinase A (PKA) binding domain. Histone deacetylase 11 (HDAC11) docks adjacent region gravin-α demyristoylates these sites. brown white...
The influence of bed composition – that is, the relative proportions different components on mixing fluidised beds containing mixtures Geldart group B and D particles is considerable importance to a variety contemporary industrial processes, such as plastic recycling biomass gasification. In this study, we use Positron Emission Particle Tracking (PEPT) analyse detailed, three-dimensional flow dynamics system and, from these measurements, determine rate function composition. Our results show...
Obestatin is a recently discovered gastrointestinal peptide with established metabolic actions, which linked to diabetes and may exert cardiovascular benefits. Here we aimed investigate the specific effects of obestatin on vascular relaxation.Cumulative relaxation responses peptides were assessed in rat isolated aorta mesenteric artery (n≥ 8) presence absence selective inhibitors. Complementary studies performed cultured bovine aortic endothelial cells (BAEC).Obestatin elicited...
Anthracycline-induced cardiotoxicity is a well-known serious clinical entity. However, detailed mechanistic insights on how short-term administration leads to late and long-lasting cardiotoxicity, are still largely undiscovered. We hypothesize that chemotherapy provokes memory effect at the level of epigenomic DNA modifications which subsequently lead even years after cessation chemotherapy.We explored temporal evolution epigenetic modifiers in early due anthracyclines by means...
Increasing SERCA2 (sarco[endo]-plasmic reticulum Ca2+ ATPase 2) activity is suggested to be beneficial in chronic heart failure, but no selective SERCA2-activating drugs are available. PDE3A (phosphodiesterase 3A) proposed present the interactome and limit activity. Disruption of from might thus a strategy develop activators.Confocal microscopy, 2-color direct stochastic optical reconstruction proximity ligation assays, immunoprecipitations, peptide arrays, surface plasmon resonance were...
Abstract Background The epigenomes of healthy and diseased human hearts were recently examined by genome-wide DNA methylation profiling. Repetitive elements, heavily methylated in post-natal tissue, have variable profiles cancer but repetitive elements the heart has never been examined. Results We analyzed from all repeat families myocardial samples, found that satellite significantly hypomethylated end-stage cardiomyopathic relative to normal controls. Satellite are almost always...
Glucagon-like peptide-1 (GLP-1) therapies are routinely used for glycaemic control in diabetes and their emerging cardiovascular actions have been a major recent research focus. In addition to GLP-1 receptor activation, the metabolically-inactive breakdown product, GLP-1(9-36)amide, also appears exert notable effects, including protection against acute cardiac ischaemia. Here, we specifically studied influence of GLP-1(9-36)amide on chronic post-myocardial infarction (MI) remodelling, which...
Abstract The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented unexpected, affecting more than 105 million people worldwide of 8 February 2020 and causing 2.3 deaths according to the World Health Organization (WHO). Not only lungs but also provoking acute respiratory distress, severe syndrome 2 (SARS-CoV-2) is able infect multiple cell types including cardiac vascular cells. Hence a significant proportion infected patients develop events, such arrhythmias heart failure....
RNA-binding proteins with prion-like domains, such as FUS and TDP-43, condense into functional liquids, which can transform pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs (24-48 nucleotides) prevent fibrillization by promoting liquid phases, distinct and, remarkably, reverse condensation fibrillization. These activities require interactions multiple domains of are...