- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- DNA Repair Mechanisms
- Birth, Development, and Health
- Diet and metabolism studies
- Diabetes and associated disorders
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Advanced Glycation End Products research
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Genetic Syndromes and Imprinting
- Diabetes Treatment and Management
- Drug Transport and Resistance Mechanisms
- Adipose Tissue and Metabolism
- Carcinogens and Genotoxicity Assessment
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Chronic Kidney Disease and Diabetes
- MicroRNA in disease regulation
Baker Heart and Diabetes Institute
2015-2025
Monash University
2016-2025
Chinese University of Hong Kong
2016-2025
University College Copenhagen
2019-2025
The University of Melbourne
2015-2024
Prince of Wales Hospital
2016-2024
Steno Diabetes Centers
2024
Capital Region of Denmark
2024
University of Hong Kong
2021-2024
City University of Hong Kong
2024
The current goal of diabetes therapy is to reduce time-averaged mean levels glycemia, measured as HbA1c, prevent diabetic complications. However, HbA1c only explains <25% the variation in risk developing Because does not correlate with glycemic variability when adjusted for blood glucose, we hypothesized that transient spikes hyperglycemia may be an HbA1c–independent factor We show induces long-lasting activating epigenetic changes promoter nuclear κB (NF-κB) subunit p65 aortic...
Dietary intake of fruit and vegetables is associated with lower incidence hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated effect a high-fiber diet supplementation short-chain fatty acid acetate on gut microbiota prevention cardiovascular disease.Gut microbiome, cardiorenal structure/function, blood pressure were examined in sham mineralocorticoid excess-treated mice control diet, or supplementation. We also determined renal cardiac transcriptome treated...
OBJECTIVE Results from the Diabetes Control Complications Trial (DCCT) and subsequent Epidemiology of Interventions (EDIC) Study more recently U.K. Prospective (UKPDS) have revealed that deleterious end-organ effects occurred in both conventional aggressively treated subjects continued to operate >5 years after patients had returned usual glycemic control is interpreted as a legacy past glycemia known “hyperglycemic memory.” We hypothesized transient hyperglycemia mediates persistent...
AimsCirculating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles and these specifically packaged by their maternal cells.
In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears play role. Here we identify Nox1 isoform playing and pharmacologically targetable role in accelerated development diabetic atherosclerosis.Human aortic endothelial cells exposed conditions showed increased...
Diabetic nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)-forming enzyme family. In rodent kidney, three isoforms catalytic subunit oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is main source renal ROS mouse model diabetic induced by streptozotocin administration ApoE(-/-) mice. Deletion Nox4, but not Nox1, resulted protection from glomerular injury evidenced...
High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, diet poor in fiber is associated with prevalence of high BP. The impact lack prebiotic and the mechanisms that lead higher BP are unknown. Here we show dietary leads development hypertensinogenic gut microbiota, hypertension its complications, demonstrate role G-protein coupled-receptors (GPCRs) sense metabolites.One hundred...
The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, neonatal retains transient capacity for regeneration, which is lost shortly after birth. Defining molecular mechanisms that govern regenerative period remains central goal cardiac biology. Here, we assemble transcriptomic framework multiple cell populations during postnatal development and injury, enables comparative analyses (neonatal) versus...
Abstract Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 identify existing gaps provide a timely update. The following methodology was applied achieve this goal: survey published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 06/30/2021 (...
This study shows how highly processed foods can cause innate immune inflammation that promotes chronic microvascular disease.
Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether for advanced glycation end products (RAGE) plays role in mediating on inflammation diabetic kidney disease. Mice with deletion displayed an abnormal phenotype that was accelerated diabetes improved co-deletion RAGE vivo....
Emerging evidence suggests that poor glycemic control mediates post-translational modifications to the H3 histone tail. We are only beginning understand dynamic role of some diverse epigenetic changes mediated by hyperglycemia at single loci, yet elevated glucose levels thought regulate genome-wide changes, and this still remains poorly understood. In article we describe H3K9/K14 hyperacetylation DNA methylation maps conferred in primary human vascular cells. Chromatin immunoprecipitation...
Recent studies have identified that first-line renoprotective agents interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore potential effects of these on modulation receptor for AGE (RAGE). Bovine aortic endothelial cells were exposed angiotensin-converting enzyme inhibitor (ACEi) ramiprilat presence high glucose demonstrated a significant...
The clonogenic (or colony forming) assay has been established for more than 50 years; the original paper describing technique was published in 19561. Apart from documenting method, initial landmark study generated first radiation-dose response curve X-ray irradiated mammalian (HeLa) cells culture1. Basically, enables an assessment of differences reproductive viability (capacity to produce progeny; i.e. a single cell form or cells) between control untreated and that have undergone various...
Epilepsy is a frequent neurological disorder, although onset and progression of seizures remain difficult to predict in affected patients, irrespective their epileptogenic condition. Previous studies animal models as well human epileptic brain tissue revealed remarkably diverse pattern gene expression implicating epigenetic changes contribute disease progression. Here we mapped for the first time global DNA methylation patterns chronic rats controls. Using methyl-CpG capture associated with...
Oxidative stress is considered a hallmark of atherosclerosis. In particular, the superoxide-generating type 1 NADPH oxidase (NOX1) has been shown to be induced and play pivotal role in early phases mouse models atherosclerosis context diabetes mellitus. Here, we investigated most abundant 4 isoform (NOX4) human advanced atherosclerosis.Plaques patients with cardiovascular events or established mellitus showed surprising reduction expression but hydrogen peroxide (H2O2)-generating (Nox4),...
Rationale: Epigenetic changes are implicated in the persisting vascular effects of hyperglycemia. The precise mechanism whereby chromatin structure and subsequent gene expression regulated by glucose endothelial cells remain to be fully defined. Objective: We have studied molecular functional Set7 methyltransferase associates with formation histone methylation response current previous exposure glucose. Methods Results: To characterize identity protein, we used overexpressing or lacking...
The spreadsheet software Microsoft Excel, when used with default settings, is known to convert gene names dates and floating-point numbers. A programmatic scan of leading genomics journals reveals that approximately one-fifth papers supplementary Excel lists contain erroneous name conversions.