A5056585372- Advanced Glycation End Products research
- Diet and metabolism studies
- Chronic Kidney Disease and Diabetes
- Complement system in diseases
- Nitric Oxide and Endothelin Effects
- Redox biology and oxidative stress
- Renal Diseases and Glomerulopathies
- Diabetes Treatment and Management
- Mitochondrial Function and Pathology
- Eicosanoids and Hypertension Pharmacology
- Adipose Tissue and Metabolism
- Dialysis and Renal Disease Management
- Liver Disease Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Diabetes and associated disorders
- Genomics, phytochemicals, and oxidative stress
- Atherosclerosis and Cardiovascular Diseases
- Circadian rhythm and melatonin
- Adipokines, Inflammation, and Metabolic Diseases
- Retinal Diseases and Treatments
- Neurological Disease Mechanisms and Treatments
- Ion Transport and Channel Regulation
- Fatty Acid Research and Health
- Glutathione Transferases and Polymorphisms
- Hemoglobinopathies and Related Disorders
Monash University
2016-2025
Australian Regenerative Medicine Institute
2021-2025
St Vincent's Hospital
2009-2022
Baker Heart and Diabetes Institute
2013-2018
Juvenile Diabetes Research Foundation
2014
The University of Melbourne
2009-2012
Saint Vincent's Catholic Medical Center
2010
St. Michael's Hospital
2009
University Health Network
2009
Royal North Shore Hospital
2009
This study shows how highly processed foods can cause innate immune inflammation that promotes chronic microvascular disease.
Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure bioenergetics have not been previously documented. present study, we map changes dynamics function rat at 4, 8, 16 32 weeks diabetes. Our data reveal that precede albuminuria...
Oxidative stress and inflammation are inextricably linked play essential roles in the initiation progression of diabetes complications such as diabetes-associated atherosclerosis nephropathy. Bolstering antioxidant defenses is an important mechanism to lessen oxidative inflammation. In this study, we have used a novel analog NFE2-related factor 2 (Nrf2) agonist bardoxolone methyl, dh404, investigate its effects on diabetic macrovascular renal injury streptozotocin-induced apolipoprotein...
The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role innate immune complement component C5a, potent mediator pathogenesis DKD clinical experimental diabetes. Marked systemic elevation C5a activity was demonstrated patients diabetes; conventional renoprotective agents did not...
Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results cardiac dysfunction and ultimately failure death. Transforming growth factor-beta (TGF-beta) is key mediator pathogenesis of remodeling following MI. We thus aimed to inhibit TGF-beta signaling using novel orally active type I receptor [activin receptor-like kinase 5 (ALK5)] inhibitor (GW788388) attenuate left ventricular rat model Sprague-Dawley rats...
Excessive reactive oxygen species play a key role in the pathogenesis of diabetic nephropathy, but to what extent these result from increased generation, impaired antioxidant systems, or both is incompletely understood. Here, we report expression, localization, and activity thioredoxin its endogenous inhibitor interacting protein (TxnIP) vivo vitro. In normal human rat kidneys, expression TxnIP mRNA was most abundant glomeruli distal nephron (distal convoluted tubule collecting ducts)....
Increasing evidence points to the fact that defects in resolution of inflammatory pathways predisposes individuals development chronic diseases, including diabetic complications such as accelerated atherosclerosis. The inflammation is dynamically regulated by production endogenous modulators inflammation, lipoxin A4 (LXA4). Here, we explored therapeutic potential LXA4 and a synthetic LX analog (Benzo-LXA4) modulate streptozotocin-induced ApoE−/− mouse human carotid plaque tissue ex vivo....
Patients with diabetes have an increased risk of developing atherosclerosis. Endothelial dysfunction, characterized by the lowered bioavailability endothelial NO synthase (eNOS)–derived NO, is a critical inducer However, protective aspect eNOS in diabetes-associated atherosclerosis remains controversial, likely consequence its capacity to release both or deleterious oxygen radicals normal and disease settings, respectively. Harnessing atheroprotective activity diabetic settings elusive, part...
Purpose: Oxidative stress is a causal factor in the development of diabetic retinopathy; however, clinically relevant strategies to treat disease by augmenting antioxidant defense mechanisms have not been fully explored. We hypothesized that boosting nuclear erythroid-2-related 2 (Nrf2) capacity with novel Nrf2 activator dh404, would protect retina diabetes including vision-threatening breakdown blood–retinal barrier (BRB) and associated damage macroglial Müller cells. Methods:...
Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications diabetes such as diabetic kidney disease. identification endogenously generated molecules that promote the physiologic inflammation suggests these bioactions may have therapeutic potential in context inflammation. Lipoxins (LXs) are lipid mediators Methods We investigated LXA 4 and a synthetic LX analog (Benzo-LXA ) therapeutics murine model disease, ApoE −/− mice...
Scope This study evaluates the effects of a chronic high protein diet (HPD) on kidney injury, intestinal permeability and gut microbiota perturbations in mouse model. Method results Mice are fed containing either 20% or 52% energy from for 24 weeks; displaced an equivalent amount wheat starch. The HPD does not alter glycemic control body weight. induces injury as evidenced by increase albuminuria, urinary molecule‐1, blood urea nitrogen, isoprostanes renal cortical NF‐κB p65 gene expression....
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency AIF known to result defective oxidative phosphorylation (OXPHOS), via loss of complex I activity assembly other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that decrease would chronic disease (CKD). Here, report partial knockdown Aif mice recapitulates many features CKD, association compensatory increase ATP pool...
Glutathione peroxidase-1 (GPx1) is highly expressed during normal retinal maturation; however, its role in retinopathy of prematurity (ROP) not fully understood. We postulated that GPx1 plays an important protecting the premature retina from oxidative injury a mouse model ROP.ROP was induced wild-type (WT) and knockout (KO) mice by exposing neonatal to 75% oxygen postnatal days 7 11, followed 1 week room air. Structural effects ROP were evaluated histology, gene expression pro-angiogenic...
There is a large body of evidence implicating mitochondrial reactive oxygen species (ROS) overproduction and oxidative stress in the development diabetic kidney disease deficiency antioxidant systems kidney, such as manganese superoxide dismutase (MnSOD/SOD2) have been identified. The proximal tubules are densely packed with mitochondria thereby providing energy via phosphorylation order to drive active transport for tubular reabsorption solutes from glomerular filtrate. We hypothesized that...
Background. Diabetic nephropathy is the leading cause of kidney failure in developed world. Tranilast has been reported to not only act as an anti-inflammatory and anti-fibrotic compound, but it also exerts anti-oxidative stress effects diabetic nephropathy. Thioredoxin-interacting protein (Txnip) endogenous inhibitor anti-oxidant thioredoxin highly up-regulated nephropathy, oxidative fibrosis. In this study, we aimed investigate whether tranilast its properties through inhibition Txnip....
Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb), have been tested in vitro studies for their ability to scavenge reactive oxygen and nitrogen species, hydrogen peroxide peroxynitrite. In this study, we investigated the efficacies of two Eb analogues, m-hydroxy (ME) ethanol-ebselen (EtE) compared these with cell based assays. We found that ME is superior attenuating activation peroxide-induced pro-inflammatory mediators, ERK P38 human aortic endothelial cells....
Type 1 diabetes (T1D) is the result of an autoimmune assault against insulin-producing pancreatic β-cells, where chronic local inflammation (insulitis) leads to β-cell destruction. T cells and macrophages infiltrate into islets early in T1D pathogenesis. These immune secrete cytokines that lead production reactive oxygen species (ROS) T-cell invasion activation. Cytokine-signaling pathways are very tightly regulated by protein tyrosine phosphatases (PTPs) prevent excessive Here, we...
Abstract Despite increasing knowledge about the factors involved in progression of diabetic complications, kidney disease (DKD) continues to be a major health burden. Current therapies only slow but do not prevent DKD. Thus, there is an urgent need develop novel therapy halt DKD and improve prognosis. In our preclinical study where we administered histone deacetylase (HDAC) inhibitor, valproic acid, streptozotocin-induced mice, albuminuria glomerulosclerosis were attenuated. Furthermore,...