A5017183758- Birth, Development, and Health
- Atherosclerosis and Cardiovascular Diseases
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Dietary Effects on Health
- Reproductive Biology and Fertility
- Biomarkers in Disease Mechanisms
- Cell Adhesion Molecules Research
- Nanoplatforms for cancer theranostics
- Pancreatitis Pathology and Treatment
- Nanoparticle-Based Drug Delivery
- Sperm and Testicular Function
- Adipokines, Inflammation, and Metabolic Diseases
- Coronary Interventions and Diagnostics
- Dendrimers and Hyperbranched Polymers
- Assisted Reproductive Technology and Twin Pregnancy
- Chemokine receptors and signaling
- Autophagy in Disease and Therapy
- Body Contouring and Surgery
- Transcranial Magnetic Stimulation Studies
- Nerve injury and regeneration
- Immune cells in cancer
- Inflammasome and immune disorders
- Climate Change and Health Impacts
South Australian Health and Medical Research Institute
2019-2025
The University of Adelaide
2014-2024
Paternal health cues are able to program the of next generation however mechanism for this transmission is unknown. Reactive oxygen species (ROS) increased in many paternal pathologies, some which offspring health, and known induce DNA damage alter methylation pattern chromatin. We therefore investigated whether a chemically induced increase ROS sperm impairs embryo, pregnancy health. Mouse was exposed 1500 µM hydrogen peroxide (H2O2), oxidative damage, did not affect motility or ability...
Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic reproductive health of male offspring, despite their control (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if from HFD fathers have heightened susceptibility HFD-induced derangements. This 2 × design saw founder males (F0) (F1) fed either or nutritionally matched CD. Regardless...
The prevalence of obesity is increasing worldwide and has tripled in men reproductive age since the 1970s. Concerningly, not only comorbid with other chronic diseases, but there mounting evidence that it increases non-communicable disease load their children (eg mortality, obesity, autism). Animal studies have demonstrated paternal risk metabolic glucose metabolism defects, obesity) disorders offspring. Epigenetic changes within sperm are clear mechanistic candidates associated both to...
Abstract There is an ever increasing body of evidence that demonstrates paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether under-nutrition can also program offspring and if any detrimental outcomes could be prevented by micronutrient supplementation (vitamins antioxidants). We discovered restricting the food intake male rodents reduced their weight, fertility, increased sperm oxidative DNA lesions global methylation....
Studies investigating whether there is a causative link between the gut microbiota and lifespan have largely been restricted to invertebrates or mice with reduced because of genetic deficiency. We investigate effect early-life antibiotic exposure on otherwise healthy, normal chow-fed, wild-type mice, monitoring these for more than 700 days in comparison untreated control mice. demonstrate emergence two different low-diversity community types, post-antibiotic (PAM) I PAM II, following...
Paternal obesity programs metabolic syndrome in offspring. Low-impact exercise obese males improves the health of female offspring, however whether this occurred male offspring remained unknown. C57BL/6NHsd (Harlan) mice were fed a control diet (CD; 6% fat, n = 7) or high-fat (HFD; 21% 16) for 18 weeks. After 9 weeks, HFD-fed either sedentary (HH, 8) undertook low-moderate (HE, another Male assessed glucose/insulin tolerance, body composition, plasma lipids, pancreatic islet cell morphology...
Objective: In-stent neoatherosclerosis is a phenomenon of percutaneous coronary intervention with stenting. Whilst similar to de novo atherosclerosis, it develops rapidly over 1-5 years rather than lifetime. No preclinical small animal models exist that allow full elucidation biology and future treatments. The aim this study was establish validate novel murine model in-stent neoatherosclerosis. Approach Results: Murine stainless-steel stents (2.5 x 0.7 mm) were deployed into donor descending...
BACKGROUND: Impaired angiogenic responses to ischemia underlie diabetic vascular complications. Reconstituted high-density lipoproteins (rHDLs) have proangiogenic effects in diabetes. The PDK4 (pyruvate dehydrogenase kinase 4)/PDC complex) axis is an oxygen-conserving mechanism that preserves endothelial cell function hypoxia. We aimed determine the role of PDK4/PDC angiogenesis, effect diabetes on its regulation response ischemia, and properties rHDL. METHODS: Expression phosphorylated PDC...
Abstract Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude vessels and cause strokes or heart attacks. It gives rise to both structural biomolecular changes in walls. Current single-modality imaging techniques each measure one these two aspects but fail provide insight into combined changes. To address this, our team has developed a dual-modality system combines optical coherence tomography (OCT) fluorescence that optimized for porphyrin lipid...
Diet-driven obesity is increasingly widespread. Its consequences pose major challenges to human health and care systems. There are MAP kinase-interacting kinases (MNKs) in mice, MNK1 MNK2. Studies have demonstrated that mice lacking either or MNK2 were partially protected against high-fat diet (HFD)-induced weight gain insulin resistance. The aims of this study evaluate the phenotype both MNKs when given an HFD, assess whether pharmacological inhibition MNK function also protects...
Autophagy and lysosomal activities play a key role in the cell by initiating carrying out degradation of misfolded proteins. Transcription factor EB (TFEB) functions as master controller biogenesis function during stress, controlling most but, importantly, not all genes. Here, we sought to better understand regulation genes whose expression does appear be controlled TFEB. Sixteen these were screened for transactivation response diverse cellular insults. mRNA levels lysosomal-associated...
The periconceptual environment represents a critical window for programming fetal growth trajectories and susceptibility to disease; however, the underlying mechanism responsible remains elusive. This study demonstrates causal link between reduction of precompaction embryonic mitochondrial function perturbed offspring subsequent metabolic dysfunction. Incubation embryos with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), which uncouples oxidative phosphorylation, significantly...
ABSTRACT Background High-density lipoprotein (HDL) nanoagents have unrealized potential for atherosclerosis theranostics. Porphyrin-lipid HDL mimetic nanoparticles (Por-HDL-NPs) incorporate porphyrin-lipid which permits near infrared fluorescence imaging and positron emission tomography (PET) through chelation of Copper-64 ( 64 Cu). The outer shell contains apolipoprotein A-I peptide R4F that interacts with scavenger receptor SR-BI, enabling macrophage targeting therapeutic effects. We...
Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian causes glucose intolerance, cardiac fibrosis adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur female P. obesus is unknown. Male were fed a high energy diet exposed to neutral (12 light:12 dark, control) or short (5 light:19 disruption) photoperiod for 20 weeks. impaired tolerance males but not females. It also increased perivascular...
Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats (Psammomys obesus). Exercise intervention can improve metabolism, insulin sensitivity, adipose tissue function protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 dark) high-energy diet. reduced intolerance. expression inflammatory marker Ccl2 Bax:Bcl2 apoptosis ratio. increased heart:body weight ratio...
Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as potential biomarker. We assessed the uptake, distribution, NO detection capacity of an irreversible, ruthenium-based, fluorescent sensor (Ru-NO) macrophages, plasma, atherosclerotic plaques. In vitro, incubation Ru-NO with human THP1 monocytes THP1-PMA macrophages caused robust detected by fluorescence using mass-cytometry, confocal microscopy, flow cytometry. had higher uptake (+13%, p < 0.05) than...
While blood-contacting materials are widely deployed in medicine vascular stents, catheters, and cannulas, devices fail situ because of thrombosis restenosis. Furthermore, microbial attachment biofilm formation is not an uncommon problem for medical devices. Even incremental improvements hemocompatible can provide significant benefits patients terms safety patency as well substantial cost savings. Herein, a novel but simple strategy described coating range materials, that be applied to...
The burden of stroke on the community is growing, and therefore, so need for a therapy to overcome disability following stroke. Cellular-based therapies are being actively investigated at pre-clinical clinical level. Studies have reported beneficial effects exogenous stem cell implantation, however, these benefits also associated with limited survival implanted cells. This exploratory study use transcranial magnetic stimulation (TMS) as complementary increase implantation human dental pulp...
Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical protein that controls synthesis in cells under stress. Although well studied cancer, less known about its roles chronic inflammatory diseases. Here, we examined regulation of macrophage cholesterol handling the context atherosclerosis. eEF2K mRNA expression and activity were upregulated murine bone marrow-derived macrophages (BMDMs) exposed to oxidized low-density lipoprotein (oxLDL). When incubated with oxLDL, BMDMs from knockout...
Abstract Introduction The asialoglycoprotein receptor 1 (ASGR1) is a hepatic that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR1 was reported to associate with 34% reduction coronary artery disease (CAD) risk, suggesting role for CAD. Aim To determine of atherosclerosis and whether deletion elicits atheroprotective effects. Methods Western blotting, mass spectrometry flow cytometry assessed expression cultured macrophages or immune cells...
Objective: Impaired angiogenic responses to ischemia underlie diabetic vascular complications. Reconstituted high-density lipoproteins (rHDL) have proangiogenic effects in diabetes. The pyruvate dehydrogenase kinase 4 (PDK4)/pyruvate complex (PDC) axis is an oxygen-conserving mechanism that preserves EC functions hypoxia. We aimed determine the role of PDK4/PDC angiogenesis, effect diabetes on its regulation response ischemia, and properties rHDL. Approach Results: In a murine wound healing...