- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Metabolism, Diabetes, and Cancer
- Apelin-related biomedical research
- Pancreatic function and diabetes
- Cardiac Ischemia and Reperfusion
- Adipose Tissue and Metabolism
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Lipid metabolism and disorders
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Sulfur Compounds in Biology
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cellular Mechanics and Interactions
- Neurological Disease Mechanisms and Treatments
- Electron Spin Resonance Studies
- Fibroblast Growth Factor Research
- Stress Responses and Cortisol
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Nitric Oxide and Endothelin Effects
- Traditional Chinese Medicine Analysis
- Lipid metabolism and biosynthesis
- Cardiac Arrest and Resuscitation
University of Manitoba
2020-2025
Memorial University of Newfoundland
2016-2024
Manitoba Beekeepers' Association
2020-2024
Hangzhou Medical College
2021-2023
Yale University
2008-2021
Zhejiang Academy of Medical Sciences
2021
Shanghai Mental Health Center
2017-2018
Shanghai Jiao Tong University
2017-2018
Cardiovascular Research Center
2009
University of British Columbia
2004-2007
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that also modulates physiologic cell signaling pathways. MIF expressed in cardiomyocytes and limits cardiac injury by enhancing AMPK activity during ischemia. Reperfusion mediated part activation of the stress kinase JNK, but whether JNK this setting unknown. We examined role regulating experimental ischemia/reperfusion mouse hearts. Isolated perfused Mif-/- hearts had greater contractile dysfunction, necrosis, than...
Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise apoptotic cell death in acutely diabetic hearts lead heart disease. At present, the source of these cardiac ROS or subcellular site GSH loss [i.e., cytosolic (cGSH) mitochondrial (mGSH) GSH] has not been completely elucidated. With use rotenone (an inhibitor electron transport chain) decrease acute streptozotocin (STZ)-induced rat heart, origin was established....
Toll-like receptor (TLR)4 regulates inflammation and metabolism has been linked to the pathogenesis of heart disease. TLR4 is upregulated in diabetic cardiomyocytes, we examined role modulating cardiac fatty acid (FA) disease nonobese (NOD) mice. Both wild-type (WT) NOD TLR4-deficient animals had increased plasma triglyceride levels after onset diabetes. However, by comparison, mouse hearts lower accumulation early stages diabetes, which was associated with a reduction myeloid...
Glucocorticoids impair insulin sensitivity. Because resistance is closely linked to increased incidence of cardiovascular diseases and given that metabolic abnormalities have been initiation heart failure, we examined the acute effects dexamethasone (DEX) on rat cardiac metabolism. Although injection DEX for 4 h was not associated with hyperinsulinemia, euglycemic-hyperinsulinemic clamp showed a decrease in glucose infusion rate. Rates glycolysis were unaffected, whereas rate oxidation...
The "fuel gauge" AMP-activated protein kinase (AMPK) facilitates ATP production to meet energy demands during metabolic stress. Given the importance of lipoprotein lipase (LPL) in providing hearts with fatty acids (FA), preferred substrate consumed by heart, objective present study was investigate whether activation AMPK influences LPL at its functionally relevant location, coronary lumen. Hearts from overnight-fasted rats were first perfused heparin release LPL, and homogenates these then...
The cellular response to stress involves the recruitment and coordination of molecular signaling pathways that prevent cell death. D-dopachrome tautomerase (DDT) is an enzyme lacks physiologic substrates in mammalian cells, but shares partial sequence structural homology with macrophage migration inhibitory factor (MIF). Here, we observed DDT highly expressed murine cardiomyocytes secreted by heart after ischemic stress. Antibody-dependent neutralization exacerbated both ischemia-induced...
Background: Telomere shortening and dysfunction may cause metabolic disorders, tissue damage age-dependent pathologies. However, little is known about the association of telomere-associated protein Rap1 with mitochondrial energy metabolism cardiac aging. Methods: Echocardiography was performed to detect structure function in Rap1+/+ Rap1-/- mice at different ages (3 months, 12 months 20 months). length, DNA damage, senescence cardiomyocyte size were analyzed using real-time PCR, Western...
Obesity is a global pandemic, but there yet no effective measure to control it. Recent metabolomics studies have identified signature of altered amino acid profiles be associated with obesity, it unclear whether these findings actionable clinical potential. The aims this study were reveal the metabolic alterations obesity and explore potential strategies mitigate obesity. We performed targeted metabolomic profiling plasma/serum samples collected from six independent cohorts conducted an...
Metformin is widely used to surmount insulin resistance (IR) and type 2 diabetes. Accumulating evidence suggests that metformin may improve IR through regulating gut microbiota bile acids. However, the underlying mechanisms remain unclear. Our metabolomic analysis showed significantly increased accumulation of tauroursodeoxycholic acid (TUDCA) in intestine liver from high-fat diet (HFD)-induced mice. TUDCA also alleviated IR, reduced oxidative stress intestinal inflammation ob/ob blocked...
Atypical antipsychotics are highly effective antischizophrenic medications but their clinical utility is limited by adverse metabolic sequelae. We investigated whether upregulation of macrophage migration inhibitory factor (MIF) underlies the insulin resistance that develops during treatment with most commonly prescribed atypical antipsychotic, olanzapine. Olanzapine monotherapy increased BMI and circulating insulin, triglyceride, MIF concentrations in drug-naive schizophrenic patients...
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating LPL its relationship with development of hypertriglyceridemia are largely unknown. WAT from obese humans exhibited high PAR2 expression, which was inversely correlated gene. Decreased expression also elevated plasma TG levels, suggesting that might regulate by downregulating LPL. In mice, aging palmitic...
Abstract Background Salidroside is a potential therapeutic agent for myocardial infarction (MI), exerting effects on macrophage migration inhibitory factor (MIF)-regulated mitochondrial quality control. Our aim was to explore the mechanism through which MIF pathway regulates salidroside-mediated resistance hypoxia-induced cardiomyocyte apoptosis. Methods Ligation surgery of left anterior descending branch coronary artery employed establish mouse model. at low and high doses administered mice...
Metformin has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK). We hypothesised that metformin could prevent both caspase-3 activation and apoptosis when induced palmitic acid.Cardiomyocytes were incubated with 1 mmol/l acid, in the absence or presence of (1-5 mmol/l). Following 16 h, cell damage was evaluated measuring lactate dehydrogenase released into incubation medium, Hoechst staining. To investigate mechanism metformin's on...
TLR3 is known to respond dsRNA from viruses, apoptotic cells, and/or necrotic cells. Dying cells are a rich source of ligands that can activate TLRs, such as TLR3. expressed in the liver likely be mediator innate activation and inflammation liver. The importance this function during acute hepatitis has not previously been fully explored. We used mouse model Con A-induced observed novel role for hepatocyte damage absence an exogenous viral stimulus. Interestingly, expression mononuclear sinus...
Urocortin 2 (Ucn2), a peptide of the corticotropin-releasing factor (CRF) family, binds with high affinity to type CRF receptors (CRFR2) on cardiomyocytes and confers protection against ischemia/reperfusion. The mechanisms by which Ucn2-CRFR2 axis mitigates ischemia/reperfusion injury remain incompletely delineated. Activation AMP-activated protein kinase (AMPK) also limits cardiac damage during AMPK is classically activated alterations in cellular energetics; however, hormones, cytokines,...