Gary Sweeney
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View article: Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study
Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study Open
Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV …
View article: IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies
IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies Open
Iron regulatory protein 1 (IRP1) is a post-transcriptional regulator of cellular iron metabolism. In mice, loss of IRP1 causes polycythemia through translational de-repression of hypoxia-inducible factor 2α (HIF2α) mRNA, which increases re…
View article: <b>ALY688 attenuates iron-induced ER stress and insulin resistance</b><b>via activation of</b><b> </b><b>ER-phagy</b>
<b>ALY688 attenuates iron-induced ER stress and insulin resistance</b><b>via activation of</b><b> </b><b>ER-phagy</b> Open
Iron overload (IO) is a common contributing factor to aspects of the metabolic syndrome (MetS), including insulin resistance. Mechanisms of IO-induced insulin resistance include elevated oxidative stress, endoplasmic reticulum (ER) stress …
View article: <b>ALY688 attenuates iron-induced ER stress and insulin resistance</b><b>via activation of</b><b> </b><b>ER-phagy</b>
<b>ALY688 attenuates iron-induced ER stress and insulin resistance</b><b>via activation of</b><b> </b><b>ER-phagy</b> Open
Iron overload (IO) is a common contributing factor to aspects of the metabolic syndrome (MetS), including insulin resistance. Mechanisms of IO-induced insulin resistance include elevated oxidative stress, endoplasmic reticulum (ER) stress …
View article: The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan
The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan Open
The gradual decline in physiological functions that comes with aging contributes to a range of chronic diseases, such as Alzheimer's, type 2 diabetes, heart failure, and osteoarthritis. Significant advancements in human longevity due to so…
View article: Selective disruption of Traf1/cIAP2 interaction attenuates inflammatory responses and rheumatoid arthritis
Selective disruption of Traf1/cIAP2 interaction attenuates inflammatory responses and rheumatoid arthritis Open
These findings reveal a previously unrecognized and crucial role for the TRAF1/cIAP2 axis in promoting inflammation and offer a promising foundation for the development of novel therapeutic strategies for inflammatory conditions, such as R…
View article: Adiponectin-receptor agonism prevents right ventricular tissue pathology in a mouse model of Duchenne muscular dystrophy
Adiponectin-receptor agonism prevents right ventricular tissue pathology in a mouse model of Duchenne muscular dystrophy Open
Cardiac fibrosis during Duchenne muscular dystrophy (DMD) arises from cellular damage and inflammation and is associated with myofibre hypertrophy and metabolic dysfunction. However, the extent to which these relationships develop across a…
View article: Autophagy deficiency exacerbated hypoxia-reoxygenation induced inflammation and cell death via a mitochondrial DNA/STING/IRF3 pathway
Autophagy deficiency exacerbated hypoxia-reoxygenation induced inflammation and cell death via a mitochondrial DNA/STING/IRF3 pathway Open
Autophagy deficiency in the cardiomyocyte setting results in detrimental effects during I/R injury in mice or H/R injury in cells, mediated in part via mtDNA/IRF3/STING pathway. As such, modulation of this pathway may yield novel and promi…
View article: Selective disruption of Traf1/cIAP2 interaction attenuates inflammatory responses and limits sepsis and rheumatoid arthritis
Selective disruption of Traf1/cIAP2 interaction attenuates inflammatory responses and limits sepsis and rheumatoid arthritis Open
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is an immune signaling adapter protein linked to increased susceptibility to rheumatoid arthritis (RA). TRAF1 has dual roles in regulating NF-κB and MAPK signaling: it promotes sig…
View article: <scp>MitoNEET</scp> preserves muscle insulin sensitivity during iron overload by regulating mitochondrial iron, reactive oxygen species and fission
<span>MitoNEET</span> preserves muscle insulin sensitivity during iron overload by regulating mitochondrial iron, reactive oxygen species and fission Open
Iron overload (IO) is known to contribute to metabolic dysfunctions such as type 2 diabetes and insulin resistance. Using L6 skeletal muscle cells overexpressing the CDGSH iron–sulfur domain‐containing protein 1 (CISD1, also known as mitoN…
View article: Recent Advances in Pre-Clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy
Recent Advances in Pre-Clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy Open
Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stresso…
View article: The adiponectin‐derived peptide <scp>ALY688</scp> protects against the development of metabolic dysfunction‐associated steatohepatitis
The adiponectin‐derived peptide <span>ALY688</span> protects against the development of metabolic dysfunction‐associated steatohepatitis Open
Metabolic dysfunction‐associated steatohepatitis (MASH) is the severe form of non‐alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking.…
View article: Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy
Recent Advances in Pre-clinical Development of Adiponectin Receptor Agonist Therapies for Duchenne Muscular Dystrophy Open
Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stresso…
View article: A novel blood-based bioassay to monitor adiponectin signaling
A novel blood-based bioassay to monitor adiponectin signaling Open
The diverse beneficial effects of adiponectin-receptor signaling, including its impact on the regulation of inflammatory processes in vivo, have resulted in development of adiponectin receptor agonists as a treatment for metabolic disorder…
View article: Impaired autophagy flux contributes to enhanced ischemia reperfusion injury in the diabetic heart
Impaired autophagy flux contributes to enhanced ischemia reperfusion injury in the diabetic heart Open
Myocardial ischemia/reperfusion (I/R) injury is exacerbated in diabetic individuals and animal models. We tested whether autophagy is an important cellular determinant of cell death. First, we utilized a cellular model of hypoxia reoxygena…
View article: Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux
Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux Open
Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery liga…
View article: Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure
Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure Open
Heart failure, a leading driver of global mortality, remains a topic of intense contemporary research interest due to the prevailing unmet need in cardiometabolic therapeutics. Numerous mechanisms with the potential to influence the onset …
View article: Cardioprotection by the adiponectin receptor agonist ALY688 in a preclinical mouse model of heart failure with reduced ejection fraction (HFrEF)
Cardioprotection by the adiponectin receptor agonist ALY688 in a preclinical mouse model of heart failure with reduced ejection fraction (HFrEF) Open
These results indicate that the adiponectin mimetic peptide ALY688 reduced PO-induced fibrosis, hypertrophy, inflammation and metabolic dysfunction and represents a promising therapeutic approach for treating HFrEF in a clinical setting.
View article: MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function
MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function Open
Cardiometabolic diseases exert a significant health impact, leading to a considerable economic burden globally. The metabolic syndrome, characterized by a well-defined cluster of clinical parameters, is closely linked to an elevated risk o…
View article: Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia
Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia Open
Cardiomyopathy is a major complication of thalassemia, yet the precise underlying molecular mechanisms remain unclear. We examined whether altered lipid metabolism is an early driving factor in the development of cardiomyopathy using the T…
View article: Copper infused fabric attenuates inflammation in macrophages
Copper infused fabric attenuates inflammation in macrophages Open
While inflammation is an important immune response for protection from infections, excessive or prolonged inflammation can lead to a variety of debilitating diseases including skin disease, diabetes, heart disease, stroke, autoimmune disea…
View article: Memory impairment in the D2.<i>mdx</i> mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688
Memory impairment in the D2.<i>mdx</i> mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688 Open
Memory impairments have been well documented in people with Duchenne muscular dystrophy (DMD). However, the underlying mechanisms are poorly understood, and there is an unmet need to develop new therapies to treat this condition. Using a n…
View article: Sterile inflammation and the NLRP3 inflammasome in cardiometabolic disease
Sterile inflammation and the NLRP3 inflammasome in cardiometabolic disease Open
Inflammation plays an important role in the pathophysiology of cardiometabolic diseases. Sterile inflammation, a non-infectious and damage-associated molecular pattern (DAMP)-induced innate response, is now well-established to be closely a…
View article: MitoNEET prevents iron overload‐induced insulin resistance in H9c2 cells through regulation of mitochondrial iron
MitoNEET prevents iron overload‐induced insulin resistance in H9c2 cells through regulation of mitochondrial iron Open
Iron overload (IO) induces insulin resistance in H9c2 cardiomyoblast cells. Here, we used H9c2 cells overexpressing MitoNEET to examine the potential for protection against iron accumulation in the mitochondria and subsequent insulin resis…
View article: The adiponectin analogue ALY688-SR attenuates diaphragm fibrosis, atrophy and mitochondrial stress in a mouse model of Duchenne muscular dystrophy
The adiponectin analogue ALY688-SR attenuates diaphragm fibrosis, atrophy and mitochondrial stress in a mouse model of Duchenne muscular dystrophy Open
Fibrosis is associated with respiratory and limb muscle atrophy in Duchenne muscular dystrophy (DMD). Current standard of care partially delays the progression of this myopathy but there remains an unmet need to develop additional therapie…
View article: Potent Anti-inflammatory Effects of the Adiponectin Receptor Agonist, ALY688
Potent Anti-inflammatory Effects of the Adiponectin Receptor Agonist, ALY688 Open
Low circulating levels of adiponectin are associated with increased inflammation in a wide range of disease states. In particular, this applies to obesity-related diseases such as type 2 diabetes, heart failure and non-alcoholic fatty live…
View article: Autophagy deficiency exacerbates iron overload induced reactive oxygen species production and apoptotic cell death in skeletal muscle cells
Autophagy deficiency exacerbates iron overload induced reactive oxygen species production and apoptotic cell death in skeletal muscle cells Open
Iron overload is associated with various pathological changes which contribute to metabolic syndrome, many of which have been proposed to occur via damaging tissue through an excessive amount of reactive oxygen species (ROS) production. In…