A5008439616- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Cardiomyopathy and Myosin Studies
- Vitamin D Research Studies
- Cardiovascular Effects of Exercise
- Hormonal Regulation and Hypertension
- Muscle metabolism and nutrition
- Genetic Neurodegenerative Diseases
- Adrenal Hormones and Disorders
- Cardiovascular Function and Risk Factors
- Nutrition and Health in Aging
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Biotin and Related Studies
- Growth Hormone and Insulin-like Growth Factors
- Pituitary Gland Disorders and Treatments
- Congenital Diaphragmatic Hernia Studies
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infectious Diseases and Gene Expression in Insects
- Biochemical effects in animals
- Prosthetics and Rehabilitation Robotics
- Reproductive Physiology in Livestock
- Ion channel regulation and function
The Ohio State University
2015-2025
Lung Institute
2023
University of Nottingham
2004
Auburn University
1983
The utrophin-dystrophin deficient (DKO) mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD). However, it is unclear as what extent muscle pathology affects metabolism. Therefore, present study was focused on understanding energy expenditure in whole animal and isolated extensor digitorum longus (EDL) determine changes metabolic enzymes. Our results show that 8 week-old DKO mice consume higher oxygen relative activity levels. Interestingly EDL...
Early treatment with heart failure drugs lisinopril and spironolactone improves skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. The angiotensin converting enzyme inhibitor mineralocorticoid receptor (MR) antagonist indirectly directly target MR. presence function of MR have not been explored. mRNA protein are present all tested muscles from both wild-type mice DMD expression is cell autonomous undifferentiated myoblasts differentiated myotubes human cultures. To...
Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD model that progresses reduced ejection fraction indicative of Adeno-associated viral (AAV) vector delivery an early generation micro-dystrophin prevented cardiac pathology and functional decline...
ABSTRACT Background Cancer cachexia is a debilitating syndrome characterized by irreversible losses in skeletal muscle mass, with or without adipose tissue. an underrecognized that impacts ~50% of all cancer patients and accounts for up to ~20% deaths. Lung remains one the deadliest cancers United States estimated 137 000 deaths year 2021 alone. highly comorbid cachexia. Pre‐clinical models are heavily relied upon study both lung cachexia; however, there need develop novel relationship...
We tested how a treadmill exercise program influences oxygen consumption, oxidative stress, and capacity in the mdx mouse, model of Duchenne muscular dystrophy.At age 4 weeks mice were subjected to twice-weekly exercise. Sedentary wild-type served as controls. Oxygen time exhaustion, myofiber damage assessed.At weeks, there was significant difference between mice. After exercise, had lower basal consumption capacity, but similar maximal consumption. Skeletal muscle from these displayed...
Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients DMD die from failure, cardiomyopathy undetectable until the teens, so trials young boys will be unknown a decade. Available animal models were sufficient to demonstrate micro-dystrophin on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency patients. However, no...
Mineralocorticoid receptor antagonists (MRAs) slow cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) and improve skeletal muscle pathology function dystrophic mice. However, glucocorticoids, known antiinflammatory drugs, remain a standard of care for DMD, despite substantial side effects. Exact mechanisms underlying mineralocorticoid (MR) signaling contribution to are unknown. Whether MRAs affect inflammation muscles how they compare glucocorticoids is unclear. The MRA...
Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) used to treat heart failure. Combined treatment with ACEi lisinopril nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition function pathology a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated is present all limb respiratory muscles functions as steroid...
FDA-approved mineralocorticoid receptor (MR) antagonists are used to treat heart failure. We have recently demonstrated efficacy of MR for skeletal muscles in addition Duchenne muscular dystrophy mouse models and that receptors present functional muscles. The goal this study was elucidate the underlying mechanisms antagonist on dystrophic demonstrate first time infiltrating myeloid cells clustered damaged areas capacity produce natural ligand MR, aldosterone, which excess is known exacerbate...
Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 usually die in the second third decades of life from respiratory failure. Symptomatic treatment includes use anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, increased risk cardiovascular disease. Novel options include blockade...
Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by the absence of functional dystrophin. There are multiple ongoing clinical trials for DMD that testing gene therapy treatments consisting adeno-associated viral (AAV) vectors carrying miniaturized versions dystrophin optimized function, termed micro-dystrophins (μDys). Utrophin, fetal homolog dystrophin, has repeatedly been reported to be upregulated in human as compensatory mechanism, but whether µDys displaces...
Angiotensin converting enzyme inhibitors (ACEi) are the current standard of care treatment for cardiac dysfunction in Duchenne muscular dystrophy patients. We previously showed with an ACEi plus mineralocorticoid receptor (MR) antagonist improves limb and respiratory skeletal muscles, addition to a dystrophic mouse model at 20 weeks-of-age.To determine whether observed preclinical benefits MR on muscles can be reproduced by increasing dosage alone. also compared functional histological...
Combined treatment with an angiotensin-converting enzyme inhibitor and a mineralocorticoid receptor (MR) antagonist improved cardiac skeletal muscle function pathology in mouse model of Duchenne muscular dystrophy. MR is present limb respiratory muscles functions as steroid hormone receptor.The goals the current study were to compare efficacy specific eplerenone non-specific spironolactone, both combination lisinopril.Three groups n=18 dystrophin-deficient, utrophin-haploinsufficient male...
SUMMARY Three ponies and 1 horse were bilaterally adrenalectomized ( badx) . The initial hypoadrenal episode after badx was reversed with 20 mg of dexamethasone dxm ) im (n = 2) or triamcinolone tmc 2). Nine crises given 4) 5). Sodium chloride retention potassium excretion documented based on changes in serum electrolytes urinary excretion. Eight intact adult horses randomly assigned to 2 groups study the effects a single injection (0.044 mg/kg body weight) mg/kg). Cortisol (hydrocortisone)...
Mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors have shown preclinical efficacy for both skeletal and cardiac muscle outcomes in young sedentary dystrophin-deficient mdx mice also haploinsufficient utrophin, a Duchenne muscular dystrophy (DMD) model. The genotypic DMD model has mild pathology, making non-curative therapeutic effects difficult distinguish at baseline. Since the benefit of mineralocorticoid been translated patients, it is important...
Mineralocorticoid receptor (MR) drugs have been used clinically for decades to treat cardiovascular diseases. MR antagonists not only show preclinical efficacy heart in Duchenne muscular dystrophy (DMD) models but also improve skeletal muscle force and membrane integrity. The mechanisms of action muscles are entirely unknown. Since present many cell types the microenvironment, it is critical define cell-intrinsic functions each type ultimately optimize antagonist use widest variety We...
Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical antagonist efficacy DMD cardiomyopathy and other cardiac diseases are defined, muscles not fully elucidated. Myofiber knockout improves force a subset of dystrophic pathology. However, signaling myeloid cells known to be major contributor efficacy. To define contributions...
Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and progenitor cells within the microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic injury, but eventually, regenerative portion cycle disrupted fibrosis replaces degenerated fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated increase function, decrease fibrosis, directly improve membrane integrity mice,...
Introduction: Duchenne muscular dystrophy (DMD) is a fatal striated muscle degenerative disease. DMD caused by loss of dystrophin protein, which results in sarcolemmal instability and cycles myofiber degeneration regeneration. Pathology exacerbated overactivation infiltrating immune cells fibroblasts, leads to chronic inflammation fibrosis. Mineralocorticoid receptors (MR), type nuclear steroid hormone receptors, are potential therapeutic targets for DMD. MR antagonists show clinical...
Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the lack of functional dystrophin protein. In preclinical research, it pertinent to analyze force muscles affected disease assess pathology and potential effectiveness therapeutic interventions. Although function at sub-maximal levels in vivo , maximal tetanic contractions are most commonly used report muscle studies. At submaximal activation, kinetics contraction relaxation heavily impacted single twitch. However, often...
A healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples serine/threonine kinases directly phosphorylating proteins function, the roles tyrosine (Y) phosphorylation have not been demonstrated. The protein TnI (troponin I) inhibitory subunit troponin complex a key regulator cardiac contraction relaxation. We previously demonstrated that TnI-Y26 decreases calcium-sensitive force...