A5031158609- Muscle Physiology and Disorders
- Nutrition and Health in Aging
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Exercise and Physiological Responses
- Autophagy in Disease and Therapy
- Diet and metabolism studies
- MicroRNA in disease regulation
- Liver Disease Diagnosis and Treatment
- Telomeres, Telomerase, and Senescence
- Amyotrophic Lateral Sclerosis Research
- GDF15 and Related Biomarkers
- Metabolism, Diabetes, and Cancer
- Anesthesia and Neurotoxicity Research
- NF-κB Signaling Pathways
- Genetic Neurodegenerative Diseases
- Plant Water Relations and Carbon Dynamics
- Intensive Care Unit Cognitive Disorders
- Cancer, Hypoxia, and Metabolism
- Circular RNAs in diseases
- Multiple Sclerosis Research Studies
- Cardiovascular Function and Risk Factors
- Neurogenetic and Muscular Disorders Research
- ATP Synthase and ATPases Research
Oklahoma City VA Medical Center
2022-2025
Oklahoma Medical Research Foundation
2020-2025
Stratford University
2024
Thomas Jefferson University Hospital
2024
Virtua Health
2024
Newark Beth Israel Medical Center
2023-2024
Kentucky State University
2022-2024
University of Arkansas at Fayetteville
2015-2023
University of Minnesota, Duluth
2022
Newcastle University
2022
Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are primary importance; however, little known about muscle perturbations prior to onset cachexia. associated with mitochondrial degeneration; yet, it remains be determined if degeneration precedes wasting in cancer our purpose was determine cancer-induced tumour-bearing mice.
Mutations of amino acid residues in the inner two-thirds S6 segment domain III rat brain type IIA Na<sup>+</sup> channel (G1460A to I1473A) caused periodic positive and negative shifts voltage dependence activation, consistent with an α-helix having one face on which mutations alanine oppose activation. outer one-third IIIS6 all favored half had strong effects inactivation from closed states without effect open-state inactivation. Only three block by local anesthetics anticonvulsants. L1465A...
Abstract Background Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer‐related death. The mechanisms controlling development tumour‐induced muscle wasting are not fully elucidated. Specifically, the progression underexplored. Therefore, we examined skeletal protein turnover throughout tumour‐bearing mice. Methods Lewis lung carcinoma (LLC) was injected into hind flank C57BL6/J mice at 8 weeks age with tumour allowed develop for 1, 2, 3, or 4...
Skeletal muscle mitochondrial degeneration is a hallmark of insulin resistance/obesity marked by lost function, enhanced ROS emission, and altered morphology which may be ameliorated physical activity (PA). However, no prior report has examined quality control regulation throughout biogenesis, fusion/fission dynamics, autophagy, permeability transition pore (MPTP) in obesity. Therefore, we determined how each process impacted Western diet (WD)-induced obesity whether voluntary PA alleviate...
Abstract Background Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and detrimental health outcomes. There emerging evidence that disuse may differentially affect males females. Cellular mechanisms contributing to the development progression of remain elusive, particularly protein turnover cascades. The purpose this study was investigate initial muscle in male female mice using well‐established model hindlimb unloading (HU). Methods One...
Abstract The goal of this study was to test the role cellular senescence plays in increased inflammation, chronic liver disease, and hepatocellular carcinoma seen mice null for Cu/Zn‐Superoxide dismutase (Sod1KO). To inhibit senescence, wildtype (WT) Sod1KO were given senolytics, dasatinib, quercetin (D + Q) at 6 months age when begin exhibiting signs accelerated aging. Seven D Q treatment reduced expression p16 livers WT levels several senescence‐associated secretory phenotype factors...
Our previous studies support a key role for mitochondrial lipid hydroperoxides as important contributors to denervation-related muscle atrophy, including atrophy associated with aging. Phospholipid hydroperoxide glutathione peroxidase 4 (GPX4) is an essential antioxidant enzyme that directly reduces phospholipid and we previously reported denervation-induced blunted in mouse model of GPX4 overexpression. Therefore, the goal present study was determine whether overexpression can reduce...
Abstract Aim Obesity is classified as a metabolic disorder that associated with delayed muscle regeneration following damage. For optimal skeletal regeneration, inflammation along extracellular matrix remodelling and growth must be tightly regulated. Moreover, the regenerative process dependent on activation of myogenic regulatory factors ( MRF s) for myoblast proliferation differentiation. The purpose this study was to determine how obesity alters inflammatory protein synthetic signalling...
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality life the immediate cause death for 20-40% patients. Multiple microRNAs (miRNAs) have been identified as being involved muscle development atrophy; however, less known specifically on miRNAs cachexia. The purpose this investigation was to examine miRNA profile skeletal induced by uncover potential with catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected...
ABSTRACT Insulin resistant diabetes, currently at epidemic levels in developed countries, begins the skeletal muscle and is linked to altered protein turnover. microRNAs downregulate targeted mRNA translation decreasing amount of translated protein, thereby regulating many cellular processes. Regulation miRNAs their function insulin resistance largely unexplored. The purpose this study was identify effects on contents with potential functions We examined miRs ‐1, ‐16, ‐23, ‐27, ‐133a, ‐133b,...
Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis associated with degeneration mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose study was investigate regulation mitochondrial autophagy quality control in following Western diet-induced obesity voluntary activity. Eight-week-old C57BL/6J mice were fed diet (WD) or normal chow (NC,...
Abstract Age‐associated loss of muscle mass and function (sarcopenia) has a profound effect on the quality life in elderly. Our previous studies show that CuZnSOD deletion mice ( Sod1 −/− mice) recapitulates sarcopenia phenotypes, including elevated oxidative stress accelerated atrophy, weakness, disruption neuromuscular junctions (NMJs). To determine whether initiated neurons adult is sufficient to induce we treated young (2‐ 4‐month‐old) Sod1flox/SlickHCre with tamoxifen generate i...
Cancer cachexia (CC) is a devastating syndrome characterized by weight loss, reduced fat mass and muscle that affects approximately 80% of cancer patients responsible for 22%–30% cancer-associated deaths. Understanding underlying mechanisms the development CC are crucial to advance therapies treat improve outcomes. multi-organ results in extensive skeletal adipose tissue wasting; however, can impair other organs such as liver, heart, brain, bone well. A considerable amount research focuses...
Abstract Background Cancer is associated with muscle atrophy (cancer cachexia) that linked to up 40% of cancer‐related deaths. Oxidative stress a critical player in the induction and progression age‐related loss mass weakness (sarcopenia); however, role oxidative cancer cachexia has not been defined. The purpose this study was examine if elevated exacerbates cachexia. Methods Cu/Zn superoxide dismutase knockout (Sod1KO) mice were used as an established mouse model stress. induced by...
Cancer-cachexia (CC) is a wasting condition directly responsible for 20-40% of cancer-related deaths. The mechanisms controlling development CC-induced muscle are not fully elucidated. Most investigations focus on the postcachectic state and do examine progression condition. We recently demonstrated mitochondrial degenerations precede in time course CC. However, extent perturbations before CC unknown. Therefore, we performed global gene expression analysis to enhance understanding...
Cancer-associated bodyweight loss (cachexia) is a hallmark of many cancers and associated with decreased quality life increased mortality. Hepatic function can dramatically influence whole-body energy expenditure may therefore significantly health during cancer progression. The purpose this study was to examine alterations in markers hepatic metabolism physiology cachexia Male C57BL/6J mice were injected 1 × 10 6 Lewis Lung Carcinoma cells dissolved 100 μL PBS allowed develop for 1, 2, 3, or...
Loss of innervation is a key driver age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced with the generation mitochondrial hydroperoxides lipid mediators produced downstream cPLA2 12/15 lipoxygenase (12/15-LOX). To define pathological impact generated in denervation-induced vivo, we treated mice liproxstatin-1, hydroperoxide scavenger. We adult male 5 mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection...
Neuronal oxidative stress has been implicated in aging and neurodegenerative disease. Here we investigated the impact of elevated induced mouse spinal cord by deletion Mn-Superoxide dismutase (MnSOD) using a neuron specific Cre recombinase Sod2 floxed mice (i-mn-Sod2 KO). neurons was associated with mitochondrial alterations peroxide generation. Phenotypically, i-mn-Sod2 KO experienced hindlimb paralysis clasping behavior extensive demyelination reduced nerve conduction velocity, axonal...
Abstract We previously reported that elevated expression of phospholipid hydroperoxide glutathione peroxidase 4, an enzyme regulates membrane lipid hydroperoxides, can mitigate sarcopenia in mice. However, it is still unknown whether a pharmacological intervention designed to modulate hydroperoxides might be effective strategy reduce aged Here we asked newly developed compound, CMD‐35647 (CMD), muscle atrophy induced by sciatic nerve transection. treated mice daily with vehicle or CMD (15...
Abstract Defects in neuromuscular innervation contribute significantly to the age-related decline muscle mass and function (sarcopenia). Our previous studies demonstrated that denervation induces mitochondrial hydroperoxide production (H 2 O lipid hydroperoxides (LOOHs)). Here we define relative contribution of electron transport chain (ETC) derived H versus cytosolic phospholipase A (cPLA ) LOOHs neurogenic atrophy. We show increases cPLA protein content, activity, metabolites downstream...
Abstract Background Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized underlie disuse‐induced atrophy. Little data exist on early mechanisms contributing onset these pathologies, nor it known how they differ between sexes. The purpose this study was examine differential conserved responses quality control in male female mice during the development progression Methods One hundred C57BL/6J (50 50...
Abstract Our laboratory previously showed lipid hydroperoxides and oxylipin levels are elevated in response to loss of skeletal muscle innervation associated with pathologies. To elucidate the pathological impact hydroperoxides, we overexpressed glutathione peroxidase 4 (GPx4), an enzyme that targets reduction membranes, adult CuZn superoxide dismutase knockout ( Sod1 KO) mice show accelerated atrophy innervation. The gastrocnemius from KO shows reduced mitochondrial respiration oxidative...
PGC-1α4 is a novel regulator of muscle hypertrophy; however, there limited understanding the regulation its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene Pgc1α4 examine response stimuli associated with altered mass.IL-6 knockout mice pharmacological experiments C2C12 myocytes were used identify transcription. To conditions, obese lean Zucker rats with/without resistance exercise (RE), ageing...