A5040092817- Muscle Physiology and Disorders
- Respiratory Support and Mechanisms
- Intensive Care Unit Cognitive Disorders
- Exercise and Physiological Responses
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Selenium in Biological Systems
- High Altitude and Hypoxia
- Adipose Tissue and Metabolism
- Long-Term Effects of COVID-19
- Medical and Biological Ozone Research
- Metabolism, Diabetes, and Cancer
- Muscle and Compartmental Disorders
- Muscle metabolism and nutrition
- Cardiovascular and exercise physiology
- Mitochondrial Function and Pathology
- Silk-based biomaterials and applications
- Muscle activation and electromyography studies
- Protease and Inhibitor Mechanisms
- Nutritional Studies and Diet
- Electrolyte and hormonal disorders
- Vitamin D Research Studies
- Thermal Regulation in Medicine
- Connective tissue disorders research
- Autophagy in Disease and Therapy
Deakin University
2017-2024
Karolinska Institutet
2020-2024
University of Copenhagen
2023-2024
Novo Nordisk Foundation
2023
Inhibition of AMP-activated protein kinase (AMPK) is under increasing investigation for its therapeutic potential in many diseases, including certain cancers. However, existing AMPK-inhibitors available as tool compounds are largely limited to compound C/dorsomorphin and SBI-0206965, both which suffer from poor selectivity off-target effects. Here we describe the structure-based molecular insights cellular actions a recently identified potent AMPK inhibitor, BAY-3827. Kinase profiling...
The AMP-activated protein kinase (AMPK) gets activated in response to energetic stress such as contractions and plays a vital role regulating various metabolic processes insulin-independent glucose uptake skeletal muscle. main upstream that activates AMPK through phosphorylation of α-AMPK Thr172 muscle is LKB1, however some studies have suggested Ca2+/calmodulin-dependent 2 (CaMKK2) acts an alternative activate AMPK. We aimed establish whether CaMKK2 involved activation promotion following A...
In Duchenne muscular dystrophy (DMD), a dysregulated extracellular matrix (ECM) directly exacerbates pathology. Glucocorticoids are beneficial therapeutics in DMD, and have pleiotropic effects on the composition processing of ECM proteins other biological contexts. The synthesis remodelling transitional versican-rich is necessary for myogenesis; whether glucocorticoids modulate this not known. Here, versican expression were examined hindlimb diaphragm muscles from mdx dystrophin-deficient...
Critical illness myopathy (CIM) is a frequently observed negative consequence of modern critical care. Chronic Janus kinase (JAK)/signal transducer and activator transcription activation impairs muscle size function prominent following mechanical ventilation. We identify pSTAT-3 in tibialis anterior CIM patients, before examining the potential benefits JAK1/2 inhibition an experimental model CIM, where mass are impaired. activates complement cascade increased monocyte infiltration soleus...
Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There interest in characterising novel genes that regulate due to their potential modify disease progression. Gene polymorphisms Selenoprotein S ( Seps1 ) are associated with elevated proinflammatory cytokines, and vitro SEPS1 protective against inflammatory stress. Given highly expressed skeletal muscle, we investigated whether the genetic reduction exacerbated mdx mouse. F1 male mice...
Selenoprotein S (Seps1) is an endoplasmic reticulum (ER) resident antioxidant implicated in ER stress and inflammation. In human vastus lateralis mouse hindlimb muscles, Seps1 localization expression were fiber-type specific. male Seps1+/- heterozygous mice, spontaneous physical activity was reduced compared with wild-type littermates ( d = 1.10, P 0.029). A similar trend also observed Seps1-/- knockout mice 1.12, 0.051). Whole body metabolism, composition, extensor digitorum longus (EDL),...
Abstract Aim Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator‐induced dysfunction (VIDD). VID increases dependence, prolongs weaning, discharge mortality rates. The Janus kinase (JAK)/Signal Transducer Activator of Transcription (STAT) pathway is implicated VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential Ruxolitinib, an FDA approved JAK1/2...
Abstract Background Old age is associated with a significantly increased mortality in COVID-19 patients exposed to long-term controlled mechanical ventilation (CMV) and suggested be due the hyperinflammatory response viral infection. However, our understanding of age-related differences CMV absence infection remains insufficient. Methods Young (7–8 months) old (28–32 F344 BN hybrid rats were ICU condition for 5 days, i.e., complete immobilization, ventilation, extensive monitoring....
Older adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest in response to resistance training. Systemic hypoxia modulates therefore this study characterized the effects normobaric on leukocyte cytokine responses older
Aberrant extracellular matrix synthesis and remodeling contributes to muscle degeneration weakness in Duchenne muscular dystrophy (DMD). ADAMTS-5, a secreted metalloproteinase with catalytic activity against versican, is implicated myogenesis inflammation. Here, using the mdx mouse model of DMD, we report increased ADAMTS-5 expression dystrophic hindlimb muscles, localized regions regeneration To investigate pathophysiological significance this, 4-week-old mice were treated an monoclonal...
The antioxidant Selenoprotein S (Seps1, Selenos) is an endoplasmic reticulum (ER)-resident protein associated with metabolic and inflammatory disease. While Seps1 highly expressed in skeletal muscle, its mechanistic role as muscle cells not well characterized. In C2C12 myotubes treated palmitate for 24 h, endogenous expression was upregulated twofold. Two different siRNA constructs were used to investigate whether decreased levels of exacerbated lipid-induced oxidative ER stress myoblasts,...
Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect muscle. This result in a loss mass (atrophy) and/or quality (reduced force per unit mass), which are prevalent chronic disease, muscle-specific immobilization, aging (sarcopenia). Skeletal animals be evaluated by range different tests. All tests have limitations related to the physiological testing environment, selection specific...
Selenoprotein S (Seps1) can be protective against oxidative, endoplasmic reticulum (ER), and inflammatory stress. Seps1 global knockout mice are less active, possess compromised fast muscle ex vivo strength, and, depending on context, heightened inflammation. Oxidative, ER, stress modulates contractile function; hence, our aim was to investigate the effects of gene dose exercise performance. −/− knockout, −/+ heterozygous, wild-type were randomized 3 days incremental, high-intensity...
Ageing causes a decline in leukocyte function and blunted responses to resistance exercise. Systemic hypoxia exposure augments the response exercise young adults, yet this remains uncharacterised older adults. This study characterised effects of normobaric on acute inflammatory cytokine We recruited 20 adults aged 60-70 years perform an bout (FiO2 14.4%; n = 10) or normoxia 20.93%; 10). Participants completed 4 × 10 repetitions lower upper body exercises at 70% their predicted 1-repetition...
Abstract There is a persistent, aberrant accumulation of V0/V1 versican in skeletal muscles from patients with Duchenne muscular dystrophy and diaphragm mdx mice. Versican provisional matrix protein implicated fibrosis inflammation various disease states, yet its role the pathogenesis not known. Here, female male hdf mice (haploinsufficient for allele) were bred. In resulting F1 -hdf pups, expression was decreased by 50% compared to littermates at 20–26 weeks age. mice, spontaneous physical...
There is growing interest in the use of systemic hypoxia to improve training adaptations resistance exercise. Hypoxia a well-known stimulator immune system, yet leukocyte responses this modality remain uncharacterised. The current study characterised acute exercise normobaric hypoxia. single-blinded, randomised trial recruited 13 healthy males aged 18-35 years perform bout (14.4% O2; n = 7) or normoxia (20.9% 6). Participants completed 4 × 10 repetitions lower and upper body exercises at 70%...
Abstract Background Controlled Mechanical Ventilation (CMV) is associated with Ventilator Induced Lung Injury (VILI) and Diaphragm Dysfunction (VIDD). VIDD delays weaning from the respirator increases risk of further complications health care costs, which are disproportionately increased increasing duration mechanical ventilation. Hypercapnia frequently observed tolerated as “permissive hypercapnia” during lung protective MV strategies. The systemic effects hypercapnia well known considered...
ABSTRACT The provisional matrix protein versican is upregulated in Duchenne muscular dystrophy. Versican heightens inflammation fibrotic diseases and involved myogenesis. In diaphragm muscles from dystrophic mdx mice, reduction attenuated macrophage infiltration improved contractile function. We investigated the association between hindlimb muscle pathology, where regeneration are increased but fibrosis minimal. Immunohistochemistry qRT-PCR were used to assess how fiber type glucocorticoids...
The proteoglycan versican is upregulated in muscular dystrophy. In fibrotic diaphragm muscles from mdx mice, reduction attenuated macrophage infiltration and improved performance. Here, hindlimb 6- 20-wk-old where pathology mild, did not decrease inflammation contractile function improvements were limited to juvenile mice. dystrophic muscles, the association between mediated by fibrosis, demonstrating interdependence immune system extracellular matrix.
Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect muscle. This result in a loss mass (atrophy) and/or quality (reduced force per unit mass), which are prevalent chronic disease, muscle-specific immobilization, aging (sarcopenia). Skeletal animals be evaluated by range different tests. All tests have limitations related to the physiological testing environment, selection specific...