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Muscle wasting

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https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#1
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27906111/the-functional-significance-of-the-skeletal-muscle-clock-lessons-from-bmal1-knockout-models
#2
REVIEW
Stefano Schiaffino, Bert Blaauw, Kenneth A Dyar
The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using different Bmal1 knockout (KO) models...
October 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906101/characterization-of-a-dmd-egfp-reporter-mouse-as-a-tool-to-investigate-dystrophin-expression
#3
Mina V Petkova, Susanne Morales-Gonzales, Karima Relizani, Esther Gill, Franziska Seifert, Josefine Radke, Werner Stenzel, Luis Garcia, Helge Amthor, Markus Schuelke
BACKGROUND: Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as a structural link between the cytoskeleton and the extracellular matrix via the dystrophin-associated protein complex (DAPC). Mutations in the dystrophin-encoding DMD gene cause X-linked dystrophinopathies with variable phenotypes, the most severe being Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting and fibrosis. However, dystrophin deficiency does not only impair the function of skeletal and heart muscle but may also affect other organ systems such as the brain, eye, and gastrointestinal tract...
July 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906076/pgc-1%C3%AE-modulates-necrosis-inflammatory-response-and-fibrotic-tissue-formation-in-injured-skeletal-muscle
#4
Ivana Dinulovic, Regula Furrer, Sabrina Di Fulvio, Arnaud Ferry, Markus Beer, Christoph Handschin
BACKGROUND: Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) exerts therapeutic effects in several muscle pathologies, but its role in damage-induced muscle regeneration is unclear. METHODS: Using muscle-specific gain- and loss-of-function models for PGC-1α in combination with the myotoxic agent cardiotoxin (CTX), we explored the role of this transcriptional coactivator in muscle damage and inflammation...
November 8, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906072/actrii-blockade-protects-mice-from-cancer-cachexia-and-prolongs-survival-in-the-presence-of-anti-cancer-treatments
#5
Shinji Hatakeyama, Serge Summermatter, Marie Jourdain, Stefan Melly, Giulia C Minetti, Estelle Lach-Trifilieff
BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. METHODS: In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model...
July 26, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906064/treatment-with-rgdf11-does-not-improve-the-dystrophic-muscle-pathology-of-mdx-mice
#6
Fabrizio Rinaldi, Yu Zhang, Ricardo Mondragon-Gonzalez, Jeffrey Harvey, Rita C R Perlingeiro
BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD...
June 14, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#7
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27901481/human-pancreatic-cancer-xenografts-recapitulate-key-aspects-of-cancer-cachexia
#8
Daniel Delitto, Sarah M Judge, Andrea E Delitto, Rachel L Nosacka, Fernanda G Rocha, Bayli B DiVita, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900362/de-novo-phip-predicted-deleterious-variants-are-associated-with-developmental-delay-intellectual-disability-obesity-and-dysmorphic-features
#9
Emily Webster, Megan T Cho, Nora Alexander, Sonal Desai, Sakkubai Naidu, Mir Reza Bekheirnia, Andrea Lewis, Kyle Retterer, Jane Juusola, Wendy K Chung
Using whole-exome sequencing, we have identified novel de novo heterozygous pleckstrin homology domain-interacting protein (PHIP) variants that are predicted to be deleterious, including a frameshift deletion, in two unrelated patients with common clinical features of developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features. A nonsense mutation in PHIP has previously been associated with similar clinical features. Patients with microdeletions of 6q14.1, including PHIP, have a similar phenotype of developmental delay, intellectual disability, hypotonia, and obesity, suggesting that the phenotype of our patients is a result of loss-of-function mutations...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27900103/muscle-wasting-associated-with-the-long-term-use-of-mtor-inhibitors
#10
Bishal Gyawali, Tomoya Shimokata, Kazunori Honda, Chihiro Kondoh, Naomi Hayashi, Yasushi Yoshino, Naoto Sassa, Yasuyuki Nakano, Momokazu Gotoh, Yuichi Ando
Some targeted therapies alter muscle mass due to interference with pathways of muscle metabolism. The effects of mammalian target of ra pamycin (mTOR) inhibitors on muscle mass have yet to be fully elucidated. In the present study, the computerized tomography (CT) scans of patients receiving mTOR inhibitors for at least 6 months taken at baseline and post-therapy were retrospectively retrieved, and body composition analyses were performed using the software, sliceOmatic version 5.0 (TomoVision, Inc., Magog, QC, Canada)...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27897432/low-skeletal-muscle-radiation-attenuation-and-visceral-adiposity-are-associated-with-overall-survival-and-surgical-site-infections-in-patients-with-pancreatic-cancer
#11
David P J van Dijk, Maikel J A M Bakens, Mariëlle M E Coolsen, Sander S Rensen, Ronald M van Dam, Martijn J L Bours, Matty P Weijenberg, Cornelis H C Dejong, Steven W M Olde Damink
BACKGROUND: Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas. METHODS: A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area...
October 26, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897418/suppression-of-muscle-wasting-by-the-plant-derived-compound-ursolic-acid-in-a-model-of-chronic-kidney-disease
#12
Rizhen Yu, Ji-An Chen, Jing Xu, Jin Cao, Yanlin Wang, Sandhya S Thomas, Zhaoyong Hu
BACKGROUND: Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF-1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation. METHODS: Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone...
November 17, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897405/premorbid-obesity-but-not-nutrition-prevents-critical-illness-induced-muscle-wasting-and-weakness
#13
Chloë Goossens, Mirna Bastos Marques, Sarah Derde, Sarah Vander Perre, Thomas Dufour, Steven E Thiessen, Fabian Güiza, Thomas Janssens, Greet Hermans, Ilse Vanhorebeek, Katrien De Bock, Greet Van den Berghe, Lies Langouche
BACKGROUND: The 'obesity paradox' of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting. METHODS: In lean and premorbidly obese mice, the effect of 5 days of sepsis-induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding...
July 20, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897403/new-genetic-signatures-associated-with-cancer-cachexia-as-defined-by-low-skeletal-muscle-index-and-weight-loss
#14
Neil Johns, Cynthia Stretch, Benjamin H L Tan, Tora S Solheim, Sveinung Sørhaug, Nathan A Stephens, Ioannis Gioulbasanis, Richard J E Skipworth, D A Christopher Deans, Antonio Vigano, James A Ross, Oliver F Bathe, Michel L Tremblay, Stein Kaasa, Florian Strasser, Bruno Gagnon, Vickie E Baracos, Sambasivarao Damaraju, Kenneth C H Fearon
BACKGROUND: Cachexia affects the majority with advanced cancer. Based on current demographic and clinical factors, it is not possible to predict who will develop cachexia or not. Such variation may, in part, be due to genotype. It has recently been proposed to extend the diagnostic criteria for cachexia to include a direct measure of low skeletal muscle index (LSMI) in addition to weight loss (WL). We aimed to explore our panel of candidate single nucleotide polymorphism (SNPs) for association with WL +/- computerized tomography-defined LSMI...
August 5, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897392/toll-like-receptor-4-signalling-mediates-inflammation-in-skeletal-muscle-of-patients-with-chronic-kidney-disease
#15
Daniela Verzola, Alice Bonanni, Antonella Sofia, Fabrizio Montecucco, Elena D'Amato, Valeria Cademartori, Emanuele Luigi Parodi, Francesca Viazzi, Chiara Venturelli, Giuliano Brunori, Giacomo Garibotto
BACKGROUND: Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine...
October 18, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27896546/jmv2894-a-novel-growth-hormone-secretagogue-accelerates-body-mass-recovery-in-an-experimental-model-of-cachexia
#16
Elena Bresciani, Laura Rizzi, Laura Molteni, Monica Ravelli, Antonella Liantonio, Khoubaib Ben Haj Salah, Jean-Alain Fehrentz, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Vittorio Locatelli, Antonio Torsello
Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats...
November 28, 2016: Endocrine
https://www.readbyqxmd.com/read/27895764/mitofusin-2-prevents-skeletal-muscle-wasting-in-cancer-cachexia
#17
Qiu-Lei Xi, Bo Zhang, Yi Jiang, Hai-Sheng Zhang, Qing-Yang Meng, Ying Chen, Yu-Song Han, Qiu-Lin Zhuang, Jun Han, Hai-Yu Wang, Jing Fang, Guo-Hao Wu
Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894277/human-limb-skeletal-muscle-wasting-and-architectural-remodeling-during-five-to-ten-days-intubation-and-ventilation-in-critical-care-an-observational-study-using-ultrasound
#18
Peter Turton, Richard Hay, Jonathon Taylor, Jamie McPhee, Ingeborg Welters
BACKGROUND: Critically ill patients frequently suffer muscle weakness whilst in critical care. Ultrasound can reliably track loss of muscle size, but also quantifies the arrangement of the muscle fascicles, known as the muscle architecture. We sought to measure both pennation angle and fascicle length, as well as tracking changes in muscle thickness in a population of critically ill patients. METHODS: On days 1, 5 and 10 after admission to critical care, muscle thickness was measured in ventilated critically ill patients using bedside ultrasound...
November 29, 2016: BMC Anesthesiology
https://www.readbyqxmd.com/read/27893707/blockade-of-the-il-6-trans-signalling-stat3-axis-suppresses-cachexia-in-kras-induced-lung-adenocarcinoma
#19
A Miller, L McLeod, S Alhayyani, A Szczepny, D N Watkins, W Chen, P Enriori, W Ferlin, S Ruwanpura, B J Jenkins
Lung cancer is the leading cause of cancer death worldwide, and is frequently associated with the devastating paraneoplastic syndrome of cachexia. The potent immunomodulatory cytokine interleukin (IL)-6 has been linked with the development of lung cancer as well as cachexia; however, the mechanisms by which IL-6 promotes muscle wasting in lung cancer cachexia are ill-defined. In this study, we report that the gp130(F/F) knock-in mouse model displaying hyperactivation of the latent transcription factor STAT3 via the common IL-6 cytokine family signalling receptor, gp130, develops cachexia during Kras-driven lung carcinogenesis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27891297/exercise-rehabilitation-following-intensive-care-unit-discharge-for-recovery-from-critical-illness-executive-summary-of-a-cochrane-collaboration-systematic-review
#20
REVIEW
Bronwen Connolly, Lisa Salisbury, Brenda O'Neill, Louise Geneen, Abdel Douiri, Michael P W Grocott, Nicholas Hart, Timothy S Walsh, Bronagh Blackwood
Skeletal muscle wasting and weakness are major complications of critical illness and underlie the profound physical and functional impairments experienced by survivors after discharge from the intensive care unit (ICU). Exercise-based rehabilitation has been shown to be beneficial when delivered during ICU admission. This review aimed to determine the effectiveness of exercise rehabilitation initiated after ICU discharge on primary outcomes of functional exercise capacity and health-related quality of life...
December 2016: Journal of Cachexia, Sarcopenia and Muscle
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