RESUMEN
BACKGROUND: Sarcopenia, characterized by degenerative skeletal muscle loss, is increasingly linked to poor surgical outcomes. Glutamine, an immune-modulating formula, may stimulate muscle protein synthesis and inhibit degradation. We used the psoas major muscle area (PMMA) at the third lumbar vertebra, normalized for height (PMMA index), as a skeletal muscle indicator. This study investigates whether perioperative glutamine supplementation mitigates psoas muscle atrophy. METHODS: We enrolled gastric adenocarcinoma (GA) patients undergoing gastrectomy. Computed tomography assessed the psoas muscle short axis. Muscle atrophy was estimated by changes between preoperative and three-month post-gastrectomy scans. Perioperative glutamine supplementation (PGS) comprised five-day parenteral plus one-month oral use. Propensity score matching minimized potential bias. A linear regression model predicted the association. RESULTS: Of 516 patients analyzed (2016-2019), 100 (19.4%) received PGS. After propensity score matching, each group contained 97 cases. The PGS group showed a significantly higher median PMMA index change than the non-PGS group (0.3 vs. -0.3 cm2/m2, p = 0.004). Multivariate analysis revealed that PGS was significantly associated with increased PMMA index (coefficient = 0.60; 95% CI: 0.19-1.01; p = 0.005). CONCLUSIONS: PGS may help restore psoas muscle atrophy in GA patients undergoing gastrectomy. The underlying mechanisms likely relate to glutamine's role in protein metabolism and immune function. Further studies are needed to elucidate these mechanisms fully.
Asunto(s)
Adenocarcinoma , Suplementos Dietéticos , Gastrectomía , Glutamina , Atrofia Muscular , Músculos Psoas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Masculino , Femenino , Gastrectomía/métodos , Glutamina/administración & dosificación , Adenocarcinoma/cirugía , Anciano , Persona de Mediana Edad , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Sarcopenia , Atención Perioperativa/métodos , Puntaje de PropensiónRESUMEN
Diabetic muscular atrophy is becoming a fast-growing problem worldwide, including sarcopenia, which is associated with substantial mortality and morbidity risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been marketed and suggested to exert protective effects on not only glycemic control but also diabetic complications in diabetic patients. In this study, we investigated the therapeutic use of GLP-1RAs exendin-4, compared to antidiabetic drug metformin, for the intervention of muscular dysfunction during diabetic conditions using a streptozotocin (STZ)-induced diabetic mouse model. The results showed that both exendin-4 and metformin could effectively alleviate hyperglycemia in diabetic mice, and also counteract diabetes-induced muscle weight loss, weaker grip, and changes in muscle fiber cross-sectional area distribution. Unexpectedly, exendin-4, but not metformin, enhanced the increased kidney weight and histological change in diabetic mice. Taken together, these findings suggest that both exendin-4 and metformin could effectively improve the diabetic hyperglycemia and muscular dysfunction; but exendin-4 may aggravate the nephropathy in STZ-induced diabetic mice.
Asunto(s)
Diabetes Mellitus Experimental , Exenatida , Receptor del Péptido 1 Similar al Glucagón , Metformina , Animales , Exenatida/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Metformina/farmacología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Ratones , Masculino , Hipoglucemiantes/farmacología , Estreptozocina , Modelos Animales de Enfermedad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Péptidos/farmacología , Ponzoñas/farmacología , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/patología , Atrofia Muscular/etiologíaRESUMEN
Breast cancer (BC) stands out as the most commonly type of cancer diagnosed in women worldwide, and chemotherapy, a key component of treatment, exacerbates cancer-induced skeletal muscle wasting, contributing to adverse health outcomes. Notably, the impact of chemotherapy on skeletal muscle seems to surpass that of the cancer itself, with inflammation identified as a common trigger for muscle wasting in both contexts. In skeletal muscle, pro-inflammatory cytokines modulate pathways crucial for the delicate balance between protein synthesis and breakdown, as well as satellite cell activation and myonuclear accretion. Physical exercise consistently emerges as a crucial therapeutic strategy to counteract cancer and chemotherapy-induced muscle wasting, ultimately enhancing patients' quality of life. However, a "one size fits all" approach does not apply to the prescription of exercise for BC patients, with factors such as age, menopause and comorbidities influencing the response to exercise. Hence, tailored exercise regimens, considering factors such as duration, frequency, intensity, and type, are essential to maximize efficacy in mitigating muscle wasting and improving disease outcomes. Despite the well-established anti-inflammatory role of aerobic exercise, resistance exercise proves equally or more beneficial in terms of mass and strength gain, as well as enhancing quality of life. This review comprehensively explores the molecular pathways affected by distinct exercise regimens in the skeletal muscle of cancer patients during chemotherapy, providing critical insights for precise exercise implementation to prevent skeletal muscle wasting.
Asunto(s)
Neoplasias de la Mama , Ejercicio Físico , Músculo Esquelético , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Calidad de Vida , Terapia por Ejercicio/métodos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Atrofia Muscular/etiología , Atrofia Muscular/metabolismoRESUMEN
BACKGROUND: The study aimed to determine the grade of retraction and atrophy according to the time elapsed in traumatic isolated full-thickness supraspinatus (SS) tears in young patients. METHODS: One thousand twenty-six patients, who underwent arthroscopic shoulder surgery, were retrospectively reviewed. Pre-operative magnetic resonance imaging (MRI) of 69 patients aged 18 to 40 years with isolated traumatic full-thickness SS lesions remaining after exclusion criteria were evaluated for tendon retraction and atrophy grades. SS retraction was determined from a T2-weighted oblique coronal MRI slice, and the atrophy grade was determined from the T1-weighted oblique sagittal MRI slice. The patients were divided into four groups 0-1 month, 1-3 months, 3-6 months, and 6-12 months according to the time between trauma and MRI. The relationship of tendon retraction and muscle atrophy with elapsed time was evaluated, in addition, comparisons between groups were made. RESULTS: Thirty-one (45%) of the patients were female and their mean age was 30 ± 7.3 (18-40) years. The mean age of men was 30.5 ± 6.9 (18-39) years (p = 0.880). The time between rupture and MRI was moderately correlated with retraction and strongly correlated with atrophy grades (r = 0.599, 0.751, respectively). It was observed that there was a statistically significant difference between the 1st (0-1 month) and 2nd (1-3 months) groups (p = 0.003, 0.001, respectively), and between the 2nd and 3rd (3-6 months) groups (p = 0.032, 0.002, respectively), but there was no significant difference between the 3rd and 4th (6-12 months) groups (p = 0.118, 0.057, respectively). In addition, there was a moderate correlation between tendon retraction and atrophy grades (r = 0.668). Power (1- b) in post hoc analysis was calculated as 0.826. CONCLUSIONS: The current study, supported by arthroscopy, showed that there is a moderate and strong positive correlation between the time elapsed after trauma and the level of retraction and degree of atrophy in traumatic full-thickness SS tears, and demonstrated the importance of early surgical intervention in young patients.
Asunto(s)
Imagen por Resonancia Magnética , Atrofia Muscular , Lesiones del Manguito de los Rotadores , Humanos , Femenino , Masculino , Adulto , Adolescente , Adulto Joven , Estudios Retrospectivos , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/patología , Atrofia Muscular/patología , Atrofia Muscular/diagnóstico por imagen , Atrofia Muscular/etiología , Factores de Tiempo , Manguito de los Rotadores/patología , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/cirugía , Artroscopía/métodos , Traumatismos de los Tendones/diagnóstico por imagen , Traumatismos de los Tendones/patología , Traumatismos de los Tendones/cirugíaRESUMEN
Background and Objectives: Muscle atrophy caused by chronic ankle instability (CAI) can incur muscle weakness, altered movement patterns, and increased risk of injury. Previous studies have investigated the effects of rehabilitative exercises and neuromuscular electrical stimulation (NMES) on characteristics in CAI individuals, but few studies have examined their effects on foot and ankle muscle morphology. This study aimed to determine the effects of rehabilitative exercises and NMES on muscle morphology and dynamic balance in individuals with CAI. Materials and Methods: Participants with CAI (n = 47) were randomly divided into control (CG), rehabilitative exercise (REG), NMES (NG), and rehabilitative exercise and NMES combined (RNG) groups. The six-week intervention program consisting of rehabilitative exercises and NMES was applied to groups excluding CG. Muscle morphology and dynamic balance were evaluated using a portable wireless diagnostic ultrasound device and dynamic balance tests. For statistical analysis, an effect size with 95% confidence interval was calculated to assess mean differences according to intervention. Results: After six weeks, significant increases in morphology and dynamic balance were observed for all muscles except flexor hallucis longus (p > 0.05) in the intervention groups except for CG. However, no significant changes were observed in the CG (p > 0.05). Conclusions: These findings suggest that intervention programs may help prevent muscle atrophy and improve balance in CAI individuals.
Asunto(s)
Terapia por Ejercicio , Inestabilidad de la Articulación , Equilibrio Postural , Humanos , Masculino , Inestabilidad de la Articulación/fisiopatología , Inestabilidad de la Articulación/rehabilitación , Femenino , Equilibrio Postural/fisiología , Adulto , Terapia por Ejercicio/métodos , Articulación del Tobillo/fisiopatología , Terapia por Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/instrumentación , Músculo Esquelético/fisiopatología , Atrofia Muscular/fisiopatología , Atrofia Muscular/rehabilitación , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Adulto Joven , Estimulación Eléctrica/métodosRESUMEN
BACKGROUNDS: Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. METHODS: Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. RESULTS: The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. CONCLUSIONS: In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.
Asunto(s)
Atrofia Muscular , Proteínas Plasmáticas de Unión al Retinol , Transducción de Señal , Animales , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Ratones , Atrofia Muscular/metabolismo , Atrofia Muscular/etiología , Proteínas de la Membrana/metabolismo , Ratones Noqueados , Modelos Animales de Enfermedad , Factor de Transcripción STAT3/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Masculino , Janus Quinasa 2/metabolismoRESUMEN
The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and ß-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.
Asunto(s)
Hemorragia Subaracnoidea , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia Subaracnoidea/terapia , Hemorragia Subaracnoidea/complicaciones , Dieta Rica en Proteínas , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Metabolómica/métodos , Atrofia Muscular/etiología , Terapia por Estimulación Eléctrica/métodos , Anciano , Metaboloma , Suplementos DietéticosRESUMEN
Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.
Asunto(s)
Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Enfermedades Musculares , Sepsis , Animales , Sepsis/complicaciones , Ratones , Masculino , Enfermedades Musculares/etiología , Enfermedades Musculares/patología , Atrofia Muscular/etiología , Atrofia Muscular/patología , Músculo Esquelético , Suspensión TraseraRESUMEN
Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear. Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1ß, TNF-α, and RhoA/ROCK were determined by Western blotting. Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably. Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.
Asunto(s)
Diafragma , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Atrofia Muscular , Enfermedad Pulmonar Obstructiva Crónica , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Animales , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Quinasas Asociadas a rho/metabolismo , Masculino , Atrofia Muscular/prevención & control , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Atrofia Muscular/etiología , Proteína de Unión al GTP rhoA/metabolismo , Diafragma/metabolismo , Diafragma/fisiopatología , Diafragma/patología , Línea Celular , Proteínas de Unión al GTP rho/metabolismo , Terapia por Ejercicio/métodos , Ratones , Pulmón/patología , Pulmón/metabolismo , Pulmón/fisiopatología , Mediadores de Inflamación/metabolismo , Condicionamiento Físico AnimalRESUMEN
OBJECTIVES: A high proportion of women with advanced epithelial ovarian cancer (EOC) experience weakness and cachexia. This relationship is associated with increased morbidity and mortality. EOC is the most lethal gynecological cancer, yet no preclinical cachexia model has demonstrated the combined hallmark features of metastasis, ascites development, muscle loss and weakness in adult immunocompetent mice. METHODS: Here, we evaluated a new model of ovarian cancer-induced cachexia with the advantages of inducing cancer in adult immunocompetent C57BL/6J mice through orthotopic injections of EOC cells in the ovarian bursa. We characterized the development of metastasis, ascites, muscle atrophy, muscle weakness, markers of inflammation, and mitochondrial stress in the tibialis anterior (TA) and diaphragm â¼45, â¼75 and â¼90 days after EOC injection. RESULTS: Primary ovarian tumour sizes were progressively larger at each time point while severe metastasis, ascites development, and reductions in body, fat and muscle weights occurred by 90 Days. There were no changes in certain inflammatory (TNFα), atrogene (MURF1 and Atrogin) or GDF15 markers within both muscles whereas IL-6 was increased at 45 and 90 Day groups in the diaphragm. TA weakness in 45 Day preceded atrophy and metastasis that were observed later (75 and 90 Day, respectively). The diaphragm demonstrated both weakness and atrophy in 45 Day. In both muscles, this pre-severe-metastatic muscle weakness corresponded with considerable reprogramming of gene pathways related to mitochondrial bioenergetics as well as reduced functional measures of mitochondrial pyruvate oxidation and creatine-dependent ADP/ATP cycling as well as increased reactive oxygen species emission (hydrogen peroxide). Remarkably, muscle force per unit mass at 90 days was partially restored in the TA despite the presence of atrophy and severe metastasis. In contrast, the diaphragm demonstrated progressive weakness. At this advanced stage, mitochondrial pyruvate oxidation in both muscles exceeded control mice suggesting an apparent metabolic super-compensation corresponding with restored indices of creatine-dependent adenylate cycling. CONCLUSIONS: This mouse model demonstrates the concurrent development of cachexia and metastasis that occurs in women with EOC. The model provides physiologically relevant advantages of inducing tumour development within the ovarian bursa in immunocompetent adult mice. Moreover, the model reveals that muscle weakness in both TA and diaphragm precedes severe metastasis while weakness also precedes atrophy in the TA. An underlying mitochondrial bioenergetic stress corresponded with this early weakness. Collectively, these discoveries can direct new research towards the development of therapies that target pre-atrophy and pre-severe-metastatic weakness during EOC in addition to therapies targeting cachexia.
Asunto(s)
Caquexia , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Mitocondrias , Debilidad Muscular , Neoplasias Ováricas , Animales , Caquexia/metabolismo , Caquexia/etiología , Caquexia/patología , Femenino , Ratones , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/complicaciones , Debilidad Muscular/metabolismo , Debilidad Muscular/etiología , Mitocondrias/metabolismo , Mitocondrias/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/metabolismo , Atrofia Muscular/etiología , Atrofia Muscular/patología , Metástasis de la Neoplasia , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Línea Celular TumoralRESUMEN
Chronic inflammation causes muscle wasting. Because most inflammatory cytokine signals are mediated via TGF-ß-activated kinase-1 (TAK1) activation, inflammatory cytokine-induced muscle wasting may be ameliorated by the inhibition of TAK1 activity. The present study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG/Jcl mice as an autoimmune arthritis animal model were treated with a small amount of mannan as an adjuvant to enhance the production of TNF-α and IL-1ß. The increase in these inflammatory cytokines caused a reduction in muscle mass and strength along with an induction of arthritis in SKG/Jcl mice. Those changes in muscle fibers were mediated via the phosphorylation of TAK1, which activated the downstream signaling cascade via NF-κB, p38 MAPK, and ERK pathways, resulting in an increase in myostatin expression. Myostatin then reduced the expression of muscle proteins not only via a reduction in MyoD1 expression but also via an enhancement of Atrogin-1 and Murf1 expression. TAK1 inhibitor, LL-Z1640-2, prevented all the cytokine-induced changes in muscle wasting. Thus, TAK1 inhibition can be a new therapeutic target of not only joint destruction but also muscle wasting induced by inflammatory cytokines.
Asunto(s)
Citocinas , Quinasas Quinasa Quinasa PAM , Atrofia Muscular , Animales , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Atrofia Muscular/etiología , Atrofia Muscular/tratamiento farmacológico , Ratones , Citocinas/metabolismo , Debilidad Muscular/metabolismo , Debilidad Muscular/tratamiento farmacológico , Miostatina/metabolismo , Miostatina/antagonistas & inhibidores , Proteínas Musculares/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , FN-kappa B/metabolismo , Inflamación/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Fosforilación/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Zearalenona/farmacología , Zearalenona/análogos & derivadosRESUMEN
Hand weakness is a frequent chief concern in neurology practice. We report a case of a 55-year-old woman presenting with a chronic, gradually worsening right hand weakness and atrophy, selectively affecting the thenar muscles, without any sensory symptoms. She had a history of carpal tunnel syndrome and previously underwent surgical carpal tunnel release. This case delves into the differential diagnosis of hand weakness and atrophy, emphasizing the significance of myotomal innervation in intrinsic hand muscles. Furthermore, it outlines a systematic approach to diagnosing an uncommon cause for a common clinical presentation, offering a comprehensive differential diagnosis, and exploring various possible causes.
Asunto(s)
Mano , Debilidad Muscular , Humanos , Femenino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/diagnóstico , Razonamiento Clínico , Diagnóstico Diferencial , Atrofia Muscular/etiología , Atrofia Muscular/diagnóstico , Atrofia , Síndrome del Túnel Carpiano/diagnósticoRESUMEN
BACKGROUND: Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer. METHODS: The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6-10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients' medical records; (v) explorative outcomes of patients' experience of the exercise program which will be evaluated using focus group/individual interviews. DISCUSSION: It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.
Asunto(s)
Neoplasias del Sistema Biliar , Neoplasias Hepáticas , Músculo Esquelético , Neoplasias Pancreáticas , Entrenamiento de Fuerza , Humanos , Entrenamiento de Fuerza/métodos , Neoplasias Pancreáticas/cirugía , Neoplasias del Sistema Biliar/complicaciones , Neoplasias del Sistema Biliar/cirugía , Músculo Esquelético/fisiopatología , Neoplasias Hepáticas/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Flujo Sanguíneo Regional , Resultado del Tratamiento , Calidad de Vida , Fuerza Muscular , Factores de Tiempo , Ejercicio Preoperatorio , Atrofia Muscular/prevención & control , Atrofia Muscular/etiología , Atrofia Muscular/fisiopatología , Sarcopenia/prevención & control , Sarcopenia/fisiopatología , Sarcopenia/etiologíaRESUMEN
Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.
Asunto(s)
Neoplasias de la Mama , MicroARNs , Músculo Esquelético , Atrofia Muscular , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Atrofia Muscular/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/patología , Atrofia Muscular/etiología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Animales , Desarrollo de Músculos/genéticaRESUMEN
Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study characterized the effect of an amino acid mixture (AA) in models of SMA, focusing on mitochondria. C57/Bl6 mice underwent immobilization of one hindlimb (I) or cardiotoxin-induced muscle injury (C) and were compared with controls (CTRL). Mice were then administered AA in drinking water for 10 days and compared to a placebo group. With respect to CTRL, I and C reduced running time and distance, along with grip strength; however, the reduction was prevented by AA. Tibialis anterior (TA) muscles were used for histology and mitochondria isolation. I and C resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio and smaller myofibers than those of CTRL. Interestingly, these alterations were lightly observed in mice treated with AA. The mitochondrial yield from the TA of I and C mice was lower than that of CTRL but not in AA-treated mice. AA also preserved mitochondrial bioenergetics in TA muscle from I and C mice. To conclude, this study demonstrates that AA prevents loss of muscle mass and function in SMA by protecting mitochondria.
Asunto(s)
Aminoácidos , Metabolismo Energético , Ratones Endogámicos C57BL , Músculo Esquelético , Atrofia Muscular , Animales , Ratones , Metabolismo Energético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Aminoácidos/farmacología , Aminoácidos/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/patología , Atrofia Muscular/etiología , Masculino , Modelos Animales de Enfermedad , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/patología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacosRESUMEN
OBJECTIVE: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. METHODS: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. RESULTS: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1ß, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. CONCLUSION: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.
Asunto(s)
Progresión de la Enfermedad , Músculo Esquelético , Atrofia Muscular , Osteoartritis , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Animales , Conejos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Osteoartritis/etiología , Osteoartritis/metabolismo , Osteoartritis/prevención & control , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Masculino , Humanos , Condicionamiento Físico Animal/fisiología , Femenino , Modelos Animales de EnfermedadRESUMEN
Sarcopenia is a prevalent and clinically significant condition, particularly among older age groups and those with chronic disease. Patients with cancer frequently suffer from sarcopenia and progressive loss of muscle mass, strength, and function. The complex interplay between cancer and its treatment, including medical therapy, radiotherapy, and surgery, significantly contributes to the onset and worsening of sarcopenia. Cancer induces muscle wasting through inflammatory processes, metabolic alterations, and hormonal imbalance. Moreover, medical and radiation therapies exert direct toxic effects on muscles, contributing to the impairment of physical function. Loss of appetite, malnutrition, and physical inactivity further exacerbate muscle wasting in cancer patients. Imaging techniques are the cornerstones for sarcopenia diagnosis. Magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry provide valuable insights into muscle structure and quality. Although each modality has advantages and limitations, magnetic resonance imaging produces high-resolution images and provides dynamic information about muscle function. Despite these challenges, addressing sarcopenia is essential for optimizing treatment outcomes and improving survival rates in patients with cancer. This review explored the factors contributing to sarcopenia in oncologic patients, emphasizing the importance of early detection and comprehensive management strategies.
Asunto(s)
Músculo Esquelético , Neoplasias , Sarcopenia , Humanos , Sarcopenia/etiología , Sarcopenia/terapia , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Músculo Esquelético/diagnóstico por imagen , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , Imagen por Resonancia Magnética/métodosRESUMEN
Muscle loss is a significant health concern, particularly with the increasing trend of population aging, and sarcopenia has emerged as a common pathological process of muscle loss in the elderly. Currently, there has been significant progress in the research on sarcopenia, including in-depth analysis of the mechanisms underlying sarcopenia caused by aging and the development of corresponding diagnostic criteria, forming a relatively complete system. However, as research on sarcopenia progresses, the concept of secondary sarcopenia has also been proposed. Due to the incomplete understanding of muscle loss caused by chronic diseases, there are various limitations in epidemiological, basic, and clinical research. As a result, a comprehensive concept and diagnostic system have not yet been established, which greatly hinders the prevention and treatment of the disease. This review focuses on Type 2 Diabetes Mellitus (T2DM)-related sarcopenia, comparing its similarities and differences with sarcopenia and disuse muscle atrophy. The review show significant differences between the three muscle-related issues in terms of pathological changes, epidemiology and clinical manifestations, etiology, and preventive and therapeutic strategies. Unlike sarcopenia, T2DM-related sarcopenia is characterized by a reduction in type I fibers, and it differs from disuse muscle atrophy as well. The mechanism involving insulin resistance, inflammatory status, and oxidative stress remains unclear. Therefore, future research should further explore the etiology, disease progression, and prognosis of T2DM-related sarcopenia, and develop targeted diagnostic criteria and effective preventive and therapeutic strategies to better address the muscle-related issues faced by T2DM patients and improve their quality of life and overall health.
Asunto(s)
Diabetes Mellitus Tipo 2 , Sarcopenia , Humanos , Sarcopenia/patología , Sarcopenia/etiología , Sarcopenia/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/epidemiología , Músculo Esquelético/patología , Atrofia Muscular/patología , Atrofia Muscular/etiología , Trastornos Musculares Atróficos/patología , Trastornos Musculares Atróficos/complicaciones , Envejecimiento/patologíaRESUMEN
OBJECTIVE: The objective of the study was to explore red cell distribution width (RDW) as a surrogate marker of inflammation, alone and in conjunction with muscle wasting to predict malnutrition-related adverse outcomes. METHODS: This was a single-center observational study including adult hospitalized patients. Demographic variables, malnutrition criteria, and RDW were captured within 24 hours of hospital admission. Correlation tests and regression models were performed between these variables (RDW and muscle wasting) and adverse outcomes (in-hospital mortality and unplanned transfer to critical care areas (CCA). RESULTS: Five hundred and forty-five patients were included in the final analysis. Muscle wasting showed an independent association with adverse outcomes in every regression model tested. RDW alone showed fair predictive performance for both outcomes' significance and the adjusted model with muscle wasting showed association only for unplanned transfer to CCA. CONCLUSION: RDW did not improve the prediction of adverse outcomes compared to muscle wasting assessed by physical examination and simple indexes for acute and chronic inflammation. Malnourished patients presented higher RDW values showing a possible metabolic profile (higher inflammation and lower muscle). It is still unknown whether nutrition support can influence RDW value over time as a response marker or if RDW can predict who may benefit the most from nutritional support.
OBJETIVO: Explorar el ancho de distribución eritrocitaria (ADE) como un marcador subrogado de inflamación, individualmente y en conjunto con el desgaste muscular, para predecir resultados adversos asociados a la desnutrición. MÉTODO: Estudio unicéntrico, observacional, incluyendo pacientes adultos hospitalizados. Se capturaron variables demográficas, criterios de desnutrición y el ADE en las primeras 24 horas de ingreso. Se realizaron pruebas de correlación y modelos de regresión entre dichas variables (ADE y desgaste) y resultados adversos (mortalidad hospitalaria y traslado no planeado a áreas críticas). RESULTADOS: Se incluyeron 545 pacientes. El desgaste muscular mostró asociación independiente con los resultados adversos en cada modelo. El ADE individualmente mostró un desempeño aceptable para la predicción de ambos resultados, y en modelos ajustados con desgaste muscular mostró asociación únicamente con traslado no planeado a áreas críticas. CONCLUSIONES: El ADE no mejoró la predicción de resultados adversos comparado con el desgaste muscular por exploración física e índices simples de inflamación. Los pacientes con desnutrición presentaron mayores valores de ADE, mostrando un posible perfil metabólico (mayor inflamación y menos músculo). Aún se desconoce si el soporte nutricional puede influenciar el ADE como un marcador de respuesta o si puede predecir una respuesta favorable al soporte nutricional.