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OBJECTIVE: To identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer. METHODS: This is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction. RESULTS: Approximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present. CONCLUSIONS: Lower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT.
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Composição Corporal , Quimiorradioterapia , Fenótipo , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Pessoa de Meia-Idade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estudos Prospectivos , Adulto , Gordura Intra-Abdominal/diagnóstico por imagem , Idoso , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/efeitos da radiação , Tomografia Computadorizada por Raios X/métodos , Fatores de RiscoRESUMO
The aim of this study was to investigate whether baseline values and acute and chronic changes in androgen receptors (AR) markers, including total AR, cytoplasmic (cAR), and nuclear (nAR) fractions, as well as DNA-binding activity (AR-DNA), are involved in muscle hypertrophy responsiveness by comparing young nonresponder and responder individuals. After 10 wk of resistance training (RT), participants were identified as nonresponders using two typical errors (TE) obtained through two muscle cross-sectional area (mCSA) ultrasound measurements (2 × TE; 4.94%), and the highest responders within our sample were numerically matched. Muscle biopsies were performed at baseline, 24 h after the first RT session (acute responses), and 96 h after the last session (chronic responses). AR, cAR, and nAR were analyzed using Western blotting, and AR-DNA was analyzed using an ELISA-oligonucleotide assay. Twelve participants were identified as nonresponders (ΔmCSA: -1.32%) and 12 as responders (ΔmCSA: 21.35%). There were no baseline differences between groups in mCSA, AR, cAR, nAR, or AR-DNA (P > 0.05). For acute responses, there was a significant difference between nonresponders (+19.5%) and responders (-14.4%) in AR-DNA [effect size (ES) = -1.39; 95% confidence interval (CI): -2.53 to -0.16; P = 0.015]. There were no acute between-group differences in any other AR markers (P > 0.05). No significant differences between groups were observed in chronic responses across any AR markers (P > 0.05). Nonresponders and responders presented similar baseline, acute, and chronic results for the majority of the AR markers. Thus, our findings do not support the influence of AR markers on muscle hypertrophy responsiveness to RT in untrained individuals.NEW & NOTEWORTHY We explored, for the first time, the influence of androgen receptor (AR) through the separation of cytoplasmic and nuclear cell fractions [i.e., cytoplasmic androgen receptor (cAR), nuclear androgen receptor (nAR), and androgen receptor DNA-binding activity (AR-DNA)] on muscle hypertrophy responsiveness to resistance training. The absence of muscle hypertrophy in naïve individuals does not seem to be explained by baseline values, and acute or chronic changes in AR markers.
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Hipertrofia , Músculo Esquelético , Receptores Androgênicos , Treinamento Resistido , Humanos , Treinamento Resistido/métodos , Receptores Androgênicos/metabolismo , Masculino , Músculo Esquelético/metabolismo , Adulto Jovem , Adulto , Biomarcadores/metabolismo , FemininoRESUMO
Previous studies have demonstrated that a low skeletal muscle mass (SMM) is an adverse factor for overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). However, its association with the treatment response has not been extensively investigated. This study aimed to determine the association between low skeletal muscle mass (SMM) and treatment response in DLBCL patients. We conducted a retrospective cohort study of 123 patients with DLBCL, in whom SMM was assessed using computed tomography before chemotherapy administration. The demographic characteristics of the patients with low SMM and those with normal SMM were not statistically different. However, there were notable differences in weight and BMI; patients with low SMM had a lower mean weight (59.2 vs 63, p = 0.002) and a higher proportion of patients with normal BMI (61.5% vs. 21.1%, p < 0.001). In addition, patients with low SMM were more likely to receive R-CHOP-like treatment (21.2% vs. 7%, p = 0.022) and experienced more delays in administration (42.9% vs. 33.3%, p = 0.452). Low SMM was not associated with failure to achieve CR (HR 1.9; 95% CI [0.9-4.1] p = 0.84), but it was reported to risk OS in univariate analysis (HR 2.1; 95% CI [1.03-4.2], p = 0.041). An interesting result was the interaction of low SMM with hypertension as a risk factor for not achieving CR (HR 2.7; 95% CI [1.1-6.5] p = 0.034) or OS (HR 7.9; 95% CI [3.4-18.8] p < 0.001). Low SMM was not a risk factor for achieving CR in patients with DLBCL and seemed to play a role in OS.
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We aimed to evaluate performance, body development, metabolism, and expression of genes related to skeletal muscle hypertrophy in non-castrated male dairy kids fed with different levels of MR during the pre-weaning period. Sixty newborn male kids, not castrated, from Saanen and Swiss Alpine breeds, with an average body weight (BW) of 3.834 ± 0.612 kg, were distributed in a randomized block design. Breeds were the block factor in the model (random effect). Kids were allocated into 2 nutrition plans (n = 30 kids per treatment) categorized as follows: low nutritional plan (LNP; 1L MR/kid/day) or high nutritional plan (HNP; 2L MR/kid/day). All kids were harvested at 45 d of life. The majority of nitrogen balance variables were affected by the nutritional plan (P < 0.050). Morphometric measures and body condition score (2.99 - LNP vs. 3.28 - HNP) were affected by nutritional plan (P < 0.050), except hip height, thoracic depth and hip width. The nutritional plan affected the body components (P < 0.050), except esophagus and trachea. Animal performance and carcass traits were influenced by nutritional plan (P < 0.050), except carcass dressing (48.56% on average). Nutritional plan affected (P < 0.050) some blood profile variables as the total cholesterol (141.35 vs. 113.25 mg/dL), triglycerides (60.53 vs. 89.05 mg/dL), LDL (79.76 vs. 33.66 g/mL) and IGF-1 (17.77 vs. 38.55 ng/mL) for LNP and HNP respectively. Hypertrophy was greater in HNP than LNP animals (P < 0.050), being represented by the proportion of sarcoplasm (39.76 vs. 31.99%). LNP had a greater mTOR abundance than HNP (P = 0.045), but AMPK was not affected by the nutritional plan. Our findings show that a higher milk replacer allowance enhances animal performance, body development, metabolic parameters, and cellular hypertrophy in pre-weaned dairy kids.
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This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.
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Fator de Indução de Apoptose , Apoptose , Jejum , Treinamento Intervalado de Alta Intensidade , Fibras Musculares de Contração Lenta , Atrofia Muscular , Miostatina , Ratos Wistar , Transdução de Sinais , Animais , Masculino , Apoptose/fisiologia , Jejum/metabolismo , Jejum/fisiologia , Miostatina/metabolismo , Treinamento Intervalado de Alta Intensidade/métodos , Ratos , Transdução de Sinais/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Fator de Indução de Apoptose/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Rápida/patologia , Endodesoxirribonucleases/metabolismo , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/metabolismo , Jejum Intermitente , Poli(ADP-Ribose) Polimerase-1RESUMO
Regeneration is a remarkable characteristic of the skeletal muscle. Triggered by common lesions, regeneration is stimulated resulting in muscle fiber repair and restoration of muscle homeostasis in normal muscle. In genetic dystrophic muscle, the cycle of degeneration/regeneration is an endless loop that leads to impaired regeneration and substitution of muscle fibers by connective and adipose tissue, causing muscle weakness. Identification and characterization of muscle regeneration steps can help discover potential therapy targets for muscle diseases and aging. Muscle regeneration markers such as the number of satellite cells in the muscle, the proportion of activated satellite cells, and the quantity of regenerating muscle fiber can be quantified using immunolabeling.Here we are presenting a quantitative method to measure muscle regeneration that can be applied to different proposals. To demonstrate the protocol applicability, we used models for acute and chronic muscle injuries. As model of acute degeneration, a wild-type C57BL6 mice with muscle injury induced by electroporation was used, and the muscle was analyzed after 5 and 10 days post-injury. DMDmdx mouse muscle was used as a model of chronic degeneration. The methodologies presented here are among the gold standard methodologies for muscle regeneration analysis and can be easily applied to any type of muscle regeneration study.
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Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, nuclear magnetic resonance imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced inflammation promote a rapid loss of muscle mass and reduction in fiber cross-sectional area by upregulation of muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1 expression, both key regulators of SkM fibers atrophy. Despite a reduction in inflammation and clearance of infectious viral particles, SkM atrophy persists until 30 days post-infection. The genomic CHIKV and MAYV RNAs were still detected in SkM in the late phase, along with the upregulation of chemokines and anti-inflammatory cytokine expression. In agreement with the involvement of inflammatory mediators on induced atrophy, the neutralization of TNF and a reduction in oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogen expression and atrophic fibers while increasing weight gain in treated mice. These data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphavirus pathogenesis and with a description of potentially new targets of therapeutic intervention.
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Vírus Chikungunya , Músculo Esquelético , Atrofia Muscular , Estresse Oxidativo , Animais , Atrofia Muscular/virologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Camundongos , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/virologia , Febre de Chikungunya/patologia , Febre de Chikungunya/virologia , Febre de Chikungunya/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Inflamação/virologia , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Replicação Viral , Camundongos Endogâmicos C57BL , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Infecções por Alphavirus/virologia , Infecções por Alphavirus/patologia , Infecções por Alphavirus/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Modelos Animais de Doenças , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: The study of dietary patterns in older adults (OA) and their association with geriatric syndromes (GS) is scarce in Latin America. OBJECTIVE: To describe the association of dietary patterns with GS in the Mexican older adult population, using data from the 2018-19 National Health and Nutrition Survey. METHODS: Dietary data were collected from 3,511 adults (≥60 years of age, both sexes) using a semi-quantitative food frequency questionnaire. Dietary patterns were derived by principal component analysis based on the consumption of 162 foods from 24 food groups. The GS studied were: frailty, depressive symptoms (DS), low appendicular skeletal muscle mass (ASMM); additionally, we studied inflammation (serum CRP>5 mg/L). Logistic regression models were used. RESULTS: Four major dietary patterns were identified: a) "Western", b) "Prudent", c) "Soups", and d) "Traditional". The middle and higher tertiles of the "Prudent" pattern were associated with lower odds of DS (OR 0.71, p = 0.04; and OR 0.61, p = 0.008), respectively. The second tertile of the "Soups" pattern was associated with lower odds of low ASMM (OR 0.68, p = 0031) and inflammation (OR 0.58, p = 0.022). The highest tertile of the "Traditional" pattern was associated with low ASMM (OR 1.55, p = 0.008) and lower odds of inflammation (OR 0.69, p = 0.044). No association was found between the "Western" dietary pattern and GS. CONCLUSIONS: Three of four major dietary patterns were associated with GS in older Mexican adults. Further studies are needed to address strategies to improve diet quality in this age group and its association with health and functional outcomes.
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Inquéritos Nutricionais , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , México/epidemiologia , Dieta , Fragilidade/epidemiologia , Idoso de 80 Anos ou mais , Inflamação/epidemiologia , Depressão/epidemiologia , Síndrome , Comportamento Alimentar , Padrões DietéticosRESUMO
To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths.
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Bothrops , Colágeno , Venenos de Crotalídeos , Hemorragia , Inflamação , Terapia com Luz de Baixa Intensidade , Músculo Esquelético , Animais , Camundongos , Terapia com Luz de Baixa Intensidade/métodos , Músculo Esquelético/efeitos da radiação , Músculo Esquelético/efeitos dos fármacos , Hemorragia/patologia , Colágeno/metabolismo , Colágeno/análise , Venenos de Crotalídeos/toxicidade , Raios Infravermelhos , Masculino , Lasers Semicondutores/uso terapêutico , Mordeduras de Serpentes/radioterapiaRESUMO
Molecular mechanisms associated to improvement of metabolic syndrome (MetS) during exercise are not fully elucidated. MetS was induced in 250 g male Wistar rats by 30% sucrose in drinking water. Control rats receiving tap water were controls, both groups received solid standard diet. After 14 weeks, an endurance exercised group, and a sedentary were formed for 8 weeks. The soleus and extensor digitorum longus (EDL) muscles were dissected to determine contractile performance, expression of myosin heavy chain isoforms, PGC1α, AMPKα2, NFATC1, MEF2a, SIX1, EYA1, FOXO1, key metabolic enzymes activities. Exercise mildly improved MetS features. MetS didn't alter the contractile performance of the muscles. Exercise didn't altered expression of PGC1α, NFATC1, SIX1 and EYA1 on MetS EDL whereas NFATC1 increased in soleus. Only citrate synthase was affected by MetS on the EDL and this was partially reverted by exercise. Soleus α-ketoglutarate dehydrogenase activity was increased by exercise but MetS rendered the muscle resistant to this effect. MetS affects mostly the EDL muscle, and endurance exercise only partially reverts this. Soleus muscle seems more resilient to MetS. We highlight the importance of studying both muscles during MetS, and their metabolic remodeling on the development and treatment of MetS by exercise.
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Metabolismo Energético , Síndrome Metabólica , Condicionamento Físico Animal , Ratos Wistar , Animais , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Ratos , Músculo Esquelético/metabolismo , Sacarose/metabolismo , Sacarose/administração & dosagem , Fibras Musculares Esqueléticas/metabolismo , Contração Muscular , FenótipoRESUMO
INTRODUCTION: The phenotypic consequences of the p.Arg577Ter variant in the α-actinin-3 (ACTN3) gene are suggestive of a trade-off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the ACTN3 p.Arg577Ter variant with long-distance endurance athlete status, using previously published data with the Brazilian population. METHODS: Genotypic data from 203 long-distance athletes and 1724 controls were analysed in a case-control approach. RESULTS: The frequency of the X allele was significantly higher in long-distance athletes than in the control group (51.5% vs. 41.4%; p = 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long-distance athlete (p = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long-distance athlete (p = 0.00017). CONCLUSION: The X allele, mainly the X/X genotype, was associated with long-distance athlete status in Brazilians.
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Actinina , Alelos , Atletas , Humanos , Brasil , Actinina/genética , Masculino , Feminino , Adulto , Estudos Retrospectivos , Estudos de Casos e Controles , Genótipo , Frequência do Gene , Resistência Física/genética , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Phase angle (PhA) is an indicator of cellular health, function, and integrity. PhA has been considered an indicator of nutritional and health status, but it is uncertain whether it could be used as a fitness or athletic performance indicator. OBJECTIVE: To analyze the relationship between PhA and the fitness and athletic performance of adolescent boxers and to know whether this association is independent of body composition. METHODS: Thirty-seven trained youth boxers (15-18 y old) participated in the study. Participants underwent anthropometry and bioelectrical impedance assessments. The following tests were conducted: Fitness-Gram battery; speed, agility, and quickness; ball throws; punch impact force; bench press maximal strength; and vertical and horizontal jumps. Linear regression models were estimated and adjusted by covariates. RESULTS: The PhA was related to upper-limb strength. Nevertheless, in linear regression models, after adjusting models by body composition, only PhA remained as a predictor of relative maximal strength. The PhA was not a predictor of speed, agility, and quickness; cardiorespiratory fitness; or lower-limb power, in which adiposity was the main predictor of fitness. CONCLUSIONS: In adolescent boxers, PhA can predict upper-limb maximal strength independently of bioelectrical impedance analysis premises. However, compared with mucle mass, PhA is not a better predictor of upper-limb maximal strength.
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Desempenho Atlético , Composição Corporal , Boxe , Impedância Elétrica , Força Muscular , Humanos , Adolescente , Desempenho Atlético/fisiologia , Masculino , Força Muscular/fisiologia , Boxe/fisiologia , Aptidão Física/fisiologia , Feminino , Antropometria , Aptidão Cardiorrespiratória/fisiologia , Teste de Esforço , Modelos Lineares , Extremidade Superior/fisiologiaRESUMO
OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.
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Composição Corporal , Neoplasias Colorretais , Comorbidade , Humanos , Masculino , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Feminino , Idoso , Estudos de Coortes , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Fatores EtáriosRESUMO
BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.
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Composição Corporal , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Desempenho Físico Funcional , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Prospectivos , Metaboloma/fisiologia , Estudos de Casos e Controles , Consumo de Oxigênio/fisiologia , Taxa de Sobrevida , Qualidade de Vida , Fibras Musculares Esqueléticas/metabolismo , Proliferação de Células , Teste de CaminhadaRESUMO
This study aimed to evaluate the prognostic value of thigh muscle assessed by CT images to predict overall mortality in patients with colorectal cancer (CRC). This was a multicenter cohort study including adults (≥ 18 years old) newly diagnosed with CRC, who performed a diagnostic computed tomography (CT) exam including thigh regions. CT images were analyzed to evaluate skeletal muscle (SM in cm2), skeletal muscle index (SMI in cm2/m2), and skeletal muscle density (SMD in HU). Muscle abnormalities (low SM, SMI, and SMD) were defined as the values below the median by sex. Kaplan-Meyer curves and hazard ratios (HRs) for low SM, SMI and SMD were evaluated for overall mortality, stratified by sex. A total of 257 patients were included in the final analysis. Patients' mean age was 62.6 ± 12.1 years, and 50.2% (n = 129) were females. In males, low thigh SMI was associated with shorter survival (log-rank P = .02). Furthermore, this low thigh SMI (cm2/m2) was independently associated with higher mortality rates (HR adjusted 2.08, 95% CI 1.03-4.18). Our additional findings demonstrated that low SMD was independently associated with overall mortality among early-stage patients (I-III) (HR adjusted 2.78, 95% CI 1.26-6.15).
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Neoplasias Colorretais , Músculo Esquelético , Coxa da Perna , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Coxa da Perna/diagnóstico por imagem , Idoso , Prognóstico , Estimativa de Kaplan-MeierRESUMO
The production and release of cortisol during stress responses are key regulators of growth in teleosts. Understanding the molecular responses to cortisol is crucial for the sustainable farming of rainbow trout (Oncorhynchus mykiss) and other salmonid species. While several studies have explored the genomic and non-genomic impacts of cortisol on fish growth and skeletal muscle development, the long-term effects driven by epigenetic mechanisms, such as cortisol-induced DNA methylation, remain unexplored. In this study, we analyzed the transcriptome and genome-wide DNA methylation in the skeletal muscle of rainbow trout seven days after cortisol administration. We identified 550 differentially expressed genes (DEGs) by RNA-seq and 9059 differentially methylated genes (DMGs) via whole-genome bisulfite sequencing (WGBS) analysis. KEGG enrichment analysis showed that cortisol modulates the differential expression of genes associated with nucleotide metabolism, ECM-receptor interaction, and the regulation of actin cytoskeleton pathways. Similarly, cortisol induced the differential methylation of genes associated with focal adhesion, adrenergic signaling in cardiomyocytes, and Wnt signaling. Through integrative analyses, we determined that 126 genes showed a negative correlation between up-regulated expression and down-regulated methylation. KEGG enrichment analysis of these genes indicated participation in ECM-receptor interaction, regulation of actin cytoskeleton, and focal adhesion. Using RT-qPCR, we confirmed the differential expression of lamb3, itga6, limk2, itgb4, capn2, and thbs1. This study revealed for the first time the molecular responses of skeletal muscle to cortisol at the transcriptomic and whole-genome DNA methylation levels in rainbow trout.
Assuntos
Metilação de DNA , Hidrocortisona , Músculo Esquelético , Oncorhynchus mykiss , Estresse Fisiológico , Transcriptoma , Animais , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Estresse Fisiológico/genética , Epigênese Genética , Epigenômica/métodos , Perfilação da Expressão Gênica , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismoRESUMO
To assess malnutrition contribution to the functional status and health related quality of life after hospitalization due to COVID-19 pneumonia, 66 selected adults referred for physical rehabilitation accepted to participate in the study; none of them required oxygen supply or had history of lung/musculoskeletal/neurological/immune/rheumatic disease or trauma, or contraindication for respiratory-function tests. At three evaluations, with 3 months in-between, assessments included: self-report of functional status, the St. George's Respiratory Questionnaire, spirometry, the 6-min-walk-test, the MRC-scale, the 30-s sit-to-stand-test, the timed-up-and-go-test, nutritional status, and ultrasound imaging (vastus medialis and diaphragm). At referral, patients had nutritional deficits with protein deficiency, which gradually improved; while muscle thickness (of both vastus medialis and diaphragm) increased, along with muscle strength and mobility (ANOVA, p < 0.05). Contrarywise, the distance covered during the 6-min-walk-test decreased (ANOVA, p < 0.05), with a negative influence from excess body mass. During rehabilitation, health-related quality of life and functional status improved, with negative influence from a history of tobacco use and referral delay, respectively. After hospitalization due to COVID-19, early diagnosis of both protein deficiency and decrease of skeletal muscle thickness could be relevant for rehabilitation, while pondering the negative impact of excess body mass on submaximal exercise performance.
Assuntos
COVID-19 , Estado Funcional , Desnutrição , Estado Nutricional , Qualidade de Vida , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Seguimentos , SARS-CoV-2/isolamento & purificação , Adulto , Hospitalização , Força Muscular/fisiologia , Inquéritos e QuestionáriosRESUMO
Carbohydrates and fats constitute our primary energy sources. The importance of each of these energy substrates varies across cell types and physiological conditions. For example, the brain normally relies almost exclusively on glucose oxidation, whereas skeletal muscle shifts from lipids toward higher carbohydrate oxidation rates as exercise intensity increases. Understanding how carbohydrates are stored in our cells and which tissues contain significant carbohydrate stores is crucial for health professionals, especially given the role of carbohydrate metabolism in various pathophysiological conditions. This laboratory activity uses a simple and low-cost iodine binding method to quantify glycogen in mouse skeletal muscle and liver samples. By integrating the results of this activity with literature data, students can determine overall glycogen storage in the human body. The primary goal of the activity is to enhance students' understanding of the importance and limitations of glycogen stores in energy metabolism.NEW & NOTEWORTHY Carbohydrates are one of the primary energy sources utilized by our cells. Liver and skeletal muscle glycogen, which are the main carbohydrate reserves in the body, play a central role in energy metabolism, especially during periods of fasting and exercise. In this laboratory activity, students measure glycogen levels in tissues to gain insights into how carbohydrates are stored in our cells and understand the role and limitations of liver and muscle carbohydrate stores.