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1.
Eur Rev Med Pharmacol Sci ; 28(6): 2161-2167, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567578

RESUMO

OBJECTIVE: The purpose of this study is to evaluate the effect of sarcopenia on overall survival and local relapse in head and neck cancer patients undergoing surgical excision. PATIENTS AND METHODS: This retrospective study includes head and neck cancer patients primarily treated with surgical excision in a tertiary care center. Patients were included if they had undergone an abdominal region Computer Tomography scan at least 45 days before the surgical excision. Hospital records were collected, and data analysis included patient demographics, comorbidities, tumor staging, surgical details, adjuvant therapy details, treatment complications, death records, and last follow-up appointment details. RESULTS: In this retrospective study, 138 head and neck cancer patients were included, with 69.6% males and 30.4% females. The mean age was 60.2±12.3 years, and the average follow-up time was 54.3±16.3 months. Sarcopenia was present in 48.6% of patients and absent in 51.4%. Sarcopenic patients had a significantly lower mean age compared to non-sarcopenic patients (p<0.05). The proportion of larynx cancer was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p<0.05). According to the American Joint Committee on Cancer (AJCC) staging, stage IV was significantly higher in the sarcopenia group (p<0.05). Local relapse was significantly higher in the sarcopenia group (p<0.05). CONCLUSIONS: The findings of this study emphasize the importance of sarcopenia evaluation in determining prognosis and identifying patients who may benefit from specialized and intensive nutritional programs. Sarcopenia harms overall survival and local relapse in head and neck cancer patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Sarcopenia , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Sarcopenia/patologia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Prognóstico , Recidiva
2.
Sci Rep ; 14(1): 7718, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565556

RESUMO

We aimed to examine the relationship between abdominal computed tomography (CT)-based body composition data and both renal function decline and all-cause mortality in patients with non-dialysis chronic kidney disease (CKD). This retrospective study comprised non-dialysis CKD patients who underwent consecutive unenhanced abdominal CT between January 2010 and December 2011. CT-based body composition was measured using semiautomated method that included visceral fat, subcutaneous fat, skeletal muscle area and density, and abdominal aortic calcium score (AAS). Sarcopenia and myosteatosis were defined by decreased skeletal muscle index (SMI) and decreased skeletal muscle density, respectively, each with specific cutoffs. Risk factors for CKD progression and survival were identified using logistic regression and Cox proportional hazard regression models. Survival between groups based on myosteatosis and AAS was compared using the Kaplan-Meier curve. 149 patients (median age: 70 years) were included; 79 (53.0%) patients had sarcopenia and 112 (75.2%) had myosteatosis. The median AAS was 560.9 (interquartile range: 55.7-1478.3)/m2. The prognostic factors for CKD progression were myosteatosis [odds ratio (OR) = 4.31, p = 0.013] and high AAS (OR = 1.03, p = 0.001). Skeletal muscle density [hazard ratio (HR) = 0.93, p = 0.004] or myosteatosis (HR = 4.87, p = 0.032) and high AAS (HR = 1.02, p = 0.001) were independent factors for poor survival outcomes. The presence of myosteatosis and the high burden of aortic calcium were significant factors for CKD progression and survival in patients with non-dialysis CKD.


Assuntos
Insuficiência Renal Crônica , Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Sarcopenia/patologia , Cálcio , Prognóstico , Estudos Retrospectivos , Músculo Esquelético/patologia , Tomografia Computadorizada por Raios X , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia
3.
Nutrients ; 16(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474784

RESUMO

The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as biomarker for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. A significant increase in SATI (Subcutaneous Adipose Tissue Index) of 0.32 (95% CI: 0.13-0.51) p = 0.001, decrease in SMI (Skeletal Muscle Index) of -0.38 (95% CI: -0.57 to -0.19) p < 0.0001, and SMD (Skeletal Muscle Density) of -0.46 (95% CI: -0.69 to -0.24) p < 0.0001 were observed. No statistical association was visible between ADT and changes in BMI (Body Mass Index), 0.05 (95% CI: -0.18-0.28), p = 0.686, and VATI (Visceral Adipose Tissue Index): 0.17 (95% CI: -0.02 to 0.37), p = 0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.


Assuntos
Neoplasias da Próstata , Sarcopenia , Masculino , Humanos , Sarcopenia/patologia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios , Androgênios , Músculo Esquelético/patologia
4.
J Neurooncol ; 167(1): 169-180, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38430419

RESUMO

PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.


Assuntos
Neoplasias Encefálicas , Fragilidade , Sarcopenia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fragilidade/complicações , Sarcopenia/complicações , Sarcopenia/patologia , Fatores de Risco , Hospitalização , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Estudos Retrospectivos
8.
Sci Rep ; 14(1): 2709, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302636

RESUMO

With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Sarcopenia , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Sarcopenia/patologia , Músculo Esquelético/patologia , Envelhecimento
9.
Nutrition ; 121: 112363, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38359703

RESUMO

BACKGROUND: Low muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). METHOD: This cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. RESULTS: A total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07-1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772-0.908; female: AUC = 0.721, 95% CI: 0.598-0.843). CONCLUSIONS: Despite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.


Assuntos
Desnutrição , Sarcopenia , Neoplasias Gástricas , Humanos , Masculino , Feminino , Neoplasias Gástricas/diagnóstico por imagem , Impedância Elétrica , Estudos Transversais , Composição Corporal/fisiologia , Músculo Esquelético/patologia , Tomografia Computadorizada por Raios X , Desnutrição/patologia , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia
10.
Geroscience ; 46(3): 3419-3428, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38315316

RESUMO

Biopsies of muscle and adipose tissue (AT) are useful tools to gain insights into the aging processes in these tissues. However, they are invasive procedures and their risk/benefit profile in older adults can be altered by sarcopenia, frailty, poor healing, and multimorbidity. Their success rates, safety, and tolerability in a geriatric population have not been reported in detail. Investigators in the Study of Muscle, Mobility, and Aging (SOMMA) performed biopsies of muscle and AT in older adults and prospectively collected data on biopsy success rates, safety, and tolerability. We report here the methods and outcomes of these two procedures. In total, 861 participants (aged 70-94) underwent percutaneous biopsies of the Vastus lateralis muscle with a Bergstrom needle. A subset (n = 241) also underwent percutaneous biopsies of the abdominal subcutaneous AT with the tumescent liposuction technique. Success rate was assessed by the percentage of biopsies yielding adequate specimens for analyses; tolerability by pain scores; and safety by frequency of adverse events. All data were prospectively collected. The overall muscle biopsy success rate was 97.1% and was modestly lower in women. The AT biopsy success rate was 95.9% and slightly lower in men. Minimal or no pain was reported in 68% of muscle biopsies and in 83% of AT biopsies. Adverse events occurred in 2.67% of muscle biopsies and 4.15% of AT biopsies. None was serious. In older adults, percutaneous muscle biopsies and abdominal subcutaneous AT biopsies have an excellent safety profile, often achieve adequate tissue yields for analyses, and are well tolerated.


Assuntos
Músculo Esquelético , Sarcopenia , Masculino , Humanos , Idoso , Feminino , Biópsia , Músculo Esquelético/patologia , Envelhecimento , Sarcopenia/patologia , Tecido Adiposo
11.
Calcif Tissue Int ; 114(4): 340-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342790

RESUMO

We aimed to investigate the relationship among probable sarcopenia, osteoporosis (OP) and supraspinatus tendon (SSP) tears in postmenopausal women. Postmenopausal women screened/followed for OP were recruited. Demographic data, comorbidities, exercise/smoking status, and handgrip strength values were recorded. Probable sarcopenia was diagnosed as handgrip strength values < 20 kg. Achilles and SSP thicknesses were measured using ultrasound. Among 1443 postmenopausal women, 268 (18.6%) subjects had SSP tears. Unilateral tears were on the dominant side in 146 (10.1%) and on the non-dominant side in 55 women (3.8%). In contrast to those without, women with SSP tears had older age, lower level of education, thinner SSP and lower grip strength (all p < 0.05). In addition, they had higher frequencies of hypertension, hyperlipidemia, DM, OP and probable sarcopenia, but lower exercise frequency (all p < 0.05). Binary logistic regression modeling revealed that age [odds ratio (OR): 1.046 (1.024-1.067 95% CI)], hypertension [OR: 1.560 (1.145-2.124 95% CI)], OP [OR: 1.371 (1.022-1.839 95% CI)] and probable sarcopenia [OR: 1.386 (1.031-1.861 95% CI)] were significant predictors for SSP tears (all p < 0.05). This study showed that age, presence of hypertension, probable sarcopenia and OP were related with SSP tears in postmenopausal women. To this end, although OP appeared to be related to SSP tears, SSP tear/thickness evaluation can be recommended for OP patients, especially those who have other risk factors such as older age, higher BMI, hypertension, and probable sarcopenia.


Assuntos
Hipertensão , Osteoporose , Lesões do Manguito Rotador , Sarcopenia , Humanos , Feminino , Manguito Rotador/patologia , Sarcopenia/complicações , Sarcopenia/epidemiologia , Sarcopenia/patologia , Força da Mão , Pós-Menopausa , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/patologia , Osteoporose/patologia , Hipertensão/patologia
12.
Diabetes Res Clin Pract ; 209: 111573, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346590

RESUMO

AIM: To assess the effects of thyroid hormones on appendicular skeletal muscle index (SMI) and hand grip strength (HGS) in people with diabetes. METHODS: This cross-sectional cohort included 1,135 participants with diabetes admitted to 3 hospitals in Japan. Multiple regression analysis was performed to determine the associations among thyroid hormone levels, SMI, and HGS. RESULTS: Of the 1,135 participants, 480 were female. Their median (interquartile range) age, body mass index, durations of diabetes, and glycated haemoglobin levels were 68 years, 24.3 kg/m2, 10 years, and 7.6 %, respectively. The median (interquartile range) SMI (kg/m2) and hand grip strength of the cohort were 7.1 kg/m2 and 28.2 kg, respectively. Positive correlations between FT3 and the FT3/FT4 ratio with SMI and HGS was observed after adjusting for covariates in males. A negative correlation was found between the FT3/FT4 ratio and sarcopenia as a result of low SMI and low HGS in the male participants but not in females (p for interaction = 0.02). CONCLUSIONS: FT3/FT4 ratios may impact skeletal muscles in people with diabetes-particularly in males. Assessments of FT3/FT4 ratios may represent key indicators of muscle mass and strength in males.


Assuntos
Diabetes Mellitus , Sarcopenia , Humanos , Masculino , Feminino , Idoso , Força da Mão/fisiologia , Estudos Transversais , Hormônios Tireóideos , Músculo Esquelético/patologia , Diabetes Mellitus/patologia , Sarcopenia/patologia , Força Muscular
13.
J Cachexia Sarcopenia Muscle ; 15(2): 466-476, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38375571

RESUMO

Exercise is recognized to play an observable role in improving human health, especially in promoting muscle hypertrophy and intervening in muscle mass loss-related diseases, including sarcopenia. Recent rapid advances have demonstrated that exercise induces the release of abundant cytokines from several tissues (e.g., liver, muscle, and adipose tissue), and multiple cytokines improve the functions or expand the numbers of adult stem cells, providing candidate cytokines for alleviating a wide range of diseases. Muscle satellite cells (SCs) are a population of muscle stem cells that are mitotically quiescent but exit from the dormancy state to become activated in response to physical stimuli, after which SCs undergo asymmetric divisions to generate new SCs (stem cell pool maintenance) and commit to later differentiation into myocytes (skeletal muscle replenishment). SCs are essential for the postnatal growth, maintenance, and regeneration of skeletal muscle. Emerging evidence reveals that exercise regulates muscle function largely via the exercise-induced cytokines that govern SC potential, but this phenomenon is complicated and confusing. This review provides a comprehensive integrative overview of the identified exercise-induced cytokines and the roles of these cytokines in SC function, providing a more complete picture regarding the mechanism of SC homeostasis and rejuvenation therapies for skeletal muscle.


Assuntos
Doenças Musculares , Sarcopenia , Células Satélites de Músculo Esquelético , Adulto , Humanos , Citocinas , Proliferação de Células , Músculo Esquelético/patologia , Sarcopenia/patologia , Doenças Musculares/patologia
14.
Nutrition ; 120: 112327, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341908

RESUMO

OBJECTIVES: Body composition on computed tomography can predict prognosis in patients with COVID-19. The reported data are based on small retrospective studies. The aim of the present study was to analyze the prognostic relevance of skeletal muscle parameter derived from chest computed tomography for prediction of 30-d mortality in patients with COVID-19 in a multicenter setting. METHODS: The clinical databases of three centers were screened for patients with COVID-19 between 2020 and 2022. Overall, 447 patients (142 female; 31.7%) were included into the study. The mean age at the time of computed tomography acquisition was 63.8 ± 14.7 y and median age was 65 y. Skeletal muscle area and skeletal muscle density were defined on level T12 of the chest. RESULTS: Overall, 118 patients (26.3%) died within the 30-d observation period. Of the patient sample, 255 patients (57.0%) were admitted to an intensive care unit and 122 patients needed mechanical ventilation (27.3%). The mean skeletal muscle area of all patients was 96.1 ± 27.2 cm² (range = 23.2-200.7 cm²). For skeletal muscle density, the mean was 24.3 ± 11.1 Hounsfield units (range = -5.6 to 55.8 Hounsfield units). In survivors, the mean skeletal muscle density was higher compared with the lethal cases (mean 25.8 ± 11.2 versus 20.1 ± 9.6; P < 0.0001). Presence of myosteatosis was independently associated with 30-d mortality: odds ratio = 2.72 (95% CI, 1.71-4.32); P = 0.0001. CONCLUSIONS: Myosteatosis is strongly associated with 30-d mortality in patients COVID-19. Patients with COVID-19 with myosteatosis should be considered a risk group.


Assuntos
COVID-19 , Sarcopenia , Idoso , Feminino , Humanos , Composição Corporal , COVID-19/complicações , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Masculino , Pessoa de Meia-Idade
15.
Sci Rep ; 14(1): 4809, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413662

RESUMO

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.


Assuntos
Carcinoma de Células Escamosas , Sarcopenia , Neoplasias do Colo do Útero , Feminino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/metabolismo , Fluordesoxiglucose F18/metabolismo , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Prognóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/metabolismo , Tomografia por Emissão de Pósitrons , Músculo Esquelético/metabolismo , Carga Tumoral , Compostos Radiofarmacêuticos , Estudos Retrospectivos
17.
Biochem Biophys Res Commun ; 696: 149542, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38244315

RESUMO

PDZ domain-containing RING finger family protein 3 (PDZRN3) is expressed in various tissues, including the skeletal muscle. Although PDZRN3 plays a crucial role in the terminal differentiation of myoblasts and synaptic growth/maturation in myogenesis, the role of this molecule in postnatal muscles is completely unknown despite its lifelong expression in myofibers. In this study, we aimed to elucidate the function of PDZRN3 in mature myofibers using myofiber-specific conditional knockout mice. After tamoxifen injection, PDZRN3 deficiency was confirmed in both fast and slow myofibers of Myf6-CreERT2; Pdzrn3flox/flox (Pdzrn3mcKO) mice. Transcriptome analysis of the skeletal muscles of Pdzrn3mcKO mice identified differentially expressed genes, including muscle atrophy-related genes such as Smox, Amd1/2, and Mt1/2, suggesting that PDZRN3 is involved in the homeostatic maintenance of postnatal muscles. PDZRN3 deficiency caused muscle atrophy, predominantly in fast-twitch (type II) myofibers, and reduced muscle strength. While myofiber-specific PDZRN3 deficiency did not influence endplate morphology or expression of neuromuscular synaptic formation-related genes in postnatal muscles, indicating that the relationship between PDZRN3 and neuromuscular junctions might be limited during muscle development. Considering that the expression of Pdzrn3 in skeletal muscles was significantly lower in aged mice than in mature adult mice, we speculated that the PDZRN3-mediated muscle maintenance system might be associated with the pathophysiology of age-related muscle decline, such as sarcopenia.


Assuntos
Músculo Esquelético , Sarcopenia , Camundongos , Animais , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Junção Neuromuscular/patologia , Sarcopenia/patologia , Mioblastos/metabolismo , Camundongos Knockout , Ubiquitina-Proteína Ligases/metabolismo
18.
J Cachexia Sarcopenia Muscle ; 15(2): 726-734, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38263932

RESUMO

INTRODUCTION: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). METHODS: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. RESULTS: The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. CONCLUSIONS: Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Sarcopenia , Humanos , Masculino , Feminino , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Sarcopenia/patologia , Lipídeos
19.
Ann Hematol ; 103(3): 771-780, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38294533

RESUMO

The objective of this study was to analyze the correlation between skeletal muscle mass and the distribution of peripheral blood lymphocytes and natural killer (NK) cells, as well as their impact on prognosis in patients with acute myeloid leukemia (AML). A retrospective analysis was conducted on 211 newly diagnosed AML patients, evaluating skeletal muscle index (SMI), NK cell proportion, and absolute value, along with relevant clinical data. Linear regression and Spearman's correlation coefficient were used to assess the relationship between various indicators and SMI, followed by multiple linear regression for further modeling. Univariate and multivariate Cox proportional hazards regression models were used to identify independent predictors for overall survival (OS). Among the 211 AML patients, 38 cases (18.0%) were diagnosed with sarcopenia. Multiple linear regression analysis included weight, fat mass, ECOG score, body mass index, and peripheral blood NK cell proportion, constructing a correlation model for SMI (R2 = 0.745). Univariate analysis identified higher NK cell count (> 9.53 × 106/L) as a poor predictor for OS. Multivariate Cox proportional hazards regression model indicated that age ≥ 60 years, PLT < 100 × 109/L, ELN high risk, sarcopenia, and B cell count > 94.6 × 106/L were independent adverse prognostic factors for AML patients. Low skeletal muscle mass may negatively impact the count and function of NK cells, thereby affecting the prognosis of AML. However, further basic and clinical research is needed to explore the specific mechanisms underlying the relationship between NK cells and SMI in AML.


Assuntos
Leucemia Mieloide Aguda , Sarcopenia , Humanos , Pessoa de Meia-Idade , Sarcopenia/patologia , Estudos Retrospectivos , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Músculo Esquelético , Células Matadoras Naturais
20.
Physiol Rep ; 12(1): e15917, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225199

RESUMO

Sarcopenia is a systemic skeletal muscle disease characterized by a decline in skeletal muscle mass and function. Originally defined as an age-associated condition, sarcopenia presently also encompasses muscular atrophy due to various pathological factors, such as intensive care unit-acquired weakness, inactivity, and malnutrition. The exact pathogenesis of sarcopenia is still unknown; herein, we review the pathological roles of the neuromuscular junction and mitochondria in this condition. Sarcopenia is caused by complex and interdependent pathophysiological mechanisms, including aging, neuromuscular junction impairment, mitochondrial dysfunction, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, and inflammation. Among these, neuromuscular junction instability and mitochondrial dysfunction are particularly significant. Dysfunction in neuromuscular junction can lead to muscle weakness or paralysis. Mitochondria, which are plentiful in neurons and muscle fibers, play an important role in neuromuscular junction transmission. Therefore, impairments in both mitochondria and neuromuscular junction may be one of the key pathophysiological mechanisms leading to sarcopenia. Moreover, this article explores the structural and functional alterations in the neuromuscular junction and mitochondria in sarcopenia, suggesting that a deeper understanding of these changes could provide valuable insights for the prevention or treatment of sarcopenia.


Assuntos
Doenças Mitocondriais , Sarcopenia , Humanos , Sarcopenia/patologia , Envelhecimento/fisiologia , Junção Neuromuscular/metabolismo , Estresse Oxidativo/fisiologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Músculo Esquelético/metabolismo
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