Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Peripheral Thyroid Hormone Sensitivity Mediates the Association Between Body Composition and Diabetes in Euthyroid Adults","authors":"Nanfang Yao, Lan Liu, Yuqi Jiang, Dongmei Wang, Qianyi Lu, Yi Zeng, Genfeng Yu, Qintao Ma, Peiyi Li, Lingling Liu, Jie Shen, Heng Wan","doi":"10.1002/jcsm.70061","DOIUrl":"10.1002/jcsm.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Body composition parameters, including fat-to-muscle ratio (FMR) and appendicular skeletal muscle mass (ASM), are closely associated with metabolic diseases. However, the mediating role of peripheral thyroid hormone sensitivity, reflected by the free triiodothyronine-to-free thyroxine ratio (FT3/FT4 ratio), in these associations remains unclear in euthyroid individuals. The current study aimed to investigate the associations of FMR and ASM/BMI with diabetes and to explore the potential mediating role of FT3/FT4 ratio in these relationships among euthyroid Chinese adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study enrolled the participants from 10 communities in Guangdong Province, China, from November 2021 to September 2022. Body composition was measured using bioelectrical impedance analysis (BIA). Diabetes was defined based on fasting plasma glucose, 2-h postload glucose or glycated haemoglobin (HbA1c). Associations of FMR and ASM adjusted for body mass index (ASM/BMI) with diabetes were assessed using multivariable logistic regression. Structural equation modelling was applied to evaluate the mediating effect of FT3/FT4 ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 5089 participants (mean age = 46 years, SD = 12) were included in the final analysis, consisting of 1957 men (38.5%) and 3132 women (61.5%). Participants in the third tertile (T3) of FMR exhibited a 79% higher prevalence of diabetes compared to those in the first tertile (T1) (OR 1.79, 95% CI 1.27–2.54) (<i>p</i> < 0.05). Conversely, those in the T3 of ASM/BMI had a 56% lower prevalence of diabetes compared to participants in T1 (OR 0.44, 95% CI 0.31–0.64) (<i>p</i> < 0.05). Restricted cubic spline analysis confirmed linear associations for both FMR and ASM/BMI with diabetes (both <i>p</i> for overall < 0.001; <i>p</i> for non-linear > 0.05). FT3/FT4 ratio significantly mediated the association between ASM/BMI and diabetes, accounting for 4.6% of the total effect (<i>p</i> < 0.05), whereas no significant mediation was observed in the FMR–diabetes pathway (<i>p</i> > 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In euthyroid individuals, higher FMR and lower ASM/BMI were independently associated with increased diabetes prevalence. The inverse relationship between ASM/BMI and diabetes may be partially mediated by FT3/FT4 ratio, highlighting peripheral thyroid hormone sensitivity as a potential mechanistic biomarker linking ASM loss to glycaemic dysregulation in euthyroid ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Diaphragm Involvement Assessed by Ultrasound With Disease Severity in Facioscapulohumeral Muscular Dystrophy","authors":"Xiang Xu, Fuze Zheng, Xin Lin, Liangliang Qiu, Long Chen, Jing Xu, Li Kang, Jie Chen, Liulei Wu, Ying Zheng, Minghui Zeng, Xiaodan Lin, Qifang He, Li Chen, Feng Lin, Ning Wang, Minting Lin, Guorong Lyu, Zhiqiang Wang","doi":"10.1002/jcsm.70057","DOIUrl":"10.1002/jcsm.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Respiratory involvement is a comorbidity that should not be overlooked in clinical practice in facioscapulohumeral muscular dystrophy type 1 (FSHD1), with a reported association for severe disease outcomes such as wheelchair dependency. However, patients with FSHD1 can have inaccurate ventilatory function assessment results, owing to facial muscle involvement. Additionally, the association between diaphragm involvement and disease severity in FSHD1 patients remains uncertain. This study aims to assess diaphragm involvement using ultrasound technology and to assess potential associations of diaphragm involvement with respiratory involvement and disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective, observational, case–control study enrolled genetically confirmed FSHD1 patients from the Chinese FSHD1 cohort and control participants (matched with FSHD1 patients at a ratio of 2:1 based on gender, age at examination and height) between January 2021 and February 2025. Ultrasound examination of the diaphragm and pulmonary function tests were performed to evaluate respiratory involvement in both FSHD1 patients and paired controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final analytical sample included 109 patients: 81 patients (median [IQR] age, 33 [23–43] years; 33 [40.7%] female) and 162 control participants (median [IQR] age, 31 [23–45] years; 66 [40.7%] woman) in the exploration cohort, and 28 patients in the validation cohort. Ultrasound parameters of the right hemidiaphragm for diaphragm excursion velocity (<i>V</i><sub>VS</sub>), maximal relaxation rate of the diaphragm (ECHO-MRR) and thickness of the diaphragm at total lung capacity (<i>Th</i><sub>TLC</sub>) displayed significant differences between the FSHD1 groups with vs. without restrictive ventilatory defect (RVD). A multivariate model (including variables of sex, age at examination, D4Z4 RUs, <i>V</i><sub>VS</sub> and ECHO-MRR) efficiently identified RVD in the ROC curve analysis with an AUC of 0.943 (0.896–0.989). In the validation cohort, applying the cut-off values for <i>V</i><sub>VS</sub> derived from ROC analysis to identify RVD in FSHD1 patients, results showed a high true positive rate of 80.0% and a true negative rate of 94.4%. Multivariate Cox regression analyses indicated low <i>V</i><sub>VS</sub> and low ECHO-MRR were independently associated with early lower extremity involvement in FSHD1, with adjusted hazard ratios (aHRs) (95% CI) of 2.353 (1.356–4.085) and 2.039 (1.186–3.504), respectively. Multivariate linear regression models indicated that lower <i>V</i><sub>VS</sub> (<i>β</i> = −1.686) and ECHO-M","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcase Inhibitor Improves Denervation-Induced Muscle Atrophy in Mice","authors":"Tomoyasu Suenaga, Shouji Matsushima, Tomoka Masunaga, Toru Hashimoto, Shingo Takada, Yoshizuki Fumoto, Soichiro Hata, Kohtaro Abe, Shintaro Kinugawa","doi":"10.1002/jcsm.70066","DOIUrl":"10.1002/jcsm.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle atrophy occurs in various situations, such as denervation, fasting and ageing. Disruption of the balance between protein synthesis and degradation plays an important role in muscle atrophy, and impaired Akt phosphorylation is considered to be crucial in this process. The attachment of an O-linked N-acetylglucosamine motif (O-GlcNAcylation), which is a post-translational modification mediated by the hexosamine biosynthetic pathway, an alternative pathway of glycolysis, is involved in the regulation of protein function. Akt O-GlcNAcylation interacts with Akt phosphorylation, thereby regulating its function. The purpose of this study was to clarify the role of O-GlcNAcylation in skeletal muscle atrophy and to identify a therapeutic target for its prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Denervation was induced by cutting the sciatic nerve on the right leg of male C57BL/6J mice. A sham operation was performed on the left leg. Three days after the operation, the mice were divided into two groups: One group was treated with the O-GlcNAcase inhibitor thiamet G (1 mg/kg body weight/day), and the other group was treated with vehicle. Seven days after the operation, the gastrocnemius muscle was collected and analysed. The effect of adeno-associated virus serotype 1–mediated suppression of O-GlcNAcase on skeletal muscle atrophy was also investigated. Finally, in C2C12 myotubes with adenovirus-mediated overexpression of wild-type Akt and O-GlcNAcylation-resistant mutant Akt (T479A), the interaction between the phosphorylation and O-GlcNAcylation of Akt was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The weight of denervated gastrocnemius muscle was decreased by 35.6% (<i>p</i> < 0.05) compared with sham. Akt phosphorylation was decreased by 27.8% (<i>p</i> < 0.05), and the expression of the muscle-specific ubiquitin ligases muscle atrophy F-box (atrogin-1) and muscle RING Finger-1 (MuRF1) was increased in denervated muscle compared with sham. Akt O-GlcNAcylation was decreased in denervated muscle compared with sham by 45.3% (<i>p</i> < 0.05), together with an 8.9-fold increase in O-GlcNAcase expression. Thiamet G reduced gastrocnemius muscle weight loss by 22.7% (<i>p</i> < 0.05) compared with vehicle, and this was achieved through an increase in Akt phosphorylation by 63.5% (<i>p</i> < 0.05) and decreases in atrogin-1 and MuRF1 expression. The inhibition of O-GlcNAcase by gene silencing also improved skeletal muscle atrophy. The overexpression of mutant Akt (T479A) showed less O-GlcNAcase inhibition-induced Akt phosphorylation than the overexpression of wil","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Muscle Quality: Exploring Leucine and Whey Protein in Sarcopenic Individuals","authors":"Aiman Ijaz,&nbsp;Huma Bader Ul Ain,&nbsp;Tabussam Tufail,&nbsp;Raima Mariam,&nbsp;Sana Noreen,&nbsp;Aniqa Amjad,&nbsp;Ali Ikram,&nbsp;Muhammad Tayyab Arshad,&nbsp;Muhammed Adem Abdullahi","doi":"10.1002/jcsm.70060","DOIUrl":"10.1002/jcsm.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is characterised by a decline in the skeletal muscle mass with increasing age. This poses many challenges to the health and independence of older individuals. New and emerging studies have focused on supplementing leucine-enriched whey protein and resistance training in older adults to mitigate the effects of sarcopenia, including significant muscle mass loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to comprehensively analyse the current literature regarding the beneficial effects of leucine-enriched whey protein supplementation in older adults. This article systematically reviewed randomised controlled trials, longitudinal studies, and meta-analyses published between 2011 and 2024. The biochemical mechanisms underlying the anabolic properties of leucine, including its role in protein synthesis and mTOR signalling pathways, were explored to elucidate its potential to enhance muscle protein accretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Findings from the reviewed studies indicate that the combined intervention of leucine-enriched whey protein supplementation and resistance training elicits favourable outcomes regarding increased lean muscle mass, muscle strength and physical performance in older adults with sarcopenia. The potential of leucine-enriched whey protein to mitigate muscle protein breakdown is discussed along with its potential synergistic effects with resistance exercise to optimise muscle adaptation. Future research directions, including investigations of optimal dosing regimens, long-term sustainability and potential contraindications, are proposed to enhance the precision and applicability of this intervention strategy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Leucine-enriched whey protein supplementation combined with resistance training is beneficial in addressing sarcopenia in older adults. This review consolidates the current understanding of this intervention, highlights its potential benefits and provides insights for future research and clinical applications in geriatric muscle health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of Low Muscle Mass With Serum Sex Hormones and Sex Hormone-Binding Globulin","authors":"Hailin Qin,&nbsp;Wenyong Jiao,&nbsp;Gui Liao","doi":"10.1002/jcsm.70056","DOIUrl":"10.1002/jcsm.70056","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The purpose of this study was to explore the associations of low muscle mass with serum sex hormones and sex hormone-binding globulin (SHBG) using data from the National Health and Nutrition Examination Survey (NHANES).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We analysed 4403 adults aged 20–59 years from the 2013–2016 NHANES. Appendicular skeletal muscle index (ASMI) was calculated as appendicular skeletal muscle (kg) divided by height squared (m&lt;sup&gt;2&lt;/sup&gt;). Low muscle mass was defined as ASMI &lt; 7.0 kg/m&lt;sup&gt;2&lt;/sup&gt; (men) or &lt; 5.5 kg/m&lt;sup&gt;2&lt;/sup&gt; (women). Logistic regression was performed separately for male and female participants to assess the associations of low muscle mass with serum sex hormones and sex hormone-binding globulin (SHBG).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The mean age of the participants was 38.6 years (± 11.35 years), and 46.3% of the participants were female. In men, both total testosterone (TT) (Model 3: OR = 1.003, 95% CI: 1.002–1.004, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and free testosterone (Model 3: OR = 1.007, 95% CI: 1.001–1.013, &lt;i&gt;p&lt;/i&gt; = 0.022) levels correlated positively with low muscle mass. The highest TT quartile had 4.529 times the odds compared to the lowest quartile (Model 3: OR = 4.529, 95% CI: 1.927–10.645, &lt;i&gt;p&lt;/i&gt; = 0.003). Each unit increase in SHBG was associated with higher odds (Model 3: OR = 1.035, 95% CI: 1.024–1.045, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The highest SHBG quartile (&gt; 45.26 nmol/L) showed 6.442-fold higher odds (Model 3: OR = 6.442, 95% CI: 3.134–13.242, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). For women, the highest estradiol quartile (&gt; 116 pg/mL) had 56.4% lower odds of low muscle mass than the lowest quartile (Model 3: OR = 0.436, 95% CI: 0.268–0.709, &lt;i&gt;p&lt;/i&gt; = 0.004). Each unit increase in free testosterone (FT) showed an inverse association (Model 3: OR = 0.710, 95% CI: 0.605–0.834, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The highest FT quartile (&gt; 3.70 pg/mL) had 73.7% lower odds (Model 3: OR = 0.263, 95% CI: 0.146–0.473, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Each unit increase in SHBG showed a positive association with low muscle mass (Model 3: OR = 1.009, 95% CI: 1.007–1.012, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The highest SHBG quartile (&gt; 87.21 nmol/L) showed 5.482-fold higher odds (Model 3: OR = 5.482, 95% CI: 2.854–10.527, &lt;i&gt;p&lt;/i&gt; &lt; 0.001).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In women, estradiol and free testosterone levels are negatively associated with low muscle mass. In men, elevated total testosterone was unexpectedly associated with an increased risk of LMM. SHBG ele","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Combined Exercise Training on Modulating Fine Particulate Matter–Induced Skeletal Muscle Damage in Offspring Gestationally Exposed","authors":"Zilin Wang,&nbsp;Wenduo Liu,&nbsp;Hyun-Jaung Sim,&nbsp;Jeong-Chae Lee,&nbsp;Sung-Ho Kook,&nbsp;Sang Hyun Kim","doi":"10.1002/jcsm.70047","DOIUrl":"https://doi.org/10.1002/jcsm.70047","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Fine particulate matter has developmental toxicity, and midgestation is an important period for the development of foetal skeletal muscle. The ability of exercise to modulate skeletal muscle damage in mice exposed to PM&lt;sub&gt;2.5&lt;/sub&gt; during gestation remains unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pregnant C57BL/6 mice were exposed to 50 μg/m&lt;sup&gt;3&lt;/sup&gt; PM&lt;sub&gt;2.5&lt;/sub&gt; for 2 h on five consecutive days starting at embryonic day 12.5 (E12.5d). Combined exercise (treadmill endurance training and weighted ladder resistance training) was followed for 8 weeks in the 4-week-old offspring to verify the regulatory effect of exercise.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Offspring exposed to PM&lt;sub&gt;2.5&lt;/sub&gt; during gestation showed lower body weight (male, −44.3%; female, −44.8%; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), lower skeletal muscle mass (male: TA fibre size, −42%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; TA mass, −37%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; gastrocnemius mass, −46.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; female: TA fibre size, −51.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; TA mass, −29.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; gastrocnemius mass, −40.7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and mitochondrial (size decreased for TEM; male: PGC-1α, +78.1%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; Tfam, +591.3%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; FIS-1, +627%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; female: Tfam, +452%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; FIS-1, +345.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) dysfunction (at 4 weeks old). They also showed catch-up growth (between 3 and 8 weeks of age; male average weight gain level, +57.9%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; female average weight gain level, +66%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), although they still showed significant mitochondrial damage and impaired glucose metabolism (at 13 weeks of age; male: mitochondrial damage for TEM; Tfam, −46%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; PINK-1, −33.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; Parkin, −62%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01; PFK-1, −17%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; female: mitochondrial damage for TEM; PFK-1, −28.7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). Combined exercise was unable to regulate the skeletal muscle system disorder that occurred in male offspring exposed to PM&lt;sub&gt;2.5&lt;/sub&gt; during pregnancy. However, it activated the mitophagy (PINK-1, +94.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05; Parkin, +90.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) in female offspring exposed to PM&lt;sub&gt;2.5&lt;/sub&gt; during pregnancy, thereby improving mitochondrial damage.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Combined exercise had bidirectional, sex-specific effects: Male offspring exhibited reduced responsiveness to exercise, with persistent mitochondrial damage, whereas female offspring showed improved mi","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Skeletal Muscle Mass Is Associated With Reduced Cytotoxic T Cell Abundance and Poor Survival in Advanced Lung Cancer","authors":"Xin Nie,&nbsp;Yan Sun,&nbsp;David P. J. van Dijk,&nbsp;Min Deng,&nbsp;Ralph Brecheisen,&nbsp;Zhaoqi Wang,&nbsp;Qingxin Xia,&nbsp;Steven M. W. Olde Damink,&nbsp;Sander S. Rensen","doi":"10.1002/jcsm.70063","DOIUrl":"10.1002/jcsm.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Body composition alterations such as skeletal muscle (SM) loss in cancer patients are associated with poor survival. In turn, immune cell-driven pathways have been linked to muscle wasting. We aimed to investigate the relationship between body composition, tumour-infiltrating lymphocytes and survival in patients with advanced lung cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied 200 patients with advanced lung cancer receiving immunotherapy (<i>n</i> = 81) or non-immunotherapy regimens (<i>n</i> = 119). Body composition including SM index (SMI) at baseline and longitudinal changes were assessed using computed tomography (CT) scans at the third lumbar vertebra. Associations between body composition parameters and overall survival (OS) were evaluated using Cox regression analysis. The median value of SMI, stratified by sex, was used as the cut-off to define groups with high and low baseline SMI. Stable SMI was defined by any increase or &lt; 2% decrease per 100 days; loss of SMI was defined by ≥ 2% decrease per 100 days. Logistic regression analysis was applied to investigate the association between SMI and peripheral circulating immune cells. Tumour-infiltrating lymphocytes were identified by immunohistochemistry, and their relationship with SMI was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SMI loss was associated with shorter OS (whole cohort: HR = 2.314, 95% CI = 1.388–3.858, <i>p</i> = 0.001; immunotherapy cohort: HR = 3.028, 95% CI = 1.113–8.236, <i>p</i> = 0.03; non-immunotherapy cohort: HR = 2.298, 95% CI = 1.191–4.435, <i>p</i> = 0.013). Low baseline SMI was associated with higher CD3⁺ T cell abundance (OR = 1.240, 95% CI = 1.080–1.424, <i>p</i> = 0.002) but lower CD3⁺ CD8⁺ T cell abundance (OR = 0.862, 95% CI = 0.762–0.974, <i>p</i> = 0.018) in peripheral blood. Subsequent SMI loss during treatment was also significantly associated with higher CD3⁺ T cell counts (OR = 3.414, 95% CI = 1.301–8.961, <i>p</i> = 0.013) and lower CD3⁺ CD8⁺ T cell abundance (OR = 0.666, 95% CI = 0.459–0.968, <i>p</i> = 0.033). Patients with stable SMI had a higher number of CD8⁺ tumour-infiltrating lymphocytes than patients with SMI loss (15.4% vs. 7.9%, <i>p</i> = 0.036).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SM loss is an independent predictor for survival in patients with advanced lung cancer and is associated with reduced peripheral and tumour-infiltrating cytotoxic T cell abundance. An inadequate antitum","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Polygonati Rhizoma Prevents Glucocorticoid-Induced Growth Inhibition of Muscle via Promoting Muscle Angiogenesis Through Deoxycholic Acid’","authors":"","doi":"10.1002/jcsm.70053","DOIUrl":"https://doi.org/10.1002/jcsm.70053","url":null,"abstract":"<p>\u0000 <span>Shi, S</span>, <span>Li, R</span>, <span>Han, Y</span>, <span>Xie, J</span>, <span>Wang, S</span>, <span>Liu, J</span>, <span>Wan, F</span>, <span>Hou, G</span>, <span>Liu, Z</span>, <span>Sun, X</span>, <span>Zuo, B</span>, <span>Jia, Z</span>, <span>Mei, Z</span>, <span>Song, T</span>. <span><i>Polygonati Rhizoma</i> Prevents Glucocorticoid-Induced Growth Inhibition of Muscle via Promoting Muscle Angiogenesis Through Deoxycholic Acid</span>. <i>J Cachexia Sarcopenia Muscle</i>. <span>2025</span> Jun; <span>16</span>(<span>3</span>):e13853. https://doi.org/10.1002/jcsm.13853.\u0000 </p><p>In Methods section ‘2.12 Cultivation of <i>Collinsella aerofaciens</i>’, the sentence ‘<i>C. aerofaciens</i> was previously isolated in our lab’. should read as:</p><p>The <i>C. aerofaciens</i> strain used in this study was provided by Dr. Qingbiao Xu from Huazhong Agricultural University.</p><p>In Acknowledgements section, the sentence: ‘The authors would like to thank all the members of the Adipo-mystery (ADM) group, Dr. Qingbiao Xu and Ms. Wenjuan Du from Huazhong Agricultural University’. should read as:</p><p>The authors would like to thank all the members of the Adipo-mystery (ADM) group from Huazhong Agricultural University.</p><p>We greatly appreciate the kindly help from Dr. Qingbiao Xu and we have discussed with him. It would be better to remove the name ‘Dr. Qingbiao Xu and Ms. Wenjuan Du’ from acknowledgements section and revise the description in methods section.</p><p>These changes are important for the accuracy and completeness of the manuscript record and will not affect the overall conclusion of the article.</p><p>We apologize for this error.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Cachexia on the Feeding Regulation of Skeletal Muscle Protein Synthesis in Tumour-Bearing Mice","authors":"Brittany R. Counts,&nbsp;Quan Zhang,&nbsp;Jessica L. Halle,&nbsp;Melissa J. Puppa,&nbsp;Stephen E. Alway,&nbsp;Junaith Mohamed,&nbsp;Jeremy P. Loenneke,&nbsp;James A. Carson","doi":"10.1002/jcsm.70064","DOIUrl":"10.1002/jcsm.70064","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cancer promotes muscle wasting through an imbalance in the tightly regulated protein synthesis and degradation processes. An array of intracellular signalling pathways, including mTORC1 and AMPK, regulate protein synthesis, and these pathways are responsive to the muscle's microenvironment and systemic stimuli. Although feeding and fasting are established systemic regulators of muscle mTORC1 and protein synthesis, the cancer environment's impact on these responses during cachexia development is poorly understood. Although the IL-6 cytokine family has been widely investigated as a driver of cachexia with several cancers, how this signalling regulates muscle responses to feeding and fasting requires further study. We investigated if the cancer environment alters the feeding and fasting regulation of skeletal muscle protein synthesis and if the IL-6 family of cytokines signalling through muscle glycoprotein 130 could regulate this response.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Male C57BL/6J mice were subcutaneously injected with 1 × 10&lt;sup&gt;6&lt;/sup&gt; LLC cells or PBS. Mice were euthanized 25–30 days post-injection after a 12-h dark cycle fast, followed by access to food pellets for 1 h (fed) or immediately sacrificed. To determine AMPK and gp13's regulation of protein synthesis and anabolic signalling, we injected tamoxifen-inducible skeletal muscle AMPKa&lt;sup&gt;&lt;b&gt;1&lt;/b&gt;&lt;/sup&gt;a&lt;sup&gt;&lt;b&gt;2&lt;/b&gt;&lt;/sup&gt; or gp130 knockout and floxed control mice with LLC cells or PBS. The gastrocnemius muscle was analysed for protein expression.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Feeding increased p-rpS6 and protein synthesis in PBS (2.2- and 0.4-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and LLC mice (1.7- and 0.9-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), but overall, LLC significantly reduced p-rpS6 and protein synthesis. Feeding only increased p-AKT in PBS mice (1.5-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In vitro LLC-conditioned media did not inhibit the insulin induction of myotube p-AKT (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and p-rpS6 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Muscle gp130 loss reduced the fasting p-AMPK induction in LLC mice but did not alter suppression of p-AKT and p-rpS6 and protein synthesis. Muscle AMPK loss increased p-rpS6 (2.1-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and protein synthesis (0.7-fold, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) in PBS mice but did not restore LLC-suppressed protein synthesis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our study provides novel insight into muscle responsiveness to feeding and fasting in a cancer environment. We find the acute anabolic response to fee","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Muscle Tissue Cell Diversity and Clinical Implications in Idiopathic Inflammatory Myopathy","authors":"Honglin Zhu,&nbsp;Yizhi Xiao,&nbsp;Shasha Xie,&nbsp;Qiming Meng,&nbsp;Ting Ding,&nbsp;Ting Huang,&nbsp;Di Liu,&nbsp;Sijia Liu,&nbsp;Xiaoli Zhang,&nbsp;Huali Zhang,&nbsp;Hui Luo","doi":"10.1002/jcsm.70043","DOIUrl":"https://doi.org/10.1002/jcsm.70043","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Idiopathic inflammatory myopathies (IIMs) exhibit diverse cellular microenvironments in muscle tissues, yet the full spectrum of cell populations and changes remains unclear. This study aimed to characterize cellular heterogeneity, explore cell–cell interactions and assess the prognostic value of cell subtype abundances across IIM subtypes in Han Chinese.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Muscle samples from six IIMs and three normal controls (NC) underwent single-cell RNA sequencing (scRNA-seq), whereas bulk RNA sequencing was performed on 203 IIMs and 19 NC. To avoid potential biases in cell proportion data from scRNA-seq, we used CIBERSORTx, a robust deconvolution method, to estimate cell subtype abundances in the large IIMs cohort. Cell–cell interaction, correlation and survival analysis were performed to investigate associations between cell subtypes, clinical features and disease progression.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We identified 10 T/NK cell types, eight monocyte/macrophage/dendritic cell types, 10 vascular-related cell types and four skeletal muscle cell types in IIM muscle tissues, with varying abundances across subgroups. Increased ISG&lt;sup&gt;hi&lt;/sup&gt; T cells (1.42% vs. 0.075% in NC) and ISG&lt;sup&gt;hi&lt;/sup&gt; monocytes (4.24% vs. 0% in NC) in dermatomyositis (DM), particularly in anti-MDA5 and anti-NXP2 patients, correlated with skin rashes and higher relapse rates. CD56&lt;sup&gt;dim&lt;/sup&gt;CD16&lt;sup&gt;dim&lt;/sup&gt;NK cells, exhibiting the highest cytotoxicity, were elevated most in anti-SRP (11.93% vs. 8.15% in NC) immune-mediated necrotizing myopathy (IMNM) and associated with severe muscle damage (&lt;i&gt;p&lt;/i&gt; = 0.0001, rho = 0.267). Reduced angiogenesis-related SERPINB2&lt;sup&gt;+&lt;/sup&gt; monocytes (37.12% vs. 46.69% in NC) predicted better outcomes in IMNM (&lt;i&gt;p&lt;/i&gt; = 0.006, HR = 0.264), whereas decreased HIF3A&lt;sup&gt;+&lt;/sup&gt;CECs (14.29% in DM vs. 16.95% in NC), essential for endothelial barrier maintenance, negatively correlated with myofiber necrosis (&lt;i&gt;p&lt;/i&gt; = 0.016, rho = −0.168) and were predictive of improved outcomes in DM (&lt;i&gt;p&lt;/i&gt; = 0.014, HR = 0.412). Elevated endothelial-like pericytes in antisynthetase syndrome (ASS, 55.34% vs. 50.02% in NC) and IMNM (54.42%) were linked to muscle damage (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001, rho = 0.272). Certain key pathways, such as angiogenesis-related pathways, were linked to better outcomes in DM (&lt;i&gt;p&lt;/i&gt; = 0.002, HR = 0.405), whereas increased cytotoxicity scores, cell chemotaxis and regulation of inflammatory response were associated with a higher risk of relapse in both DM and IMNM. We also observed a reduction in Type I muscle fibres (22.66% in ASS vs. 66","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 5","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144909975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}