Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Association of Dietary Choline Intake With Incidence of Frailty: A Nationwide Prospective Cohort Study From China","authors":"Lian-hong Chen,&nbsp;Jian-feng Zhong,&nbsp;Ying-ying Niu,&nbsp;Cheng-ping Li,&nbsp;Jing Li,&nbsp;Zhi-quan Diao,&nbsp;Hao-yu Yan,&nbsp;Miao Xu,&nbsp;Wen-qi Huang,&nbsp;Zhi-tong Xu,&nbsp;Chang Su,&nbsp;Dan Liu","doi":"10.1002/jcsm.13796","DOIUrl":"https://doi.org/10.1002/jcsm.13796","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emerging evidence suggests that dietary choline is a modifiable nutritional factor linked to various health outcomes. However, most existing studies have focused on isolated health conditions, lacking a comprehensive assessment of overall health status. This study aimed to investigate the association between total dietary choline intake and frailty incidence among Chinese adults, considering its derivatives, soluble forms (water-soluble and lipid-soluble) and food sources (animal-derived and plant-derived).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants without frailty at baseline were enrolled from the China Health and Nutrition Survey (CHNS), with follow-up from 2004 to 2016. Dietary intake was assessed using three consecutive 24-h dietary recalls to estimate total dietary choline intake, its derivatives, soluble forms and food sources. Frailty status was evaluated using a frailty index (FI), with frailty defined as an FI &gt; 0.21. Cox proportional hazards regression and restricted cubic splines were used to analyse the associations between dietary choline intake and frailty incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 10 310 participants (mean age: 46.4 years [SD: 14.5]; 52.6% female) were eligible. During a median follow-up of 6.1 years, 1150 incident frailty cases were recorded. Cox models with penalized splines showed an L-shaped association between total dietary choline intake and frailty incidence. Compared with participants in the lowest quartile of total choline intake, those in the 2nd to 4th quartiles had lower odds of frailty, with hazard ratios (HRs) of 0.84 (95% CI: 0.71, 0.98), 0.80 (95% CI: 0.67, 0.95) and 0.75 (95% CI: 0.61, 0.93), respectively. Intake of lipid-soluble choline in the 2nd to 4th quartiles was associated with an 18% (HR: 0.82; 95% CI: 0.69, 0.98) to 23% (HR: 0.77; 95% CI: 0.63, 0.95) reduction in the odds of frailty. Participants in the 3rd to 4th quartiles of phosphatidylcholine intake exhibited 19% (HR: 0.81; 95% CI: 0.68, 0.96) to 23% (HR: 0.77; 95% CI: 0.63, 0.94) lower odds of frailty. Choline intake from plant-derived food sources was significantly associated with reduced odds of frailty (HR: 0.83; 95% CI: 0.69, 0.99).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Moderate to high dietary choline intake (171.00–464.99 mg/day), particularly phosphatidylcholine (145.20–304.93 mg/day), may be associated with reduced odds of frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787054","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":"Nestin Regulates Autophagy-Dependent Ferroptosis Mediated Skeletal Muscle Atrophy by Ubiquitinating MAP 1LC3B","authors":"Shunshun Han,&nbsp;Xiyu Zhao,&nbsp;Chunlin Yu,&nbsp;Can Cui,&nbsp;Yao Zhang,&nbsp;Qing Zhu,&nbsp;Mohan Qiu,&nbsp;Chaowu Yang,&nbsp;Huadong Yin","doi":"10.1002/jcsm.13779","DOIUrl":"https://doi.org/10.1002/jcsm.13779","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Programmed cell death plays a critical role in skeletal muscle atrophy. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various diseases, but its role in skeletal muscle atrophy remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ferroptosis in skeletal muscle atrophy was investigated using two models: dexamethasone (Dex)-induced atrophy (<i>n</i> = 6 independent cell cultures per group) and simulated microgravity (<i>n</i> = 6 mice per group). Conditional Nestin knockout (KO) mice were generated using CRISPR/Cas9 (<i>n</i> = 6–8 mice per group), with wild-type (WT) controls (<i>n</i> = 6–8). Phenotypic analyses included histopathology (HE staining), functional assessments (muscle strength, weight analysis, treadmill), and dystrophy evaluation (dystrophin staining). Molecular analyses involved flow cytometry, ELISA, transmission electron microscopy, PI staining, and IP/MS to delineate Nestin-regulated ferroptosis pathways in skeletal muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ferroptosis was significantly activated in both atrophy models, with a 2.5-fold increase in lipid peroxidation (<i>p</i> &lt; 0.01), a 2-fold accumulation of Fe²⁺ (<i>p</i> &lt; 0.01) and a 50% reduction in Nestin expression (<i>p</i> &lt; 0.001). Nestin KO mice exhibited exacerbated muscle atrophy, showing a 40% decrease in muscle weight (<i>p</i> &lt; 0.01) and a 30% reduction in muscle strength (<i>p</i> &lt; 0.05) compared to WT mice. Nestin overexpression mitigated Dex-induced ferroptosis, reducing lipid peroxidation by 40%, decreasing Fe²⁺ accumulation by 50% (<i>p</i> &lt; 0.01), and improving muscle function by 30% (<i>p</i> &lt; 0.05). Mechanistically, Nestin interacted with MAP 1LC3B (LC3B) to catalyse LC3B polyubiquitination at lysine-51, reducing LC3B availability for autophagy and inhibiting autophagy flux by 60% (<i>p</i> &lt; 0.01), leading to a 50% reduction in ferroptosis (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study identifies Nestin as a critical regulator of ferroptosis-autophagy crosstalk in skeletal muscle atrophy. Targeting Nestin-LC3B ubiquitination may offer novel therapeutic strategies for preventing muscle wasting in diseases such as cachexia and sarcopenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770098","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":"Calcium Handling Machinery and Sarcomere Assembly are Impaired Through Multipronged Mechanisms in Cancer Cytokine-Induced Cachexia","authors":"Luis Vincens Gand,&nbsp;Chiara Lanzuolo,&nbsp;Mugeng Li,&nbsp;Valentina Rosti,&nbsp;Natalie Weber,&nbsp;Dongchao Lu,&nbsp;Christian Bär,&nbsp;Thomas Thum,&nbsp;Andreas Pich,&nbsp;Theresia Kraft,&nbsp;Mamta Amrute-Nayak,&nbsp;Arnab Nayak","doi":"10.1002/jcsm.13776","DOIUrl":"https://doi.org/10.1002/jcsm.13776","url":null,"abstract":"&lt;p&gt;The precisely arranged sarcomeres are the fundamental units of striated muscle cells that produce force from ATP-dependent cross-bridge cycling between actin (thin filaments) and myosin (thick filaments) to bear load and drive movement. During excitation–contraction coupling (ECC) process, calcium (Ca&lt;sup&gt;2+&lt;/sup&gt;) is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR1), activating thin filament and enabling acto-myosin cross-bridge cycling, and hence myocyte contraction [&lt;span&gt;1, 2&lt;/span&gt;]. The dihydropyridine receptor (DHPR) α1s subunit physically interacts with RyR1, inducing an opening of the channel as the result of an action potential [&lt;span&gt;1&lt;/span&gt;]. Muscle relaxation follows the transfer of Ca&lt;sup&gt;2+&lt;/sup&gt; ions to the SR through the calcium ATPase pump SERCA1. Thus, a precise sarcomeric assembly, a proper Ca&lt;sup&gt;2+&lt;/sup&gt; transient, and correct interplay between these two systems is critical for primary muscle cell functions, i.e., contraction and force generation. Molecular insights in various aspects of these processes remain poorly determined. A detailed understanding of it is critical to apprehend not only muscle physiology but muscle wasting conditions as well.&lt;/p&gt;&lt;p&gt;Cancer triggers cachexia, which is a severe muscle wasting disorder associated with up to 80% of cancer patients [&lt;span&gt;3&lt;/span&gt;]. Cancer cytokine-induced cachexia (CIC) is defined by ongoing involuntary loss of muscle and/or fat mass and is not reversible by common treatments [&lt;span&gt;4&lt;/span&gt;], with an estimated high mortality rate ranges from 20% to 50% in cancer patients depending on cancer types [&lt;span&gt;5&lt;/span&gt;]. The effective dose of cancer therapeutics, particularly chemotherapy, is calculated based on body surface area [&lt;span&gt;6, 7&lt;/span&gt;]. Thus, CIC additionally aggravates the patient's responsiveness to therapies [&lt;span&gt;8&lt;/span&gt;]. Tumour-released pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α), interferon gamma (INF-γ), interleukin 6 (IL-6), induce degradation of myofibril proteins, especially myosin heavy chain (MyHC), through NF-κB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells)-MuRF1 (muscle RING-finger protein-1) ubiquitin-proteasome pathway [&lt;span&gt;9&lt;/span&gt;]. Furthermore, NF-κB downregulates the master transcription factor MyoD and thereby suppresses skeletal muscle differentiation of myogenic progenitor cells [&lt;span&gt;10, 11&lt;/span&gt;]. Besides Murf1, other E3 ligases including Atrogin1 and UBR2 are also upregulated and modify thick filament proteins for degradation [&lt;span&gt;12, 13&lt;/span&gt;]. Pro-inflammatory cytokines also contribute to insulin resistance and suppression of the insulin-like growth factor I (IGF1)-Akt pathway, further deteriorating the catabolic condition [&lt;span&gt;14&lt;/span&gt;]. Moreover, upregulation of the metal-ion transporter ZRT- and IRT-like protein 14 (ZIP14) has been shown in cachectic skeletal muscles of mice and in human patients with metastatic cancer in response to ca","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13776","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770123","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":"Prediction Models for Risk of Cardiorespiratory Morbidity/Mortality and Fracture Among Young Adults With Cerebral Palsy","authors":"Daniel G. Whitney,&nbsp;Edward A. Hurvitz","doi":"10.1002/jcsm.13640","DOIUrl":"https://doi.org/10.1002/jcsm.13640","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;There is a dearth of screening tools for cardiorespiratory disease and fracture risk, such as risk prediction models, for adults with cerebral palsy (CP). There is heterogeneity of pathophysiology related to the severity of CP and aging, such that a suite of risk prediction models may be needed. Differentiating by sarcopenia versus frailty syndromes may be a useful, physiologic-based framework to develop a suite of cardiorespiratory disease and fracture risk prediction models for adults with CP. The study objective was to determine if risk prediction models including widely available variables that are CP non-specific and that may capture the physiologic components of frailty provide clinically useful prediction of salient health issues for young adults with CP.&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;This retrospective cohort study used medical records from 01/01/2012 to 10/2/2022 from 18–40-year-olds with CP at a single Medical Centre. Logistic regression models were developed for three separate outcomes: 3-year risk of respiratory morbidity/mortality, cardiovascular morbidity/mortality and fracture. The following predictors were included: age, sex, intellectual disabilities, epilepsy and four serum biomarkers (creatinine, glucose, calcium, carbon dioxide) from the clinical Basic/Comprehensive Metabolic Panel assay. Model performance measures were evaluated, including discrimination (c-statistic) and calibration. Internal validation was assessed, and optimism-corrected c-statistics were computed using the bootstrap resampling method to assess model overfitting.&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;There were 805 young adults with CP with an average (SD) age of 26.5 (6.6) years and 47.8% were female. Over the 3-year follow-up, 24.6% had incident respiratory morbidity/mortality, 8.9% had incident cardiovascular morbidity/mortality and 7.0% had an incident fracture. The c-statistic (95% CI) was 0.74 (0.70–0.78) for respiratory morbidity/mortality, 0.63 (0.57–0.70) for cardiovascular morbidity/mortality and 0.65 (0.58–0.73) for fracture. The optimism-corrected c-statistic was similar for respiratory morbidity/mortality (0.73) but lower for cardiovascular morbidity/mortality (0.58) and fracture (0.59), suggesting evidence of model overfitting. All models showed good calibration based on the slope of the predicted risk versus observed risk around 1.0 and the Hosmer–Lemeshow goodness-of-fit test, &lt;i&gt;P&lt;/i&gt; = 0.305–0.903. However, the range of predicted risks was limited to ~20% for cardiovascular morbidity/mortality and ~55% for fracture, suggesting that these models have limited value for those with","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770411","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":"Long-Term Effects of High-Intensity Aerobic Training on Metabolic Syndrome: An 8-Year Follow-Up Randomized Clinical Trial","authors":"Felix Morales-Palomo,&nbsp;Alfonso Moreno-Cabañas,&nbsp;Laura Alvarez-Jimenez,&nbsp;Diego Mora-Gonzalez,&nbsp;Ricardo Mora-Rodriguez","doi":"10.1002/jcsm.13780","DOIUrl":"https://doi.org/10.1002/jcsm.13780","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;Metabolic syndrome (MetS) is a set of five cardiometabolic risk factors that typically worsen with age. One exercise-training programme is effective at improving those factors in middle-aged individuals with MetS. To our knowledge, exercise-training efficacy as MetS individuals age has not been explored. This study determined the effectiveness of a periodized exercise training programme for individuals with MetS after a follow-up period of 8 years.&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;Forty-seven individuals with MetS were block-randomized into an EXERCISE (&lt;i&gt;n&lt;/i&gt; = 22, 52 ± 8 years old, 23% women) or a CONTROL group (&lt;i&gt;n&lt;/i&gt; = 25, 53 ± 8 years old, 32% women). Both groups received standard health care, including medical counselling and lifestyle advice at least every 6 months, while participants in EXERCISE also underwent a supervised exercise programme. The intervention lasted 8 years and consisted of 4 months per year (November to March) of high-intensity interval training thrice weekly. At baseline, and after 4 and 8 years of treatment, we assessed body composition, MetS components (i.e., MetS &lt;i&gt;Z&lt;/i&gt; score), medication use, cardiorespiratory fitness (CRF; assessed by VO&lt;sub&gt;2MAX&lt;/sub&gt;) and maximal leg cycling power output (W&lt;sub&gt;MAX&lt;/sub&gt;).&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;Paradoxically, MetS &lt;i&gt;Z&lt;/i&gt; score and body weight were reduced after 8 years (subjects aged from 52 to 60 years old) in both groups (time effect &lt;i&gt;p&lt;/i&gt; &lt; 0.001 and &lt;i&gt;p&lt;/i&gt; = 0.008; time × group interaction &lt;i&gt;p&lt;/i&gt; = 0.253 and &lt;i&gt;p&lt;/i&gt; = 0.130). However, in those 8 years, the medicine use score increased threefold in CONTROL (137% increase; from 1.7 to 3.9; &lt;i&gt;p&lt;/i&gt; &lt; 0.001) while it did not change in EXERCISE (33%; from 2.0 to 2.7; &lt;i&gt;p&lt;/i&gt; = 0.066). In 8 years, CRF and W&lt;sub&gt;MAX&lt;/sub&gt; increased in EXERCISE by 14% (3.4 ± 5.6 mL·kg&lt;sup&gt;−1&lt;/sup&gt;·min&lt;sup&gt;−1&lt;/sup&gt;) and 4% (7 ± 37 W) while decreasing in CONTROL by −7% (−1.6 ± 3.4 mL·kg&lt;sup&gt;−1&lt;/sup&gt;·min&lt;sup&gt;−1&lt;/sup&gt;) and −14% (−24 ± 27 W) being different between groups after 4 and 8 years (both time × group interaction &lt;i&gt;p&lt;/i&gt; = 0.002). Pearson correlations showed that MetS &lt;i&gt;Z&lt;/i&gt; score improvements were significantly associated with increases in medication use score in the CONTROL group (&lt;i&gt;r&lt;/i&gt; = 0.491; &lt;i&gt;p&lt;/i&gt; = 0.013) and with W&lt;sub&gt;MAX&lt;/sub&gt; enhancement in the EXERCISE group (&lt;i&gt;r&lt;/i&gt; = 0.613; &lt;i&gt;p&lt;/i&gt; = 0.002).&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 data suggest that annual exercise training has similar clinical efficacy to tripl","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749855","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":"Low Visceral Adipose Tissue Predicts the Outcome of Neoadjuvant Chemotherapy for Colorectal Liver Metastases: A Multicentre Real-World Study","authors":"Yizhen Chen,&nbsp;Hangdong Jia,&nbsp;Rong Ye,&nbsp;Zhenyuan Zhou,&nbsp;Weijie Chen,&nbsp;Ming Zheng,&nbsp;Yuanyuan Zheng","doi":"10.1002/jcsm.13785","DOIUrl":"https://doi.org/10.1002/jcsm.13785","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Visceral obesity (VO), associated with excessive visceral adipose tissue (VAT), has been extensively studied in cancer. However, whether low VAT can predict the prognosis of colorectal liver metastases (CRLM) undergoing neoadjuvant chemotherapy (NAC) remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicentre real-world cohort study analysed data from initially resectable CRLM patients who received NAC. The predictive effect of VAT on progression-free survival (PFS) and overall survival (OS) was evaluated using restricted cubic splines (RCS). VAT was categorized into low/normal VAT and VO groups using X-tile. The prognostic differences were further assessed through Kaplan–Meier (KM) analysis. The impact of changes in VAT (ΔVAT) after NAC was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1524 CRLM patients, 1105 patients (72.51%) were under 65 years old, with a median VAT of 84.00 (36.24–148.00) cm². Of all patients, 804 (52.76%) were female. A U-shaped nonlinear relationship was observed between VAT and both PFS/OS (<i>p</i> &lt; 0.001). Compared with the normal VAT, both low VAT and VO groups showed worsened PFS and OS (<i>p</i> &lt; 0.05). The 3-year PFS rate was 31.6%, 69.0% and 42.0% in the low, normal VAT and VO groups (<i>p</i> &lt; 0.05). The 3-year OS rate was 76.4%, 88.9% and 79.4% in the low, normal VAT and VO groups (<i>p</i> &lt; 0.05). There was also a nonlinear relationship between VAT and NAC-related adverse events, objective response rate and postoperative complications (<i>p</i> &lt; 0.001). An increase in ΔVAT in the low VAT group was associated with better PFS and OS (<i>p</i> &lt; 0.05). In the VO group, both increases and decreases in ΔVAT were associated with worsened PFS and OS (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to reveal that low VAT and VO can predict PFS and OS in CRLM patients undergoing NAC. Baseline VAT and ΔVAT may serve as important indicators for risk stratification and personalized treatment in CRLM patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749622","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":"Nuciferine Attenuates Cancer Cachexia-Induced Muscle Wasting in Mice via HSP90AA1","authors":"Xueyan An,&nbsp;Lisha Ma,&nbsp;Yulan Bai,&nbsp;Chaoyue Chen,&nbsp;Ji Liu,&nbsp;Awaguli Dawuti,&nbsp;Kewu Zeng,&nbsp;Baoxue Yang,&nbsp;Bo Han,&nbsp;Abudumijiti Abulizi","doi":"10.1002/jcsm.13777","DOIUrl":"https://doi.org/10.1002/jcsm.13777","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;Around 80% of patients with advanced cancer have cancer cachexia (CC), a serious complication for which there are currently no FDA-approved treatments. Nuciferine (NF) is the main active ingredient of lotus leaf, which has anti-inflammatory, anti-tumour and other effects. The purpose of this work was to explore the target and mechanism of NF in preventing cancer cachexia-induced muscle atrophy.&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;The action of NF against CC-induced muscle atrophy was determined by constructing an animal model with a series of behavioural tests, H&amp;E staining and related markers. Network pharmacology and molecular docking were used to preliminarily determine the mechanism and targets of NF against CC-induced muscle atrophy. The mechanisms of NF in treating CC-induced muscle atrophy were verified by western blotting. Molecular dynamics simulation (MD), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) were used to validate the key target of NF.&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;After 13 days of NF treatment, the reduction of limb grip strength and hanging time in LLC model mice increased by 29.7% and 192.2% (&lt;i&gt;p&lt;/i&gt; ≤ 0.01; &lt;i&gt;p&lt;/i&gt; ≤ 0.001). Gastrocnemius and quadriceps muscles weight/initial body weight (0.98 ± 0.11 and 1.20 ± 0.17) and cross-sectional area of muscle fibres (600–1600 μm&lt;sup&gt;2&lt;/sup&gt;) of NF-treated mice were significantly higher than those of the model group (0.84 ± 0.10, 0.94 ± 0.09, 400–800 μm&lt;sup&gt;2&lt;/sup&gt;, respectively) (&lt;i&gt;p&lt;/i&gt; ≤ 0.01; &lt;i&gt;p&lt;/i&gt; ≤ 0.01; &lt;i&gt;p&lt;/i&gt; ≤ 0.001). NF treatment also decreased the MyHC (myosin heavy chain) degradation and the protein levels of muscle-specific E3 ubiquitin ligases Atrogin1 and MuRF1 in the model group (&lt;i&gt;p&lt;/i&gt; ≤ 0.001; &lt;i&gt;p&lt;/i&gt; ≤ 0.01; &lt;i&gt;p&lt;/i&gt; ≤ 0.05). Network pharmacology revealed that NF majorly targeted AKT1, TNF and HSP90AA1 to regulate PI3K-Akt and inflammatory pathways. Molecular docking predicted that NF bound best to HSP90AA1. Mechanism analysis demonstrated that NF regulated NF-κB and AKT–mTOR pathways for alleviating muscle wasting in tumour bearing mice. The results of MD, DARTS and SPR further confirmed that HSP90AA1 was the direct target of NF.&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;Overall, we first discovered that NF retards CC-induced muscle atrophy by regulating AKT–mTOR and NF-κB signalling pathways through directly binding HSP90AA1, suggesting that NF may be an effective treatment for cancer cachexia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 &lt;","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749621","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":"Plasma Extracellular Vesicles Biomarkers Linked to Lower Muscle Mass, Function and Physical Performance in Sarcopenia","authors":"Ji Yeon Kim,&nbsp;Tae-Hwan Gil,&nbsp;Hyo Gyeong Lee,&nbsp;Ji-Won Shin,&nbsp;Dong-Hyun Jang,&nbsp;Hyeon Soo Kim,&nbsp;Seung Shin Park,&nbsp;Sang Wan Kim,&nbsp;Chan Soo Shin,&nbsp;Sung Hye Kong,&nbsp;Ok Hee Jeon","doi":"10.1002/jcsm.13784","DOIUrl":"10.1002/jcsm.13784","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;As society ages, identifying individuals at risk of sarcopenia becomes essential. Several plasma biomarkers are used to assess musculoskeletal status, but their results are inconsistent. Extracellular vesicles (EVs) are investigated as disease biomarkers due to their role in transporting molecules and influencing cellular processes. This study investigated the correlation of known sarcopenia biomarkers—adiponectin, myostatin, P3NP, CRP and TNF-α—measured from plasma-derived EVs with muscle mass, function and performance in an Osteoporosis Sarcopenia cohort at the Seoul National University Bundang Hospital.&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 mass was evaluated by measuring appendicular skeletal muscle mass (ASM) using dual X-ray absorptiometry and calculated as ASM/height&lt;sup&gt;2&lt;/sup&gt;. Hand grip strength was measured using a hydraulic hand dynamometer for muscle function and physical performance based on the Short Physical Performance Battery (SPPB), walking speed and the five-time-sit-to-stand test. Density gradient ultracentrifugation was used to isolate EVs from the plasma, followed by confirming the expression of sarcopenia biomarkers. Multivariate regression analysis, adjusted for sex, age, body mass index, smoking, drinking, and bone density, was performed.&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 participants was 74.3 ± 12.1 years (range, 52.0–96.0), with 88.2% being female. Plasma-derived EV levels of myostatin and P3NP were significantly associated with walking speed (&lt;i&gt;ꞵ&lt;/i&gt; = −0.309, &lt;i&gt;p&lt;/i&gt; = 0.014) and SPPB (&lt;i&gt;ꞵ&lt;/i&gt; = −0.276, &lt;i&gt;p&lt;/i&gt; = 0.029), respectively. TNF-α levels were strongly correlated with hand grip strength (&lt;i&gt;ꞵ&lt;/i&gt; = −0.313, &lt;i&gt;p&lt;/i&gt; = 0.013). Using receiver-operating characteristic curve analysis, cutoff values for three factors were determined, allowing participants to be categorized into high and low groups. Low myostatin group had a higher hand grip strength (19.63 kg vs. 17.14 kg, &lt;i&gt;p&lt;/i&gt; = 0.027) and faster five-time-sit-to-stand test times (17.34 s vs. 23.72 s, &lt;i&gt;p =&lt;/i&gt; 0.032). Low P3NP levels showed a stronger grip strength (19.87 kg vs. 16.81 kg, &lt;i&gt;p&lt;/i&gt; = 0.008), better SPPB scores (9.10 vs. 8.03, &lt;i&gt;p =&lt;/i&gt; 0.006) and five-time-sit-to-stand times (18.31 s vs. 21.87 s, &lt;i&gt;p&lt;/i&gt; = 0.002). Low TNF-α levels were linked to better walking speeds (0.82 m/s vs. 0.64 m/s, &lt;i&gt;p&lt;/i&gt; = 0.009) and lower SARC-F scores (1.73 vs. 3.26, &lt;i&gt;p&lt;/i&gt; = 0.029).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our research confirmed that EVs-derived my","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737017","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":"Balancing LncRNA H19 and miR-675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity","authors":"Yao Gao,&nbsp;Md Nazmul Hossain,&nbsp;Liang Zhao,&nbsp;Xiangdong Liu,&nbsp;Yanting Chen,&nbsp;Jeanene Marie Deavila,&nbsp;Mei-Jun Zhu,&nbsp;Gordon K. Murdoch,&nbsp;Min Du","doi":"10.1002/jcsm.13791","DOIUrl":"10.1002/jcsm.13791","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;Maternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA &lt;i&gt;H19&lt;/i&gt; and its first exon derived &lt;i&gt;microRNA675&lt;/i&gt; (&lt;i&gt;miR675&lt;/i&gt;) in prenatal muscle development remain to be examined. &lt;i&gt;H19&lt;/i&gt;/&lt;i&gt;Igf2&lt;/i&gt; are in the same imprinting cluster with &lt;i&gt;H19&lt;/i&gt; expressed from the maternal allele while &lt;i&gt;Igf2&lt;/i&gt; expresses paternally. &lt;i&gt;H19&lt;/i&gt; contains a G-rich loop, and KH-type splicing regulatory protein (KHSRP) mediates the biogenesis of pre-&lt;i&gt;miRNAs&lt;/i&gt; containing G-rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis.&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;Single-cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of &lt;i&gt;H19&lt;/i&gt; and &lt;i&gt;miR657&lt;/i&gt; in myogenesis were further analysed in P19 embryonic cells via CRISPR/dCas9-mediated &lt;i&gt;H19&lt;/i&gt; activation and inhibition. The epigenetic changes of &lt;i&gt;H19&lt;/i&gt; were analysed by methylated DNA immunoprecipitation, and allele-targeted analysis of &lt;i&gt;H19&lt;/i&gt; was performed by crossing C57BL/6J and CAST/EiJ mice.&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;Transcriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis-related GO biological processes were down-regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as &lt;i&gt;Myf5&lt;/i&gt;, &lt;i&gt;Myod1&lt;/i&gt;, &lt;i&gt;Myog&lt;/i&gt;, &lt;i&gt;Mef2c&lt;/i&gt; and &lt;i&gt;Myh3&lt;/i&gt; (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). MO altered epigenetic modifications of the &lt;i&gt;H19&lt;/i&gt; genomic cluster, showing a decreased methylation level in &lt;i&gt;H19&lt;/i&gt; imprinting control region (&lt;i&gt;p &lt;&lt;/i&gt; 0.05) and a diallelic expression pattern of &lt;i&gt;H19&lt;/i&gt;, which elevated its expression in MO embryos. Overexpression of &lt;i&gt;H19&lt;/i&gt; inhibited myogenesis in P19 cells, but &lt;i&gt;miR675&lt;/i&gt; promoted myogenesis, suggesting the critical regulatory roles of bioconversion of &lt;i&gt;H19&lt;/i&gt; to &lt;i&gt;miR675&lt;/i&gt;. A KHSRP mediates the biogenesis of &lt;i&gt;miR675&lt;/i&gt;, a process that relies on its phosphorylation by IGF2/AKT signalling. Knocking-down of KHSRP and inhibition of AKT abolished &lt;i&gt;miR675&lt;/i&gt; biogenesis. MO suppressed IGF2/AKT signalling and blocked KHSRP-dependent &lt;i&gt;miR675&lt;/i&gt; biogenesis in embryos.&lt;/p&gt;\u0000 &lt;/","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737016","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":"A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses","authors":"Qian Ren,&nbsp;Jinrong Liang,&nbsp;Yanmei Su,&nbsp;Ruijing Tian,&nbsp;Junxian Wu,&nbsp;Sheng Ge,&nbsp;Peizhan Chen","doi":"10.1002/jcsm.13778","DOIUrl":"10.1002/jcsm.13778","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;Low serum vitamin D status was reported to be associated with reduced muscle mass; however, it is inconclusive whether this relationship is causal. This study used data from the National Health and Nutrition Examination Survey (NHANES) and two-sample Mendelian randomization (MR) analyses to ascertain the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] and appendicular muscle mass (AMM).&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;In the NHANES 2011–2018 dataset, 11 242 participants (5588 males and 5654 females) aged 18–59 years old were included, and multivariant linear regression was performed to assess the relationship between 25(OH)D and AMM measured by dual-energy X-ray absorptiometry. In two-sample MR analysis, 167 single nucleotide polymorphisms significantly associated with serum 25(OH)D at the genome-wide association level (&lt;i&gt;p&lt;/i&gt; &lt; 5 × 10&lt;sup&gt;−8&lt;/sup&gt;) were applied as instrumental variables (IVs) to assess vitamin D effects on AMM in the UK Biobank (417 580 Europeans) using univariable and multivariable MR (MVMR) models.&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;In the NHANES dataset, serum 25(OH)D concentrations were positively associated with AMM (&lt;i&gt;β&lt;/i&gt; = 0.013, SE = 0.001, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) in all participants, after adjustment for age, race, season of blood collection, education, income, body mass index and physical activity. In stratification analysis by sex, males (&lt;i&gt;β&lt;/i&gt; = 0.024, SE = 0.002, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) showed more pronounced positive associations than females (&lt;i&gt;β&lt;/i&gt; = 0.003, SE = 0.002, &lt;i&gt;p&lt;/i&gt; = 0.024). In univariable MR, genetically higher serum 25(OH)D levels were positively associated with AMM in all participants (&lt;i&gt;β&lt;/i&gt; = 0.049, SE = 0.024, &lt;i&gt;p&lt;/i&gt; = 0.039) and males (&lt;i&gt;β&lt;/i&gt; = 0.057, SE = 0.025, &lt;i&gt;p&lt;/i&gt; = 0.021), but only marginally significant in females (&lt;i&gt;β&lt;/i&gt; = 0.043, SE = 0.025, &lt;i&gt;p&lt;/i&gt; = 0.090) based on IVW models was noticed. No significant pleiotropy effects were detected for the IVs in the two-sample MR investigations. In MVMR analysis, a positive causal effect of 25(OH)D on AMM was observed in the total population (&lt;i&gt;β&lt;/i&gt; = 0.116, SE = 0.051, &lt;i&gt;p&lt;/i&gt; = 0.022), males (&lt;i&gt;β&lt;/i&gt; = 0.111, SE = 0.053, &lt;i&gt;p&lt;/i&gt; = 0.036) and females (&lt;i&gt;β&lt;/i&gt; = 0.124, SE = 0.054, &lt;i&gt;p&lt;/i&gt; = 0.021).&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 results suggested a positive causal effect of serum 25(OH)D concentration on AMM; however, more researches are warranted to unveil the underlying biological mechanisms and evaluate the effects o","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737071","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}