Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Targeting Drug Delivery System to Skeletal Muscles: A Comprehensive Review of Different Approaches","authors":"Xiaofang Li,&nbsp;Jintao Xu,&nbsp;Shanshan Yao,&nbsp;Ning Zhang,&nbsp;Bao-Ting Zhang,&nbsp;Zong-Kang Zhang","doi":"10.1002/jcsm.13691","DOIUrl":"10.1002/jcsm.13691","url":null,"abstract":"<p>The skeletal muscle is one of the largest organs in the body and is responsible for the mechanical activity required for posture, movement and breathing. The effects of current pharmaceutical therapies for skeletal muscle diseases are far from satisfactory; approximately 24% of Duchenne muscular dystrophy (DMD) trials have been terminated because of unsatisfactory outcomes. The lack of a skeletal muscle-targeting strategy is a major reason for these unsuccessful trials, contributing to low efficiency and severe side effects. The development of targeting strategies for skeletal muscle-specific drug delivery has shown the potential for increasing drug concentrations in the skeletal muscle, minimising off-target effects, and thereby improving the therapeutic effects of drugs. Over the past few decades, novel methods for specifically delivering cargo to skeletal muscles have been developed. In this review, we categorise targeting methods into four types: peptides, antibodies, small molecules and aptamers. Most research has focused on peptide and antibody ligands, and there are several well-established drugs in this category; however, drawbacks such as protease degradation and immunogenicity limit their use. Aptamers and small molecules have low immunogenicity and are simple to chemically produce. However, small molecule ligands generally exhibit lower affinity because of their small size and high mobility. Aptamers are promising ligands for skeletal muscle-targeting delivery systems. Additionally, if the active site of the cargo is located inside the cell, an internalisation pathway becomes necessary. The order of internalisation ligands and targeting ligands in the complex is a crucial factor, because an inappropriate order could lead to much lower targeting and internalisation efficiencies. Moreover, ligand density also merits consideration, as increasing the density of the targeting ligands may result in steric hindrance, which could impact the accessibility of the receptor and cause enlargement of the targeted ligands. More efforts are required to optimise drug delivery systems that specifically recognise skeletal muscle, with the aim of enhancing quality of life and promoting patient well-being.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192484","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 Impact of Physical Activity on Mortality in Adults With Multimorbidity: A 12-Year Cohort Longitudinal Study From the Survey on Health, Ageing and Retirement in Europe","authors":"Nicola Veronese,&nbsp;Francesco Saverio Ragusa,&nbsp;André Hajek,&nbsp;Brendon Stubbs,&nbsp;Lee Smith,&nbsp;Mario Barbagallo,&nbsp;Ligia Juliana Dominguez,&nbsp;Luigi Fontana,&nbsp;Pinar Soysal,&nbsp;Shaun Sabico,&nbsp;Nasser M. Al-Daghri","doi":"10.1002/jcsm.13695","DOIUrl":"10.1002/jcsm.13695","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;While physical activity (PA) is known to reduce mortality in the general population, this relationship in individuals with multimorbidity (≥ 2 chronic conditions) is unclear. This longitudinal study aimed to investigate whether there is a long-term association between PA levels and mortality rates over a 12-year period in adults with multimorbidity.&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;Data were obtained from eight waves of the Survey of Health, Ageing and Retirement in Europe (SHARE), from 28 European countries. PA levels were self-reported via computer-assisted personal interviews. Mortality during the follow-up period was assessed using data obtained from caregivers through end-of-life interview. Multimorbidity was identified based on the presence of two or more 15 self-reported chronic diseases/conditions. Cox's regression analysis, adjusted for potential confounders, was used to assess the association between PA level and mortality. &lt;i&gt;p&lt;/i&gt;-values were calculated using the Jonckheere–Terpstra test for continuous variables and the Mantel–Haenszel Chi-square test for categorical variables, stratified by PA level.&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 study included 9216 participants with multimorbidity (mean age 69 ± 10.1 years; 58.7% were women). Among those with multimorbidity, individuals with high PA level were significantly younger, more frequently men, less impaired in activities of daily living, less educated and less frequently obese than those with very low level of PA (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 for all comparisons). Over the 12 years of follow-up, mortality incidence was three times higher in individuals with multimorbidity and very low PA levels than those with multimorbidity and high levels of PA. After adjusting for confounders, the risk of mortality was significantly lower for participants with moderately low PA levels (HR = 0.64; 95% CI: 0.59–0.71; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), moderately high PA levels (HR = 0.53; 95% CI: 0.47–0.60; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and high PA levels (HR = 0.49; 95% CI: 0.43–0.55; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) compared to those with very low PA levels.&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;Findings from the present study suggest that people with multimorbidity who had lower levels of PA were three times more likely to die prematurely after 12 years than adults with multimorbidity and higher levels of PA at baseline. These findings underscore the importance of promoting physical activity in adults with multimorbidity to reduce the risk of premature mortal","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192494","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":"Skeletal Muscle Mitochondrial and Autophagic Dysregulation Are Modifiable in Spinal Muscular Atrophy","authors":"Andrew I. Mikhail,&nbsp;Sean Y. Ng,&nbsp;Donald Xhuti,&nbsp;Magda A. Lesinski,&nbsp;Jennifer Chhor,&nbsp;Marc-Olivier Deguise,&nbsp;Yves De Repentigny,&nbsp;Joshua P. Nederveen,&nbsp;Rashmi Kothary,&nbsp;Mark A. Tarnopolsky,&nbsp;Vladimir Ljubicic","doi":"10.1002/jcsm.13701","DOIUrl":"10.1002/jcsm.13701","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;Spinal muscular atrophy (SMA) is a health- and life-limiting neuromuscular disorder. Although varying degrees of mitochondrial abnormalities have been documented in SMA skeletal muscle, the influence of disease progression on pathways that govern organelle turnover and dynamics are poorly understood. Thus, the purpose of this study was to investigate skeletal muscle mitochondria during SMA disease progression and determine the effects of therapeutic modalities on organelle biology.&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;&lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/+&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/−&lt;/i&gt;&lt;/sup&gt; severe SMA-like mice were used to investigate mitochondrial turnover and dynamics signalling. Muscles were analysed at postnatal day 9 (P9), P13 or P21 to address pre-symptomatic, early symptomatic and late symptomatic periods of the disorder. Additionally, we utilized an acute dose of exercise and urolithin A (UA) to stimulate organelle remodelling in skeletal muscle of SMA mice in vivo and in SMA patient-derived myotubes in vitro, respectively.&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;&lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/+&lt;/i&gt;&lt;/sup&gt; and &lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/−&lt;/i&gt;&lt;/sup&gt; mice demonstrated similar levels of muscle mitochondrial oxidative phosphorylation (OxPhos) proteins throughout disease progression. In contrast, at P21 the mRNA levels of upstream factors important for the transcription of mitochondrial genes encoded by the nuclear and mitochondrial DNA, including &lt;i&gt;nuclear respiratory factor 2&lt;/i&gt;, &lt;i&gt;sirtuin 1&lt;/i&gt;, &lt;i&gt;mitochondrial transcription factor A&lt;/i&gt; and &lt;i&gt;tumour protein 53&lt;/i&gt;, were upregulated (+31%–195%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) in &lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/−&lt;/i&gt;&lt;/sup&gt; mice relative to &lt;i&gt;Smn&lt;/i&gt;&lt;sup&gt;&lt;i&gt;2B/+&lt;/i&gt;&lt;/sup&gt;. Early and late symptomatic skeletal muscle from SMA-like mice showed greater autophagosome formation as denoted by more phosphorylated autophagy related 16-like 1 (p-ATG16L1&lt;sup&gt;Ser278&lt;/sup&gt;) puncta (+60%–80%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), along with a build-up of molecules indicative of damaged mitochondria such as BCL2 interacting protein 3, Parkin and PTEN-induced kinase 1 (+100%–195%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Furthermore, we observed a fragmented mitochondrial phenotype at P21 that was concomitant with abnormal splicing of &lt;i&gt;Optic atrophy 1&lt;/i&gt; transcripts (−53%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). A single dose of exercise augmented the expression of &lt;i&gt;citrate synthase&lt;/i&gt; (+43%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and corrected the over-assembly of autophagosomes (−64%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). In patient muscle cells, UA treatment stimulated autophagic flux, increased the expression of OxPhos proteins (+15%–47%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and improved m","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083699","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":"Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na-MRI in Dysferlinopathy and Healthy Controls","authors":"Mary A. Neal,&nbsp;Carla F. Bolano-Diaz,&nbsp;Mark Richardson,&nbsp;Jassi Michell-Sodhi,&nbsp;Robert Muni-Lofra,&nbsp;Meredith K. James,&nbsp;Kieren G. Hollingsworth,&nbsp;Heather Hilsden,&nbsp;Ian Wilson,&nbsp;Andrew M. Blamire,&nbsp;Volker Straub,&nbsp;Peter E. Thelwall,&nbsp;Jordi Diaz-Manera","doi":"10.1002/jcsm.13709","DOIUrl":"10.1002/jcsm.13709","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;Dysferlin plays a key role in cell membrane repair; its absence or malfunction in patients with dysferlin-deficient limb girdle muscular dystrophy leads to muscle fibre death. Muscle magnetic resonance (MR) imaging allows non-invasive and repeatable measurements that can report on pathological changes observed in dysferlinopathy patients (DP). We aimed to demonstrate the feasibility of utilising volume-localised &lt;sup&gt;23&lt;/sup&gt;Na spectroscopy as a novel approach to characterise muscle Na&lt;sup&gt;+&lt;/sup&gt; content and biexponential T&lt;sub&gt;2&lt;/sub&gt;* at rest, and dynamically post-exercise, in patients with dysferlinopathy and in matched healthy controls.&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;Adult DP and age and sex matched healthy volunteers (HV) were recruited and scanned on a 3 T clinical MR scanner. Following baseline scans, participants performed physiotherapist-guided isometric dorsiflexion contractions until &lt;i&gt;tibialis anterior&lt;/i&gt; (TA) muscle exhaustion. Dynamic volume-localised sodium-23 (&lt;sup&gt;23&lt;/sup&gt;Na)- and proton (&lt;sup&gt;1&lt;/sup&gt;H)-MR scans were acquired serially for 35 min post-exercise. MR data were analysed to determine TA lipid content, change in TA sodium content, biexponential sodium T&lt;sub&gt;2&lt;/sub&gt;* properties and TA water &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2&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;Ten DP (mean age ± standard deviation [SD]: 38.0 ± 10.8 years; 80% female) and 10 HV (mean age ± SD: 38.9 ± 11.5 years) were scanned. Baseline muscle water &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2&lt;/sub&gt; and sodium concentration were significantly higher in DP compared to matched controls (&lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2 DP&lt;/sub&gt; [SD] = 33.8 [2.7] ms, &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2 HV&lt;/sub&gt; = 29.3 [1.1] ms, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; [&lt;sup&gt;23&lt;/sup&gt;Na]&lt;sub&gt;DP&lt;/sub&gt; = 36.2 [11.4] mM, [&lt;sup&gt;23&lt;/sup&gt;Na]&lt;sub&gt;HV&lt;/sub&gt; = 19.6 [3.1] mM, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2&lt;/sub&gt; and sodium content in healthy controls showed significant post-exercise elevation with a slower time-to-peak for sodium content compared to &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2&lt;/sub&gt;. &lt;sup&gt;1&lt;/sup&gt;H T&lt;sub&gt;2&lt;/sub&gt; and sodium content change post-exercise was highly variable in the DP group. Notably, &lt;sup&gt;23&lt;/sup&gt;Na dynamics in one DP with normal muscle fat fraction were similar to HV. Biexponential &lt;sup&gt;23&lt;/sup&gt;Na T&lt;sub&gt;2&lt;/sub&gt;* was measured at baseline in HV (T&lt;sub&gt;2&lt;/sub&gt;*&lt;sub&gt;slow&lt;/sub&gt; = 13.4 [2.3] ms, T&lt;sub&gt;2&lt;/sub&gt;*&lt;sub&gt;fast&lt;/sub&gt; = 2.2 [1.3] ms), and DP (T&lt;sub&gt;2&lt;/sub&gt;*&lt;sub&gt;slow&lt;/sub&gt; = 14.0 [1.5] ms and T&lt;sub&gt;2&lt;/sub&gt;*&lt;sub&gt;fast&lt;/sub&gt; = 1.0 [0.5] m). Equivalent measurements post-exercise revealed an increase in the fraction of the slow-relaxing component in HV (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), consiste","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083702","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":"Melatonin Ameliorates Age-Related Sarcopenia via the Gut–Muscle Axis Mediated by Serum Lipopolysaccharide and Metabolites","authors":"Ling-Shan Zhou,&nbsp;Yuan Yang,&nbsp;Li Mou,&nbsp;Xin Xia,&nbsp;Min Liu,&nbsp;Ling-Jie Xu,&nbsp;Rong Liu,&nbsp;Jun-Ping Liu,&nbsp;Hai-Yan Zhang,&nbsp;Xiao-Jun Ao,&nbsp;Chang-Jiang Liu,&nbsp;Qian Xiao,&nbsp;Shi-Xiong Liu","doi":"10.1002/jcsm.13722","DOIUrl":"10.1002/jcsm.13722","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;Sarcopenia affects the quality of life and increases adverse outcomes in the elderly. However, as a potential safe and effective remedy to many age-related disorders, little is known about the protective effect of melatonin against sarcopenia, especially the underlying mechanisms of pathophysiology related to the gut–muscle axis.&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 young (4 months) and old-aged (24 months) wild-type C57BL/6J male mice were included in this study, of which the old-aged mice in the experimental group were treated with 10 mg/kg/day of melatonin for 16 weeks. After that, muscle strength, muscle mass and the cross-sectional area (CSA) of the gastrocnemius muscle fibres were measured. Then, the putative pathways, based on the data obtained from 16S rDNA sequencing of the gut microbiota, RNA sequencing of gastrocnemius muscle and serum untargeted metabolomics, were screened out by the integrated multiomics analysis and validated using immunohistochemistry, ELISA and TUNEL staining. C2C12 myoblasts were treated with LPS. Flow cytometric analysis and western blotting were applied to detect cell apoptosis and protein expressions of Tnfrsf12a and caspase8, respectively. In addition, the mediation analysis was carried out to infer the causal role of the microbiome in contributing to the skeletal muscle through metabolites.&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;Melatonin treatment ameliorated age-related declines in muscle strength (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), muscle mass (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) and CSA of the gastrocnemius muscle fibres (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), as well as changed the gut microbial composition (beta-diversity analysis; &lt;i&gt;R&lt;/i&gt; = 0.513, &lt;i&gt;p&lt;/i&gt; = 0.005). The integrated multiomics analysis implied two main mechanisms about the impact of melatonin-related modifications in the gut microbiota on sarcopenia. First, a lower serum lipopolysaccharide (LPS) level associated with the altered gut microbiota was observed in melatonin-treated mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and was most relevant to the transcription level of Tnfrsf12a in skeletal muscle (&lt;i&gt;R&lt;/i&gt; = 0.926, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Further bioinformatics analyses and in vitro experiments showed that LPS could contribute to skeletal muscle apoptosis by regulating the Tnfrsf12a/caspase-8 signalling pathway. Second, melatonin significantly altered serum metabolites (variable importance on projection (VIP) &gt; 1.5, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Mediation models showed that changes in the gut microbiome also influenced skeletal muscle through these metabolites (27 linkages; BH-adjusted &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083685","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":"Nicotinamide Phosphoribosyltransferase Acetylation Mediating Muscle Dysfunction Contributes to Sleep Apnoea in Obesity","authors":"Liu Zhang,&nbsp;Ya Ru Yan,&nbsp;Shi Qi Li,&nbsp;Ying Ni Lin,&nbsp;Yi Wang,&nbsp;Yu Qing Wang,&nbsp;Ning Li,&nbsp;Fang Ying Lu,&nbsp;Xian Wen Sun,&nbsp;Li Yue Zhang,&nbsp;Jian Ping Zhou,&nbsp;Yong Jie Ding,&nbsp;Qing Yun Li","doi":"10.1002/jcsm.13693","DOIUrl":"10.1002/jcsm.13693","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obstructive sleep apnoea (OSA) occurs frequently among individuals with obesity, which is attributed to upper airway muscle dysfunction. Muscle function is regulated by the dynamic balance of the nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH), which is controlled by the enzyme nicotinamide phosphoribosyltransferase (NAMPT). Elevated NAMPT levels have been found in individuals with obesity. However, the role of NAMPT in obesity-induced muscle impairment has not been fully clarified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 110 participants (70 moderate-to-severe OSA vs. 40 mild or no OSA) underwent electrical impedance mammography and polysomnography. C57BL/6J mice with high-fat diet-induced obesity (DIO) and control group were utilized for their characterizations, which included forced running wheel tests, glucose tolerance tests, haematoxylin and eosin staining, immunostaining, magnetic resonance imaging, whole-body plethysmography, electromyographic techniques, western blot, NAMPT enzymatic activity assays and NAD+/NADH ratio measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with moderate–severe OSA have a significant decrease in lean mass percentage of upper airway muscles compared with those in controls (<i>p</i> &lt; 0.01). In vivo, a high-fat diet reduced the levels of NAD-dependent deacetylase sirtuin-1 (SIRT1) (<i>p</i> &lt; 0.01), which plays a crucial role in the deacetylation of NAMPT. The reduction in SIRT1-mediated NAMPT deacetylation (<i>p</i> &lt; 0.001) resulted in decreased NAMPT activity (<i>p</i> &lt; 0.01), leading to a decrease in NAD+/NADH ratio (<i>p</i> &lt; 0.05) and decreased the myosin heavy chain isoform (MyHC) I level (<i>p</i> &lt; 0.05), thereby affecting the effectiveness of upper airway muscle and ultimately leading to upper airway collapse (101.0 vs. 81.7 pixels, <i>p</i> = 0.02). The introduction of estradiol mitigated high-fat diet-induced muscle dysfunction by enhancing expression of SIRT1 and inhibiting the acetylation of NAMPT, reducing upper airway collapse (81.7 vs. 96.7 pixels, <i>p</i> = 0.06).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the crucial role of SIRT1-mediated NAMPT deacetylation on obesity-induced muscle dysfunction, suggesting targeting NAMPT has the potential to reverse the obesity induced muscle dysfunction and provide effective treatment options for OSA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084078","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":"Prevalence and Prognostic Significance of Sarcopenia in Gynecologic Oncology: A Systematic Review and Meta-Analysis","authors":"Chen Jiang,&nbsp;Qin Chen,&nbsp;Danping Yu,&nbsp;Qianqian Zhou,&nbsp;Cong Tang,&nbsp;Chenping Qiao","doi":"10.1002/jcsm.13699","DOIUrl":"10.1002/jcsm.13699","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia in gynaecologic oncology patients has garnered increasing attention, but its prevalence has not been comprehensively summarized. This study aims to integrate the prevalence of sarcopenia in this population through systematic evaluation and meta-analysis, providing a reference for future clinical research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A computerized search of PubMed, Embase, The Cochrane Library, Web of Science and other databases was conducted to collect relevant literature on the prevalence of sarcopenia in gynaecologic oncology patients and its impact on prognosis, with a timeframe from the inception of the databases to July 2024. Two researchers independently screened the literature, extracted information and assessed the risk of bias. After evaluating the risk of bias, a meta-analysis was performed using RevMan5.4 software. This systematic review was conducted using a previously published study protocol (PROSPERO: CRD42024565094).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 24 studies encompassing 4136 patients were included. The meta-analysis revealed that the prevalence of sarcopenia in gynaecologic oncology patients was 38.8% (<i>I</i>² = 96%, 95% CI [0.49–0.79], <i>p</i> &lt; 0.001). Subgroup analysis indicated that the prevalence of sarcopenia was higher among patients with endometrial cancer or ovarian cancer, those over 60 years of age, individuals with a body mass index (BMI) greater than 25 kg/m², those diagnosed using the psoas muscle index (PMI) and patients assessed at the L4 vertebra. Overall survival (OS) was significantly lower in patients with gynaecologic tumours combined with sarcopenia compared to those with gynaecologic tumours alone. However, no significant differences were observed in progression-free survival (PFS), mortality or length of hospital stay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sarcopenia has a high prevalence in gynaecologic oncology patients. Healthcare professionals should prioritize early screening and preventive measures for high-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076840","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":"Fat-Free Mass: Friend or Foe to Metabolic Health?","authors":"Christopher J. Oliver,&nbsp;Mike Climstein,&nbsp;Nedeljka Rosic,&nbsp;Anja Bosy-Westphal,&nbsp;Grant Tinsley,&nbsp;Stephen Myers","doi":"10.1002/jcsm.13714","DOIUrl":"10.1002/jcsm.13714","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;Fat mass (FM) and fat-free mass (FFM) are body composition estimates commonly reported in research studies and clinical settings. Recently, fat-free mass indexed to height (fat-free mass index; FFMI) has been shown to be positively associated with impaired insulin sensitivity or insulin resistance. Consequently, hypertrophic resistance training which can increase FFM was also questioned. This paper sets out to evaluate these propositions.&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 this narrative review, we discuss possible reasons that link FFMI to adverse metabolic health outcomes including the limitations of the body composition model that utilizes FFM. The safety of resistance training is also briefly discussed.&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;Approximately 50% of FFM is comprised of skeletal muscle (SM), with the other 50% being viscera, skin, and bone; FFM and SM cannot be conflated. FFM and fat mass (FM) can both rise with increasing body weight and adiposity, indicating a positive correlation between the two compartments. Risk assessment models not adequately adjusting for this correlation may cause erroneous conclusions, however which way FM and FFM are indexed. Adipose tissue accumulation with weight gain, measured by dual-energy X-ray absorptiometry or bioelectrical impedance, can inflate FFM estimates owing to increased connective tissue. Increased adiposity can also result in fat deposition within skeletal muscle disrupting metabolic health. Importantly, non-skeletal muscle components of the FFM, i.e., the liver and pancreas, both critical in metabolic health, can also be negatively affected by the same lifestyle factors that impact SM. The most frequently used body composition techniques used to estimate FM and FFM cannot detect muscle, liver or pancreas fat infiltration. Prospective evidence demonstrates that resistance training is a safe and effective exercise modality across all ages, especially in older adults experiencing age- or disease-related declines in muscle health.&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;The association between FFM and insulin resistance is largely an artefact driven by inadequate assessment of skeletal muscle. If FM and FFM are used, at the minimum, they need to be evaluated in context with one another. Body composition methods, such as magnetic resonance imaging, which measures skeletal muscle rather than fat-free mass, and adipose tissue as well as muscle ectopic fat, are preferred methods. Resistance training is important in achieving","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076829","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 Exercise on Spexin and Follistatin in Elderly Individuals","authors":"Elif Yıldırım Ayaz,&nbsp;Berna Dincer,&nbsp;Gülser Cinbaz,&nbsp;Esra Karacan,&nbsp;Reyhan Kaygusuz Benli,&nbsp;Emel Mete,&nbsp;Hilal Bilgiç,&nbsp;Banu Mesci","doi":"10.1002/jcsm.13692","DOIUrl":"10.1002/jcsm.13692","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;In adipose tissue–muscle crosstalk mechanisms, the interaction of adipokines and myokines is known to be critical for maintaining the body's metabolic balance in age-related metabolic disorders. The aim of the study investigate the effects of 12 weeks of aerobic and resistance exercise training on spexin and follistatin and their relationship with each other.&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 study was a multicentre, randomized controlled study conducted at two assisted living facilities with participants aged ≥ 65. Among the 66 subjects, 33 were allocated to the exercise group (E) and 33 to the control group (C). The exercise group was administered 50 min of exercise by expert physiotherapists 1 day a week for 12 weeks. Participants in the intervention groups performed exercise assignments two extra days a week, tailored to their specific circumstances and supervised by the institution's physiotherapists. Spexin, follistatin and measurements of metabolic syndrome parameters were performed at the beginning and after 12 weeks.&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 62 participants who completed the study (E &lt;i&gt;n&lt;/i&gt; = 31, C &lt;i&gt;n&lt;/i&gt; = 31) was 73.25 ± 6.44 years, and 62.9% were female. While spexin (E = 1090.94 ± 533.66, C = 1142.91 ± 550.68 pg/mL, &lt;i&gt;p&lt;/i&gt; &gt; 0.05) and follistatin (E = 50.52 ± 24.35, C = 50.00 ± 23.52 ng/mL, &lt;i&gt;p&lt;/i&gt; &gt; 0.05) values were similar in the two groups at baseline, the values of spexin (E = 1311.32 ± 513.66, C = 1033.27 ± 486.48, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.387) and follistatin (E = 64.79 ± 32.35, C = 48.16 ± 26.27, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; &lt;i&gt;η&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.267) in the exercise group were higher than in the control group at week 12. At the 12th week, neck circumference (38.32 ± 3.41, 37.16 ± 3.15, &lt;i&gt;p&lt;/i&gt; = 0.002), waist circumference (102.64 ± 13.38, 98.54 ± 14.47, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), hip circumference (105.70 ± 15.43, 102.93 ± 13.48, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), body fat mass (22.69 ± 7.39, 20.45 ± 6.22, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and systolic and diastolic blood pressure (137.19 ± 13.80, 124.9 ± 15.18, &lt;i&gt;p&lt;/i&gt; = 0.0001, 77.38 ± 12.10, 72.61 ± 9.26, &lt;i&gt;p&lt;/i&gt; = 0.043) decreased, and body muscle mass (46.32 ± 8.43, 49.03 ± 8.58, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) increased in the exercise group compared to baseline. A correlation was observed between the change in follistatin level and the change in spexin level (&lt;i&gt;r&lt;/i&gt; = 0.438, &lt;i&gt;p&lt;/i&gt; = 0.001). A negative correlation was found between the amount of decrease in body fat mass and the decrease in spexin level (&lt;i&gt;r&lt;/i&gt; = −0.380, &lt;i&gt;p&lt;/i&gt; = 0.005). A positive correlation was foun","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076839","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":"Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice","authors":"Jeong Hwan Park,&nbsp;Jongsoo Mok,&nbsp;Seoah Park,&nbsp;Dooho Kim,&nbsp;Min-Su Kang,&nbsp;Tae Sub Park,&nbsp;Joonghoon Park","doi":"10.1002/jcsm.13704","DOIUrl":"10.1002/jcsm.13704","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;Muscle diseases are serious challenges to human health. Prokineticin receptor 1 (PROKR1) has emerged as a potential target to improve muscle function through increasing oxidative muscle fibres, but there are no clinically applicable synthetic PROKR1 agonists.&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;Drugs with biological properties of prokineticin 2 (PK2) were discovered through connectivity map (CMap) analysis. Their effects on PROKR1 were evaluated using molecular docking, PROKR1 signalling and competitive binding assays. Pregnant dams were fed diets containing varying celecoxib concentrations (0, 500, 1000 and 1500 ppm) from gestation day 5 through weaning. Offspring were given high-fat diets (HFD) from weaning until 20 weeks old, and body composition, insulin resistance, energy expenditure, exercise performance and histological analysis of muscle tissues were evaluated.&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;Celecoxib, with a connectivity score of 64.19 to PK2 and a docking score of −9.0 to PROKR1, selectively activated Gs signalling at 4 μM of EC&lt;sub&gt;50&lt;/sub&gt; and increased NR4A2 protein levels by 1.6-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) in PROKR1-overexpressing cells. It competitively inhibited PK2 binding to PROKR1 and reduced cAMP accumulation. In murine and human myotubes, celecoxib increased Prokr1 protein levels by 1.8-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), pCreb by 1.5-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and Nr4a2 by 1.3-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). It also elevated Myh7 index by 2.2-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), mitochondrial content by 1.6-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and fatty acid oxidation (FAO) activity by 4.1-fold (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Offspring exposed to celecoxib during pre- and postnatal muscle development exhibited activated Prokr1 signalling, enhanced oxidative muscle fibre formation and improved muscle phenotype despite HFD. At weaning, both male and female offspring showed dose-dependent increases in lean mass (&gt; 9.35%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and grip strength (&lt; 18.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). At 12 weeks old, mice displayed a dose-dependent decrease in weight loss (&gt; 13.3%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), increased lean mass (&gt; 16.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), improved insulin resistance (&gt; 70.4%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), energy expenditure (&gt; 173%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and grip strength (&gt; 23.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Celecoxib also increased Myh7-positive muscle fibre composition (&gt; 10.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and mitochondrial mass (&gt; 32.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) in the gastrocnemius and soleus muscles, accompanied by significant Prokr1 signalling activation. These effects persisted in both male and fem","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 1","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056612","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}