Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"SRSF1 Is Crucial for Maintaining Satellite Cell Homeostasis During Skeletal Muscle Growth and Regeneration","authors":"Zhenzhen Wang, Qian Peng, Zhige Zhang, Xue You, Huimin Duan, Rula Sha, Ningyang Yuan, Zhigang Li, Zhiqin Xie, Jun Han, Ying Feng","doi":"10.1002/jcsm.13607","DOIUrl":"https://doi.org/10.1002/jcsm.13607","url":null,"abstract":"The splicing factor SRSF1 emerges as a mater regulator of cell proliferation, displaying high expression in actively proliferative satellite cells (SCs). In SRSF1 knockout mice (KO) generated via <i>MyoD-Cre</i>, early mortality and muscle atrophy are observed during postnatal muscle growth. Despite these findings, the precise mechanisms through which SRSF1 loss influences SCs' functions and its role in muscle regeneration remain to be elucidated.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"33 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Health Associations With Height‐Normalised Abdominal Body Composition Indices: A Single‐Centre Cross‐Sectional Study","authors":"Yupeng Liu, Hangqian He, Keyu Qian, Yufeng Huang, Xuemei Ao, Xudong Shi, Binye Ruan, Ru Xue, Xiaoyi Fu, Shuran Wang","doi":"10.1002/jcsm.13609","DOIUrl":"https://doi.org/10.1002/jcsm.13609","url":null,"abstract":"BackgroundTraditional metrics such as body mass index (BMI) and waist circumference (WC) fail to accurately assess the health outcomes associated with abdominal adiposity, because they neglect the intricacies of adipose tissue distribution. Notably, the variability in body composition scaled to height remains underexplored in Chinese demographics. This study introduces height‐normalised indices of abdominal adiposity using computed tomography (CT) scans and further assesses their associations with various health outcomes.MethodsIn a large, diverse Chinese population (<jats:italic>n</jats:italic> = 1054 healthy individuals; <jats:italic>n</jats:italic> = 1159 with dyslipidemia; <jats:italic>n</jats:italic> = 803 with diabetes; <jats:italic>n</jats:italic> = 1289 with cardio‐cerebrovascular diseases; <jats:italic>n</jats:italic> = 1108 with cancers; and <jats:italic>n</jats:italic> = 509 with abnormal bone mas), abdominal CT scans were performed and allometric growth model analyses were used to derive height‐normalised indices (body composition/height<jats:sup><jats:italic>β</jats:italic></jats:sup>). Logistic regression models assessed the associations between these indices and health outcomes.ResultsDistinct scaling powers were observed for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT), as well as for sagittal diameter (SAD), with marked sex differences. Powers for VAT were 1.786 ± 1.270 for males and 1.274 ± 0.692 for females. Powers for SAT were 2.266 ± 0.856 for males and 1.656 ± 0.497 for females. Powers for TAT were 2.141 ± 0.967 for males and 1.438 ± 0.489 for females. Powers for SAD were 0.646 ± 0.217 for males and 0.678 ± 0.141 for females. After controlling for age, BMI and WC, VAT/height<jats:sup><jats:italic>β</jats:italic></jats:sup>, TAT/height<jats:sup><jats:italic>β</jats:italic></jats:sup> and SAD/height<jats:sup><jats:italic>β</jats:italic></jats:sup> retained their significantly positive associations with the odds of health outcomes, whereas SAT/height<jats:sup><jats:italic>β</jats:italic></jats:sup> did not.ConclusionsOur findings endorse the clinical utility of height‐normalised indices, particularly VAT/height<jats:sup><jats:italic>β</jats:italic></jats:sup>, TAT/height<jats:sup><jats:italic>β</jats:italic></jats:sup> and SAD/height<jats:sup><jats:italic>β</jats:italic></jats:sup>, in health outcomes assessment. These indices, grounded in robust empirical data, underscore the necessity of a nuanced approach in obesity‐related health evaluations, advocating for a departure from conventional methods like BMI.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"70 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between dynapenic obesity and risk of cardiovascular disease: The Hisayama study","authors":"Yu Setoyama, Takanori Honda, Takahiro Tajimi, Satoko Sakata, Emi Oishi, Yoshihiko Furuta, Mao Shibata, Jun Hata, Takanari Kitazono, Yasuharu Nakashima, Toshiharu Ninomiya","doi":"10.1002/jcsm.13564","DOIUrl":"https://doi.org/10.1002/jcsm.13564","url":null,"abstract":"BackgroundDynapenic obesity is a condition characterized by high adiposity levels combined with muscle dysfunction. Although high adiposity and muscle loss/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population‐based prospective longitudinal study in Japan.MethodsA total of 2490 community‐dwelling Japanese aged 40–79 years (42.5% males, mean age 57.7 ± 10.6 years) without a history of CVD were followed up for a median of 24 years. Handgrip strength was classified as low, medium, or high by age‐ and sex‐specific tertiles. Body mass index (BMI) levels were categorized as lean (&lt;18.5 kg/m<jats:sup>2</jats:sup>), normal (18.5–24.9 kg/m<jats:sup>2</jats:sup>), or obese (≥25.0 kg/m<jats:sup>2</jats:sup>). Dynapenic obesity was defined as having both low handgrip strength and obesity. The outcomes were defined as the first‐ever development of CVD (defined as stroke or coronary heart disease). The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of CVD were estimated using a Cox proportional hazards model, in which participants with high handgrip strength and normal BMI were used as a reference group. Mediation analyses used serum high‐sensitivity C‐reactive protein (hs‐CRP) and homeostatic model assessment for insulin resistance (HOMA‐IR) as mediators.ResultsDuring the follow‐up period, 482 participants developed CVD events (324 cases of stroke and 209 of coronary heart disease). The multivariable‐adjusted risk of CVD increased significantly among participants with dynapenic obesity compared with the reference group (HR 1.49, 95% CI 1.03–2.17). An analysis by age groups showed a further increase in the risk of CVD among participants with dynapenic obesity aged less than 65 years (HR 1.66, 95% CI 1.04–2.65). In mediation analyses for participants aged less than 65 years, serum hs‐CRP was shown to be a significant mediator explaining 13.8% of the association between dynapenic obesity and the development of CVD, while HOMA‐IR explained 12.2% of this relationship.ConclusionsDynapenic obesity was a significant risk factor for the development of CVD in a general Japanese population. This association was more pronounced among those aged &lt;65 years. Inflammation, and possibly glucose metabolism, might partly mediate this association. Our findings suggest that preventing muscle dysfunction as well as appropriate weight control, especially in middle‐age, are important for preventing the development of CVD.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"192 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of computed tomography-derived body composition and complications after colorectal cancer surgery: A systematic review and meta-analysis.","authors":"Claire P M van Helsdingen, Job G A van Wijlick, Ralph de Vries, Nicole D Bouvy, Mariska M G Leeflang, Robert Hemke, Joep P M Derikx","doi":"10.1002/jcsm.13580","DOIUrl":"https://doi.org/10.1002/jcsm.13580","url":null,"abstract":"<p><p>The prediction of the risk of developing complications after colorectal surgery for colorectal carcinoma remains imprecise. Body composition measurements on a computed tomography (CT) scan can potentially contribute to a better preoperative risk assessment. The aim of this systematic review is to evaluate the evidence for the use of body composition measurements on CT scans to predict short-term complications after colorectal cancer surgery. A literature search (in PubMed, Embase and Web of Science) was performed up to 1 August 2022. Two researchers independently screened the articles, extracted data and assessed the quality of the studies using the Quality in Prognosis Studies tool. The primary outcome measure was the occurrence of complications within 30 days after surgery. Meta-analysis was conducted using a random-effects model to synthesize a pooled odds ratio (OR). The study protocol was registered in PROSPERO (CRD42021281010). Forty-five articles with a total of 16 537 patients were included. In total, 26 body composition measures were investigated: 8 muscle-related measures, 11 adipose tissue measures, 4 combined muscle and adipose tissue measures, and 3 other measures. These were investigated as potential predictors for more than 50 differently defined postoperative complications. Meta-analysis was only possible for two measurements and showed that higher amounts of visceral fat increase the risk of developing overall complications (OR: 2.52 [1.58-4.00], P < 0.0001) and anastomotic leakage (OR: 1.76 [1.17-2.65], P = 0.006). A wide variety of body composition measurements on preoperative CT scans have been investigated as a predictive factor for postoperative complications. Visceral fat appeared to be associated with overall complications and anastomotic leakage; however, the association is weak, and its clinical relevance or applicability is questionable. The current evidence is limited by methodological heterogeneity and the risk of bias. To improve comparability of results across studies and improve decision-making, future studies should use standardized methods for measuring body composition on CT scans, outcome definitions and statistical analyses.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'Total Magnesium Intake and Risk of Frailty in Older Women' by Struijk Et Al.","authors":"Long Guo, Qing Lan, Ming Zhou, Fei Liu","doi":"10.1002/jcsm.13592","DOIUrl":"https://doi.org/10.1002/jcsm.13592","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Perioperative Skeletal Muscle Index Change With Outcome in Colorectal Cancer Patients.","authors":"Zhenhui Li, Guanghong Yan, Mengmei Liu, Yanli Li, Lizhu Liu, Ruimin You, Xianshuo Cheng, Caixia Zhang, Qingwan Li, Zhaojuan Jiang, Jinqiu Ruan, Yingying Ding, Wenliang Li, Dingyun You, Zaiyi Liu","doi":"10.1002/jcsm.13594","DOIUrl":"https://doi.org/10.1002/jcsm.13594","url":null,"abstract":"<p><strong>Background: </strong>The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients.</p><p><strong>Methods: </strong>This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: high_pre-high_post, high_pre-low_post, low_pre-high_post and low_pre-low_post. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models.</p><p><strong>Results: </strong>A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with high_pre-high_post, those with high_pre-low_post (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with low_pre-low_post were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with low_pre-high_post had similar risk of RFS compared to those with high_pre-high_post at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05).</p><p><strong>Conclusions: </strong>Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal and progressive coenzyme Q₁₀ administration to mitigate muscle dysfunction in mitochondrial disease.","authors":"Juan Diego Hernández-Camacho, Cristina Vicente-García, Lorena Ardila-García, Ana Padilla-Campos, Guillermo López-Lluch, Carlos Santos-Ocaña, Peter S Zammit, Jaime J Carvajal, Plácido Navas, Daniel J M Fernández-Ayala","doi":"10.1002/jcsm.13574","DOIUrl":"https://doi.org/10.1002/jcsm.13574","url":null,"abstract":"<p><strong>Background: </strong>ADCK genes encode aarF domain-containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult-onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid β-oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ₁₀, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention.</p><p><strong>Methods: </strong>We used Adck2 heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests.</p><p><strong>Results: </strong>We demonstrated that Adck2 heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). Adck2 heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ₁₀ could mitigate these embryonic defects. Heterozygous Adck2 mice also showed a decrease in myogenic cell differentiation, with more severe consequences in 'aged' mice (41.63% smaller) (P < 0.01). Consequently, heterozygous Adck2 mice displayed accelerated muscle wasting associated with ageing in muscle structure (P < 0.05), muscle function (less grip strength capacity) (P < 0.001) and muscle mitochondrial respiration (P < 0.001). Furthermore, progressive CoQ₁₀ administration conferred protective effects on mitochondrial function (P < 0.0001) and skeletal muscle (P < 0.05).</p><p><strong>Conclusions: </strong>Our work uncovered novel aspects of CoQ deficiencies, revealing defects during embryonic development in mammals for the first time. Additionally, we identified the gradual establishment and progression of the deleterious Adck2 mouse phenotype. Importantly, CoQ₁₀ supplementation demonstrated a protective effect when initiated during development.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Male Sex and Ageing are Independent Risk Factors for Sarcopenia Stage in Patients With Chronic Kidney Disease Not Yet on Dialysis.","authors":"Yi-Fang Huang, Shih-Ping Liu, Chih-Hsin Muo, Chen-Yi Lai, Chung-Ta Chang","doi":"10.1002/jcsm.13612","DOIUrl":"https://doi.org/10.1002/jcsm.13612","url":null,"abstract":"<p><strong>Background: </strong>The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD.</p><p><strong>Methods: </strong>The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance.</p><p><strong>Results: </strong>Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001).</p><p><strong>Conclusions: </strong>This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tensile force impairs lip muscle regeneration under the regulation of interleukin-10.","authors":"Xu Cheng, Jinfeng Dou, Jinggui Li, Yixuan Huang, Bing Shi, Jingtao Li","doi":"10.1002/jcsm.13584","DOIUrl":"https://doi.org/10.1002/jcsm.13584","url":null,"abstract":"<p><strong>Background: </strong>Orbicularis oris muscle, the crucial muscle in speaking, facial expression and aesthetics, is considered the driving force for optimal lip repair. Impaired muscle regeneration remains the main culprit for unsatisfactory surgical outcomes. However, there is a lack of study on how different surgical manipulations affect lip muscle regeneration, limiting efforts to seek effective interventions.</p><p><strong>Methods: </strong>In this study, we established a rat lip surgery model where the orbicularis oris muscle was injured by manipulations including dissection, transection and stretch. The effect of each technique on muscle regeneration was examined by histological analysis of myogenesis and fibrogenesis. The impact of tensile force was further investigated by the in vitro application of mechanical strain on cultured myoblasts. Transcriptome profiling of muscle satellite cells from different surgical groups was performed to figure out the key factors mediating muscle fibrosis, followed by therapeutic intervention to improve muscle regeneration after lip surgeries.</p><p><strong>Results: </strong>Evaluation of lip muscle regeneration till 56 days after injury revealed that the stretch group resulted in the most severe muscle fibrosis (n = 6, fibrotic area 48.9% in the stretch group, P < 0.001, and 25.1% in the dissection group, P < 0.001). There was the lowest number of Pax7-positive nuclei at Days 3 and 7 in the stretch group (n = 6, P < 0.001, P < 0.001), indicating impaired satellite cell expansion. Myogenesis was impaired in both the transection and stretch groups, as evidenced by the delayed peak of centrally nucleated myofibers and embryonic MyHC. Meanwhile, the stretch group had the highest percentage of Pdgfra⁺ fibro-adipogenic progenitors infiltrated area at Days 3, 7 and 14 (n = 6, P = 0.003, P = 0.006, P = 0.037). Cultured rat lip muscle myoblasts exhibited impaired myotube formation and fusion capacity when exposed to a high magnitude (ε = 2688 μ strain) of mechanical strain (n = 3, P = 0.014, P = 0.023). RNA-seq analysis of satellite cells isolated from different surgical groups demonstrated that interleukin-10 was the key regulator in muscle fibrosis. Administration of recombinant human Wnt7a, which can inhibit the expression of interleukin-10 in cultured satellite cells (n = 3, P = 0.041), exerted an ameliorating effect on orbicularis oris muscle fibrosis after stretching injury in surgical lip repair.</p><p><strong>Conclusions: </strong>Tensile force proved to be the most detrimental manoeuvre for post-operative lip muscle regeneration, despite its critical role in correcting lip and nose deformities. Adjunctive biotherapies to regulate the interleukin-10-mediated inflammatory process could facilitate lip muscle regeneration under conditions of high surgical tensile force.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Cachexia and First-Line Systemic Therapy for Previously Untreated Advanced Non-Small Cell Lung Cancer: NEJ050A.","authors":"Keita Miura, Takehito Shukuya, Naoki Furuya, Ryo Morita, Akira Kisohara, Atsuto Mouri, Satoshi Watanabe, Hisashi Tanaka, Aya Hirata, Taiki Hakozaki, Kosuke Hamai, Naoko Matsumoto, Kana Watanabe, Hironori Ashinuma, Eisaku Miyauchi, Koji Sugano, Shinobu Hosokawa, Koji Amano, Satoshi Morita, Kunihiko Kobayashi, Makoto Maemonodo, Kazuhisa Takahashi","doi":"10.1002/jcsm.13606","DOIUrl":"https://doi.org/10.1002/jcsm.13606","url":null,"abstract":"<p><strong>Background: </strong>Cancer cachexia complicates advanced non-small cell lung cancer (NSCLC); however, it remains unclear how often cachexia occurs and how it affects the course of chemotherapy in patients receiving first-line systemic therapy.</p><p><strong>Methods: </strong>We conducted a multicentre, prospective observational study and enrolled previously untreated NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 and cachexia between September 2020 and September 2021. The primary outcome measure was the trends in the Functional Assessment of Anorexia/Cachexia Treatment and Anorexia/Cachexia Subscale [FAACT (A/CS)] scores by cohort. Secondary outcome measures included the incidence of cachexia before the initiation of first-line systemic therapy, quality of life (QOL) measures, body weight (BW) changes, and efficacy and safety of first-line systemic therapy.</p><p><strong>Results: </strong>A total of 887 consecutive patients with previously untreated advanced NSCLC and ECOG PS of 0-2 who were initiated on first-line systemic therapy were evaluated. A total of 281 patients (31.7%) experienced BW loss consistent with the criteria of cachexia, and 186 were evaluated for QOL, BW and outcome measurements. Overall, 180/186 patients received first-line systemic therapy. Cohort 1 (targeted therapy), cohort 2 [cytotoxic chemotherapy (CTx) ± immune checkpoint inhibitors (ICIs)] and cohort 3 (ICIs) included 42, 98 and 40 patients, respectively. There were significant variations in QOL trends by cohort, with chemotherapy-associated emesis affecting early appetite-related QOL. The change in the FAACT (A/CS) score at 1 week from baseline was worse in cohort 2 (the least square mean change ± standard error: -3.0 ± 0.9) than in cohorts 1 (1.6 ± 1.2, p = 0.003) and 3 (1.8 ± 1.0, p = 0.002); meanwhile, the change at 6 weeks was worse in cohort 1 (-1.5 ± 1.2) than in cohorts 2 (3.6 ± 0.9, p = 0.001) and 3 (3.5 ± 1.1, p = 0.004). BW reduction was observed in all cohorts within 6 weeks of therapy initiation. The targeted therapy cohort demonstrated superior progression-free survival (PFS) and overall survival (OS) to CTx ± ICIs cohort or ICIs cohort (median PFS was 9.7 months, 6.3 months, 3.1 months, in cohort 1, 2, 3, respectively (cohort 1 vs. cohort 2: HR, 0.58, p = 0.018; cohort 1 vs. cohort 3: HR, 0.41, p = 0.001); median OS was not reached, 15.8 months, 9.9 months, respectively (cohort 1 vs. cohort 2: HR, 0.52, p = 0.033; cohort 1 vs. cohort 3: HR, 0.37, p = 0.003).</p><p><strong>Conclusions: </strong>Approximately 1/3 patients with previously untreated advanced NSCLC have cachexia. Appetite-related QOL trends vary based on the type of first-line systemic therapy in cachectic NSCLC patients, and the PFS and OS of these patients seemed to be shorter.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}