Journal of Cachexia Sarcopenia and Muscle最新文献

{"title":"Co-morbid sarcopenia and low bone mineral density in young paediatric cancer survivors","authors":"Andres Marmol-Perez, Esther Ubago-Guisado, Jose J. Gil-Cosano, Francisco J. Llorente-Cantarero, Juan Francisco Pascual-Gázquez, Manuel Muñoz-Torres, Vicente Martinez-Vizcaino, Kirsten K. Ness, Jonatan R. Ruiz, Luis Gracia-Marco","doi":"10.1002/jcsm.13563","DOIUrl":"10.1002/jcsm.13563","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD <i>Z</i>-score in young paediatric cancer survivors with sarcopenia confirmed/probable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm<sup>2</sup>) and appendicular lean mass index (ALMI, kg/m<sup>2</sup>). ‘No sarcopenia’ was defined when muscle strength was >decile 2. ‘Sarcopenia probable’ was defined when muscle strength was ≤ decile 2 and ALMI Z-score was > −1.5 standard deviation (SD). ‘Sarcopenia confirmed’ was defined when muscle strength was ≤ decile 2 and ALMI <i>Z</i>-score ≤ −1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD <i>Z</i>-score < −1.0).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (−1.2 [95% CI: −1.5 to −0.8] vs. 0.2 [−0.2 to 0.6], <i>P</i> < 0.001), lumbar spine (−0.7 [−1.1 to −0.3] vs. 0.4 [0.0 to 0.8], <i>P</i> < 0.001), total hip (−0.5 [−0.9 to −0.2] vs. 0.4 [0.1 to 0.8], <i>P</i> < 0.001), and femoral neck (−1.0 [−1.4 to −0.6] vs. 0.1 [−0.3 to 0.4], <i>P</i> = 0.001). Compared with survivors with sarcopenia probable, survivors with sarcopenia confirmed had significantly lower aBMD <i>Z</i>-score at total body (−1.2 [−1.5 to −0.8] vs. −0.2 [−0.7 to 0.4], <i>P</i> = 0.009), total hip (−0.5 [−0.9 to −0.2] vs. 0.5 [−0.1 to 1.0], <i>P</i> = 0.010), and femoral neck (−1.0 [−1.4 to −0.6] vs. 0.1 [−0.5 to 0.7], <i>P</i> = 0.014). Survivors with sarcopenia confirmed were at higher risk of low aBMD <i>Z</i>-score at the total body (OR: 6.91, 95% CI: 2.31–24.15), total hip (OR: 2.98, 1.02–9.54), and femoral neck (OR: 4.72, 1.72–14.19), than those without sarcopenia. Survivors with sarcopenia probable were at higher risk of low aBMD <i>Z</i>-score at the total body (OR: 4.13, 1.04–17.60) than those without sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007922","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 maternal lifestyle in pregnancy: Implications for foetal skeletal muscle development","authors":"Haijun Sun,&nbsp;Meixia Chen,&nbsp;Jialong Liao,&nbsp;Linjuan He,&nbsp;Boyang Wan,&nbsp;Jingdong Yin,&nbsp;Xin Zhang","doi":"10.1002/jcsm.13556","DOIUrl":"10.1002/jcsm.13556","url":null,"abstract":"<p>The world is facing a global nutrition crisis, as evidenced by the rising incidence of metabolic disorders such as obesity, insulin resistance and chronic inflammation. Skeletal muscle is the largest tissue in humans and plays an important role in movement and host metabolism. Muscle fibre formation occurs mainly during the embryonic stage. Therefore, maternal lifestyle, especially nutrition and exercise during pregnancy, has a critical influence on foetal skeletal muscle development and the subsequent metabolic health of the offspring. In this review, the influence of maternal obesity, malnutrition and micronutrient intake on foetal skeletal muscle development is systematically summarized. We also aim to describe how maternal exercise shapes foetal muscle development and metabolic health in the offspring. The role of maternal gut microbiota and its metabolites on foetal muscle development is further discussed, although this field is still in its ‘infancy’. This review will provide new insights to reduce the global crisis of metabolic disorders and highlight current gaps to promote further research.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999072","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":"Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study","authors":"Min-gu Kang,&nbsp;Ji Yeon Baek,&nbsp;Yunju Jo,&nbsp;Dongryeol Ryu,&nbsp;Il-Young Jang,&nbsp;Hee-Won Jung,&nbsp;Beom-Jun Kim","doi":"10.1002/jcsm.13561","DOIUrl":"10.1002/jcsm.13561","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;Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index—a comprehensive measure of biological aging in a nationally representative cohort of community-dwelling older adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a population-based, cross-sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non-frail (FI ≤ 0.15), pre-frail (0.15 &lt; FI ≤ 0.25), or frail (FI &gt; 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay.&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 controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non-frail counterparts (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Furthermore, serum UA concentrations demonstrated a positive correlation with the FI (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), and the odds ratio for frailty per 1 mg/dL increase in serum UA was 1.22 (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Additionally, older adults in the highest quartile of UA levels exhibited a significantly higher FI and 1.66-fold increased odds of frailty compared with those in the lowest quartile (&lt;i&gt;P&lt;/i&gt; = 0.011 and &lt;i&gt;P&lt;/i&gt; = 0.005, respectively).&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;These findings suggest that elevated circulating UA levels may act as a pro-aging factor rather than an anti-aging one in older adults, highlighting its potential role in accelerating biological aging. The data further support the utility of serum UA as a potential blood-based biomarker for frailty in this demographic, contributing to the expanding evidence on its significance in geriatric health assessments.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 &lt;/div","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999071","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":"Change in physical activity and its association with decline in kidney function: A UK Biobank-based cohort study","authors":"Qiaoling Liu,&nbsp;Carlos Celis-Morales,&nbsp;Jennifer S. Lees,&nbsp;Naveed Sattar,&nbsp;Frederick K. Ho,&nbsp;Jill P. Pell,&nbsp;Patrick B. Mark,&nbsp;Paul Welsh","doi":"10.1002/jcsm.13551","DOIUrl":"10.1002/jcsm.13551","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort study was constructed using the UK Biobank. Changes in physical activity were self-reported as metabolic equivalent task (MET) minutes/week. eGFR was calculated using SCr and cystatin C (CysC). Cox and nonlinear regressions with restricted cubic splines were applied to explore the association between changes in physical activity and rapid decline of kidney function (RDKF, eGFR annual decrease ≥3 mL/min/1.73 m²), and the annual change of eGFR. An exploratory analysis of cardiorespiratory fitness as the exposure was conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 11 757 participants, the median follow-up time was 4.4 years. Participants whose PA decreased by 1000 MET minutes/week at the follow-up assessment had a 2% reduction in risk of developing RDKF_SCr (HR = 0.98, 95% CI: 0.96, 1.00). In contrast, a 1000 MET minutes/week increase in PA was associated with a 4% reduction in risk of developing RDKF_CysC (HR = 0.96, 95% CI: 0.93, 0.99). A PA increase of 1000 MET minutes/week was associated with eGFR_CysC annual increase of 0.04 mL/min/1.73 m² (95% CI: 0.03, 0.06) but no significant changes in eGFR_SCr.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this general population study, there are differing associations between changes in PA and changes in kidney function depending on the kidney biomarker used. Increasing PA is modestly associated with improving annual eGFR_CysC and reduced risk of RDKF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999070","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":"Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism","authors":"Yu-Ning Fann,&nbsp;Wan-Huai Teo,&nbsp;Hsin-Chen Lee,&nbsp;Chen-Chung Liao,&nbsp;Yeou-Guang Tsay,&nbsp;Tung-Fu Huang,&nbsp;Jeng-Fan Lo","doi":"10.1002/jcsm.13549","DOIUrl":"10.1002/jcsm.13549","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;Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co-chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular &lt;i&gt;Dnaja3&lt;/i&gt; haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We generated mouse strain with &lt;i&gt;Dnaja3&lt;/i&gt; heterozygosity (&lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt;) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and &lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt; mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and &lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt; mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short-term and long-term GMI treatment were administrated intraperitoneally to the &lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt; young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, 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;Muscular &lt;i&gt;Dnaja3&lt;/i&gt; heterozygosity resulted in impaired locomotor activity (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), reduced muscular cross-sectional area (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), and up-regulation of lipogenesis (ACC2) and pro-inflammation (STAT3) in skeletal muscles (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Primary myoblasts from the &lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt; mice displayed impaired mitochondrial respiration (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) and imbalanced mitochondrial ROS levels. A systemic proteomic analysis of the purified mitochondria from the primary myoblasts was conducted to show the abnormalities in mitochondrial function and fatty acid metabolism (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001). At age of 13 to 14 months, the &lt;i&gt;HSA-Dnaja3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;f/+&lt;/i&gt;&lt;/sup&gt; mice displayed increased body fat mass (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), reduced fat-free mass (&lt;i&gt;P&lt;/i&gt; &lt; 0.01), and impaired glucose and insulin tolerance (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). The short-term GMI treatment improved locomotor activity (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) and down-regulated the protein levels of STAT3 (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), ACC2, and mitochondrial respiratory complex III (UQCRC2) (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) via DNAJA3 activation. The long-term GMI treatment ameliorated ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915606","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":"Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy","authors":"Alexis Boulinguiez,&nbsp;Jamila Dhiab,&nbsp;Barbara Crisol,&nbsp;Laura Muraine,&nbsp;Ludovic Gaut,&nbsp;Corentin Rouxel,&nbsp;Justine Flaire,&nbsp;Hadidja-Rose Mouigni,&nbsp;Mégane Lemaitre,&nbsp;Benoit Giroux,&nbsp;Lucie Audoux,&nbsp;Benjamin SaintPierre,&nbsp;Arnaud Ferry,&nbsp;Vincent Mouly,&nbsp;Gillian Butler-Browne,&nbsp;Elisa Negroni,&nbsp;Alberto Malerba,&nbsp;Capucine Trollet","doi":"10.1002/jcsm.13546","DOIUrl":"10.1002/jcsm.13546","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;Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the &lt;i&gt;PAPBN1&lt;/i&gt; gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD.&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 study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of &lt;i&gt;gastrocnemius&lt;/i&gt; and &lt;i&gt;soleus&lt;/i&gt; muscles was performed, inducing hypertrophy of the &lt;i&gt;plantaris&lt;/i&gt; muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted.&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;Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both &lt;i&gt;tibialis anterior&lt;/i&gt; (+24%, **&lt;i&gt;P&lt;/i&gt; = 0.0026) and &lt;i&gt;gastrocnemius&lt;/i&gt; (+18%, ****&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) as well as enhanced collagen deposition (+20%, **&lt;i&gt;P&lt;/i&gt; = 0.0064 in the &lt;i&gt;tibialis anterior&lt;/i&gt;; +35%, **&lt;i&gt;P&lt;/i&gt; = 0.0042 in the &lt;i&gt;gastrocnemius&lt;/i&gt;) in the exercised A17 OPMD mice. In the supraphysiological resistance overload protocol, we also observed an increased collagen deposition (×2, ****&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) in the &lt;i&gt;plantaris&lt;/i&gt; muscle of A17 OPMD mice which was associated with larger muscle mass (×2, ****&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and fibre cross sectional area (×2, ***&lt;i&gt;P&lt;/i&gt; = 0.0007) and increased absolute maximal force (×2, ****&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) as well as a reduction in PABPN1 aggregate number (−16%, ****&lt;i&gt;P&lt;/i&gt; &lt; 0.0001).&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;Running exercise and mechanical overloa","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900293","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":"l-Carnitine relieves cachexia-related skeletal muscle fibrosis by inducing deltex E3 ubiquitin ligase 3L to negatively regulate the Runx2/COL1A1 axis","authors":"Zongliang Lu,&nbsp;Li Wang,&nbsp;Zhenyu Huo,&nbsp;Na Li,&nbsp;Ning Tong,&nbsp;Feifei Chong,&nbsp;Jie Liu,&nbsp;Yaowen Zhang,&nbsp;Hongxia Xu","doi":"10.1002/jcsm.13544","DOIUrl":"10.1002/jcsm.13544","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cancer cachexia-induced skeletal muscle fibrosis (SMF) impairs muscle regeneration, alters the muscle structure and function, reduces the efficacy of anticancer drugs, diminishes the patient's quality of life and shortens overall survival. RUNX family transcription factor 2 (Runx2), a transcription factor, and collagen type I alpha 1 chain (COL1A1), the principal constituent of SMF, have been linked previously, with Runx2 shown to directly modulate COL1A1 mRNA levels. &lt;span&gt;l&lt;/span&gt;-Carnitine, a marker of cancer cachexia, can alleviate fibrosis in liver and kidney models; however, its role in cancer cachexia-associated fibrosis and the involvement of Runx2 in the process remain unexplored.&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;Female C57 mice (48 weeks old) were inoculated subcutaneously with MC38 cells to establish a cancer cachexia model. A 5 mg/kg dose of &lt;span&gt;l&lt;/span&gt;-carnitine or an equivalent volume of water was administered for 14 days via oral gavage, followed by assessments of muscle function (grip strength) and fibrosis. To elucidate the interplay between the deltex E3 ubiquitin ligase 3L(DTX3L)/Runx2/COL1A1 axis and fibrosis in transforming growth factor beta 1-stimulated NIH/3T3 cells, a suite of molecular techniques, including quantitative real-time PCR, western blot analysis, co-immunoprecipitation, molecular docking, immunofluorescence and Duolink assays, were used. The relevance of the DTX3L/Runx2/COL1A1 axis in the gastrocnemius was also explored in the in vivo model.&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;span&gt;l&lt;/span&gt;-Carnitine supplementation reduced cancer cachexia-induced declines in grip strength (&gt;88.2%, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and the collagen fibre area within the gastrocnemius (&gt;57.9%, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). At the 5 mg/kg dose, &lt;span&gt;l&lt;/span&gt;-carnitine also suppressed COL1A1 and alpha-smooth muscle actin (α-SMA) protein expression, which are markers of SMF and myofibroblasts. Analyses of the TRRUST database indicated that Runx2 regulates both COL1A1 and COL1A2. In vitro, &lt;span&gt;l&lt;/span&gt;-carnitine diminished Runx2 protein levels and promoted its ubiquitination. Overexpression of Runx2 abolished the effects of &lt;span&gt;l&lt;/span&gt;-carnitine on COL1A1 and α-SMA. Co-immunoprecipitation, molecular docking, immunofluorescence and Duolink assays confirmed an interaction between DTX3L and Runx2, with &lt;span&gt;l&lt;/span&gt;-carnitine enhancing this interaction to promote Runx2 ubiquitination. &lt;span&gt;l&lt;/span&gt;-Carnitine supplementation restored DTX3L levels to those observed under non-cachectic conditions, both in vitro and in vivo. Knockdown of DTX3L abolished the effects of &lt;span&gt;l&lt;/span&gt;-","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873688","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 mortality burden of cachexia or weight loss in patients with colorectal or pancreatic cancer: A systematic literature review","authors":"Richard F. Dunne,&nbsp;Jeffrey Crawford,&nbsp;Karen E. Smoyer,&nbsp;Thomas D. McRae,&nbsp;Michelle I. Rossulek,&nbsp;James H. Revkin,&nbsp;Lisa C. Tarasenko,&nbsp;Philip D. Bonomi","doi":"10.1002/jcsm.13510","DOIUrl":"10.1002/jcsm.13510","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase^® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (<i>n</i> = 23) or univariate (<i>n</i> = 3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877942","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":"Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats","authors":"Mathieu Horeau,&nbsp;Melissa Delalande,&nbsp;Martine Ropert,&nbsp;Patricia Leroyer,&nbsp;Brice Martin,&nbsp;Luz Orfila,&nbsp;Olivier Loréal,&nbsp;Frédéric Derbré","doi":"10.1002/jcsm.13547","DOIUrl":"10.1002/jcsm.13547","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;Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI.&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;Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (&lt;i&gt;n&lt;/i&gt; = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot.&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;Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), liver (LIC; +198%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), spleen (SIC; +76.1%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), and transferrin saturation (TS) in serum (+53.3%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and SIC (+30.1%, &lt;i&gt;P&lt;/i&gt; = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and a decrease of TFRC protein levels (−36%; −50%, respectively, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). HU males also exhibited an increase of splenic &lt;i&gt;HO-1&lt;/i&gt; and &lt;i&gt;NRF2&lt;/i&gt; mRNA levels, (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), as well as HU females (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, &lt;i&gt;P&lt;/i&gt; = 0.004) while only a trend is observed in males (+17.5%, &lt;i&gt;P&lt;/i&gt; = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, +22%, &lt;i&gt;P&lt;/i&gt; = 0.011, respectively) and in females (+369%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, +21.9%, &lt;i&gt;P&lt;/i&gt; = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (−68.9%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, −76.8%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, respectively) and females (−75.9%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, −62.9%, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (−39.9% for males &lt;i&gt;P&lt;/i&gt; = 0.010 and −49.1% for females &lt;i&gt;P&lt;/i&gt; &lt; 0.001).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Taken together, these data support that, in rats (1) extr","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754219","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":"Roles of programmed death-1 and muscle innate lymphoid cell-derived interleukin 13 in sepsis-induced intensive care unit-acquired weakness","authors":"Yuichi Akama,&nbsp;Eun Jeong Park,&nbsp;Naoko Satoh-Takayama,&nbsp;Atsushi Ito,&nbsp;Eiji Kawamoto,&nbsp;Arong Gaowa,&nbsp;Eri Matsuo,&nbsp;Satoshi Oikawa,&nbsp;Masafumi Saito,&nbsp;Shigeaki Inoue,&nbsp;Takayuki Akimoto,&nbsp;Kei Suzuki,&nbsp;Motomu Shimaoka","doi":"10.1002/jcsm.13548","DOIUrl":"10.1002/jcsm.13548","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;Intensive care unit-acquired weakness (ICU-AW) is a syndrome characterized by a long-term muscle weakness often observed in sepsis-surviving patients during the chronic phase. Although ICU-AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death-1 (PD-1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU-AW remains to be elucidated. Here, we study how PD-1 deficiency affects sepsis-induced skeletal muscle dysfunction in a preclinical sepsis model.&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;Chronic sepsis model was developed by treating wild-type (WT) and PD-1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15–17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL-13) and PD-1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow-twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). In an &lt;i&gt;in vitro&lt;/i&gt; study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL-13 followed by gene expression measurements.&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;WT septic mice exhibited decreased muscle weight (quadriceps, &lt;i&gt;P&lt;/i&gt; &lt; 0.01; gastrocnemius, &lt;i&gt;P&lt;/i&gt; &lt; 0.05; and tibialis anterior, &lt;i&gt;P&lt;/i&gt; &lt; 0.01) and long-term muscle weakness (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), whereas PD-1 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow-twitch specific mRNAs, including myoglobin (&lt;i&gt;Mb&lt;/i&gt;), troponin I type 1 (&lt;i&gt;Tnni1&lt;/i&gt;), and myosin heavy chain 7 (&lt;i&gt;Myh7&lt;/i&gt;) were decreased in WT skeletal muscle (&lt;i&gt;Mb&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; &lt;i&gt;Tnni1&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.05; and &lt;i&gt;Myh7&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (&lt;i&gt;Mb&lt;/i&gt;, not significant; &lt;i&gt;Tnni1&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; and &lt;i&gt;Myh7&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow-twitch mRNAs, which was restored by IL-13 (&lt;i&gt;Mb&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; &lt;i&gt;Tnni1&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.001; and &lt;i&gt;Myh7&lt;/i&gt;, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). IL-13 production was significantly higher in ILC2s compared to T cells in skeletal muscle (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). IL-13-producing ILC2s in skeletal muscle were examined and found to increase in PD-1 KO septic mice, compared with WT septic mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). ILC2-derived IL-13 was increased by PD-1 KO se","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625523","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}