Dietary Patterns and Geriatric Syndromes in older Mexican adults: Analysis of the 2018-19 National Health and Nutrition Survey.

BACKGROUND: The study of dietary patterns in older adults (OA) and their association with geriatric syndromes (GS) is scarce in Latin America. OBJECTIVE: To describe the association of dietary patterns with GS in the Mexican older adult population, using data from the 2018-19 National Health and Nutrition Survey. METHODS: Dietary data were collected from 3,511 adults (≥60 years of age, both sexes) using a semi-quantitative food frequency questionnaire. Dietary patterns were derived by principal component analysis based on the consumption of 162 foods from 24 food groups. The GS studied were: frailty, depressive symptoms (DS), low appendicular skeletal muscle mass (ASMM); additionally, we studied inflammation (serum CRP>5 mg/L). Logistic regression models were used. RESULTS: Four major dietary patterns were identified: a) "Western", b) "Prudent", c) "Soups", and d) "Traditional". The middle and higher tertiles of the "Prudent" pattern were associated with lower odds of DS (OR 0.71, p = 0.04; and OR 0.61, p = 0.008), respectively. The second tertile of the "Soups" pattern was associated with lower odds of low ASMM (OR 0.68, p = 0031) and inflammation (OR 0.58, p = 0.022). The highest tertile of the "Traditional" pattern was associated with low ASMM (OR 1.55, p = 0.008) and lower odds of inflammation (OR 0.69, p = 0.044). No association was found between the "Western" dietary pattern and GS. CONCLUSIONS: Three of four major dietary patterns were associated with GS in older Mexican adults. Further studies are needed to address strategies to improve diet quality in this age group and its association with health and functional outcomes.

A comprehensive atlas of pig RNA editome across 23 tissues reveals RNA editing affecting interaction mRNA-miRNAs.

RNA editing is a co-transcriptional/post-transcriptional modification that is mediated by the ADAR enzyme family. Profiling of RNA editing is very limited in pigs. In this study, we collated 3813 RNA-seq data from the public repositories across 23 tissues and carried out comprehensive profiling of RNA editing in pigs. In total, 127,927 A-to-I RNA editing sites were detected. Our analysis showed that 98.2% of RNA editing sites were located within repeat regions, primarily within the pig-specific SINE retrotransposon PRE-1/Pre0_SS elements. Subsequently, we focused on analyzing specific editing sites (SESs) in skeletal muscle tissues. Functional enrichment analyses suggested that they were enriched in signaling pathways associated with muscle cell differentiation, including DMD, MYOD1 and CAV1 genes. Furthermore, we discovered that RNA editing event in the 3`UTR of CFLAR mRNA influenced miR-708-5p binding in this region. In this study, the panoramic RNA editing landscape of different tissues of pigs was systematically mapped, and RNA editing sites and genes involved in muscle cell differentiation were identified. In summary, we identified modifications to pig RNA editing sites and provided candidate targets for further validation.

Aqueous Extract of Wolfberry Alleviates Aging-Related Skeletal Muscle Dysfunction by Modulating PRRs Signaling Pathways and Enhancing DNA Repair.

Aging can lead to a series of degenerative changes in skeletal muscle, which would negatively impact physical activity and the quality of life of the elderly. Wolfberry contains numerous bioactive substances. It's vital to further explore the mechanisms underlying its healthy effects on skeletal muscle function during aging progress. This study discusses the benefits and mechanisms of aqueous extract of wolfberry (AEW) to protect skeletal muscle from aging-related persistent DNA damage based on its anti-inflammatory activity. It is found that AEW improves muscle mass, strength, and endurance, modulates the expression of Atrogin-1, MyH, and MuRF-1, and decreases oxidative stress and inflammation levels in aging mice, which is consistent with the in vitro results. Mechanistically, AEW inhibits the pattern recognition receptors (PRRs) pathway induced by inflammatory gene activation, suggesting its potential in response to DNA damage. AEW is also observed to mitigate chromatin decompaction. Network pharmacology is conducted to analyze the potential targets of AEW in promoting DNA repair. In conclusion, the study shows the anti-aging effects of AEW on skeletal muscle by promoting DNA repair and reducing the transcriptional activity of inflammatory factors. AEW intake may become a potential strategy for strengthening skeletal muscle function in the elderly.

Association between serum vitamin D levels and skeletal muscle indices in an older Japanese population: The SONIC study.

AIM: Vitamin D (VD) affects skeletal muscles. The high prevalence of VD deficiency in Japan may lead to decreased skeletal muscle mass and strength, increasing the prevalence of sarcopenia. Therefore, we aimed to investigate the association between serum VD levels and skeletal muscle indices in a Japanese community-dwelling older population. METHODS: We extracted data from the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. We analyzed the data for participants in the 70s and 90s age groups. Skeletal mass index (SMI) using bioimpedance analysis, grip strength, walking speed, and serum VD levels using 25-hydroxyvitamin D [25(OH)D] were measured. RESULTS: We analyzed the data of 310 participants in their 70s and 48 in their 90s. Mean serum 25(OH)D levels were 21.6 ± 5.0 ng/mL in the 70s group and 23.4 ± 9.1 ng/mL in the 90s group. In the 70s group, serum 25(OH)D levels correlated with SMI (r = 0.21, P < 0.0001) and grip strength (r = 0.30, P < 0.0001). Serum 25(OH)D levels were independently associated with SMI after adjusting for sex, body mass index, and serum albumin levels. In the 90s group, serum 25(OH)D levels were correlated with SMI (r = 0.29, P = 0.049) and grip strength (r = 0.34, P = 0.018). However, the multivariate analysis showed no independent association between SMI, grip strength, and serum 25(OH)D levels. CONCLUSION: In a cross-sectional analysis of an older population, serum VD levels were associated with SMI and grip strength, and this association was more pronounced in the 70s group than in the 90s group. Our results suggest that serum VD levels maintain skeletal muscle mass and grip strength. Geriatr Gerontol Int 2024; ••: ••-••.

l-Carnitine relieves cachexia-related skeletal muscle fibrosis by inducing deltex E3 ubiquitin ligase 3L to negatively regulate the Runx2/COL1A1 axis.

BACKGROUND: 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. l-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. METHODS: Female C57 mice (48 weeks old) were inoculated subcutaneously with MC38 cells to establish a cancer cachexia model. A 5 mg/kg dose of l-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. RESULTS: l-Carnitine supplementation reduced cancer cachexia-induced declines in grip strength (>88.2%, P < 0.05) and the collagen fibre area within the gastrocnemius (>57.9%, P < 0.05). At the 5 mg/kg dose, l-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, l-carnitine diminished Runx2 protein levels and promoted its ubiquitination. Overexpression of Runx2 abolished the effects of l-carnitine on COL1A1 and α-SMA. Co-immunoprecipitation, molecular docking, immunofluorescence and Duolink assays confirmed an interaction between DTX3L and Runx2, with l-carnitine enhancing this interaction to promote Runx2 ubiquitination. l-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 l-carnitine on Runx2, COL1A1 and α-SMA in vitro. The expression of DTX3L was negatively correlated with the levels of Runx2 and COL1A1 in untreated NIH/3T3 cells. CONCLUSIONS: This study revealed a previously unrecognized link between Runx2 and DTX3L in SMF and demonstrated that l-carnitine exerted a significant therapeutic impact on cancer cachexia-associated SMF, potentially through the upregulation of DTX3L.

Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRß pathway in vivo and in vitro in mice.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

IGF-1 and myostatin-mediated co-regulation in skeletal muscle and bone of Daurian ground squirrels (Spermophilus dauricus) during different hibernation stages.

Muscle and bone are cooperatively preserved in Daurian ground squirrels (Spermophilus dauricus) during hibernation. As such, we hypothesized that IGF-1 and myostatin may contribute to musculoskeletal maintenance during this period. Thus, we systematically assessed changes in the protein expression levels of IGF-1 and myostatin, as well as their corresponding downstream targets, in the vastus medialis (VM) muscle and femur in Daurian ground squirrels during different stages. Group differences were determined using one-way analysis of variance (ANOVA). Results indicated that the co-localization levels of IGF-1 and its receptor (IGF-1R) increased by 50% during the pre-hibernation period (PRE) and by 35% during re-entry into torpor (RET) compared to the summer active period (SA). The phosphorylation level of FOXO1 in the VM muscle increased by 50% in the torpor (TOR) group and by 82% in the inter-bout arousal (IBA) group compared to the PRE group. The phosphorylation level of SGK-1 increased by 54% in the IBA group and by 62% in the RET group compared to the SA group. In contrast, the protein expression of IGF-1 and phosphorylation levels of PI3K, Akt, mTOR, and GSK3ß in the VM muscle showed no obvious differences among the different groups. ß-catenin protein expression was up-regulated by 84% in the RET group compared to the SA group, while the content of IGF-1 protein, correlation coefficients of IGF-1 and IGF-1R, and phosphorylation levels of PI3K, Akt, and GSK3ß in the femur showed no significant differences among groups. Regarding myostatin and its downstream targets, myostatin protein expression decreased by 70% in the RET group compared to the SA group, whereas ActRIIB protein expression and Smad2/3 phosphorylation in the VM muscle showed no obvious differences among groups. Furthermore, Smad2/3 phosphorylation decreased by 58% in the TOR group and 53% in the RET group compared to the SA group, whereas ActRIIB protein expression in the femur showed no obvious differences among groups. Overall, the observed changes in IGF-1 and myostatin expression and their downstream targets may be involved in musculoskeletal preservation during hibernation in Daurian ground squirrels.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle.

INTRODUCTION: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS: Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS: Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS: Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.

Association between serum cotinine and muscle mass: results from NHANES 2011-2018.

PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Extracellular vesicle miR-206 improves chronic binge alcohol mediated decreased myoblast differentiation in SIV-infected female macaques.

Alcohol misuse in people with HIV (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells, or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The current study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreased myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 months. Myotube and myotube derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 (HDAC4) and paired box 7 (PAX7) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation.

Gastroesophageal Junction Adenocarcinoma With Skeletal Muscle Metastases: A Case Report and Literature Review.

Esophageal and gastroesophageal junction (GEJ) malignancies are aggressive, and survival is poor once metastasis occurs. The most common sites of metastatic involvement include the liver, lymph nodes, lung, peritoneum, adrenal glands, bone, and brain, while skeletal muscle (SM) involvement is rare. We report a case of a 68-year-old female who presented with intractable emesis for one month and was found to have a primary GEJ adenocarcinoma measuring up to 6.7 cm. Endoscopic biopsy revealed poorly differentiated GEJ adenocarcinoma with positive AE1/AE3 immunostains. Positron emission tomography/computed tomography and magnetic resonance imaging revealed metastases to the omentum and left lower extremity SMs, including the proximal adductor longus, adductor magnus, and gluteus minimus. This study reviews the literature on SM metastasis in esophageal and GEJ cancer, GEJ cancer classification, incidence, treatment, and prognosis.

TAM-associated CASQ1 mutants diminish intracellular Ca2+ content and interfere with regulation of SOCE.

Tubular aggregate myopathy (TAM) is a rare myopathy characterized by muscle weakness and myalgia. Muscle fibers from TAM patients show characteristic accumulation of membrane tubules that contain proteins from the sarcoplasmic reticulum (SR). Gain-of-function mutations in STIM1 and ORAI1, the key proteins participating in the Store-Operated Ca2+ Entry (SOCE) mechanism, were identified in patients with TAM. Recently, the CASQ1 gene was also found to be mutated in patients with TAM. CASQ1 is the main Ca2+ buffer of the SR and a negative regulator of SOCE. Previous characterization of CASQ1 mutants in non-muscle cells revealed that they display altered Ca2+dependent polymerization, reduced Ca2+storage capacity and alteration in SOCE inhibition. We thus aimed to assess how mutations in CASQ1 affect calcium regulation in skeletal muscles, where CASQ1 is naturally expressed. We thus expressed CASQ1 mutants in muscle fibers from Casq1 knockout mice, which provide a valuable model for studying the Ca2+ storage capacity of TAM-associated mutants. Moreover, since Casq1 knockout mice display a constitutively active SOCE, the effect of CASQ1 mutants on SOCE inhibition can be also properly examined in fibers from these mice. Analysis of intracellular Ca2+ confirmed that CASQ1 mutants have impaired ability to store Ca2+and lose their ability to inhibit skeletal muscle SOCE; this is in agreement with the evidence that alterations in Ca2+entry due to mutations in either STIM1, ORAI1 or CASQ1 represents a hallmark of TAM.

The validity and reliability of quadriceps twitch force as a measure of skeletal muscle fatigue while cycling.

The measurement of skeletal muscle fatigue in response to cycling exercise is commonly done in isometric conditions, potentially limiting its ecological validity, and creating challenges in monitoring the time course of muscle fatigue across an exercise bout. This study aimed to determine if muscle fatigue could be reliably assessed by measuring quadriceps twitch force evoked while pedaling, using instrumented pedals. Nine participants completed three laboratory visits: a step incremental test to determine power output at lactate threshold, and on separate occasions, two constant-intensity bouts at a power output 10% above lactate threshold. Femoral nerve electrical stimulation was applied to elicit quadriceps twitch force both while pedaling (dynamic) and at rest (isometric). The test-retest reliability of the dynamic twitch forces and the agreement between the dynamic and isometric twitch forces were evaluated. Dynamic twitch force was found to have excellent reliability in an unfatigued state (intraclass correlation coefficient (ICC) = 0.920 and mean coefficient of variation (CV) = 7.5%), and maintained good reliability at task failure (ICC = 0.846 and mean CV = 11.5%). When comparing dynamic to isometric twitch forces across the task, there was a greater relative decline in the dynamic condition (P = 0.001). However, when data were normalized to the 5 min timepoint when potentiation between conditions was presumed to be more similar, this difference disappeared (P = 0.207). The reliability of this method was shown to be commensurate with the gold standard method utilizing seated isometric dynamometers and offers a new avenue to monitor the kinetics of muscle fatigue during cycling in real time.

T-cell immunosuppression in sepsis is augmented by sciatic denervation-induced skeletal muscle atrophy.

Skeletal muscle atrophy is a known risk factor for immunosuppressive conditions and for a poor prognosis in sepsis. However, its immunopathology has not been experimentally elucidated. This study investigated the effects of skeletal muscle atrophy on the immunopathology of sepsis. Male C57BL/6J mice were subjected to sciatic denervation (DN) and caecal ligation and puncture (CLP) to induce muscle atrophy or sepsis. The macrophages, myeloid-derived suppressor cells (MDSC), and T-cells in peritoneal and spleen were analysed using flow cytometry. DN-induced muscle atrophy did not affect macrophage and MDSC populations. In contrast, the percentage of cytotoxic T-lymphocyte-associated antigen (CTLA)-4+ CD4+ T-cells, programmed death (PD)-1+ CD8+ T-cells, regulatory T-cells, and the CTLA-4+ regulatory T-cells was statistically significantly higher in DN-CLP mice than in sham-CLP mice. Skeletal muscle atrophy before sepsis triggers excessive T cell immunosuppression, which may contribute to the exacerbation of sepsis under skeletal muscle atrophy.

The association of appendicular skeletal muscle mass with anthropometric, body composition, nutritional, inflammatory, and metabolic variables in non-dialysis-dependent chronic kidney disease men.

Background: Muscle atrophy affects more than 50% of patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. It is crucial to understand the mechanisms involved in the muscle atrophy in CKD and search for specific determinants of skeletal muscle mass loss, especially those which are available in everyday medical practice. This study aimed to evaluate the association between appendicular skeletal muscle mass (ASM) and anthropometric, body composition, nutritional, inflammatory, metabolic, and kidney function variables in non-dialysis-dependent CKD men. Methods: A total of 85 men with CKD and eGFR lower than 60 mL/min/1.73 m2 were included in the cross-sectional study: 24 participants with eGFR 59-45 mL/min/1.73 m2, 32 individuals with eGFR 44-30 mL/min/1.73 m2, and 29 men with eGFR ≤29 mL/min/1.73 m2. ASM was estimated by bioimpedance spectroscopy (BIS) with the use of a Body Composition Monitor (BCM). To evaluate ASM from BCM, Lin's algorithm was used. Among anthropometric parameters, height, weight, and body mass index (BMI) were measured. Serum laboratory measurements were grouped into kidney function, nutritional, inflammatory, and metabolic parameters. Results: ASM was significantly associated with anthropometric and body composition variables. According to the anthropometric parameters, ASM correlated positively with weight, height, and BMI (p < 0.001 and r = 0.913, p < 0.001 and r = 0.560, and p < 0.001 and r = 0.737, respectively). Among body composition variables, ASM correlated significantly and positively with lean tissue mass (LTM) (p < 0.001, r = 0.746), lean tissue index (LTI) (p < 0.001, r = 0.609), fat mass (p < 0.001, r = 0.489), and fat tissue index (FTI) (p < 0.001, r = 0.358). No other statistically significant correlation was found between ASM and kidney, nutritional, metabolic, and inflammatory variables. Conclusion: In male patients with CKD stages G3-G5 not treated with dialysis, ASM correlates significantly and positively with anthropometric and body composition parameters such as weight, height, BMI, LTM, LTI, fat mass, and FTI. We did not observe such relationship between ASM and kidney function, nutritional, metabolic, and inflammatory variables.

The role and mechanism of ß-catenin-mediated skeletal muscle satellite cells in osteoporotic fractures by Jian-Pi-Bu-Shen formula.

Osteoporosis is a metabolic bone disease. ß-Catenin is associated with fractures. Jian-Pi-Bu-Shen (JPBS) can promote the healing of osteoporotic fractures (OPF). However, the mechanism of ß-catenin-mediated skeletal muscle satellite cells (SMSCs) in OPF by the JPBS is unclear. SMSCs were isolated and divided into five groups. The results showed that the survival rate of SMSCs was significantly higher in the low, medium, and high dose JPBS-containing serum groups after 7 days of incubation. The ALP activity and the number of SMSCs mineralized in the JPBS-containing serum intervention group were elevated. Axin, GSK-3ß, ß-catenin siRNAs were constructed and transfected into cells. Transfection of siRNAs reduced Axin, GSK-3ß, and ß-catenin expressions, respectively. ß-Catenin-siRNA reversed ALP activity, the number of SMSCs mineralized, and the expression of ß-catenin, BMP2, Runx2, COL-I, SP7/Ostrix, Osteocalcin, and BMP-7. Transcriptomic results suggested that the TNF signaling pathway associated with OPF was enriched. SD rats were subjected to the construction of OPF model by removing the ovaries. JPBS decreased the levels of PINP, ALP, CTX, and NTX through ß-catenin in OPF rats, while increasing Runx2, ß-catenin expressions through ß-catenin at the broken end of fractures. Moreover, JPBS decreased BMC, BMD, and BV/TV and improved pathological damage through ß-catenin in OPF rats. JPBS decreased the expression of Axin, GSK-3ß mRNA, and protein, but increased the expressions of ß-catenin, Pax7, COL-II, COL-II, BMP2, and Runx2 through ß-catenin in OPF rats. In conclusion, JPBS inhibits Axin/GSK-3ß expression, activates the ß-catenin signaling, and promotes the osteogenic differentiation of SMSCs.

Parameter optimization for proton density fat fraction quantification in skeletal muscle tissue at 7 T.

OBJECTIVE: To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7 T. MATERIALS AND METHODS: Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12). Additionally, methods to reduce phase errors arising at 7 T were evaluated. Finally, PDFF values measured at 7 T in calf muscle tissue of healthy subjects (n = 9) and patients with fatty replacement of muscle tissue (n = 3) were compared to 3 T results. RESULTS: Simulations, phantom and in vivo measurements showed the importance of using optimized TEs for the fat-water separation at 7 T. Fat-water swaps could be mitigated using a phase demodulation with an additional B0 map, or by shifting the TEs to longer values. Muscular PDFF values measured at 7 T were comparable to measurements at 3 T in both healthy subjects and patients with increased fatty replacement. CONCLUSION: PDFF determination in calf muscle tissue is feasible at 7 T using a chemical shift-based approach with optimized acquisition and post-processing parameters.

Near-infrared spectroscopy (NIRS) in vivo assessment of skeletal muscle oxidative capacity: a comparison of results from short versus long exercise protocols and reproducibility in non-athletic adults.

Background: Near-infrared spectroscopy (NIRS) provides a non-invasive, cost-effective method for assessing skeletal muscle oxidative capacity when combined with a short exercise protocol and arterial occlusions. However, the impact of different exercise protocols and reproducibility of the method in non-athletic adults have not previously been assessed. Methods: Young, non-athletic adults (YA) were invited to perform a short duration, fast frequency contraction (SF) exercise protocol and a long duration slow frequency (LS) contraction protocol, combined with NIRS measurements and arterial occlusions to assess skeletal muscle oxidative capacity. YA and older non-athletic adults (OA; >65 years old) were invited to perform the SF exercise protocol twice to assess the reproducibility of this oxidative capacity measurement. Results: We included 25 participants (14 male (56%), age range: 18-86 years) in the analyses. There was a strong positive correlation and good agreement between time constants derived following the SF and LS exercise protocols (Lin's concordance correlation coefficient: 0.69, p-value < 0.001 mean bias [LoA]: -3.2 [-31.0, 24.4] seconds. There was a strong positive correlation and good agreement between time constants derived from the SF exercise protocol in the YA & OA group (Lin's concordance correlation coefficient: 0.63, p-value < 0.001; mean bias [LoA] -6.4 [-34.0, 21.3] seconds). Conclusion: These data provide evidence to suggest that NIRS is a reliable in vivo method for the assessment of skeletal muscle oxidative capacity irrespective of exercise protocol duration or muscle contraction frequency. NIRS-measured oxidative capacity via the SF exercise protocol was reproducible in non-athletic adults with a wide range in age.

Combination of transcriptomics and proteomics for analyzing potential biomarker and molecular mechanism underlying skeletal muscle atrophy.

BACKGROUND: The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently. METHODS: Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes. RESULTS: By combination of transcriptomics, proteomics and RT-qPCR results, we identified 14 key genes (Cav1, Col3a1, Dnaja1, Postn, Ptges3, Cd44, Clec3b, Igfbp6, Lamc1, Alb, Itga6, Mmp2, Timp2 and Cd9) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested Cd9 was probably the biomarker for skeletal muscle atrophy. CONCLUSIONS: Our study hinted that Cd9 was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids. SIGNIFICANCE: The present study holds the subsequent significance: Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found Cd9 is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.