In vitro modeling of skeletal muscle ischemia-reperfusion injury based on sphere differentiation culture from human pluripotent stem cells.

Skeletal muscle ischemia-reperfusion (IR) injury poses significant challenges due to its local and systemic complications. Traditional studies relying on two-dimensional (2D) cell culture or animal models often fall short of faithfully replicating the human in vivo environment, thereby impeding the translational process from animal research to clinical applications. Three-dimensional (3D) constructs, such as skeletal muscle spheroids with enhanced cell-cell interactions from human pluripotent stem cells (hPSCs) offer a promising alternative by partially mimicking human physiological cellular environment in vivo processes. This study aims to establish an innovative in vitro model, human skeletal muscle spheroids based on sphere differentiation from hPSCs, to investigate human skeletal muscle developmental processes and IR mechanisms within a controlled laboratory setting. By eticulously recapitulating embryonic myogenesis through paraxial mesodermal differentiation of neuro-mesodermal progenitors, we successfully established 3D skeletal muscle spheroids that mirror the dynamic colonization observed during human skeletal muscle development. Co-culturing human skeletal muscle spheroids with spinal cord spheroids facilitated the formation of neuromuscular junctions, providing functional relevance to skeletal muscle spheroids. Furthermore, through oxygen-glucose deprivation/re-oxygenation treatment, 3D skeletal muscle spheroids provide insights into the molecular events and pathogenesis of IR injury. The findings presented in this study significantly contribute to our understanding of skeletal muscle development and offer a robust platform for in vitro studies on skeletal muscle IR injury, holding potential applications in drug testing, therapeutic development, and personalized medicine within the realm of skeletal muscle-related pathologies.

Circular RNA circMYLK4 shifts energy metabolism from glycolysis to OXPHOS by binding to the calcium channel auxiliary subunit CACNA2D2.

Skeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation (OXPHOS). The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca2+ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid ß-oxidation enhances the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.

Nuclear receptor Nur77 and Yin-Yang 1 synergistically increase mitochondrial abundance and activity in macrophages.

Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved regulation of mitochondrial genes and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at mitochondrial ribosomal protein gene loci in macrophages. Nur77 and YY1 co-expression synergistically increases Mrpl1 expression as well as mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.

The effects of exercise and mitochondrial transplantation alone or in combination against Doxorubicin-induced skeletal muscle atrophy.

Doxorubicin (DOX) is a chemotherapy drug used to treat various types of cancer, but it is associated with significant side effects such as skeletal muscle atrophy. Exercise has been found to prevent skeletal muscle atrophy through the modulation of mitochondrial pathways. Mitochondrial transplantation (MT) may mitigate toxicity, neurological disorders, kidney and liver injury, and skeletal muscle atrophy. The objective of this study was to evaluate the effects of MT, exercise, and MT with exercise on DOX-induced skeletal muscle atrophy. Male Sprague Dawley rats were randomly assigned to the following groups: control, DOX, MT with DOX, exercise with DOX, and exercise with MT and DOX. A 10-day treadmill running exercise and MT (6.5 µg/100 µL) to tibialis anterior (TA) muscle were administered prior to a single injection of DOX (20 mg/kg). Our data showed that exercise and MT with exercise led to an increase in cross-sectional area of the TA muscle. Exercise, MT and MT with exercise reduced inflammation and maintained mitochondrial enzyme activity. Additionally, exercise and MT have been shown to regulate mitochondrial fusion/fission. Our findings revealed that exercise and MT with exercise prevented oxidative damage. Furthermore, MT and MT with exercise decreased apoptosis and MT with exercise triggered mitochondrial biogenesis. These findings demonstrate the importance of exercise in the prevention of skeletal muscle atrophy and emphasize the significant benefits of MT with exercise. To the best of our knowledge, this is the first study to demonstrate the therapeutic effects of MT with exercise in DOX-induced skeletal muscle atrophy.

Skeletal muscle metabolic dysfunction with circulating carboxymethyl-lysine in dietary food additive-induced leaky gut.

Impaired intestinal permeability induces systemic inflammation and metabolic disturbance. The effect of a leaky gut on metabolism in skeletal muscle, a major nutrient consumer, remains unclear. In this study, we aimed to investigate the glucose metabolic function of the whole body and skeletal muscles in a mouse model of diet-induced intestinal barrier dysfunction. At Week 2, we observed higher intestinal permeability in mice fed a titanium dioxide (TiO2)-containing diet than that of mice fed a normal control diet. Subsequently, systemic glucose and insulin tolerance were found to be impaired. In the skeletal muscle, glucose uptake and phosphorylation levels in insulin signaling were lower in the TiO2 group than those in the control group. Additionally, the levels of pro-inflammatory factors were higher in TiO2-fed mice than those in the control group. We observed higher carboxymethyl-lysin (CML) levels in the plasma and intestines of TiO2-fed mice and lower insulin-dependent glucose uptake in CML-treated cultured myotubes than those in the controls. Finally, soluble dietary fiber supplementation improved glucose and insulin intolerance, suppressed plasma CML, and improved intestinal barrier function. These results suggest that an impaired intestinal barrier leads to systemic glucose intolerance, which is associated with glucose metabolism dysfunction in the skeletal muscles due to circulating CML derived from the intestine. This study highlights that the intestinal condition regulates muscle and systemic metabolic health.

Discipline-specific Torque-Velocity Profiles and Musculotendinous Morphology in Athletes.

OBJECTIVES: The aim of this study was to compare torque-velocity profiles, muscle architecture, tendon dimensions, and bilateral-symmetry between competitive cyclists (CY), competitive runners (RN), ice-hockey players (IH), basketball players (BP), and physically-active individuals (CN) (n=10 for each group). METHODS: Vastus lateralis (VL) muscle and patellar tendon (PT) structures were determined with B-mode ultrasonography, and maximal knee extensor isokinetic torque was assessed at three different velocities. RESULTS: Optimal torque and velocity were lower in runners than CY, BP and IH (p<0.05). Maximal power was similar between the athlete groups but greater than CN (p<0.05). Furthermore, RN and BP reached their peak-torque at longer muscle lengths compared to IH and CY (p<0.05). RN had the lowest VL muscle thickness and the greatest fascicle length, while CY had the greatest pennation angle (p<0.05). CY had the greatest PT thickness, particularly at the proximal and medial sites, while BP at the distal point (p<0.05), with similar trends observed for PT cross-sectional-area. CONCLUSIONS: Our findings show that even if power generating capacity is similar between athletic disciplines, there are discipline-specific muscle adaptations, where particularly runners appear to have muscles adapted for speed rather than torque development, while in cyclists, velocity is sacrificed for torque development.

Sex difference in skeletal muscle mass in relation to metabolic dysfunction-associated steatotic liver disease: a propensity score matching study.

BACKGROUND: While low muscle mass is considered a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), whether the relationship is independent of fat mass remains unclear. OBJECTIVES: This study aims to clarify the association between the sex-specific height-adjusted low skeletal muscle mass index (LSMI) and MASLD. METHODS: Data from the 2008-2010 Korean National Health and Nutrition Examination Survey were analyzed. LSMI was defined using the 2019 Asian Working Group for Sarcopenia. The non-alcoholic fatty liver disease-liver fat score was used to assess MASLD. Gender-specific 1:1 propensity score matching (PSM) was performed to mitigate the confounding effects of anthropometric variables and lifestyles. Conditional logistic analysis was used on the dataset after PSM to estimate the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: After PSM, the prevalence of MASLD was significantly higher in men with LSMI than in those without LSMI (37.4% vs. 29.6%). No significant difference was observed in the prevalence of MASLD between groups after PSM in women (20.4% vs. 20.3%). Conditional logistic analysis revealed that the odds of having MASLD were significantly higher in men with LSMI compared to those without LSMI (OR = 1.38, 95% CI: 1.09-1.75), while no significant association was found in women with LSMI (OR = 1.10, 95% CI: 0.87-1.40). CONCLUSION: Height-adjusted LSMI is an independent factor associated with MASLD in the condition of the same level of fat mass in men. Further prospective studies in diverse populations are needed to confirm our findings.

Competing endogenous RNA networks were associated with fat accumulation in skeletal muscle of aged male mice.

Muscle aging contributed to morbidity and mortality in the elderly adults by leading to severe outcomes such as frailty, falls and fractures. Post-transcriptional regulation especially competing endogenous RNA (ceRNA) mechanism may modulate the process of skeletal muscle aging. RNA-seq was performed in quadriceps of 6-month-old (adult) and 22-month-old (aged) male mice to identify differentially expressed ncRNAs and mRNAs and further construct ceRNA networks. Decreased quadriceps-body weight ratio and muscle fiber cross-sectional area as well as histological characteristics of aging were observed in the aged mice. Besides, there were higher expressions of atrogin-1 and MuRF-1 and lower expression of Myog, Myf4 and Myod1 in the quadriceps of aged mice relative to that of adult mice. The expression of 85 lncRNAs, 52 circRNAs, 10 miRNAs and 277 mRNAs were significantly dysregulated in quadriceps between the two groups, among which two ceRNA networks lncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b were constructed. Level of triglycerides and expression of PPARγ, C/EBPα, FASN and leptin were elevated and the expression of adiponectin was reduced in quadriceps of aged mice compared with that of adult mice. LncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b were possibly associated with the adipogenesis and fat accumulation in skeletal muscle of age male mice.

Skeletal muscle PGC-1α remodels mitochondrial phospholipidome but does not alter energy efficiency for ATP synthesis.

Background: Exercise training is thought to improve the mitochondrial energy efficiency of skeletal muscle. Some studies suggest exercise training increases the efficiency for ATP synthesis by oxidative phosphorylation (OXPHOS), but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes could contribute to improved OXPHOS efficiency (ATP produced by O2 consumed or P/O). Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional co-activator that coordinately regulates exercise-induced adaptations including mitochondria. We hypothesized that increased PGC-1α activity is sufficient to remodel mitochondrial membrane lipids and promote energy efficiency. Methods: Mice with skeletal muscle-specific overexpression of PGC-1α (MCK-PGC-1α) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by western blot assay. High-resolution respirometry and fluorometry analysis were used to characterize mitochondrial bioenergetics (ATP production, O2 consumption, and P/O) for permeabilized fibers and isolated mitochondria. Results: Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK-PGC-1α mice revealed that PGC-1α increases the concentrations of cone-shaped lipids such as phosphatidylethanolamine (PE), cardiolipin (CL), and lysophospholipids, while decreases the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidic acid (PA). However, while PGC-1α overexpression increased the abundance of OXPHOS enzymes in skeletal muscle and the rate of O2 consumption (JO2), P/O values were unaffected with PGC-1α in permeabilized fibers or isolated mitochondria. Conclusions: Collectively, overexpression of PGC-1α promotes the biosynthesis of mitochondrial PE and CL but neither PGC-1α nor the mitochondrial membrane lipid remodeling induced in MCK-PGC-1α mice is sufficient to increase the efficiency for mitochondrial ATP synthesis. These findings suggest that exercise training may increase OXPHOS efficiency by a PGC-1α-independent mechanism, and question the hypothesis that mitochondrial lipids directly affect OXPHOS enzymes to improve efficiency for ATP synthesis.

Muscle Protein Synthesis in Response to Plant-Based Protein Isolates With and Without Added Leucine Versus Whey Protein in Young Men and Women.

Background: Plant-based protein supplements often contain lower amounts of leucine and other essential amino acids (EAAs), potentially making them less effective in stimulating muscle protein synthesis (MPS) than animal-based proteins. Combining plant proteins could improve the EAA profile and more effectively support MPS. Objectives: The aim of this study was to determine the effect of a novel plant-based blend protein (PBP), PBP with added leucine (PBP + Leu) to levels equivalent to whey protein isolate (WHEY) on aminoacidemia and MPS responses in young men and women. We hypothesized that PBP + Leu would stimulate MPS equivalent to WHEY, and both would be greater than PBP. Methods: We employed a randomized, double-blind, crossover study consisting of 3 separate study visits to compare PBP, PBP + Leu, and WHEY. To measure MPS response to ingestion of the supplements, a primed continuous infusion of L-[ring13C6] phenylalanine was administered for 8 h at each study visit. Skeletal muscle tissue and blood samples were collected to measure aminoacidemia and MPS. Results: All protein supplements increased mixed MPS above postabsorptive levels (P < 0.001). However, MPS increase following ingestion of PBP was less than that following ingestion of PBP + Leu (P = 0.002) and WHEY (P = 0.046). There were no differences in MPS between PBP + Leu and WHEY (P = 0.052). Conclusions: Consumption of PBP isolate with added leucine stimulated MPS to a similar extent as whey protein in young men and women. PBPs containing higher leucine content promote anabolism to a similar extent as animal-based proteins.This study was registered at clinicaltrials.gov as NCT05139160.

Embryonic Cadaverine Signaling: Implications for Plasma Free Amino Acid and Skeletal Muscle Energy Metabolism in Newly Hatched Chicks.

Cadaverine is a bioactive substance derived from lysine degradation by lysine decarboxylase and has gained attention for its physiological effects. Studies in rodents have revealed its role as a cell growth regulator, particularly intestinal bacterial-produced cadaverine. However, the nutritional and physiological roles of cadaverine during the embryonic period remain unclear, especially considering the immature state of the gut microbiota and digestive functions during this stage. This study explored the potential functions of cadaverine as a nutritional and metabolic signal during chicken embryonic development. Experiments were conducted using an in ovo administration method to evaluate the effects of nutritional bioactive substances on developing chicken embryos. Although there were no observable changes in body or organ weights of newly hatched chicks following in ovo cadaverine administration to day 18 chick embryos, plasma tryptophan, Nτ-methylhistidine, and Nπ-methylhistidine concentrations decreased and the gene expression of insulin/insulin-like growth factor 1 signaling in skeletal muscle was upregulated. These findings imply that cadaverine influences tryptophan metabolism and skeletal muscle catabolism during the embryonic period, suggesting its role as a bioactive factor contributing to energy metabolism signaling in skeletal muscle.

"Aberrant" expression of skeletal muscle markers in neuroendocrine carcinomas: a significant diagnostic pitfall.

In this study, we investigate the expression of muscle markers, including the specific skeletal muscle markers myogenin and myoD1, in neuroendocrine carcinomas (NECs). The study included 23 NECs from various sites (14 small cell NECs and 9 large cell NECs). These were stained with desmin, myogenin and myoD1. Positive staining with at least one muscle marker was observed in 14 cases (61%). 8 (35%), 8 (35%) and 11 (48%) of the cases were positive with desmin, myogenin and myoD1 respectively. In most, but not all, cases positive staining was focal generally involving < 10% of tumour cells. Expression of muscle markers is not uncommon in NECs. This represents an important diagnostic pitfall of which pathologists should be aware. In reporting this phenomenon, we speculate on the pathogenesis of this "aberrant" expression of muscle markers.

CT-based muscle and adipose measurements predict prognosis in patients with digestive system malignancy.

The role of skeletal muscle and adipose tissue in the progression of cancer has been gradually discussed, but it needs further exploration. The objective of this study was to provide an in-depth analysis of skeletal muscle and fat in digestive malignancies and to construct novel predictors for clinical management. This is a retrospective study that includes data from Cancer Center, the First Hospital of Jilin University. Basic characteristic information was analyzed by T tests. Correlation matrices were drawn to explore the relationship between CT-related indicators and other indicators. Cox risk regression analyses were performed to analyze the association between the overall survivals (OS) and various types of indicators. A new indicator body composition score (BCS) was then created and a time-dependent receiver operating characteristic curve was plotted to analyze the efficacy of the BCS. Finally, a nomogram was produced to develop a scored-CT system based on BCS and other indicators. C-index and calibration curve analyses were performed to validate the predictive accuracy of the scored-CT system. A total of 575 participants were enrolled in the study. Cox risk regression model revealed that VFD, L3 SMI and VFA/SFA were associated with prognosis of cancer patients. After adjustment, BCS index based on CT was significantly associated with prognosis, both in all study population and in subgroup analysis according to tumor types (all study population: HR 2.036, P < 0.001; colorectal cancer: HR 2.693, P < 0.001; hepatocellular carcinoma: HR 4.863, P < 0.001; esophageal cancer: HR 4.431, P = 0.008; pancreatic cancer: HR 1.905, P = 0.016; biliary system malignancies: HR 23.829, P = 0.035). The scored-CT system was constructed according to tumor type, stage, KPS, PG-SGA and BCS index, and it was of great predictive validity. This study identified VFD, L3 SMI and VFA/SFA associated with digestive malignancies outcomes. BCS was created and the scored-CT system was established to predict the OS of cancer patients.

Preoperative risk factors for skeletal muscle mass loss in patients with biliary tract cancer.

BACKGROUND: Endoscopic retrograde cholangiography (ERC)-related procedures, usually performed before biliary tract cancer (BTC) surgery, are associated with increased risk for various complications, which can cause sarcopenia. No study has previously elucidated the relationship between preoperative ERC-related procedures and sarcopenia/skeletal muscle mass loss. METHODS: Patients with BTC who underwent radical surgical resection following ERC-related procedures were included. Skeletal muscle mass was evaluated using the psoas muscle mass index (PMI), which was determined using computed tomography images, and the change in PMI before the initial pre-ERC and surgery (ΔPMI) was calculated. Risk factors for advanced skeletal muscle mass loss, defined as a large ΔPMI, were evaluated. RESULTS: The study cohort included 90 patients with a median age of 72 (interquartile range, 65-75) years. The median PMI pre-ERC and surgery was 4.40 and 4.15 cm2/m2, respectively (p < .01). The median ΔPMI was -6.2% (interquartile range, -10.9% to 0.5%). By multivariate analysis, post-ERC pancreatitis and cholangitis before surgery were independent predictive factors for large PMI loss (odds ratio, 4.57 and 3.18, respectively; p = .03 and p = .02, respectively). CONCLUSIONS: Skeletal muscle mass decreases preoperatively in most patients with BTC undergoing ERC. Post-ERC pancreatitis and cholangitis before surgery were independent risk factors for large skeletal muscle mass loss.

Gut microbiota depletion delays somatic peripheral nerve development and impairs neuromuscular junction maturation.

Gut microbiota is responsible for essential functions in human health. Several communication axes between gut microbiota and other organs via neural, endocrine, and immune pathways have been described, and perturbation of gut microbiota composition has been implicated in the onset and progression of an emerging number of diseases. Here, we analyzed peripheral nerves, dorsal root ganglia (DRG), and skeletal muscles of neonatal and young adult mice with the following gut microbiota status: a) germ-free (GF), b) gnotobiotic, selectively colonized with 12 specific gut bacterial strains (Oligo-Mouse-Microbiota, OMM12), or c) natural complex gut microbiota (CGM). Stereological and morphometric analyses revealed that the absence of gut microbiota impairs the development of somatic median nerves, resulting in smaller diameter and hypermyelinated axons, as well as in smaller unmyelinated fibers. Accordingly, DRG and sciatic nerve transcriptomic analyses highlighted a panel of differentially expressed developmental and myelination genes. Interestingly, the type III isoform of Neuregulin1 (NRG1), known to be a neuronal signal essential for Schwann cell myelination, was overexpressed in young adult GF mice, with consequent overexpression of the transcription factor Early Growth Response 2 (Egr2), a fundamental gene expressed by Schwann cells at the onset of myelination. Finally, GF status resulted in histologically atrophic skeletal muscles, impaired formation of neuromuscular junctions, and deregulated expression of related genes. In conclusion, we demonstrate for the first time a gut microbiota regulatory impact on proper development of the somatic peripheral nervous system and its functional connection to skeletal muscles, thus suggesting the existence of a novel 'Gut Microbiota-Peripheral Nervous System-axis.'

Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial.

BACKGROUND: Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer. METHODS: The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6-10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients' medical records; (v) explorative outcomes of patients' experience of the exercise program which will be evaluated using focus group/individual interviews. DISCUSSION: It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

A Cross-Sectional Study on Metabolic Syndrome Parameters, the Nutritional Index, and Physical Status Associated with or Without the Possible Diagnosed Sarcopenia in Older Women Using A Propensity Score Matching Method.

Objectives: To develop strategies against sarcopenia, physiological and biochemical data in older women were analyzed using propensity score matching. Methods: Fifty-six women aged ≥75 years with the AWGS calf circumference <33 cm were included in the sarcopenia risk group. Low muscle strength (handgrip strength <18kg) or low physical performance (five-times-sit-to-stand test ≥12s) were used the possible-sarcopenia group. Propensity score matching adjusted for age and BMI was performed between the possible-sarcopenia group with low muscle strength (or physical performance) and the sarcopenia risk group without low muscle strength (or physical performance). The comparison included nutritional index, metabolic syndrome parameters, BMD, and skeletal muscle mass index score between both groups. Results: The possible-sarcopenia group with low muscle strength exhibited significantly lower BMD (p=0.014) and skeletal muscle mass index score (p=0.002) compared to the sarcopenia risk group without low muscle strength. The possible-sarcopenia group with low physical performance exhibited significantly lower AST (p=0.034) compared to the sarcopenia risk group without low physical performance. Conclusion: These results suggest that older women with possible sarcopenia and low muscle strength may have reduced BMD and skeletal muscle mass index.

A Study of the Relationship Between the Triglyceride-Glucose Index and Skeletal Muscle Mass in a General Chinese Population.

Objective: There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. Methods: We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). Results: With TyG index increased, RSMI levels significantly reduced(P < .001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = -0.320) and females (r = -0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P < .05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. Conclusion: TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss.

Acetate derived from the intestinal tract has a critical role in maintaining skeletal muscle mass and strength in mice.

Acetate is a short-chain fatty acid (SCFA) that is produced by microbiota in the intestinal tract. It is an important nutrient for the intestinal epithelium, but also has a high plasma concentration and is used in the various tissues. Acetate is involved in endurance exercise, but its role in resistance exercise remains unclear. To investigate this, mice were administered either multiple antibiotics with and without oral acetate supplementation or fed a low-fiber diet. Antibiotic treatment for 2 weeks significantly reduced grip strength and the cross-sectional area (CSA) of muscle fiber compared with the control group. Intestinal concentrations of SCFAs were reduced in the antibiotic-treated group. Oral administration of acetate with antibiotics prevented antibiotic-induced weakness of skeletal muscle and reduced CSA of muscle fiber. Similarly, a low-fiber diet for 1 year significantly reduced the CSA of muscle fiber and fecal and plasma acetate concentrations. To investigate the role of acetate as an energy source, acetyl-CoA synthase 2 knockout mice were used. These mice had a shorter lifespan, reduced skeletal muscle mass and smaller CSA of muscle fiber than their wild type littermates. In conclusion, acetate derived from the intestinal microbiome can contribute to maintaining skeletal muscle performance.

Anti-oxidative and anti-inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia-reperfusion injury in rats.

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.