Muscle Fiber Area Research Articles

HBMSC-EVs alleviate weightlessness-induced skeletal muscle atrophy by suppressing oxidative stress and inflammation

BackgroundMuscle disuse and offloading in microgravity are likely the primary factors mediating spaceflight-induced muscle atrophy, for which there is currently no effective treatment other than exercise. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) possess anti-inflammatory and antioxidant properties, offering a potential strategy for combating weightless muscular atrophy.MethodsIn this study, human BMSCs-EVs (hBMSC-EVs) were isolated using super-centrifugation and characterized. C2C12 myotube nutrition-deprivation and mice tail suspension models were established. Subsequently, the diameter of C2C12 myotubes, Soleus mass, cross-sectional area (CSA) of muscle fibers, and grip strength in mice were assessed to investigate the impact of hBMSC-EVs on muscle atrophy. Immunostaining, transmission electron microscopy observation, and western blot analysis were employed to assess the impact of hBMSC-EVs on muscle fiber types, ROS levels, inflammation, ubiquitin–proteasome system activity, and autophagy lysosome pathway activation in skeletal muscle atrophy.ResultsThe active hBMSC-EVs can be internalized by C2C12 myotubes and skeletal muscle. hBMSC-EVs can effectively reduce C2C12 myotube atrophy caused by nutritional deprivation, with a concentration of 10 × 108 particles/mL showing the best effect (P < 0.001). Additionally, hBMSC-EVs can down-regulate the protein levels associated with UPS and oxidative stress. Moreover, intravenous administration of hBMSC-EVs at a concentration of 1 × 1010 particles/mL can effectively reverse the reduction in soleus mass (P < 0.001), CSA (P < 0.01), and grip strength (P < 0.001) in mice caused by weightlessness. They demonstrate the ability to inhibit protein degradation mediated by UPS and autophagy lysosome pathway, along with the suppression of oxidative stress and inflammatory responses. Furthermore, hBMSC-EVs impede the transition of slow muscle fibers to fast muscle fibers via upregulation of Sirt1 and PGC-1α protein levels.ConclusionsOur findings indicate that hBMSC-EVs are capable of inhibiting excessive activation of the UPS and autophagy lysosome pathway, suppressing oxidative stress and inflammatory response, reversing muscle fiber type transformation, effectively delaying hindlimb unloading-induced muscle atrophy and enhancing muscle function. Our study has further advanced the understanding of the molecular mechanism underlying muscle atrophy in weightlessness and has demonstrated the protective effect of hBMSC-EVs on muscle atrophy.

Exploring variances in meat quality between Qingyuan partridge chicken and Cobb broiler: Insights from combined multi-omics analysis.

Previously, animal breeding prioritized enhancing key economic traits to improve production efficiency, leading to a gradual difference in meat quality. However, the genetic factors influencing meat quality remain unclear. To identify key genetic pathways contributing to meat quality, native Chinese yellow-feathered chicken (Qingyuan Partridge Chicken, QPC; female, n=10), and commercial chicken broiler (Cobb broiler, CB; female, n=10) were used for meat quality assessment through metabolomics, proteomics, and phosphoproteomics sequencing. The results show that QPC had lower pH (93.12%), shear force (81.46%), cooking loss (69.29%), moisture content (93.24%) and muscle fiber area (46.04%), but higher meat color values (a*(163.65%) and b*(250.27%)), drip loss (146.32%), and intramuscular fat content (382.01%) than CB (p < 0.05). Metabolomic, proteomic, and phosphoproteomic analyses were jointly conducted, revealing significant differences in energy metabolism strategies. Higher glycolytic enzyme activity was observed in QPC (ENO1, GAPDH, GPI, PFKM, PKM, and TPI1, p < 0.05), while more energetic phosphate compounds were stored in CB. CB had higher Na+/K+ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca2+ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC. In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca2+. These results suggest CB is more contractile than QPC, contributing to meat quality between CB and QPC.

MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis.

Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both in vitro and in vivo, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model. Enforced miR-495 expression by its mimic could enormously facilitate the differentiation and regeneration of both mouse myoblast C2C12cells and muscle satellite cells. Furthermore, MyoD was proved as the directly interacted gene of miR-495, and their interaction was crucial for myotube formation. Enforced miR-495 expression could intensively strengthen the muscle mass, in situ muscular electrophysiological indexes, including peak tetanic tension (Po) and peak twitch tension (Pt), and the cross-sectional areas (CSA) of muscle fibers via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 signaling pathway, indicating that miR-495 can be proposed as an effective target for muscle atrophy treatment induced by in the mechanical unloading, random rotating and aging.

Melatonin Ameliorates Age-Related Sarcopenia via the Gut-Muscle Axis Mediated by Serum Lipopolysaccharide and Metabolites.

Sarcopenia affects the quality of life and increases adverse outcomes in the elderly. However, as a potential safe and effective remedy to many age-related disorders, little is known about the protective effect of melatonin against sarcopenia, especially the underlying mechanisms of pathophysiology related to the gut-muscle axis. The young (4 months) and old-aged (24 months) wild-type C57BL/6J male mice were included in this study, of which the old-aged mice in the experimental group were treated with 10 mg/kg/day of melatonin for 16 weeks. After that, muscle strength, muscle mass and the cross-sectional area (CSA) of the gastrocnemius muscle fibres were measured. Then, the putative pathways, based on the data obtained from 16S rDNA sequencing of the gut microbiota, RNA sequencing of gastrocnemius muscle and serum untargeted metabolomics, were screened out by the integrated multiomics analysis and validated using immunohistochemistry, ELISA and TUNEL staining. C2C12 myoblasts were treated with LPS. Flow cytometric analysis and western blotting were applied to detect cell apoptosis and protein expressions of Tnfrsf12a and caspase8, respectively. In addition, the mediation analysis was carried out to infer the causal role of the microbiome in contributing to the skeletal muscle through metabolites. Melatonin treatment ameliorated age-related declines in muscle strength (p < 0.05), muscle mass (p < 0.01) and CSA of the gastrocnemius muscle fibres (p < 0.01), as well as changed the gut microbial composition (beta-diversity analysis; R = 0.513, p = 0.005). The integrated multiomics analysis implied two main mechanisms about the impact of melatonin-related modifications in the gut microbiota on sarcopenia. First, a lower serum lipopolysaccharide (LPS) level associated with the altered gut microbiota was observed in melatonin-treated mice (p < 0.001) and was most relevant to the transcription level of Tnfrsf12a in skeletal muscle (R = 0.926, p < 0.001). Further bioinformatics analyses and invitro experiments showed that LPS could contribute to skeletal muscle apoptosis by regulating the Tnfrsf12a/caspase-8 signalling pathway. Second, melatonin significantly altered serum metabolites (variable importance on projection (VIP) > 1.5, p < 0.05). Mediation models showed that changes in the gut microbiome also influenced skeletal muscle through these metabolites (27 linkages; BH-adjusted p < 0.05). Our study revealed functional insights and a putative causality for the role of the gut-muscle axis in the mechanism of melatonin ameliorating age-related sarcopenia, namely, inhibition of the LPS-induced Tnfrsf12a/caspase-8 signalling pathway or serum metabolites as intermediates in the gut-muscle axis.

Photobiomodulation and aquatic training reduce TNF-α expression and enhance muscle fiber area in Wistar rats with compensatory hypertrophy.

This study aims to assess the effects of aquatic training (AT) and its combination with photobiomodulation (PBM) on cytokine synthesis and plantar muscle morphology during compensatory hypertrophy (H) in Wistar rats. H was induced by bilateral ablation of synergistic muscles, and PBM using a laser (780nm). AT involved 60min sessions, 5 times/week, for 7 and 14 days. Muscle weight relative to body weight did not differ significantly between groups. TNF-α synthesis levels decreased in the H + AT + PBM group at 7 days compared to H Control. IL-6 and IL-1β levels showed no significant changes. Cross-sectional area (CSA) was higher in H + AT + PBM at 7 days and 14 days compared to H + AT and H Control. Fiber diameter increased in H + AT and H + AT + PBM compared to H at 14 days. AT with PBM decreased TNF-α expression, increased CSA and fiber diameter, whereas AT alone increased fiber diameter. In conclusion, the combination of photobiomodulation (PBM) therapy and aquatic training (AT) effectively reduced TNF-α levels while increasing muscle fiber diameter and cross-sectional area (CSA). Furthermore, AT alone demonstrated the capacity to maintain fiber diameter.

Type 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p/NAMPT Pathway.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among patients with diabetes that is mainly attributed to mitochondrial dysfunction. Therefore, we investigated the mechanisms underlying diabetic myopathy development, focusing on the role of microRNAs (miRs). Zebrafish were fed a high-sugar diet for 8 weeks and immersed in a glucose solution to establish a model of T2DM. Notably, the fish exhibited impaired blood glucose homeostasis, increased lipid accumulation in the skeletal muscles, and decreased insulin levels in the skeletal muscle. Additionally, we observed various symptoms of diabetic myopathy, including a decreased cross-sectional area of skeletal muscle fibers, increased skeletal muscle fibrosis, a significant decline in exercise capacity, and a significant decrease in mitochondrial respiratory function. Mechanistically, bioinformatic analysis combined with various molecular analyses showed that the miR-139-5p/NAMPT pathway was involved in long-term high-glucose-induced mitochondrial dysfunction in the skeletal muscle, leading to diabetic myopathy. Conclusively, this study provides a basis for the development of novel strategies for the prevention and treatment of diabetic myopathy.

A Cervus Elaphus and Eucommia Ulmoides Extract Blend Attenuates Muscle Atrophy by Regulating Protein Metabolism and Antioxidant Activity.

Here, we investigated whether a mixture of Cervus elaphus and Eucommia ulmoides (1:3, KGC01CE) could suppress muscle atrophy in H2O2-induced C2C12 cells and dexamethasone-injected mice. Our results revealed that KGC01CE effectively safeguarded against H2O2-induced muscle atrophy in C2C12 cells compared with the same mixture at other ratios. We demonstrated that dexamethasone elicited oxidative stress in muscle tissue and decreased the grip strength and cross-sectional areas of muscle fibers; however, oral administration of KGC01CE (1:3) suppressed these dexamethasone-induced changes. Furthermore, oral KGC01CE (1:3) administration suppressed the expression of protein degradation-associated factors, myostatin, muscle RING finger 1, and atrogin-1 in muscle tissue from dexamethasone-injected mice. Oral KGC01CE administration stimulated protein synthesis by stimulating the PI3K/Akt/mTOR pathway in muscle tissue from dexamethasone-injected mice. These findings indicate that KGC01CE can suppress dexamethasone injection-induced muscle atrophy by inhibiting protein degradation and promoting muscle hypertrophy. Therefore, KGC01CE supplementation helps prevent muscle atrophy in mice and may be beneficial against various components of muscle atrophy.

The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status.

Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 × 10-12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status.

Metformin inhibits muscle atrophy through the PI3K/AKT/mTOR pathway in a rat model of acute rotator cuff tears.

Muscle atrophy after the rupture of a rotator cuff (RC) tendon is a major factor that increases the risk of secondary complications and re-rupture. Metformin, a type 2 diabetes treatment, can be used to modulate intracellular signaling pathways that promote muscle growth. This study aimed to verify whether systemic metformin administration could prevent supraspinatus (SS) atrophy after RC rupture in a rat model. This study is a comparative animal study aimed at investigating the effects of metformin. Twelve-week-old male Sprague-Dawley rats were used. The metformin group was administered intraperitoneal injection with 50 mg/kg metformin daily for 6 weeks after the RC tendon was cut, while the control group was given 0.9% saline solution. All rats were weighed and sacrificed 6 weeks after their surgery; then, SS were collected, and individual SS weights were measured. The expression of muscle atrophy genes was determined through quantitative reverse transcription polymerase chain reaction, and the amount of signal metabolism regulatory protein was measured by western blotting. Muscle atrophy and fatty infiltration (FI) were evaluated by histological staining. Six weeks after RC tendon rupture, the SS weight in the metformin group was significantly higher than in the control group. Western blotting analysis revealed that the expression levels of phosphatidylinositol 3-kinase (P = .002), protein kinase B (P = .001), and mammalian targets of rapamycin (P = .009) protein were significantly higher in the metformin group than in the control group. The muscle atrophy-related marker genes Atrogin-1 (P = .036) and MuRF-1 (P < .000) in the metformin group were downregulated. The morphology of the SS, whose atrophy was prevented by metformin, had fewer wide pores and less reduced muscle fiber area than those of the control group. Muscle tissue staining analysis showed that FI was significantly suppressed by systemic metformin administration compared with that of the control group both qualitatively and quantitatively (P = .032). Metformin elicited an FI-suppressing effect by downregulating the adipogenic genes PPAR-γ (P = .001) and C/EBP-α (P< .001). Metformin significantly prevented SS atrophy by activating the PI3K/AKT/mTOR pathway in an acute RC tear rat model. It also suppressed FI by downregulating adipogenic factors in the late stage of RC tear. These results strongly supported the usefulness of metformin for high-quality muscle preservation after RC rupture in clinical practice.

Exploring the molecular basis of efficient feed utilization in low residual feed intake slow-growing ducks based on breast muscle transcriptome

Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an experimental facility until they were culled at 42 d of age. Thirty high RFI (HRFI) and 30 low RFI (LRFI) birds were selected to evaluate their growth performance, carcass characteristics, and muscle development. Transcriptome and weighted gene co-expression correlation network analyses of pectoral muscles were conducted on six LRFI and six HRFI ducks. The results revealed that selecting for LRFI significantly reduced feed consumption (P < 0.05) and improved feed efficiency without affecting the growth performance, slaughter rate, or meat quality of ducks (P > 0.05). Moreover, compared with HRFI ducks, LRFI ducks had a lower pectoral muscle fat content (P < 0.05), larger muscle fiber diameter and area (P < 0.05), and lower muscle fiber density (P < 0.05). There were significant differences in gene expression between LRFI and HRFI ducks, with 102 upregulated and 258 downregulated genes, which were enriched in the PPAR signaling pathway, adipocytokine signaling pathway, actin cytoskeleton regulation, ECM-receptor interaction, and focal adhesion. The expression of genes associated with fat and energy metabolism, including ACSL6, PCK1, APOC3, HMGCS2, PRKAG3, and G6PC1, was downregulated in LRFI ducks, and weighted gene co-expression correlation network analysis identified PRKAG3 as a hub gene. Our findings indicate that reduced mitochondrial energy metabolism may contribute to the RFI of slow-growing ducks, with PRKAG3 playing a pivotal role in this biological process. These findings provide novel insights into the molecular changes underlying RFI variation in slow-growing ducks.

Targeting Metastasis in Head and Neck Squamous Cell Carcinoma Using Follistatin mRNA Lipid Nanoparticles.

Metastatic progression significantly reduces survival rates and complicates treatment strategies in various cancers. Our study introduces an mRNA therapy for metastasis inhibition by targeting activin A overexpression, a pivotal driver of metastasis and cachexia. Utilizing follistatin mRNA lipid nanoparticles, we effectively downregulated activin A both locally in the tumor environment and systemically. This led to a reduction in tumor burden and suppression of metastatic spread in a murine head and neck squamous cell carcinoma model. Treated mice exhibited minimal metastatic occurrence compared to controls. Additionally, our therapy preserved the cross-sectional area of muscle fibers and adipose tissues, combating the muscle and fat wasting typically observed in cancer-associated cachexia. The therapy also demonstrated a favorable safety profile, underscoring its potential for clinical translation. By integrating metastasis-suppressing and cachexia-alleviating mechanisms, our approach represents a promising advancement in comprehensive cancer management. Considering the widespread upregulation of activin A in many cancer types, our therapy holds considerable potential for application across a broad spectrum of oncologic treatments.

Glycyrrhiza uralensis extract improves dexamethasone-induced sarcopenia via regulating myostatin- and FoxO3a-mediated E3 ubiquitin ligase

Sarcopenia affects the skeletal muscle system and impairs physical activity. This study investigated the effects of Glycyrrhiza uralensis (GU) extract on ameliorating dexamethasone (DEX)-induced sarcopenia in C2C12 myoblasts and C57BL/6J mice. Initially, network pharmacology analysis determined the association between GU and DEX-induced sarcopenia and predicted potentially related signaling pathways. Subsequently, the protective effects of different GU extracts on DEX-induced damage in C2C12 myotubes were evaluated by cell viability assays and Jenner and Giemsa (J&G) staining. Finally, the GU extract screened in vitro was evaluated by body composition analysis, grip strength and endurance tests, serum analysis, histological analysis, and protein expression level analysis in DEX-induced C57BL/6J mice. Network pharmacology confirmed the correlation between GU and DEX-induced sarcopenia involving TNF, MSTN, and FoxO signaling pathways. In DEX-induced damaged myotubes, only GU water extract (GW) dose-dependently increased cell viability. J&G staining of GW-treated myotubes revealed that GW increased the cell fusion index, maturation index and myotube diameter, attenuating DEX-induced cell damage. Oral administration of GW at doses above 300 mg/kg/day restored lean body mass lost due to DEX and subsequently reduced body fat. GW also enhanced grip strength and endurance, reduced muscle tissue injury, and increased the cross-sectional area of muscle fibers in DEX-induced mice. GW reduced the inflammatory response by alleviating serum TNF-α levels and ultimately decreased E3 ubiquitin ligase (MAFbx and MuRF-1) by downregulating myostatin and promoting FoxO3a phosphorylation. These results suggest that GU inhibits muscle protein degradation and is a potential food and medicinal homolog for preventing or treating sarcopenia.

Analysis of lncRNAs and Their Regulatory Network in Skeletal Muscle Development of the Yangtze River Delta White Goat.

lncRNA (long non-coding RNA) has been confirmed to be associated with growth, development, cell proliferation, and other biological processes. This study explored the potential role and dynamic change process of lncRNAs and related ceRNA (competitive endogenous RNA) networks in skeletal muscle development of the Yangtze River Delta White (YDW) goat, and to analyze the differences in muscle fiber characteristics and meat quality levels of goats at different growth stages. In this study, we compared the expression profiles of lncRNAs in the M. Longissimus dorsi of the YDW goats at different stages of growth and development by RNA sequencing. The results revealed that, in terms of muscle fiber characteristics, muscle fiber diameter and muscle fiber area were significantly larger in 6-month-old and 10-month-old goats than those in 2-month-old goats (p < 0.01). In terms of muscle quality, a* and b* values of 6-month-old goats were significantly higher than those of 2-month-old goats (p < 0.01). Additionally, the a*, b*, and L* values of 6-month-old goats were significantly higher than those of 10-month-old goats (p < 0.01). The pH at 45 min post-mortem (pH45min) in 10-month-old goats was significantly higher than that in 2-month-old goats (p = 0.006). However, the pH at 24 h post-mortem (pH24h) in 10-month-old goats was significantly lower than that in both 2-month-old and 6-month-old goats (p < 0.01). Shear force increased gradually with age (p < 0.05), while there was no significant difference in drip loss among the different age groups (p > 0.05). Among the identified lncRNA expression profiles, a total of 3073 lncRNAs were found, including 2676 known lncRNAs and 397 novel lncRNAs. Of these, 110, 93, and 99 lncRNAs were specifically expressed in 2-month-old, 6-month-old, and 10-month-old goats, respectively. The lncRNA target gene enrichment analysis showed that they were mainly involved in actin binding, the actin cytoskeleton, the myocardin complex, as well as the AMPK, FoxO, and GnRH signaling pathways. When constructing the lncRNA-miRNA-mRNA ceRNA network, it was found that the ceRNA networks centered on chi-miR-758 and chi-miR-127-5p were involved in muscle development across all three periods, suggesting that they may play an important role in goat muscle growth and development.

Relationship between histological findings of vastus lateralis muscle and function after total hip arthroplasty in patients with hip fracture: a prospective cohort study.

We aimed to examine the histological characteristics of vastus lateralis muscles in patients undergoing total hip arthroplasty (THA) following femoral neck fractures and to explore the correlation between muscle fiber types and postoperative functional recovery. 34 patients undergoing THA for femoral neck fractures were included. A biopsy of the vastus lateralis muscle was performed during surgery, followed by immunohistochemical staining. Subsequently, image analysis was conducted to measure the average area of muscle fiber types and the number of type I and II muscle fibers, and the ratio of the area and the number of type II muscle fibers. Functional recovery was assessed 2 weeks post-surgery using the Short Physical Performance Battery (SPPB). A significant positive correlation was observed between type II muscle fibers and SPPB scores. The ratio of type II muscle fiber area and number strongly correlated with the SPPB scores, indicating a robust static association. The average area of type II fibers showed a strong correlation (r = 0.63, P < 0.001), as did the number of type II fibers (r = 0.53, P = 0.001). Moreover, the ratio of type II muscle fiber area and number significantly correlated with SPPB scores (area: r = 0.77, P < 0.001; number: r = 0.51, P = 0.002), indicating that larger and more numerous type II fibers are associated with better physical performance. The reduction of type II muscle fibers was strongly correlated with a low SPPB postoperative functional recovery in patients who underwent THA following femoral neck fractures.

Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy

Sepsis-induced myopathy (SIM) has been recognized as a critical risk factor for the development of acquired muscle weakness among patients in the intensive care unit. These individuals frequently encounter inadequate dietary intake and malnutrition. With the aggravation of the severity of the person’s condition, leading to increased skeletal muscle protein breakdown and reduced synthesis, which is an urgent problem to be solved in clinical nutritional treatment. Whole milk protein powder (WMPP) has promising bioactive nutrients and holds promising potential for enhancing skeletal muscle mass. The study was designed to delve into the potential effects and mechanisms of WMPP intervention for increaseing skeletal muscle mass on SIM mice. Our results clearly show that the intervention with WMPP can significantly improve the exercise capacity and skeletal muscle mass in SIM mice. It significantly increases the diameter and cross-sectional area (CSA) of skeletal muscle fibers, while effectively reducing the excessive aggregation of collagen fibers and the abnormal accumulation of adipose tissue in the skeletal muscle of SIM mice. Moreover, WMPP intervention also significantly alleviated the oxidative stress status of mitochondria, which subsequently enhanced the expression of mitochondrial metabolic enzymes. The mechanism may be associated with decreased AMPK phosphorylation in skeletal muscle tissue and simultaneously increased phosphorylation of mTOR, p70S6K1, and 4EBP-1 in SIM mice. In summary, the WMPP intervention significantly enhances exercise capacity and skeletal muscle mass while mitigating the oxidative stress status of mitochondria. Furthermore, it regulates skeletal muscle anabolism via the AMPK/mTOR signaling pathway in SIM mice.

Ighmbp2 mutations and disease pathology: Defining differences that differentiate SMARD1 and CMT2S

Mutations in the Immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene result in two distinct diseases, SMA with Respiratory Distress Type I (SMARD1) and Charcot Marie Tooth Type 2S (CMT2S). To understand the phenotypic and molecular differences between SMARD1 and CMT2S, and the role of IGHMBP2 in disease development, we generated mouse models based on six IGHMBP2 patient mutations. Previously, we reported the development and characterization of Ighmbp2D564N/D564N mice and in this manuscript, we examine two mutations: D565N (D564N in mice) and H924Y (H922Y in mice) in the Ighmbp2H922Y/H922Y and Ighmbp2D564N/H922Y contexts. We found significant differences between these mouse models, providing critical insight into the role of IGHMBP2 in the pathogenesis of SMARD1 and CMT2S. Importantly, these studies also demonstrate how disease pathogenesis is significantly altered in the context of Ighmbp2 D564N and H922Y homozygous recessive and compound heterozygous mutations. Notably, there were short-lived and long-lived lifespan cohorts within Ighmbp2D564N/H922Y mice with early (P12/P16) respiratory pathology serving as a key predictor of lifespan. Despite differences in lifespan, motor function deficits initiated early and progressively worsened in all Ighmbp2D564N/H922Y mice. There was decreased limb skeletal muscle fiber area and increased neuromuscular junction (NMJ) denervation in Ighmbp2D564N/H922Y mice. Consistent with CMT2S, Ighmbp2H922Y/H922Y mice did not have altered lifespans nor respiratory pathology. Interestingly, Ighmbp2H922Y/H922Y limb muscle fibers demonstrated an increase in muscle fiber area followed by a reduction while changes in NMJ innervation were minimal even at P180. This is the first study that demonstrates differences associated with IGHMBP2 function within respiration with those within limb motor function. Significant to our understanding of IGHMBP2 function, we demonstrate that there is a direct correlation between disease pathogenesis associated with these IGHMBP2 patient mutations and IGHMBP2 biochemical activity. Importantly, these studies reveal the dynamic differences that are presented when either a single mutant protein is present (IGHMBP2-D564N or IGHMBP2-H922Y) or two mutant proteins are present (IGHMBP2-D564N and IGHMBP2-H922Y) within cells.

Effect of Dietary Digestible Protein Levels on Muscle Growth and Oxidative Stress in Amazonian Pintado (Pseudoplatystoma reticulatum × Leiarius marmoratus).

This study aimed to evaluate the effects of dietary digestible protein levels on the growth dynamics and oxidative stress status of white muscle fibers in Amazonian Pintado (Pseudoplatystoma reticulatum × Leiarius marmoratus). Four hundred and fifty-five juveniles of Amazonian Pintado were fed diets containing varying digestible protein levels (225, 250, 275, 300, 325, 350, or 375 g kg-1) for 75 days. At the end of the experiment, the fish were fasted for 24 h, anesthetized, and euthanized to obtain muscle samples. The linear and quadratic effects of dietary digestible protein levels on white muscle fiber diameter, metabolite concentrations, and oxidative stress were assessed. The results revealed that increasing dietary digestible protein levels linearly raised the concentrations of free amino acids and total proteins in muscle tissue but also led to elevated levels of TBARS, indicating increased oxidative stress. Notably, the average area of muscle fibers with a cell area greater than 1133 µm2 decreased, reflecting restricted muscle hypertrophy, whereas glycogen and glucose levels also declined. These findings suggest that although high dietary digestible protein enhances protein and free amino acid concentrations in muscle tissue, it may compromise muscle hypertrophy and increase oxidative damage in Amazonian Pintado, underscoring the complexity of optimizing diet formulation.

Effect of Photobiomodulation on an Experimental Model ofLower Limb Ischemia.

Photobiomodulation (PBM) has been shown to be promising for the promotion of angiogenesis. The present study investigated the effects of PBM on vascularization in an animal model of peripheral artery disease. Wistar rats were divided into three groups. The control group received no procedures. The ischemia group was submitted to ligation of the femoral artery of the hindleg. The ischemia + PBM group was submitted to ligation of the femoral artery followed by PBM (660 and 808 nm, 100 mW, 4 J) over the site. Animals with ischemia treated with PBM exhibited comparable results to the control group with regards to the diameter of the α-SMA+ vessels, cross-sectional area of muscle fibers, percentage of collagen and serum concentration of IL-17A, as well as similarities in terms of vertical mobility, temperature of the hindleg, number of acts of grooming, and percentage of movement, indicating a condition like that of limbs unaffected by ischemia.

A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia.

Mutations in the well-known Myostatin (MSTN) produce a 'double-muscle' phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant 'double-muscle' phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

Specific tension of human muscle in vivo: a systematic review.

The intrinsic force production capability of human muscle can be expressed as "Specific Tension," or, the maximum force generated per cross-sectional area of muscle fibers. This value can be used to determine, for example, whether muscle quality changes during exercise, atrophy, disease, or hypertrophy. A value of 22.5 N/cm2 for mammalian muscle has generally become accepted based on detailed studies of small mammals. Determining the specific tension of human muscle is much more challenging as almost all determinations are indirect. Calculation of human muscle specific tension requires an understanding of that muscle's contribution to joint torque, its activation magnitude, tendon compliance, and joint moment arm. Determining any of these parameters is technically challenging in humans and thus, it is no surprise that human specific tension values reported vary from 2 to 73 N/cm2. In this systematic review, we screened 1,506 published papers and identified the 30 studies published between 1983 and 2023 that used appropriate methods and which reported 96 human specific tension values. We weighted each parameter based on whether it was directly measured, estimated, or calculated based on the literature, with decreasing weighting used, the more indirect the methods. Based on this exhaustive review of the relevant human literature, we suggest that the most accurate value that should be used for human muscle specific tension is 26.8 N/cm2.