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BACKGROUND: Rotator cuff muscle degeneration (muscle atrophy, fibrosis and fatty infiltration) is a common condition after rotator cuff tears, which seriously affects shoulder function and surgical outcomes. Ginsenoside Rg1 has biological effects such as anti-oxidation, anti-apoptosis and lipid-lowering. However, the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE: To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS: Sixty C57BL/6J mice were randomly divided into sham group, model group, ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group, with 15 mice in each group. The skin of the right shoulder of mice in the sham group was cut and sutured. Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups. Supraspinatus tendon and suprascapular nerve compression were administrated. Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation, while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively, once a day, for 6 weeks. Mice were assessed for limb function by gait analysis the day after the last injection. After euthanasia, the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility. Muscle tissue was stained with oil red O and Masson. RT-PCR was used to detect the expression of atrophy, fibrosis, and fatty infiltration related genes. RESULTS AND CONCLUSION: Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased paw print area and step length (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility (P < 0.05), and significantly decreased wet muscle mass reduction ratio, fatty infiltration area ratio, and collagen fiber area ratio (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy, fibrosis, and fatty infiltration related genes (P < 0.05). There was no significant difference in paw print area, supraspinatus muscle contractility, and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups (P > 0.05), and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group (P < 0.05). To conclude, ginsenoside Rg1 could significantly reduce muscle atrophy, fibrosis and fatty infiltration following massive rotator cuff tear in mice, which is beneficial to improve muscle strength and limb function. [ABSTRACT FROM AUTHOR]

Necroptosis is a regulated form of cell death with implications in various physiological and pathological processes in multiple tissues. However, the relevant findings from post-mitotic tissues, such as skeletal muscle, are scarce. This review summarizes the potential contributions of necroptosis to skeletal muscle health and diseases. It first discusses the physiological roles of necroptosis in muscle regeneration and development. It then summarizes the contributions of necroptosis to the pathogenesis of multiple muscle diseases, including muscular dystrophies, inflammatory myopathies, cachexia, and neuromuscular disorders. Lastly, it unravels the gaps in our understanding and therapeutic challenges of inhibiting necroptosis as a potential intervention for muscle diseases. Specifically, the findings from the transgenic animal models and the use of pharmacological inhibitors of necroptosis are discussed with relevance to improving the structure and/or function of skeletal muscle in various diseases. Recent developments from experimental animal models and clinical data are presented to discuss the roles of necroptosis in skeletal muscle health and diseases. [ABSTRACT FROM AUTHOR]

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between immune cell phenotypes and muscle atrophy. Data on immune cell phenotypes were obtained from a research cohort containing data on 731 immune cell phenotypes and data on muscle atrophy were sourced from a Finnish database. MR analysis was performed using the MR-Egger method, weighted median, inverse variance weighting, heterogeneity testing, sensitivity analysis, and multiplicity analysis, with results subjected to false discovery rate(FDR) correction. Additionally, the UK Biobank cohort was utilized as an external validation. A total of 31 immune phenotypes with causal relationships with muscle atrophy were identified, including various phenotypes of conventional dendritic cells, myeloid cells, T cells/B cells/natural killer cells, regulatory cells, and T cell maturation stages. Among them, 12 immune phenotypes were identified as exhibiting a positive causal relationship with muscle atrophy, while 19 immune phenotypes were demonstrated to have a negative causal association, highlighting the complex interactions between immune cells and muscle health. The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186). A significant positive correlation was revealed by external datasets between the CD25 on IgD + CD38- immune phenotype and the risk of muscle atrophy, which was consistent with the trend observed in the training group (OR = 1.1041, 95% CI: 1.1005–1.1076, P = 0.0263). No evidence of pleiotropy was observed, and the reliability of these findings was demonstrated by the leave-one-out analysis. The findings highlight significant correlations between certain immune cell features and muscle atrophy, providing potential targets for further investigation of immunological mechanisms and therapeutic interventions for this condition. [ABSTRACT FROM AUTHOR]

In the process of the upper limb rehabilitation, the rehabilitation effect is often evaluated from the perspective of the motor function of limbs. However, the state of muscle atrophy is also a noteworthy indicator reflecting the rehabilitation effect. We proposed a wearable solution for the monitoring and grade assessing of local muscle atrophy based on wearable bioimpedance (BioZ) sensors. This work elaborates on the theoretical basis, procedure, and key influencing factors of the proposed solution, and the feasibility and effectiveness have been verified through in vitro and in vivo experiments. A total of 25 phantoms in different CSA (cross-sectional area) and FMR (fat-to-muscle ratio) values were designed to simulate different stages of muscular atrophy, and a linear correlation was observed between BioZ, CSA, and FMR, with an R-squared value of 0.898. The relative impedance difference of 38 patients with unilateral muscle atrophy was 5.231% larger than that of 30 healthy control samples on average (p < 0.05). These results demonstrate the correlation between muscle atrophy and BioZ. As the proof-of-concept for graded assessment, the results analyzed by support vector machines (SVMs) show that the accuracy of three-level classification can reach 94.1% using the five-fold cross-validation. [ABSTRACT FROM AUTHOR]

Background: Animal models focusing on neuromuscular outcomes are crucial for understanding the mechanisms of intensive care unit-acquired weakness (ICU-AW) and exploring potential innovative prevention and treatment strategies. Aim: To analyse and evaluate preclinical ICU-AW models. Methods: We manually searched five English and four Chinese databases from 1 January 2002, to 1 February 2024, and reviewed related study references. Fulltext publications describing animal models of muscle weakness and atrophy in critical illness were included. Detailed information about model types, animal species, sex, age, induction methods, outcome measures, drawbacks and strengths was extracted from each included study. Results: A total of 3,451 citations were initially retrieved, with 84 studies included in the final analysis. The most frequently studied animal model included rodents (86.9%), 64.3% of which were male animals. ICU-AW animal models were mostly induced by comprehensive intensive care unit (ICU) interventions (38.1%) and sepsis (51.2%). Most studies focused on limb muscles (66.7%), diaphragm muscles (21.4%) or both (9.5%). Reported outcomes primarily included muscular pathological changes (83.3%), electrophysiological examinations of muscles (57.1%) and animal grip strength (16.6%). However, details such as animal age, mortality data, experimental design, randomisation, blinding, sample size and interventions for the experimental group and/or control group were inadequately reported. Conclusion: Many preclinical models are used to study ICU-AW, but the reporting of methodological details is often incomplete. Although current ICU animal models can mimic the characteristics of human ICU-AW, there is no standard model. Future preclinical studies should develop a standard ICU-AW animal model to enhance reproducibility and improve scientific rigor in exploring the mechanisms and potential treatment of ICU-AW. [ABSTRACT FROM AUTHOR]

Abstract\nKey pointsBackground: Diabetes patients’ quality of life can be severely impacted by diabetic muscle atrophy.Aim: This study aimed to explore the impact of high-intensity exercise (HIE) alongside insulin treatment on muscle atrophy in a rat model of type 1 diabetes mellitus (T1DM).Methodology: Fifty rats were allocated into five groups; Group 1, control sedentary (CS), T1DM was elicited in the rest of the groups by giving them Streptozotocin (STZ) (60 mg/kg), where group 2 (DS) remained sedentary, while groups 3,4,5 were treated with insulin after induction of diabetes. Group 4 (DI+MIE) and 5 (DI+ HIE) underwent moderate and high-intensity exercise, respectively.Results: HIE for 14 days combined with insulin treatment significantly restored muscle strength and mass with a significant modification in the mitophagy-related proteins and fibroblast growth factor 21 (FGF 21) compared to other treated groups.Conclusion: This study concluded that there is a therapeutic role for HIE with insulin against T1DM-induced muscle atrophy.T1DM induces loss of skeletal muscle mass and strength.T1DM enhances muscle atrophy-related genes (MAFbx and MuRF1) and impairs mitochondrial function.HIE alongside insulin treatment restores muscle mass, strength, and histological architecture in T1DM-induced muscle atrophy model.HIE alongside insulin treatment over MIE moderated the mitochondrial dysfunction via modulation of the mitophagy-related mediators (BNIP3, Parkin, P62, and LC3II/LC3I) and FGF 21 expression.T1DM induces loss of skeletal muscle mass and strength.T1DM enhances muscle atrophy-related genes (MAFbx and MuRF1) and impairs mitochondrial function.HIE alongside insulin treatment restores muscle mass, strength, and histological architecture in T1DM-induced muscle atrophy model.HIE alongside insulin treatment over MIE moderated the mitochondrial dysfunction via modulation of the mitophagy-related mediators (BNIP3, Parkin, P62, and LC3II/LC3I) and FGF 21 expression. [ABSTRACT FROM AUTHOR]

In the pathophysiology of osteoarthritis and osteoporosis, articular cartilage and bone represent the target tissues, respectively, but muscle is also involved. Since many changes in energy metabolism occur in muscle with aging, the aim of the present work was to investigate the involvement of carnitine palmitoyl transferase 1b (Cpt1b) in the muscle pathophysiology of the two diseases. Healthy subjects (CTR, n = 5), osteoarthritic (OA, n = 10), and osteoporotic (OP, n = 10) patients were enrolled. Gene expression analysis conducted on muscle and myoblasts showed up-regulation of CPT1B in OA patients; this result was confirmed by immunohistochemical and immunofluorescence analyses and enzyme activity assay, which showed increased Cpt1b activity in OA muscle. In addition, CPT1B expression resulted down-regulated in cultured OP myoblasts. Given the potential involvement of Cpt1b in the modulation of oxidative stress, we investigated ROS levels, which were found to be lower in OA myoblasts, and gene expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (Nox4), which resulted up-regulated in OA cells. Finally, the immunofluorescence of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) showed a decreased expression in OP myoblasts, with respect to CTR and OA. Contextually, through an ultrastructural analysis conducted by Transmission Electron Microscopy (TEM), the presence of aberrant mitochondria was observed in OP muscle. This study highlights the potential role of Cpt1b in the regulation of muscle homeostasis in both osteoarthritis and osteoporosis, allowing for the expansion of the current knowledge of what are the molecular biological pathways involved in the regulation of muscle physiology in both diseases. [ABSTRACT FROM AUTHOR]

Cachexia is a late consequence of various diseases that is characterized by systemic muscle loss, with or without fat loss, leading to significant mortality. Multiple signaling pathways and molecules that increase catabolism, decrease anabolism, and interfere with muscle regeneration are activated. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in cachexia muscle atrophy. This review mainly provides the mechanisms of specific ncRNAs to regulate muscle loss during cachexia and discusses the role of ncRNAs in cachectic biomarkers and novel therapeutic strategies that could offer new insights for clinical practice. [ABSTRACT FROM AUTHOR]

In response to peroxynitrite (ONOO−) generation, myogenic stem satellite cell activator HGF (hepatocyte growth factor) undergoes nitration of tyrosine residues (Y198 and Y250) predominantly on fast IIa and IIx myofibers to lose its binding to the signaling receptor c‐met, thereby disturbing muscle homeostasis during aging. Here we show that rat anti‐HGF monoclonal antibody (mAb) 1H41C10, which was raised in‐house against a synthetic peptide FTSNPEVRnitroY198EV, a site well‐conserved in mammals, functions to confer resistance to nitration dysfunction on HGF. 1H41C10 was characterized by recognizing both nitrated and non‐nitrated HGF with different affinities as revealed by Western blotting, indicating that the paratope of 1H41C10 may bind to the immediate vicinity of Y198. Subsequent experiments showed that 1H41C10‐bound HGF resists peroxynitrite‐induced nitration of Y198. A companion mAb‐1H42F4 presented similar immuno‐reactivity, but did not protect Y198 nitration, and thus served as the control. Importantly, 1H41C10‐HGF also withstood Y250 nitration to retain c‐met binding and satellite cell activation functions in culture. The Fab region of 1H41C10 exerts resistivity to Y250 nitration possibly due to its localization in the immediate vicinity to Y250, as supported by an additional set of experiments showing that the 1H41C10‐Fab confers Y250‐nitration resistance which the Fc segment does not. Findings highlight the in vitro preventive impact of 1H41C10 on HGF nitration‐dysfunction that strongly impairs myogenic stem cell dynamics, potentially pioneering cogent strategies for counteracting or treating age‐related muscle atrophy with fibrosis (including sarcopenia and frailty) and the therapeutic application of investigational HGF drugs. [ABSTRACT FROM AUTHOR]

Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life‐saving intervention for patients in respiratory failure, an unintended side‐effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV‐induced diaphragmatic weakness is labelled as 'ventilator‐induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox‐regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV‐induced changes in the structure/function of diaphragm muscle and discusses the cell‐signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field. [ABSTRACT FROM AUTHOR]

Fermented red ginseng (FRG) enhances the bioactivity and bioavailability of ginsenosides, which possess various immunomodulatory, antiaging, anti-obesity, and antidiabetic properties. However, the effects of FRG extract on muscle atrophy and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects of FRG extract on muscle atrophy using both in vitro and in vivo models. In vitro experiments used dexamethasone (DEX)-induced C2C12 myotubes to assess cell viability, myotube diameter, and fusion index. In vivo experiments were conducted on hind limb immobilization (HI)-induced mice to evaluate grip strength, muscle mass, and fiber cross-sectional area (CSA) of the gastrocnemius (GAS), quadriceps (QUA), and soleus (SOL) muscles. Molecular mechanisms were investigated through the analysis of key signaling pathways associated with muscle protein synthesis, energy metabolism, and protein degradation. FRG extract treatment enhanced viability of DEX-induced C2C12 myotubes and restored myotube diameter and fusion index. In HI-induced mice, FRG extract improved grip strength, increased muscle mass and CSA of GAS, QUA, and SOL muscles. Mechanistic studies revealed that FRG extract activated the insulin-like growth factor 1/protein kinase B (Akt)/mammalian target of rapamycin signaling pathway, promoted muscle energy metabolism via the sirtuin 1/peroxisome proliferator-activated receptor gamma-coactivator-1α pathway, and inhibited muscle protein degradation by suppressing the forkhead box O3a, muscle ring-finger 1, and F-box protein (Fbx32) signaling pathways. FRG extract shows promise for ameliorating muscle atrophy by modulating key molecular pathways associated with muscle protein synthesis, energy metabolism, and protein degradation, offering insights for future drug development. [ABSTRACT FROM AUTHOR]

As effective treatments for sarcopenia other than exercise have not yet been established, research is needed on treatment methods using drugs that can control muscle atrophy. Therefore, in this study, we aimed to assess the use of intramuscular sustained-release drug delivery systems and direct intramuscular injection for the control of muscle atrophy. First, we evaluated the inhibitory effects of camphor on skeletal muscle atrophy in vitro. L6 skeletal muscle cells were analyzed by WST-1 cell viability, 3D tomographic lipid accumulation, and mitochondrial length. These results indicated that camphor significantly regulates L6 cell atrophy. Next, we established poly(lactic-co-glycolic acid) (PLGA)-based microspheres loaded with camphor (PLGA-camphor), with each PLGA-camphor microsphere have a size of ~ 66–75 μm. Camphor was released ~ 93.29% over 10 days. Finally, we administered the PLGA-camphor by intramuscular injection in the starved fed mice model and performed immunohistological and histological analyses. The results indicate that PLGA-camphor is able to significantly regulate skeletal muscle atrophy in vivo. Our results suggest that PLGA-camphor may affect skeletal muscle atrophy. In the present study, our research findings indicate that camphor significantly reduces muscle atrophy in vitro. It used gravity to load camphor into PLGA-based microspheres, which were 66–75 μm in size. The sustained release properties of PLGA-camphor microsphere were shown to release 93.29% of camphor over ten days. When directly injected into the muscle of mice with muscular dystrophy, the PLGA-camphor microsphere resulted in a noteworthy reduction in muscle atrophy, particularly in the starved-induced muscle atrophy model mice. Our results suggest that PLGA-camphor microsphere could be a promising method for addressing skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. The back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA was recovered at 20 weeks. SDH staining was lower in CKD than in control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time. [ABSTRACT FROM AUTHOR]

Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin C, as an essential nutrient, has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia. Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia. OBJECTIVE: To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia, and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence. METHODS: The first author performed a computer search of PubMed, Web of Science, CNKI and other databases for relevant studies involving vitamin C in sarcopenia. The search keywords were “vitamin C, ascorbic acid, L-ascorbic acid, ascorbate, antioxidants, oxidative stress, sarcopenia, muscular atrophy, muscle weakness, muscle development, skeletal muscle regenerate, muscles, skeletal muscle” in English and Chinese, respectively. The search period was from each database inception to July 2023. After screening, 85 articles were included for further review. RESULTS AND CONCLUSION: Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia. In addition, vitamin C supplementation is also useful for improving skeletal muscle mass, strength and physical function with potential synergistic effects in exercise strategies for sarcopenia. The effects of vitamin C on sarcopenia may be via the following biological mechanisms: vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle, thus positively regulating protein metabolic homeostasis, and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function. In addition, vitamin C affects myoblast proliferation, differentiation and myotube size, mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways, which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue. The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors, such as the choice of supplementation dose and duration, the design of exercise prescription when vitamin C is combined with an exercise intervention, and the assessment of the redox status of the individual. It is recommended that future studies should be conducted in older patients with sarcopenia (< 50 μmol/L) with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1 000 mg/d vitamin C (for 6 months or longer) with at least two or more types of multi-type combined exercise, with supplementation timed to take place at 1 hour after the end of the exercise, and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored. In conclusion, the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more, while the appropriate design of exercise prescriptions (especially the type and intensity of exercise) needs to be further determined. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy occurs in several pathological conditions. Among other reasons, high-dose or long-term administration of glucocorticoids increases circulating glucocorticoid levels and causes muscle atrophy. The purpose of this study was to investigate whether Lithospermum erythrorhizon and Lonicera japonica complex extract (LELJ) has a beneficial effect on dexamethasone (Dexa)-induced muscle atrophy. In Dexa-induced myotube atrophy, treatment with LELJ increased myotube diameter, decreased the expression of muscle atrophy markers, and increased the expression of myosin heavy chain (MHC) isoforms. Supplementation with LELJ improved muscle function and performance in mice with Dexa-induced muscle atrophy as demonstrated by grip strength and running tests. Additionally, it increased skeletal muscle mass, size, and expression of MHC isoforms and protein synthesis-related markers. Furthermore, it reduced the upregulated protein levels of skeletal muscle atrophy markers in Dexa-treated mice. Supplementation with LELJ reversed Dexa-induced translocation of the glucocorticoid receptor and forkhead box O3 from the cytosol to the nucleus in skeletal muscles. LELJ also ameliorated age-related muscle loss by extending lifespan and increasing locomotor capacity in Caenorhabditis elegans. We identified loganin and lithospermic acid as bioactive compounds of LELJ and found that treatment with these agents increased myotube diameter, MHC isoform, and puromycin protein levels, and decreased atrophy markers in Dexa-treated myotubes. The current findings underscore how LELJ can prevent Dexa-induced skeletal muscle atrophy, attributing the effects to loganin and lithospermic acid. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is the reduction in muscle mass and function caused by an imbalance in protein synthesis and degradation. Inflammation has been shown to accelerate protein degradation during periods of muscle inactivity. We investigated the potential therapeutic effects of beetroot extract (BRE) in reducing inflammation and oxidative stress to prevent muscular atrophy after a short period of immobilization. We divided 36 male BALB/c mice into three groups: control, muscular atrophy mice, and muscular atrophy mice treated with BRE (n = 12). Each group was further divided into two subgroups: (1) 7‐day immobilization and (2) 10‐day recovery. BRE was administered orally at a dose of 300 mg/kg for 17 days. We assessed the anti‐inflammatory and antioxidative effects of BRE using ELISA and RT‐PCR assays. Hematoxylin–eosin staining was used to measure the cross‐sectional area (CSA) of muscle fibers, and grip strength tests were performed to assess muscle strength. BRE administration increased muscle weight, CSA, and grip strength in mice with immobilization‐induced muscle atrophy. It also suppressed inflammation and oxidative stress biomarkers in atrophic muscle fibers. Higher nitrate levels and lower Troponin I (TnI) concentrations were observed in the BRE‐treated group, indicating improved muscle function and structure. These findings suggest that BRE may have therapeutic benefits in improving muscle mass and function and warrant further studies in humans, particularly in individuals with low physical activity levels. [ABSTRACT FROM AUTHOR]

Cachexia is a wasting syndrome that manifests in more than half of all cancer patients. Cancer‐associated cachexia negatively influences the survival of patients and their quality of life. It is characterized by a rapid loss of adipose and skeletal muscle tissues, which is partly mediated by inflammatory cytokines. Here, we explored the crucial roles of interleukin‐6 (IL‐6) family cytokines, including IL‐6, leukemia inhibitory factor, and oncostatin M, in the development of cancer cachexia. These cytokines have been shown to exacerbate cachexia by promoting the wasting of adipose and muscle tissues, activating mechanisms that enhance lipolysis and proteolysis. Overlapping effects of the IL‐6 family cytokines depend on janus kinase/signal transducer and activator of transcription 3 signaling. We argue that the blockade of these cytokine pathways individually may fail due to redundancy and future therapeutic approaches should target common downstream elements to yield effective clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. Methods: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry. Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high- and lowdose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs). Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-β1 (TGF-β1). AM may be involved in regulating the AR/TGF-β1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-β1/p-smads expression levels were considerably increased. Conclusion: AM could ameliorate PF and related muscle atrophy via the cotarget AR and modulated AR/TGF-β1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-β1/smads pathway. This study explored the traditional Chinese medicine theory of "same treatment for different diseases," and supplied the pharmacological evidence of "AM can treat flaccidity syndrome." [ABSTRACT FROM AUTHOR]

Oxidative stress contributes to the loss of skeletal muscle mass and function in cancer cachexia. However, this outcome may be mitigated by an improved endogenous antioxidant defence system. Here, using the well‐established oxidative stress‐inducing muscle atrophy model of Lewis lung carcinoma (LLC) in 13‐week‐old male C57BL/6J mice, we demonstrate that extracellular superoxide dismutase (EcSOD) levels increase in the cachexia‐prone extensor digitorum longus muscle. LLC transplantation significantly increased interleukin‐1β (IL‐1β) expression and release from extensor digitorum longus muscle fibres. Moreover, IL‐1β treatment of C2C12 myotubes increased NBR1, p62 phosphorylation at Ser351, Nrf2 nuclear translocation and EcSOD protein expression. Additional studies in vivo indicated that intramuscular IL‐1β injection is sufficient to stimulate EcSOD expression, which is prevented by muscle‐specific knockout of p62 and Nrf2 (i.e. in p62 skmKO and Nrf2 skmKO mice, respectively). Finally, since an increase in circulating IL‐1β may lead to unwanted outcomes, we demonstrate that targeting this pathway at p62 is sufficient to drive muscle EcSOD expression in an Nrf2‐dependent manner. In summary, cancer cachexia increases EcSOD expression in extensor digitorum longus muscle via muscle‐derived IL‐1β‐induced upregulation of p62 phosphorylation and Nrf2 activation. These findings provide further mechanistic evidence for the therapeutic potential of p62 and Nrf2 to mitigate cancer cachexia‐induced muscle atrophy. Key points: Oxidative stress plays an important role in muscle atrophy during cancer cachexia.EcSOD, which mitigates muscle loss during oxidative stress, is upregulated in 13‐week‐old male C57BL/6J mice of extensor digitorum longus muscles during cancer cachexia.Using mouse and cellular models, we demonstrate that cancer cachexia promotes muscle EcSOD protein expression via muscle‐derived IL‐1β‐dependent stimulation of the NBR1‐p62‐Nrf2 signalling pathway.These results provide further evidence for the potential therapeutic targeting of the NBR1‐p62‐Nrf2 signalling pathway downstream of IL‐1β to mitigate cancer cachexia‐induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight‐week‐old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post‐surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin‐1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non‐ischaemic limbs of HLI mice by day 7 (7.3‐ and 2.3‐fold greater than Sham, respectively, P < 0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross‐sectional area than the non‐ischaemic limb (724 ± 28 vs. 916 ± 46 μm2, P = 0.01), but the non‐ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7‐day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. Highlights: What is the central question of this study?Does hindlimb ischaemia‐induced inflammation cause acute immune, inflammatory and morphological alterations in remote non‐ischaemic skeletal muscle?What is the main finding and its importance?Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non‐ischaemic skeletal muscle; however, morphological changes did not occur in non‐ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline. [ABSTRACT FROM AUTHOR]

Sarcopenia is a common and natural condition in the elderly, and leads to loss of muscle mass and function. In the presbylarynx there is atrophy of the vocal folds, however the degree of vocal muscle atrophy is poorly studied and the results are contradictory. Aims: The aim of this study was to evaluate the effect of aging on the vocal muscle (thyroarytenoid muscle). Thirteen larynxes removed during necropsy from 13 cadavers were included into two age groups: Control group – G1 (n5), between 25 and 40 years; Elderly Group - GI (n-8), aged 70 years or older. The vocal folds were dissected and prepared for scanning electron microscopy, ensuring a cross-section in the musculature area to allow measurements of muscle fiber parameters. Images were analyzed and photographed at different magnifications. Through the ImageJ software, ten distinct fields of each part were selected. Parameters studied: area, perimeters and diagonals of the thyroarytenoid muscle bundles of both groups. The cross-sectional areas, perimeters and diagonals of the muscle fibers of the thyroarytenoid muscle of the elderly group were significantly smaller than those of the control group. We demonstrated that the vocal muscle is affected in the presbylarynx, with a reduction of its muscle fibers, corresponding to muscle atrophy. However, these findings may not be directly related to vocal symptoms because the patient may develop muscle compensatory mechanisms capable of reducing glottic insufficiency [ABSTRACT FROM AUTHOR]

Prolonged exposure to high dosages of dexamethasone, which is a synthetic glucocorticoid and a well-known anti-inflammatory drug, may lead to an increase in reactive oxygen species production, contributing to muscle wasting. The prevention of muscle atrophy by ingestion of functional foods is an attractive issue. In the last decade, natural antioxidant compounds have been increasingly investigated as promising molecules able to counteract oxidative-stress-induced muscle atrophy. Recently, we have demonstrated the antioxidant properties of two main olive oil polyphenols also known for their anticancer and anti-inflammatory activities in different cell models. Here, the preventive effect of tyrosol on dexamethasone-induced muscle atrophy has been investigated by means of morpho-functional approaches in C2C12 myotubes. Dexamethasone-treated cells showed a reduced fiber size when compared to control ones. While long and confluent myotubes could be observed in control samples, those exposed to dexamethasone appeared as immature syncytia. Dysfunctional mitochondria and the accumulation of autophagic vacuoles contributed to myotube degeneration and death. Tyrosol administration before glucocorticoid treatment prevented muscle wasting and rescued mitochondrial and lysosomal functionality. These findings demonstrate that tyrosol attenuates dexamethasone-induced myotube damage, and encourage the use of this natural molecule in preclinical and clinical studies and in synergy with other functional foods or physical activity with the aim to prevent muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy or sarcopenia is the loss of muscle mass and strength and leads to an increased risk of disability and death including osteoporotic fractures. Currently, there are no available clinical biologic agents for the treatment of sarcopenia. Since exosomes have become increasingly attractive as a novel therapeutic approach due to their ability to facilitate cell-cell transfer of proteins and RNAs, promoting cell repair and function recovery, we hypothesized that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) might benefit muscle atrophy in age-related and dexamethasone-induced sarcopenia animal models. Methods: HucMSC-Exos were harvested by ultrafast centrifugation and identified by transmission electron microscopy, particle size analysis, and Western blot analysis. The effects of hucMSC-Exos on muscle atrophy were evaluated using age-related and dexamethasone-induced muscle atrophy mice models. Body weight, grip strength, muscle weight, and muscle histology of these mice were assessed. The expression levels of muscle RING finger 1 (MuRF1) and muscle atrophy F-box (atrogin-1) were measured by Western blot. Dexamethasone-induced C2C12 myotube atrophy was used to establish the cell model of muscle atrophy. Myotube diameter was evaluated by immunofluorescence staining. Bioinformatic analysis, RNA sequencing analysis, and Western blot analysis were performed to explore the underlying mechanisms. Results: In vivo experiments, hucMSC-Exos demonstrated a remarkable capacity to improve grip strength, increase muscle mass, and muscle fiber cross-sectional area, while concurrently reducing the expression of MuRF1 and atrogin-1 in age-related and dexamethasone-induced muscle atrophy mice. In vitro experiments, hucMSC-Exos can promote the proliferation of C2C12 cells, and rescue the dexamethasone-induced decline in the viability of C2C12 myotubes. In addition, hucMSC-Exos can increase the diameter of C2C12 myotubes, and reduce dexamethasone-induced upregulation of MuRF1 and atrogin-1. Combined with bioinformatics analysis and RNA sequencing analysis, we further showed that miR-132-3p was one of the essential miRNAs in hucMSC-Exos and played an important role by targeting FoxO3. Conclusion: Our findings suggested that hucMSC-Exos can improve age-related and dexamethasone-induced muscle atrophy in mice models. This study first demonstrated that hucMSC-Exos may ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis. These data may provide novel and valuable insights into the clinical transformation of hucMSC-Exos for the treatment of sarcopenia. The translational potential of this article: HucMSC-Exos are easily available for clinical application, this study further consolidates the evidence for the clinical transformation potential of hucMSC-Exos for sarcopenia and provides its new target pathway.

Sarcopenia is a condition characterized by a progressive loss of muscle mass and function which are influenced by certain factors such as aging, nutritional deficiencies, and chronic diseases. Despite numerous efforts to prevent or treat sarcopenia, effective therapeutic options for this disease remain limited. This study aims to evaluate the effects of KGC01CE treatment, a mixture of Cervus elaphus (Ce) and Eucommia ulmoides (Eu), which are well-known traditional herbal medicines in Asia, on age-related muscle loss and functional decline in aged rats. KGC01CE has been found to be more effective than the individual extracts in inhibiting dexamethasone (DEX)-induced muscle atrophy and improving muscle mass and grip strength in C2C12 cells and aged rats. Moreover, animal studies were conducted to determine the minimum effective dose, and a 12-week oral administration of KGC01CE treatment at doses of 50, 100, and 200 mg/kg to 15-month-old aged rats resulted in a dose-dependent increase in lean mass, muscle mass, grip strength, and muscle cross-sectional area (CSA), which had decreased due to aging. Furthermore, it was shown that KGC01CE activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and inhibited the expression of muscle-degrading proteins MuRF, Atrogin-1, and myostatin. These results suggest that KGC01CE treatment may effectively prevent muscle loss and functional decline, providing a novel therapeutic strategy for sarcopenia.

Abstract Background Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. Methods Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. Results A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. Conclusions EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

Abstract Background Overeating and inactivity are associated with type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and db/db/mice, a model representing this condition. Methods The study involved housing 8‐week‐old db/m and db/db mice for 8 weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next‐generation sequencing; cytokine arrays of serum; assessment of metabolites in skeletal muscle, stool, and serum; and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&Tag. Results Compared with db/m mice, db/db mice had 22.4% lower grip strength and approximately five times the visceral fat weight (P

Abstract Background Age‐related sarcopenia, characterized by reduced skeletal muscle mass and function, significantly affects the health of the elderly individuals. Oxidative stress plays a crucial role in the development of sarcopenia. Tripartite motif containing 16 (TRIM16) is implicated in orchestrating antioxidant responses to mitigate oxidative stress, yet its regulatory role in skeletal muscle remains unclear. This study aims to elucidate the impact of TRIM16 on enhancing antioxidant response through SIRT‐1, consequently mitigating age‐related oxidative stress, and ameliorating muscle atrophy. Methods Aged mouse models were established utilizing male mice at 18 months with D‐galactose (D‐gal, 200 mg/kg) intervention and at 24 months with natural aging, while 3‐month‐old young mice served as controls. Muscle cell senescence was induced in C2C12 myoblasts using 30 g/L D‐gal. TRIM16 was overexpressed in the skeletal muscle of aged mice and silenced/overexpressed in C2C12 myoblasts. The effects of TRIM16 on skeletal muscle mass, grip strength, morphological changes, myotube formation, myogenic differentiation, and muscle atrophy indicators were evaluated. Reactive oxygen species (ROS) levels and oxidative stress‐related parameters were measured. The SIRT‐1 inhibitor EX‐527 was employed to elucidate the protective role of TRIM16 mediated through SIRT‐1. Results Aged mice displayed significant reductions in lean mass (−11.58%; −14.47% vs. young, P

Abstract Background Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age‐related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. Methods We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. Results Thirty‐nine older individuals were non‐sarcopenic (NS), 31 pre‐sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross‐sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P

Abstract Skeletal muscle atrophy occurs in several pathological conditions. Among other reasons, high-dose or long-term administration of glucocorticoids increases circulating glucocorticoid levels and causes muscle atrophy. The purpose of this study was to investigate whether Lithospermum erythrorhizon and Lonicera japonica complex extract (LELJ) has a beneficial effect on dexamethasone (Dexa)-induced muscle atrophy. In Dexa-induced myotube atrophy, treatment with LELJ increased myotube diameter, decreased the expression of muscle atrophy markers, and increased the expression of myosin heavy chain (MHC) isoforms. Supplementation with LELJ improved muscle function and performance in mice with Dexa-induced muscle atrophy as demonstrated by grip strength and running tests. Additionally, it increased skeletal muscle mass, size, and expression of MHC isoforms and protein synthesis-related markers. Furthermore, it reduced the upregulated protein levels of skeletal muscle atrophy markers in Dexa-treated mice. Supplementation with LELJ reversed Dexa-induced translocation of the glucocorticoid receptor and forkhead box O3 from the cytosol to the nucleus in skeletal muscles. LELJ also ameliorated age-related muscle loss by extending lifespan and increasing locomotor capacity in Caenorhabditis elegans. We identified loganin and lithospermic acid as bioactive compounds of LELJ and found that treatment with these agents increased myotube diameter, MHC isoform, and puromycin protein levels, and decreased atrophy markers in Dexa-treated myotubes. The current findings underscore how LELJ can prevent Dexa-induced skeletal muscle atrophy, attributing the effects to loganin and lithospermic acid.

Abstract Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight‐week‐old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post‐surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin‐1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non‐ischaemic limbs of HLI mice by day 7 (7.3‐ and 2.3‐fold greater than Sham, respectively, P

BACKGROUND: Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus. Swimming may be a potential intervention for joint contracture due to the special physical properties of water. OBJECTIVE: To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into a blank control group (n=8) and a joint contracture group (n=16). After the surgical operation of knee joint contracture rat models, the joint contracture group was randomly subdivided into a surgical control group (n=8) and a swimming treatment group (n=8). Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks. At the 6th week after surgery, the body mass, knee joint range of motion, and quadriceps diameter were tested, and the diameter/body mass index was calculated. Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle, and Masson staining was used to observe fibrotic changes in the knee joint capsule. Furthermore, the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris. RESULTS AND CONCLUSION: Compared with the blank control group, the knee range of motion decreased in the surgical control and swimming treatment groups (P < 0.01), and knee extension deficit and arthrogenic extension deficit were significantly increased (P < 0.01), the diameter of the quadriceps muscle was decreased (P < 0.01), the joint capsule showed significant fibrosis, the quadriceps muscle was atrophied, and the diameter/body mass index was decreased (P < 0.01). Compared with the surgical control group, the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter (P < 0.01), and significant improvement in joint capsule fibrosis and quadriceps atrophy. Compared with the blank control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group (P < 0.01). Compared with the surgical control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group. Compared with the blank control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased (P < 0.05). Compared with the surgical control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased (P < 0.05). To conclude, early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats, decreases MuRF1 expression in the quadriceps muscle, and increases joint range of motion and quadriceps diameter, thereby inhibiting the development of joint contracture. [ABSTRACT FROM AUTHOR]

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-β-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-β-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.

Objective: Robotic thoracic surgery provides another minimally invasive approach in addition to video-assisted thoracoscopic surgery (VATS) that yields less pain and faster recovery compared with open surgery. However, robotic incisions are generally placed more inferiorly, which may increase the risk of intercostal nerve injury that affects the abdominal wall. We hypothesized that a robotic approach causes greater ipsilateral rectus muscle atrophy compared with open and VATS approaches. Methods: The cross-sectional area and density of bilateral rectus abdominis muscles were measured on computed tomography scans in patients who underwent lobectomy in 2018. The differences between the contralateral and ipsilateral muscles were compared between preoperative and 6-month surveillance scans. Changes were compared among the open, VATS, and robotic approaches through a mixed effects model after adjustments of correlation and covariates. Results: Of 99 lobectomies, 25 (25.3%) were open, 56 (56.6%) VATS, and 18 (18.1%) robotic. The difference between the contralateral and ipsilateral rectus muscle cross-sectional area was significantly larger at 6 months after robotic surgery compared with open (31.4% vs 9.5%, P = .049) and VATS (31.4% vs 14.1%, P = .021). There were no significant differences in the cross-sectional area between the open and VATS approach. Conclusions: In this retrospective analysis, there was greater ipsilateral rectus muscle atrophy associated with robotic thoracic surgery compared with open or VATS approaches. These findings should be correlated with clinical symptoms and followed to assess for resolution or persistence.

Abstract Background The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. The mechanisms that interconnect both processes at the transcriptional level remain underexplored. Nr2f6, a nuclear receptor, regulates metabolism and cell differentiation in peripheral tissues. However, its role in the skeletal muscle is still elusive. Here, we aimed to investigate the effects of Nr2f6 modulation on muscle biology in vivo and in vitro. Methods Global RNA‐seq was performed in Nr2f6 knockdown C2C12 myocytes (N = 4–5). Molecular and metabolic assays and proliferation experiments were performed using stable Nr2f6 knockdown and Nr2f6 overexpression C2C12 cell lines (N = 3–6). Nr2f6 content was evaluated in lipid overload models in vitro and in vivo (N = 3–6). In vivo experiments included Nr2f6 overexpression in mouse tibialis anterior muscle, followed by gene array transcriptomics and molecular assays (N = 4), ex vivo contractility experiments (N = 5), and histological analysis (N = 7). The conservation of Nr2f6 depletion effects was confirmed in primary skeletal muscle cells of humans and mice. Results Nr2f6 knockdown upregulated genes associated with muscle differentiation, metabolism, and contraction, while cell cycle‐related genes were downregulated. In human skeletal muscle cells, Nr2f6 knockdown significantly increased the expression of myosin heavy chain genes (two‐fold to three‐fold) and siRNA‐mediated depletion of Nr2f6 increased maximal C2C12 myocyte's lipid oxidative capacity by 75% and protected against lipid‐induced cell death. Nr2f6 content decreased by 40% in lipid‐overloaded myotubes and by 50% in the skeletal muscle of mice fed a high‐fat diet. Nr2f6 overexpression in mice resulted in an atrophic and hypoplastic state, characterized by a significant reduction in muscle mass (15%) and myofibre content (18%), followed by an impairment (50%) in force production. These functional phenotypes were accompanied by the establishment of an inflammation‐like molecular signature and a decrease in the expression of genes involved in muscle contractility and oxidative metabolism, which was associated with the repression of the uncoupling protein 3 (20%) and PGC‐1α (30%) promoters activity following Nr2f6 overexpression in vitro. Additionally, Nr2f6 regulated core components of the cell division machinery, effectively decoupling muscle cell proliferation from differentiation. Conclusions Our findings reveal a novel role for Nr2f6 as a molecular transducer that plays a crucial role in maintaining the balance between skeletal muscle contractile function and oxidative capacity. These results have significant implications for the development of potential therapeutic strategies for metabolic diseases and myopathies.

Abstract The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

Abstract Background The study aimed to determine the grade of retraction and atrophy according to the time elapsed in traumatic isolated full-thickness supraspinatus (SS) tears in young patients. Methods One thousand twenty-six patients, who underwent arthroscopic shoulder surgery, were retrospectively reviewed. Pre-operative magnetic resonance imaging (MRI) of 69 patients aged 18 to 40 years with isolated traumatic full-thickness SS lesions remaining after exclusion criteria were evaluated for tendon retraction and atrophy grades. SS retraction was determined from a T2-weighted oblique coronal MRI slice, and the atrophy grade was determined from the T1-weighted oblique sagittal MRI slice. The patients were divided into four groups 0–1 month, 1–3 months, 3–6 months, and 6–12 months according to the time between trauma and MRI. The relationship of tendon retraction and muscle atrophy with elapsed time was evaluated, in addition, comparisons between groups were made. Results Thirty-one (45%) of the patients were female and their mean age was 30 ± 7.3 (18–40) years. The mean age of men was 30.5 ± 6.9 (18–39) years (p = 0.880). The time between rupture and MRI was moderately correlated with retraction and strongly correlated with atrophy grades (r = 0.599, 0.751, respectively). It was observed that there was a statistically significant difference between the 1st (0–1 month) and 2nd (1–3 months) groups (p = 0.003, 0.001, respectively), and between the 2nd and 3rd (3–6 months) groups (p = 0.032, 0.002, respectively), but there was no significant difference between the 3rd and 4th (6–12 months) groups (p = 0.118, 0.057, respectively). In addition, there was a moderate correlation between tendon retraction and atrophy grades (r = 0.668). Power (1- b) in post hoc analysis was calculated as 0.826. Conclusions The current study, supported by arthroscopy, showed that there is a moderate and strong positive correlation between the time elapsed after trauma and the level of retraction and degree of atrophy in traumatic full-thickness SS tears, and demonstrated the importance of early surgical intervention in young patients.

Abstract Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta‐analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: −0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse‐induced muscle atrophy. Although the meta‐analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse‐induced decline in either outcome measurement. Additional high‐quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

Abstract Background Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine‐to‐inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post‐transcriptional modification of genome‐encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity‐associated NAFLD and sarcopenia remains unclear. Methods ADAR2+/+/GluR‐BR/R mice (wild type [WT]) and ADAR2−/−/GluR‐BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high‐fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross‐sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. Results ADAR2 KO mice fed with HFD exhibited lower body weight (−7.7%, P

Background: Physical inactivity and subsequent muscle atrophy are highly prevalent in neurocritical care and are recognized as key mechanisms underlying intensive care unit acquired weakness (ICUAW). The lack of quantifiable biomarkers for inactivity complicates the assessment of its relative importance compared to other conditions under the syndromic diagnosis of ICUAW. We hypothesize that active movement, as opposed to passive movement without active patient participation, can serve as a valid proxy for activity and may help predict muscle atrophy. To test this hypothesis, we utilized non-invasive, body-fixed accelerometers to compute measures of active movement and subsequently developed a machine learning model to predict muscle atrophy. Methods: This study was conducted as a single-center, prospective, observational cohort study as part of the MINCE registry (metabolism and nutrition in neurointensive care, DRKS-ID: DRKS00031472). Atrophy of rectus femoris muscle (RFM) relative to baseline (day 0) was evaluated at days 3, 7 and 10 after intensive care unit (ICU) admission and served as the dependent variable in a generalized linear mixed model with Least Absolute Shrinkage and Selection Operator regularization and nested-cross validation. Results: Out of 407 patients screened, 53 patients (age: 59.2 years (SD 15.9), 31 (58.5%) male) with a total of 91 available accelerometer datasets were enrolled. RFM thickness changed − 19.5% (SD 12.0) by day 10. Out of 12 demographic, clinical, nutritional and accelerometer-derived variables, baseline RFM muscle mass (beta − 5.1, 95% CI − 7.9 to − 3.8) and proportion of active movement (% activity) (beta 1.6, 95% CI 0.1 to 4.9) were selected as significant predictors of muscle atrophy. Including movement features into the prediction model substantially improved performance on an unseen test data set (including movement features: R2 = 79%; excluding movement features: R2 = 55%). Conclusion: Active movement, as measured with thigh-fixed accelerometers, is a key risk factor for muscle atrophy in neurocritical care patients. Quantifiable biomarkers reflecting the level of activity can support more precise phenotyping of ICUAW and may direct tailored interventions to support activity in the ICU. Studies addressing the external validity of these findings beyond the neurointensive care unit are warranted. Trial registration: DRKS00031472, retrospectively registered on 13.03.2023. [ABSTRACT FROM AUTHOR]

A growing body of research has provided evidence that de novo expression of connexin hemichannels and upregulation of pannexin hemichannels (Cx HCs and Panx HCs, respectively) in the cytoplasmic membrane of skeletal muscle (sarcolemma) are critical steps in the pathogenesis of muscle dysfunction of many genetic and acquired muscle diseases. This review provides an overview of the current understanding of the molecular mechanisms regulating the expression of Cx and Panx HCs in skeletal muscle, as well as their roles in both muscle physiology and pathologies. Additionally, it addresses existing gaps in knowledge and outlines future challenges in the field. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of extremely low-frequency electromagnetic fields (ELF-EMF) on myogenesis during the early stage of denervated muscle atrophy in Sprague-Dawley (SD) rats. Methods: a total of 36 female SD rats were fed in cages and divided into three groups: the normal control group, the muscle atrophy group and the 10Hz/1.5mT magnetic field group. The rats in the 10Hz/1.5mT magnetic field group received a magnetic field intervention for 2h per day. The posterior muscle groups of the lower limbs of rats were sampled on the first, second, third and fourth weeks for evaluating the underlying changes. The harvested tissues were stained with hematoxylin–eosin (HE) dye to observe the morphology of the muscle atrophy and to measure the muscle fiber cross-sectional area ratio. A reverse transcription polymerase chain reaction was used to detect the expression of Myf5 mRNA in each group. The myogenesis-related proteins in the harvested muscle tissue were detected by western blot assay. Results: (1) HE staining showed that with the extension of denervation time, the structural disorder of muscle fibers was aggravated, and in the second week of the denervated muscle atrophy, muscle fiber cross-sectional area tended to increase in the 10Hz/1.5mT magnetic field group. Overall muscle atrophy was inevitable. (2) Results of RT-PCR showed that the expression of Myf5 mRNA in the 10Hz/1.5mT magnetic field group was significantly high in the second week of denervation, and the difference was statistically significant compared with the muscle atrophy group (*p<0.05). (3) Western blot analysis showed that the expression of MYF5 proteins in the 10Hz/1.5mT magnetic field group was significantly higher than that in the muscle atrophy group (**p<0.01) in the second week of denervation. Further, the expression of MYOG protein in the 10Hz/1.5mT magnetic field group was significantly higher than that in the muscle atrophy group (****p<0.0001). Conclusions: 10Hz/1.5mT ELF-EMF can significantly promote myogenesis during early denervated muscle atrophy in SD rats. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the selective degeneration of upper and lower motor neurons, leading to progressive muscle weakness and atrophy. The mean survival time is two to five years. Although the hunt for drugs has greatly advanced over the past decade, no cure is available for ALS yet. The role of intense physical activity in the etiology of ALS has been debated for several decades without reaching a clear conclusion. The benefits of organized physical activity on fitness and mental health have been widely described. Indeed, by acting on specific mechanisms, physical activity can influence the physiology of several chronic conditions. It was shown to improve skeletal muscle metabolism and regeneration, neurogenesis, mitochondrial biogenesis, and antioxidant defense. Interestingly, all these pathways are involved in ALS pathology. This review will provide a broad overview of the effect of different exercise protocols on the onset and progression of ALS, both in humans and in animal models. Furthermore, we will discuss challenges and opportunities to exploit physiological responses of imposed exercise training for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)/silent information regulator 1 (Sirt-1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) mitochondrial biogenesis pathway and the Akt/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration. [ABSTRACT FROM AUTHOR]

Background: The traditional open midline posterior cervical spine fusion procedure has several shortcomings. It can cause soft tissue damage, muscle atrophy, compromise of the lateral masses and painful prominent posterior cervical instrumentation or spinous process if there is dehiscence of the fascia. Additionally, patients frequently experience the rapid development of adjacent segment disease, which can result in the reemergence of debilitating pain and functional impairment. Clinical relevance: Tissue-sparing posterior cervical fusion is an alternative method for treating patients with symptomatic cervical degenerative disc disease. However, widespread clinical adoption has been challenged by ambiguity, misunderstandings and misinterpretations regarding appropriate procedural reimbursement coding. Technological advancement: The tissue-sparing posterior cervical fusion procedure was approved by the US Food and Drug Administration (FDA) in 2018 (CORUS™ Spinal System and CAVUX® Facet Fixation System (CORUS/CAVUX); Providence™ Medical Technology). This technique addresses the concerns with traditional spine fusion methods by achieving the stability and outcomes of posterior cervical fusion without the morbidity associated with significant muscle stripping in the traditional approach. This technology uses specialized implants and instrumentation to perform all of the steps required to facilitate bone fusion and provide stability while minimizing tissue disruption. The technique involves extensive bone preparation for fusion and placement of specialized stabilization implants that span the facet joint, promoting natural bone growth and fusion while reducing the need for extensive exposure. This procedure provides an effective, less invasive solution for patients with cervical degenerative disc disease. Reimbursement and coding clarity: The article provides a comprehensive rationale for appropriate reimbursement coding for tissue-sparing posterior cervical fusion. This is a critical aspect for the adoption and accessibility of medical technologies. This information is crucial for practitioners and healthcare administrators, ensuring that innovative procedures are accurately coded and reimbursed. Procedural details and clinical evidence: By detailing the procedural steps, instruments used and the physiological basis for the procedure, this article serves as a valuable educational resource for spine surgeons and payers to appropriately code for this procedure. Conclusions: The description of work for CORUS/CAVUX is equivalent to the current surgical standard of lateral mass screw fixation with decortication and onlay posterior grafting to facilitate posterior fusion. Thus, it is recommended that CPT codes 22600/22840 be used, as they best reflect the surgical approach, instrumentation, decortication, posterior cervical fusion and bone grafting procedures. [ABSTRACT FROM AUTHOR]

The elimination of ground reaction force (support withdrawal) vastly affects slow postural muscles in terms of their regulation and structure. One of the effects of support withdrawal in this study was an immediate postural muscle inactivation, followed by the daily gradual development of spontaneous activity of the slow postural soleus muscle in response to rat hindlimb suspension to mimic space flight. The origin of this activity is somewhat akin to muscle spasticity after spinal cord injuries and is the result of KCC2 content decline in the spinal cord's motor neurons. However, the physiological consequences of unloading-induced spontaneous activity remain unexplored. We have conducted an experiment with the administration of a highly specific KCC2 activator during 7-day unloading. For this experiment, 32 male Wistar rats were divided into 4 groups: C+placebo, C+CLP-290 (100 mg/kg b w), 7HS+placebo, and 7HS+CLP—hindlimb-suspended group with CLP-290 administration (100 mg/kg b w). The soleus muscles of the animals were dissected and analyzed for several proteostasis- and metabolism-related parameters. CLP-290 administration to the unloaded animals led to the upregulation of AMPK downstream (p-ACC) and mTOR targets (p-p70S6k and p-4E-BP) and an enhanced PGC1alpha decrease vs. the 7HS group, but neither prevented nor enhanced atrophy of the soleus muscle or myofiber CSA. [ABSTRACT FROM AUTHOR]

Spontaneous resolution of a spinoglenoid notch ganglion cyst (SGC) without surgical treatment has been rarely reported; however, we have encountered this phenomenon occasionally. Therefore, we aimed to describe a case series of consecutive patients with SGC in whom it spontaneously resolved without surgical treatment. We retrospectively reviewed 12 patients with magnetic resonance imaging (MRI)-confirmed SGC in whom it resolved without surgical treatment between January 2011 and March 2023. We included patients without abnormally increased signal intensity or muscle atrophy due to denervation from suprascapular neuropathy on MRI. Resolution of the SGC was confirmed via MRI or ultrasound at the follow-up visit, and suprascapular neuropathy was assessed using electromyography and nerve conduction studies when needed. For functional assessments, the visual analog scale for pain and active range of motion of the shoulder were used to compare pre and postresolution follow-ups. Eleven men and 1 woman with a median age of 54.0 years (interquartile range [IQR] 37.0-65.3) were included in this study. The SGCs resolved spontaneously at a median of 13.2 months with an IQR of 8.2-23.0 after initial evaluation using MRI. The SGCs were multiloculated cysts with superior labrum anterior and posterior II-IX lesions, with a median diameter of 2.5 cm (IQR 2.0-2.8). The median visual analog scale for pain (pre-resolution 5.0 [IQR 4.0-7.0] vs postresolution 1.0 [IQR 0.0-1.0], P =.002) and internal rotation at the back (preresolution 8.0 [IQR 7.0-10.3] vs postresolution 7.5 [IQR 7.0-8.0], P =.034) were significantly improved after the resolution. Surgical treatment may not be necessary in all cases of SGC. Nonsurgical treatment may be a viable option in the absence of suprascapular nerve involvement or superior labrum anterior and posterior-related physical findings. [ABSTRACT FROM AUTHOR]

Background/Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is a commonly performed procedure in patients with liver cirrhosis to treat portal hypertension-related conditions, including variceal bleeding and refractory ascites. However, while the increased risk of hepatic encephalopathy (HE) after TIPS is important to consider when determining whether a patient is a good candidate for TIPS, currently there is no widely used method to predict the development of post-TIPS HE, although the model for end-stage liver disease (MELD) score is used to predict post-TIPS mortality. We conducted a systematic review and meta-analysis to evaluate sarcopenia as a risk factor for HE and mortality in patients undergoing TIPS. Methods: A comprehensive search strategy was used to identify reports of post-TIPS HE and mortality in sarcopenia vs. non-sarcopenia patients with liver cirrhosis who received TIPS in March 2023. Open Meta Analyst was used to compute the results. Results: Twelve studies with 2056 patients met inclusion criteria and were included in the final meta-analysis. Sarcopenia was associated with a significantly higher post-TIPS HE rate than non-sarcopenia (risk ratio [RR]: 1.68, 95% CI: 1.48–1.92, p < 0.00001, I2 = 65%), as well as a significantly higher post-TIPS mortality rate (RR: 1.73, 95% CI: 1.14–2.64, p < 0.00001, I2 = 87%). Conclusion: Patients with sarcopenia have a significantly increased risk of post-TIPS HE and mortality. Presence of sarcopenia should be considered when weighing the risks and benefits of performing TIPS in patients with cirrhosis. Further studies are needed to determine the clinical utility of important risk factors such as sarcopenia on post-TIPS outcomes. [ABSTRACT FROM AUTHOR]