Increased Grip Strength Research Articles

The role of gut microbiota on skeletal muscle strength in LDLR knockdown aging mice

To investigate the role of gut microbiota and bile acids metabolism on skeletal muscle strength in low density lipoprotein receptor (LDLR) knockdown aging mice. Forty-eight male C57BL/6J mice were employed in the experiment, twelve adult mice and twelve old mice were separately knocked down skeletal muscle LDLR (ALKd group, OLKd group). Other adult mice and old mice were injected with empty vectors as control (Acon group, Ocon group). After eight weeks of injection, each mouse was tested for skeletal muscle strength. The serum glycolipid biomarkers, the gut microbiota composition, the ileum apical sodium-dependent bile acid transporter (ASBT), farnesoid X receptor (FXR), fibroblast growth factor 15 (FGF15), and gastrocnemius fibroblast growth factor receptor 4 (FGFR4) were detected. When compared to the Ocon group, increased grip strength, and the relative abundance of Akkermansia and Ileibacterium were found in the OLKd group. The FGF15 protein of the ileum and FGFR4 protein of the gastrocnemius were found to increase in the OLKd group than those of the Ocon group. The gut microbiota and bile acid metabolism both play an important role in the partially improved skeletal muscle strength of LDLR knockdown aging mice.

Modified Five-item Frailty Index (mFI-5) versus Grip Strength as predictors of length of stay, discharge to home, and early surgical complications in patients undergoing long segment fusion.

Modified Five-item Frailty Index (mFI-5) versus Grip Strength as predictors of length of stay, discharge to home, and early surgical complications in patients undergoing long segment fusion.

On the repeatability of wrinkling topography patterns in the fingers of water immersed human skin.

On the repeatability of wrinkling topography patterns in the fingers of water immersed human skin.

Synergistic Effects of Riluzole and Sodium Butyrate on Barrier Function and Disease Progression of Amyotrophic Lateral Sclerosis Through the Gut-Neuron Axis.

Emerging evidence has shown that gut-brain barrier dysfunction occurs at the early stages of ALS. Previous studies demonstrated that sodium butyrate significantly prolonged the life span of ALS mice. Riluzole is the first FDA-approved drug for ALS treatment. We hypothesize that Riluzole and sodium butyrate combined treatment further decreases aggregation of the h-SOD1G93A, restores the gut-brain barrier function, and delays ALS progression. SOD1G93A mice (9-10-week-old) were treated with Riluzole (10 mg/kg, I.P. daily), sodium butyrate (2% in drinking water), or Riluzole and sodium butyrate combination for 6 weeks. The Riluzole/butyrate combination showed a significantly longer rotarod time, increased grip strength, and enhanced intestinal barrier, as compared with Riluzole or sodium butyrate-only treatment. More reduction of h-SOD1G93A aggregation was observed in the colon, spinal cord lumbar, and brain cortex with Riluzole and sodium butyrate combination, compared with Riluzole or sodium butyrate-only treatment. Tight junction proteins (ZO-1 and Claudin-5) significantly increased in the colon, spinal cord lumbar, and brain cortex of mice with Riluzole and sodium butyrate treatment. The Riluzole and sodium butyrate combination reduced serum lipopolysaccharides and h-SOD1G93A aggregation, and inflammatory cytokines more than those in Riluzole or sodium butyrate-only treatment. Overall, Riluzole and sodium butyrate treatment is more effective than either Riluzole or sodium butyrate-only in delaying ALS progress. It provides a potential therapeutic strategy and mechanism by restoring barrier function through the gut-brain axis for ALS.

Upregulation of FAM129B protects against glucocorticoid-induced skeletal muscle atrophy via regulating long non-coding RNA NEAT1.

Upregulation of FAM129B protects against glucocorticoid-induced skeletal muscle atrophy via regulating long non-coding RNA NEAT1.

Mechanism of Naoxintong Capsules in treatment of rats with multiple cerebral infarctions and myocardial injury based on HIF-1α/VEGF pathway

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.

Exploring the protective effect of metformin against sarcopenia: insights from cohort studies and genetics

BackgroundThe impact of metformin on sarcopenia remains uncertain. This study aimed to investigate whether metformin influences sarcopenia risk and evaluate the effects of potential drug targets on sarcopenia traits.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) (n = 3549) to assess the association between metformin use and sarcopenia risk in elderly patients with type 2 diabetes. Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) from UK Biobank (n = 1,366,167) and FinnGen (n = 218,007), with expression quantitative trait loci (eQTL) as instrumental variables, examined the causal effect of metformin-related targets on sarcopenia traits, while molecular docking explored the interaction between metformin and its drug targets.ResultsMetformin use was associated with increased grip strength (OR = 2.46; 95% CI 1.49–2.38) and skeletal muscle mass (OR = 1.24; 95% CI 0.20–2.28), as well as reduced mortality (HR = 0.62; 95% CI 0.54–0.71). MR analysis suggested a possible link between GDF15 gene expression and sarcopenia traits, with no evidence of genetic confounding. Molecular docking indicated stable binding between metformin and GDF15.ConclusionThis study suggests that metformin may lower sarcopenia risk, particularly in elderly patients with type 2 diabetes, with GDF15 identified as a promising target for sarcopenia treatment.

Ligandrol lowers endurance and negatively affects lipid and hormonal profile of male rats.

Selective androgen receptor modulators are currently not approved but are widely used in gyms. In the present study, the effects of ligandrol and its combination with endurance training on functional and clinically important parameters were studied in male healthy rats. Fourteen-week-old male rats were divided into four groups: two training (40min, 5 times/week) and two non-training (5min, 3 times/week). The velocity was 25m/min at a track elevation of 5° for all groups. Ligandrol (0.4mg/kg body weight, 5 times/week) was administered to one training and one non-training group and vehicle to the other groups (n = 10 per group) for 8weeks. We conducted functional tests and examined morphometric, functional, hematological, hormonal, and clinical chemistry indicators in rats and histological and gene expression analyses in gastrocnemius muscle. Endurance training had a positive effect on all functional tests and increased vascular endothelial growth factor a (Vegf-a) gene expression. Ligandrol treatment reduced submaximal endurance, maximal oxygen consumption, concentrations of glucose, follicle-stimulating hormone, and testosterone. It increased grip strength, triglycerides, and total cholesterol concentrations and had no effect on maximal sprinting speed, maximal time to exhaustion, hematological and morphometric parameters, and gene expression of myostatin and insulin-like growth factor 1. The negative effects of ligandrol treatment outweighed its benefits in this study. Endurance training alone had favorable effects, and its combination with ligandrol did not seem to have an advantage. In the training group, ligandrol decreased Vegf-a gene expression and the size of muscle fibers type I and IIa.

Impact of Oral Health Interventions on Sarcopenia and Frailty in Older Adults: A Systematic Review.

Background/Objectives: Frailty and sarcopenia are geriatric syndromes associated with increased vulnerability to adverse health outcomes, including functional decline, disability, and mortality. Emerging evidence suggests that oral health interventions may play a role in mitigating these conditions. This systematic review aims to evaluate the impact of oral health interventions on frailty and sarcopenia in older adults. Methods: A systematic search was conducted in PubMed, Scopus, and SciELO databases for studies published up to December 2023. Inclusion criteria comprised experimental and quasi-experimental studies assessing dental interventions and their effects on frailty and sarcopenia in individuals aged 60 years and older. The primary outcomes included frailty index, grip strength, walking speed, and functional dentition. Study quality was assessed using GRADEpro. Results: Eight studies were included. Preventive oral hygiene interventions improved oral health but did not significantly impact frailty scores. Oral exercises significantly improved muscle strength and weight, leading to frailty score reductions (-1.1 points, 95% CI: -1.5 to -0.7, p < 0.01). Swallowing therapies were linked to increased grip strength (+1.8 kg, p = 0.03) and walking speed (+0.2 m/s, p = 0.04), with corresponding frailty index reductions (-0.8 points, 95% CI: -1.2 to -0.4, p = 0.01). The certainty of evidence ranged from very low to moderate. Conclusions: Oral health interventions, particularly oral exercises and swallowing therapies, show potential in reducing frailty and sarcopenia-related outcomes in older adults. However, methodological heterogeneity and low-certainty evidence highlight the need for high-quality, large-scale trials with standardized assessment measures to establish definitive clinical recommendations.

Genetic evidence for the effects of glucokinase activation on frailty-related outcomes: A Mendelian randomisation study.

We aimed to use the Mendelian randomisation (MR) design to investigate the potential causal effects of glucokinase (GK) activation on frailty-related outcomes and to explore the potential mediating effects of metabolic and inflammatory biomarkers. Seventeen independent single-nucleotide polymorphisms (SNPs) located within the GCK gene and significantly correlated with the glycated haemoglobin (HbA1c) level were used as genetic proxies for the effect of GK activation. We employed two-sample MR analysis to assess the relationship between genetically proxied GK activation and multifactorial frailty-related outcomes (frailty index, grip strength, walking pace, appendicular lean mass [ALM] and telomere length) We also explored the potential mediating effects using two-step MR. Genetically proxied GK activation was significantly associated with a lower frailty index (beta: -0.161 per 1% decrease in HbA1c level due to GK activation, 95% confidence interval: -0.282 to -0.040, false discovery rate-adjusted p = 0.011). Additionally, GK activation showed significant associations with increased grip strength, higher ALM, faster walking pace and longer telomere length. GK activation also demonstrated a significant indirect effect on total grip strength and telomere length by reducing C-reactive protein levels (proportion of mediation: 6.79% to 8.21%). Our study provides genetic evidence supporting the causal effects of GK activation on lowering the risk of frailty. These findings suggest that GK activators (GKAs) may aid in the management of frailty and sarcopaenia in people with diabetes; however, future randomized controlled trials are necessary to validate these results and establish their clinical applicability.

Zinc Alleviates Diabetic Muscle Atrophy via Modulation of the SIRT1/FoxO1 Autophagy Pathway Through GPR39.

Muscle atrophy is a severe complication of diabetes, with autophagy playing a critical role in its progression. Zinc has been shown to alleviate hyperglycaemia and several diabetes-related complications, but its direct role in mediating diabetic muscle atrophy remains unclear. This study explores the potential role of zinc in the pathogenesis of diabetic muscle atrophy. In vivo, C57BL/6J mice were induced with diabetes by streptozotocin (STZ) and treated with ZnSO₄ (25 mg/kg/day) for six weeks. Gastrocnemius muscles were collected for histological analysis, including transmission electron microscopy (TEM). Serum zinc levels were measured by ICP-MS. Protein expression was evaluated using immunofluorescence (IF), immunohistochemistry (IHC) and Western blotting (WB). Bioinformatics analysis was used to identify key genes associated with muscle atrophy. Invitro, a high-glucose-induced diabetic C2C12 cell model was established and received ZnSO₄, rapamycin, SRT1720, TC-G-1008, or GPR39-CRISPR Cas9 intervention. Autophagy was observed by TEM, and protein expression was assessed by IF and WB. Intracellular zinc concentrations were measured using fluorescence resonance energy transfer (FRET). In vivo, muscle atrophy, autophagy activation, and upregulation of SIRT1 and FoxO1, along with downregulation of GPR39, were confirmed in the T1D group. ZnSO₄ protected against muscle atrophy and inhibited autophagy (T1D + ZnSO₄ vs. T1D, all p < 0.0001), as evidenced by increased grip strength (212.40 ± 11.08 vs. 163.90 ± 10.95 gf), gastrocnemius muscle index (10.67 ± 0.44 vs. 8.80 ± 0.72 mg/g), muscle fibre cross-sectional area (978.20 ± 144.00 vs. 580.20 ± 103.30 μm2), and serum zinc levels (0.2335 ± 0.0227 vs. 0.1561 ± 0.0123 mg/L). ZnSO₄ down-regulated the expression of Atrogin-1 and MuRF1, and decreased the formation of autophagosomes in the gastrocnemius muscle of T1D mice (all p < 0.0001). RNA-seq analysis indicated activation of the SIRT1/FoxO1 signalling pathway in diabetic mice. ZnSO₄ down-regulated LC3B, SIRT1 and FoxO1, while upregulating P62 and GPR39 (all p < 0.05). Invitro, muscle atrophy, autophagy activation, and down-regulation of GPR39 were confirmed in the diabetic cell model (all p < 0.05). Both ZnSO₄ and TC-G-1008 down-regulated Atrogin-1, LC3B, SIRT1, and FoxO1, and up-regulated P62 and GPR39, inhibiting autophagy and improving muscle atrophy (all p < 0.05). The beneficial anti-atrophic effects of ZnSO₄ are diminished following treatment with SRT1720 or RAPA. Upon GPR39 knockout, SIRT1, FoxO1, and Atrogin-1 were upregulated, while P62 was downregulated. Intracellular zinc concentrations in ZnSO₄-treated group remained unchanged (p > 0.05), indicating that zinc supplementation did not affect zinc ion entry but acted through the cell surface receptor GPR39. ZnSO4 inhibits excessive autophagy in skeletal muscle and alleviates muscle atrophy in diabetic mice via the GPR39-SIRT1/FoxO1 axis. These findings suggest that zinc supplementation may offer a potential therapeutic strategy for managing diabetic muscle atrophy.

Return to play and outcomes of surgically treated upper limb nerve entrapment in athletes: a systematic review.

Athletes face a higher risk of upper limb nerve entrapment due to repetitive stress, trauma, and biomechanics. Diagnosis is challenging, and delayed treatment can impair performance. When conservative care fails, surgery may be needed to restore function and enable return to play (RTP). This systematic review adhered to PRISMA guidelines and evaluated surgical outcomes, RTP rates, and complications in athletes with upper limb nerve entrapment. A comprehensive search was conducted using MeSH terms and keywords for surgical interventions, nerve entrapment syndromes, and sports. Eligible studies included case series, cohort studies, and comparative studies that reported postoperative outcomes in athletes. Data extraction included nerve involvement, surgical techniques, clinical outcomes, and RTP rates. Thirty-one studies, comprising 1,297 athletes across 23 sports, were included. The most common nerve entrapments involved the ulnar nerve (50.1%), brachial plexus (39.2%), and suprascapular nerve (9.5%). Surgical interventions included ulnar nerve decompression/transposition, first rib resection with scalenectomy for thoracic outlet syndrome (TOS), and suprascapular nerve decompression. RTP rates ranged from 62 to 100%, with an average of 87%. Suprascapular nerve decompression had the highest RTP success (100%), while TOS demonstrated greater variability (62.5-97%). Functional improvements included pain reduction, increased grip strength, and enhanced patient-reported outcomes. The overall complication rate was low, but TOS procedures had the highest reoperation rates (3.8-27%). Surgical treatment of upper limb nerve entrapment in athletes yields high RTP rates and functional recovery. Ulnar and suprascapular nerve decompressions show consistent success, while TOS surgery outcomes vary.

Berberine attenuates obesity-induced skeletal muscle atrophy via regulation of FUNDC1 in skeletal muscle of mice

Skeletal muscle atrophy is a complication of obesity, partially induced by impaired mitophagy. This study investigates whether Berberine(BBR) protects mice from obese skeletal muscle atrophy and the underlying molecular mechanism. Twenty C57BL/6 mice were fed a high-fat diet until they weighed more than 20% of the average body weight of the control group. The mice were then divided into two groups and gavaged with BBR or vehicle for 8 weeks. 10 mice were used as controls. Fasting blood glucose was measured, an oral glucose tolerance test was performed, and the mice were measured for grip strength and exercise capacity. H&E and Oil Red O staining were used to observe the pathological changes of skeletal muscle. MURF1, FBXO32, BAX, BCL2, P62, LC3 and mitophagy receptor FUNDC1 were observed in mice. BBR was intervened in C2C12 myotubes. The role of FUNDC1 was verified by RNA interference. We found that BBR treatment increased grip strength and improved muscle function. BBR not only reduced weight gain, excessive lipid accumulation and hyperlipidemia, but also ameliorated obesity-induced skeletal muscle atrophy and apoptosis. BBR promoted autophagy and increased FUNDC1 protein expression. The same positive effects were observed after BBR intervening on C2C12 myotubes, whereas FUNDC1 RNA interference attenuated the anti-skeletal muscle atrophy effect of BBR. These results suggest that BBR ameliorated obesity-induced skeletal muscle atrophy in mice by modulating the skeletal muscle mitophagy receptor FUNDC1, which may be a potential therapeutic target for obesity-induced skeletal muscle atrophy.

Keratocan Improves Muscle Wasting in Sarcopenia by Promoting Skeletal Muscle Development and Fast-Twitch Fibre Synthesis.

Osteosarcopenia refers to the co-occurrence of osteoporosis and sarcopenia, which are characterized by progressive bone density and muscle mass loss, respectively. Muscle and bone are regulated by many common genes and pathways, enabling potential co-treatment. Because keratocan protects against osteoporosis, we hypothesized it may also protect against sarcopenia, implying a new co-intervention target. This study aimed to elucidate the role and molecular mechanisms of keratocan in skeletal muscle. We analysed keratocan expression in the muscles of aged mice and patients with osteosarcopenia and during the differentiation of C2C12 myoblasts. The regulatory role of keratocan was assessed by knocking down or overexpressing keratocan in C2C12 cells and examining any effects on myogenic proliferation and differentiation. RNA sequencing analysis was also performed on these cells. The relationship between keratocan and enriched signalling pathways was verified using pathway inhibitors or agonists. Finally, adeno-associated virus-9 containing a muscle-specific promoter was injected into SAMP8 senile mice to observe the effects of keratocan overexpression. Keratocan expression was significantly lower in the skeletal muscles of aging mice (-2.02-fold, p < 0.01) and patients with osteosarcopenia (-1.78-fold, p < 0.001) compared with that in controls. Keratocan overexpression resulted in a significant increase in the proliferation indices CCND1 (+1.43-fold, p < 0.001), Ki67 (+2.30-fold, p < 0.001) and PCNA (+1.975-fold, p < 0.01) and the differentiation indices MyoD1 (+2.156-fold, p < 0.001), MyoG (+1.52-fold, p < 0.05) and myosin heavy chain (MyHC; +2.849-fold, p < 0.01); conversely, the muscle atrophy indices MuRF-1 (-30%, p < 0.01), atrogin-1 (-87%, p < 0.01) and myostatin (-24%, p < 0.01) were significantly decreased. PI3K/AKT/mTOR was identified as a potential pathway for keratocan regulation in C2C12 cells. PI3K inhibitor LY294002 reversed the promotion of myogenesis by keratocan overexpression, while PI3K activator 740Y-P reversed the inhibitory effect of keratocan knockdown on myogenesis, promoting myofibre development and ameliorating muscle atrophy in SAMP8 aging mice. This was evidenced by increased mean muscle cross-sectional area (+38%, p < 0.0001) and muscle mass (+7%, p < 0.01) and decreased fibrosis (-40%, p < 0.01). Furthermore, keratocan facilitated the conversion of slow-to-fast muscle fibres through the PI3K/AKT/mTOR pathway, characterized by significantly increased grip strength (+42%, p < 0.01) and maximum running speed (+19%, p < 0.001), and decreased fatigue time (+13%, p < 0.05). Keratocan ameliorates muscle atrophy by activating the PI3K/AKT/mTOR pathway, promoting muscle satellite cell proliferation and myogenic differentiation, and facilitating the conversion of slow-to-fast muscle fibres. Our findings demonstrate the potential of keratocan as a novel therapeutic target for osteosarcopenia.

Aptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function.

Muscle atrophy is associated with Type 2 diabetes mellitus, which reduces the quality of life and lacks effective treatment strategies. Previously, it was determined that human umbilical cord mesenchymal stromal cell (hucMSC)-derived exosomes (EXOs) ameliorate diabetes-induced muscle atrophy. However, the systemic application of EXOs is less selective for diseased tissues, which reduces their efficacy and safety associated with their nonspecific biological distribution invivo. Therefore, improving exosomal targeting is imperative. In this study, a skeletal muscle-specific aptamer (Apt) was used to explore the effects of Apt-functionalized EXOs derived from hucMSCs in diabetes-associated muscle atrophy and its specific mechanisms. Diabetic db/db mice and C2C12 myotubes were used to explore the effects of MSC-EXOs or Apt-EXOs in alleviating muscle atrophy. Grip strength, muscle weight and muscle fibre cross-sectional area (CSA) were used to evaluate skeletal muscle strength and muscle mass. Western blot analysis of muscle atrophy signalling, including MuRF1 and Atrogin 1 and the mitochondrial complex and Seahorse analysis were performed to investigate the underlying mechanisms of MSC-EXOs or Apt-EXOs on muscle atrophy. MSC-EXOs increased grip strength (p = 0.0002) and muscle mass (p = 0.0044 for tibialis anterior (TA) muscle, p = 0.002 for soleus (SO) muscle) in db/db mice. It also increased the CSA of muscle fibres (p = 0.0011 for all fibres, p = 0.0036 for slow muscle fibres and p = 0.0089 for fast muscle fibres) and the percentage of slow-to-fast muscle fibres (p = 0.0109). However, Atrogin 1 (p = 0.0455) and MuRF1 expression (p = 0.0168) was reduced. MSC-EXOs activated SIRT1/FoxO1/3a signalling and enhanced mitochondrial function in db/db mice and C2C12 myotubes. SIRT1 knockdown decreased the beneficial antiatrophic effects of MSC-EXOs. Additionally, Apt conjugation increased the effect of MSC-EXOs on muscle atrophy and myofiber-type transition (p = 0.0133 for grip strength, p = 0.0124 for TA muscle weight, p = 0.0008 for SO muscle weight, p < 0.0001 for CSA of all muscle fibres, p = 0.0198 for CSA of slow muscle fibres, p = 0.0213 for CSA of fast muscle fibres, p = 0.011 for percentage of slow-fast muscle fibres, p = 0.0141 for Atrogin 1 expression and p = 0.005 for MuRF1 expression). The results suggest that hucMSC-derived exosomes ameliorate diabetes-associated muscle atrophy by enhancing SIRT1/FoxO1/3a-mediated mitochondrial function and that Apt conjugation strengthens the effects of MSC-EXOs on muscle atrophy. These findings demonstrate the therapeutic potential of muscle-targeted MSC-EXOs for the treatment of muscle atrophy.

The Combined Effect of Multisensory Stimulation and Therapist Support on Physical and Mental Health of Older Adults Living in Nursing Homes: Pilot Randomized Controlled Trial.

Increasing life expectancy has led to a rise in nursing home admissions, a context in which older adults often experience chronic physical and mental health conditions, chronic pain, and reduced well-being. Nonpharmacological approaches are especially important for managing older adults' chronic pain, mental health conditions (such as anxiety and depression), and overall well-being, including sensory stimulation (SS) and therapist support (TS). However, the combined effects of SS and TS have not been investigated. This randomized controlled trial examines the specific and combined effects of brief SS and TS interventions on older adults' physical and mental health and pain intensity levels, among individuals living in nursing homes. A total of 96 patients aged 65-99 years from a nursing home were randomly assigned to 3 groups: SS, TS, and combined SS+TS interventions, each delivered as four 20-minute sessions. SS was implemented using a multisensory Snoezelen room. Pain intensity levels (per a Visual Analog Scale), blood pressure, heart rate, blood oxygen saturation, and hand grip strength (using a Jamar hand dynamometer) were measured before and after each of the 4 weekly therapeutic sessions. In addition, life satisfaction (per the Satisfaction with Life Scale) and anxiety (per the 7-item General Anxiety Disorder Scale) were evaluated before and after the whole intervention. Mixed model analyses tested the relative efficacy of the 3 interventions, applying simple slope analysis with Tukey correction. Study rationale and analytical plans were preregistered. The combined intervention of SS and TS (SS+TS) resulted in reduced pain levels compared with SS (B=0.209, P=.006) and TS alone (B=0.23, P=.002) over 4 sessions (F6,266=2.62; P=.017; R2=0.23). Further, the combined SS+TS intervention resulted in reduced systolic blood pressure versus SS (B=0.09, P=.01) and TS alone (B=0.016, P<.001) groups (F6,272=5.42; P<.001; R2=0.29). In addition, the combined SS+TS intervention resulted in an increased grip strength versus SS (B=-0.35, P=.003) and TS alone (B=-0.032, P=.008) groups (F6,273=2.25; P=.04; R2=0.19). Moreover, combined SS+TS resulted in an improvement in life satisfaction (B=-4.29, P<.0001) compared with SS (B=-2.38, P=.0042) and TS alone (B=-1.20, P=.13) groups (F2,39=3.47; P=.04). Finally, SS+TS demonstrated greater improvement in symptoms of general anxiety disorder (B=10.64, P<.0001) compared with SS (B=3.30 P=.01) and TS alone (B=1.13, P=.37) (F2,38=13.5; P<.001) groups. No differences between the interventions were shown for blood oxygen saturation (F6,273=2.06; P=.06), diastolic blood pressure (F6,272=1.12; P=.35), and heart rate (F6,273=1.33; P=.23). The combined intervention of SS and TS showed therapeutic benefits for pain management and physical and mental health of older adults living in nursing homes, relative to each therapeutic component in isolation. This brief intervention can be readily implemented to improve well-being and optimize therapeutic resources in nursing home settings. ClinicalTrials.gov NCT05394389; https://clinicaltrials.gov/ct2/show/NCT05394389.

Effects of Instrument-Assisted Soft Tissue Mobilization and Extracorporeal Shock Wave Therapy in Individuals With Lateral Elbow Pain: A Randomized Single-Blind Clinical Trial.

In lateral elbow pain (LEP), it is important to improve pain, grip strength, and function. The aim of this study is to compare the effects of Instrument-Assisted Soft Tissue Mobilization (IASTM) and extracorporeal shock wave therapy (ESWT) methods on pain, grip strength, and function in LEP. Randomized single-blind clinical trial. Forty-eight adults with LEP were randomly assigned to the IASTM, ESWT, and control groups. Home exercise consisting of special static stretching and eccentric strengthening exercises was given to the control group. The ESWT group received a total of 8 sessions of ESWT in addition to home exercise. The IASTM group received a total of 8 sessions of IASTM in addition to home exercise. The visual analog scale for pain, hydraulic hand dynamometer for grip strength, and Patient-Rated Tennis Elbow Evaluation scale for functionality were used for assessment. Data were collected at baseline, after intervention, and at 4-weeks postintervention. At the end of the treatment and the 4-week follow-up, a decrease in pain scores and improvement in muscle strength and functionality was detected in all 3 groups (P < .001). IASTM applications were more effective than ESWT and control groups in reducing pain both after application and at follow-up (P < .001), whereas ESWT application was also effective compared with the control group (P < .001). IASTM applications were more effective than the ESWT and control groups in reducing Patient-Rated Tennis Elbow Evaluation total scores both after the applications and follow-up (P < .001). IASTM was more effective in grip strength than ESWT and control groups (P < .001). It was determined that IASTM and ESWT treatments were effective in reducing pain and increasing grip strength and functionality in both the short and long term in patients with LEP. It was determined that IASTM treatment was superior to ESWT treatment in reducing pain and improving grip strength and functionality.

Quercetin attenuates cisplatin-induced fatigue through mechanisms associated with the regulation of the HPA axis and MCP-1 signaling.

Cancer-related fatigue (CRF) is a common symptom induced by chemotherapy. The main objective of the present study was to investigate whether quercetin regulates the hypothalamic-pituitary-adrenal (HPA) axis and chemoattractant protein-1 (MCP-1) signaling, two factors contributing to CRF in mice exposed to cisplatin. Male BALB/c mice were randomly assigned to the following five groups for 15 weeks: Control, CDDP, CDDP+TAK779 (an antagonist of MCP-1 receptor, human CC chemokine receptor R2 (CCR2)), CDDP+OQ (a diet containing 1% quercetin) and CDDP+IQ (quercetin given by ip, 10 mg/kg, 3 times/week). The results first showed that OQ and IQ significantly increased grip strength and locomotor activity, decreased plasma cortisol/corticosterone levels, and decreased the corticotropin releasing hormone (CRH) mRNA level in the brain tissues in mice exposed to CDDP. OQ and IQ also decreased CDDP-induced plasma levels of MCP-1 as well as the mRNA expression of MCP-1 and CCR2 in the brain stem. TAK779 significantly increased grip strength and tended to decrease the cortisol/corticosterone levels in CDDP-exposed mice, indicating the association between the HPA axis and MCP-1 signaling. Taken together, the study suggests that quercetin could attenuate CDDP-induced CRF through the mechanisms associated with downregulation of the HPA axis and MCP-1 signaling in mice.

Predicting grip strength-related frailty in middle-aged and older Chinese adults using interpretable machine learning models: a prospective cohort study.

Frailty is an emerging global health burden, and there is no consensus on the precise prediction of frailty. We aimed to explore the association between grip strength and frailty and interpret the optimal machine learning (ML) model using the SHapley Additive exPlanation (SHAP) to predict the risk of frailty. Data for the study were extracted from the China Health and Retirement Longitudinal Study (CHARLS) database. Socio-demographic, medical history, anthropometric, psychological, and sleep parameters were analyzed in this study. We used the least absolute shrinkage and selection operator (LASSO) regression to filter the model for the best predictor variables and constructed six ML models for predicting frailty. The feature performance of six ML models was compared based on the area under the receiver operating characteristic curve (AUROC) and the light gradient boosting machine (LightGBM) model was selected as the best predictive frailty model. We used SHAP to interpret the LightGBM model and to reveal the decision-making process by which the model predicts frailty. A total of 10,834 eligible participants were included in the study. Using the lowest quartile of grip strength as a reference, grip strength was negatively associated with the risk of frailty when grip strength was >29.00 kg for males or >19.00 kg for females (p < 0.001). The LightGBM model predicted frailty with optimal performance with an AUROC of 0.768 (95% CI 0.741 ~ 0.795). The SHAP summary plot showed that all features predicted frailty in order of importance, with cognitive function being considered the most important predictive feature. The poorer the cognitive function, nighttime sleep duration, body mass index (BMI), and grip strength, the higher the risk of frailty in middle-aged and older adults. The SHAP individual force plot clearly shows that the LightGBM model predicts frailty in the individual decision-making process. The grip strength-related LightGBM prediction model based on SHAP has high accuracy and robustness in predicting the risk of frailty. Increasing grip strength, cognitive function, nighttime sleep duration, and BMI reduce the risk of frailty and may provide strategies for individualized management of frailty.

A055: The Relationship Between Grip Strength and Quality of Life in the Elderly Based

Background: The World Health Organization (WHO) has launched the "Decade of Healthy Ageing" from 2021 to 2030 to address the challenges of a rapidly ageing global population. The extension of human lifespan is a manifestation of social progress, but aging and increased longevity may be accompanied by problems such as reduced physical and mental abilities and increased risk of diseases, which affects quality of life (QOL). Grip as an indicator of strength and is associated with physical activity in older adults. It is readily applicable in clinical and community settings, and there is an association between grip strength and health-related quality of life, but the evidence for the strength of the association is inconsistent. Currently, there is no consensus on the threshold value of grip strength in older adults. The purpose of this study was to study the dose-effect relationship between grip strength and quality of life in the elderly, and to explore modifiable factors affecting quality of life in the elderly, so as to provide effective theoretical basis for realizing healthy aging. Methods: A total of 105 elderly people over 60 years old were selected from 3 communities in Beijing. Grip strength was measured by hand-held grip-o-meter and quality of life was assessed by SF-36 scale. Based on controlling confounding factors, the dose-effect relationship between grip strength and quality of life was analyzed with the restricted cubic spline model. Result: The results showed that there was a dose-effect relationship between grip strength level and physiological content score (P &lt; 0.01). Increased grip strength levels helped improve quality of life in older adults; however, grip strength was not significantly associated with mental health (P &gt; 0.05). When grip strength was lower than 27.7 KG (50th percentile), with the increase of the grip strength level, the physiological content comprehensive score of the elderly increased faster. When the total physical activity was greater than 27.7 KG, the improvement of the comprehensive physiological content score of the elderly slowed down. Conclusion: The findings help to understand the relationship between quality of life and grip strength in older adults and provides a reference for formulating policies to promote healthy aging. The maintenance of grip strength above 27.7 KG may help delay the decline of quality of life in the elderly and can be used as a reference index to evaluate the physical health of the elderly.