Assessing skeletal muscle mass and lean body mass: an analysis of the agreement among dual X-ray absorptiometry, anthropometry, and bioelectrical impedance.

Introduction: Methods of body composition estimation such as dual-energy X-ray absorptiometry (DXA), anthropometry, and bioimpedance (BIA) are used for the estimation of skeletal muscle mass (SMM) and lean body mass (LBM). No previous studies have examined whether these methods generate comparable results, or whether they are valid by using DXA as the reference. The aims of the present investigation were: (a) to assess the differences between DXA, anthropometry, and BIA in the estimation of SMM and LBM, taking into consideration the impact of sex and hydration status; and (b) to examine the agreement of anthropometry and BIA as compared to DXA for the estimation of SMM and LBM. Methods: A descriptive cross-sectional design was followed with 262 healthy young adults (159 males and 103 females). LBM and SMM were assessed by anthropometry with the formulas from Lee et al. and Kulkarni et al. for LBM; and Kerr (opt a), Kerr (opt b), Lee et al., Poortmans, Matiegka, Martin et al., Drinkwater and Ross, and Heymsfield et al. for SMM; by BIA with the formula reported by the TANITA MC-780-MA software for LBM and SMM; and DXA with the formula reported by the Hologic Horizon software for LBM, and the conversion by Kim et al. for SMM. Results: Significant differences were found for both SMM and LBM in kg, and percentages between most methods and formulas for the overall sample (p < 0.001-0.003) and divided by sex (p < 0.001-0.035). Hydration status did not have a significant effect on the differences between methods and formulas (p = 0.058-0.870). Lin's coefficient revealed limited agreement among the majority of formulas and methods (CCC = 0.007-0.880). The Bland-Altman analysis showed significant differences in most methods and formulas, both in the overall sample and divided by sex, when using SMM and LBM with DXA as the reference (p < 0.001-0.030). Conclusion: There is a lack of agreement between methods and formulas for assessing SMM and LBM. Sex was found to be a significant factor in this analysis. Furthermore, significant differences were observed between most formulas and methods as compared to DXA, except for the equations to estimate SMM with anthropometry by Poortmans.

Changes in Skeletal Muscle Mass in the First 3 Months Following Gastrointestinal Cancer Surgery: A Prospective Study.

BACKGROUND: Surgical resection is the primary treatment for gastrointestinal (GI) cancers, but postoperative skeletal muscle loss (SML) is common and linked to poor prognosis. This study aims to identify patterns of muscle change, examine its association with quality of life (QoL), and explore predictors of SML in the first 3 months. PATIENTS AND METHODS: A prospective cohort study was conducted on patients newly diagnosed with GI cancer and undergoing surgery in China between September 2021 and May 2022. Skeletal muscle mass (SMM) and QoL were assessed at admission, 7 days, 1 month, and 3 months post-surgery. Demographic, clinical data, and biomarkers were collected. Missing data were imputed using multiple imputation. Data were analyzed using growth mixture modelling, bivariate analyses, and logistic regression. RESULTS: A total of 483 patients completed baseline assessment. Of the 242 patients with complete muscle assessments, 92% experienced SML. Three distinct patterns of muscle change were identified: 57% had normal preoperative SMM with mild postoperative SML, 16% had low preoperative SMM with moderate SML, and 27% had normal preoperative mass but severe postoperative SML. Moderate/severe SML was associated with more postoperative complications, poorer health, and higher symptom burden. Independent predictors included advanced age, preoperative sarcopenia, advanced cancer stage, and low prognostic nutrition index (PNI ≤ 45). The results did not change when using imputed values. CONCLUSIONS: Although SML is prevalent, patterns of muscle change are heterogeneous among patients. Advanced age, preoperative sarcopenia, advanced cancer stage, and cancer-related inflammation are predictors for moderate/severe SML, highlighting the need for early detection and management.

Regulatory role of N6-Methyladenosine on skeletal muscle development in Hu sheep.

N6-Methyladenosine (m6A) RNA modification plays an essential role in many biological processes. To investigate the regulatory role of m6A on the skeletal muscle development in Hu sheep, this study took newborn Hu sheep (b_B Group) and six-month-old Hu sheep (s_B Group) as the objects. MeRIP-seq and RNA-Seq analysis techniques were used to detect differentially methylated genes (DMGs) and differentially expressed genes (DEGs) in the longissimus dorsi muscle of Hu sheep at different months of age. Then, conjoint analysis was further employed to screen for key genes involved in skeletal muscle development that are modified by m6A and expressed by mRNA. According to the results of the MeRIP-seq analysis, there were 285 m6A differentially methylated peaks (DMPs) in total between b_B Group and s_B Group, with 192 significant upregulated peaks and 93 significant downregulated peaks. GO and KEGG analysis revealed that DMGs are mainly enriched in actin-binding, cellular transport, and metabolic pathways. According to the results of the RNA-seq analysis, there were 4,349 DEGs in total between b_B Group and s_B Group, with 2010 upregulated genes and 2,339 downregulated genes. DEGs are found to be mainly enriched in the regulation of actin cytoskeleton tissue, AMPK and FoxO signaling pathways, etc. The conjoint analysis demonstrated that 283 genes were both modified by m6A and expressed by mRNA. Among them, three genes relevant to muscle growth (RGMB, MAPK8IP3, and RSPO3) were selected as candidates for quantitative validation, and the results were in line with the sequencing results. The results mentioned above all suggest that m6A plays a certain role in the skeletal muscle development in Hu sheep.

Matrisome proteomics reveals novel mediators of muscle remodeling with aerobic exercise training.

Skeletal muscle has a unique ability to remodel in response to stimuli such as contraction and aerobic exercise training. Phenotypic changes in muscle that occur with training such as a switch to a more oxidative fiber type, and increased capillary density contribute to the well-known health benefits of aerobic exercise. The muscle matrisome likely plays an important role in muscle remodeling with exercise. However, due to technical limitations in studying muscle ECM proteins, which are highly insoluble, little is known about the muscle matrisome and how it contributes to muscle remodeling. Here, we utilized two-fraction methodology to extract muscle proteins, combined with multiplexed tandem mass tag proteomic technology to identify 161 unique ECM proteins in mouse skeletal muscle. In addition, we demonstrate that aerobic exercise training induces remodeling of a significant proportion of the muscle matrisome. We performed follow-up experiments to validate exercise-regulated ECM targets in a separate cohort of mice using Western blotting and immunofluorescence imaging. Our data demonstrate that changes in several key ECM targets are strongly associated with muscle remodeling processes such as increased capillary density in mice. We also identify LOXL1 as a novel muscle ECM target associated with aerobic capacity in humans. In addition, publically available data and databases were used for in silico modeling to determine the likely cellular sources of exercise-induced ECM remodeling targets and identify ECM interaction networks. This work greatly enhances our understanding of ECM content and function in skeletal muscle and demonstrates an important role for ECM remodeling in the adaptive response to exercise. The raw MS data have been deposited to the ProteomeXchange with identifier PXD053003.

Digoxin and exercise effects on skeletal muscle Na+,K+-ATPase isoform gene expression in healthy humans.

In muscle, digoxin inhibits Na+,K+-ATPase (NKA) whereas acute exercise can increase NKA gene expression, consistent with training-induced increased NKA content. We investigated whether oral digoxin increased NKA isoform mRNA expression (qPCR) in muscle at rest, during and post-exercise in 10 healthy adults, who received digoxin (DIG, 0.25 mg per day) or placebo (CON) for 14 days, in a randomised, double-blind and cross-over design. Muscle was biopsied at rest, after cycling 20 min (10 min each at 33%, then 67% V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{peak}}}}$ ), then to fatigue at 90% V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{peak}}}}$ and 3 h post-exercise. No differences were found between DIG and CON for NKA α1-3 or ß1-3 isoform mRNA. Both α1 (354%, P = 0.001) and ß3 mRNA (P = 0.008) were increased 3 h post-exercise, with α2 and ß1-2 mRNA unchanged, whilst α3 mRNA declined at fatigue (-43%, P = 0.045). In resting muscle, total ß mRNA (∑(ß1+ß2+ß3)) increased in DIG (60%, P = 0.025) and also when transcripts for each isoform were normalised to CON then either summed (P = 0.030) or pooled (n = 30, P = 0.034). In contrast, total α mRNA (∑(α1+α2+α3), P = 0.348), normalised then summed (P = 0.332), or pooled transcripts (n = 30, P = 0.717) did not differ with DIG. At rest, NKA α1-2 and ß1-2 protein abundances were unchanged by DIG. Post-exercise, α1 and ß1-2 proteins were unchanged, but α2 declined at 3 h (19%, P = 0.020). In conclusion, digoxin did not modify gene expression of individual NKA isoforms at rest or with exercise, indicating NKA gene expression was maintained consistent with protein abundances. However, elevated resting muscle total ß mRNA with digoxin suggests a possible underlying ß gene-stimulatory effect. HIGHLIGHTS: What is the central question of this study? Na+,K+-ATPase (NKA) in muscle is important for Na+/K+ homeostasis. We investigated whether the NKA-inhibitor digoxin stimulates increased NKA gene expression in muscle and exacerbates NKA gene responses to exercise in healthy adults. What is the main finding and its importance? Digoxin did not modify exercise effects on muscle NKA α1-3 and ß1-3 gene transcripts, which comprised increased post-exercise α1 and ß3 mRNA and reduced α3 mRNA during exercise. However, in resting muscle, digoxin increased NKA total ß isoform mRNA expression. Despite inhibitory-digoxin or acute exercise stressors, NKA gene regulation in muscle is consistent with the maintenance of NKA protein contents.

Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments.

Sarcopenic obesity (SO) is a metabolic disorder with increasing prevalence. It is characterized by a reduction in skeletal muscle mass and strength. Resveratrol (RSV) is one of the most frequently used herbs in the treatment of skeletal muscle atrophy. However, the precise mechanism of the action of RSV in SO remains unclear. The objective of this study was to examine the pharmacological mechanism of RSV in the context of SO through the lens of network pharmacology, to validate these findings through in vivo experimentation. A list of potential RSV targets was compiled by retrieving the data from multiple databases. This list was then cross-referenced with a list of potential targets related to SO. The intersections of RSV- and SO-related targets were analyzed using Venn diagrams. To identify the core genes, a protein-protein interaction (PPI) network of the intersection targets was constructed and subsequently analyzed. Molecular docking was used to predict RSV binding to its core targets. A high-fat diet was used to induce SO in mice. These findings indicated that RSV may prevent SO by acting on 11 targets. Among these, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are considered core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the anti-SO effect of RSV was predominantly linked to metabolic disease-related pathways, including those associated with nonalcoholic fatty liver disease. The anti-inflammatory effects of RSV were confirmed in vivo in an SO mouse model. This study contributes to a more comprehensive understanding of the key mechanisms of the action of RSV against SO and provides new possibilities for drug development in the pathological process of SO.

Effect of Perioperative Physical Activity on Skeletal Muscle Loss 6 Months After Esophageal Cancer Surgery.

Background/Aim: Sarcopenia contributes to a poor prognosis in patients with esophageal cancer; thus, any clinical support that prevents loss of skeletal muscle mass preoperatively and postoperatively should be actively investigated. This study aimed to evaluate physical activity during the perioperative period and its impact on postoperative skeletal muscle mass. Patients and Methods: Sixty-two patients who underwent esophagostomy at the Hamamatsu University School of Medicine between 2019 and 2023 were evaluated. The physical activity (measured by the step count) of patients scheduled for esophagectomy was assessed preoperatively using a fitness tracker. The percentage change in skeletal muscle mass index (SMI) was calculated preoperatively and 6 months postoperatively. Factors associated with decreased SMI 6 months after esophagectomy were analyzed using multivariate analysis. Results: The median decrease in SMI was -6.2%. Multivariate analysis revealed that factors associated with the reduction of SMI were age >69 years [odds ratio (OR)=7.21, 95% confidence interval (CI)=1.36-38.19, p=0.020], preoperative step count <7,800 steps/day (OR=5.17, 95% CI=1.38-19.33, p=0.015), and postoperative step count <2,400 steps/day (OR=3.55, 95% CI=1.01-12.45, p=0.048). Conclusion: A low perioperative step count and older age were significant risk factors for skeletal muscle loss in patients with esophageal cancer undergoing surgery. For patients with a low number of steps in the perioperative period or for older patients, interventions to increase the number of steps may prevent skeletal muscle loss.

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00-1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: -0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Transcriptional and morphological responses following distinct muscle contraction protocols for Snell dwarf (Pit1dw/dw) mice.

The Snell dwarf mouse (Pit1dw/dw), an animal model of congenital combined pituitary hormone deficiency, displays skeletal muscle weakness. While enhanced responsivity to repeated exposures of muscle contractions have been documented for Snell dwarf mice, the response following single exposure to distinct contraction protocols remained uncharacterized. The purpose of this study was to investigate the muscle recovery of Snell dwarf and control littermate mice following a single exposure to two separate protocols-an intermittent slow velocity (30°/s) contraction protocol or a continuous rapid velocity (500°/s) contraction protocol. Following both protocols for control mice, torque values were 30% and 80% of pre-protocol values at 5 min and 3 days, respectively. At 10 days, performance returned to baseline for the 30°/s protocol and were depressed for the 500°/s protocol. For Snell dwarf mice following both protocols, torques were depressed to 5% of pre-protocol values at 5 min and returned to baseline by 3 days. Recovery following the 30°/s protocol for control mice and both protocols for Snell dwarf mice coincided with increased transcriptional output, upregulation of cytokine-mediated signaling genes, and a distribution shift to smaller muscle fibers with reduced area per nucleus. These features represent efficacious remodeling ubiquitous across distinct contraction paradigms in the context of the Pit1 mutation.

Role of mesenchymal stem cells in sepsis and their therapeutic potential in sepsis­associated myopathy (Review).

Sepsis­induced myopathy (SIM) is one of the leading causes of death in critically ill patients. SIM mainly involves the respiratory and skeletal muscles of patients, resulting in an increased risk of lung infection, aggravated respiratory failure, and prolonged mechanical ventilation and hospital stay. SIM is also an independent risk factor associated with increased mortality in critically ill patients. At present, no effective treatment for SIM has yet been established. However, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach and have been utilized in the treatment of various clinical conditions. A significant body of basic and clinical research supports the efficacy of MSCs in managing sepsis and muscle­related diseases. This literature review aims to explore the relationship between MSCs and sepsis, as well as their impact on skeletal muscle­associated diseases. Additionally, the present review discusses the potential mechanisms and therapeutic benefits of MSCs in the context of SIM.

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

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

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

BACKGROUND: Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD. METHODS: In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted. RESULTS: Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P = 0.0026) and gastrocnemius (+18%, ****P < 0.0001) as well as enhanced collagen deposition (+20%, **P = 0.0064 in the tibialis anterior; +35%, **P = 0.0042 in the gastrocnemius) in the exercised A17 OPMD mice. In the supraphysiological resistance overload protocol, we also observed an increased collagen deposition (×2, ****P < 0.0001) in the plantaris muscle of A17 OPMD mice which was associated with larger muscle mass (×2, ****P < 0.0001) and fibre cross sectional area (×2, ***P = 0.0007) and increased absolute maximal force (×2, ****P < 0.0001) as well as a reduction in PABPN1 aggregate number (-16%, ****P < 0.0001). CONCLUSIONS: Running exercise and mechanical overload led to very different outcome in skeletal muscles of A17 mice. Both types of exercise enhanced collagen deposition but while the running protocol increased aggregates, the OVL reduced them. More importantly OVL reversed muscle atrophy and maximal force in the A17 mice. Our study performed in a relevant model gives an indication of the effect of different types of exercise on OPMD muscle which should be further evaluated in humans for future recommendations as a part of the lifestyle of individuals with OPMD.

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

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

Association between skeletal muscle mass and treatment response in patients with diffuse large B-cell lymphoma.

Previous studies have demonstrated that a low skeletal muscle mass (SMM) is an adverse factor for overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). However, its association with the treatment response has not been extensively investigated. This study aimed to determine the association between low skeletal muscle mass (SMM) and treatment response in DLBCL patients. We conducted a retrospective cohort study of 123 patients with DLBCL, in whom SMM was assessed using computed tomography before chemotherapy administration. The demographic characteristics of the patients with low SMM and those with normal SMM were not statistically different. However, there were notable differences in weight and BMI; patients with low SMM had a lower mean weight (59.2 vs 63, p = 0.002) and a higher proportion of patients with normal BMI (61.5% vs. 21.1%, p < 0.001). In addition, patients with low SMM were more likely to receive R-CHOP-like treatment (21.2% vs. 7%, p = 0.022) and experienced more delays in administration (42.9% vs. 33.3%, p = 0.452). Low SMM was not associated with failure to achieve CR (HR 1.9; 95% CI [0.9-4.1] p = 0.84), but it was reported to risk OS in univariate analysis (HR 2.1; 95% CI [1.03-4.2], p = 0.041). An interesting result was the interaction of low SMM with hypertension as a risk factor for not achieving CR (HR 2.7; 95% CI [1.1-6.5] p = 0.034) or OS (HR 7.9; 95% CI [3.4-18.8] p < 0.001). Low SMM was not a risk factor for achieving CR in patients with DLBCL and seemed to play a role in OS.

A comprehensive single-cell RNA transcriptomic analysis identifies a unique SPP1+ macrophages subgroup in aging skeletal muscle.

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging.

Gut matters in microgravity: potential link of gut microbiota and its metabolites to cardiovascular and musculoskeletal well-being.

The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth.