Muscle Growth Research Articles

Comparative transcriptome analyses of cardiac tissue reveals differential gene expression profiles in sheep in response to altitudinal adaptation

The present study aims to elucidate the transcriptomic changes occurring in the cardiac tissue of sheep breeds acclimated to highland versus lowland regions in India. The Changthangi sheep thrives in cold arid highlands of Ladakh in contrast to the Muzzafarnagri sheep which is native to the sub-tropical plains characterized by sweltering heat and high humidity. Four biological replicates of heart tissue from each breed were used to generate the RNA sequencing data. Both breeds exhibited high expression of genes related to crucial cardiac functions such as muscle contraction, hypertrophy and calcium ion homeostasis. Differential gene expression analysis identified distinct expression profiles associated with altitudinal adaptation, with enrichment of apoptotic signals in Changthangi and glycosaminoglycan metabolism in Muzzafarnagri sheep. Gene co-expression network highlighted the significance of apoptosis and EGFR pathway that may orchestrate adaptive responses to low oxygen levels in Changthangi sheep found in high altitude. The nodal genes identified in Muzzafarnagri sheep play essential roles in stress responses and MAPK signaling pathways, pivotal for cellular adaptation and survival under adverse conditions. The key genes identified within our study present compelling candidates for future studies in altitudinal adaptation in ovines. This comprehensive analysis provides valuable insights into the genetic basis of cardiac adaptation to altitude in sheep, shedding light on the molecular pathways involved in physiological adjustments to high-altitude environments.

Skeletal muscle hypertrophy: cell growth is cell growth.

Roberts et al. have provided an insightful counterpoint to our review article on the utility of the synergist ablation model. The purpose of this review is to provide some further dialogue regarding the strengths and weaknesses of the synergist ablation model. Specifically, we highlight that the robustness of the model overshadows surgical limitations. We also compare the transcriptomic responses to synergist ablation in mice and resistance exercise in humans to identify common pathways. We conclude that "cell growth is cell growth" and that the mechanisms available to cells to accumulate biomass and increase in size are similar across cell types and independent of the rate of growth.

Dynamic alternations of three-dimensional chromatin architecture contribute to phenotypic characteristics of breast muscle in chicken

Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens.

Correlation of Gestational Age with Anterior-Posterior Thigh Diameter Measured by Two-Dimensional Sonography

Background: Anterior-posterior thigh diameter measurement via two-dimensional sonography (2D-US) correlates with fetal gestational age and reflects the growth and development of fetal thigh muscles and bones. This measurement, alongside estimated gestational age, offers valuable insights into fetal well-being and growth during pregnancy. This study aimed to evaluate the correlation of gestational age with anterior-posterior thigh diameter measured by two-dimensional sonography and estimated gestational age. Methods: This cross-sectional study was conducted at the Department of Radiology and Imaging, Mymensingh Medical College & Hospital, Mymensingh, Bangladesh from January 2010 to January 2012. As the study subjects, a total of 250 healthy women between the 24th and 38th weeks of normal pregnancy were enrolled by using a purposive sampling technique. For data analysis, SPSS version 23.0 was used. Results: The mean age of the participants was 24.79 ± 4.71 years with a range from 18 to 35 years. More than one-third (34.0%) of the women were in the age range of 21-25 years. The mean gestational age of all participants was 30.93 ± 4.32 weeks. Primigravida accounted for more than half (56.4%) of them. A statistically significant positive correlation was observed between fetal anterior-posterior thigh diameter and gestational age (p<0.001. Conclusion: There is a statistically significant positive correlation between fetal anterior-posterior thigh diameter and gestational age.

Are calves trainable? Low-intensity calf muscle training with or without blood flow restriction: a randomized controlled trial

Abstract Objectives Whether low-load resistance training (RT) without muscle failure, with or without blood flow restriction (BFR), is sufficient to increase strength and muscle growth of calf muscles in trained individuals is still unclear. This study aimed to compare the effects of low-intensity BFR RT vs. traditional low-intensity RT (noBFR) with moderate training volume on strength and circumference. Methods We designed a parallel, randomized controlled trial including 36 RT-trained participants (BFR: 7 females, 32.9 ± 8.8 years, 11 males, 28.4 ± 3.6 years; noBFR; 8 females, 29.6 ± 3.4 years; 10 males, 28.6 ± 4.9 years) who underwent eight weeks of twice-weekly low-load RT with 16 weekly RT sets (30 % of one-repetition maximum [1RM]). RT consisted of bilateral calf raises and seated unilateral calf raises, each conducted with 4 sets (30, 15, 15, 15 repetitions not to failure) of either BFR or noBFR. Outcome measures included calf circumference (CC), leg stiffness (LS), and various strength tests (seated and standing calf raise 1RM, isokinetic strength of plantar- and dorsiflexion). Results There were no significant interactions or group effects for most measures. Both groups showed significant improvements in seated calf raise strength (p=0.046, η 2 p=0.17). Pairwise comparisons indicated moderate to large effect sizes for strength improvements (standardized mean differences: 0.35–1.11), but no changes in calf circumference were observed in either group. Conclusions Low-load RT with and without BFR are useful to increase strength without necessarily affecting hypertrophy. Low-intensity BFR training did not confer additional benefits over traditional low-intensity RT for calf muscle strength or circumference, questioning its general advantage under such conditions.

Fatty liver as a risk factor for cardiovascular diseases: retrospective analysis of data from patients of the Geriatrics Clinic of University Clinical Hospital in Wrocław

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disorder affecting about 25% of the global population. The causes of its development include poor diet, low physical activity, overweight, obesity, older age, diabetes, and lipid disorders. Non-alcoholic fatty liver disease is identified by some researchers as a hepatic manifestation of metabolic syndrome. It has been observed that patients with NAFLD have an increased risk of cardiovascular events, as well as a higher number of deaths from myocardial infarction compared to the general population. A retrospective analysis was conducted on the data of 237 patients diagnosed with hepatic steatosis, treated in the Department of Geriatrics at the University Clinical Hospital in Wrocław from 2019 to 2022, focusing on coexisting overweight, obesity, and concomitant diseases. Laboratory results and the degree of left ventricular muscle hypertrophy were analyzed. Parameters assessed by echocardiography, including interventricular septal thickness in diastole (IVSd), left ventricular posterior wall thickness in diastole (LVPWd), and IVSd + LVPWd/2, were used to evaluate left ventricular hypertrophy. Data from 237 patients were analyzed: 79 men (age: 77.2±7.1 years) and 158 women (age: 78.4±7.7 years). Body mass index (BMI) values for men and women were 30.5±5.0 kg/m² and 31.9±5.6 kg/m², respectively. There was a positive correlation between BMI and the degree of left ventricular hypertrophy for the parameters IVSd (ρ = 0.36, p < 0.001), LVPWd (ρ = 0.36, p < 0.001), and IVSd + LVPWd/2 (ρ = 0.38, p < 0.001). The study demonstrated a moderate positive correlation between BMI and the degree of left ventricular hypertrophy in patients diagnosed with hepatic steatosis. These findings indicate the necessity of actively searching for cardiovascular risk factors, including the evaluation of echocardiographic parameters in patients with NAFLD. Med Pr Work Health Saf. 2024;75(3):223-231.

Structural changes and contractility in muscle assessed by magnetic resonance imaging in individuals with ryanodine receptor 1-related rhabdomyolysis or myalgia.

Ryanodine receptor 1 (RYR1)-related myopathies associated with variants in the RYR1 gene present with a wide range of symptoms and severity. Two of the milder phenotypes associated with dominant pathogenic variants in RYR1 are rhabdomyolysis and myalgia. Only a few studies have investigated the muscle function and structure of individuals with RYR1-related rhabdomyolysis/myalgia objectively, showing inconsistent results. This study aimed to describe structural changes and contractility of muscles in individuals with RYR1-related rhabdomyolysis/myalgia. We investigated 15 individuals with dominant variants in the RYR1-gene and compared them with 15 age-, sex-, and body mass index (BMI)-matched controls using MRI, stationary isokinetic dynamometry, and comprehensive clinical evaluation. No significant differences were found between individuals with RYR1-related rhabdomyolysis/myalgia and healthy controls in peak torque, fat fraction, cross-sectional area, contractile cross-sectional area, or contractility (p > .05) in muscles of the lower back (MRI data only), thigh, or calf. On clinical examination, three individuals exhibited weakness in hip or back extension on the Medical Research Council (MRC) test and eight had muscle hypertrophy. Individuals with weakness were not hypertrophic. Most individuals with RYR1-related rhabdomyolysis/myalgia have close to normal strength, and normal fat fraction and contractility of muscles, and therefore constitute a mild phenotype of RYR1-related myopathies.

Dynamic phenotypic shifts and M2 receptor downregulation in bladder smooth muscle cells induced by mirabegron.

Mirabegron is available for treatment of overactive bladder (OAB). However, mechanisms underlying symptom improvements and long-term effects on bladder smooth muscle cells are uncertain. Contractility and growth of bladder smooth muscle contribute to OAB, and depend on smooth muscle phenotypes, and on muscarinic receptor expression. Here, we examined prolonged exposure to mirabegron (20-48h) on phenotype markers, muscarinic receptor expression, and phenotype-dependent functions in human bladder smooth muscle cells (hBSMC). Expression of markers for contractile (calponin, MYH11) and proliferative (MYH10, vimentin) phenotypes, proliferation (Ki-67), and of muscarinic receptors were assessed by RT-PCR. Proliferation, viability, actin organization and contractions in cultured hBSMC were examined by EdU, CCK-8, phalloidin staining and matrix contraction assays. Calponin-1 mRNA decreased with 100nM and 150nM mirabegron applied for 20h (0.56-0.6 fold of controls). Decreases were resistant to the β3-AR antagonist L-748,337 (0.34-0.55 fold, 100-150nM, 20h). After 40h, decreases occured in the presence of L-748,337, but not without L-748,337. MYH11 mRNA increased with 150nM mirabegron (40h, 1.9 fold). This was partly preserved with L-748,337, but not observed after 20h mirabegron exposure. Vimentin mRNA reduced with 150nM mirabegron after 20h, but not after 40h, with and without L-748,337 (0.71-0.63 fold). MYH10 mRNA expression remained unaffected by mirabegron. Exposure to 150nM mirabegron increased Ki-67 mRNA after 20h in the presence of, but not without L-748,337, and after 40h without, but not with L-748,337. Proliferation rates and actin organization were stable with 50-150nM mirabegron (24h, 48h). Viability increased significantly after mirabegron exposure for 20h, and by trend after 40h, which was fully sensitive to L-748,337. M2 mRNA was reduced by 20h mirabegron, which was resistant to L-748,337. Carbachol (3µM) enhanced time-dependent contractions of hBSMC, which was inhibited by mirabegron (150nM) in late phases (24h), but not in early phases of contractions. Conclusion: Mirabegron induces dynamic phenotype alterations and M2 downregulation in hBSMC, which is paralleled by time-shifted anticontractile effects. Phenotype transitions may be involved in improvements of storage symptoms in OAB by mirabegron.

Microvascular Reactivity Is Greater Following Blood Flow Restriction Resistance Exercise Compared with Traditional Resistance Exercise.

Perlet, MR, Hosick, PA, Licameli, N, and Matthews, EL. Microvascular reactivity is greater following blood flow restriction resistance exercise compared with traditional resistance exercise. J Strength Cond Res XX(X): 000-000, 2024-Chronic blood flow restriction (BFR) resistance exercise can improve muscular strength, hypertrophy, and microvasculature function, but the acute microvascular effects are unknown. We aimed to test the effects of acute BFR resistance exercise on postexercise microvascular reactivity in an exercising muscle and nonexercising muscle compared with traditional resistance exercise (TRE). Twenty-five adults (men = 14, women = 11, age: 22 ± 3 years, body mass: 71.69 ± 14.49 kg, height: 170 ± 10 cm) completed barbell back squat 1-repetition maximum (1RM) testing followed by 2 randomized and counterbalanced resistance exercise visits separated by ≥48 hours. The 2 visits involved either BFR (4 sets of 30-15-15-15 repetitions at 30% 1RM, with 60-second rest intervals) or TRE (4 sets of 10 repetitions at 70% 1RM, 60-second rest intervals). During each exercise visit, a pre- and postbarbell back squat vascular occlusion test was performed using near-infrared spectroscopy to measure skeletal muscle oxygen (SmO2) in the vastus lateralis (VL) and flexor carpi radialis (FCR). Two-way repeated-measures ANOVA found an interaction effect (p = 0.020) for SmO2 reactivity in the VL. Post hoc analysis found greater reactive hyperemia postexercise in the VL for the BFR condition (p < 0.001) but not the TRE condition (p ≥ 0.05). There were no time, condition, or interaction effects (all p > 0.05) for the same analysis in the FCR. This analysis suggests that BFR, but not TRE, lead to acutely improved microvasculature function. Moreover, it suggests that the effects of BFR resistance exercise are local to the exercised or occluded limb and not systemic.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety

Ethnopharmacological relevanceThe safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. Aim of the studyThe current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. MethodologyCEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. ResultsBased on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. ConclusionThis study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Association analysis of indel variants and gene expression identifies MDM4 as a novel locus for skeletal muscle hypertrophy and power athlete status.

Insertions and deletions (indels) are the second most common type of variation in the human genome. However, limited data on their associations with exercise-related phenotypes have been documented. The aim of the present study was to examine the association between 18,370 indel variants and power athlete status, followed by additional studies in 357,246 individuals. In the discovery phase, the D allele of the MDM4 gene rs35493922 I/D polymorphism was over-represented in power athletes compared with control subjects (P=7.8×10-9) and endurance athletes (P=0.0012). These findings were replicated in independent cohorts, showing a higher D allele frequency in power athletes compared with control subjects (P=0.016) and endurance athletes (P=0.031). Furthermore, the D allele was positively associated (P=0.0013) with greater fat-free mass in the UK Biobank. MDM4 encodes a protein that inhibits the activity of p53, which induces muscle fibre atrophy. Accordingly, we found that MDM4 expression was significantly higher in the vastus lateralis of power athletes compared with endurance athletes (P=0.0009) and was positively correlated with the percentage of fast-twitch muscle fibres (P=0.0062) and the relative area occupied by fast-twitch muscle fibres (P=0.0086). The association between MDM4 gene expression and an increased proportion of fast-twitch muscle fibres was confirmed in two additional cohorts. Finally, we found that the MDM4 DD genotype was associated with increased MDM4 gene expression in vastus lateralis and greater cross-sectional area of fast-twitch muscle fibres. In conclusion, MDM4 is suggested to be a potential regulator of muscle fibre specification and size, with its indel variant being associated with power athlete status. HIGHLIGHTS: What is the central question of this study? Which indel variants are functional and associated with sport- and exercise-related traits? What is the main finding and its importance? Out of 18,370 tested indels, the MDM4 gene rs35493922 I/D polymorphism was found to be the functional variant (affecting gene expression) and the most significant, with the deletion allele showing associations with power athlete status, fat-free mass and cross-sectional area of fast-twitch muscle fibres. Furthermore, the expression of MDM4 was positively correlated with the percentage of fast-twitch muscle fibres and the relative area occupied by fast-twitch muscle fibres.

Physical therapy for muscle strengthening in individuals with amyotrophic lateral sclerosis: A protocol for a systematic review and meta-analysis.

People with Amyotrophic Lateral Sclerosis (ALS) can present initially muscle weakness, which is a debilitating symptom that may be improved by engaging in muscle strengthening activities. Currently, the effects of motor interventions for muscle strengthening in people with ALS are unclear. This review intends to analyze the effects of motor interventions for muscle strengthening in individuals with ALS. Randomized, non-randomized, and quasi-experimental clinical trials assessing individuals with ALS of both sexes, aged 18 years or older, who have received motor interventions for muscle strengthening considering all practices that can lead to increased strength, endurance, power and muscular hypertrophy will be included. No restriction on language, location, or publication date will be applied. MEDLINE, EMBASE, Cochrane Library (CENTRAL), SPORTDiscus, and Physiotherapy Evidence Database (PEDro) databases will be searched. The US National Institutes of Health Ongoing, ClinicalTrials.gov, and the reference lists of included studies will also be searched. Two reviewers will independently screen titles and abstracts and extract data from included studies. The methodological quality of the included studies will be assessed by the PEDro scale and the certainty of the evidence by the GRADE approach. Disagreements will be resolved by a third researcher. Findings will be presented in text and table formats. A meta-analysis will compare the effects of motor interventions for muscle strengthening versus placebo or other interventions.

Comparison of Muscle Adaptation to Blood Flow-Restricted Versus Traditional Resistance Training in Healthy Adults: A Brief Systematic Review and Meta-analysis

ABSTRACT The primary aim of this study was to systematically compare the effectiveness of blood flow restriction training (BFR) versus traditional resistance training (TRT) to improve muscle size in healthy adults. Secondary outcomes were improvements in muscle strength and endurance. We performed a systematic search with meta-analysis. Using predetermined criteria, 541 unique articles were identified through databases and bibliographies. After screening titles, abstracts, and full texts, 20 articles were included in the review. All 20 articles evaluated muscle hypertrophy, 19 evaluated strength, and 1 evaluated endurance in response to BFR and TRT. Data from 10 articles were included in the meta-analysis. In the qualitative analysis, TRT and BFR increased muscle size without differences between conditions for at least 1 hypertrophy outcome in 13 studies, and TRT or BFR differentially improved hypertrophy in 5 studies. TRT and BFR increased strength without differences between conditions for at least 1 outcome in 15 studies, and TRT or BFR differentially improved strength in 9 studies. Results from the meta-analysis indicate no differences in muscle size (ES = 0.045, 95% CI [−0.278 to 0.367]) or strength (ES = −0.149, 95% CI [−0.439 to 0.141]) improvements with BFR versus TRT. Practitioners can implement BFR training to increase muscle size and strength as appropriate, especially for training periods of 8 weeks or longer.

Muscle hypertrophy response across four muscles involved in the bench press exercise: Randomized 10 weeks training intervention

Background and purposeResistance training exercise provides increases in muscle size and is used by coaches and health care professional as a tool to improve functional performance. The aim of the present study was to investigate the effect of 10 weeks of resistance training program performed on the bench press (BP) exercise on the hypertrophic responses of four different muscles (pectoralis major, anterior and medial deltoid, brachii, and pectoralis minor) involved in the task compared to controls. MethodsTwenty-four healthy males were recruited, and thirteen performed a resistance training intervention while eleven were control. RT group trained for 10 weeks and the protocol consisted of a time under tension for each set of 36s (3–4 sets) with 12 repetitions with an intensity of 50–55% of the 1RM, a training frequency of 3 times a week, with a 3 min rest between sets. Muscle cross-sectional area (CSA) was measure by magnetic resonance imaging. ResultsIndividuals in the RT group demonstrated higher changes in CSA of the pectoralis major, pectoralis minor, anterior deltoid, and triceps brachii (P ≤ 0.019) than in the Control group. It was identified in the RT group higher increases in CSA of all muscles compared to medial deltoid (P ≤ 0.016), while pectoralis major demonstrated larger increases in CSA than pectoralis minor and triceps brachii (P ≤ 0.030). ConclusionsWe demonstrated that 10 weeks of resistance training performed on the BP exercise led to increases in muscle size of the muscles involved in the task, but not in the same magnitude.

A Neural Network Model for Efficient Musculoskeletal-Driven Skin Deformation

We present a comprehensive neural network to model the deformation of human soft tissues including muscle, tendon, fat and skin. Our approach provides kinematic and active correctives to linear blend skinning [Magnenat-Thalmann et al. 1989] that enhance the realism of soft tissue deformation at modest computational cost. Our network accounts for deformations induced by changes in the underlying skeletal joint state as well as the active contractile state of relevant muscles. Training is done to approximate quasistatic equilibria produced from physics-based simulation of hyperelastic soft tissues in close contact. We use a layered approach to equilibrium data generation where deformation of muscle is computed first, followed by an inner skin/fascia layer, and lastly a fat layer between the fascia and outer skin. We show that a simple network model which decouples the dependence on skeletal kinematics and muscle activation state can produce compelling behaviors with modest training data burden. Active contraction of muscles is estimated using inverse dynamics where muscle moment arms are accurately predicted using the neural network to model kinematic musculotendon geometry. Results demonstrate the ability to accurately replicate compelling musculoskeletal and skin deformation behaviors over a representative range of motions, including the effects of added weights in body building motions.

MuSK-BMP signaling in adult muscle stem cells maintains quiescence and regulates myofiber size.

MuSK, in its role as a BMP co-receptor, regulates adult muscle stem cell quiescenceThe MuSK-BMP pathway acts cell autonomouslyIncreased muscle size and function with preservation of myonuclear density and stemness in mice with attenuated MuSK-BMP signaling.

In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent.

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused "other anabolic agent" (subclass S1.2. of the "anabolic agents" class S1) from the World Anti-Doping Agency's (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

Serum Myostatin is Associated With Central-to-Peripheral Arterial Stiffness Gradient in Healthy Adolescents: The MACISTE Study.

Myostatin is a protein compound, structurally related to the transforming growth factor-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. It exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. A cohort of 128 healthy subjects (mean age 17 ± 2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. The mean cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s, and PWVr was 0.75 ± 0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71 ± 0.1, 0.74 ± 0.1, 0.7 ± 0.1, 0.77 ± 0.1, P for trend = 0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (P = 0.01) and a negative one with LDL-cholesterol (P = 0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent of SBP values, age, sex, heart rate, BMI, HDL-cholesterol, and HOMA Index. In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall.

Unlocking Phytate with Phytase: A Meta-Analytic View of Meat-Type Chicken Muscle Growth and Bone Mineralization Potential.

The inclusion of exogenous phytase in P- and Ca-deficient diets of broilers to address the growing concern about excessive P excretion into the environment over the years has been remarkably documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with a meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to achieve the following: (1) quantitatively summarize the size of phytase effect on growth performance, bone strength and mineralization in broilers fed diets deficient in P and Ca and (2) estimate and explore the heterogeneity in the effect size of outcomes using subgroup and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration's SYRCLE risk of bias checklists for animal studies. Applying the random effects models, Hedges' g effect size of supplemented phytase was calculated using the R software (version 4.3.3, Angel Food Cake) to determine the standardized mean difference (SMD) at a 95% confidence interval. Subgroup analysis and meta-regression were used to further explore the effect size heterogeneity (PSMD ≤ 0.05, I2 > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and improves FCR at each time point of growth (p < 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (p < 0.0001) of broilers fed P- and Ca-deficient diets. The results of the subgroup and meta-regression analyses showed that the age and strain of broiler, dietary P source, and the duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary-available phosphorus and calcium and improve ADFI, BWG, and FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and the bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and the duration of phytase exposure rather than the dosage.

Mature adipocytes inhibit differentiation of myogenic cells but stimulate proliferation of fibro-adipogenic precursors derived from trout muscle in vitro

Interactions between tissues and cell types, mediated by cytokines or direct cell–cell exchanges, regulate growth. To determine whether mature adipocytes influence the in vitro growth of trout mononucleated muscle cells, we developed an indirect coculture system, and showed that adipocytes (5 × 106 cells/well) derived from perivisceral adipose tissue increased the proliferation (BrdU-positive cells) of the mononucleated muscle cells (26% vs. 39%; p < 0.001) while inhibiting myogenic differentiation (myosin+) (25% vs. 15%; p < 0.001). Similar effects were obtained with subcutaneous adipose tissue-derived adipocytes, although requiring more adipocytes (3 × 107 cells/well vs. 5 × 106 cells/well). Conditioned media recapitulated these effects, stimulating proliferation (31% vs. 39%; p < 0.001) and inhibiting myogenic differentiation (32 vs. 23%; p < 0.001). Adipocytes began to reduce differentiation after 24 h, whereas proliferation stimulation was observed after 48 h. While adipocytes did not change pax7+ and myoD1/2+ percentages, they reduced myogenin+ cells showing inhibition from early differentiation stage. Finally, adipocytes increased BrdU+ cells in the Pdgfrα+ population but not in the myoD+ one. Collectively, our results demonstrate that trout adipocytes promote fibro-adipocyte precursor proliferation while inhibiting myogenic cells differentiation in vitro, suggesting the key role of adipose tissue in regulating fish muscle growth.