Muscle Growth Research Articles

Influence of intramuscular steroid receptor content and fiber capillarization on skeletal muscle hypertrophy.

Multiple intramuscular variables have been proposed to explain the high variability in resistance training induced muscle hypertrophy across humans. This study investigated if muscular androgen receptor (AR), estrogen receptor α (ERα) and β (ERβ) content and fiber capillarization are associated with fiber and whole-muscle hypertrophy after chronic resistance training. Male (n = 11) and female (n = 10) resistance training novices (22.1 ± 2.2 years) trained their knee extensors 3×/week for 10 weeks. Vastus lateralis biopsies were taken at baseline and post the training period to determine changes in fiber type specific cross-sectional area (CSA) and fiber capillarization by immunohistochemistry and, intramuscular AR, ERα and ERβ content by Western blotting. Vastus lateralis volume was quantified by MRI-based 3D segmentation. Vastus lateralis muscle volume significantly increased over the training period (+7.22%; range: -1.82 to +18.8%, p < 0.0001) but no changes occurred in all fiber (+1.64%; range: -21 to +34%, p = 0.869), type I fiber (+1.33%; range: -24 to +41%, p = 0.952) and type II fiber CSA (+2.19%; range: -23 to +29%, p = 0.838). However, wide inter-individual ranges were found. Resistance training increased the protein expression of ERα but not ERβ and AR, and the increase in ERα content was positively related to changes in fiber CSA. Only for the type II fibers, the baseline capillary-to-fiber-perimeter index was positively related to type II fiber hypertrophy but not to whole muscle responsiveness. In conclusion, an upregulation of ERα content and an adequate initial fiber capillarization may be contributing factors implicated in muscle fiber hypertrophy responsiveness after chronic resistance training.

Blood Flow Restriction Therapy After Anterior Cruciate Ligament Reconstruction

Anterior cruciate ligament reconstruction (ACLR) rehabilitation necessitates restoration of quadriceps strength to minimize reinjury and optimize return to sport (RTS). Patients recovering from ACLR are limited by pain and activity restrictions, resulting in quadriceps muscle atrophy. Blood flow restriction (BFR) therapy involves performing exercises while a specialized blood pressure cuff is applied to the proximal aspect of the operative extremity and inflated to 40% to 90% of the arterial occlusion pressure, as determined using Doppler ultrasonography. BFR is theorized to induce an anaerobic environment and metabolic stress during exercise, promoting muscle hypertrophy and strength gains. Although the physiological mechanism has not been fully elucidated, it is theorized that BFR combined with low-load resistance training could yield muscle adaptations comparable to those of high-load resistance training. For ACLR patients with pain and restrictions precluding high-intensity strength training, incorporation of BFR into postoperative rehabilitation protocols could help mitigate quadriceps weakness and promote RTS. Randomized controlled trials report a prolonged, dose-dependent relation between BFR use and quadriceps and hamstring strength gains, improved bone and muscle mass, and earlier RTS, whereas other studies report no significant difference in quadriceps size, strength, or patient satisfaction compared with controls. Furthermore, although generally considered safe, there are rare reports of associated adverse events such as rhabdomyolysis, and BFR should be avoided in patients with a history of thromboembolic disease or peripheral vasculopathy. The literature examining BFR after ACLR is heterogeneous; lacks standardization; and contains broad variation in reported cuff pressures, as well as timing and duration of BFR use, among protocols. Although the use of BFR after ACLR shows promise, further study is necessary to elucidate the efficacy, safety, and optimal protocols.

Radiofrequency and Electrical Muscle Stimulation: A Synergistic Treatment That Achieves Lipolysis and Circumferential Waist Reduction in Non-Invasive Body Contouring

Abstract Background Surgeons and providers in aesthetic medicine seek non-invasive devices that can be utilized for safe, efficient and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. Objectives To determine the efficacy of body contouring after three treatments using the non-invasive Transform (InMode, Lake Forest, CA) device. Methods A prospective, multi-center study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft tissue thickness, waist circumference, histologic evaluation, patient comfort and satisfaction assessments. Results Forty-four patients were successfully enrolled in the study and completed the series of three treatments which involved combined electrical muscle stimulation (EMS) and non-invasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a decrease in soft-tissue thickness (average 3.1mm; p=0.001), there was a significant decrease in caliper measurements of peri-umbilical skin thickness (p&amp;lt;0.003) and the average reduction of abdominal circumference was 1.9cm (p&amp;lt;0.0001) three months after the treatment series. Histology confirmed subcutaneous adipolysis without damaging the dermal layer. Patients reported a high degree of satisfaction with the overall result (p=0.003) and that each of the three treatments were progressively more comfortable (p&amp;lt;0.005). Conclusions This study demonstrates that a series of simultaneous non-invasive RF with EMS treatments to the abdomen decreases subcutaneous soft tissue thickness of the treated area. These comfortable treatments ultimately result in a high degree of patient satisfaction at three months.

Whole-genome selection signature differences between Chaohu and Ji'an red ducks.

Assessing the genetic structure of local varieties and understanding their genetic data are crucial for effective management and preservation. However, the genetic differences among local breeds require further explanation. To enhance our understanding of their population structure and genetic diversity, we conducted a genome-wide comparative study of Chaohu and Ji'an Red ducks using genome sequence and restriction site-associated DNA sequencing technology. Our analysis revealed a distinct genetic distinction between the two breeds, leading to divided groups. The phylogenetic tree for Chaohu duck displayed two branches, potentially indicating minimal impact from artificial selection. Additionally, our ROH (runs of homozygosity) analysis revealed that Chaohu ducks had a lower average inbreeding coefficient than Ji'an Red ducks. We identified several genomic regions with high genetic similarity in these indigenous duck breeds. By conducting a selective sweep analysis, we identified 574 candidate genes associated with muscle growth (BMP2, ITGA8, MYLK, and PTCH1), fat deposits (ELOVL1 and HACD2), and pigmentation (ASIP and LOC101797494). These results offer valuable insights for the further enhancement and conservation of Chinese indigenous duck breeds.

Autonomic Rebound Following Maximal Exercise in Bodybuilders and Recreationally Active Participants

The off-season for natural bodybuilders (BB) is characterized by increased training loads and fluctuations in caloric intake, which may lead to insufficient recovery. The autonomic nervous system (ANS) plays a pivotal role in recovery. The purpose of this study was to evaluate resting ANS activity and recovery following a maximal exercise bout in off-season BB and compare them to those of recreationally active individuals. Fifteen males participated; 7 recreationally active (RA) (24.6 ± 2.1 years, 81.1 ± 10.8 kg) and 8 BB (21.8 ± 2.9 years, 89.3 ± 13.0 kg). Each performed a graded exercise test. Heart rate variability (HRV) was measured at rest and during a 45 min recovery period. HRV was analyzed as: root mean square of successive differences (lnRMSSD), standard deviation of normal-to-normal sinus beats (lnSDNN), high frequency (lnHF), low frequency (lnLF), and the ratio of low frequency to high frequency (lnLF/lnHF). A one-way ANOVA showed no differences for any resting marker of HRV, HR, and HR recovery. A significant depression in all markers of HRV was observed in the BB group at the 15 min point, and no recovery was observed before 45 min when compared to RA. The results of this study demonstrated depressed HRV recovery following the graded exercise test in BB when compared to the RA group.

Lower face contouring through botulinum toxin therapy: an overview

Botulinum toxin (Botox) has been used cosmetically to reduce and prevent wrinkles since 1989, but its application has since expanded to include treatment of other patient concerns, including masseter muscle hypertrophy. Abnormal enlargement of the masseter, a muscle located in the jaw, can give patients a larger or squarish facial appearance; the injection of Botox, through causing temporary paralysis of the masseter and a resultant reduction in muscle activity, can lead to a slimmer and less square jawline. However, careful patient selection is required, and approaches to injection technique and dosage vary. Francesca Ramadan provides an overview.

Timing matters? The effects of two different timing of high protein diets on body composition, muscular performance, and biochemical markers in resistance-trained males

BackgroundIt is unclear whether resistance training in combination with different timing of protein intake might have differential effects on muscle hypertrophy, strength, and performance. Therefore, we compared the effects of 8 weeks of resistance training combined with two different high-protein diet strategies (immediately pre-and after, or 3 h pre and after exercise) in resistance-trained males.MethodsForty resistance-trained males (24 ± 4 years) performed 8 weeks of resistance training combined with 2 g kg−1 d−1 protein. Body composition, muscular performance, and biochemical markers were assessed pre and post-intervention.ResultsNine participants (four from 3 h group and five from the immediate group) withdrew from the study. Therefore, 31 participants completed the study. All measures of skeletal muscle mass, Australian pull-up, and muscle strength, significantly increased post-intervention in both groups (p &amp;lt; 0.05). The biochemical marker urea also significantly increased from pre to post in both groups (p &amp;lt; 0.05). There were no significant between-group differences (p &amp;gt; 0.05).ConclusionHigh-protein diet enhances muscular performance and skeletal muscle mass in resistance-trained males, irrespective of intake time. Consequently, the total daily protein intake appears to be the primary factor in facilitating muscle growth induced by exercise.

Cerebral cortex activation and functional connectivity during low-load resistance training with blood flow restriction: An fNIRS study.

Despite accumulating evidence that blood flow restriction (BFR) training promotes muscle hypertrophy and strength gain, the underlying neurophysiological mechanisms have rarely been explored. The primary goal of this study is to investigate characteristics of cerebral cortex activity during BFR training under different pressure intensities. 24 males participated in 30% 1RM squat exercise, changes in oxygenated hemoglobin concentration (HbO) in the primary motor cortex (M1), pre-motor cortex (PMC), supplementary motor area (SMA), and dorsolateral prefrontal cortex (DLPFC), were measured by fNIRS. The results showed that HbO increased from 0 mmHg (non-BFR) to 250 mmHg but dropped sharply under 350 mmHg pressure intensity. In addition, HbO and functional connectivity were higher in M1 and PMC-SMA than in DLPFC. Moreover, the significant interaction effect between pressure intensity and ROI for HbO revealed that the regulation of cerebral cortex during BFR training was more pronounced in M1 and PMC-SMA than in DLPFC. In conclusion, low-load resistance training with BFR triggers acute responses in the cerebral cortex, and moderate pressure intensity achieves optimal neural benefits in enhancing cortical activation. M1 and PMC-SMA play crucial roles during BFR training through activation and functional connectivity regulation.

#1688 Association of baseline serum activin levels with left atrial diameter at 5 years post-kidney transplantation: results from the KNOW-KT

Abstract Background and Aims Serum activin A inhibits muscle growth, promotes apoptosis, and impairs heart function. However, the role of serum activin remains unclear in kidney transplant patients, where cardiovascular complications are a significant cause of morbidity and mortality. In this multicenter, observational cohort study, we investigated a potential association of pre-transplant serum activin levels with the left atrial (LA) diameter, an indicator of diastolic burden and a predictor of cardiovascular complications, to indirectly assess the impact of pre-transplant activin levels on heart function in kidney transplant patients. Method Overall, 602 kidney transplant patients from KNOW-KT (Korean cohort study for outcome in patients with kidney transplantation) were analyzed. Activin levels were measured at baseline immediately before kidney transplantation (KT). The primary outcome was the LA diameter that was measured by transthoracic echocardiography at 5 years after KT. Results The mean age of study population was 45.4 years and 221 (46.7%) patients were men. Pre-transplant serum activin levels were 718.4 ± 363.2 (mean ± standard deviation). When activin levels were divided into categorical variables according to the median value, the ejection fraction of LV showed a lower tendency in the high-activin group (64.3 ± 7.0) compared to the low-activin group (65.3 ± 6.2); however, there was no statistical significance (P=0.069). LV diastolic dimension was significantly higher in the high-activin group (47.3 ± 5.3) compared to the low-activin group (46.3 ± 5.5) (P=0.021). Notably, the post-transplant LA diameter was 37.0 ± 7.0 mm in the low-activin group and 39.1 ± 6.5 mm in the high-activin group, showing a significant difference (P&amp;lt;0.001). The multivariate linear regression coefficient for association between activin groups and LA diameter was 1.08 (95% confidence interval [CI], 0.67-2.10, P=0.037). In an additional logistic regression analysis of LA diameter groups, the high activin group was significantly associated with the high LA diameters compared to the low-activin group in multivariate analysis (adjusted odds ratio [OR], 2.04; 95% CI, 1.34-3.09, P=0.001). When activin levels were used as a continuous variable, adjusted ORs of activin for high LA diameters were 1.29 (95% CI, 1.04-1.60, P=0.018). Conclusion Pre-transplant serum activin levels were independently associated with a higher post-transplant LA diameter, suggesting that activin may negatively affect heart functions in kidney transplant patients. Therefore, activin may be a potential prognostic and therapeutic target in kidney transplant patients.

Molecular cloning of TPM3 gene in qinchuan cattle and its effect on myoblast proliferation and differentiation

Tropomyosin 3 (TPM3) plays a significant role as a regulatory protein in muscle contraction, affecting the growth and development of skeletal muscles. Despite its importance, limited research has been conducted to investigate the influence of TPM3 on bovine skeletal muscle development. Therefore, this study revealed the role of TPM3 in bovine myoblast growth and development. This research involved conducting a thorough examination of the Qinchuan cattle TPM3 gene using bioinformatics tools to examine its sequence and structural characteristics. Furthermore, TPM3 expression was evaluated in various bovine tissues and cells using quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that the coding region of TPM3 spans 855 bp, with the 161st base being the T base, encoding a protein with 284 amino acids and 19 phosphorylation sites. This protein demonstrated high conservation across species while displaying a predominant α-helix secondary structure despite being an unstable acidic protein. Notably, a noticeable increase in TPM3 expression was observed in the longissimus dorsi muscle and myocardium of calves and adult cattle. Expression patterns varied during different stages of myoblast differentiation. Functional studies that involved interference with TPM3 in Qinchuan cattle myoblasts revealed a very significantly decrease in S-phase cell numbers and EdU-positive staining (P < 0.01), and disrupted myotube morphology. Moreover, interference with TPM3 resulted in significantly (P < 0.05) or highly significantly (P < 0.01) decreased mRNA and protein levels of key proliferation and differentiation markers, indicating its role in the modulation of myoblast behavior. These findings suggest that TPM3 plays an essential role in bovine skeletal muscle growth by influencing myoblast proliferation and differentiation. This study provides a foundation for further exploration into the mechanisms underlying TPM3-mediated regulation of bovine muscle development and provides valuable insights that could guide future research directions as well as potential applications for livestock breeding and addressing muscle-related disorders.

MTORC1 and BMP-Smad1/5 Regulation of Serum-Stimulated Myotube Hypertrophy: A Role for Autophagy.

Protein synthesis regulation is critical for skeletal muscle hypertrophy; yet, other established cellular processes are necessary for growth-related cellular remodeling. Autophagy has a well-acknowledged role in muscle quality control, but evidence for its role in myofiber hypertrophy remains equivocal. Both mTORC1 and BMP-Smad1/5 signaling are reported regulators of myofiber hypertrophy; however, gaps remain in our understanding of how this regulation is integrated with the growth processes and autophagy regulation. Therefore, we investigated the mTORC1 and Smad1/5 regulation of protein synthesis and autophagy flux during serum-stimulated myotube growth. Chronic serum stimulation experiments were performed on day-5 differentiated C2C12 myotubes incubated in differentiation media (2%HS) or growth media (5%FBS) for 48 hours. Rapamycin or LDN193189 were dosed for 48 hours to inhibit mTORC1 and BMP-Smad1/5 signaling, respectively. Acute serum stimulation was examined in day-7 differentiated myotubes. Protein synthesis was measured by puromycin incorporation. Bafilomycin A1 and immunoblotting for LC3B were used to assess autophagy flux. Chronic serum stimulation increased myotube diameter 22%, total protein 21%, total RNA 100%, Smad1/5 phosphorylation 404%, and suppressed autophagy flux. Rapamycin, but not LDN193189, blocked serum-induced myotube hypertrophy and the increase in total RNA. Acute serum stimulation increased protein synthesis 111%, Smad1/5 phosphorylation 559%, rpS6 phosphorylation 117%, and suppressed autophagy flux. Rapamycin increased autophagy flux during acute serum stimulation. These results provide evidence for mTORC1, but not BMP-Smad1/5 signaling, being required for serum-induced myotube hypertrophy and autophagy flux by measuring LC3BII/I expression. Further investigation is warranted to examine the role of autophagy flux in myotube hypertrophy.

The Clinical Management of Electrical Stimulation Therapies in the Rehabilitation of Individuals with Spinal Cord Injuries.

Background: People with spinal cord injuries (SCIs) often have trouble remaining active because of paralysis. In the past, exercise recommendations focused on the non-paralyzed muscles in the arms, which provides limited benefits. However, recent studies show that electrical stimulation can help engage the paralyzed extremities, expanding the available muscle mass for exercise. Methods: The authors provide an evidence-based approach using expertise from diverse fields, supplemented by evidence from key studies toward the management of electrical stimulation therapies in individuals with SCIs. Literature searches were performed separately using the PubMed, Medline, and Google Scholar search engines. The keywords used for the searches included functional electrical stimulation cycling, hybrid cycling, neuromuscular electrical stimulation exercise, spinal cord injury, cardiovascular health, metabolic health, muscle strength, muscle mass, bone mass, upper limb treatment, diagnostic and prognostic use of functional electrical stimulation, tetraplegic hands, and hand deformities after SCI. The authors recently presented this information in a workshop at a major rehabilitation conference. Additional information beyond what was presented at the workshop was added for the writing of this paper. Results: Functional electrical stimulation (FES) cycling can improve aerobic fitness and reduce the risk of cardiovascular and metabolic diseases. The evidence indicates that while both FES leg cycling and neuromuscular electrical stimulation (NMES) resistance training can increase muscle strength and mass, NMES resistance training has been shown to be more effective for producing muscle hypertrophy in individual muscle groups. The response to the electrical stimulation of muscles can also help in the diagnosis and prognosis of hand dysfunction after tetraplegia. Conclusions: Electrical stimulation activities are safe and effective methods for exercise and testing for motor neuron lesions in individuals with SCIs and other paralytic or paretic conditions. They should be considered part of a comprehensive rehabilitation program in diagnosing, prognosing, and treating individuals with SCIs to improve function, physical activity, and overall health.

Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats.

The rate and magnitude of skeletal muscle wasting after severe spinal cord injury (SCI) exceeds most other disuse conditions. Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post-SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes. Four-month-old Sprague-Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1week, 2weeks, 1month and 3months post-surgery (n=6-7 per group per timepoint). RNA was extracted from muscles for bulk RNA-sequencing analysis (n=3-5 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age-matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles. SCI produced immediate and persistent hindlimb paralysis, with Basso-Beattie-Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25-50% lower soleus mass and myofiber atrophy versus SHAM (P<0.05 at all timepoints). Transcriptional comparisons of SCI versus SHAM resulted in 184 DEGs (1week), 436 DEGs (2weeks), 133 DEGs (1month) and 1200 DEGs (3months). Upregulated atrophy-related genes included those associated with cell senescence, nuclear factor kappa B, ubiquitin proteasome and unfolded protein response pathways, along with upregulated genes that negatively influence muscle growth through the transforming growth factor beta pathway and inhibition of insulin-like growth factor-I/Akt/mechanistic target of rapamycin and p38/mitogen-activated protein kinase signalling. Genes associated with extracellular matrix (ECM), including collagens, collagen crosslinkers, proteoglycans and those regulating ECM integrity, were enriched within upregulated DEGs at 1week but subsequently downregulated at 2weeks and 3months and were accompanied by >50% higher ECM areas and hydroxyproline levels in SCI muscles (P<0.05). Myofiber remodelling genes were enriched in upregulated DEGs at 2weeks and 1month and were downregulated at 3months. Genes that regulate neuromuscular junction remodelling were evident in muscles post-SCI, along with slow-to-fast fibre-type shifts: 1 week and 2 weeks SCI muscles were composed of 90% myosin heavy chain (MHC) type I fibres, which decreased to only 16% at 3months and were accompanied by 50% fibres containing MHC IIX (P<0.05). Metabolism genes were enriched in upregulated DEGs at 1month and were further enriched at 3months. Our results substantiate many known pathologic features of SCI-induced wasting in rat skeletal muscle and identify a progressive and dynamic transcriptional landscape within the post-SCI soleus. Future studies are warranted to consider these therapeutic treatment windows when countering SCI muscle pathology.

Dietary glycine supplementation activates mTOR signaling pathway in tissues of pigs with intrauterine growth restriction.

The mechanistic target of rapamycin (mTOR) cell signaling pathway serves as the central mechanism for the regulation of tissue protein synthesis and growth. We recently reported that supplementing 1% glycine to corn- and soybean meal-based diets enhanced growth performance between weaning and market weights in pigs with intrauterine growth restriction (IUGR). Results of recent studies have revealed an important role for glycine in activating mTOR and protein synthesis in C2C12 muscle cells. Therefore, the present study tested the hypothesis that dietary glycine supplementation enhanced the mTOR cell signaling pathway in skeletal muscle and other tissues of IUGR pigs. At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of two groups: supplementation with either 1% glycine or 1.19% L-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Tissues were obtained from the pigs within 1wk after the feeding trial ended at 188 d of age to determine the abundances of total and phosphorylated forms of mTOR and its two major downstream proteins: eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and ribosomal protein S6 kinase-1 (p70S6K). Results showed that IUGR decreased (P < 0.05) the abundances of both total and phosphorylated mTOR, 4EBP1, and p70S6K in the gastrocnemius muscle and jejunum. In the longissimus lumborum muscle of IUGR pigs, the abundances of total mTOR did not differ (P > 0.05) but those for phosphorylated mTOR and both total and phosphorylated 4EBP1 and p70S6K were down-regulated (P < 0.05), when compared to NBW pigs. These adverse effects of IUGR in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum were prevented (P < 0.05) by dietary glycine supplementation. Interestingly, the abundances of total or phosphorylated mTOR, 4EBP1, and p70S6K in liver were not affected (P > 0.05) by IUGR or glycine supplementation. Collectively, our findings indicate that IUGR impaired the mTOR cell signaling pathway in tissues of pigs and that adequate glycine intake was crucial for maintaining active mTOR-dependent protein synthesis for the growth and development of skeletal muscle.

The Use of Anabolic Steroids by Bodybuilders in the State of Sergipe, Brazil.

Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive-analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex (p = 0.492), age (p = 0.460), family income (p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved (p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% (n = 20), irritability at 32.1% (n = 19), alopecia (hair loss), and nervousness at 23.7% (n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% (n = 9), liver disease at 28.0% (n = 7), and cancer (non-specific) at 8.0% (n = 2). We concluded that, regardless of the athletes' socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes.

Unlocking Strength: The Powerful Impact of Ashwagandha (Withania somnifera) Supplementation on Resistance Training

Withania somnifera, commonly known as ashwagandha, has gained popularity in recent years among individuals interested in healthy lifestyles, natural medicine, and sports. This review aims to summarize the current knowledge regarding the effects of ashwagandha supplementation on various aspects of physical performance, particularly in the context of resistance training. Studies have shown that ashwagandha can positively impact muscle strength, with significant increase of muscle force and power output. Additionally, it has demonstrated potential in modulating body composition, with reduction of body fat percentage noted in certain populations. However, results of studies on ashwagandha’s effect on muscle size remain inconclusive and may depend on various factors such as training status and individual responses. In terms of endurance, ashwagandha supplementation has been associated with improvement in maximal oxygen uptake, indicating enhanced aerobic capacity and delayed exhaustion during endurance activities. Furthermore, ashwagandha was shown to aid muscle recovery by reducing exercise-induced muscle damage and inflammatory response, potentially accelerating the muscle regeneration process. Ashwagandha may also influence hormone levels, such as testosterone and cortisol, with potential implications for muscle growth and recovery. However, further research is needed to fully understand the mechanisms underlying these effects. Overall, ashwagandha supplementation appears to hold promise for enhancing physical performance and overall well-being. Further research is needed to elucidate optimal dosages, long-term safety, and potential interactions with other supplements or medications.

Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway

BackgroundGut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development.ResultsHere, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding.ConclusionsThis study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development.

Skeletal muscle hypertrophy rewires glucose metabolism: An experimental investigation and systematic review.

Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P=0.01) and serine synthesis pathway (serine: -36.8%; P=0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P=0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P=0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-13C6]glucose is increasingly incorporated by ~13% (P=0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P=0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P<0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n=450243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P<5.0e-8). Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.

Is sleep bruxism in obstructive sleep apnea only an oral health related problem?

BackgroundThe etiology of sleep bruxism in obstructive sleep apnea (OSA) patients is not yet fully clarified. This prospective clinical study aimed to investigate the connection between probable sleep bruxism, electromyographic muscle tone, and respiratory sleep patterns recorded during polysomnography.Methods106 patients with OSA (74 males, 31 females, mean age: 56.1 ± 11.4 years) were divided into two groups (sleep bruxism: SB; no sleep bruxism: NSB). Probable SB were based on the AASM criteria: self-report of clenching/grinding, orofacial symptoms upon awakening, abnormal tooth wear and hypertrophy of the masseter muscle. Both groups underwent clinical examination for painful muscle symptoms aligned with Temporomandibular Disorders Diagnostic Criteria (DC/TMD), such as myalgia, myofascial pain, and headache attributed to temporomandibular disorder. Additionally, non-complaint positive muscle palpation and orofacial-related limitations (Jaw Functional Limited Scale-20: JFLS-20) were assessed. A one-night polysomnography with electromyographic masseter muscle tone (EMG) measurement was performed. Descriptive data, inter-group comparisons and multivariate logistic regression were calculated.ResultsOSA patients had a 37.1% prevalence of SB. EMG muscle tone (N1-N3, REM; P = 0.001) and the number of hypopneas (P = 0.042) were significantly higher in the sleep bruxism group. While measures like apnea–hypopnea-index (AHI), respiratory-disturbance-index (RDI), apnea index (AI), hypopnea-index (HI), number of arousals, and heart rate (1/min) were elevated in sleep bruxers, the differences were not statistically significant. There was no difference in sleep efficiency (SE; P = 0.403). Non-complaint masseter muscle palpation (61.5%; P = 0.015) and myalgia (41%; P = 0.010) were significant higher in SB patients. Multivariate logistic regression showed a significant contribution of EMG muscle tone and JFLS-20 to bruxism risk.ConclusionIncreased EMG muscle tone and orofacial limitations can predict sleep bruxism in OSA patients. Besides, SB patients suffer more from sleep disorder breathing. Thus, sleep bruxism seems to be not only an oral health related problem in obstructive apnea. Consequently, interdisciplinary interventions are crucial for effectively treating these patients.Trial registrationThe study was approved by the Ethics Committee of Philipps-University Marburg (reg. no. 13/22—2022) and registered at the “German Clinical Trial Register, DRKS” (DRKS0002959).

Secondary Lipid Oxidation Products as Modulators of Calpain-2 Functionality In Vitro.

The objective was to understand the impacts of secondary lipid oxidation products on calpain-2 activity and autolysis and, subsequently, to determine the quantity and localization of modification sites. 2-Hexenal and 4-hydroxynonenal incubation significantly decreased calpain-2 activity and slowed the progression of autolysis, while malondialdehyde had minimal impact on calpain-2 activity and autolysis. Specific modification sites were determined with LC-MS/MS, including distinct malondialdehyde modification sites on the calpain-2 catalytic and regulatory subunits. 2-Hexenal modification sites were observed on the calpain-2 catalytic subunit. Intact protein mass analysis with MALDI-MS revealed that a significant number of modifications on the calpain-2 catalytic and regulatory subunits are likely to exist. These observations confirm that specific lipid oxidation products modify calpain-2 and may affect the calpain-2 functionality. The results of these novel experiments have implications for healthy tissue metabolism, skeletal muscle growth, and post-mortem meat tenderness development.