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PURPOSE: Endurance exercise induces muscle fiber-type shifting and autophagy; however, the potential role of autophagy in muscle fiber-type transformation remains unclear. This study examined the relationship between muscle fiber-type shifting and autophagy in the soleus (SOL) and extensor digitorum longus (EDL) muscles, which are metabolically discrete muscles. METHODS: Male C57BL/6J mice were randomly assigned to sedentary control (CON) and exercise (EXE) groups. After 1 week of acclimation to treadmill running, the mice in the EXE group ran at 12-15 m/min, 60 min/day, 5 days/week for 6 weeks. All mice were sacrificed 90 min after the last exercise session, and the targeted tissues were rapidly dissected. The right side of the tissues was used for western blot analysis, whereas the left side was subjected to immunohistochemical analysis. RESULTS: Endurance exercise resulted in muscle fiber-type shifting (from type IIa to type I) and autophagy (an increase in LC3-II) in the SOL muscle. However, muscle fiber-type transformation and autophagy were not correlated in the SOL and EDL muscles. Interestingly, in contrast to the canonical autophagy signaling pathways, our study showed that exercise-induced autophagy concurs with enhanced anabolic (increased p-AKTSer473/AKT and p-mTOR/mTORSer2448 ratios) and suppressed catabolic (reduced p-AMPKThr172/AMPK ratio) states. CONCLUSION: Our findings demonstrate that chronic endurance exercise-induced muscle fiber-type transformation and autophagy occur in a muscle-specific manner (e.g., SOL). More importantly, our study suggests that endurance training-induced SOL muscle fiber-type transition may underlie metabolic modulations caused by the AMPK and AKT/mTOR signaling pathways rather than autophagy.

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BACKGROUND: Anterior tarsal tunnel (ATT) syndrome is caused by the compression of the deep fibular nerve (DFN) within the ATT beneath the inferior extensor retinaculum, bounded by the tendons of the extensor hallucis longus (EHL) and extensor digitorum longus (EDL). Compression may result from direct trauma, repetitive mechanical irritation, and thrombosis of the dorsalis pedis artery. Injury to the contents of ATT could occur during ankle arthroscopy. Therefore, this study was undertaken to provide a detailed description of the anatomy of the ATT and its clinical implications. MATERIALS AND METHODS: Ten formalin-fixed cadavers were utilized for the study. The ATT was identified between the tendons of the EHL and EDL. The length at the medial and lateral boundaries and the width at the proximal end, middle, and distal end of the ATT were measured using a digital Vernier calliper. RESULT: The mean length of the medial border of the tunnel was 31.42±8.44 mm, while the lateral border was 20.39±4.39 mm. The width of the ATT increased from the proximal to the distal end. DFN was related to the DPA laterally in 15 limbs and medially in five limbs within the tunnel. CONCLUSION: The present study not only describes the intricate anatomy of the ATT but also describes the patterns of DFN and DPA within the tunnel. Understanding the anatomy of ATT is crucial, as it paves the way for safe and efficient surgical interventions, thereby significantly reducing the risk of neurovascular damage during surgical procedures.

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A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at four times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the four time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.

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BACKGROUND: Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30-150 nm that are secreted by cells and taken up by recipient cells to mediate communication. Exosome-mediated muscle-fat tissue crosstalk is a newly discovered mechanism that may have an important effect on intramuscular fat deposition and with that on meat quality. Various of adipose tissue-derived exosomes have been discovered and identified, but the identification and function of muscle exosomes, especially porcine fast/slow myotube exosomes, remain unclear. Here, we first isolated and identified exosomes secreted from porcine extensor digitorum longus (EDL) and soleus (SOL), which represent fast and slow muscle, respectively, and further explored their effects on lipid accumulation in longissimus dorsi adipocytes. RESULTS: Porcine SOL-derived exosomes (SOL-EXO) and EDL-derived exosomes (EDL-EXO) were first identified and their average particle sizes were approximately 84 nm with double-membrane disc- shapes as observed via transmission electron microscopy and scanning electron microscopy. Moreover, the intramuscular fat content of the SOL was greater than that of the EDL at 180 days of age, because SOL intramuscular adipocytes had a stronger lipid-accumulating capacity than those of the EDL. Raman spectral analysis revealed that SOL-EXO protein content was much greater than that of EDL-EXO. Proteomic sequencing identified 72 proteins that were significantly differentially expressed between SOL-EXO and EDL-EXO, 31 of which were downregulated and 41 of which were upregulated in SOL-EXO. CONCLUSIONS: Our findings suggest that muscle-fat tissue interactions occur partly via SOL-EXO promoting adipogenic activity of intramuscular adipocytes.

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Folic acid fortification of all white flour, enriched pasta, and cornmeal products became mandatory in Canada to reduce risk of neural tube defects at birth. Furthermore, Health Canada and the Society of Obstetricians and Gynaecologists of Canada recommend women take daily prenatal folic acid supplements in addition to folic acid fortified foods during pregnancy. However, the influence of maternal folic acid supplementation on offspring development, specifically the highly abundant and metabolically active skeletal muscle, is currently unknown. Thus, the purpose of this study was to determine the effect of supplemental folic acid (four times higher than normal dietary consumption), in utero and throughout suckling on muscle size, function, and metabolism in male and female CD-1 mouse offspring. The major findings were that maternal exposure to supplemental folic acid (i) had no impact on postpartum growth rates or muscle mass in female and male offspring, (ii) had no impact on skeletal muscle contractile kinetics in females and male offspring, and (iii) increased maximal phosphofructokinase activity in extensor digitorum longus of female and male offspring. These findings suggest that exposure to folic acid supplementation in utero and throughout suckling at levels four times higher than recommended had minimal effect on skeletal muscle size, function, and metabolism regardless of sex. Future research is needed explore the underlying biological pathways and mechanisms affected by folic acid supplementation during pregnancy and lactation on offspring skeletal muscle tissue, specifically in humans.

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The extensor digitorum longus is a source of much anatomic variation, mostly related with extra tendinous slips or their unusual insertions. This report describes a new configuration of the extensor digitorum longus with two heads and two main tendons which bifurcate into five slips. These slips undergo further divisions and establish connections between the each other. Our findings provide a greater insight into the intricacies of human morphology.

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PURPOSE: Peroneus tertius (PT) or Fibularis tertius, a muscle of the anterior compartment of the leg is very distinctive to the Homo sapiens. This is because of the evolutionary acquisition of bipedal gait along with the eversion of the foot, which are unique to humans. It is considered as the fifth tendon of the extensor digitorum longus. Variations in the attachments of PT can cause stress fractures like the Jones fracture. PT has been extensively used in tendoplasty, tendon transfer and resection of the foot. The study aims to transpose the knowledge in variations of the morphology of PT from bench to bedside. METHODS: Routine dissection of a 64-year-old male cadaver revealed bilateral variations in the insertion of PT. This was documented photographically. The findings prompted a systematic literature review on the morphological variations of PT. An exhaustive search was undertaken through PubMed and Google Scholar databases to identify the published literature related to variations in the morphology of PT. Related anatomical studies of the variations in peroneus tertius were identified and a review of the literature was performed. RESULTS: Variations in the insertion of PT were observed bilaterally in the cadaver dissected by us. Statistical analysis revealed the absence of PT in 7.03% of lower limbs. 10% of studies showed accessory and duplicated PT each. Out of 20 articles reviewed, 51 lower limbs showed variation in origin, 230 lower limbs showed variations in insertion and 161 lower limbs showed other variations. CONCLUSION: PT muscle flap and tendon grafts are used in correcting the laxity of the ankle joint and foot drop. Absence of PT plays a crucial role in altering the mechanics of stress fractures of the 5th metatarsal. Thus, knowledge of the morphology of PT is crucial for plastic surgeons and orthopedic surgeons.

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Muscle atrophy is characterized by the loss of muscle function. Many efforts are being made to prevent muscle atrophy, and exercise is an important alternative. Methylglyoxal is a well-known causative agent of metabolic diseases and diabetic complications. This study aimed to evaluate whether methylglyoxal induces muscle atrophy and to evaluate the ameliorative effect of moderate-intensity aerobic exercise in a methylglyoxal-induced muscle atrophy animal model. Each mouse was randomly divided into three groups: control, methylglyoxal-treated, and methylglyoxal-treated within aerobic exercise. In the exercise group, each mouse was trained on a treadmill for 2 weeks. On the last day, all groups were evaluated for several atrophic behaviors and skeletal muscles, including the soleus, plantaris, gastrocnemius, and extensor digitorum longus were analyzed. In the exercise group, muscle mass was restored, causing in attenuation of muscle atrophy. The gastrocnemius and extensor digitorum longus muscles showed improved fiber cross-sectional area and reduced myofibrils. Further, they produced regulated atrophy-related proteins (i.e., muscle atrophy F-box, muscle RING-finger protein-1, and myosin heavy chain), indicating that aerobic exercise stimulated their muscle sensitivity to reverse skeletal muscle atrophy. In conclusion, shortness of the gastrocnemius caused by methylglyoxal may induce the dynamic imbalance of skeletal muscle atrophy, thus methylglyoxal may be a key target for treating skeletal muscle atrophy. To this end, aerobic exercise may be a powerful tool for regulating methylglyoxal-induced skeletal muscle atrophy.

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OBJECTIVE: The aim of this study was to examine the effects of probiotic supplementation on extensor digitorum longus (EDL) regeneration after grafting in mice. METHODS: EDL muscles were ortho-transplanted in mice. The experimental group was given 1 ×  108 colony-forming units/g body weight of Lactobacillus rhamnosus daily after EDL muscle transplantation surgeries. EDL muscle transplants were recovered after 3, 5, 7, and 14 d post-transplantation from the control as well as the experimental animals and processed for histologic analysis. RESULTS: At day 3 post-transplantation, the inflammatory cells had infiltrated into the grafted EDL muscles and the central section of the grafted tissue contained necrotic fibers. At day 5 post-transplantation, the concentration of inflammatory cells increased further and degenerative muscle fibers were being replaced with centrally nucleated muscle cells. The average cross-sectional area non-grafted EDL and grafted muscle in the probiotic supplemented mice at day 7 increased to 48% and 23% (P = 0.002), respectively, compared with the respective values in the control animals. Whereas in non-grafted and grafted EDL muscle it could approach 8% and 36% (P = 0.008), respectively at 14 d compared with the corresponding values of the control EDL muscle transplants. The number of muscle fibers in the non-grafted and grafted probiotic-supplemented groups increased to12% and 20% (P = 0.045) at day 7 compared with the control EDL muscle. In non-grafted and grafted EDL muscle, the number of regenerated muscle fibers increased to 73% and 64% (P = 0.110) at day 14 compared with control EDL grafted muscle. CONCLUSION: Results of the present study regarding better regeneration of skeletal muscle fibers in the probiotic-supplemented mice than the control grafts warrant further molecular-level investigation to understand the underlying mechanism mediating the process of skeletal muscle fiber regeneration. Probiotics possibly modulate the process of muscle fiber regeneration by adjusting the composition of gut microbiota.

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PURPOSE: We want to evaluate the feasibility of transferring a motor branch of the anterior tibial muscle (ATM) to the extensor digitorum longus (EDL) to evaluate this procedure in patients with spastic equinovarus foot (EVF) following post-stroke hemiplegia. METHODS: Ten cadaveric dissections from five fresh frozen human cadavers were performed to establish the anatomic feasibility of transferring a motor branch of the deep peroneal nerve, usually destinated to the ATM, to the branch of the EDL to manage spastic EVF. RESULTS: Six cases (60%) presented three branches destinated to the ATM, one case (10%) presented give branches, and three cases (30%) had four branches. In all specimens, the coaptation between the motor branch to the ATM, referred as the "effector" branch, and the branch of the EDL "receiver" branch was feasible without tension and did not require any intraneural dissection. CONCLUSION: This anatomical study confirms the feasibility of transferring a motor branch from the ATM to the EDL to correct a spastic EVF.

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We previously reported the significant increase in limb muscle strength and cross-sectional area of the type IIb muscle fibers in the extensor digitorum longus (EDL) muscle in a type 2 diabetic animal model, with Spontaneously Diabetic Torii (SDT) fatty rats (n = 6) undergoing regular treadmill exercise from 8 to 16 weeks of age compared with sedentary SDT fatty rats (n = 6). This study investigated the mechanism by which exercise training prevented skeletal muscle wasting in the EDL muscle of the SDT fatty rats. The endurance exercise for 8 weeks downregulated the expression of muscle RING-finger protein-1 (an E3 ubiquitin ligase) and upregulated the expression of CD31, insulin receptor substrate-2, and phosphorylated endothelial nitric oxide synthase in the EDL muscle of 16-week-old SDT fatty rats.Endurance exercise training might reduce muscle wasting by preventing muscle degradation and increasing the angiogenic response in the EDL muscle in type 2 diabetes.

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Disuse muscle atrophy is usually accompanied by changes in skeletal muscle structure, signaling, and contractile potential. Different models of muscle unloading can provide valuable information, but the protocols of experiments with complete immobilization are not physiologically representative of a sedentary lifestyle, which is highly prevalent among humans now. In the current study, we investigated the potential effects of restricted activity on the mechanical characteristics of rat postural (soleus) and locomotor (extensor digitorum longus, EDL) muscles. The restricted-activity rats were kept in small Plexiglas cages (17.0 × 9.6 × 13.0 cm) for 7 and 21 days. After this, soleus and EDL muscles were collected for ex vivo mechanical measurements and biochemical analysis. We demonstrated that while a 21-day movement restriction affected the weight of both muscles, in soleus muscle we observed a greater decrease. The maximum isometric force and passive tension in both muscles also significantly changed after 21 days of movement restriction, along with a decrease in the level of collagen 1 and 3 mRNA expression. Furthermore, the collagen content itself changed only in soleus after 7 and 21 days of movement restriction. With regard to cytoskeletal proteins, in our experiment we observed a significant decrease in telethonin in soleus, and a similar decrease in desmin and telethonin in EDL. We also observed a shift towards fast-type myosin heavy chain expression in soleus, but not in EDL. In summary, in this study we showed that movement restriction leads to profound specific changes in the mechanical properties of fast and slow skeletal muscles. Future studies may include evaluation of signaling mechanisms regulating the synthesis, degradation, and mRNA expression of the extracellular matrix and scaffold proteins of myofibers.

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Postactivation potentiation refers to an acute enhancement of contractile properties following muscle activity. Previously, the effects of prior muscle activation on eccentric force at tetanic activation frequencies have only been sparsely reported. This paper aimed to study acute activity-induced effects on eccentric force of slow and fast-twitch muscles and characterize them in relation to postactivation potentiation. We elicited eccentric contractions in isolated rat extensor digitorum longus and soleus muscles by actively lengthening muscles at a constant velocity. We assessed contractile properties by measuring force over shortly interspaced, identical eccentric, and isometric contractions. We then analyzed stretch force, isometric peak force, rate of force development, and relaxation times. Finally, we compared the time courses for the development and cessation of changes in stretch force to known features of postactivation potentiation. In extensor digitorum longus, muscles stretch force consistently increased in a contraction-to-contraction manner by up to 49% [95% confidence interval (CI): 35-64%] whereas isometric peak force simultaneously showed minor declines (8%, 95% CI: 5-10%). The development and cessation of eccentric force potentiation coincided with the development of twitch potentiation and increases in rate of force development. In soleus muscles we found no consistent eccentric potentiation. Characterization of the increase in eccentric force revealed that force only increased in the very beginning of an active stretch. Eccentric force at tetanic activation frequencies potentiates substantially in extensor digitorum longus muscles over consecutive contractions with a time course coinciding with postactivation potentiation. Such eccentric potentiation may be important in sport performance.NEW & NOTEWORTHY Force during eccentric contractions can increase to a magnitude that may have profound consequences for our understanding of skeletal muscle locomotion. This increase in eccentric force occurs over consecutive, shortly interspaced, tetanic contractions in rat extensor digitorum longus muscles-not in rat soleus muscles-and coincides with well-known traits of postactivation potentiation. Eccentric force potentiation may significantly enhance muscle performance in activities involving stretch-shortening cycles.

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BACKGROUND: Arthroscopy of the ankle is an important surgical technique that has become increasingly popular over the years due to its usefulness in the treatment of many ankle conditions. Nevertheless, it's not deprived of complications. Extensor hallucis longus (EHL) tendon ruptures following anterior ankle arthroscopy have only been reported 3 times in the literature. CASE REPORT: We report the case of a 52-year-old female submitted to ankle arthroscopy with removal of a bony fragment located at the tip of the lateral malleolus and ATFL ligament repair (arthroscopic Bröstrom-Gould). At the sixth postoperative week, she experienced a sudden "pop" located at the anterior aspect of the ankle with inability to actively extend the hallux and difficulty in walking barefoot with disruption of normal gait. MRI showed a complete rupture of the extensor hallucis longus tendon with approximately 6 cm separation between the tendon ends. Surgical treatment was performed: tendinous transfer of the extensor digitorum longus (EDL) to the EHL using a Pulvertaft technique. At the 12th postoperative week, the patient could actively extend the hallux and the second toe with a range of motion similar to the contralateral foot. CONCLUSION: This case reports a delayed EHL tendon rupture following ankle arthroscopy treated surgically with a good functional result. To our knowledge, this is the first published case of delayed EHL tendon rupture following anterior ankle arthroscopy treated surgically with a tendinous transfer of the EDL to the EHL. The possible causes leading to this complication and the different surgical techniques that could have been used to treat this pathology were discussed.

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A fluorescent dye commonly used to image tissues under load (5-DTAF) has previously been shown to stiffen tendons. This study hypothesized that 5-DTAF staining stiffens tendons through reduced fiber sliding, altering the rate at which crimped collagen fibers straighten under load. This was tested by using reflected cross-polarized light microscopy to measure fiber crimp period of cervine extensor digitorum longus tendon specimens under axial load. Specimens were treated with either phosphate buffered saline (negative control), genipin (positive control), or 5-DTAF. In saline treated specimens, crimp period (relative to unstretched) increased at approximately 2.5 times the applied axial strain, indicating substantial fiber sliding. In both 5-DTAF and genipin treated specimens, this ratio was reduced to 1:1, indicating no fiber sliding. These results add further evidence that care should be taken when using 5-DTAF to stain tissue for studying microscale deformations in tissues.

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Neuromuscular efficiency is defined as the ratio of work output to stimulation rate. The purpose of these experiments was to test the hypothesis that neuromuscular efficiency would be increased in proportion to posttetanic potentiation, that is, the stimulation-induced increase in work output displayed by rodent fast-twitch muscle. To this end, extensor digitorum longus muscles from wild-type and skeletal myosin light chain kinase knockout (skMLCK-/- ) mice were surgically isolated and suspended in vitro (25°C). Concentric force development during shortening at 70% of maximal unloaded shortening velocity was tested at stimulus frequencies between 10 and 80 Hz both before and after a potentiating tetanus. A strong genotype-dependent difference in the potentiation of concentric work output was observed; concentric work output of wild-type muscles was increased by 51%-88% while that of skMLCK-/- muscles was increased by only 20%-34% across the frequencies tested. As a result, comparison of work - frequency plots revealed that the frequency required for peak and 50% peak unpotentiated work of wild-type muscles was decreased from ~80 to 52 Hz and from ~48 to 21 Hz, respectively. By contrast, the frequency required for peak and 50% peak unpotentiated work of skMLCK-/- muscles was decreased from ~80 to 68 Hz and from ~51 to 41 Hz, respectively. Thus, wild-type muscles with the ability to phosphorylate myosin displayed larger increases in neuromuscular efficiency than skMLCK-/- muscles (25-30 vs 10-15 Hz, respectively). This suggests that the presence of myosin phosphorylation may ameliorate or mitigate fatigue mechanisms associated with high-frequency stimulation rates.

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PURPOSE: The double tendon of extensor digitorum longus (EDL) muscle was observed on the left leg of a 80-year-old male cadaver. METHODS: A male cadaver 80 years old was subjected to routine anatomical dissection for research and teaching purposes. RESULTS: The main tendon of the EDL muscle started just at the end of the muscle belly. However, the accessory tendon started at the tendinous end of the muscle as a continuation of the muscle. The main and accessory tendons split into two more slips after passing through the same tunnel below the extensor retinaculum. There was also difference on ending of the tendon slips of EDL muscle. The main tendon divided into two tendinous slips on the dorsum of the foot attached to the second and third toes. The accessory tendon divided into two tendinous slips on the dorsum of the foot attached to the fourth and the fifth toes. CONCLUSION: Knowledge of the tendons and anatomical differences of this muscle is important for surgeons in interventional procedures involving the dorsum of the foot.

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Background: Sarcopenia is an age-related skeletal muscle dysfunction syndrome that is lacking validated treatments. Maximizing muscle strength in young adulthood may be a promising way to prevent sarcopenia in the elderly. The phytomolecule puerarin has been extensively used in clinical practice and reported to increase energy metabolism in skeletal muscle by directly targeting the skeletal muscle fiber. However, the bioavailability of puerarin is very poor, and almost 93% of puerarin stays in the intestine until excretion. Therefore, we hypothesize that puerarin may regulate gut microbiota to improve skeletal muscle strength and/or mass in adults. Methods: Twenty three-month old male Sprague Dawley rats were divided into two groups according to average weights, puerarin group (puerarin dissolved in 0.5% CMC-Na, 150 â€‹mg/kg/day, N â€‹= â€‹10), and control group (equal volume 0.5% CMC-Na, N â€‹= â€‹10). The treatment lasted for 8 weeks. Muscle weight, muscle fiber types and cross-sectional area (CSA), ex vivo muscle contraction test and grip strength were measured. 16S rDNA sequencing was employed to evaluate the gut microbiota composition in the sample of cecal content. Short-chain fatty acids (SCFAs) in cecal and serum were analyzed by gas chromatography-mass spectrometry. Adenosine triphosphate (ATP) concentration in skeletal muscle was also detected. Pearson's correlation was used to analyze the relations between SCFAs, ATP concentration and muscle function. Results: After puerarin treatment, grip strength, the specific twitch force, and the tetanic forces in the soleus (SOL) and extensor digitorum longus (EDL) muscle were significantly higher than those of the control group. The percentage and CSA of type II muscle fiber in EDL was higher in the puerarin group than those in the control group. Puerarin treatment significantly changed the gut microbial constitutes. Two SCFAs-productive microbiota, the families Peptococcaceae and Closteridiales, were significantly higher in the puerarin group than those in the control group, while the ratio of Prevotellaceae/Bacteroidaceae (P/B), a muscle atrophy indicator, was lower in the puerarin group. As expected, there were significant linear correlations between the concentrations of SCFAs, including cecal total SCFAs, serum n-butyric acid and total SCFAs, and skeletal muscle strength and function, including the twitch force and tetanic force of SOL and EDL, as well as the forelimb grip strength. Conclusion: In conclusion, puerarin improved the forelimb grip strength and muscle contraction function in young adult rats. The underlying mechanism may include that puerarin increased SCFAs production by regulating gut microbiota, augmented ATP synthesis and skeletal muscle strength. The translational potential of this article : Our study finds that a clinical used phytomolecule puerarin has the potential of improving skeletal muscle strength in young adult rats. As puerarin has long-term clinical experience and shows good safety, it might be a potential candidate for developing muscle strengthening agents.

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Background: Sarcopenia is a new and emerging risk factor aggravating the quality of life of elderly population. Because Korean Red Ginseng (RG) is known to have a great effect on relieving fatigue and enhancing physical performance, it is invaluable to examine its potential as an anti-sarcopenic drug. Methods: Anti-sarcopenic effect of non-saponin fraction of Korean Red Ginseng (RGNS) was evaluated in C2C12 myoblasts treated with C2-ceramide to induce senescence phenotypes, and 22-month-old mice fed with chow diet containing 2% RGNS (w/w) for 4 further months. Results: The RGNS treatment significantly alleviated cellular senescence indicated by intracellular lipid accumulation, increased amount of lysosomal ß-galactosidase, and reduced proliferative capacity in C2C12 myoblasts. This effect was not observed with saponin fraction. In an aged mouse, the 4-month-RGNS diet significantly improved aging-associated loss of muscle mass and strength, assessed by the weights of hindlimb skeletal muscles such as tibialis anterior (TA), extensor digitorum longus (EDL), gastrocnemius (GN) and soleus (SOL), and the cross-sectional area (CSA) of SOL muscle, and the behaviors in grip strength and hanging wire tests, respectively. During the same period, an aging-associated shift of fast-to slow-twitch muscle in SOL muscle was also retarded by the RGNS treatment. Conclusions: These findings suggested that the long-term diet of RGNS significantly prevented aging-associated muscle atrophy and reduced physical performance, and thus RGNS has a strong potential to be developed as a drug that prevents or improves sarcopenia.

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Ecccentric muscle contractions are fundamental to everyday life. They occur markedly in jumping, running, and accidents. Following an initial force rise, stretching of a fully activated muscle can result in a phase of decreasing force ("Give") followed by force redevelopment. However, how the stretch velocity affects "Give" and force redevelopment remains largely unknown. We investigated the force produced by fully activated single-skinned fibers of rat extensor digitorum longus muscles during long stretches. Fibers were pulled from length 0.85 to 1.3 optimal fiber length at a rate of 1%, 10%, and 100% of the estimated maximum shortening velocity. "Give" was absent in slow stretches. Medium and fast stretches yielded a clear "Give." After the initial force peak, forces decreased by 11.2% and 27.8% relative to the initial peak force before rising again. During the last half of the stretch (from 1.07 to 1.3 optimal fiber length, which is within the range of the expected descending limb of the force-length relationship), the linear force slope tripled from slow to medium stretch and increased further by 60% from medium to fast stretch. These results are compatible with forcible cross-bridge detachment and redevelopment of a cross-bridge distribution, and a viscoelastic titin contribution to fiber force. Accounting for these results can improve muscle models and predictions of multibody simulations.NEW & NOTEWORTHY Eccentric muscle contractions are part of our daily lives. We found that force increased monotonically during slow stretches of fully activated muscle fibers, whereas higher stretch velocities resulted in an increasing drop in force after an initial increase and a final steeper rise in force. Cross-bridges cannot explain the observed force traces. This requires a viscoelastic non-cross-bridge contribution. Considering these results can improve muscle models and predictions of multibody simulations.

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