Plantaris Research Articles

Better maintenance of enzymatic capacity and higher levels of substrate transporter proteins in skeletal muscle of aging female mice.

This study investigated sex-specific differences in high-energy phosphate, glycolytic, and mitochondrial enzyme activities and also metabolite transporter protein levels in the skeletal muscles of adult (5 months old), middle-aged (12 months old), and advanced-aged (24 months old) mice. While gastrocnemius glycogen content increased with age regardless of sex, gastrocnemius triglyceride levels increased only in advanced-aged female mice. Aging decreased creatine kinase and adenylate kinase activities in the plantaris muscle of both sexes and in the soleus muscle of male mice but not in female mice. Irrespective of sex, phosphofructokinase and lactate dehydrogenase (LDH) activities decreased in the plantaris and soleus muscles. Additionally, hexokinase activity in the plantaris muscle and LDH activity in the soleus muscle decreased to a greater extent in aged female mice compared with those in aged male mice. Mitochondrial enzyme activities increased in the plantaris muscle of aged female mice but did not change in male mice. The protein content of the glucose transporter 4 in the aged plantaris muscle and fatty acid translocase/cluster of differentiation 36 increased in the aged plantaris and soleus muscles of both sexes, with a significantly higher content in female mice. These findings suggest that females possess a better ability to maintain metabolic enzyme activity and higher levels of metabolite transport proteins in skeletal muscle during aging, despite alterations in lipid metabolism. Our data provide a basis for studying muscle metabolism in the context of age-dependent metabolic perturbations and diseases that affect females and males differently.

Glycative stress inhibits hypertrophy and impairs cell membrane integrity in overloaded mouse skeletal muscle.

Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism. Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)-treated and AGE-treated groups. Mice in the AGE-treated group were intraperitoneally administered AGEs (0.5mg/g) once daily, whereas those in the BSA-treated group received an equal amount of BSA (0.5mg/g) as the vehicle control. After 7days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1mg/mL) to examine cell adhesion and cell membrane permeability. Continuous AGE administration increased the levels of fluorescent AGEs, Nε-(carboxymethyl) lysine, and methylglyoxal-derived hydroimidazolone-1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross-sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE-treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K-means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin-glycoprotein complex proteins and cell adhesion-related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability. This study indicates that glycative stress may be a novel pathogenic factor in skeletal muscle dysfunctions by causing loss of membrane integrity and preventing muscle mass gain.

Postural control and ankle joint functions: an investigation on collegiate female volleyball players

PurposeAnkle injuries are common in volleyball players and are linked to the athlete’s postural control. The aim of the report is to investigate the differences between ankle functions and postural control ability of volleyball players and controls, and also the relationship between the variables in order to understand the factors affecting postural control.Methods40 female participants (age: 21.18 ± 0.27, volleyball players/controls: 20/20) were included in the study. Ankle functions (joint range of motion (ROM), joint position sense (JPS), vibration and isometric muscle strength) and postural control variables (anterior-posterior and medial-lateral sway velocity, ellipse area and perimeter) were evaluated by static stability test. The differences between the groups and the correlation between variables were analysed.ResultsSignificant differences favoured the volleyball group in ankle dorsiflexion, inversion, and eversion ROM, JPS, dorsiflexor and plantar flexor isometric muscle strength, and postural control variables (p < 0.05). However, the control group demonstrated superior vibration sensitivity on the 1st and 5th metatarsal heads (p < 0.05). A significant correlation was observed between the anterior-posterior sway velocity and dorsiflexion ROM, medial-lateral sway velocity and sway area with inversion ROM, sway area and vibration threshold in the 1st and 5th metatarsal heads (p < 0.05).ConclusionsVolleyball players showed better results in ankle ROM, JPS, muscle strength and postural control. In addition to the similarities in ankle plantar flexion ROM, invertor and evertor isometric muscle strength between the groups, the controls showed better vibration sensitivity; which reveals potential causes of ankle injuries in volleyball players. Ankle function variables are found to be linked to postural control, highlighting the need to evaluate these functions for injury prevention.

Endurance training increases mitochondrial myoglobin and enhances its interaction with complex IV in rat plantaris muscle.

Endurance exercise training is known to increase mitochondrial respiration in skeletal muscle. However, the molecular mechanisms behind this are not fully understood. Myoglobin (Mb) is a member of the globin family, which is highly expressed in skeletal and cardiac muscles. We recently found that Mb localizes inside mitochondria in skeletal muscle and interacts with cytochrome c oxidase subunit IV (COXIV), a subunit of mitochondrial complex IV, which regulates respiration by augmenting complex IV activity. In the present study, we investigated the effect of endurance training on Mb-COXIV interaction within mitochondria in rat skeletal muscle. Eight-week-old male Wistar rats were subjected to 6-week treadmill running training. Forty-eight hours after the last training session, the plantaris muscle was removed under anesthesia and used for biochemical analysis. The endurance training increased mitochondrial content in the skeletal muscle. It also augmented complex IV-dependent oxygen consumption and complex IV activity in isolated mitochondria from skeletal muscle. Furthermore, endurance training increased Mb expression at the whole muscle level. Importantly, mitochondrial Mb content and Mb-COXIV binding were increased by endurance training. These findings suggest that an increase in mitochondrial Mb and the concomitant enhancement of Mb interaction with COXIV may contribute to the endurance training-induced upregulation of mitochondrial respiration by augmenting complex IV activity.

Tibial nerve branching pattern and compatibility of branches for the deep fibular nerve.

In individuals who develop drop foot due to nerve loss, several methods such as foot-leg orthosis, tendon transfer, and nerve grafting are used. Nerve transfer, on the other hand, has been explored in recent years. The purpose of this study was to look at the tibial nerve's branching pattern and the features of its branches in order to determine the suitability of the tibial nerve motor branches, particularly the plantaris muscle motor nerve, for deep fibular nerve transfer. There were 36 fixed cadavers used. Tibial nerve motor branches were observed and measured, as were the lengths, distributions, and thicknesses of the common fibular nerve and its branches at the bifurcation region. The motor branches of the tibial nerve that supply the soleus muscle, lateral head, and medial head of the gastrocnemius were studied, and three distinct forms of distribution were discovered. The motor branch of the gastrocnemius medial head was commonly observed as the first branch to divide, and it appeared as a single root. The nerve of the plantaris muscle was shown to be split from many origins. When the thickness and length of the motor branches measured were compared, the nerve of the soleus muscle was determined to be the most physically suited for neurotization. In today drop foot is very common. Traditional methods of treatment are insufficient. Nerve transfer is viewed as an application that can both improve patient outcomes and hasten the patient's return to society. The nerve of the soleus muscle was shown to be the best candidate for transfer in our investigation.

Beneficial effects of resistance training on both mild and severe mouse dystrophic muscle function as a preclinical option for Duchenne muscular dystrophy.

Mechanical overloading (OVL) resulting from the ablation of muscle agonists, a supra-physiological model of resistance training, reduces skeletal muscle fragility, i.e. the immediate maximal force drop following lengthening contractions, and increases maximal force production, in mdx mice, a murine model of Duchene muscular dystrophy (DMD). Here, we further analyzed these beneficial effects of OVL by determining whether they were blocked by cyclosporin, an inhibitor of the calcineurin pathway, and whether there were also observed in the D2-mdx mice, a more severe murine DMD model. We found that cyclosporin did not block the beneficial effect of 1-month OVL on plantaris muscle fragility in mdx mice, nor did it limit the increases in maximal force and muscle weight (an index of hypertrophy). Fragility and maximal force were also ameliorated by OVL in the plantaris muscle of D2-mdx mice. In addition, OVL increased the expression of utrophin, cytoplamic γ-actin, MyoD, and p-Akt in the D2-mdx mice, proteins playing an important role in fragility, maximal force gain and muscle growth. In conclusion, OVL reduced fragility and increased maximal force in the more frequently used mild mdx model but also in D2-mdx mice, a severe model of DMD, closer to human physiopathology. Moreover, these beneficial effects of OVL did not seem to be related to the activation of the calcineurin pathway. Thus, this preclinical study suggests that resistance training could have a potential benefit in the improvement of the quality of life of DMD patients.

Effects of hindlimb unloading on the mevalonate and mechanistic target of rapamycin complex 1 signaling pathways in a fast-twitch muscle in rats.

Fast-twitch muscles are less susceptible to disuse atrophy, activate the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, and increase protein synthesis under prolonged muscle disuse conditions. However, the mechanism underlying prolonged muscle disuse-induced mTORC1 signaling activation remains unclear. The mevalonate pathway activates the mTORC1 signaling pathway via the prenylation and activation of Ras homolog enriched in brain (Rheb). Therefore, we investigated the effects of hindlimb unloading (HU) for 14 days on the mevalonate and mTORC1 signaling pathways in the plantaris muscle, a fast-twitch muscle, in adult male rats. Rats were divided into HU and control groups. The plantaris muscles of both groups were harvested after the treatment period, and the expression and phosphorylation levels of metabolic and intracellular signaling proteins were analyzed using Western blotting. We found that HU increased the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme of the mevalonate pathway, and activated the mTORC1 signaling pathway without activating AKT, an upstream activator of mTORC1. Furthermore, HU increased prenylated Rheb. Collectively, these findings suggest that the activated mevalonate pathway may be involved in the activation of the Rheb/mTORC1 signaling pathway without AKT activation in fast-twitch muscles under prolonged disuse conditions.

Lactate administration induces skeletal muscle synthesis by influencing Akt/mTOR and MuRF1 in non-trained mice but not in trained mice.

The perception regarding lactate has changed over the past decades, and some of its physiological roles have gradually been revealed. However, the effects of exogenous lactate on skeletal muscle synthesis remain unclear. This study aimed to confirm the effects of a 5-week lactate administration and post-exercise lactate administration on skeletal muscle synthesis. Thirty-two Institute of Cancer Research mice were randomly assigned to non-trained + placebo, non-trained + lactate, trained + placebo, and trained + lactate groups. Furthermore, 3 g/kg of lactate or an equivalent volume of saline was immediately administered after exercise training (maximum oxygen uptake: 70%). Lactate administration and/or exercise training was performed 5 days/week for 5 weeks. After the experimental period, it was observed that lactate administration tended to elevate skeletal muscle weight, increased protein kinase B (p < 0.05) and mammalian target of rapamycin (p < 0.05) mRNA levels, and decreased muscle ring-finger protein-1 expression (p < 0.05). Lactate administration after exercise training significantly enhanced plantaris muscle weight; however, it had no additional effects on most signaling factors. This study demonstrated that a 5-week lactate administration could stimulate skeletal muscle synthesis, and lactate administration after exercise training may provide additional effects, such as increasing skeletal muscle.

Diet-induced obesity does not exacerbate cachexia in male mice bearing Lewis-lung carcinoma tumors.

Cachexia is a muscle-wasting syndrome commonly observed in patients with cancer, which can significantly worsen clinical outcomes. Because of a global rise in obesity, the coexistence of cachexia in obese individuals poses unique challenges, with the impact of excessive adiposity on cachexia severity and underlying pathophysiology not well defined. Understanding the interplay between cachexia and obesity is crucial for improving diagnosis and treatment strategies for these patients; therefore, the present study examined differences in cachexia between lean and obese mice bearing Lewis lung carcinoma (LLC) tumors. Nine-week-old, male C57Bl6J mice were placed on either a chow or a high-fat diet (HFD) for 9 wk. After the diet intervention, mice were inoculated with LLC or vehicle. Markers of cachexia, such as body and muscle loss, were noted in both chow and HFD groups with tumors. Tumor weight of HFD animals was greater than that of chow. LLC tumors reduced gastrocnemius, plantaris, and soleus mass, regardless of diet. The tibialis anterior and plantaris mass and cross-sectional area of type IIb/x fibers in the gastrocnemius were not different between HFD-chow, HFD-tumor, and chow-tumor. Using RNA sequencing (RNA-seq) of the plantaris muscle from chow-tumor and HFD-tumor groups, we identified ∼400 differentially expressed genes. Bioinformatic analysis identified changes in lipid metabolism, mitochondria, bioenergetics, and proteasome degradation. Atrophy was not greater despite larger tumor burden in animals fed an HFD, and RNA-seq data suggests that partial protection is mediated through differences in mitochondrial function and protein degradation, which may serve as future mechanistic targets.NEW & NOTEWORTHY This study provides timely information on the interaction between obesity and cancer cachexia. Lean and obese animals show signs of cachexia with reduced body weight, adipose tissue, and gastrocnemius muscle mass. There was not significant wasting in the tibialis anterior, plantaris, or fast twitch fibers in the gastrocnemius muscle of obese animals with tumors. RNA-seq analysis reveals that obese tumor bearing animals had differential expression of mitochondria- and degradation-related genes, which may direct future studies in mechanistic research.

Nanoporous graphene-based thin-film microelectrodes for in vivo high-resolution neural recording and stimulation

One of the critical factors determining the performance of neural interfaces is the electrode material used to establish electrical communication with the neural tissue, which needs to meet strict electrical, electrochemical, mechanical, biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin-film technology and its engineering to form flexible neural interfaces. The developed technology allows the fabrication of small microelectrodes (25 µm diameter) while achieving low impedance (∼25 kΩ) and high charge injection (3–5 mC cm−2). In vivo brain recording performance assessed in rodents reveals high-fidelity recordings (signal-to-noise ratio >10 dB for local field potentials), while stimulation performance assessed with an intrafascicular implant demonstrates low current thresholds (<100 µA) and high selectivity (>0.8) for activating subsets of axons within the rat sciatic nerve innervating tibialis anterior and plantar interosseous muscles. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical (12 week) and intraneural (8 week) implantation. This work describes a graphene-based thin-film microelectrode technology and demonstrates its potential for high-precision and high-resolution neural interfacing.

Ladder-based resistance training with the progression of training load altered the tibial nerve ultrastructure and muscle fiber area without altering the morphology of the postsynaptic compartment.

Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce. Therefore, the present study aimed to compare the morphological response induced by different LRT protocols in the ultrastructure of the tibial nerve and morphology of the motor endplate and muscle fibers of the soleus and plantaris muscles of young adult Wistar rats. Rats were divided into groups: sedentary control (control, n = 9), a predetermined number of climbs and progressive submaximal intensity (fixed, n = 9), high-intensity and high-volume pyramidal system with a predetermined number of climbs (Pyramid, n = 9) and lrt with a high-intensity pyramidal system to exhaustion (failure, n = 9). myelinated fibers and myelin sheath thickness were statistically larger in pyramid, fixed, and failure. myelinated axons were statistically larger in pyramid than in control. schwann cell nuclei were statistically larger in pyramid, fixed, and failure. microtubules and neurofilaments were greater in pyramid than in control. morphological analysis of the postsynaptic component of the plantar and soleus muscles did not indicate any significant difference. for plantaris, the type i myofibers were statistically larger in the pyramid and fixed compared to control. the pyramid, fixed, and failure groups for type ii myofibers had larger csa than control. for soleus, the type i myofibers were statistically larger in the pyramid than in control. pyramid and fixed had larger csa for type ii myofibers than control and failure. the pyramid and fixed groups showed greater mass progression delta than the failure. We concluded that the LRT protocols with greater volume and progression of accumulated mass elicit more significant changes in the ultrastructure of the tibial nerve and muscle hypertrophy without endplate changes.

Capitalizing on skin in orthotics design: the effects of texture on plantar intrinsic foot muscles during locomotion.

Foot orthoses (FO) are a commonly prescribed intervention to alter foot function during walking although their effects have been primarily studied in the extrinsic muscles of the foot. Furthermore, enhancing sensory feedback under the foot sole has been recently shown to alter extrinsic muscle activity during gait; however, the effects of FOs with enhanced sensory feedback on plantar intrinsic foot muscles (PIFMs) remain unknown. Thus, the purpose of this study was to investigate the effect of FOs with and without sensory facilitation on PIFM activity during locomotion. Forty healthy adults completed a series of gait trials in non-textured and textured FOs when walking over hard and soft flooring. Outcome measures included bilateral joint kinematics and electromyography (EMG) of four PIFMs. Results of this study highlight the distinct onset and cessations of each PIFM throughout the stance phase of gait. PIFMs remained active during mid-stance when wearing FOs and textured FOs facilitated muscle activity across the stance phase of gait. Increasing cutaneous input from foot sole skin, via the addition of texture under the foot sole, appears to alter motor-neuron pool excitation of PIFMs. Future academics are encouraged to increase our understanding on which pathologies, diseases, and/or medical conditions would best benefit from textured FOs.

Additive impact of soy protein dietary intake and exercise on visceral fat mass reduction and mitochondrial complex I activation in skeletal muscle.

Soy protein has shown remarkable effectiveness in reducing fat mass compared with other protein sources, and exercise has the potential to further enhance this fat loss effect. Previous studies have demonstrated that soy protein intake leads to decreased fatty acid synthesis, which contributes to its fat-loss properties. However, the exact mechanism by which these lipids are consumed remains unclear. To investigate this, we conducted a comprehensive study using C57/BL6 male mice, comparing the effects of soy and casein proteins with and without exercise (Casein-Sed, Casein-Ex, Soy-Sed, and Soy-Ex groups) under high- and low-protein conditions (14% or 40% protein). Our findings revealed that combining soy protein intake with exercise significantly reduced epididymal white adipose tissue (eWAT) weight, particularly in the high-protein diet group. Further analysis revealed that exercise increased the expression of lipid oxidation-regulatory proteins, including mitochondrial oxidative phosphorylation protein (OXPHOS) complexes, in the plantaris muscle regardless of the protein source. Although soy protein intake did not directly affect muscle mitochondrial protein expression, the activity of OXPHOS complex I was additively enhanced by exercise and soy protein under the 40% protein condition. Notably, complex I activity inversely correlated with eWAT weight in the soy protein diet group. These results highlight the potential link between improved complex I activity induced by soy protein and fat mass reduction, which emphasizes the promising benefits of combining soy protein with exercise in promoting fat loss.NEW & NOTEWORTHY The findings revealed that soy protein intake combined with exercise resulted in reduced adipose tissue weight compared with that obtained with casein protein intake. Furthermore, the joint impact of exercise and soy protein consumption resulted in enhanced activity of oxidative phosphorylation protein (OXPHOS) complex I in fast-twitch muscles, which appears to be associated with fat mass reduction. These findings elucidate the potential additive effects of soy protein and exercise on body weight management.

Plantar intrinsic foot muscle activity and its relationship with postural sway during tiptoe standing in ballet dancers and non-dancers

BackgroundMinimizing postural sway during tiptoe standing is essential for ballet dancers. Investigation of the activity of the plantar intrinsic foot muscles (PIFMs) may provide insight into postural sway in dancers. Herein, we compared PIFM activity during tiptoe standing between dancers and non-dancers and examined its relationship with postural sway. MethodsWe enrolled 14 female ballet dancers and 13 female non-dancers. Electromyography (EMG) amplitudes of 64 channels of PIFMs and center of pressure (COP) data were recorded during bipedal tiptoe standing tasks performed with ankle plantarflexion angles of 20°, 40°, and 60° (dancers only). The EMG amplitudes were normalized to those during the maximum voluntary contraction, and the muscle activity level and its coefficient of variation over time (EMG-CVtime) during the task were assessed. Standard deviations in the anteroposterior and mediolateral directions, velocity, and area were calculated from the COP data. ResultsMost COP and EMG variables were significantly lower in dancers than in non-dancers in both the 20° and 40° tasks (p < 0.05). Significant correlations were found between most combinations of the COP and EMG variables in both the 20° and 40° tasks in the whole cohort (r = 0.468–0.807, p ≤ 0.014). In the 60° task in dancers, COP velocity was strongly correlated with EMG-CVtime (r = 0.700, p = 0.005). ConclusionThese results provide novel evidence that the PIFMs do not require high activity, but rather that its low, steady activity is the key, to achieve less postural sway during bipedal tiptoe standing in dancers.

Stuart has got the PoWeR! Skeletal muscle adaptations to a novel heavy progressive weighted wheel running exercise model in C57BL/6 mice.

Murine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named 'PoWeR', was previously developed to serve as a more translatable alternative to involuntary resistance-type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic-to-oxidative shift in muscle fibre type. Thus, PoWeR reflects a blended resistance/endurance model. In an attempt to bias PoWeR further towards resistance-type exercise, we developed a novel heavy PoWeR model (hPoWeR) utilizing higher wheel loads (max of 12.5g vs 6g). Adult male C57BL/6 mice voluntarily performed an 8-week progressive loading protocol (PoWeR or hPoWeR). Running distance peaked at ∼5-6kmday-1 in both treatments and was maintained by PoWeR mice, but declined in the hPoWeR mice as load increased beyond 7.5g. Peak isometric force of the gastrocnemius-soleus-plantaris complex tended to increase in wheel running treatments. Soleus mass increased by 19% and 24% in PoWeR and hPoWeR treatments, respectively, and plantaris fibre cross-sectional area was greater in hPoWeR, compared to PoWeR. There were fewer glycolytic and more oxidative fibres in the soleus and plantaris muscles in the PoWeR treatment, but not hPoWeR. Collectively, these data suggest hPoWeR may modestly alter skeletal muscle supporting the aim of better reflecting typical resistance training adaptations, in line with decreased running volume and exposure to higher resistance. Regardless, PoWeR remains an effective hypertrophic concurrent training model in mice.

A three-headed plantaris muscle fused with Kaplan fibers: potential clinical significance.

The plantaris is a short, small muscle that usually originates at the popliteal surface of the femur and has a long, thin tendon that typically inserts into the calcaneal tuberosity. Its role and degree of development have been objects of debate for years. Some authors consider it a vestigial muscle while others believe it is a process of its development. The clinical significance of plantaris muscle is usually related to its morphological variation, which is common and well described in the literature. These variations are often a risk factor for many ailments and disorders. We would like to present another, very rare case of three-headed plantaris muscle (fused with distal Kaplan fibers), and consider what clinical implications it may have.

Effect of Low-Load Blood Flow Restriction Training on Patients With Functional Ankle Instability: A Randomized Controlled Trial.

Decreased muscle strength and balance in patients with functional ankle instability (FAI) can be effectively improved by ankle strength training. Low-load blood flow restriction (LL-BFR) training increases muscle size and strength, but there is limited evidence from studies on muscle strength and balance in FAI patients. To study the effects of LL-BFR training versus high-load training (HLT) on muscle strength and balance in FAI patients. Randomized controlled trial. Forty-six young adults with a history of FAI. Participants in the LL-BFR and HLT groups performed 4 sets (30 × 15 × 15 × 15) of ankle training at 20% to 40% of the one-repetition maximum and 70% to 85% one-repetition maximum, respectively, twice a week for 6weeks. Plantar flexion, dorsiflexion, inversion, and eversion muscle strength, and the Y-balance test scores were assessed at baseline and after 3 and 6weeks; the thickness of the tibialis anterior, triceps surae, and peroneus longus muscles were assessed at baseline and after 6weeks. Inversion, eversion, dorsiflexion, and plantar flexion muscle strength; tibialis anterior, triceps surae, and peroneus longus thickness; and Y-balance test scores were significantly increased in the LL-BFR group after 3 and 6weeks compared with baseline (P < .05), with no significant difference between the LL-BFR and HLT groups after 6weeks (P > .05). However, at the end of 3weeks, eversion muscle strength and Y-balance test scores were significantly higher in the LL-BFR group than in the HLT group (P < .05). Over 6weeks, LL-BFR training was as effective as HLT in improving ankle muscle strength, muscle thickness, and balance in FAI patients, but LL-BFR training improved the ankle eversion muscle strength and dynamic balance more than HLT did in the early stages of the intervention. This finding will provide a new intervention strategy for the clinical rehabilitation of FAI patients.

Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy.

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is a treatment for colorectal cancer that can induce persistent fatigue and metabolic dysfunction. Regular exercise after chemotherapy cessation is widely recommended for cancer patients and has been shown to improve fatigue resistance in mice. However, gaps remain in understanding whether the early systemic and skeletal muscle adaptations to regular exercise are altered by prior FOLFOX chemotherapy treatment. Furthermore, the effects of exercise duration on early metabolic and skeletal muscle transcriptional adaptations are not fully established. Purpose: Investigate the effects of prior FOLFOX chemotherapy treatment on the early adaptations to repeated short- or long-duration treadmill exercise, including the fasting regulation of circulating metabolic regulators, skeletal muscle COXIV activity and myokine/exerkine gene expression in male mice. Methods: Male C57BL6/J mice completed 4 cycles of FOLFOX or PBS and were allowed to recover for 4-weeks. Subsets of mice performed 14 sessions (6d/wk, 18m/min, 5% grade) of short- (10min/d) or long-duration (55min/d) treadmill exercise. Blood plasma and muscle tissues were collected 48-72h after the last exercise bout for biochemical analyses. Results: Long-duration exercise increased fasting plasma osteocalcin, LIF, and IL-6 in healthy PBS mice, and these changes were ablated by prior FOLFOX treatment. Slow-oxidative soleus muscle COXIV activity increased in response to long-duration exercise in PBS mice, which was blocked by prior FOLFOX treatment. Fast-glycolytic plantaris muscle COXIV activity increased with short-duration exercise independent of FOLFOX administration. There was a main effect for long-duration exercise to increase fasting muscle IL-6 and COXIV mRNA expression independent of FOLFOX. FOLFOX administration reduced muscle IL-6, LIF, and BDNF mRNA expression irrespective of long-duration exercise. Interestingly, short-duration exercise suppressed the FOLXOX induction of muscle myostatin mRNA expression. Conclusion: FOLFOX attenuated early exercise adaptations related to fasting circulating osteocalcin, LIF, and IL-6. However, prior FOLFOX treatment did not alter the exercise adaptations of plantaris muscle COXIV activity and plasma adiponectin. An improved understanding of mechanisms underlying exercise adaptations after chemotherapy will provide the basis for successfully treating fatigue and metabolic dysfunction in cancer survivors.

Inhibition of p53-MDM2 binding reduces senescent cell abundance and improves the adaptive responses of skeletal muscle from aged mice.

Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice. The goal of this study was to determine if a novel pharmaceutical agent (BI01), which functions by upregulating p53 through inhibition of binding to MDM2, the primary p53 regulatory protein, improves muscle regeneration and hypertrophy in old mice. BI01 effectively reduced the number of senescent cells in vitro but had no effect on MPC survival or proliferation at a comparable dose. Following repeated oral gavage with 2mg/kg of BI01 (OS) or vehicle (OV), old mice (24months) underwent unilateral BaCl2 injury in the tibialis anterior (TA) muscle, with PBS injections serving as controls. After 7days, satellite cell number was higher in the TA of OS compared to OV mice, as was the expression of genes involved in ATP production. By 35days, old mice treated with BI01 displayed reduced senescent cell burden, enhanced regeneration (higher muscle mass and fiber cross-sectional area) and restoration of muscle function relative to OV mice. To examine the impact of 2mg/kg BI01 on muscle hypertrophy, the plantaris muscle was subjected to 28days of mechanical overload (MOV) in OS and OV mice. In response to MOV, OS mice had larger plantaris muscles and muscle fibers than OV mice, particularly type 2b + x fibers, associated with reduced senescent cells. Together our data show that BI01 is an effective senolytic agent that may also augment muscle metabolism to enhance muscle regeneration and hypertrophy in old mice.

A RARE ANATOMICAL VARIATION OF BILATERAL BICIPITAL ORIGIN OF PLANTARIS MUSCLE: A CASE REPORT

The posterior calf group, plantaris muscle has a small fusiform muscle belly and a long slender tendon sandwiched between the soleus and gastrocnemius muscles. The case was reported during routine dissection at National institute of Ayurveda Deemed university, Jaipur. The subject was 31year-old male cadaver of north Indian origin. The Bilateral Bicipital origin of Plantaris Muscle was observed during the cadaveric dissection of the popliteal region. Two distinct PMS (Plantaris Muscles) were present, the SPM (superior Plantaris Muscle) and IPM (Inferior Plantaris Muscle). While the SPM originates from the lower lateral supracondylar ridge and the knee capsule, the IPM originates from the femoral condyle and SPM tendon splitting in to one part at the distal belly. The lateral side of the IPM tendon travels between GM (Gastrocnemius Muscle) and SM (Soleus Muscle) and ends at the calcaneal tendon. SPM and the medial side of the IPM tendon run along with the IPM tendon and insert at the fascia at the inner surface of proximal 1/3of the medial head of GM. The present case report introduces a new variation of the PM that should be taken into consideration.