Muscle Differentiation Research Articles

Time-series transcriptomics reveals distinctive mRNA expression dynamics associated with gene ontology specificity and protein expression in skeletal muscle after electrical stimulation-induced resistance exercise.

Resistance exercise upregulates and downregulates the expression of a wide range of genes in skeletal muscle. However, detailed analysis of mRNA dynamics such as response rates and temporal patterns of the transcriptome after resistance exercise has not been performed. We aimed to clarify the dynamics of time-series transcriptomics after resistance exercise. We used electrical stimulation-induced muscle contraction as a resistance exercise model (5 sets × 10 times of 3 s of 100-Hz electrical stimulation) on the tibialis anterior muscle of rats and measured the transcriptome in the muscle before and at 0, 1, 3, 6, and 12 h after muscle contractions by RNA sequencing. We also examined the relationship between the parameters of mRNA dynamics and the increase in protein expression at 12 h after muscle contractions. We found that the function of the upregulated genes differed after muscle contractions depending on their response rate. Genes related to muscle differentiation and response to mechanical stimulus were enriched in the sustainedly upregulated genes. Furthermore, there was a positive correlation between the magnitude of upregulated mRNA expression and the corresponding protein expression level at 12 h after muscle contractions. Although it has been theoretically suggested, this study experimentally demonstrated that the magnitude of the mRNA response after electrical stimulation-induced resistance exercise contributes to skeletal muscle adaptation via increases in protein expression. These findings suggest that mRNA expression dynamics such as response rate, a sustained upregulated expression pattern, and the magnitude of the response contribute to mechanisms underlying adaptation to resistance exercise.

Computed Tomography and Magnetic Resonance Imaging Features of Gracilis Myopathy in Dogs.

Gracilis myopathy is a well-recognized syndrome of weight-bearing gait abnormality; however, detailed description of computed tomography (CT) and magnetic resonance imaging (MRI) features of gracilis myopathy is lacking in the literature. This study aims to describe in detail CT and MRI features of gracilis myopathy. This is a retrospective study. Medical records of dogs with characteristic gait and available pelvic limb MRI or CT, presenting to four referral institutions, were reviewed. Seven cases with MRI (3/7) or CT (4/7) were included, all German Shepherd dogs. MRI findings in all cases included a well-defined, T1-/T2-/proton density-weighted hypointense band along the axial margin of the gracilis muscle, shorter affected muscles, thickening and T2W/STIR hyperintensity with contrast enhancement at the symphyseal tendon, and concurrent focal indentation of the axial border of the gracilis muscle. CT findings included a hyperattenuating band (4/4), single instances of contrast enhancement at the origin of the muscle, thickening of the tendon at the origin and insertion, and concurrent thickening at the musculotendinous muscle. CT and MRI can present advantages in correctly identifying the specific muscles affected within the gracilis-semitendinosus muscle complex. Both modalities can localize anatomically lesions in detail, for instance at the origin or insertion of the muscle, which could present advantages in novel treatment strategies for this condition.

The effectiveness of neuromuscular training warm-up program for injury prevention in adolescent male basketball players

ABSTRACT This study evaluated the effects of a neuromuscular training (NMT) warm-up program on injury incidence, neuromuscular function, and program adherence, maintenance and acceptance in adolescent basketball players. A total of 275 players from 20 Slovenian teams (15 ± 1.7 years of age), were randomized into an intervention group (IG, n=129) and a control group (CG, n=146). Over three months, the IG incorporated NMT into their warm-ups, while the CG followed their usual practice. Measurements of body anthropometry, muscle contractile properties, and balance were taken before and after the intervention. Also, the injury incidence, training adherence and maintenance were reported. Both groups showed improved balance, with no significant difference between them. However, IG demonstrated reduced delay times in specific muscles, indicating improved neuromuscular function. Injury prevalence proportion (%) during the whole study period was higher in the control group compared to intervention (IG: 10.9% vs. CG: 23.3%), and incidence rate. Moreover, the incidence rate ratio for sustaining an injury was 2.6 on average (ranging from 0.88 to 7.07 for tendon and muscle injuries, respectively), indicating significantly lower injury risk in IG than CG. These findings highlight the effectiveness of NMT warm-ups in reducing injury risk and enhancing neuromuscular function, emphasizing the value of structured injury prevention strategies in youth sports..

CircAGO3 facilitates NF-κB pathway-mediated inflammatory atrophy in chicken skeletal muscle via the miR-34b-5p/TRAF3 axis.

Circular RNAs have emerged as critical regulators of gene expression across various biological systems. In this study, circAGO3, originating from exons 5, 6, 7, and 8 of the AGO3 gene in chickens, is characterized for its stability and differential expression during both embryonic and post-hatch stages. Overexpression of circAGO3 in chicken skeletal muscle markedly disrupts myogenesis by downregulating muscle differentiation markers and upregulating genes associated with muscle atrophy. RNA sequencing and functional analyses further delineate circAGO3's involvement in modulating inflammatory responses through the NF-κB signaling pathway, mediated by its interaction with miR-34b-5p. These findings highlight circAGO3's potential importance in poultry production by uncovering its regulatory roles in skeletal muscle development and inflammation, positioning it as a promising target for enhancing muscle growth and health in poultry farming.

Histologic and immunohistochemical analysis of connective tissue changes in patients with intestinal sutures failure

Objective. To determine the role of connective tissue pathology in the development of intestinal suture failure in order to improve the results of treatment of patients with this complication. Materials and methods. The study included 45 patients with intestinal suture failure who were treated at the Shalimov National Research Center for Surgery and Transplantation of the National Academy of Medical Sciences of Ukraine in 2017–2023. Results. A comprehensive study of fragments of small and large intestine tissues revealed similar morphological changes in patients with phenotypic signs of undifferentiated connective tissue dysplasia and intestinal sutures failure. Immunohistochemical examination of tissues with monoclonal antibodies to α–smooth muscle actin in both groups of patients revealed uneven, focal expression in smooth muscle differentiation cells and fibroblasts; with monoclonal antibodies to type IV collagen – moderate positive expression in the basal membrane of blood vessels, in smooth muscle cells of the muscle layer of the vessel wall, in areas of connective tissue, which meant pathological remodeling of connective tissue. Conclusions. The similar results of histological and immunohistochemical studies in patients with signs of undifferentiated connective tissue dysplasia and intestinal sutures failure confirm the influence of connective tissue pathology on the development of this complication.

Expression of distal limb patterning genes in Hypsibius exemplaris indicate regionalization and suggest distal identity of tardigrade legs.

Panarthropods, a major group of invertebrate animals comprised of arthropods, onychophorans, and tardigrades, are the only limb-bearing members of Ecdysozoa. The complexity and versatility of panarthropod paired limbs has prompted great interest in their development to better understand the formation of these structures and the genes involved in this process. However, studies of limb patterning and development are overwhelmingly focused on arthropods, followed by select work on onychophorans but almost entirely lacking for tardigrades. This model organism bias is inherently limited and precludes a comparative analysis of how panarthropod legs originated, have evolved, and the likely limb patterning genes present in the earliest panarthropod ancestors. In this study, we investigated tardigrade homologs of seven arthropod distal limb patterning genes (apterous, aristaless, BarH1, clawless, Lim1, rotund, and spineless) to better characterize tardigrade limb development in a comparative context. We detected homologs of all seven genes in the eutardigrade Hypsibius exemplaris and heterotardigrade Echiniscoides cf. sigismundi suggesting their conservation in both tardigrade lineages. Hybridization chain reaction experiments in H. exemplaris reveal a regionalized expression pattern for the genes aristaless, BarH1, clawless, rotund and spineless. The observed regionalized expression of the distal limb patterning genes in H. exemplaris might reflect the external morphological features of tardigrade legs, such as the distal claws, sensory organs in the proximal region, and specific muscle attachment sites. The comparison between the expression of these limb patterning genes in H. exemplaris relative to other panarthropods suggests their conserved role in the last common panarthropod ancestor, such as establishing the distal limb end and the distribution of sensory structures. Our results support the hypothesis that tardigrade legs are homologous to the distal region of other panarthropod limbs, as suggested by previous work on the expression of leg gap genes in H. exemplaris.

Optimisation of cell fate determination for cultivated muscle differentiation.

Production of cultivated meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibres in vitro. Although these formulations can drive myogenic differentiation levels comparable to serum-starvation-based protocols, the resulting cultures are often heterogeneous, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. To address this problem, we employed RNA sequencing to analyse heterogeneity in differentiating bovine satellite cells at single-nucleus resolution, identifying distinct cellular subpopulations including proliferative cells that fail to exit the cell cycle and quiescent 'reserve cells' that do not commit to myogenic differentiation. Our findings indicate that the MEK/ERK, NOTCH, and RXR pathways are active during the initial stages of myogenic cell fate determination, and by targeting these pathways, we can promote cell cycle exit while reducing reserve cell formation. This optimised medium formulation consistently yields fusion indices close to 100% in 2D culture. Furthermore, we demonstrate that these conditions enhance myotube formation and actomyosin accumulation in 3D bovine skeletal muscle constructs, providing proof of principle for the generation of highly differentiated cultivated muscle with excellent mimicry to traditional muscle.

Dichloroacetate, a pyruvate dehydrogenase activator, alleviates high-fat-induced impairment of myogenic differentiation in skeletal muscles.

Obesity-induced impairment of myogenic differentiation leads to muscle loss and sarcopenia. Pyruvate dehydrogenase (PDH) plays a crucial role in glucose metabolism and is associated with muscle differentiation. However, the effect of dichloroacetate (DCA), a PDH activator, on obesity-induced impairment of myogenic differentiation remains unknown. Here, we evaluated the effects of DCA treatment on high-fat intake-induced impairment of myogenic differentiation in C2C12 cells and C57BL/6 mice. In C2C12 cells, DCA treatment improved PDH activity that was reduced by palmitate (PAL) and decreased the lactate concentrations in the media. Additionally, DCA reversed PAL- and high-fat diet (HFD)-induced decrease in the expression of myoblast determination protein 1 (MyoD), myogenin (MyoG) and myosin heavy chain (MyHC) in C2C12 cells and C57BL/6 mice. To explore the possible mechanism, DCA treatment restored the levels of p-Akt, p-FoxO1, p-FoxO3a and p-p38 MAPK levels in PAL-treated C2C12 cells. Moreover, the protective effects of DCA were reversed by treatment with the Akt inhibitor MK2206 in C2C12 cells. In summary, DCA treatment alleviated high-fat intake-induced impairment of myogenic differentiation via Akt signalling, suggesting its potential in treating obesity-associated muscle loss and sarcopenia.

Volumetric body composition analysis of the Cancer Genome Atlas reveals novel body composition traits and molecular markers Associated with Renal Carcinoma outcomes

Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric techniques, demonstrating potential limitations with level-based approaches for assessing outcomes. In addition, we identify gene expression signatures in normal kidney that correlate with fat and muscle body composition traits that can be used to predict sex-specific outcomes in renal cell carcinoma.

Ythdf2 facilitates precursor miR-378/miR-378-5p maturation to support myogenic differentiation.

Ythdf2 is known to mediate mRNA degradation in an m6A-dependent manner, and it has been shown to play a role in skeletal muscle differentiation. Recently, Ythdf2 was also found to bind to m6A-modified precursor miRNAs and regulate their maturation. However, it remains unknown whether this mechanism is related to the regulation of myogenesis by Ythdf2. Here, we observed that Ythdf2 knockdown significantly suppressed myotube formation and impacted miRNAs expression during myogenic differentiation. Through integrated analysis of miRNA and mRNA sequencing data, miR-378 and miR-378-5p were identified as important targets of Ythdf2 in myogenesis. Mechanically, Ythdf2 was found to interact with core components of the pre-miRNA processor complex, namely DICER1 and TARBP2, thereby facilitating the maturation of pre-miR-378/miR-378-5p in an m6A-dependent manner and resulting in an increase in the expression levels of mature miR-378 and miR-378-5p. Moreover, the downregulation of either miR-378 or miR-378-5p significantly inhibited myotube formation, while the forced expression of miR-378 or miR-378-5p could partially rescued Ythdf2 knockdown-induced suppression of myogenic differentiation by activating the mTOR pathway. Collectively, our results for the first time suggest that Ythdf2 regulates myogenic differentiation via mediating pre-miR-378/miR-378-5p maturation, which might provide new insights into the molecular mechanisms underlying m6A modification in the regulation of myogenesis.

The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers

BackgroundVitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited.ResultsIn this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern.ConclusionsOur results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands.

Orangutans and chimpanzees produce morphologically varied laugh faces in response to the age and sex of their social partners

Laugh faces of humans play a key role in everyday social interactions as a pervasive tool of communication across contexts. Humans often vary the degree of mouth opening and teeth exposure when producing these facial expressions, which may depend on who their social partner is (e.g., their gender and age as well as their social relationship), serving this way different functions. Although it was found that laugh faces show evolutionary continuity across humans and non-human great apes according to the Principle of Maximum Parsimony, little is known about the function of laugh face variations from an evolutionary perspective. Hence, the present work examined the morphology of laugh faces in orangutan and chimpanzee dyadic play to test if they are modified with dependence on the playmate’s characteristics (sex, age and social relationship). In total, we analysed over 600 facial expressions of 14 orangutans and 17 chimpanzees by coding the specific muscle activations (Action Units, i.e. AUs) contributing to these expressions, using OrangFACS and ChimpFACS, respectively. Our results suggest that age difference and, to a lesser extent, playmate sex influence laugh face morphology in both taxa, but in opposite ways. While the orangutans of our study seem to expose their upper teeth (with AU10) and to pull the mouth corners (with AU12) more towards weaker partners (younger and female), possibly to communicate non-hostility, the chimpanzees showed both upper and lower teeth exposure (with AU10 and AU16) more often when interacting with the stronger partners (older individuals), possibly to communicate submissiveness. These findings suggest that the ability of humans to modify laugh faces with dependence on social partner characteristics has most likely evolved from pre-existing traits, going back at least to the last common ancestor of today’s great apes, including humans.

Effects of Extrinsic and Intrinsic Motivation on Selective Activation of Shoulder Girdle Muscles During the Barbell Bench Press Exercise

Background/Objectives: This study aimed to investigate the effects of intrinsic and extrinsic motivation on selective muscle activation of the shoulder girdle during the barbell bench press. Specifically, this research focused on how attentional focus on individual muscles, such as the anterior deltoid (AD), pectoralis major (PM), and triceps brachii long (TBL), could influence their electromyographic (EMG) activity during the exercise. Methods: Twelve male participants, with at least five years of strength training experience, performed bench press exercises under two conditions: with extrinsic motivation (no specific focus on muscle activity) and with intrinsic motivation (internal focus on specific muscles). Surface electromyography (sEMG) was used to measure muscle activity during three sets of bench presses at 60% of one repetition maximum (1RM). Participants were instructed to focus on the activation of specific muscles in a randomized sequence. Results: The intrinsic motivation condition significantly increased muscle activation compared to extrinsic motivation. Electromyographic activity of the AD, PM, and TBL muscles was notably higher when participants focused their attention on these muscles. AD activation increased from 71.78 ± 11.13%MVC (extrinsic) to 88.03 ± 8.84%MVC (intrinsic) (p = 0.0019), while PM and TBL activation also demonstrated significant increases under intrinsic focus. Conclusions: The study concludes that intrinsic motivation, or an internal focus on specific muscle activation, can significantly enhance EMG activity in target muscles during the bench press exercise. This finding has important implications for resistance training and rehabilitation, where focused muscle activation can be utilized to improve training outcomes and muscle engagement.

Evaluation of Guanidinoacetic Acid Supplementation on Finishing Beef Steer Growth Performance, Skeletal Muscle Cellular Response, and Carcass Characteristics.

This study elucidated the effects of dosage-dependent guanidinoacetic acid (GAA) supplementation on growth performance, muscle responses, and carcass characteristics in finishing beef steers. Thirty crossbred Red Angus beef steers (395 ± 28.09kg) were randomly assigned one of three treatments during a 146-day feedlot study: basal diet without GAA supplementation (CONTROL), 1g of GAA per 100kg of BW daily (LOWGAA), and 2g of GAA per 100kg of BW daily (HIGHGAA). Individual feed intake was monitored daily, growth performance parameters were collected every 28 days, and longissimus muscle (LM) biopsies occurred every 56 days. In biopsied LM, greater (P = 0.048) mRNA expression of IGF-1 was observed in LOWGAA steers on d 112 compared to the CONTROL group. LOWGAA steers also exhibited greater expression of myosin heavy chain (MHC) I compared to CONTROL steers (P < 0.05) and MHC IIA compared to both CONTROL and HIGHGAA treatment groups (P < 0.01) on d 112. GAA supplementation resulted in no change in carcass characteristics, serum and LM tissue metabolites, LM composition, and Warner-Bratzler shear force (WBSF) values (P > 0.05). Data collected from this study demonstrate the influence of GAA supplementation on the gene expression of MHC isoforms and their role in skeletal muscle growth, differentiation, and muscle fiber-typing.

Clinical and Structural Results Following Arthroscopic and Open Repair of Isolated Subscapularis Tears.

Objective: With advances in techniques, arthroscopic repair of isolated subscapularis tendon tears has become increasingly popular in recent years. The aim of this study was to analyze the clinical and structural results of arthroscopic repair versus the gold standard of open repair. It is a prospective cohort study with a control group; evidence level III. Methods: In a prospective study performed at two centers, 18 patients with an isolated subscapularis tear were treated with arthroscopic repair (ARG) and 16 patients with open repair (ORG) using a uniform single-row suture anchor repair technique in both groups. The subscapularis function was assessed using specific clinical tests (belly-press and lift-off tests), strength testing and shoulder function with the use of the Constant-Murley score (CMS). Standardized magnetic resonance imaging (MRI) was used to evaluate the postoperative subscapularis muscle-tendon status. Results: At a minimum follow-up of 48 months, the CMS increased from a mean of 54 points preoperatively to a mean of 86 points postoperatively in the ARG (p < 0.01) and from 50 points to 85 points postoperatively in the ORG (p < 0.01). Specific subscapularis tests (belly-press test and lift-off test) were significantly improved from the preoperative to the postoperative status in both repair groups (p < 0.05). Despite a subscapularis tendon healing rate of over 90% on MRI scans in both repair groups, the incomplete correction of specific muscle tests was a frequent postoperative finding. Conclusions: Arthroscopic repair of isolated subscapularis tears achieved equivalent clinical and structural results compared to the gold standard of open repair.

Evaluation of Lateral and Medial Parts of the Hamstring Muscle Fatigue Symmetry in Professional Footballers Cleared to Play After ACL Reconstruction.

Objectives: Rupture of the anterior cruciate ligament (ACL) is a severe injury common in sports. It also has a high rate of re-injury. The aim of this work was to assess hamstring muscle fatigue in active football players after ACL reconstruction who were cleared to play and to determine symmetry between the lateral and medial hamstring muscles. Methods: In professional football players post ACL reconstruction (n = 25) and non-injured players (n = 26), the bioelectrical activity of the medial (biceps femoris-BF) and lateral (semimembranosus and semitendinosus-SEM) hamstring muscles was measured during 60 s of isometric contraction. The fatigue variables were calculated using the Continuous Wavelet Transform (CWT) tool. Results: The football players following ACL reconstruction demonstrated significant asymmetry in fatigue of the lateral and medial hamstring muscles, with greater fatigue in the SEM compared to the BF muscle. Moreover, in those after reconstruction, the changes are more pronounced, with higher muscle fatigue in both limbs (they have lower MDF than non-injured players) and more severe SEM muscle insufficiency (noted in both limbs but with greater intensity in the non-operated one). Conclusions: The higher SEM muscle fatigue observed in this study influenced the lateral-to-medial activation ratio within the hamstring muscle, which may be a probable cause of this muscle's insufficiency in laterally stabilizing the knee in the frontal and transverse plane. Furthermore, the hamstring muscles after reconstruction were more fatigued in both limbs, which may be another risk factor for ACL graft rupture. Therefore, increased fatigue in specific hamstring muscles may indicate the direction in which knee stabilization is compromised due to ACL overload. A muscle that becomes fatigued and inefficient more quickly also becomes ineffective in performing its function sooner, which can lead to increased overloading forces acting on the ACL graft.

Muscle RING-finger proteins (MuRF) regulate protein kinase A activity via retrograde vesicular transport of PKA RI-alpha

Abstract Background Muscle RING finger (MuRF) proteins are muscle-restricted E3 ubiquitin ligases that control protein degradation in striated muscles. MuRF proteins have coordinate functions for maintenance of striated muscle structure and function that depends on their target proteins. MuRF1 is a key enzyme in muscle atrophy. MuRF2 and MuRF3 bind to and stabilize microtubules which affects striated muscle differentiation and contraction. Although some MuRF-interaction partners have been described only few have been proven to be targeted for proteasomal degradation. To better understand the function of MuRF proteins, we set out to identify and functionally characterize novel MuRF target proteins. Methods and Results Stable isotope labeling of amino acids in cell culture followed by affinity purification and quantitative mass spectrometry analysis (SILAC-AP-MS) was used to identify the interactome of MuRF proteins. We identified the mammalian retromer subunit sorting nexin 5 (SNX5) that is involved in subcellular trafficking as a novel MuRF2 and MuRF3 interaction partner. Coimmunoprecipitation experiments and immunocytochemistry confirmed physical interaction and colocalization between SNX5 and MuRF2 or MuRF3. The interaction domains were mapped. MuRF2, MuRF3 and SNX5 were colocalized to early endosomes at microtubules in myocytes. MuRF2 mediated the ubiquitin proteasome system-dependent degradation of SNX5 in a RING-finger dependent manner, whereas MuRF3 stabilized SNX5. Using mass spectrometry, we identified the regulatory subunit of protein kinase A (PKA-RI-α) as a cargo of SNX5 coated early endosomes in myocytes. CRISPR-Cas9 and siRNA experiments showed that SNX5 regulates PKA activity by stabilizing PKA-RI-α in myocytes. Deletion of SNX5 resulted in PKA activation and inhibition of the HDAC5-MEF2 axis that disturbed myogenic differentiation. Conclusion MuRF2 and MuRF3 play opposing roles in SNX5-mediated retrograde transport of early endosomes along microtubules in myocytes. This mechanism is involved in regulation of PKA catalytic activity via stabilization of PKA-RI-α and controls differentiation of striated muscles.

Feasibility of a new bicycle ergometer with adjustable pedaling configuration for personalized lower limb rehabilitation

Muscle atrophy due to prolonged immobilization leads to severe dysfunction and progression of disease and injury. This highlights the necessity for early rehabilitation, even during the non-ambulatory stages. As manifestations vary among individuals, target-specific rehabilitation is crucial for achieving optimal outcomes. Conventional bicycle ergometers, despite their wide usage in rehabilitation and sports training, fail to adequately recruit the muscles that predominantly operate in the coronal or axial plane. This is thought to be due to the restriction of pedaling trajectory in the sagittal plane. This study introduces a new bicycle ergometer capable of tilting the pedaling plane and adjusting the pedal orientation, in order to alter muscle recruitment patterns and limb alignments. A biomechanical analysis of eight healthy volunteers suggests that our device can elicit dynamic valgus/varus alignment and alter the axial rotations of the lower extremities. An electromyography analysis revealed a significant increase in the activation of specific muscle groups, particularly the abductors and adductors, suggesting promising results for targeted muscle recruitment. We expect this ergometer to provide a new method for target-specific rehabilitation and the treatment of bedridden patients or those with weak muscles.

Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation

Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation

Interferon-β-Induced Injury During Pediatric Muscle Differentiation: Insight Into Juvenile Dermatomyositis Pathogenesis.

Juvenile dermatomyositis (JDM) involves up-regulated type I interferons (IFNs), including IFNβ, yet pathologic mechanisms remain poorly understood. We aimed to characterize the functional and structural effects of IFNβ on in vitro human pediatric myoblast growth and differentiation in a three-dimensional skeletal muscle model (myobundles). Myobundles fabricated from myoblasts of a healthy pediatric donor were exposed to IFNβ at 0 to 5,600 IU/mL during growth (days 1-4), differentiation (days 4-11), and/or mature (days 11-18) periods. To assess myobundle structure and function, contractile force, kinetics, and fatigue were measured at day 18 with subsequent immunohistochemistry. Myobundles were not functionally affected by IFNβ exposure during growth period alone. However, when IFNβ exposure continued through differentiation, myobundles became dysfunctional (P < 0.0001). IFNβ during differentiation or mature periods alone resulted in dose-dependent decreases in contractility, with greater decrease in the differentiation alone group (P < 0.0001). Twitch kinetics and fatigue remained largely unchanged when myobundles were exposed to IFNβ only during growth, yet twitch time slowed (P < 0.005) and fatigue decreased (P < 0.002) when myobundles were exposed during differentiation or mature stages alone. Nuclei density and myofiber size and organization also decreased when IFNβ was added during differentiation period alone. IFNβ decreases pediatric myobundle contractile function most significantly during differentiation of myoblasts to myotubes. Function is not affected when IFNβ exposure is limited to myoblast proliferation alone. These findings implicate a pathologic role for IFNβ in JDM by impairing myoblast differentiation, leading to subsequent loss of function and ongoing need for muscle regeneration and repair.