Comparison of psoas major activation during standing hip flexion between chronic low back pain and healthy populations.

BACKGROUND: The psoas major (PM) has been identified as a potential contributor to chronic low back pain (LBP). However, few studies have investigated the effects of upright functional movement on PM activation in cLBP individuals. OBJECTIVE: This cross-sectional study aims to compare PM muscle activation characteristics in chronic LBP (cLBP) and healthy subjects during the transition from quiet double-leg standing to standing hip flexion. METHODS: Ultrasound Imaging was used to assess PM thickness at the lumbar vertebral level of L4-5 in 12 healthy and 12 cLBP participants. The changes in thickness between the test positions were utilized as a proxy for PM activation. RESULTS: The cLBP group exhibited greater thickness changes on the non-dominant side PM during contralateral hip flexion but not ipsilateral hip flexion (p= 0.369) compared to their healthy counterparts (p= 0.011; cLBP: resting 27.85 mm, activated 34.63 mm; healthy: resting 29.51 mm, activated 29.00 mm). There were no significant differences in dominant side PM thickness changes between the two groups during either contralateral or ipsilateral hip flexion (p= 0.306 and p= 0.077). CONCLUSION: Our findings suggest a potential overactivation of the PM in the cLBP population. This insight may aid in the development of tailored rehabilitation programs.

Acute effects of caffeine supplementation on kinematics and kinetics of sprinting.

We investigated the acute effects of caffeine supplementation (6 mgï½¥kg-1 ) on 60-m sprint performance and underlying components with a step-to-step ground reaction force measurement in 13 male sprinters. After the first round sprint as a control, caffeine supplementation-induced improvement in 60-m sprint times (7.811 s at the first versus 7.648 s at the second round, 2.05%) were greater compared with the placebo condition (7.769 s at the first versus 7.768 s at the second round, 0.02%). Using average values for every four steps, in the caffeine condition, higher running speed (all six step groups), higher step frequency (5th-16th and 21st-24th step groups), shorter support time (all the step groups except for 13th-16th step) and shorter braking time (9th-24th step groups) were found. Regarding ground reaction forces variables, greater braking mean force (13th-19th step group), propulsive mean force (1st-12th and 17th-20th step groups), and effective vertical mean force (9th-12th step group) were found in the caffeine condition. For the block clearance phase at the sprint start, push-off and reaction times did not change, while higher total anteroposterior mean force, average horizontal external power, and ratio of force were found in the caffeine condition. These results indicate that, compared with placebo, acute caffeine supplementation improved sprint performance regardless of sprint sections during the entire acceleration phase from the start through increases in step frequency with decreases in support time. Moreover, acute caffeine supplementation promoted increases in the propulsive mean force, resulting in the improvement of sprint performance.

Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) formula Banxia Xiexin decoction (BXD) has definite therapeutic effect in treating stress-induced gastric ulceration (SIGU) and many other gastrointestinal diseases, but its effect on gastric lymphatic pumping (GLP) remains unclear. AIM OF THE STUDY: Elucidating the role of GLP in SIGU and BXD treatment, and exploring the molecular mechanisms of GLP regulation. MATERIALS AND METHODS: In vivo GLP imaging were performed on SIGU rat model, and the lymphatic dynamic parameters were evaluated. Gastric antrum tissues and serum were collected for macroscopic, histopathological and ulcerative parameters analysis. Gastric lymphatic vessel (GLV) tissues were collected for RNA-Seq assays. Differentially expressed genes (DEGs) were screened from RNA-Seq result and submitted for transcriptomic analysis. Key DEGs and their derivative proteins were measured by qRT-PCR and WB. RESULTS: GLP was significantly suppressed in SIGU rats. BXD could recover GLP, ameliorate stomach lymphostasis, and alleviate the ulcerative damage. Transcriptome analysis of GLV showed the top up-DEGs were concentrated in smooth muscle contraction signaling pathway, while the top the down-DEGs were concentrated in energy metabolism pathways especially fatty acid degradation pathway, which indicated BXD can promote lymphatic smooth muscle contraction, regulate energy metabolism, and reduce fatty acid degradation. The most possible target of these mechanisms was the lymphatic smooth muscle cells (LSMCs) which drove the GLP. This speculation was further validated by the qRT-PCR and WB assessments for the level of key genes and proteins. CONCLUSIONS: By activating the smooth muscle contraction signaling pathway, restoring energy supply, modulating energy metabolism program and reducing fatty acid degradation, BXD effectively recovered GLP, mitigated the accumulation of inflammatory cytokines and metabolic wastes in the stomach, which importantly contributes to its efficacy in treating SIGU.

TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes Ca2+ and Na+ Influx.

Airway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca2+ influx. Major channels involved in Ca2+ influx in ASM cells are L-type voltage-dependent Ca2+ channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM. Mechanical stimuli, such as contraction, can activate TRPV4. We investigated the possible activation of TRPV4 by histamine (His)- or carbachol (CCh)-induced contraction in guinea pig ASM. In single myocytes, the TRPV4 agonist (GSK101) evoked an increase in [Ca2+]i, characterized by a slow onset and a plateau phase. The TRPV4 antagonist (GSK219) decreased channel activity by 94%, whereas the Ca2+-free medium abolished the Ca2+ response induced by GSK101. Moreover, GSK101 caused Na+ influx in tracheal myocytes. GSK219 reduced the Ca2+ peak and the Ca2+ plateau triggered by His or CCh. TRPV4 blockade shifted the concentration-response curve relating to His and CCh to the right in tracheal rings and reduced the maximal contraction. Finally, the activation of TRPV4 in single myocytes increased the Ca2+ refilling of the SR. We conclude that contraction of ASM cells after stimulation with His or CCh promotes TRPV4 activation, the subsequent influx of Ca2+ and Na+, and the opening of L-VDCCs. The entry of Ca2+ into ASM cells via TRPV4 and L-VDCCs contributes to optimal smooth muscle contraction.

Low-Salt Diet Regulates the Metabolic and Signal Transduction Genomic Fabrics, and Remodels the Cardiac Normal and Chronic Pathological Pathways.

Low-salt diet (LSD) is a constant recommendation to hypertensive patients, but the genomic mechanisms through which it improves cardiac pathophysiology are still not fully understood. Our publicly accessible transcriptomic dataset of the left ventricle myocardium of adult male mice subjected to prolonged LSD or normal diet was analyzed from the perspective of the Genomic Fabric Paradigm. We found that LSD shifted the metabolic priorities by increasing the transcription control for fatty acids biosynthesis while decreasing it for steroid hormone biosynthesis. Moreover, LSD remodeled pathways responsible for cardiac muscle contraction (CMC), chronic Chagas (CHA), diabetic (DIA), dilated (DIL), and hypertrophic (HCM) cardiomyopathies, and their interplays with the glycolysis/glucogenesis (GLY), oxidative phosphorylation (OXP), and adrenergic signaling in cardiomyocytes (ASC). For instance, the statistically (p < 0.05) significant coupling between GLY and ASC was reduced by LSD from 13.82% to 2.91% (i.e., -4.75×), and that of ASC with HCM from 10.50% to 2.83% (-3.71×). The substantial up-regulation of the CMC, ASC, and OXP genes, and the significant weakening of the synchronization of the expression of the HCM, CHA, DIA, and DIL genes within their respective fabrics justify the benefits of the LSD recommendation.

Neuromuscular Anatomy and Motor Patterns at the Base of Calling Behaviour in the Female Spongy Moth Lymantria dispar.

"Calling behaviour" is a stereotyped rhythmic motor pattern displayed by female moths, by which they emit the sex pheromone to attract of conspecific males. Calling occurs through a squeezing mechanism based on the turtleneck-like folding and unfolding of the ovipositor cuticle during its telescopic extensions and retractions. This mechanism is under the control of the terminal abdominal ganglion (TAG). By combining anatomical and electrophysiological approaches, here we studied the morpho-functional organisation of the abdominal muscles and the activity of motoneurons from TAG nerve N4-N6 as correlated to the ovipositor movements during calling in the female spongy moth Lymantria dispar. Our results show that the three abdominal segments S7, S8 and S9 (ovipositor) are highly specialized structures containing cuticular appendages, hinges, apodemes and several large muscles, innervated by N4 and especially by N5. N6 mainly innervates the oviductal tract. We also identified a number of motor units from N4 and N5, the spike activity of which is correlated with the ovipositor movements during calling. In conclusion, the release of sex pheromones in the female spongy moth is obtained by extensions and retractions of the ovipositor operated by a coordinated motor program, which is mainly sustained by the activity of a few motor units under the control of TAG nerves N4 and N5.

Effects of lunges inserted in walking (eccentric walking) on lower limb muscle strength, physical and cognitive function of regular walkers.

INTRODUCTION: Walking is a popular exercise but does not increase lower limb muscle strength and balance. We hypothesized that muscle strength, physical and cognitive function would be improved by inserting lunges in conventional walking. METHODS: Eleven regular walkers (54-88 years) who had more than 5000 steps in exercise walking a day at least 5 days a week participated in this study. They walked as usual for the first 4 weeks and included lunges and descending stairs or slope walking (i.e., eccentric walking) for the next 8 weeks. The steps of eccentric walking were gradually increased from 100 to 1000 steps per week over 8 weeks. RESULTS: The average steps per day were 10,535 ± 3516 in the first 4 weeks, and 10,118 ± 3199 in the eccentric walking period without a significant difference. No significant changes in maximal voluntary isometric contraction torque of the knee extensors (MVC), 30-s chair stand (CS), 2-min step, balance assessed by center of pressure movement area with eyes close, sit and reach, a digit symbol substitution test (DSST) for cognitive function were observed in the first 4 weeks. However, significant (P < 0.05) improvements were evident in MVC (18.6 ± 15.7%), CS (24.2 ± 17.3%), balance ( - 45.3 ± 34.5%), and DSST (20.8 ± 16.7%) from weeks 4 to 12. Serum complement component 1q concentration decreased (P < 0.05) from weeks 4 to 12, although no changes in serum glucose, triglyceride, and cholesterol concentrations were observed. CONCLUSION: These results supported the hypothesis, and suggest that eccentric walking provides effects that are not achieved by conventional walking.

Mechanisms of myosin II force generation. Insights from novel experimental techniques and approaches.

Myosin II is a molecular motor that converts chemical energy derived from ATP hydrolysis into mechanical work. Myosin II isoforms are responsible for muscle contraction and a range of cell functions relying on the development of force and motion. When the motor attaches to actin, ATP is hydrolyzed, and inorganic phosphate (Pi) and ADP are released from its active site. These reactions are coordinated with changes in the structure of myosin, promoting the so called "power-stroke" that causes sliding of actin filaments. The general features of the myosin-actin interactions are well accepted, but there are critical issues that remain poorly understood, mostly due to technological limitations. In recent years, there has been a significant advance in structural, biochemical, and mechanical methods that have advanced the field considerably. New modeling approaches have also allowed researchers to understand actomyosin interactions at different levels of analysis. This paper reviews recent studies looking into the interaction between myosin II and actin filaments, which leads to the power stroke and force generation. It reviews studies conducted with single myosin molecules, myosins working in filaments, muscle sarcomeres, myofibrils and fibers. It also reviews the mathematical models that have been used to understand the mechanics of myosin II, in approaches focusing on single molecules to ensembles. Finally, it includes brief sections on translational aspects, and how changes in the myosin motor by mutations and/or posttranslational modifications may cause detrimental effects in diseases and aging, among other conditions, and how myosin II has become an emerging drug target.

Finite element model of ocular adduction with unconstrained globe translation.

Details of the anatomy and behavior of the structures responsible for human eye movements have been extensively elaborated since the first modern biomechanical models were introduced. Based on these findings, a finite element model of human ocular adduction is developed based on connective anatomy and measured optic nerve (ON) properties, as well as active contractility of bilaminar extraocular muscles (EOMs), but incorporating the novel feature that globe translation is not otherwise constrained so that realistic kinematics can be simulated. Anatomy of the hemisymmetric model is defined by magnetic resonance imaging. The globe is modeled as suspended by anatomically realistic connective tissues, orbital fat, and contiguous ON. The model incorporates a material subroutine that implements active EOM contraction based on fiber twitch characteristics. Starting from the initial condition of 26° adduction, the medial rectus (MR) muscle was commanded to contract as the lateral rectus (LR) relaxed. We alternatively modeled absence or presence of orbital fat. During pursuit-like adduction from 26 to 32°, the globe translated 0.52 mm posteriorly and 0.1 mm medially with orbital fat present, but 1.2 mm posteriorly and 0.1 mm medially without fat. Maximum principal strains in the optic disk and peripapillary reached 0.05-0.06, and von-Mises stress 96 kPa. Tension in the MR orbital layer was ~ 24 g-force after 6° adduction, but only ~ 3 gm-f in the whole LR. This physiologically plausible simulation of EOM activation in an anatomically realistic globe suspensory system demonstrates that orbital connective tissues and fat are integral to the biomechanics of adduction, including loading by the ON.

Pelvic floor status in opera singers. a pilot study using transperineal ultrasound.

BACKGROUND: Control of pelvic floor muscles (PFM) is emphasized as important to obtain functional breath support in opera singing, but there is not much research that proves PFM function as part of breath support in classical singing. Transperineal ultrasound is a reliable method for quantification of PFM contraction in urogynecology. Our aim was to establish if transperineal ultrasound can be used for observation of movement of the PFM during singing and to quantify pelvic floor contraction. METHODS: Cross sectional study of 10 professional opera singers examined with transperineal ultrasound in the supine position at rest and contraction, and standing at rest and during singing. Levator hiatal area was measured in a 3D rendered volume. Levator hiatal anteroposterior (AP) diameter and bladder neck distance from symphysis were measured in 2D images. RESULTS: The AP diameter was shortened from supine rest to contraction (15 mm), standing (6 mm) and singing (9 mm), all p < 0.01. The bladder neck had a non-significant descent of 3 mm during singing. The mean proportional change in AP diameter from rest to contraction was 24.2% (moderate to strong contraction) and from rest to singing was 15% (weak to moderate contraction). CONCLUSIONS: Transperineal ultrasound can be used to examine the PFM during singing. The classically trained singers had good voluntary PFM contraction and moderate contraction during singing. AP diameter was significantly shortened from supine to upright position, with further shortening during singing, confirming that female opera singers contracted their pelvic floor during singing.

Control of motor output during steady submaximal contractions is modulated by contraction history.

The purpose of the study was to investigate the influence of contraction history on force steadiness and the associated EMG activity during submaximal isometric contractions performed with the dorsiflexor muscles. The key feature of the protocol was a triangular ramp contraction performed in the middle of a steady contraction at a lower target force. The target force during the ramp contraction was 20% MVC greater than that during the steady contraction. Thirty-seven healthy individuals (21 men and 16 women) performed the submaximal tasks with the ankle dorsiflexors. Electromyography (EMG) signals were recorded from tibialis anterior with a pair of surface electrodes. The coefficient of variation for force was significantly greater during the second steady contraction compared with the first one at each of the seven target forces (p < 0.015; d = 0.38-0.92). Although the average applied force during the steady contractions before and after the triangular contraction was the same (p = 0.563), the mean EMG amplitude for the steady contractions performed after the triangular contraction was significantly greater at each of the seven target forces (p < 0.0001; d = 0.44-0.68). Also, there were significant differences in mean EMG frequency between the steady contractions performed before and after the triangular contraction (p < 0.01; d = 0.13-0.82), except at 10 and 20% MVC force. The greater force fluctuations during a steady submaximal contraction after an intervening triangular contraction indicate a change in the discharge characteristics of the involved motor units.

A low-cost 2-D sarcomere model to demonstrate titin-related mechanisms for force production.

Given the recently proposed three-filament theory of muscle contraction, we present a low-cost physical sarcomere model aimed at illustrating the role of titin in the production of active force in skeletal muscle. With inexpensive materials, it is possible to illustrate actin-myosin cross-bridge interactions between the thick and thin filaments and demonstrate the two different mechanisms by which titin is thought to contribute to active and passive muscle force. Specifically, the model illustrates how titin, a molecule with springlike properties, may increase its stiffness by binding free calcium upon muscle activation and reducing its extensible length by attaching itself to actin, resulting in the greater force-generating capacity after an active than a passive elongation that has been observed experimentally. The model is simple to build and manipulate, and demonstration to high school students was shown to result in positive perception and improved understanding of the otherwise complex titin-related mechanisms of force production in skeletal and cardiac muscles.NEW & NOTEWORTHY Our physical sarcomere model illustrates not only the classic view of muscle contraction, the sliding filament and cross-bridge theories, but also the newly discovered role of titin in force regulation, called the three-filament theory. The model allows for easy visualization of the role of titin in muscle contraction and aids in explaining complex muscle properties that are not captured by the traditional cross-bridge theory.

In vivo heat production dynamics during a contraction-relaxation cycle in rat single skeletal muscle fibers.

Skeletal muscle generates heat via contraction-dependent (shivering) and independent (nonshivering) mechanisms. While this thermogenic capacity of skeletal muscle undoubtedly contributes to the body temperature homeostasis of animals and impacts various cellular functions, the intracellular temperature and its dynamics in skeletal muscle in vivo remain elusive. We aimed to determine the intracellular temperature and its changes within skeletal muscle in vivo during contraction and following relaxation. In addition, we tested the hypothesis that sarcoplasmic reticulum Ca2+ ATPase (SERCA) generates heat and increases the myocyte temperature during a transitory Ca2+-induced contraction-relaxation cycle. The intact spinotrapezius muscle of anesthetized adult male Wistar rats (n = 18) was exteriorized and loaded with the fluorescent probe Cellular Thermoprobe for Fluorescence Ratio (49.3 µM) by microinjection over 1 s. The fluorescence ratio (i.e., 580 nm/515 nm) was measured in vivo during 1) temperature increases induced by means of an external heater, and 2) Ca2+ injection (3.9 nL, 2.0 mM). The fluorescence ratio increased as a linear function of muscle surface temperature from 25 °C to 40 °C (r2 = 0.97, P < 0.01). Ca2+ injection (3.9 nL, 2.0 mM) significantly increased myocyte intracellular temperature: An effect that was suppressed by SERCA inhibition with cyclopiazonic acid (CPA, Ca2+: 38.3 ± 1.4 °C vs Ca2++CPA: 28.3 ± 2.8 °C, P < 0.01 at 1 min following injection). While muscle shortening occurred immediately after the Ca2+ injection, the increased muscle temperature was maintained during the relaxation phase. In this investigation, we demonstrated a novel model for measuring the intracellular temperature of skeletal muscle in vivo and further that heat generation occurs concomitant principally with SERCA functioning and muscle relaxation.

Brain activation associated with low- and high-intensity concentric versus eccentric isokinetic contractions of the biceps brachii: An fNIRS study.

Studies have shown that neural responses following concentric (CON) and eccentric (ECC) muscle contractions are different, which suggests differences in motor control associated with CON and ECC contractions. This study aims to determine brain activation of the left primary motor cortex (M1) and left and right dorsolateral prefrontal cortices (DLPFCs) during ECC and CON of the right bicep brachii (BB) muscle at low- and high-contraction intensities. Eighteen young adults (13M/5F, 21-35 years) were recruited to participate in one familiarization and two testing sessions in a randomized crossover design. During each testing session, participants performed either ECC or CON contractions of the BB (3 sets × 8 reps) at low- (25% of maximum ECC/CON, 45°/s) and high-intensity (75% of maximum ECC/CON, 45°/s) on an isokinetic dynamometer. Eleven-channel functional near-infrared spectroscopy was used to measure changes in oxyhemoglobin (O2 Hb) from the left M1, and left and right DLPFC during ECC and CON contractions. Maximum torque for ECC was higher than CON (43.3 ± 14.1 vs. 46.2 ± 15.7 N m, p = 0.025); however, no differences in O2 Hb were observed between contraction types at low or high intensities in measured brain regions. High-intensity ECC and CON contractions resulted in greater increases in O2 Hb of M1 and bilateral DLPFC compared to low-intensity ECC and CON contractions (p = 0.014). Our findings suggest no differences in O2 Hb responses between contraction types at high and low intensities. High-contraction intensities resulted in greater brain activation of the M1 and bilateral DLPFC, which may have implications for neurorehabilitation to increase central adaptations from exercise.

Eccentric cycling involves greater mental demand and cortical activation of the frontoparietal network.

Eccentric, compared to concentric exercise, is proposed to involve different neuro-motor processing strategies and a higher level of mental demand. This study compared eccentric and concentric cycling at matched perceived effort and torque for the mental demand and related-cortical activation patterns. Nineteen men (30 ± 6 years) performed four different 5-min cycling conditions at 30 RPM on a semi-recumbent isokinetic cycle ergometer: (1) concentric at a moderate perceived effort (23 on the CR100® scale) without torque feedback; (2) concentric and (3) eccentric at the same average torque produced in the first condition; and (4) eccentric at the same moderate perceived effort than the first concentric condition. The conditions two to four were randomized. After each condition, mental demand was monitored using the NASA Task Load Index scale. Changes in oxy-(O2 Hb) and deoxy-(HHb) hemoglobin during exercise were measured over both prefrontal cortices and the right parietal lobe from a 15-probe layout using a continuous-wave NIRS system. Mental demand was significantly higher during eccentric compared to concentric cycling (+52%, p = 0.012) and when the exercise intensity was fixed by the torque rather than the perceived effort (+70%, p < 0.001). For both torque- or perceived effort-matched exercises, O2 Hb increased significantly (p < 0.001) in the left and right prefrontal cortices, and right parietal lobe, and HHb decreased in the left, and right, prefrontal cortices during eccentric compared to concentric cycling. This study supports that acute eccentric cycling, compared to concentric cycling, involves a higher mental demand, and frontoparietal network activation.

Understanding bacterial infiltration of the pancreas through a deformable pancreatic duct.

Tiny amount of bacteria are found in the pancreas in pancreatitis and cancer, which seemed involved in inflammation and carcinogenesis. However, bacterial infiltration from the duodenum is inhibited by the physical defense mechanisms such as bile flow and the sphincter of Oddi. To understand how the bacteria possibly infiltrate the pancreas through a deformable pancreatic duct, influenced by the periodic contractions of the sphincter of Oddi, a mathematical model of bacterial infiltration is developed that considered large deformation, fluid flow, and bacterial transport in a deformable pancreatic duct. In addition, the sphincter's contraction wave is modeled by including its propagation from the pancreas toward the duodenum. Simulated structure of the deformed duct with the relaxed sphincter and simulated bile distribution agreed reasonably well with the literature, validating the model. Bacterial infiltration from the duodenum in a deformable pancreatic duct, following the sphincter's contraction, is counteracted by a gradual peristalsis-like deformation of the pancreatic duct, due to an antegrade contraction wave propagation from the pancreas to the duodenum, Parametric sensitivity analysis demonstrated that bacterial infiltration is increased with lower bile and pancreatic juice flow rate, greater contraction amplitude and frequency, thinner wall thickness, and retrograde contraction wave propagation. Since contraction waves following retrograde propagation are increased in patients with common bile duct stones and pancreatitis, they may possibly be factors for continuum inflammation of pancreas. (224 words).

In vivo cytosolic H2O2 changes and Ca2+ homeostasis in mouse skeletal muscle.

Hydrogen peroxide (H2O2) and calcium ions (Ca2+) are functional regulators of skeletal muscle contraction and metabolism. Although H2O2 is one of the activators of the type-1 ryanodine receptor (RyR1) in the Ca2+ release channel, the interdependence between H2O2 and Ca2+ dynamics remains unclear. This study tested the following hypotheses using an in vivo model of mouse tibialis anterior (TA) skeletal muscle. 1) Under resting conditions, elevated cytosolic H2O2 concentration ([H2O2]cyto) leads to a concentration-dependent increase in cytosolic Ca2+ concentration ([Ca2+]cyto) through its effect on RyR1; and 2) in hypoxia (cardiac arrest) and muscle contractions (electrical stimulation), increased [H2O2]cyto induces Ca2+ accumulation. Cytosolic H2O2 (HyPer7) and Ca2+ (Fura-2) dynamics were resolved by TA bioimaging in young C57BL/6J male mice under four conditions: 1) elevated exogenous H2O2; 2) cardiac arrest; 3) twitch (1 Hz, 60 s) contractions; and 4) tetanic (30 s) contractions. Exogenous H2O2 (0.1-100 mM) induced a concentration-dependent increase in [H2O2]cyto (+55% at 0.1 mM; +280% at 100 mM) and an increase in [Ca2+]cyto (+3% at 1.0 mM; +8% at 10 mM). This increase in [Ca2+]cyto was inhibited by pharmacological inhibition of RyR1 by dantrolene. Cardiac arrest-induced hypoxia increased [H2O2]cyto (+33%) and [Ca2+]cyto (+20%) 50 min postcardiac arrest. Compared with the exogenous 1.0 mM H2O2 condition, [H2O2]cyto after tetanic muscle contractions rose less than one-tenth as much, whereas [Ca2+]cyto was 4.7-fold higher. In conclusion, substantial increases in [H2O2]cyto levels evoke only modest Ca2+ accumulation via their effect on the sarcoplasmic reticulum RyR1. On the other hand, contrary to hypoxia secondary to cardiac arrest, increases in [H2O2]cyto from muscle contractions are small, indicating that H2O2 generation is unlikely to be a primary factor driving the significant Ca2+ accumulation after, especially tetanic, muscle contractions.NEW & NOTEWORTHY We developed an in vivo mouse myocyte H2O2 imaging model during exogenous H2O2 loading, ischemic hypoxia induced by cardiac arrest, and muscle contractions. In this study, the interrelationship between cytosolic H2O2 levels and Ca2+ homeostasis during muscle contraction and hypoxic conditions was revealed. These results contribute to the elucidation of the mechanisms of muscle fatigue and exercise adaptation.

Mechanical stress can regulate temporomandibular joint cavitation via signalling pathways.

The temporomandibular joint (TMJ), composed of temporal fossa, mandibular condyle and a fibrocartilage disc with upper and lower cavities, is the biggest synovial joint and biomechanical hinge of the craniomaxillofacial musculoskeletal system. The initial events that give rise to TMJ cavities across diverse species are not fully understood. Most studies focus on the pivotal role of molecules such as Indian hedgehog (Ihh) and hyaluronic acid (HA) in TMJ cavitation. Although biologists have observed that mechanical stress plays an irreplaceable role in the development of biological tissues and organs, few studies have been concerned with how mechanical stress regulates TMJ cavitation. Based on the evidence from human or other animal embryos today, it is implicated that mechanical stress plays an essential role in TMJ cavitation. In this review, we discuss the relationship between mechanical stress and TMJ cavitation from evo-devo perspectives and review the clinical features and potential pathogenesis of TMJ dysplasia.

Expression and electrophysiological characteristics of VGSC during mouse myoblasts differentiation.

Voltage-gated sodium channels (VGSC) are essential for triggering and relaying action potentials (AP), which perform critical functions in a variety of physiological processes, such as controlling muscle contractions and facilitating the release of neurotransmitters. In this study, we used a mouse C2C12 cell differentiation model to study the molecular expression and channel dynamics of VGSC and to investigate the exact role of VGSC in the development of muscle regeneration. Immunofluorescence, Real-time quantitative polymerase chain reaction, Western blot, and whole-cell patch clamp were employed for this purpose in mouse myoblasts. The findings revealed an increase in intracellular sodium concentration, NaV1.4 gene expression, and protein expression with the progress of differentiation (days 0, 1, 3, 5 and 7). Furthermore, VGSC dynamics exhibit the following characteristics: ① The increase of sodium current (INa); ② The decrease in the activation threshold and the voltage trigger maximum of INa; ③ A positive shift in the steady-state inactivation curve; ④ The recovery of INa during repolarization is delayed, the activity-dependent decay rate of INa was accelerated, and the proportionate amount of the fraction of activated channels was reduced. Based on these results, it is postulated that the activation threshold of AP could be decreased, and the refractory period could be extended with the extension of differentiation duration, which may contribute to muscle contraction. Taken together, VGSC provides a theoretical and empirical basis for exploring potential targets for neuromuscular diseases and other therapeutic muscle regeneration dysfunctions.