Frontiers in Physiology最新文献

Introduction: The use of ergogenic compounds has gained increasing popularity among individuals who wish to improve performance and recover faster from their workouts. Among these products is citrulline malate (CitMal), a popular dietary supplement that is suggested to enhance nitric oxide (NO)-mediated vasodilation and muscle blood flow.

Methods: To evaluate effects on arterial function, flow-mediated dilation (FMD) of the brachial artery during active hyperemia was measured in 12 healthy, recreationally active males (23 ± 3 years) before and after (60- and 120-min post) consuming either 6 g CitMal, 12 g CitMal, or a taste-matched placebo. The study used a randomized, double-blind, placebo-controlled, within-subject counterbalanced crossover design with ≥7-day washouts.

Results: Repeated measures ANOVA revealed no significant interaction (p = 0.315) or time effect (p = 0.649) in corrected FMD% at 60- and 120-min after intake of placebo, 6 g CitMal, and 12 g CitMal. There were also no significant differences (p = 0.301) between doses at any timepoint. A subgroup of six participants completed two additional visits to assess the effect of CitMal ingestion on serum markers involved in NO production. Over 120-min post-consumption, both doses significantly increased peak serum concentrations of citrulline (6 g: 504.7 ± 139.7; 12 g: 881.9 ± 216.7 μM), arginine (6 g: 70.2 ± 20.4; 12 g: 101.8 ± 36.2 μM), and ornithine (6 g: 27.9 ± 14.2; 12 g: 56.5 ± 30.0 μM) from baseline (all p < 0.001), with greater increases following 12 g (all p < 0.05). Likewise, arginine-to-dimethylarginine ratios (SDMA and ADMA) increased from baseline (SDMA, 6 g: 114.1 ± 24.2; 12 g: 166.2 ± 43.7; ADMA, 6 g: 119.2 ± 31.8; 12 g: 169.1 ± 29.1; all p < 0.001), with greater increases following 12 g (p < 0.05).

Discussion: Collectively, these findings suggest that neither 6 g nor 12 g of CitMal significantly enhance FMD within 120 min, despite marked increases in biochemical markers favorable to NO production. To our knowledge, this is the first study to compare acute doses of CitMal up to 12 g in relation to brachial artery FMD. These results indicate that acute vascular responses to CitMal may be limited by physiological ceiling effects and that potential vascular benefits may depend on longer-term supplementation, the presence of an exercise stimulus, or populations with impaired endothelial function.

Cerebral ischemia-reperfusion injury remains a leading cause of mortality and disability despite advances in reperfusion therapy. Traditional research has focused on individual cell death pathways, yet pharmacological blockade of single pathways provides only partial neuroprotection, suggesting that dying cells engage multiple death routes simultaneously. This review examines whether PANoptosis, an inflammatory cell death modality characterized by concurrent activation of apoptotic, necroptotic, and pyroptotic pathways, occurs in cerebral ischemia-reperfusion injury. The analysis demonstrates that mitochondrial dysfunction serves as the central convergence point orchestrating multi-pathway death activation across distinct temporal phases. Ischemia creates metabolic crisis that primes mitochondria without triggering irreversible commitment. Reperfusion causes explosive mitochondrial collapse through oxidative stress, releasing danger signals that simultaneously engage multiple death pathways. Impaired mitochondrial quality control then sustains inflammatory amplification over extended periods. Multiple lines of evidence support this framework, including concurrent rather than sequential appearance of pathway markers, mixed morphological features within individual cells, pathway redundancy demonstrated by incomplete single-target protection, and mechanistic convergence at the mitochondrial level. Cellular responses vary among neurons, astrocytes, microglia, and endothelial cells but share the common feature of coordinated multi-pathway activation. This integrated understanding explains why single-pathway therapeutic approaches have failed clinically and suggests that effective neuroprotection requires targeting upstream mitochondrial dysfunction or addressing pathway redundancy through multi-target interventions.

Objectives: To investigate the effects of three distinct post-activation potentiation (PAP) interventions-neuromuscular electrical stimulation (NMES), elastic band resistance, and squats-on neuromuscular activation during the smashing technique in high-level badminton athletes recovering from meniscus injuries. Furthermore, to elucidate the underlying mechanisms at the neuromotor control level through analyses of muscle synergy and intermuscular coherence.

Methods: Eighteen high-level male badminton athletes in the recovery phase of meniscus injuries were recruited. Surface electromyographic signals were recorded during forehand smash execution following respective interventions: squats, elastic band resistance, and NMES. Non-negative matrix factorization (NMF) analyzed muscle synergies, extracting synergistic module counts, muscle weights, and activation duration parameters. Time-frequency coherence (TFC) was calculated for specific muscle pairs.

Results: The resistance band group (RBG) exhibited a significantly higher number of synergies (5.0 ± 0.63) compared to the squat group (SG) (3.33 ± 0.52, p = 0.005) and the electrical stimulation group (ESG) (2.33 ± 0.82, p < 0.001). In terms of muscle activation weights, the ESG showed markedly increased contributions from key lower limb muscles across multiple synergy modules. E.g., in SYN4, activation weights for gastrocnemius medialis (GM) and lateralis (GL) in the ESG (GM: 0.25 ± 0.31; GL: 0.28 ± 0.28) were significantly higher than in the SG (GM: 0.08 ± 0.20; GL: 0.06 ± 0.09) (p < 0.05), representing an increase exceeding 200%. Intermuscular coherence analysis revealed that the ESG demonstrated superior coherence across α, β, and γ bands for several trunk-limb muscle pairs. E.g., within the α band, the biceps BB-LD pair in the ESG was significantly higher than in both the SG (p = 0.002) and the EBG (p = 0.007).

Conclusion: Neuromuscular electrical stimulation effectively optimizes muscle coordination patterns during smash execution in athletes recovering from meniscal injuries. It enhances activation of key muscle groups and multi-band neural coordination, representing an efficient rehabilitation strategy for neuromuscular control function optimization.

Objectives: To evaluate the impact of an ecological bouldering fatigue protocol and quantify acute changes in climbing-specific motor performance and visuospatial working memory in indoor climbers.

Methods: Non-randomised pre-post study in 28 indoor boulderers (18 male, 10 females; 15-34 years). Participants attempted sex- and skill-matched problems on a 15° overhanging Kilter Board to volitional exhaustion. Pre- and post-fatigue assessments included finger-hang endurance, pinch-grip strength, explosive pulling power, static balance, upper-limb dynamic stability, and visuospatial working memory.

Results: The protocol achieved all feasibility criteria. The intervention produced physiological stress (heart rate +60 bpm from baseline: 118.9 ± 22.0 to 178.6 ± 11.1; RPE 14.7 ± 1.8) and forearm-related termination in 75%. Performance changes: finger-hang endurance -34.2% (d_z = -0.85, p < 0.001); pinch-grip strength -5.8% (d_z = -0.53, p = 0.009); explosive pulling power -4.8% (d_z = -0.52, p = 0.010), and visuospatial working memory +16.4% (d_z = 0.54, p = 0.008). Static balance and upper-limb stability showed trivial non-significant change.

Conclusion: A brief, standardised, sex- and skill-matched bouldering protocol was feasible and induced climbing-specific fatigue. The observed improvement in visuospatial working memory challenges simple fatigue-impairment assumptions. This ecologically valid protocol provides a foundation for future work on motor-cognitive interactions and injury-relevant performance in climbing athletes.

Background: The temporomandibular joint (TMJ) relies on a fibrocartilaginous disc for stabilization and load distribution. When the disc degenerates, current replacement options fail to restore native biomechanics. Developing effective implants requires detailed knowledge of the disc's structure. The present work provides a full-volume, three-dimensional characterization of collagen fiber architecture and anisotropy in a large animal model with anatomical and functional similarities to the human joint.

Methods: A multimodal 3D imaging workflow was implemented, combining cone-beam CT for anatomical context and synchrotron phase-contrast micro-CT for high-resolution visualization of the ovine temporomandibular joint disc, cartilage, ligament, and subchondral bone. Deep-learning segmentation enabled full-volume tissue segmentation. Fiber orientation and anisotropy were quantified using mean intercept length (Mean Intercept Length)-derived eigenvector fields, with analysis performed across anatomical axes and planes. Histological sections validated fiber segmentation and regional differences in extracellular matrix organization.

Results: The lamb TMJ disc displayed a heterogeneous but highly ordered collagen network. Strong lateromedial alignment formed frontal-plane reinforcement bands, while a craniocaudal tensile corridor dominated the sagittal plane, and mixed lateromedial-ventrodorsal orientations characterized the transverse plane. Anisotropy was highest in the peripheral rims and lower in the central zone, reflecting a functional division between stabilization and deformation. Quantitative analysis demonstrated an orthotropic organization, with distinct dominant fiber populations aligned along the lateral-medial, ventral-dorsal, and cranial-caudal axes. Subchondral bone beneath the disc exhibited a fine, highly anisotropic trabecular lattice with reduced spacing, complementing the disc's structural organization.

Conclusion: This study provides the first full-volume, plane-resolved 3D description of collagen anisotropy in the ovine TMJ disc. The orthotropic fiber architecture and regional anisotropy gradients identified here clarify direction-dependent mechanical behavior and offer quantitative benchmarks for the design of biomimetic scaffolds and regenerative TMJ disc replacements.

Background: Nutritional supplementation is widely used to support sports performance; however, evidence specific to volleyball players remains fragmented. This systematic review and meta-analysis aimed to evaluate the effects of nutritional supplementation on physical performance and sport-specific skills in competitive volleyball players.

Methods: Following PRISMA guidelines, five electronic databases were systematically searched. Randomized controlled trials investigating acute or chronic nutritional supplementation in healthy volleyball players were included. Outcomes included vertical jump performance, muscle strength, agility, and sport-specific technical skills. Risk of bias was assessed using the Cochrane tool, and random-effects meta-analyses were performed.

Results: Thirteen randomized controlled trials involving 240 participants were included. Nutritional supplementation was associated with significant improvements in vertical jump performance (SMD = 0.47, 95% CI: 0.24-0.70), muscle strength (SMD = 0.43, 95% CI: 0.17-0.69), agility (SMD = 0.89, 95% CI: 0.54-1.24), and sport-specific technical skills (SMD = 0.63, 95% CI: 0.31-0.95). Subgroup analyses indicated beneficial effects following both acute and chronic supplementation protocols, with minimal statistical heterogeneity across outcomes.

Conclusion: Within the available evidence, nutritional supplementation may contribute to improvements in selected physical performance and sport-specific skill outcomes in competitive volleyball players. These findings may inform evidence-based nutritional strategies aimed at supporting sports performance in volleyball, while highlighting the need for larger, ecologically valid trials.

Objective: This study aimed to investigate the effects of fatigue on the control mechanism of the lower limb neuromuscular system during running.

Methods: The study participants were 25 male running enthusiasts (age: 20.9 ± 1.6 years; height: 174.8 ± 4.5 cm; body mass: 70.3 ± 5.2 kg) with more than 3 years of running experience. Surface electromyography (sEMG), motion capture, and heart rate monitoring technologies were used to obtain data for analysis in three dimensions: muscle activation, joint co-activation, and muscle synergy. The participants began running at 8 km/h, with the speed increased by 1 km/h every 2 min until their heart rate reached 75% of the estimated maximum heart rate (MHR), after which an individualized constant-speed phase was performed. Peak fatigue state was determined by two criteria: heart rate reaching 90% of MHR and a Borg scale score of ≥17. Data were compared before and after fatigue. Muscle synergies were extracted using non-negative matrix factorization (NNMF), and the number of modules was determined when the variance accounted for (VAF) first reached 95%.

Results: The results showed that muscle activation exhibited phase-specific changes after fatigue: During the stance phase, the root mean square (RMS) values of the quadriceps femoris (QF) and gluteus maximus (GM) increased significantly (p < 0.05). During the swing phase, the RMS value of the tibialis anterior (TA) increased significantly while that of the GM decreased significantly (p < 0.05). The joint co-activation ratio (CAR) increased significantly only at the ankle joint during the swing phase (p < 0.05). There was no significant difference in the number of muscle synergy modules (p > 0.05). However, the activation timing of the early stance module was significantly advanced (p < 0.05), and the muscle weights within the modules also changed; for example, the weights of the vastus lateralis (VL) and lateral head of the gastrocnemius (GL) decreased, while the weight of the TA increased (p < 0.05).

Conclusion: Our results indicate that under running-induced fatigue, the lower limb neuromuscular system maintains motor output based on the principle of "stability first" through three approaches: "selective compensation" to activate muscles, "rigidity enhancement" to stabilize distal joints, and "timing adjustment" to optimize synergy modules. The findings may contribute to training optimization and help reduce the likelihood of potential injuries.

Chronic refractory hiccups significantly impair quality of life, especially with prolonged symptom duration. This case highlights the therapeutic potential of a combined interventional approach in managing chronic refractory hiccups, particularly in patients with prolonged symptom duration unresponsive to conventional treatments. A 52-year-old man presented with a 20-year history of persistent, debilitating hiccups, often triggered after meals and resistant to pharmacological therapy. His symptoms had worsened in recent years, occasionally accompanied by reflux and vomiting, with minimal relief from anti-reflux medications and neural supplements. Further evaluation revealed pathological acid reflux and excessive supra-gastric belching, suggesting gastroesophageal reflux disease (GERD) as a contributing factor. After comprehensive assessment and informed consent, the patient underwent a series of ultrasound-guided interventions, including bilateral stellate ganglion blocks (SGBs) and phrenic nerve blocks. Although initial symptom relief was achieved, hiccups partially recurred, prompting the use of pulsed radiofrequency modulation (PNRF) of the phrenic nerve in combination with targeted analgesic injections. Following treatment, the patient experienced a significant and sustained reduction in hiccup frequency and severity, with only occasional brief relapses. Continued follow-up and additional sessions of phrenic nerve modulation resulted in further symptom control. This case underscores the effectiveness of integrating sympathetic and somatic nerve modulation, particularly ultrasound-guided SGB and PNRF, in cases of intractable hiccups. Such a multimodal, image-guided strategy may offer meaningful relief for patients suffering from chronic, treatment-resistant hiccups and demonstrates the value of personalized, interventional pain management in complex functional disorders.

Introduction: The urinary steroid module of the Athlete Biological Passport (ABP), monitoring biomarkers over time is limited in female athletes. A serum steroid module has been implemented, including testosterone (T), androstenedione (A4) and the T/A4 ratio, being more stable regarding hormonal fluctuations in women. Acute training may increase serum T and decrease the urinary excretion of androgens. Moreover, the urinary levels of ABP metabolites have been shown to be lower in female athletes compared to sedentary controls. One hypothesis is elimination of some of the androgens via sweat. Therefore, it is of interest to study the urinary and circulatory steroids in relation to training and sweat production.

Material and methods: 30 healthy female athletes and 26 untrained BMI-matched controls were included. The athlete's urine and fluid intake was collected over 48 h during a rest- and a training day, and the controls for 24 sedentary hours. Estimated sweat loss was calculated. For the athletes, dried blood spots (DBS) were collected at rest, before and after training and the day after training. Urine was analyzed for the urinary steroid profile by gas chromatography-tandem mass spectrometry and DBS for T and A4 by liquid chromatography-tandem mass spectrometry.

Results: Sweat production was elevated in athletes during the training day versus the rest day, but there were no differences compared to the controls. No significant intra-individual variation (CV %) in urinary steroid profiles was observed; however, controls excreted higher absolute levels of urinary A and 5αAdiol. In DBS, T remained stable whereas a minor increase in A4 was noted in samples taken the day after training. For the T/A4 ratio changes were observed in samples taken after exercise only.

Conclusion: T and A4 in DBS were not affected by acute training. As DBS sample time differed during the day the minor changes in A4 and the T/A4 ratio may be due to diurnal variation and not training dependent effects. In urine certain urinary steroids were lower in the female athletes compared to controls. These results may be of interest when interpreting results of the ABP.

Objective: This study aimed to elucidate the potential targets and molecular mechanisms underlying arecoline-induced oral submucous fibrosis through integrated transcriptomic profiling and experimental validation.

Methods: Transcriptomic sequencing was first employed to identify key pathways and targets influenced by arecoline in rat oral mucosa and whole blood. Subsequently, in vitro experiments using human primary oral mucosal fibroblasts (hOMFs) were conducted to validate the molecular mechanisms.

Results: In vivo experiments demonstrated that chronic topical application of arecoline significantly reduced oral opening distance and induced histopathological features of oral submucous fibrosis (OSF), including epithelial atrophy, collagen deposition, and elevated TGF-β expression. Transcriptomic analysis revealed significant enrichment of pathways associated with fibrosis, including PPAR signaling, AMPK signaling, p53 signaling, and Hippo signaling pathways. In vitro validation further confirmed that arecoline dose-dependently upregulated α-SMA and Col1a1 expression, enhanced fibroblast proliferation, and activated Hippo pathway effectors (YAP/TAZ).

Conclusion: These findings highlight the Hippo signaling pathway as a critical mediator of arecoline-induced OSF, providing novel insights for therapeutic targeting and mechanistic exploration in OSF management.