Frontiers in Physiology最新文献

Purpose: Selective inhibition of atrial proarrhythmicity can be therapeutic for reducing the atrial fibrillation (AF) burden. Atrial-selective K⁺-channel blockade (mainly Kv1.5 and Kv4.3 channels conducting the sustained I_Kur and transient I_to outward currents) promises to suppress AF with a favorable benefit-to-harm ratio. The mechanisms underlying the efficacy of K⁺ channel blockade under arrhythmic conditions and its association with electrophysiological and contractile remodeling in AF remain to be investigated.

Methods: Using our electromechanically coupled model MBS2023, we have simulated the effects of 4-aminopyridine (4-AP) and AVE0118 at different basic cycle lengths (2-0.25s). We have dissociated the primary and secondary responses to determine the drug's underlying mechanisms of action. We have analyzed the effects of K⁺-channel blockers under arrhythmogenic conditions induced by either forward excitation-contraction coupling (ECC) or mechano-calcium feedback.

Results: At the basal rate, the voltage-mediated increase in I_Kr induced by 4-AP shortens the action potential duration (APD) under sinus rhythm (SR), whereas a surge in I_CaL prolongs APD under AF. 4-AP can exacerbate the vulnerability to phase 2 early afterdepolarizations (EADs) by slowing repolarization and prolonging myofilament activation. K⁺-channel blockade can decimate the susceptibility of delayed afterdepolarizations (DADs) by eliminating the cytosolic Ca²⁺ overload. The slowing of repolarization induced by 4-AP can suppress the reopening of Na⁺ channels during phase 3 EADs.

Conclusion: In both types of EAD, a shorter, Ca²⁺-desensitized sarcomere can reduce the propensity for AF in the model. In general, K⁺ channel blockade has anti-arrhythmic potential to suppress phase 3 EADs by slowing repolarization.

[This corrects the article DOI: 10.3389/fphys.2025.1706730.].

Objective: This study aimed to systematically compare the efficacy of various recovery strategies for improving neuromuscular function, muscle damage, and subjective fatigue in elite soccer players following matches or validated simulations, and to provide evidence-based guidance for clinical practice.

Methods: Following PRISMA-NMA guidelines, we systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus for randomized controlled trials evaluating post-match or post-simulation recovery strategies in professional and semi-professional soccer players. A Bayesian random-effects model was applied to conduct the network meta-analysis. Effect sizes were reported as mean differences (MD) with 95% credible intervals (CrI), and intervention efficacy was quantified using Surface Under the Cumulative Ranking (SUCRA) values.

Results: Twenty-three RCTs involving 388 participants and 17 recovery interventions were included. Key findings were as follows: (1) Far-infrared therapy (FIR) was most effective in improving Countermovement jump (CMJ) height (SUCRA = 98.3%); (2) Intermittent negative pressure therapy (INPT) produced the greatest reduction in Creatine kinase (CK) levels (SUCRA = 91.0%); (3) Portable cold compression therapy (PCMcold) had the strongest effect on alleviating Muscle soreness (MS) (SUCRA = 98.9%); (4) FIR and Intermittent vascular occlusion (IVO) significantly improved Maximal voluntary contraction (MVC), although Hyperoxic gas (Hyp) ranked highest (SUCRA = 89.8%); and (5) no intervention significantly improved 20-m sprint performance (all 95% CrI included zero), and although IVO ranked first (SUCRA = 84.5%), its evidence reliability was low.

Conclusion: Personalized post-match recovery in elite soccer should be based on specific targets. FIR is recommended for CMJ restoration, INPT for muscle damage repair, PCMcold for reducing subjective soreness, and FIR may be considered for MVC recovery. No superior intervention was identified for 20-m sprint recovery; therefore, basic recovery measures are advised. Future multi-arm RCTs are required to validate combined recovery strategies and standardize intervention parameters.

Objectives: This systematic review and meta-analysis examined the effects of plyometric training (PT) on the physical fitness of adolescent team-sport athletes.

Methods: We systematically searched the PubMed, Web of Science, Scopus, and Embase databases. The methodological quality of the studies was evaluated using the Cochrane Risk of Bias Tool (ROB-2). Meta-analyses were conducted using RevMan 5.4 and STATA 15.0.

Results: A total of 31 studies involving 1,033 athletes (906 males and 127 females) were ultimately included. PT improved jump performance, including countermovement jump (ES = 0.89), countermovement jump with arms (ES = 1.00), squat jump (ES = 0.48), and standing long jump (ES = 1.10). PT also improved linear sprint over ≤10-m (ES = -0.59), 20-m (ES = -0.42), and 30-m (ES = -0.97), and improved change-of-direction (ES = -0.73).

Conclusion: Plyometric training can significantly improve the jumping performance, linear sprint and change-of-direction in adolescent team-sport athletes. Athletes aged 16-18.99 years may show larger improvements, and interventions lasting ≥8 to <10 weeks may be associated with more consistent gains, particularly for Countermovement Jump, SJ, ≤10-m linear sprint, and 20-m linear sprint. In contrast, increasing the total number of jumps was not consistently associated with greater training effects.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251034889.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), yet its progressive fibrosis cannot be solely attributed to hyperglycemia-induced oxidative stress or glomerular hypertension. Increasing evidence highlights that the bidirectional interaction between metabolic disturbances and immune activation-termed immunometabolic interactions-plays a pivotal role in driving DKD progression. Chronic metabolic stress, encompassing hyperglycemia, lipotoxicity, mitochondrial dysfunction, and gut-derived metabolites, reprograms innate and adaptive immune cells into pro-inflammatory and pro-fibrotic states. In turn, these activated immune cells exacerbate metabolic damage by promoting reactive oxygen species (ROS) overproduction, disrupting mitochondrial homeostasis, and facilitating extracellular matrix accumulation, thereby creating a self-amplifying loop that accelerates renal fibrosis. Key immunometabolic regulators, including HIF-1α, AMPK, mTOR, and SIRT1, coordinate metabolic signals with immune responses, providing novel mechanistic insights into DKD beyond traditional models. Recent therapeutic advances-such as Sodium-Glucose Cotransporter 2(SGLT2) inhibitors, GLP-1 receptor agonists, mineralocorticoid receptor antagonists, and multi-target natural compounds-offer renoprotective effects, partly by modulating these immunometabolic pathways. Fibrotic remodeling represents a core pathological tissue restructuring event in the kidney, typified by excessive extracellular matrix accumulation and irreversible structural destruction, which is coordinately propelled by the dual drivers of systemic metabolic disorders and local immune activation. A more precise characterization of immunometabolic alterations across disease stages, aided by single-cell and spatial multi-omics technologies, will be essential for identifying causal mechanisms rather than mere associations. Such discoveries could facilitate stage-specific, metabolism-immune-targeted interventions to prevent or slow fibrotic remodeling in DKD.

Background: Cadmium (Cd) is a hazardous ecological contaminant implicated in substantial oxidative stress (OS), nitrative stress, inflammation, apoptosis and fibrosis, particularly in the heart and liver.

Objective: This study aims to contrast the protective effects of "Canagliflozin; Cana" versus "Sitagliptin; Sita" in countering the chronic Cd-induced cardiac and hepatic damage.

Methods: Four groups of adult male Wistar rats (6 each) were created: Control, Cd-exposed; rats received 100 mg/L CdCl₂ via drinking water, Cd + Cana; rats received Cana 10 mg/kg, orally in parallel with CdCl₂ (100 mg/L), and Cd + Sita; rats received Sita 10 mg/kg, orally concomitant with CdCl₂ (100 mg/L). Following a 12-week course of treatment of all regimens, serum glucose, albumin, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine Kinase-MB (CK-MB), Troponin I and Troponin C (cTnC) were measured. Cardiac and hepatic tissues were subjected to quantitative real-time polymerase chain reaction assays for Notch1, transforming growth factor-β, SMAD3, alpha-smooth muscle actin (α-SMA), and SMAD7 expression levels. In addition, interleukin-10/-1β, tumor necrosis factor-α, reduced glutathione, and malondialdehyde were evaluated. Besides, there was a cardiac and hepatic histological evaluation after hematoxylin and eosin, and Masson staining, as well as immunohistochemistry measurement of caspase 3, nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS). Results were analyzed using one-way ANOVA followed by Tukey's post hoc and then represented as mean ± standard deviation. Differences among groups were considered statistically significant when p value is ≤0.05.

Results: There were no substantial changes in blood glucose levels across all groups, which confirmed the model's normoglycemic nature. Therefore, independent from their glycemic effect, both Cana and Sita significantly but comparably (p > 0.05) improved cardiac and hepatic OS, inflammation, apoptosis, and fibrosis associated with chronic Cd exposure. However, Cana demonstrated greater improvement (p < 0.05) in serum CK-MB and cTnC, cardiac (α-SMA) and hepatic (collagen area%) fibrosis, cardiac and hepatic apoptosis (caspase 3%), inflammation (NF-κB%) and nitrative stress (iNOS%) and restored their architecture.

Conclusion: Both medications showed comparable cardio-hepatic protective effects. Yet, Cana outperformed Sita as a potentially effective therapy to counteract the negative consequences of chronic Cd-induced cardiac and hepatic pathologies.

The purpose of this pilot study was to develop and characterize an in vivo porcine model of hyperoxaluria using intravenous infusion of sodium oxalate (NaOx). Two experimental regimens were developed to replicate acute and follow up chronic hyperoxaluria. In the acute model, 3 different doses of 1% NaOx were administered over 15 h, resulting in a dose-dependent increase in plasma oxalate concentration (Cmax: 42.4-122.4 µM) and transient hyperoxaluria, with a return to baseline values 6-8 h after stopping the infusion of NaOx solution. In the chronic model, repeated infusions of NaOx for 7-11 days directly after acute tests led to persistent hyperoxalemia (up to 302.4 µM), clinical deterioration and dose-dependent calcium oxalate (CaOx) deposits in renal tissue (1.85%-9.55% of renal surface area), consistent with impaired renal function. The model represents the key clinical features of both rapidly inducible and reversible hyperoxalemia and hyperoxaluria, as well as the progressive nephrocalcinosis. Due to the physiological similarity between pigs and humans, the proposed porcine model could be considered as a quick and valuable tool for studying the pathophysiology of oxalate excess and testing the efficacy of new therapies to counteract its toxicity.

Objective: This pilot study investigated potential adaptations in limb occlusion pressure (LOP) and compared LOP between low-load resistance training with blood flow restriction (LL-BFR) and traditional moderate-load training (ML) over 9 weeks in patients with knee osteoarthritis (KOA). Secondarily, we compared systolic blood pressure (SBP) and diastolic blood pressure (DBP) adaptations between these groups.

Methods: Seventeen KOA patients were randomly assigned to the LL-BFR or ML groups. The LL-BFR group performed 75 repetitions (10% 1RM; 60% of LOP). The ML group performed 24 repetitions (60% 1RM; 10% [SHAM] of LOP). In both groups, exercises involving LOP were bilateral hack machine squat and knee extension exercises. LOP, SBP, and DBP were measured before and every 3 weeks until the ninth training week.

Results: After 9 weeks, there were no statistically significant changes in LOP, SBP, or DBP within or between groups. LOP decreased by -32.9 mmHg (95% CI: -68.9 to 3.2) in LL-BFR and -17.2 mmHg (95% CI: -49.0 to 14.6) in ML, achieving clinical significance [relative error variance (REV) = 14.6 mmHg]. SBP decreased by -7.5 mmHg (95% CI: -15.6 to 0.6) in LL-BFR and -1.1 mmHg (95% CI: -8.2 to 6.0) in ML. DBP decreased by -3.7 mmHg (95% CI: -9.2 to 1.7) in LL-BFR and -1.9 mmHg (95% CI: -6.8 to 2.9) in ML.

Conclusion: We observed a non-significant trend toward a reduction in LOP following 9 weeks of LL-BFR in patients with KOA, with a mean point estimate that exceeded a pre-defined threshold for clinical significance, although the wide confidence intervals indicate substantial uncertainty. Furthermore, SBP and DBP showed no significant changes, and no group differences emerged across outcomes. Practically, these findings suggest that LOP remains stable throughout a rehabilitation program, potentially reducing the burden of frequent LOP reassessment in clinical LL-BFR applications.

Trial registration: https://ensaiosclinicos.gov.br/rg/RBR-6pcrfm/.

Introduction: In the present study we aim to determine the effects of different inhibitors of the late sodium current (I_Na,late) on vascular responses to adrenergic stimuli, both endogenous and exogenous.

Methods: The study was performed using specific inhibitors of I_Na,late as GS-967, GS-6615 and Ranolazine (RAN). Rings from rabbit aorta were placed in organ baths chambers.

Results: Electrical Field Stimulation (EFS) (2, 4 and 8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, or guanethidine (10^-6 M). The intervention of I_Na,late was observed by incubating the aortic segments with GS-967, GS-6615 or RAN. Concentration-response curves to GS-967, GS-6615 or RAN were constructed in rings precontracted with noradrenaline, endothelin-1 or KCl with or without specific inhibitors (L-NAME, nimesulide, SC-560, verapamil, nifedipine, apamin or charybdotoxin). Contraction to noradrenaline were elicited in the absence or presence of I_Na,late inhibitors (GS-967, GS-6615 or RAN). EFS induced frequency-dependent contractions of rings, mediated by noradrenaline acting on α₁-adrenoceptors. I_Na,late blockers GS-967 and GS-6615 reduced vasoconstriction induced by sympathetic nerve stimulation, effect reversed by charybdotoxin, implicating large-conductance Ca²⁺-activated K⁺ channels. RAN elicited an attenuation of nerve-induced vasoconstriction, with 20% of this effect mediated via large-conductance Ca²⁺-activated K⁺ channels. The predominant mechanism involved competitive antagonism of RAN at α₁-adrenergic receptors.

Discussion: These findings suggest distinct mechanisms of action among I_Na,late blockers, highlighting the involvement of large-conductance Ca²⁺-activated K⁺ channels in GS-967 and GS-6615 effects, and a competitive α₁-adrenoceptor antagonism for RAN. Taken together, our results indicate that GS-967, GS-6615 and RAN decrease vasoconstrictor responses due to both neural and noradrenaline-induced adrenergic stimuli. We can suggest that the use of GS-967, GS-6615 and Ranolazine may be interesting in clinical procedures involving hyperstimulation of the adrenergic nervous system.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that impairs physical function, reduces quality of life, and is associated with psychological burdens such as anxiety and depression. While non-steroidal anti-inflammatory drugs (NSAIDs) and biologic therapies are standard treatments, exercise therapy is crucial for maintaining mobility and function. This study aimed to comprehensively compare the effects of 12 exercise interventions on AS patients' disease activity and chest expansion (CE) via network meta-analysis (NMA) and dose-response meta-analysis, and explore dose-dependent effects to inform personalized exercise prescriptions.

Methodology: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, randomized controlled trials (RCTs) were searched from PubMed, Cochrane Library, Embase, and Web of Science until December 31, 2024. Eligible studies included adults with American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)-diagnosed AS, comparing exercise with conventional treatment/placebo/no intervention, with outcomes of Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and CE. Two reviewers screened literature, extracted data, and assessed bias using the Cochrane Handbook. NMA and dose-response analysis (expressed as metabolic equivalents of task (MET) minutes/week) were performed (Prospero: CRD420251001511).

Results: Thirty-two RCTs with 1757 participants were included. NMA showed hippotherapy simulation (HS) was most effective for reducing BASFI; aerobic exercise (AE) + Pilates was superior for BASDAI and BASMI; AE + Stretching Exercise (SE)+Supervise best improved CE. Dose-response analysis revealed non-linear relationships, with specific effective dose ranges identified for each outcome. Subgroup and sensitivity analyses confirmed result robustness.

Conclusion: Exercise interventions, especially HS, AE + Pilates, and AE + SE + Supervise, effectively improve AS patients' disease activity and CE. Non-linear dose-response relationships emphasize personalized prescriptions, providing evidence-based guidance for integrating exercise into AS management, with future large-scale RCTs needed to validate dose effects.