Frontiers in Physiology最新文献

This review aims to present a current overview of the role of mitophagy in breast cancer progression, especially from the point of view of when the cancer is in the untreated state or under chemotherapeutic treatment. We aim to explain the apparently contradictory results as reported in numerous studies on the differential role of mitophagy in breast cancer. We propose that different levels of reactive oxygen species (ROS), and the balance between mitophagy and apoptosis under different conditions are the major reasons to explain for the "discrepancy". If the cancer cells are untreated, a medium level of ROS promotes cancer progression. Mitophagy inhibition, which leave the dysfunctional mitochondria to generate more ROS, would therefore increase cancer progression. On the other hand, if the cancer cells are undergoing chemotherapeutic treatment, the excessively high level of ROS generated would stimulate both mitophagy and apoptosis, where mitophagy would inhibit apoptosis. In this case, inhibiting mitophagy would potentiate apoptosis and therefore enhance treatment effectiveness. The molecular mechanisms underlying the regulation between mitophagy and apoptosis are also discussed in this review. In summary, the review shall provide important insights for the role of mitophagy in breast cancer. It is proposed that the identification of the molecules involved in balancing mitophagy and apoptosis, and combined therapeutic strategies are the key areas for future exploration.

Introduction: In contemporary research practice, high-intensity interval training (HIIT) has received growing attention compared to other types of endurance training [e.g., moderate-intensity continuous training (MICT)]. This is primarily related to HIIT's ability to induce higher metabolic stress, driving an increased exerkine secretory response (i.e., of specific proteins) compared to MICT. To date, previous reviews on HIIT have primarily focused on single exerkines, while a more comprehensive analysis, as required to gain a more comprehensive understanding of the complex exercise-related physiological processes, is absent.

Methods: To reduce non-exercise protocol-related outcome heterogeneity, the rigorous inclusion criteria (i.e., exercise intensity in the HIIT adjusted for the target population of healthy, diseased, or older individuals, and not taking any medications) were applied.

Results: A total of 39 studies were selected for the systematic review, with fourteen, twenty-two, and three for the acute, chronic, and both acute and chronic effects of HIIT on exerkine concentrations, respectively. Acute HIIT appears to result in greater changes in BDNF and VEGF concentration than the control group performing lower-intensity exercise or no exercise. Metabolically active exerkine, such as adiponectin, mainly fluctuates among overweight and obese participants.

Discussion: This systematic review did not yield any definitive results regarding alterations in IGF-1, irisin, cortisol, and interleukin levels. Tendentially, HIIT is more effective than MICT and non-exercise interventions to induce a greater secretory response of certain exerkines, such as BDNF, VEGF and adiponectin. Evidence regarding exerkine secretion in response to HIIT among older adults remains limited, highlighting the need for further investigation.

Systematic review registration: Identifier CRD420251003743.

A 57-year-old male patient presented with paroxysmal palpitations for 2 years. The patient's blood pressure was 120/76 mmHg; his heart rate was 149 beats/min. The presenting electrocardiogram showed a wide QRS complex tachycardia with an irregular rhythm. The RR intervals were irregular, and there were more complex QRS waves than P waves. The patient was first diagnosed with ventricular tachycardia. The ECG during sinus rhythm revealed a complete right bundle-branch block. The patient underwent an invasive electrophysiological study and was then diagnosed with atrioventricular nodal reentrant tachycardia (AVNRT). Following successful slow pathway radiofrequency ablation (located at the anterior part of the coronary sinus ostium), tachycardia was no longer inducible.

Introduction: Heart rate variability (HRV) is a vital metric for assessing cardiovascular health, psychological stress, and sleep quality. Non-contact HRV monitoring offers advantages in safety, comfort, and hygiene, making it an increasingly attractive solution.

Methods: In this study, we propose a high-precision, non-contact HRV analysis method using a 77 GHz multiple-input multiple-output (MIMO) frequency-modulated continuous wave (FMCW) radar system. The proposed method first employs an optimized Capon beamforming algorithm to accurately localize the heart and enhance intermediate frequency (IF) signals from the heart's direction. A modified differentiate and cross-multiply (MDACM) algorithm is then used to demodulate the phase sequence, yielding a raw vital sign signal that includes both respiratory and cardiac components. This signal is further processed using a six-level wavelet packet transform (WPT), from which specific wavelet coefficients (6th to 12th bands at level six) are selected to reconstruct the seismocardiogram (SCG) signal. To extract precise inter-beat interval (IBI) sequences, a robust aortic valve opening (AO) point detection algorithm is developed. Time-domain HRV indices-including the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD), and the percentage of successive normal-to-normal intervals differing by more than 50 milliseconds (ms) (pNN50)-are then computed from the IBI sequence. To validate the approach, we developed a synchronized data acquisition system combining radar and electrocardiogram (ECG) sensors and collected data from 13 participants-each person collected data for 10 min.

Results: Experimental results demonstrate the effectiveness of our method, achieving average errors of 4.11 ms in SDNN, 8.05 ms in RMSSD, and 2.15% in pNN50 compared to ECG-derived ground truth.

Discussion: These results outperform existing non-contact HRV monitoring techniques and highlight the method's potential for practical, continuous, and unobtrusive cardiovascular monitoring.

Purpose: To compare auto-regulated velocity-based training (VBT) with traditional fixed percentage-based training (PBT) on neuromuscular performance in collegiate sprinters.

Methods: Twenty resistance-trained males performed 6 weeks of back squat exercise 3 times per week. Both groups completed five sets of five repetitions with 3-min inter-set rest, matched for exercise selection and volume. The VBT group adjusted load based on real-time barbell velocity to maintain a target mean propulsive velocity of ∼0.54 m·s^-1 (≈80% 1RM), whereas the PBT group trained with a fixed 80% of pre-intervention 1RM without further adjustment. Countermovement jump (CMJ), Standing long jump (SLJ), 20-m sprint times (T20-m), maximal strength (1RM back squat), and COD (T-test) were measured pre- and post-intervention.

Results: Both groups significantly improved CMJ height (VBT: +7.8%, ES = 0.48; PBT: +6.7%, ES = 0.44), relative peak power output (VBT: +4.1%, ES = 0.85; PBT: +3.8%, ES = 0.35), SLJ performance (VBT: +1.0%, ES = 0.37; PBT: +1.8%, ES = 0.15), T20-m sprint times (VBT: -3.7%, ES = 1.30; PBT: -1.6%, ES = 0.51), maximal strength (VBT: +16.4%, ES = 1.57; PBT: +11.5%, ES = 0.94), and COD performance (VBT: -3.2%, ES = 0.54; PBT: -1.5%, ES = 0.39). VBT elicited significantly greater improvements than PBT in 1RM strength, T20-m, and COD performance (P < 0.05), whereas changes in CMJ and SLJ did not differ between groups (P > 0.05).

Conclusion: Both training methods improved CMJ, SLJ, T20-m, 1RM back squat, and COD performance, but VBT may be slightly favorable for collegiate sprinters focusing on maximal strength, sprint performance, and COD compared to PBT.

Sarcopenia, an age-related syndrome characterized by the progressive decline of skeletal muscle mass and function, threatens the health of older adults through underlying mechanisms that include dysregulated protein metabolism, autophagy-mitochondrial dysfunction, chronic inflammation, and impaired regenerative capacity of muscle stem cells. Exercise-derived circulating exosomes, which act as key mediators of intercellular communication, show considerable potential in mitigating sarcopenia-related damage. In this review, we summarize the biogenesis of exercise-induced exosomes, encompassing both ESCRT-dependent and independent pathways, secretion regulated by RAB and SNARE proteins, and their release mediated through mechanical, calcium, metabolic, and neuroendocrine signaling during exercise. We further elaborate on the systemic roles of these exosomes in muscle repair, including alleviating lipotoxicity via the FGF21-adiponectin axis, maintaining protein homeostasis through dual regulation by miR-29c, and ameliorating the inflammatory microenvironment via modulation of macrophage polarization. Finally, we discuss the translational promise of exosomes as therapeutic targets and outline future research directions, offering a conceptual framework for understanding exercise-mediated muscle protection and developing novel interventions.

SPECC1L encodes a cytoskeletal scaffolding protein that interacts with filamentous actin, microtubules, and cell junctional components. In humans, autosomal dominant mutations in SPECC1L cause a syndrome characterized by craniofrontonasal anomalies including broad nasal bridge, ocular hypertelorism, prominent forehead, and cleft lip/palate. Complete loss of SPECC1L in mice on a homogeneous genetic background results in perinatal lethality, accompanied by subtle cranial differences and incompletely penetrant cleft palate. This lethality limits postnatal analysis of craniofacial development. Because cranial neural crest cells (CNCCs) contribute extensively to the formation of anterior craniofacial structures, we investigated whether disruption of SPECC1L in CNCCs contributes to the craniofrontonasal phenotypes observed in SPECC1L-related syndrome. We generated a Specc1l-floxed allele and crossed it with the Wnt1-Cre2 deleter strain, which drives Cre recombinase expression in the dorsal neuroectoderm and NCCs. Most homozygous Specc1l ^ΔCNCC mutants survived postnatally and exhibited hallmark features of the human SPECC1L-related syndrome, including shortened skulls, reduced frontal bone area, nasal defects, and midface hypoplasia. The cranial mesenchyme of Specc1l ^ΔCNCC mice displayed shortened primary cilia and increased Hedgehog (Hh) signaling activity at E13.5, as evidenced by enhanced GLI1 immunostaining. These defects were also observed early in E9.5 facial prominences, indicating that they may drive the adult phenotype. Collectively, Specc1l ^ΔCNCC mice provide a novel model for investigating the roles of CNCCs, primary cilia, and Hh signaling in frontonasal prominence and midfacial development.

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.].