Frontiers in Physiology最新文献

Objective: This study aimed to investigate the role of Tmem45b, a gene expressed in itch-associated Dorsal root ganglion (DRG) neurons, in the regulation of itch sensation.

Methods: The expression of Tmem45b was examined in DRG neurons. These neurons included Nppb-, Mrgpra3-, and Mrgprd-positive subtypes, which are known to mediate itch. Behavioral response to various pruritogens including β-alanine, chloroquine, histamine, serotonin, and N-met-LTC4 were assessed on Mrgprd-cre::Tmem45b^flox/flox conditional knockout (cKO) mice. Chronic itch was evaluated using both atopic dermatitis-like and dry skin-like mouse models. To investigate intracellular calcium dynamics, calcium imaging was performed on dissociated DRG neurons. Additionally, bulk RNA-seq was conducted on DRG from Tmem45b cKO mice to assess transcriptomic changes. Serca1 expression and the calcium storage capacity of the endoplasmic reticulum (ER) were analyzed following Tmem45b deletion.

Results: Tmem45b was found to be expressed in itch-associated DRG neurons. In Tmem45b cKO mice, scratching behavior was reduced in response to β-alanine but increased in response to chloroquine. Notably, chronic itch was alleviated in Tmem45b-deficient mice. Calcium imaging revealed that Tmem45b cKO impaired calcium responses to β-alanine and allyl isothiocyanate, but not to chloroquine. Mechanistically, Tmem45b deficiency led to a significant downregulation of Serca1, reducing ER calcium storage capacity. Pharmacological inhibition of Serca1 in DRG neurons similarly suppressed intracellular calcium release in response to β-alanine and chloroquine.

Conclusion: Tmem45b plays a critical role in nonhistaminergic itch by regulating ER calcium homeostasis through Serca1. Its deficiency reduces itch behavior and impairs calcium signaling in DRG neurons, suggesting that Tmem45b is a potential therapeutic target for chronic itch.

Background and aims: Thyroid hormones critically regulate cardiovascular homeostasis, with thyroid dysfunction established as an independent risk factor for coronary artery disease. While free triiodothyronine (FT3) to free thyroxine (FT4) ratio reflects peripheral thyroid hormone conversion efficiency, its prognostic utility for anatomical severity of coronary lesions in acute coronary syndrome (ACS) remains undetermined.

Methods and results: This observational study enrolled a total of 431 ACS patients who underwent coronary angiography. The anatomical severity of coronary lesions was quantified by SYNTAX score. Patients were stratified into three groups based on tertiles of the FT3/FT4 ratio: T1 (FT3/FT4 ≤0.27, n = 144), T2 (0.27 < FT3/FT4 ≤0.33, n = 144), and T3 (FT3/FT4 >0.33, n = 143). They were further categorized into low-risk (baseline SYNTAX score [bSS] <23) or mid-/high-risk (bSS ≥23) subgroups based on bSS. Compared with the T1 group, patients in the T2 and T3 groups had significantly lower bSS values. Multivariate logistic regression analysis demonstrated that the T3 group had a 53% lower risk of mid-/high-risk SYNTAX scores than the T1 group (odds ratio [OR] 0.470; 95% confidence interval [CI]: 0.227-0.971; P = 0.041). The area under the receiver operating characteristic curve (AUC) for the FT3/FT4 ratio in predicting mid-/high-risk SYNTAX scores was 0.656 (95% CI: 0.587-0.724; P < 0.001). Clinical decision curve analysis confirmed the clinical utility of the FT3/FT4 ratio for this prediction. Additionally, restricted cubic spline analysis revealed a negative dose-response relationship between the FT3/FT4 ratio and SYNTAX scores (non-linear P = 0.017).

Conclusion: Impaired peripheral thyroid hormone (increased of the FT3/FT4 ratio) conversion efficiency was independently associated with increased coronary anatomical complexity in ACS patients.

Objective: This study systematically evaluated the effects of high-intensity interval training (HIIT) on circulatory indicators in sedentary populations. Following the framework of systematic review and meta-analysis, it synthesized current evidence to support the evidence-based application of HIIT in exercise interventions for sedentary individuals.

Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered on PROSPERO. We searched PubMed, Web of Science, Embase, and CNKI for studies published between January 2000 and July 2025. Inclusion criteria used the PICOS framework: Participants (sedentary individuals), Intervention (HIIT), Comparison (control), Outcomes (blood pressure, pulse wave velocity, flow-mediated dilation, heart rate), and Study type randomized controlled trials. The search yielded 434 records. After duplicate removal and screening, 14 RCTs (500 participants) were included. The Cochrane Risk of Bias tool assessed study quality, and analyses used RevMan 5.4.

Results: Significant differences were observed between the HIIT and control groups in several outcomes: systolic blood pressure (SBP) (MD = -5.02, 95% CI: -7.29 to -2.76, P < 0.0001), diastolic blood pressure (DBP) (MD = -2.43, 95% CI: -4.08 to -0.79, P = 0.004), pulse wave velocity (PWV) (MD = -0.28, 95% CI: -0.56 to -0.01, P = 0.04), flow-mediated dilation (FMD) (SMD = 1.12, 95% CI: 0.32-1.92, P = 0.006), and heart rate (MD = -0.36, 95% CI: -0.69 to -0.03, P = 0.03). Subgroup analysis of FMD revealed no heterogeneity in studies with a mean participant age of >30 years (P = 0.38, I² = 0%). However, substantial heterogeneity remained in studies with a mean age ≤30 years (P = 0.0003, I² = 79%), suggesting age may be a major source of heterogeneity.

Conclusion: HIIT effectively improves key circulatory indicators in sedentary populations, including blood pressure, vascular elasticity, and endothelial function, making it a valuable exercise strategy for vascular health management. However, further high-quality and standardized clinical trials are needed to confirm its long-term efficacy and safety.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD420251106079.

Dissolved oxygen (DO) in aquatic ecosystems plays a pivotal role in fish farming, serving as a critical determinant for the sustainable development of aquaculture practices. When fish suffer hypoxic stress, they undergo a cascade of physiological adaptations. In this study, healthy E. cyanopodus were subjected to experimental treatments under normoxic (6.0 ± 0.05 mg/L) and hypoxic (1.6 ± 0.05 mg/L) conditions for 1 (H1), 3 (H3), 6 (H6), and 9 (H9) h to evaluate physiological responses. Liver RNA-seq analysis identified 6152 differentially expressed genes (DEGs) between the control group (H0) and the four hypoxia-treated groups (H1, H3, H6, H9). RNA-seq results indicated that hypoxia for 3-6 h was the key duration when significant physiological changes occurred in E. cyanopodus. KEGG enrichment analysis revealed significant involvement of these DEGs in key hypoxia-responsive pathways, including HIF-1 signaling, Glutathione metabolism, p53 signaling, PPAR signaling, and PI3K-Akt signaling pathways. These DEGs primarily played function in biological processes, including glycolysis/gluconeogenesis (aldob, hk, ldh-a, pparα, eno1, gpt), pyruvate metabolism (aldocb, ldh-a, fabp1), immune response (pnp, cxcl5, tnf-α, il1-β, il12-β), and apoptosis regulation (bax, bcl2, casp3). Their coordinated expression played a crucial role in mediating hypoxic adaptation of the liver and brain in E. cyanopodus. Three immune-related enzymes (AKP, ALT, AST), and two metabolic-related enzymes (GLU, LDH) were significantly expressed at 3 and 6 h. These results exactly proved that 3-6 h of hypoxic stress was the key period when E. cyanopodus experienced significant physiological changes. This study elucidated key physiological response changes underlying hypoxic stress in E. cyanopodus, which provided both theoretical framework for understanding hypoxic adaptation and practical insights for developing hypoxia-resistant breeding strategies.

Background: Rowing is a whole-body sport characterized by high-intensity efforts that require simultaneous aerobic and anaerobic energy provision. Although endurance physiology is well documented, the acute systemic responses to competitive rowing remain insufficiently understood. The present study examined endocrine stress responses, leukocyte redistribution, and muscle damage dynamics following a 2,000-m rowing time trial in elite male athletes.

Methods: Twenty national-level rowers (age: 20.4 ± 1.2 years; height: 180.0 ± 4.3 cm; body mass: 80.6 ± 8.7 kg) completed a standardized 2,000-m ergometer test. Venous blood samples were collected at baseline (PRE), immediately post-exercise (POST), and 30 min after exercise cessation (REC30). Serum cortisol was quantified by radioimmunoassay, plasma catecholamines by high-performance liquid chromatography, leukocyte subpopulations by flow cytometry, and muscle damage markers (creatine kinase [CK], lactate dehydrogenase [LDH]) by enzymatic analysis. Normality was evaluated, and repeated-measures ANOVA or Friedman tests were applied with Bonferroni-adjusted post-hoc comparisons.

Results: Mean performance time was 6:49.6 ± 14.7 min, corresponding to a mean power output of 328.4 ± 34.1 W. Cortisol, epinephrine, and norepinephrine increased markedly at POST (p < 0.001) and remained elevated at REC30. Total white blood cells, neutrophils, monocytes, eosinophils, and basophils peaked at POST and declined toward baseline by REC30. Lymphocytes rose at POST but decreased below baseline at REC30 (p < 0.001), and the neutrophil-to-lymphocyte ratio exhibited a biphasic pattern. CK and LDH increased acutely at POST and partially regressed at REC30, remaining above baseline.

Discussion: These findings indicate that maximal rowing performance elicits pronounced endocrine activation, transient immune redistribution, and acute muscle damage. Tailored recovery strategies may be necessary to counteract immune suppression and support sustained performance in elite rowers.

Background: Calcium (Ca) leak from the sarcoplasmic reticulum contributes to cardiac arrhythmias, yet the structural mechanisms regulating spontaneous Ca release from ryanodine receptor type 2 (RyR2) clusters remain poorly understood.

Methods: We developed a computational model in which each RyR2 channel comprises four interacting subunits embedded within spatially organized clusters. This framework captures both cooperative gating within individual channels and coupling between neighboring channels.

Results: Our simulations reveal that spontaneous Ca spark timing depends exponentially on RyR2 cluster structural integrity. This exponential sensitivity means that modest disruptions in cluster structure, such as partial fragmentation, can increase spontaneous Ca spark frequency by 100-1,000 fold.

Conclusions: Cluster structural integrity provides a powerful control mechanism for Ca leak and represents a promising therapeutic target for restoring Ca homeostasis in cardiac myocytes.

Background: Glucose homeostasis is regulated by both central and peripheral systems to maintain metabolic stability during periods of feeding, fasting, and stress. Orexins A and B, hypothalamic neuropeptides traditionally associated with arousal and feeding behavior, are increasingly recognized for their pivotal role in glucose homeostasis via neural and endocrine mechanisms. This review synthesizes the available data orexinergic-glucose pathway.

Method: Following PRISMA guidelines, a systematic search of PubMed and Wiley Online Library identified original studies (between January 1999 and May 2025) examining orexin's impact on glucose homeostasis in mammalian models. Molecular mechanisms were analyzed and grouped by tissues: central nervous system (CNS), pancreas, liver, skeletal muscle, adipose or vascular tissue, gut, and whole-body systems.

Results: Thirty studies were included. Central orexin neurons integrate glycemic inputs via the autonomic nervous system (ANS). Orexin-A stimulates insulin secretion and β-cell proliferation through OX1R/PI3K/Akt/ERK1/2 signaling. It suppresses hepatic gluconeogenesis via PGC-1α downregulation and enhances insulin sensitivity. In adipose tissue, it promotes GLUT4 translocation and adiponectin via PPARγ/C/EBPα, while protecting endothelium from high-glucose damage via SIRT1/NLRP3 inhibition. In the gut, orexin inhibits SGLT-1-mediated glucose absorption through OX1R/OX2R. Systemic orexin deficiency induces insulin resistance, reversible by treatment.

Conclusion: The orexinergic pathway serves as a metabolic integrator, linking central glucose sensing with peripheral utilization. Its context-dependent duality, promoting glucose release in hypoglycemia and insulin sensitivity in hyperglycemia, highlights a unique regulatory role. Orexin receptors are promising therapeutic targets for diabetes and metabolic syndrome. Sex-stratified human studies are needed, as preclinical data reveal marked sexual dimorphism in orexin-mediated glucose regulation, with males exhibiting greater metabolic vulnerability to orexin deficiency.

Background: Fibromyalgia syndrome (FMS) is a chronic disorder marked by widespread pain. While aerobic exercise (AE) is widely recommended, its isolated effect and the optimal regimen and dose remain unclear. This study aimed to clarify the independent effect of pure AE on pain in FMS and identify the most effective exercise parameters and dose-response relationship.

Methods: We systematically searched PubMed, Cochrane, Embase, and Web of Science up to June 2025 for randomized controlled trials (RCTs) examining AE's effect on FMS pain. Subgroup analyses were performed by age, baseline pain level, exercise type, and protocol characteristics. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated, and dose-response relationships were explored.

Results: Fourteen RCTs with 777 participants were included. AE significantly reduced pain compared with controls [SMD = -1.07; 95% CI: -1.57 to -0.57], especially in patients aged 45-60 years and those with chronic severe pain. The most effective intervention was moderate-intensity, water-based AE performed for 60 min per session, 1-2 times weekly, over 12-16 weeks. Dose-response analysis identified an optimal dose of 470 MET-min/week [SMD = -1.71; 95% CrI: -1.90 to -1.14], with an effective range of 75-750 MET-min/week.

Conclusion: This meta-analysis confirms the efficacy of AE in reducing pain in FMS. AE significantly alleviates pain in fibromyalgia, with moderate-intensity, water-based, showing the most effective results. These findings provide strong evidence for incorporating AE as a key non-pharmacological strategy in the management of fibromyalgia, especially for patients with more severe pain. The identified optimal exercise parameters offer clear guidance for clinical practice, supporting the use of tailored exercise regimens in patient care.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251086595.

Introduction: The longissimus dorsi muscle of Bactrian camels holds significant biological and economic value. However, the cellular heterogeneity, lineage differentiation patterns, and intercellular communication mechanisms underlying its skeletal muscle development remain unclear, which has hampered the advancement of precise regulation of camel meat quality traits and genetic improvement of the breed. Accordingly, there is an urgent need to elucidate the developmental regulatory mechanisms of this muscle tissue at the single-cell level.

Methods: In this study, longissimus dorsi muscle tissues from 4-day-old (juvenile) and 5-year-old (adult) Bactrian camels were selected as research subjects. Integrated single-nucleus RNA sequencing (snRNA-seq) was employed to obtain gene expression data, which was coupled with Monocle2 pseudotime analysis, CellChat-based intercellular communication dissection, Gene Ontology (GO) enrichment analysis, and C2C12 cell functional validation experiments to conduct a systematic investigation into the cellular characteristics and developmental mechanisms of the Bactrian camel longissimus dorsi muscle.

Results: A total of 14 cell clusters were identified, and the cellular composition of muscle tissues differed significantly between age groups-juvenile camel muscles were enriched with proliferative cell populations such as muscle satellite cells (MuSCs) and fibroblast-like progenitor cells (FAPs), while adult camel muscles were dominated by mature type IIX/IIA fast-twitch muscle fibers. Further analysis revealed that MuSCs exhibited bidirectional differentiation potential towards type I slow-twitch muscle fibers and type IIA/IIX fast-twitch muscle fibers, and the PCDH7 gene was found to promote myogenic differentiation. Additionally, four FAP subpopulations were characterized, among which the MME⁺ FAP subpopulation was closely associated with intramyocellular fat (IMF) deposition.

Discussion: This study, for the first time, constructed a single-cell atlas and intercellular communication network of the Bactrian camel longissimus dorsi muscle, uncovered the key regulatory mechanisms governing its skeletal muscle development, and identified functionally important regulatory targets such as PCDH7. These findings not only provide a theoretical basis for the precise improvement of camel meat quality but also laid the groundwork for in-depth investigations into the adaptive evolutionary mechanisms of camel skeletal muscle.