Frontiers in PhysiologyPub Date : 2025-09-24eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1635983
Aranyak Chakravarty, Debjit Kundu, Mahesh V Panchagnula, Alladi Mohan, Neelesh A Patankar
{"title":"Perspectives on physics-based one-dimensional modeling of lung physiology.","authors":"Aranyak Chakravarty, Debjit Kundu, Mahesh V Panchagnula, Alladi Mohan, Neelesh A Patankar","doi":"10.3389/fphys.2025.1635983","DOIUrl":"10.3389/fphys.2025.1635983","url":null,"abstract":"<p><p>The need to understand how infection spreads to the deep lung was acutely realized during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. The challenge of modeling virus laden aerosol transport and deposition in the airways, coupled with mucus clearance, and infection kinetics, became evident. This perspective provides a consolidated view of coupled one-dimensional physics-based mathematical models to probe multifaceted aspects of lung physiology. Successes of 1D trumpet models in providing mechanistic insights into lung function and optimalities are reviewed while identifying limitations and future directions. Key non-dimensional numbers defining lung function are reported. The need to quantitatively map various pathologies on a physics-based parameter space of non-dimensional numbers (a virtual disease landscape) is noted with an eye on translating modeling to clinical practice. This could aid in disease diagnosis, get mechanistic insights into pathologies, and determine patient specific treatment plan. 1D modeling could, thus, be an important tool in developing novel measurement and analysis platforms that could be deployed at point-of-care.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1635983"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-24eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1625137
Nicola Loi, Francesca Ginatempo, Mohammed Zeroual, Lucia Ventura, Antonella Cano, Carmen Oneto, Paola Ortu, Maria Rita Piras, Franca Deriu
{"title":"A new index of cortical plasticity induced by paired associative stimulation to describe cognitive status in aged healthy subjects.","authors":"Nicola Loi, Francesca Ginatempo, Mohammed Zeroual, Lucia Ventura, Antonella Cano, Carmen Oneto, Paola Ortu, Maria Rita Piras, Franca Deriu","doi":"10.3389/fphys.2025.1625137","DOIUrl":"10.3389/fphys.2025.1625137","url":null,"abstract":"<p><strong>Introduction: </strong>Cortical plasticity is a key factor for cognitive skills, and paired associative stimulation (PAS) is useful to study it in humans. Currently, due to the number of non-responders to PAS and discrepancies in the post-PAS time-points assessed, a plasticity index describing PAS effects and correlating it to cognitive status is lacking. Therefore, this study investigated which PAS index better discriminates between responders (RRs) and non-responders (NRs) and correlates with cognitive status.</p><p><strong>Methods: </strong>Seventy-six healthy aged subjects (67.0 ± 7.2 y.o., 35 males) were enrolled. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Addenbrooke's Cognitive Assessment (ACER) were used to assess cognitive status. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle at baseline and after 0, 10, 20, and 30 min from PAS, pairing peripheral median nerve stimulation with a transcranial magnetic stimulation stimulus over the left primary motor cortex. MEP amplitude was used to calculate the grand average (GrA), which is the mostused PAS plasticity index, along with two newly introduced indexes: the curve concavity (CC) and the pre- vs. post-PAS difference (PPPD). CC described the curve shape of the PAS effects, while PPPD calculated the significant differences between the baseline and post-PAS MEP amplitude.</p><p><strong>Results: </strong>CC demonstrated good consistency as PAS-plasticity index with high odds ratios and sensibility in the discrimination of responsiveness to PAS; PPPD had higher specificity in the identification of RRs. Only the MoCA score was significantly higher (p = 0.006) in RRs than in NRs when the two groups were discriminated according to CC, and it significantly correlated with CC (p = 0.013).</p><p><strong>Discussion: </strong>In conclusion, CC may represent a potential PAS-plasticity index to describe the cortical plasticity and cognitive status in humans, with a possible practical application in patients with cognitive impairment.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1625137"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-24eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1654725
J Bergqvist, F Reite, F Edin, L Schiöler, M Börjesson, S Steinsvåg, S Pettersson, J Hellgren
{"title":"Effects of oral, oronasal, and oronasal breathing with a decongested nose during incremental maximal exercise testing of well-trained endurance athletes: a randomized cross-over study.","authors":"J Bergqvist, F Reite, F Edin, L Schiöler, M Börjesson, S Steinsvåg, S Pettersson, J Hellgren","doi":"10.3389/fphys.2025.1654725","DOIUrl":"10.3389/fphys.2025.1654725","url":null,"abstract":"<p><strong>Introduction: </strong>Nasal breathing is preferable for persons at rest and remains partially active during oronasal breathing in exercise. However, its potential contribution to performance-particularly in cases with a decongested nose-remains understudied in well-trained athletes. This study investigates whether nasal airflow during oronasal breathing influences performance in well-trained, endurance athletes. Specifically, we examine whether nasal decongestion during oronasal breathing enhances ventilatory efficiency and, thereby, improves time-to-exhaustion (TTE), maximal oxygen uptake ( <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub>), and maximum power output (W<sub>max</sub>), as compared to oral-only breathing.</p><p><strong>Methods: </strong>Twelve male, well-trained cyclists/triathlon athletes (mean <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub>, 67.2 ± 5.5 mL kg<sup>-1</sup>·min<sup>-1</sup>) with age range of 30.6 ± 8.7 years, were included. Two characterization tests were performed: 1) an incremental cycle test to determine <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> and W<sub>max</sub>; and 2) a familiarization trial of the experimental exercise protocol. The three experimental exercise trials consisted of five 6-min submaximal steady-state levels (50 W and 100 W at 50 rpm for the first two stages, followed by 40%, 58%, and 75% of the individual W<sub>max</sub> at 80 rpm), concluding with a TTE test.</p><p><strong>Results: </strong>There were no significant differences between the three breathing modes (p > 0.05) in terms of the cardiopulmonary or performance parameters, including the rate of perceived exertion, respiratory frequency, mean minute ventilation, <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub>, and W<sub>max</sub>. Although not statistically significant (p > 0.05) TTE was 2.8% and 4.2% longer during oronasal and decongested oronasal breathing, respectively, as compared to oral-only breathing. The mean capillary blood lactate level was significantly (p < 0.05) lower immediately after and 3 min after the TTE test in the oral-only breathing condition (9.12 ± 2.20 mmol/L), as compared with the oronasal (9.83 ± 2.19 mmol/L, Cohen's <i>d</i> = 0.43) and decongested-nose (9.81 ± 2.29 mmol/L, <i>d</i> = 0.41) conditions.</p><p><strong>Conclusion: </strong>Oral-only breathing is associated with a non-significant shorter TTE than oronasal breathing with or without nasal decongestion, although it results in significantly lower mean capillary blood lactate levels following maximal aerobic exercise. These findings suggest that a single, low-resistance oral breathing route reduces lactate accumulation under maximal effort, whereas oronasal breathing-particularly in the presence of nasal decongestion-may be more beneficial for sustaining endurance.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1654725"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study on the differences in peripheral fatigue responses elicitation effects of bench press training with different loads and tempos based on electromyography and motion sensors.","authors":"Bin Yan, Zhicong Li, Chunwei Li, Chongyang Han, Siqi Yao, DongDong Ma, Wenzhong Zhang","doi":"10.3389/fphys.2025.1661217","DOIUrl":"10.3389/fphys.2025.1661217","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effects of bench press training with different loads (60% 1RM vs. 80% 1RM) and tempos (maximal velocity X/0/X/0 vs. medium tempo 2/0/2/0) on peripheral fatigue responses in bodybuilders, assessing the specific roles of neuromuscular activation, metabolic stress, and kinetic performance.</p><p><strong>Methods: </strong>Ten experienced male bodybuilders performed four training protocols to exhaustion in a randomized crossover design. Electromyography (EMG) was used to record muscle activation (normalized as %MVIC) and spectral shifts (Median Frequency - MDF) from the pectoralis major, anterior deltoid, and triceps brachii muscles. Biochemical assessment involved measuring blood lactate concentrations pre- and post-exercise to quantify metabolic stress. Motion sensors (Vmaxpro) were employed to capture barbell kinematics-including mean velocity (MV), peak velocity (PV), mean power (MP), peak power (PP), and time under tension (TUT)-providing direct measures of neuromuscular performance and fatigue-related velocity loss.</p><p><strong>Results: </strong>A significant interaction between load and tempo was found for all fatigue markers (p < 0.05). The combination of high load and fast tempo (80% 1RM, X/0/X/0) induced the most pronounced peripheral fatigue, evidenced by the highest muscle activation (%MVIC) and blood lactate levels, coupled with the greatest declines in MDF (indicating neuromuscular fatigue), velocity, and power output.</p><p><strong>Conclusion: </strong>The interaction of load and tempo critically determines the pattern and magnitude of acute peripheral fatigue. High-load fast-tempo training elicits multifaceted fatigue across neuromuscular, metabolic, and performance domains, whereas a high-load medium-tempo protocol results in less fatigue despite longer TUT. These findings provide a scientific basis for precise fatigue management in resistance programming.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1661217"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-23eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1625283
Jinjin Dai, Zicheng Dai, Yahui Ding
{"title":"Influence of trunk strength on sprint performance in swimmers: a cross-sectional analysis of torque-velocity relationships.","authors":"Jinjin Dai, Zicheng Dai, Yahui Ding","doi":"10.3389/fphys.2025.1625283","DOIUrl":"10.3389/fphys.2025.1625283","url":null,"abstract":"<p><p>This cross-sectional study assessed trunk strength at 60°/s and 120°/s angular velocities in swimmers and its relationship to 100-m sprint performance. Thirty-two elite swimmers (age: 19.49 ± 1.44 years; height: 177.77 ± 6.84 cm; body mass: 71.88 ± 8.50 kg) underwent isokinetic trunk testing and timed sprints. All tests demonstrated excellent reliability (ICC >0.96). Swimmers had significantly greater peak torque in extension compared to flexion (<i>p</i> < 0.01), and higher torque in left versus right rotation, though the latter was not significant. Contrary to the hypotheses, peak torque at 120°/s did not correlate more strongly with performance than at 60°/s, and rotation torque did not surpass flexion/extension metrics. After Benjamini-Hochberg FDR correction for 24 comparisons, no significant correlations remained (q < 0.05), indicating initial associations were likely confounded by sex differences. These results suggest training should emphasize inter-segmental coordination over isolated strength gains, focusing on torque transfer from trunk to extremities. Interpretation of high-velocity torque data requires caution due to potential acceleration artifacts at early peak angles (5°-7°).</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1625283"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-23eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1663657
Lisa Kullik, Eduard Isenmann, Jan Schalla, Michael Kellmann, Sarah Jakowski
{"title":"The impact of menstrual cycle phase and symptoms on sleep, recovery, and stress in elite female basketball athletes: a longitudinal study.","authors":"Lisa Kullik, Eduard Isenmann, Jan Schalla, Michael Kellmann, Sarah Jakowski","doi":"10.3389/fphys.2025.1663657","DOIUrl":"10.3389/fphys.2025.1663657","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to examine the influence of menstrual cycle phases and symptom burden on sleep quality and recovery-stress states in elite female basketball players.</p><p><strong>Methods: </strong>Initially, twelve elite athletes participated in a 3-month observational study, which included psychometric screening using validated questionnaires and daily monitoring of menstrual symptoms, subjective sleep quality, sleep parameters, and recovery-stress states. The final analysis included eight athletes (26.75 ± 5.63 years, 178.62 ± 7.48 cm, 68.94 ± 7.13 kg, average cycle length of 29.00 ± 1.20 days, menstruation duration of 5.75 ± 0.71 days). In addition to self-reported data, objective menstrual cycle parameters were collected using the Ava fertility tracker. To verify cycle regularity, salivary hormone samples were collected twice weekly. Data analysis was conducted using linear mixed modeling to account for repeated measures and intra-individual variation.</p><p><strong>Results: </strong>Across both approaches, menstrual cycle phases showed only limited and inconsistent associations with sleep and recovery-stress states. In contrast, higher daily symptom burden and greater overall symptom severity were consistently associated with poorer sleep quality, reduced recovery, and elevated stress. Additionally, sleep behavior significantly influenced both sleep and recovery outcomes.</p><p><strong>Conclusion: </strong>Symptom burden appears to be a more relevant factor than menstrual phase in determining sleep and recovery-stress states in elite female athletes. These findings support individualized monitoring approaches that include menstrual symptoms tracking. Psychoeducation on sleep hygiene and menstrual health should be integrated into elite sports environments to strengthen athlete well-being. Overall, the study highlights the importance of multidimensional, athlete-centered strategies that combine behavioral, hormonal, and symptom-based data to optimize performance and recovery.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1663657"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-23eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1649477
Song Hao, Luo Yuxiao, Li Huilan, Hua Jun, Liu Dong
{"title":"Correlation analysis of osteoporosis and vertebral endplate defects using CT and MRI imaging: a retrospective cross-sectional study.","authors":"Song Hao, Luo Yuxiao, Li Huilan, Hua Jun, Liu Dong","doi":"10.3389/fphys.2025.1649477","DOIUrl":"10.3389/fphys.2025.1649477","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) and vertebral endplate defects are important manifestations of vertebral degenerative changes that greatly affect the quality of life of elderly people. This study investigated the potential association between vertebral endplate defects and osteoporosis using imaging modalities.</p><p><strong>Methods: </strong>Computed tomography (CT), magnetic resonance imaging (MRI), bone mineral density (BMD) and other relevant imaging data, as well as age, sex, body mass index (BMI), and degree of low back pain data, were retrospectively analysed. The vertebral Hounsfield unit (HU) value and the maximum width and maximum depth of the vertebral endplate defect were measured and standardized. A HU <110 was defined as OP. Logistic regression was used to identify the risk factors for vertebral endplate defects.</p><p><strong>Results: </strong>Demographic data from a total of 199 patients were included in this study, along with data from 995 vertebral bodies. The relationships between the HU value and other data between the vertebral body defect group and the nonvertebral body defect group were compared. We found significant differences in age (70.6 ± 8.4 vs. 63.8 ± 9.5, p < 0.001), sex (male/female) (26/69 vs. 43/61, p < 0.05), BMI (23.8 ± 3.4 vs. 24.8 ± 3.4, p < 0.05), and total spine HUs (84.65 ± 35.49 vs. 124.86 ± 49.59, p < 0.001). The lower HU group had larger endplate defects (p < 0.001, p < 0.01), and the lower endplates had a greater standardized defect width and cumulative defect score than the upper endplates (p < 0.01). There were statistically significant associations between endplate defects and age (OR = 1.0, p = 0.042) and total spine HUs (OR = 0.98, p = 0.001).</p><p><strong>Conclusion: </strong>There was a correlation between OP and the size of the vertebral endplate defect, and the defect size increased with decreasing bone mass. According to our results, vertebral endplate defects are more likely to occur in elderly individuals, females, and individuals with OP. With respect to the spinal structure, vertebral endplate defects are more likely to occur in the upper lumbar spine. Age and bone mass are the main factors associated with vertebral endplate defects.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1649477"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-23eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1654369
Yanhong Su, Meng Wang, Juan Chen, Yanan Bao, Ruikang Wen, Hui-Wen Ren, Zhi-Lin Luan
{"title":"Progress in understanding how clock genes regulate aging and associated metabolic processes.","authors":"Yanhong Su, Meng Wang, Juan Chen, Yanan Bao, Ruikang Wen, Hui-Wen Ren, Zhi-Lin Luan","doi":"10.3389/fphys.2025.1654369","DOIUrl":"10.3389/fphys.2025.1654369","url":null,"abstract":"<p><p>The circadian system, primarily governed by the suprachiasmatic nucleus of the hypothalamus, consists of a central clock and peripheral clocks distributed across various body tissues. Clock genes generate a 24-h oscillatory cycle via a transcription-translation feedback loop (TTFL). Emerging evidence has identified circadian rhythm disruption as a significant contributor to the risk of metabolic disorders. With aging, the function of circadian rhythms declines, leading to metabolic dysfunction in multiple organs. This article reviews the molecular mechanisms underlying circadian rhythm disruption during aging, with a focus on telomere homeostasis, SIRT1-mediated epigenetic regulation, and the NAD<sup>+</sup> metabolic pathway, and systematically analyzes the characteristics of rhythm imbalance in different metabolic organs. A comprehensive understanding of the correlation between circadian rhythms and aging is essential for developing strategies to combat aging and metabolic diseases.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1654369"},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in PhysiologyPub Date : 2025-09-22eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1616994
Tiziana Bachetti, Simona Bagnasco, Giuseppe Santamaria, Maria Francesca Bedeschi, Francesca Menni, Igor Catalano, Luigina Spaccini, Francesco Cavigioli, Francesco Morandi, Isabella Ceccherini
{"title":"The <i>PHOX2B</i> c.428A>G missense variant affects post-transcriptional regulation and may explain the absence of neural crest-derived tumors in congenital central hypoventilation syndrome.","authors":"Tiziana Bachetti, Simona Bagnasco, Giuseppe Santamaria, Maria Francesca Bedeschi, Francesca Menni, Igor Catalano, Luigina Spaccini, Francesco Cavigioli, Francesco Morandi, Isabella Ceccherini","doi":"10.3389/fphys.2025.1616994","DOIUrl":"10.3389/fphys.2025.1616994","url":null,"abstract":"<p><strong>Introduction: </strong>Heterozygous mutations in the paired-like homeobox 2b (PHOX2B) gene cause congenital central hypoventilation syndrome (CCHS). While polyalanine expansions are almost exclusively associated with isolated CCHS, missense, nonsense, and frameshift mutations are mainly identified in syndromic CCHS, presenting with Hirschsprung disease (CCHS + HSCR) alone and/or together with neuroblastoma (CCHS + HSCR + NB). CCHS-associated missense mutations occur in the PHOX2B homeodomain, where impaired transcriptional activity has been suggested as their functional effect. However, the molecular pathogenesis underlying their association with HSCR- and/or NB-associated CCHS has not been investigated to date.</p><p><strong>Methods: </strong>we applied an <i>in silico</i> analysis and a minigene approach in vitro to test the effect of the <i>PHOX2B</i> c.428A>G missense variant on the splicing of intron 2.</p><p><strong>Results: </strong>we demonstrate that the missense c.428A>G variant, reported by us and others in a set of CCHS + HSCR cases but never associated with NB, not only causes the amino acid change p.Q143R change but also disrupts the intron 2 splice donor site, producing an aberrant mRNA transcript and likely a hypomorphic, dysfunctional protein.</p><p><strong>Discussion: </strong>We, therefore, propose that in the presence of splicing defects of PHOX2B, a loss-of-function mechanism may underlie CCHS + HSCR and potentially explain the absence of neural-crest-derived tumors.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1616994"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a refined neonatal rabbit model of necrotizing enterocolitis with relatively longer survival.","authors":"Qing-Qing Guo, Hao Lin, Zhi-Xin Wang, Jian-Bo Wen, Juan-Juan Yang, Shi-Yun Lu","doi":"10.3389/fphys.2025.1643482","DOIUrl":"10.3389/fphys.2025.1643482","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop an animal model that closely replicates the clinical features of necrotizing enterocolitis (NEC), thereby providing a supportive platform for ongoing NEC research.</p><p><strong>Methods: </strong>36 two-week-old neonatal suckling rabbits were randomly assigned to three groups: normal group (Group A, n = 12), traditional group (Group B, n = 12), and modified group (Group C, n = 12). Daily monitoring of general condition, post-modeling survival rate, and survival time was conducted in neonatal rabbits. Histopathological assessment of intestinal morphology was performed using hematoxylin and eosin staining, with scoring conducted to evaluate modeling success. Serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), occludin, zonula occludens-1 (ZO-1), and zonulin were quantified using ELISA. Protein expression levels of occludin and ZO-1 in intestinal tissues were analyzed via Western blot.</p><p><strong>Results: </strong>Modified group exhibited significantly higher survival rates and prolonged survival time compared to traditional group (p < 0.05). Both model groups demonstrated elevated serum levels of CRP, TNF-α, IL-10, along with reduced concentrations of occluding, ZO-1 and zonulin when compared to normal group (p < 0.05). Similarly, intestinal expression levels of occludin and ZO-1 were significantly lower in both model groups relative to control (p < 0.05). However, no significant differences were observed between model groups in these parameters (p > 0.05).</p><p><strong>Conclusion: </strong>Our study successfully established a novel neonatal rabbit model of NEC with prolonged survival time by refining conventional modeling methodologies, thereby providing a new platform for investigating NEC pathogenesis and therapeutic interventions.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1643482"},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}