Frontiers in Physiology最新文献

{"title":"Size and site matter: the influence of corpus callosum subregional lesions on the magnitude of cross-education of strength.","authors":"Marco Morrone, Gianluca Martinez, Antonio Achene, Mariano Scaglione, Salvatore Masala, Andrea Manca, Franca Deriu","doi":"10.3389/fphys.2025.1554742","DOIUrl":"10.3389/fphys.2025.1554742","url":null,"abstract":"<p><strong>Introduction: </strong>Cross-education is an established yet not fully understood phenomenon involving interhemispheric processes within the corpus callosum (CC) that result in strength gains in the untraining limb following training of the contralateral homologous muscles. There is a substantial lack of cross-education studies employing lesional models. This study employed the model of multiple sclerosis, a condition typically featuring demyelinating callosal lesions, to pinpoint CC subregions that mediate cross-education, potentially fostering the mechanistic understanding of the interlimb transfer.</p><p><strong>Methods: </strong>Nine individuals with relapsing-remitting multiple sclerosis (median Expanded Disability Status Scale: 3.5) and focal CC lesions underwent a 6-week, high-intensity isokinetic training program (≥80% maximal effort at 10°/s) targeting their stronger ankle dorsiflexors. Sagittal FLAIR MRI scans were segmented into five CC subregions (CC1-CC5), with lesion volumes quantified for each subregion. Strength (peak concentric torque at 10°/s) was measured bilaterally before (PRE) and after (POST) training to determine cross-education, defined as the percentage increase in torque of the untrained, weaker limb. Correlations between lesion volumes in CC subregions and cross-education were analyzed.</p><p><strong>Results: </strong>Both the trained (+21.5 ± 15.8%, p = 0.002) and untrained (+35.2 ± 24.9%, p = 0.003) limbs demonstrated post-training strength gains, reducing but not eliminating inter-limb asymmetry. Lesions specifically in the rostral body (CC2) correlated with reduced cross-education magnitude (rs = -0.670, p = 0.048) and smaller improvements in strength asymmetry (rs = 0.809, p = 0.008). No associations were detected in other CC subregions.</p><p><strong>Conclusion: </strong>These findings highlight the pivotal role of specific CC subregions, particularly the rostral body, in mediating cross-education of strength. These findings advance our understanding of CC role in the interhemispheric dynamics underpinning cross-education. Routine MRI can identify patients without CC2 lesions who may benefit from cross-education, providing a practical approach to improving muscle strength when weaker muscles cannot be directly trained.</p><p><strong>Clinical trial registration: </strong>ClinicaTrials.Gov, identifier NCT02010398.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1554742"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596603","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":"Connexin hemichannels and early atrophic signaling in muscle during sepsis.","authors":"Elisa Balboa, Fujiko Saavedra, Luis A Cea, Aníbal A Vargas, Tomás Regueira, Juan C Sáez","doi":"10.3389/fphys.2025.1514769","DOIUrl":"10.3389/fphys.2025.1514769","url":null,"abstract":"<p><p>Sepsis pathogenesis is complex, and effective treatments are limited, leading to high mortality rates between 20% and 55%. Early identification of factors contributing to sepsis-related muscle dysfunction is critical for risk stratification and potential therapeutic development. The immune response during sepsis affects skeletal muscles, contributing to organ dysfunction and worsening prognosis. In this study, we explore the role of connexin hemichannels (Cx HCs) in the early changes in muscle homeostasis during sepsis. Using a cecal ligature and puncture (CLP)-induced sepsis model, we assessed IL-6 levels, weight loss, myofiber cross-sectional area, resting membrane potential, and connexin expression in control and Cx43/Cx45-deficient mice. CLP induced IL-6 elevation, sarcolemma permeabilization, reduced membrane potential, and activation of the ubiquitin-proteasome pathway in control mice, while Cx43/45-deficient mice exhibited reduced all CLP-induced muscle alterations. These findings suggest that Cx43 and Cx45 are involved in the early development of muscle alterations during sepsis.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1514769"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596598","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":"The effects of training intervention on the prevention of knee joint injuries: a systematic review and meta-analysis.","authors":"Gangbin Zheng, Sai Zeng, Tiangeng Li, Liang Guo, Ling Li","doi":"10.3389/fphys.2025.1455055","DOIUrl":"10.3389/fphys.2025.1455055","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of neuromuscular, core strength, balance, and proprioceptive training on preventing knee injuries in young athletes, to identify optimal intervention characteristics.</p><p><strong>Methods: </strong>This review followed the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search of English and Chinese literature in databases included PubMed, Web of Science, EBSCO, CNKI, and Wanfang, covering studies published from January 1, 2000, to 12 April 2024. Inclusion criteria targeted randomized controlled trials (RCTs) on training interventions aimed at knee injury prevention among young athletes. The analysis used a random-effects model to pool data from studies meeting our criteria, ensuring a comprehensive evaluation of intervention effectiveness.</p><p><strong>Results: </strong>A total of 19 randomized controlled trials (RCTs) involving 28,176 subjects were included. The meta-analysis showed that training intervention programs reduced the risk of lower extremity knee injuries by 25% (RR = 0.75, 95% CI: 0.65-0.85). The most notable effects were observed in intervention with exercise duration of 5-15 min, frequencies of 4-5 times per week, and program lengths exceeding 26 weeks.</p><p><strong>Conclusion: </strong>The findings highlight the effectiveness of specific training interventions in reducing knee injury risk among athletes. These insights provide a clear framework for designing training routines that effectively prevent knee injuries.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1455055"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596607","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":"Acute effects of caffeine and paracetamol on velocity and power in resistance exercise.","authors":"Bela Scapec, Jozo Grgic, Dorian Varovic, Pavle Mikulic","doi":"10.3389/fphys.2025.1536591","DOIUrl":"10.3389/fphys.2025.1536591","url":null,"abstract":"<p><p>This study aimed to explore the isolated and combined effects of caffeine and paracetamol (acetaminophen) on velocity and power in resistance exercise. Twenty-eight resistance-trained men and women participated in this randomized, double-blind, placebo-controlled, crossover study. The participants performed three sets of the bench press with 75% of one-repetition maximum to momentary muscular failure after ingesting a placebo, caffeine (3 mg/kg), paracetamol (1,500 mg), or caffeine + paracetamol 45 min before exercise. Velocity and power of the repetitions in each set were analysed. Compared to placebo, only isolated caffeine ingestion increased mean velocity (<i>d</i> = 0.34), and mean power (<i>d</i> = 0.17) in the first set. No significant differences between the conditions were observed for any of the analysed outcomes in the second and third sets. Our results indicate that only isolated caffeine ingestion improves velocity and power in resistance exercise, even though these effects are not consistent across all sets. Paracetamol ingestion was not ergogenic, even when combined with caffeine. These results highlight that analgesics may be ineffective in improving resistance exercise performance.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1536591"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596594","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":"The relationship and agreement between systemic and local breakpoints in locomotor and non-locomotor muscles during single-leg cycling.","authors":"Markus Tilp, Nina Mosser, Gudrun Schappacher-Tilp, Annika Kruse, Philipp Birnbaumer, Gerhard Tschakert","doi":"10.3389/fphys.2025.1465344","DOIUrl":"10.3389/fphys.2025.1465344","url":null,"abstract":"<p><strong>Introduction: </strong>There is a well-established relationship between the respiratory compensation point (RCP) and local muscular breakpoints determined from near-infrared spectroscopy (NIRS) and electromyography (EMG). However, these breakpoints have not yet been compared both in locomotor and non-locomotor muscles simultaneously in single-leg cycling exercise. Therefore, the aim of the study was to investigate the relationship and agreement between systemic and local breakpoints in locomotor and non-locomotor muscles.</p><p><strong>Method: </strong>Data from twelve physically-active participants (25.5 ± 3.9 years, 176.1 ± 11.6 cm, 71.2 ± 9.4 kg, 4 females) who completed a continuous single-leg step incremental cycling test (10 W min^-1) with their right leg were included in the analysis. Ventilation and gas exchange were recorded to determine RCP. Surface EMG (sEMG) and NIRS signals were measured from both vasti lateralis muscles and breakpoints were determined from root mean Q square sEMG and deoxygenated hemo- and myoglobin signal m[HHb].</p><p><strong>Results: </strong>There was no significant difference in the power output at RCP (127.3 ± 21.8 W) and local muscular breakpoints both from the locomotor (m[HHb]: 119.7 ± 23.6 W, sEMG: 126.6 ± 26.0 W) and non-locomotor (m[HHb]: 117.5 ± 17.9 W, sEMG: 126.1 ± 28.4 W) muscles. Breakpoints also showed significant (p < 0.01) correlations (r = 0.67-0.90, ICC = 0.80-0.94) to each other with weaker correlations in the non-locomotor muscle (r = 0.66-0.86, ICC = 0.74-0.90). Despite the strong correlations, high individual variability and weak limits of agreement (up to -32.5-46.5 W) and substantial absolute differences (10.2-16.7 W) were observed which indicates that these breakpoints cannot be used interchangeably.</p><p><strong>Discussion: </strong>These findings offer further insights into the mechanistic relationship between local and systemic physiological response to exercise with increasing workload. We conclude that, despite strong correlations, local muscular breakpoints do not have to coincide with systemic boundaries of physiological domains.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1465344"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596612","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":"Mechanical countermeasures for spaceflight-associated neuro-ocular syndrome during 30-days of head down tilt bed rest: design, implementation, and tolerability.","authors":"Stefan Moestl, Laura De Boni, Jan-Niklas Hoenemann, Tilmann Kramer, Jan Schmitz, Dominik Pesta, Timo Frett, Maria Bohmeier, Petra Frings-Meuthen, Ann Charlotte Ewald, Andrea Nitsche, Patricia Loehr, Alexandra Noppe, Nicolas Klischies, Alex S Huang, Steven S Laurie, Karina Marshall-Goebel, Brandon R Macias, Jens Tank, Jens Jordan, Edwin Mulder","doi":"10.3389/fphys.2025.1530783","DOIUrl":"10.3389/fphys.2025.1530783","url":null,"abstract":"<p><p>After longer duration space missions, some astronauts experience structural and functional changes in the eye and structural changes in the brain, termed Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Countermeasures against SANS are required to minimize potential operation impacts and negative long-term health consequences. Headward fluid shifts, which appear to promote SANS, provide a target for countermeasures. The SANS countermeasures study, a 30 days strict head down tilt bed rest (HDTBR) study, tested two mechanical countermeasures aimed at reversing cephalad fluid overload. This work presents design and methodology of the study with a focus on countermeasure implementation and tolerability. Following baseline evaluations, participants were randomized to four groups and HDTBR commenced: Daily application of 25 mmHg lower body negative pressure for 6 h, six-hour bilateral venous constrictive thigh cuffs following moderate cycling exercise on 6 days per week, a negative control group without countermeasures, and a positive control group with HDTBR interruption for 6 h per day by sitting upright. The potential of these countermeasures for future space applications was examined in 86 different experiments, which will be reported elsewhere. Comfort ratings ranging from 1 (very uncomfortable) to 5 (very comfortable) were used to asses tolerability. Overall, 47 participants (20 women) completed the study. Out of 4,032 h scheduled for both countermeasures, 10.5 h were not performed due to medical issues unrelated to the countermeasures. Mean comfort ratings were 3.9 in men and 4.4 in women in the lower body negative pressure group (p = 0.1356) and 4.2 in men and 3.9 in women in the thigh cuff group (p = 0.1604). We conclude that both countermeasures were well tolerated and applied under well controlled conditions, thus, allowing for meaningful analyses of efficacy in attenuating HDTBR effects.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1530783"},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596601","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":"Heterogeneity of ventricular action potentials in neonatal rat cardiomyocytes and methodological aspects of patch clamp measurements.","authors":"Pascal Syren, Anna Zlatopolskaia, Claus Bruehl, Axel Schöffel, Teresa Caspari, Chiara Heß, Norbert Frey, Dierk Thomas, Patrick Lugenbiel","doi":"10.3389/fphys.2025.1537345","DOIUrl":"10.3389/fphys.2025.1537345","url":null,"abstract":"<p><p>Measurement of the ventricular action potential (AP) via whole-cell patch clamp is an important contributor to cardiac electrophysiological research. Neonatal rat ventricular cardiomyocytes (NRVCM) are a commonly used model, in particular for stressor- or drug-related questions. High variability of APs and individual methodological settings hinder comparison both in individual studies and, to an even greater degree, between different projects. This study aims to describe sources of AP heterogeneity in NRVCM related to patch clamp measurement with a focus on resolvable causes. Therefore, AP of NRVCM were induced in whole-cell configuration and measured in current-clamp mode. The effects of varying setup temperature, electrode resistance, resting- (RMP), respectively holding membrane potential (HMP), induction approach, current pulse duration and amplitude plus total assay duration were studied and compared to systematically analyzed literature. We analyzed the impact on different output parameters, namely, maximal upstroke velocity (dV/dt), maximal AP amplitude (APA) and AP duration at different percentages (XX%) of repolarization, APD_XX. In a comparative literature research, we found that mean APD₉₀ in between 27.0 and 560.7 ms (own data 59.7 ± 5.8 ms) were described, with high variability and likely non-Gaussian distribution. In this study, APD₉₀, APD₅₀ and APD₃₀, are decreased at more negative RMP (respectively HMP) values. E.g., APD₉₀ is shortened by ∼60% after lowering HMP from -70 mV to -90 mV) while dV/dt and APA are increased at a more negative HMP. Pulse duration in induction did not affect main AP parameters itself, but induction energy levels above 1.5-fold the threshold energy level increased APA, while APD₅₀ and APD₉₀ were shortened. During series of APs at 1 Hz, spike duration (APD₉₀) decreased by ∼27%, with stable AP after the third repetitive AP. Spike duration did also decreased by ∼40% after prolongated measurements for 21 min, indicating degradation of electrophysiological properties. To improve data quality in NRVCM-APs, we suggest using a constant HMP, adjustment of current pulse amplitude to the individual cells' threshold and the use of repetitive AP-inductions. Finally, we suggest the use of nonparametric statistical methods for statistical analysis. These aspects could reduce variability and lead to more reliable and comparable data.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1537345"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585304","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":"Inverse association between atherogenic index of plasma and testosterone in US adult males: A large cross-sectional study from the NAHNES 2011-2016.","authors":"Tanjian Li, Lulu Chen, Xin Liang, Xinya Li, Yaqin Li, Yuting Huang, Yu Wang","doi":"10.3389/fphys.2025.1504778","DOIUrl":"10.3389/fphys.2025.1504778","url":null,"abstract":"<p><strong>Background and objectives: </strong>The atherogenic index of plasma (AIP), defined as log10 (triglycerides/high-density lipoprotein cholesterol), serves as a biomarker for atherosclerosis and cardiovascular disease (CVD). It is also associated with conditions such as type 2 diabetes, insulin resistance, depression, and both cardiovascular and overall mortality. Serum lipids have been proven to influence serum testosterone levels, and AIP is a significant marker of lipid levels. We hypothesize that AIP may have a specific relationship with testosterone. This article aims to evaluate the correlation between AIP and total testosterone (TT), as well as testosterone deficiency (TD), among the U.S. population.</p><p><strong>Methods: </strong>Data were collected from the National Health and Nutrition Examination Survey (NHANES) database between 2011 and 2016. This study was categorized into four groups based on the quartiles of AIP. Weighted multivariate linear regression and logistic regression were utilized to evaluate the relationships between AIP and TT, TD. Restricted cubic spline (RCS) was used to investigate the non-linear association between AIP and TT and TD. The subgroup analysis method was employed to investigate the relationships between AIP and TT, TD across various stratifications. Ultimately, the sensitivity study involved a comparison of weighted and unweighted data analyses to ascertain the stability of the conclusions.</p><p><strong>Results: </strong>A total of 2,572 participants were included in the final study. After adjusting for all confounding factors, multivariate linear regression showed that AIP was independently negatively associated with TT (β = -93.42, 95%CI: -123.66, -63.18, P < 0.001), and multivariate logistic regression showed that AIP level was associated with higher risk of TD (OR = 3.45, 95%CI: 2.09, 5.69, P < 0.001). In the quartile of AIP, TT levels decreased the most (β = -74.81, 95%CI: -105.27, -44.35, p < 0.001) and the risk of TD was highest (OR = 2.89, 95%CI: 1.70, 4.93, p < 0.001). In addition, stratified analyses showed similar results in all subgroups except those with diabetes (P for interaction >0.05 for all comparisons). The final sensitivity analysis revealed that elevated AIP were also associated with decreased TT (β = -101.74, 95%CI: -123.18, -80.3, P < 0.001) and increased incidence of TD (OR = 3.01, 95%CI: 2.17, 4.17, P < 0.001) on unweighted data.</p><p><strong>Conclusion: </strong>Increased levels of AIP correlate with decreased TT levels and a higher prevalence of TD. Additional research is necessary to investigate the underlying mechanisms connecting them.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1504778"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585334","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":"Circadian rhythm, glucose metabolism and diabetic complications: the role of glucokinase and the enlightenment on future treatment.","authors":"Zhijun Zhang, Shuo Wang, Ling Gao","doi":"10.3389/fphys.2025.1537231","DOIUrl":"10.3389/fphys.2025.1537231","url":null,"abstract":"<p><p>The circadian clock, an innate timing mechanism, governs a variety of physiological activities by producing near-24-h cycles in gene expression. These cycles are reflected in patterns of metabolism and behavior. This system consists of two parts: one is the central clock located in the suprachiasmatic nucleus of the hypothalamus, and the other is the peripheral clock located in tissues throughout the body. Glucokinase, also termed hexokinase 4, is a member of the hexokinase family. It acts as a glucose sensor, plays a pivotal role in glucose homeostasis. Here, we review the role of circadian rhythm in glucose metabolism across various tissues, look into the molecular mechanism of circadian disruption involvement in glucose metabolism and diabetic complications, with a particular focus on the role of glucokinase. Finally, we propose potential strategies for effectively treating metabolic disorders and diabetic complications by modulating circadian rhythm glucokinase.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1537231"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585270","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":"Sex-dependent alterations of colonic epithelial permeability: relevance to irritable bowel syndrome.","authors":"Muriel Larauche, Swapna Mahurkar-Joshi, Mandy Biraud, Tiffany Ju, Emeran A Mayer, Lin Chang","doi":"10.3389/fphys.2025.1509935","DOIUrl":"10.3389/fphys.2025.1509935","url":null,"abstract":"<p><strong>Introduction: </strong>Increased intestinal permeability is a possible pathophysiological mechanism of irritable bowel syndrome (IBS). Increased colonic epithelial permeability is associated with visceral nociception in rodents and abdominal pain severity in IBS patients. Although IBS is more common in women, most studies on IBS-associated epithelial dysfunction have largely overlooked sex as a biologic variable.</p><p><strong>Methods: </strong>Men and women with Rome III- and Rome IV-positive IBS and HCs rated GI symptoms including abdominal pain severity at baseline, 24 h prior and immediately post procedure. Epithelial function was assessed <i>ex vivo</i> in Ussing chambers using sigmoid colon biopsies, by monitoring short-circuit current (Isc), transepithelial electrical resistance (TEER) and mucosal permeability to FITC-dextran 4 kDa (FD4). Biopsies tight junction protein mRNA expression was assessed using RNA seq. Statistical analyses included a framework of General Linear Models and linear contrast analyses performed using R software.</p><p><strong>Results: </strong>44 IBS patients (66% women, 30 years) and 19 HCs (53% women, 28 years) were enrolled. The proportion of women was not different between groups. As a group, IBS patients exhibited lower TEER compared to HCs (16.9 ± 5.5 vs. 21.5 ± 6.5 Ω/cm², p = 0.01, FDR = 0.02), but no difference in FD4 serosal concentration or Isc (basal or stimulated). Within men, IBS had lower TEER vs. HCs, but there was no disease difference within women. Independent of diagnosis, women had 1.3-fold lower TEER concentration and 1.5-fold higher FD4 serosal concentration than men. These sex differences were also seen within HCs, although within IBS, FD4 permeability only showed a trend to be higher in women vs. men. Abdominal pain ratings and IBS severity scores were not associated with TEER or FD4 concentration.</p><p><strong>Discussion: </strong>Our study confirms prior reports that IBS patients demonstrate altered sigmoid colonic epithelial function and shows for the first time that these are independent of sex. However, sex differences in sigmoid colonic epithelial function are observed independently of disease status. Further studies are needed to delineate if intestinal permeability interacts with other factors in the pathophysiology of IBS and if these interactions differ by sex.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1509935"},"PeriodicalIF":3.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585335","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}