Experimental Physiology最新文献

{"title":"Disordered pancreatic and gastrointestinal hormone responses to nutrient stimulation in Zambian children with severe acute malnutrition.","authors":"Ellen Besa, Ruth Phiri, Andreck Tembo, Gwen Nayame, Amon Ngongola, Jens Rehfeld, Bolette Hartmann, Gary Frost, Douglas C Heimburger, Paul Kelly","doi":"10.1113/EP093962","DOIUrl":"10.1113/EP093962","url":null,"abstract":"<p><p>Nutrient sensing enables the body to detect and respond to nutrient availability through hormonal regulation. In this study, we examined nutrient-stimulated hormonal responses in children with severe acute malnutrition (SAM) compared with hospitalized (HC) and community (CC) child comparators. Basal and fed blood samples were collected from participants before and after consumption of a liquid meal. In the basal state, children with SAM showed significantly higher circulating concentrations of insulin, C-peptide, peptide tyrosine tyrosine (PYY), ghrelin, glucagon, glucagon-like peptide 1 (GLP-1) and glucagon like peptide 2 (GLP-2), in comparison to one or both comparators. After feeding, insulin, C-peptide, cholecystokinin, PYY and GLP-1 increased in all groups, indicating some level of preserved nutrient sensing. GLP-2 increased significantly in SAM and hospitalized children, and a reduction in ghrelin was observed in children with SAM. No significant changes were detected for glucagon, leptin or secretin in any group. Disordered responses, defined as zero or positive postprandial responses in ghrelin and zero or negative postprandial responses in the other hormones, were seen in all children. Significantly higher percentages of children with SAM had disordered responses compared with the non-malnourished children, particularly for insulin (23%) and C-peptide (16%), suggestive of altered pancreatic hormonal regulation in SAM. These findings highlight the need for improved nutritional interventions for affected children.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4552-4564"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and biochemical factors associated with insulin therapy in gestational diabetes: The role of OGTT-based groups.","authors":"Libera Troìa, Martina Garassino, Riccardo Bertinato, Caroline Leitao Thomaz, Giulia Turatello, Chiara Airoldi, Alessandro Libretti, Daniela Surico, Valentino Remorgida","doi":"10.1113/EP093778","DOIUrl":"10.1113/EP093778","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) represents one of the most common metabolic disorders of pregnancy. This study aimed to identify clinical and biochemical factors associated with antenatal insulin therapy, focusing on the association with oral glucose tolerance test (OGTT)-based phenotypes. Retrospective observational study among GDM women, divided according to their treatment (nutritional therapy (NT) or insulin therapy). GDM was classified into three phenotypes based on OGTT results: isolated fasting hyperglycaemia (IFH-GDM), isolated post-load hyperglycaemia (IPH-GDM) and combined hyperglycaemia (CH-GDM). Maternal demographic, obstetric and biochemical data were analysed. Multivariable logistic regression analysis was performed to identify factors independently associated with insulin therapy. Among 458 women, 39.3% required insulin therapy. Independent factors associated with the use of insulin therapy included pre-pregnancy obesity (odds ratio (OR) 2.07, 95% CI: 1.21-3.55), spontaneous miscarriage history (OR 1.89, 95% CI: 1.21-2.93), pregestational hypothyroidism (OR 2.63, 95% CI: 1.08-6.42), GDM diagnosis at 24-28 weeks versus earlier diagnosis (OR 0.45, 95% CI: 0.28-0.72), and GDM phenotype. Compared with IFH-GDM, IPH-GDM was associated with a lower risk of insulin therapy (OR 0.51, 95% CI: 0.31-0.84), whereas CH-GDM was associated with a higher risk (OR 1.90, 95% CI: 1.10-3.31). In conclusion, women with fasting and combined hyperglycaemia represent the highest-risk group for insulin therapy. Integrating OGTT-based phenotypes with clinical risk factors was associated with increased likelihood of insulin therapy requirement and may support individualized clinical assessment.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4541-4551"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct electrophysiology and dopaminergic modulation of medium spiny neurons across divisions of the tail striatum and the dorsolateral striatum.","authors":"Bronwyn Riley, Luke E Hallum, Srdjan M Vlajkovic, Johanna M Montgomery, Peter S Freestone","doi":"10.1113/EP094001","DOIUrl":"10.1113/EP094001","url":null,"abstract":"<p><p>The striatum is a brain region within the basal ganglia that plays a crucial role in generating behaviour and mediating perception. The tail striatum (TS) is a poorly understood striatal domain with predominantly sensory functions. Recent evidence supports that abnormal TS dopamine transmission in dopaminergic disease contributes to sensory symptoms by dysregulating TS medium spiny neurons (MSNs). Importantly, the ventral TS is segregated into medial, intermediate and lateral divisions in which TS-MSNs express D1 and D2 dopamine receptors unevenly, but the functional significance of this is unclear. We aimed to gain insight into the functional significance of this organisation and to investigate how TS-MSNs are modulated by dopamine. We used whole-cell patch clamping in rat (P45-55, both sexes) brain slices to conduct the first in-depth electrophysiological characterisation of TS-MSNs and compared them across divisions. The adjacent dorsolateral striatum (DLS) was included for comparison. We also investigated how bath-applied dopamine and selective dopamine agonists SKF38393 and quinpirole modulate MSNs in each region. We found that TS-MSNs are electrophysiologically distinct from DLS-MSNs, reflecting the established functional differences between these domains. TS-MSNs were more depolarised than DLS-MSNs at rest and had lower rheobase. We also identified functional heterogeneity across the TS divisions. The intermediate division had higher rheobase than the medial or lateral divisions. At rheobase, lateral division TS-MSNs showed higher firing frequencies than medial or intermediate division TS-MSNs. Finally, TS-MSNs showed weaker modulation by dopamine, SKF38393 and quinpirole than DLS-MSNs, which was also uneven across divisions. These data provide a novel electrophysiological characterisation of TS-MSNs, showing they are functionally distinct from DLS-MSNs and heterogeneous across divisions, which could have implications for dopaminergic diseases.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4827-4851"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and lifelong exercise modulate the tumorigenic potential of human lung cancer cells and their susceptibility to cisplatin.","authors":"Carlos M Soares, João P Moura, Leonardo M R Ferreira, Ana Pedrosa, Pedro Filipe, Luís Rama, Ana M Teixeira, Ana M Urbano","doi":"10.1113/EP093973","DOIUrl":"10.1113/EP093973","url":null,"abstract":"<p><p>The association between higher levels of physical activity and lower cancer risk and mortality is well established. However, a causal link is yet to be proven. Recent studies showed a decrease in the proliferation rates of cultured human cancer cells when the human serum used to stimulate them was conditioned by acute exercise. Here, we tested the hypothesis that serum mediates some of the putative benefits of exercise on cancer through alterations to the growth pattern and susceptibility to chemotherapy agents of cancer cells. To this end, human non-small cell lung cancer cells were exposed to serum, collected before or after an acute exercise intervention, from two cohorts that differed significantly in their levels of physical activity and, accordingly, cardiorespiratory fitness, but were otherwise identical (non-exercisers and master athletes). Serum levels of glucose, lipids, albumin, C-reactive protein and cytokines were determined, and the impact of the serum responses to acute and lifelong exercise on cancer cell growth pattern and susceptibility to cisplatin were analysed. We found that acute exercise decreased the proliferation rate of the cells, yet shortened the lag phase of the cells after detachment, whereas lifelong exercise had the opposite effects. Significantly, we showed, for the first time, that lifelong exercise increased susceptibility to a chemotherapy agent, which might contribute to the decreased cancer mortality rates found among those cancer patients who exercise regularly. Similar to the cellular effects, changes to serum cytokine levels (several of them linked to the senescence-associated secretory phenotype) depended on whether serum was conditioned by acute exercise or by lifelong exercise.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4688-4704"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature dependence of HCN channel kinetics: A systematic comparison across mammalian isoforms and species.","authors":"Rajnish Ranjan, Emmanuelle Logette, Mirjia Herzog, Valerie Buchillier, Enrico Scantamburlo, Henry Markram","doi":"10.1113/EP093939","DOIUrl":"10.1113/EP093939","url":null,"abstract":"<p><p>Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important regulators of cardiac pacemaking and neuronal excitability, yet their temperature dependence has not been compared systematically across mammalian isoforms and species in standardized experimental conditions. Here, we performed a standardized electrophysiological characterization of mouse, rat and human HCN isoforms using stable CHO cell lines and automated patch-clamp recordings across multiple temperatures and pharmacological conditions. Among the four isoforms, HCN3 did not generate detectable currents when expressed as a homomeric channel in the conditions tested, suggesting that additional factors might be required for functional activity. Comparative analysis of the remaining isoforms revealed a conserved kinetic hierarchy, with HCN1 exhibiting the fastest activation kinetics, HCN2 intermediate kinetics and HCN4 the slowest, and temperature accelerated channel gating across isoforms. Canonical modulation by cAMP and ZD7288 further showed that key regulatory features of HCN channels could be quantified reproducibly in identical experimental conditions. Together, these results provide a standardized comparative framework for interpreting HCN channel behaviour across physiological temperatures and species and establish a public reference dataset for future experimental and computational studies.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4659-4687"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The sympathetic baroreflex across the lifespan: Is loss of hysteresis a stop on the road to dysfunction?","authors":"Maria C R G Trindade, Qudus A Ojikutu, Igor A Fernandes","doi":"10.1113/EP094341","DOIUrl":"https://doi.org/10.1113/EP094341","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The theoretical basis of reservoir pressure in arteries.","authors":"Kim H Parker, Alun D Hughes","doi":"10.1113/EP092913","DOIUrl":"10.1113/EP092913","url":null,"abstract":"<p><p>The separation of measured arterial pressure into a reservoir pressure and an excess pressure was introduced over 20 years ago as a heuristic hypothesis. Since then it has gained some traction through epidemiological studies that show that various measures of reservoir and excess pressure are independent risk factors for cardiovascular disease. We demonstrate that a two-time asymptotic analysis of the 1-D conservation equations in each artery coupled with the separation of the arteries into inviscid and viscid arteries, based on their resistance or drag coefficients, results in a formal derivation of the reservoir pressure. The most important result of this analysis is that flow in the arteries can be considered quasi-steady during every interval on the slow time scale. The slow-time conservation equations involve a drag coefficient that models the effect of viscosity on the flow. We separate the arteries into the larger inviscid arteries where viscosity is negligible and the smaller viscid arteries where it is not. The slow time pressure in the inviscid arteries is shown to be spatially uniform but varying in time. We identify this pressure as the reservoir pressure. Dynamic analysis using mass and energy conservation in the inviscid arteries shows that the reservoir pressure accounts for the storage of potential energy by the distension of the elastic inviscid arteries during early systole and its release during late systole and diastole. This analysis thus provides a formal derivation of the reservoir pressure and ascribes its physical meaning.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of acute mountain sickness occurring at 4554 m using overnight pulse oximetry from lower altitude: A pilot study.","authors":"Luke Cutts, Kim Ashdown, Ciaran Simpkins, Will Trender, Sarah Clarke, John Delamere, Samuel J E Lucas, Kelsey Elizabeth Joyce","doi":"10.1113/EP093777","DOIUrl":"https://doi.org/10.1113/EP093777","url":null,"abstract":"<p><p>Acute mountain sickness (AMS) affects many individuals ascending to high altitude annually, carrying potential morbidity and mortality risks (e.g., high-altitude cerebral oedema). The objective of this pilot study was to record overnight pulse oximetry during ascent to 4554 m and determine whether: (1) extracted overnight biomarkers had any relationship to AMS; and (2) AMS at 4554 m could be predicted by oximetry biomarkers using classification models trained/validated on overnight data from lower altitudes. Twenty lowlanders (five females, 36.8 ± 18.5 years old) completed a 4 day ascent to 4554 m, where AMS status was determined by clinical examination. Oximetry was recorded continuously each night, with >40 biomarkers extracted and compared between AMS and non-AMS. Exploratory classification models (5-fold cross-validation) were tested for nightly data with a systematic approach to feature selection. Model performances were evaluated based on predictions of AMS at 4554 m. A significant effect of ascent was observed for many overnight biomarkers; however, no effect of AMS status was evident, nor were any differences observed between AMS and non-AMS for any overnight biomarkers during ascent. AMS at 4554 m was most accurately predicted from overnight recordings collected at 2600 m (accuracy, 100%; true positive rate, 100%) and 3647 m (accuracy, 80%; true positive rate, 90.9%) using k-nearest neighbour and support vector machine classification models. Biomarkers were extracted from overnight oximetry recordings, with limited differences observed between AMS and non-AMS. In conclusion, AMS at 4554 m can be predicted from overnight oximetry using machine learning; however, these preliminary findings need confirmation in a larger cohort, with additional investigation into the most clinically relevant biomarkers.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Printing knowledge in microgravity: PULSE and the education needed for space biomedicine.","authors":"Sarah Baatout, Michela Candotti, Kevin Tabury, Bjorn Baselet, Damian M Bailey, Lorenzo Moroni","doi":"10.1113/EP094256","DOIUrl":"10.1113/EP094256","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Running-based rehabilitation does not improve muscle function after volumetric muscle loss despite improving hindlimb weight-bearing asymmetry in mice.","authors":"Angela S Bruzina, Molly R Weberg, Ryan J Willoughby, Gordon L Warren, Jarrod A Call, Sarah M Greising","doi":"10.1113/EP094201","DOIUrl":"10.1113/EP094201","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) is a traumatic skeletal muscle injury characterized by chronic functional impairments in the affected muscle and adjacent uninjured bone. Rehabilitative strategies aimed at restoring limb function following VML, including voluntary running, have shown limited efficacy and in some cases have been detrimental. One potential explanation is disproportional loading of the uninjured contralateral limb during running, but evaluation of unilateral weight-bearing following VML has not been explored. This study was designed to evaluate if the limited response to rehabilitation following VML could be explained by limb loading asymmetry. Twelve-week-old C57Bl/6J mice (n = 24; equal males/females) were randomized to three groups: Naïve-Run, VML, and VML-Run. Two weeks post-VML, mice in running groups were provided free access to wheels for 6 weeks. Weight-bearing asymmetry was assessed before injury and biweekly thereafter. Terminally at ∼20 weeks of age, in vivo muscle function was evaluated, and muscles and bones were saved for analyses. Prior to injury, no difference in weight-bearing asymmetry was observed across groups. VML-injured mice exhibited similar weight-bearing asymmetries prior to running. Following 6 weeks of running, VML-Run mice regained weight-bearing symmetry comparable to Naïve-Run. Despite this, remaining muscle function remained persistently impaired following VML injury. Collectively this works suggests that voluntary running promotes favourable weight-bearing adaptations following VML, but does not improve muscle function or the mechanical properties of the adjacent bone.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}