Experimental Physiology最新文献

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The impact of biological sex and stroke volume constituents on heterogeneity in the Q ̇ $dot{Q}$ – V ̇ O 2 ${{dot{V}}_{{{{mathrm{O}}}_2}}}$ relationship and skeletal muscle saturation during cycling 生理性别和脑卒中容积成分对循环过程中Q / V / O关系异质性和骨骼肌饱和度的影响。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-07-22 DOI: 10.1113/EP093845
Adam N. Di Salvo, Sinan Osman, Jacob L. Schwartz, Nino Nikolovski, Robert F. Bentley
{"title":"The impact of biological sex and stroke volume constituents on heterogeneity in the \u0000 \u0000 \u0000 Q\u0000 ̇\u0000 \u0000 $dot{Q}$\u0000 –\u0000 \u0000 \u0000 \u0000 V\u0000 ̇\u0000 \u0000 \u0000 O\u0000 2\u0000 \u0000 \u0000 ${{dot{V}}_{{{{mathrm{O}}}_2}}}$\u0000 relationship and skeletal muscle saturation during cycling","authors":"Adam N. Di Salvo, Sinan Osman, Jacob L. Schwartz, Nino Nikolovski, Robert F. Bentley","doi":"10.1113/EP093845","DOIUrl":"10.1113/EP093845","url":null,"abstract":"<p>Interindividual variability in the cardiac output (<span></span><math>\u0000 <semantics>\u0000 <mover>\u0000 <mi>Q</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <annotation>$dot{Q}$</annotation>\u0000 </semantics></math>) to the rate of oxygen consumption (<span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <msub>\u0000 <mi>O</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{{{{mathrm{O}}}_2}}}$</annotation>\u0000 </semantics></math>) slope (<span></span><math>\u0000 <semantics>\u0000 <mover>\u0000 <mi>Q</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <annotation>$dot{Q}$</annotation>\u0000 </semantics></math>–<span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <msub>\u0000 <mi>O</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{{{{mathrm{O}}}_2}}}$</annotation>\u0000 </semantics></math>) in healthy males is related to stroke volume (SV); however, the impact of differences in left ventricular (LV) structure and function as well as biological sex on this slope is unclear. The <span></span><math>\u0000 <semantics>\u0000 <mover>\u0000 <mi>Q</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <annotation>$dot{Q}$</annotation>\u0000 </semantics></math>–<span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <msub>\u0000 <mi>O</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{{{{mathrm{O}}}_2}}}$</annotation>\u0000 </semantics></math> slope, LV function, convective oxygen delivery and vastus lateralis skeletal muscle oxygen saturation were assessed in 42 untrained, healthy individuals (25 ± 5 years, 50% female) during submaximal semi-upright cycling up to 120 W, followed by progressive exercise to exhaustion. There was considerable variability in the submaximal <span></span><math>\u0000 <semantics>\u0000 <mover>\u0000 <mi>Q</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <annotation>$dot{Q}$</annotation>\u0000 ","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4382-4396"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561167","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}
引用次数: 0
Splenic contraction associated with sudden, transient hypotension and sympathoexcitation in humans 脾收缩与人类突发性、短暂性低血压和交感神经兴奋有关。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-07-17 DOI: 10.1113/EP093761
Angelica Lodin-Sundström, Gabriel Axelsson, Lisa Ljungberg, Mats H. Linér, Bodil Sjögreen, Johan P. A. Andersson
{"title":"Splenic contraction associated with sudden, transient hypotension and sympathoexcitation in humans","authors":"Angelica Lodin-Sundström,&nbsp;Gabriel Axelsson,&nbsp;Lisa Ljungberg,&nbsp;Mats H. Linér,&nbsp;Bodil Sjögreen,&nbsp;Johan P. A. Andersson","doi":"10.1113/EP093761","DOIUrl":"10.1113/EP093761","url":null,"abstract":"<p>The spleen is traditionally recognised for its roles in immunity and blood filtration, and it is known to contract and release stored erythrocytes in hypoxic conditions. Recent findings suggest that the spleen may also contribute to cardiovascular regulation. This study investigated whether the spleen contracts during conditions that activate the sympathetic nervous system, including transient hypotension and psychophysiological stress responses. Eighteen healthy volunteers underwent four interventions known to be associated with either unloading of the arterial baroreceptors or sympathoexcitation: head-up tilt, cold-pressor test, thigh-cuff release and maximal-duration apnoea. Splenic volume was assessed repeatedly using ultrasound imaging, and cardiovascular variables were recorded continuously. All interventions elicited significant reductions in splenic volume (head-up tilt −5.3%, <i>P</i> = 0.0386; cold-pressor test −6.6%, <i>P</i> &lt; 0.001; thigh-cuff release −11.9%, <i>P</i> = 0.00118; apnoea −9.3%, <i>P</i> = 0.00159; Wilcoxon's signed rank test vs. baseline), indicating that splenic contraction occurs not only during hypoxic conditions (apnoea) but also in response to baroreceptor unloading (head-up tilt, thigh-cuff release) and general sympathetic activation (cold-pressor test). These findings suggest that the spleen may act as a constitutive effector of the sympathetic nervous system, possibly contributing to short-term blood pressure regulation. The results highlight a previously underappreciated role of the spleen in cardiovascular homeostasis and raise new questions about its contribution to systemic vascular control and stress physiology.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4368-4381"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469833","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}
引用次数: 0
Multi-omics identifies promoter methylation and gene expression changes associated with human skeletal muscle atrophy. 多组学鉴定与人类骨骼肌萎缩相关的启动子甲基化和基因表达变化。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-08-24 DOI: 10.1113/EP093999
Jamie-Lee M Thompson, Thomas M Doering, Boris P Budiono, Kristen L Mackenzie-Shalders, Kevin J Ashton, Paul J Dunn, Vernon G Coffey
{"title":"Multi-omics identifies promoter methylation and gene expression changes associated with human skeletal muscle atrophy.","authors":"Jamie-Lee M Thompson, Thomas M Doering, Boris P Budiono, Kristen L Mackenzie-Shalders, Kevin J Ashton, Paul J Dunn, Vernon G Coffey","doi":"10.1113/EP093999","DOIUrl":"10.1113/EP093999","url":null,"abstract":"<p><p>Skeletal muscle atrophy is a secondary complication in the aetiology of injury and chronic disease. Identifying mechanisms that control muscle mass is necessary to characterise atrophy and develop prevention strategies. We aimed to integrate transcriptomic and epigenomic data to identify key regulatory pathways controlled by promoter DNA methylation during muscle unloading. Twenty-one healthy men (20-40 years) completed a 4-week standardised exercise programme prior to a 14-day knee brace immobilisation with dietary control. Skeletal muscle mass and strength were assessed before and after immobilisation and biopsies were collected (m. vastus lateralis) before, at 3 days, and at completion at 14 days. RNA and DNA were isolated and analysed using Illumina RNA sequencing and DNA methylation 850K EPIC BeadChips. The 14-day immobilisation decreased muscle mass (∼9%; P < 0.0001) and strength (∼16%; P < 0.0001). At 3 days, most biological processes (BPs) were upregulated/hypomethylated (157 gene sets); upregulated BPs included cell signalling and protein ubiquitination and downregulated BPs included metabolism. After 14 days, BPs were predominantly downregulated/hypermethylated, including translation and ribosome biogenesis. Across both time points, HDAC4, GADD45A and CHRNA1 emerged as methylation-regulated candidate mediators of atrophy. HDAC4 and GADD45A showed strong correlations primarily at day 3, and CHRNA1 remained significant at both time points, extending prior observations in animals to human skeletal muscle. We have characterised changes in gene expression related to hypo- and hyper-methylation during muscle unloading in humans. These data extend our understanding of the regulatory processes that occur during skeletal muscle atrophy that, at the individual gene level, may be useful in developing strategies for reducing muscle wasting.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4763-4780"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812307","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}
引用次数: 0
The longevity dividend: Why governments and markets must catch up 长寿红利:为什么政府和市场必须迎头赶上。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-09-02 DOI: 10.1113/EP092866
Nikodem Grzesiak, Serena Kern-Libera, Richard Faragher, Annalisa Jenkins, Guy Coughlan, Damian Miles Bailey, Carina Kern
{"title":"The longevity dividend: Why governments and markets must catch up","authors":"Nikodem Grzesiak,&nbsp;Serena Kern-Libera,&nbsp;Richard Faragher,&nbsp;Annalisa Jenkins,&nbsp;Guy Coughlan,&nbsp;Damian Miles Bailey,&nbsp;Carina Kern","doi":"10.1113/EP092866","DOIUrl":"10.1113/EP092866","url":null,"abstract":"&lt;p&gt;‘How much’ often matters less than ‘how fast’. Financial systems might comfortably accommodate a decade increase in life expectancy if it emerges gradually over half a century, but could they accommodate the same increase within 5 years?&lt;/p&gt;&lt;p&gt;Economies are built to absorb gradual change and are much less comfortable with discontinuities. Human longevity may be approaching that kind of discontinuity. The latest scientific advances point to the emergence of what we have termed ‘system-level’ therapeutics (Kern, Jenkins et al., &lt;span&gt;2025&lt;/span&gt;; Kern et al., &lt;span&gt;2024&lt;/span&gt;), capable of bringing about rapid, non-linear changes in both healthspan and lifespan trajectories, challenging the incremental paradigms that underpin current economic and demographic forecasting models. If they do, governments, healthcare systems, insurers and pension funds will have to respond to a break with history, not a continuation of it.&lt;/p&gt;&lt;p&gt;In this paper, we introduce a new conceptual framework that classifies therapeutic interventions according to their biological scope: symptom-management, single-disease causal therapeutics and system-level therapeutics. The first two categories represent the traditional paradigm of medicine, in which therapies are directed at managing symptoms or treating individual diseases. In contrast, the third captures an emerging generation of system-level interventions that target shared biological mechanisms across multiple age-related diseases simultaneously (Kern, Jenkins et al., &lt;span&gt;2025&lt;/span&gt;). We outline the expected effects of each category on healthspan, lifespan and downstream economic outcomes. The framework provides a structured way to compare both conventional and the latest emerging therapeutic strategies and to trace how their differing biological impacts propagate through healthcare systems, labour markets, public finances, insurance, and economic productivity.&lt;/p&gt;&lt;p&gt;Blockbuster glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Ozempic, Rybelsus and Wegovy) and dulaglutide (Trulicity), together with the dual glucose-dependent insulinotropic polypeptide (GIP)–GLP-1 receptor agonist tirzepatide (Mounjaro and Zepbound), are proving to be far more than weight-loss treatments. Originally introduced for the treatment of type 2 diabetes, these therapies have since expanded to obesity and are now being evaluated for cardiovascular disease and multiple other conditions, with emerging interest in their potential effects on healthy ageing (Ryan et al., &lt;span&gt;2024&lt;/span&gt;; Zheng et al., &lt;span&gt;2024&lt;/span&gt;). Importantly, these benefits are not solely indirect consequences of weight reduction; emerging evidence points to previously unanticipated direct biological effects and novel therapeutic targets (e.g., GLP-1 may have direct effect on endothelial senescence). This trajectory foreshadows a broader shift in therapeutic potential: from highly indication-specific drugs focused on symptom management toward mecha","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4270-4276"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879543","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}
引用次数: 0
Intensity-dependent ventilatory and cardiopulmonary patterns during exercise in trained individuals with cerebral palsy: An exploratory study 训练有素的脑瘫患者运动期间强度依赖性通气和心肺模式:一项探索性研究。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-09-11 DOI: 10.1113/EP093890
Se-Hee Park, Hwan Kim, Min-Goo Lee
{"title":"Intensity-dependent ventilatory and cardiopulmonary patterns during exercise in trained individuals with cerebral palsy: An exploratory study","authors":"Se-Hee Park,&nbsp;Hwan Kim,&nbsp;Min-Goo Lee","doi":"10.1113/EP093890","DOIUrl":"10.1113/EP093890","url":null,"abstract":"<p>Cerebral palsy (CP) is associated with altered exercise physiology, but it remains unclear how ventilatory and cardiopulmonary responses are expressed under high physiological demand in individuals with CP. Six athletes with CP (spastic CP: <i>n</i> = 3, all GMFCS III, all male, mean age 24 years; ataxic CP: <i>n</i> = 3, GMFCS I/I/III, two female, mean age 28 years) and three non-disabled controls (CON: two female, mean age 28 years) performed a heart rate-matched incremental rowing protocol. Oxygen uptake, minute ventilation (<span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <mi>E</mi>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{mathrm{E}}}$</annotation>\u0000 </semantics></math>), tidal volume (<i>V</i><sub>T</sub>), respiratory frequency and O<sub>2</sub> pulse were described across sitting rest and target heart rate stages of 120, 140, 160 and 180 bpm. Descriptive analyses with effect sizes were performed. Peak <span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <msub>\u0000 <mi>O</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation>\u0000 </semantics></math>, recorded at the 180-bpm stage, appeared lower in CP subtypes than in CON (spastic CP: 33.9, 44.8, 31.7; ataxic CP: 35.3, 32.3, 28.3; CON: 49.3, 39.8, 48.5 mL kg<sup>−</sup><sup>1</sup> min<sup>−</sup><sup>1</sup>). With increasing exercise intensity, O<sub>2</sub> pulse tended to increase progressively in CON and ataxic CP; in spastic CP, the increase appeared more attenuated. <i>V</i><sub>T</sub> appeared lower in CP than CON across all stages. At the 180-bpm stage, spastic CP showed a narrow inter-individual <span></span><math>\u0000 <semantics>\u0000 <msub>\u0000 <mover>\u0000 <mi>V</mi>\u0000 <mo>̇</mo>\u0000 </mover>\u0000 <mi>E</mi>\u0000 </msub>\u0000 <annotation>${{dot{V}}_{mathrm{E}}}$</annotation>\u0000 </semantics></math> range (71.4–88.3 L min<sup>−</sup><sup>1</sup>) relative to CON (90.3–138.3 L min<sup>−</sup><sup>1</sup>); ataxic CP showed wide variability (48.3–112.9 L min<sup>−</sup><sup>1</sup>). Intensity-dependent changes in O<sub>2</sub> pulse and ventilatory patterning appeared to differ between CP subtypes and CON, suggesting these variables may reflect subtype-specific exercise physiology in CP.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4337-4343"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944645","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}
引用次数: 0
Systemic pirfenidone treatment fails to mitigate fibrosis and compromises functional recovery in a porcine model of volumetric muscle loss 在猪体积肌肉损失模型中,全身吡非尼酮治疗不能减轻纤维化并损害功能恢复。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-07-30 DOI: 10.1113/EP093693
Jessica M. Motherwell, Ondine Eken, Claudia E. Hernandez, Christopher L. Dearth, Stephen M. Goldman
{"title":"Systemic pirfenidone treatment fails to mitigate fibrosis and compromises functional recovery in a porcine model of volumetric muscle loss","authors":"Jessica M. Motherwell,&nbsp;Ondine Eken,&nbsp;Claudia E. Hernandez,&nbsp;Christopher L. Dearth,&nbsp;Stephen M. Goldman","doi":"10.1113/EP093693","DOIUrl":"10.1113/EP093693","url":null,"abstract":"<p>Repurposing clinically approved antifibrotic agents presents a potential near-term therapeutic strategy to mitigate the extensive fibrotic scarring that follows severe volumetric muscle loss (VML) injury and inhibits functional recovery. We hypothesized that daily oral administration of pirfenidone, an FDA-approved antifibrotic, would mitigate the overwhelming fibrotic response and facilitate functional recovery in a clinically relevant porcine VML model. Yorkshire-cross pigs (<i>n</i> = 12) underwent VML or sham surgery in the peroneus tertius muscle and were subsequently allocated to pirfenidone treatment or untreated controls. At the 4-week study endpoint, the affected muscles underwent comprehensive histological, biochemical, transcriptional and neuromuscular functional assessments. Transcription profiling demonstrated that pirfenidone downregulated key pro-inflammatory cytokine and chemokine regulators involved in excessive fibrosis, including TNF, CCL3L1 and CCL2. While pirfenidone treatment failed to reduce total collagen deposition, evidenced by picrosirius red quantification and hydroxyproline content, it did result in a less dense collagen fibre architecture, suggestive of altered tissue remodelling. However, pirfenidone treatment impaired functional recovery through reduced contractile output and resulted in stagnant weight gain compared to the untreated cohort. This work demonstrates that systemic pirfenidone administration failed to meaningfully reduce fibrosis and subsequently worsened functional capacity following VML, similar to previous antifibrotic studies. The functional deficits and stagnant weight gains observed here underscore a critical knowledge gap regarding the impact of systemic antifibrotics on contractile recovery, necessitating a rigorous re-evaluation of delivery routes, dosages and administration timelines to ensure that future therapies for fibrotic scarring do not inadvertently hinder the physiological recovery of VML-injured muscle.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4286-4295"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13422706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629871","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}
引用次数: 0
Circulating granulocyte colony-stimulating factor as a sex-unbiased global marker of lung and colorectal cancer cachexia pre-clinical models. 循环粒细胞集落刺激因子作为肺癌和结直肠癌恶病质临床前模型的性别无偏全球标志物。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-08-13 DOI: 10.1113/EP093809
Francielly Morena, Eleanor R Schrems, Ana Regina Cabrera, Ruqaiza Muhyudin, Sepideh Shakeri, Stavroula Tsitkanou, Mark Viggars, Tyrone A Washington, Nicholas P Greene
{"title":"Circulating granulocyte colony-stimulating factor as a sex-unbiased global marker of lung and colorectal cancer cachexia pre-clinical models.","authors":"Francielly Morena, Eleanor R Schrems, Ana Regina Cabrera, Ruqaiza Muhyudin, Sepideh Shakeri, Stavroula Tsitkanou, Mark Viggars, Tyrone A Washington, Nicholas P Greene","doi":"10.1113/EP093809","DOIUrl":"10.1113/EP093809","url":null,"abstract":"<p><p>Cancer cachexia, affecting up to 80% of patients with advanced cancer, is characterized by metabolic and inflammatory dysregulation driven by tumour- and host-derived factors. Although cytokines are central to cachexia pathogenesis, their circulating profiles and transcriptional relevance across models and sexes remain incompletely defined. We characterized plasma cytokines and skeletal muscle inflammatory signatures in multiple cachexia models, including Lewis Lung Carcinoma (LLC), Colon-26 (C26) and Apc<sup>Min/+</sup> mice. Animals were monitored for 4 weeks (LLC), 25 days (C26) or until ∼20 weeks of age (Apc<sup>Min/+</sup>) per model appropriate endpoints. Publicly available RNA-sequencing datasets from gastrocnemius (LLC) and tibialis anterior (C26 and Apc<sup>Min/+</sup>) muscles were integrated with plasma profiling using a Mouse Cytokine/Chemokine 32-Plex assay. To enhance accessibility and reproducibility, we developed an interactive Shiny application - thecachexiatlas/Cytokine Explorer - enabling dynamic visualization of cytokine levels, transcriptional signatures and phenotype correlations across models and sexes. Cytokine receptor encoding genes (Il6ra, Il4ra, Csf3, Osmr) and inflammatory pathways were consistently enriched in skeletal muscle of cachectic animals across models and sexes. Among circulating cytokines, granulocyte colony-stimulating factor (G-CSF) was uniquely elevated in all models and both sexes. Elevated G-CSF levels exhibited stronger negative correlations with tibialis anterior muscle mass than the commonly used cytokine interleukin (IL)-6, particularly when expressed as the ratio of G-CSF to the anti-inflammatory cytokine IL-13. The G-CSF:IL-13 ratio may represent a robust global biomarker of cachexia severity. The Cytokine Explorer Shiny app provides an open, interactive platform to facilitate hypothesis generation and advance research in cancer cachexia.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4705-4721"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723844","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}
引用次数: 0
Effects of dietary nitrate supplementation on peak oxygen uptake following 10 days of Ramadan fasting in healthy adults. 膳食硝酸盐补充对健康成人斋月禁食10天后峰值摄氧量的影响
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-08-18 DOI: 10.1113/EP093800
Mikail M Bhimani, Julian C Bommarito, Natalie I Miners, Pardeep K Khangura, Rileigh K Stapleton, Ashly Sharma, Johan S Thiessen, Nicolas O Cyr, Devin G McCarthy, Jianzhang Dong, Clara E Cho, Philip J Millar
{"title":"Effects of dietary nitrate supplementation on peak oxygen uptake following 10 days of Ramadan fasting in healthy adults.","authors":"Mikail M Bhimani, Julian C Bommarito, Natalie I Miners, Pardeep K Khangura, Rileigh K Stapleton, Ashly Sharma, Johan S Thiessen, Nicolas O Cyr, Devin G McCarthy, Jianzhang Dong, Clara E Cho, Philip J Millar","doi":"10.1113/EP093800","DOIUrl":"10.1113/EP093800","url":null,"abstract":"<p><p>Ramadan is a sacred religious practice observed by Muslims that involves abstaining from food and water from sunrise to sunset for 1 month. Prior work has reported that peak oxygen uptake ( <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> ) can decline during Ramadan in parallel with reduced physical activity. We investigated whether dietary nitrate supplementation could attenuate the decrease in <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> during 10 days of Ramadan fasting. In a randomized design, 21 healthy participants (13 females) were assigned to ingest 70 mL of beetroot juice (∼6.45 mmol nitrate; n = 10), twice a day for 10 days consecutively, or a non-supplement control (n = 11). The <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> was assessed by indirect calorimetry during a maximal cycle ergometer ramp test. After 10 days of Ramadan fasting, the change in body mass was not different between groups [change (∆), -0.91 ± 1.3 vs. -0.27 ± 1.2 kg (control vs. nitrate), P = 0.25], nor were the changes in resting systolic (P = 0.21) or diastolic (P = 0.53) blood pressure or urine specific gravity (P = 0.17). Subjective sleep quality declined over time in both groups (P < 0.01). Participants self-reported a decline (n = 17) or no change (n = 4) in regular physical activity, and the number of exercise bouts during the 10 days of Ramadan did not differ between groups (2.5 ± 2.0 vs. 3.3 ± 2.4, P = 0.44). Absolute <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> decreased in the control group compared with the dietary nitrate supplementation group (∆, -155 ± 168 vs. +67 ± 162 mL min<sup>-1</sup>, P < 0.01), as did <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> relative to body mass (∆, -2.4 ± 2.5 vs. +0.3 ± 1.9 mL kg<sup>-1</sup> min<sup>-1</sup>, P = 0.02) and peak power output (∆, -12 ± 16 vs. ∆+2 ± 10 W, P = 0.04). Dietary nitrate supplementation might represent a practical nutritional strategy to preserve aerobic capacity during Ramadan fasting.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4636-4645"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789940","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}
引用次数: 0
Acute exercise-induced lipolysis and increase in levels of fatty acid esters of hydroxy fatty acids in adipose tissue are impaired in obese and aged mice. 急性运动诱导的脂肪分解和脂肪组织中羟基脂肪酸脂肪酸酯水平的增加在肥胖和老年小鼠中受到损害。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-07-25 DOI: 10.1113/EP093561
Marko Mitrovic, Olga Horakova, Martin Riecan, Veronika Kleinova, Tomas Cajka, Lenka Rossmeislova, Ondrej Kuda, Martin Rossmeisl
{"title":"Acute exercise-induced lipolysis and increase in levels of fatty acid esters of hydroxy fatty acids in adipose tissue are impaired in obese and aged mice.","authors":"Marko Mitrovic, Olga Horakova, Martin Riecan, Veronika Kleinova, Tomas Cajka, Lenka Rossmeislova, Ondrej Kuda, Martin Rossmeisl","doi":"10.1113/EP093561","DOIUrl":"10.1113/EP093561","url":null,"abstract":"<p><p>Improving adipose tissue (AT) metabolism through exercise might increase production of lipokines from the fatty acid esters of hydroxy fatty acids (FAHFA) family. Although exercise training can increase insulin sensitivity and levels of specific FAHFA in AT and the circulation in humans, the effects of acute exercise on FAHFA levels remain unclear. Previously untrained lean, obese and aged male C57BL/6J mice were subjected to acute treadmill exercise. AT lipolysis, metabolomic profile and FAHFA levels were analysed at baseline and 0 and 3 h postexercise. Baseline AT levels of FAHFA, particularly those containing mono- and polyunsaturated fatty acids, were lower in obese and aged mice compared with lean mice. AT-specific expression of genes related to de novo lipogenesis and lipolysis was reduced, particularly in obese mice, whereas expression of FAHFA hydrolysis-related genes was higher in aged mice. In lean mice, acute exercise increased plasma non-esterified fatty acids and their release from AT explants, which was suppressed in obese and aged counterparts. Only in lean animals, acute exercise led to a time-dependent increase in total FAHFA levels in AT, with the most pronounced increase observed in 13/12-regioisomers from different FAHFA subfamilies. The effect of acute exercise on AT FAHFA levels was stronger than that of fasting alone, revealing palmitoleic acid-containing FAHFA as the most differentiating regioisomers. In contrast, plasma FAHFA levels were minimally affected in all groups. In conclusion, acute exercise increases FAHFA levels in AT but not in plasma, and this effect appears to be negatively affected by obesity and ageing.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4457-4497"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590917","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}
引用次数: 0
Stretch versus shortening contractions subsequently decrease versus increase neural drive to the human tibialis anterior. 拉伸与缩短收缩随后减少与增加神经驱动到人类胫骨前肌。
IF 3 4区 医学
Experimental Physiology Pub Date : 2026-10-01 Epub Date: 2026-09-12 DOI: 10.1113/EP094110
Brent James Raiteri, Karla Friederike Bosse, Marta Boccardo, Alain Charles Vandal, Daniel Hahn
{"title":"Stretch versus shortening contractions subsequently decrease versus increase neural drive to the human tibialis anterior.","authors":"Brent James Raiteri, Karla Friederike Bosse, Marta Boccardo, Alain Charles Vandal, Daniel Hahn","doi":"10.1113/EP094110","DOIUrl":"10.1113/EP094110","url":null,"abstract":"<p><p>EMG-based muscle force predictions are often inaccurate following active muscle stretch or shortening because of residual force enhancement (rFE) or depression (rFD), respectively, which can alter the neural drive to a muscle. However, the extent of neural drive modulation attributable to rFE or rFD remains unknown owing to the limited spatial sampling of intramuscular EMG. Therefore, we combined two blind-source separation approaches with high-density surface EMG and mixed-effects modelling to assess changes in neural drive from more representative motor unit samples. Seventeen participants performed dorsiflexion contractions at 20% and 40% of maximum voluntary torque in three conditions: stretch-hold, shortening-hold and fixed-end reference (REF) conditions. The ankle dorsiflexion torques and angles were matched using dynamometry to the REF condition during a steady state following a 1-s 25° stretch or shortening, during which we decomposed tibialis anterior high-density EMG recordings. Normalised EMG amplitudes were ∼2% lower following stretch and 1% and 3% higher following shortening relative to REF at 20% and 40% of maximum voluntary torque (P ≤ 0.008), respectively. Discharge rates from 19 matched motor units per person on average obtained via DEMUSE and MUedit were similar (P = 0.666). Following stretch and shortening, discharge rates were ∼1 Hz lower (P ≤ 0.029) and 0 (P = 0.459) to 1 Hz higher (P < 0.001) relative to REF, respectively. More unique motor units were also detected following shortening. These findings indicate that to account for rFE or rFD, neural drive is respectively decreased or increased via reduced or additional motor unit recruitment and discharge rate modulation, with a contraction intensity-specific rate modulation following active shortening.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4793-4813"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955222","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}
引用次数: 0
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