Experimental Physiology最新文献

{"title":"Muscle fibre type shift in COPD: Adaptive, maladaptive or a bit of both?","authors":"Jacob Peter Hartmann, Hannah G Caldwell, Ulrik Winning Iepsen","doi":"10.1113/EP092126","DOIUrl":"https://doi.org/10.1113/EP092126","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Bezold-Jarisch reflex: Hubris and (n)emesis in the clinical assessment of acute inferior wall myocardial infarction.","authors":"Ronan M G Berg, Reza Jabbari","doi":"10.1113/EP092587","DOIUrl":"https://doi.org/10.1113/EP092587","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress and hormonal status influence orexin-1 receptor expression in structures regulating cardiorespiratory responses to CO₂.","authors":"Stéphanie Fournier, Julie Plamondon, Denis Richard, Richard Kinkead","doi":"10.1113/EP092431","DOIUrl":"https://doi.org/10.1113/EP092431","url":null,"abstract":"<p><p>Excessive cardiorespiratory responses to CO₂ are a hallmark of panic disorder (PD). Female sex and exposure to early life stress are risk factors for PD. Neonatal maternal separation (NMS; 3 h/day, postnatal days 3-12) augments the ventilatory response to CO₂ by ∼35% relative to controls; this effect is most notable during pro-oestrus but is not observed in males. Orexin-1 receptor (OX1-R) antagonism attenuates the CO₂ response of NMS females. In the limbic system, stress and ovarian hormones influence OX1-R expression, but the impact of these factors on OX1-Rs in regions regulating the cardiorespiratory responses to CO₂ is unknown. Here, we hypothesised that ovarian hormones and NMS determine OX1-R expression in structures regulating the CO₂ response; we used in situ hybridisation to quantify OX-1R mRNA expression in the brains of adult NMS and control rats. Brains were harvested from females that were either in pro-oestrus (high ovarian hormones) or 2 weeks post ovariectomy (OVX; low ovarian hormones); males were included for comparison. Hormonal status influenced the intensity of the OX1-R signal in the medial amygdala, raphe obscurus (RObs) and the A5 area, but the direction of the changes (increase vs. decrease) was structure-specific. Significant NMS × hormonal status interactions were noted in the dorsal raphe, the locus coeruleus, the nucleus of the solitary tract and the A5 area; the effects were structure-specific. As the dorsal raphe was the only structure in which the changes in OX1-R expression matched the sex-specific effect of NMS on the CO₂ response, this structure likely contributes to respiratory manifestations of PD.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unilateral electrical stimulation of mice induces transcriptional response in stimulated leg with limited effect on non-stimulated contralateral leg.","authors":"Takanaga Shirai, Kazuki Uemichi, Tohru Takemasa, Yu Kitaoka","doi":"10.1113/EP092394","DOIUrl":"https://doi.org/10.1113/EP092394","url":null,"abstract":"<p><p>Electrical stimulation is widely used to investigate localised muscle adaptations, with applications in both sports and rehabilitation. However, the systemic effects of electrical stimulation, particularly in the contralateral muscles that are not directly stimulated, are not well understood. This study investigated whether unilateral electrical stimulation induces transcriptional changes in both the electrically stimulated (ES) and non-stimulated (non-ES) contralateral legs, compared with the legs of sedentary control mice. RNA-sequence analysis revealed that 1320 and 55 genes were differentially expressed in the ES and non-ES, respectively, compared with controls using DEseq2 (false discovery rate cutoff = 0.05, minimal fold change = 1.5). Gene ontology and pathway enrichment analyses identified that the biological processes of immune response, muscle development, and response to stimuli were upregulated in the ES leg, while immune response and stress signalling were upregulated in the non-ES leg. Although the non-ES leg exhibited minimal transcriptional changes, Tbc1d1, which enhances glucose uptake, and Mss51, a regulator of mitochondrial function, were upregulated while Ddit4, a negative regulator of mammalian/mechanistic target of rapamycin signalling, and stress responsive protein Gadd45g were downregulated. These findings aid the understanding of molecular mechanisms underlying the cross-education effect and suggest that contralateral effects of electrical stimulation are limited, despite potential signalling across the legs.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistency of endothelial function across two consecutive oral contraceptive pill cycles.","authors":"Lindsay A Lew, Desiree Tugwell, Tess Leavitt, Melanie Vitez, Emily J Ferguson, Kyra E Pyke","doi":"10.1113/EP092399","DOIUrl":"https://doi.org/10.1113/EP092399","url":null,"abstract":"<p><p>Oral contraceptive pills (OCPs), composed of an active pill (AP; synthetic hormone) and a placebo pill (PP; synthetic hormone-free) phase, might impact endothelial function across the OCP cycle depending on the synthetic hormone composition (type and dose). Only one study has investigated very low-dose second-generation OCP users, finding impaired endothelial function in the AP versus PP phase. No studies have reported individual changes in endothelial function across OCP phases, and no studies have examined repeatability of endothelial function across multiple OCP cycles. Owing to the consistency of synthetic hormone exposure in OCP users, we hypothesized that group and individual flow-mediated dilatation (FMD) responses to the OCP phase would be consistent across two OCP cycles. Endothelial function was assessed by FMD via Duplex ultrasound in 17 very low-dose second-generation OCP users (19 ± 2 years of age) during the AP phase and PP phase for two consecutive OCP cycles. Individual responses were classified using a threshold of ±2 × typical error. There was a main effect of phase such that FMD was lower in the AP versus PP phase (P = 0.022; AP = 4.3% ± 1.3%, PP = 5.4% ± 1.4%). Threshold analysis revealed no consistent responders, and there was no relationship between Δ%FMD in cycle 1 and cycle 2 (P = 0.220; r = -0.314). Overall, these results suggest that exposure to the synthetic hormones in second-generation OCPs might be detrimental to vascular function, although this was not demonstrated to be a consistent trait-like response at the individual level over two cycles.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxysteroid 17β-dehydrogenase 13 (Hsd17b13) knockdown attenuates liver steatosis in high-fat diet obese mice.","authors":"Shehroz Mahmood, Nicola Morrice, Dawn Thompson, Sara Milanizadeh, Sophie Wilson, Philip D Whitfield, George D Mcilroy, Justin J Rochford, Nimesh Mody","doi":"10.1113/EP092535","DOIUrl":"https://doi.org/10.1113/EP092535","url":null,"abstract":"<p><p>Hydroxysteroid 17β-dehydrogenase 13 (HSD17B13) loss-of-function gene variants are associated with a decreased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Our RNA-seq analysis of steatotic liver from obese mice ± fenretinide treatment identified major beneficial effects of fenretinide on expression of hepatic genes including Hsd17b13. We sought to determine the relationship between Hsd17b13 expression and MASLD and to validate it as a therapeutic target by liver-specific knockdown. Hsd17b13 expression, which is unique to hepatocytes and associated with the lipid droplet, was elevated in multiple models of MASLD and normalised with the prevention of obesity and steatotic liver. Direct, liver-specific, shRNA-mediated knockdown of Hsd17b13 (shHsd17b13) in high-fat diet (HFD)-obese mice, markedly improved hepatic steatosis with no effect on body weight, adiposity or glycaemia. shHsd17b13 decreased elevated serum alanine aminotransferase (ALT), serum fibroblast growth factor 21 (FGF21) levels, and markers of liver fibrosis, for example, expression of Timp2. shHsd17b13 knockdown in HFD-obese mice and Hsd17b13 overexpression in cells reciprocally regulated expression of lipid metabolism genes, for example, Cd36. Global lipidomic analysis of liver tissue revealed a major decrease in diacylglycerols (e.g. DAG 34:3) with shHsd17b13 expression and an increase in phosphatidylcholines containing polyunsaturated fatty acids (PUFA) for example, phosphatidylcholine (PC) 34:3 and PC 42:10. Expression of key genes involved in phospholipid and PUFA metabolism, for example, Cept1, was also reciprocally regulated suggesting a potential mechanism of Hsd17b13 biological function and role in MASLD. In conclusion, Hsd17b13 knockdown in HFD-obese adult mice was able to alleviate MASLD via regulation of fatty acid and phospholipid metabolism, thereby confirming HSD17B13 as a genuine therapeutic target for MASLD and the development of liver fibrosis.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular pathophysiology of chronic kidney disease-mineral and bone disorder: Focus on the fibroblast growth factor 23-Klotho axis and bone turnover dynamics.","authors":"Alief Waitupu, Laras Pratiwi, Henry Sutanto, Djoko Santoso, Decsa Medika Hertanto","doi":"10.1113/EP092401","DOIUrl":"https://doi.org/10.1113/EP092401","url":null,"abstract":"<p><p>Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a major complication of chronic kidney disease (CKD), characterized by disruptions in mineral metabolism, abnormal bone turnover and vascular calcification, which collectively increase the risk of fractures and cardiovascular disease. This review examines the molecular mechanisms underlying CKD-MBD, with a particular focus on the fibroblast growth factor 23 (FGF23)-Klotho axis - a key regulator of phosphate balance, vitamin D activation and parathyroid hormone secretion. In CKD, elevated FGF23 levels and reduced Klotho expression contribute to mineral homeostasis disturbances and bone abnormalities. The dysregulation of this pathway plays a central role in CKD-MBD pathophysiology and its associated complications. Emerging therapies, such as anti-FGF23 antibodies and recombinant Klotho, hold promise for modulating FGF23 activity and restoring mineral balance. This review highlights the importance of individualized treatment strategies based on bone turnover patterns and FGF23-Klotho axis dysfunction. Advancing our understanding of these molecular mechanisms will aid in the development of more effective diagnostic tools and therapeutic interventions to improve CKD-MBD outcomes.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blistering barnacles: Space physiology in The Adventures of Tintin.","authors":"Jacob P Hartmann, Mathis B Mottelson, Rasmus H Dahl, Ronni R Plovsing, Ronan M G Berg","doi":"10.1113/EP092571","DOIUrl":"https://doi.org/10.1113/EP092571","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marie Krogh's contributions to the study of thyroid physiology and pathophysiology.","authors":"Per Karkov Cramon, Mathias Loft, Ronan M G Berg","doi":"10.1113/EP092572","DOIUrl":"https://doi.org/10.1113/EP092572","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic sustained hypoxia alters the pattern of diaphragm electrical activity in anaesthetized rats","authors":"Jamal Khalilpour,&nbsp;Mohammad Reza Alipour,&nbsp;Parviz Shahabi","doi":"10.1113/EP092211","DOIUrl":"10.1113/EP092211","url":null,"abstract":"<p>Chronic sustained hypoxia (CSH) is known to induce functional and structural changes in the respiratory system. The diaphragm, as the main inspiratory muscle of mammals, is particularly important in the neuromotor regulation of respiration. Diaphragm electromyography (dEMG) records the sum of motor unit action potentials (MUAP) and provides information regarding motor unit recruitment and frequency coding during muscle contraction. We aimed to assess changes in dEMG activity following CSH. Herein, eight male Wistar rats (2–3 months) were subjected to CSH (10 ± 0.5% O₂) for 10 successive days. <i>In vivo</i> dEMG recording was employed to assess changes in the diaphragm electrical activity. Filtered and rectified dEMGs were used for further analyses. Findings showed that CSH for 10 consecutive days significantly changed the pattern of dEMG signals. The slope of the rising phase of RMS-enveloped dEMG bursts was much steeper in CSH rats compared to normoxic control rats (rise time: 373 vs. 286 ms; <i>P </i>= 0.005). Burst frequency significantly decreased following CSH (59 vs. 42 bursts/min; <i>P</i> = 0.0001), which was associated with a significant increase in burst amplitude (<i>P</i> = 0.039) and inter-burst duration (0.65 vs. 0.88 s; <i>P</i> = 0.041). Power spectral density analyses showed that the mean frequency (293 vs. 266 Hz; <i>P</i> = 0.033) and high-frequency to low-frequency power ratio (<i>P</i> = 0.009) of dEMG signals significantly declined in CSH rats. Notably, the regularity of frequency and amplitude of dEMG signals did not change significantly following CSH.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"110 4","pages":"599-609"},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/EP092211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482554","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}