Experimental Physiology最新文献

{"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":"Clinical significance of exercise-induced hypoalgesia in individuals with temporomandibular disorders and neck pain: A clinical trial protocol.","authors":"Luiz Felipe Tavares, Ana Izabela Sobral de Oliveira-Souza, Vladimir Aron, Ana Beatriz Oliveira, Henrik Bjarke Vaegter, Susan Armijo-Olivo","doi":"10.1113/EP091879","DOIUrl":"https://doi.org/10.1113/EP091879","url":null,"abstract":"<p><p>Evidence reports positive effects of neck motor control and aerobic exercises (AEs) to improve pain in individuals with temporomandibular disorders (TMD) and neck pain. A single bout of exercise typically leads to an increase in pain thresholds up to 30 min post-exercise, known as exercise-induced hypoalgesia (EIH). Studies evaluating the effects of aerobic and neck motor control exercises on EIH in individuals with chronic neck pain and TMD are limited. Measuring treatment effects and determining the clinical significance based on exercise types and loads and EIH response can improve clinical outcomes and adherence to exercise programmes. This study was designed to determine the clinical significance of EIH after neck motor control and aerobic training in participants with TMD and neck pain. Participants between 18 and 60 years with neck pain and/or TMD will be randomized to neck motor control or aerobic training groups. Participants will be assessed before, immediately after and 15 min after three treatment sessions within a 12-week exercise programme. Assessments will include pain intensity, pressure pain thresholds and tolerance of masticatory and neck muscles, and the Global Rating of Change Scale. EIH response will be calculated in absolute and relative changes by subtracting the post- from the pre-exercise values. Distribution-based (e.g., effect size) and anchor-based (e.g., receiver operating characteristics) methods will be performed to determine the clinical significance of EIH (minimal important difference).</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482555","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, Mohammad Reza Alipour, Parviz Shahabi","doi":"10.1113/EP092211","DOIUrl":"https://doi.org/10.1113/EP092211","url":null,"abstract":"<p><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. In vivo 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; P = 0.005). Burst frequency significantly decreased following CSH (59 vs. 42 bursts/min; P = 0.0001), which was associated with a significant increase in burst amplitude (P = 0.039) and inter-burst duration (0.65 vs. 0.88 s; P = 0.041). Power spectral density analyses showed that the mean frequency (293 vs. 266 Hz; P = 0.033) and high-frequency to low-frequency power ratio (P = 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":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-tone suppression between the ultrasounds above and within the hearing range in mice.","authors":"Noriko Nagase, Hirokazu Kousaki, Bakushi Ogawa, Kazuhiro Horii, Iori Niitsu Morimoto, Chikara Abe, Takenori Ogawa, Fumiaki Nin","doi":"10.1113/EP092317","DOIUrl":"https://doi.org/10.1113/EP092317","url":null,"abstract":"<p><p>Hearing range differs among various species. Ultrasound, which is audible to microbats and dolphins, is inaudible to humans through air conduction. However, it can create an auditory sensation when the stimulation is transmitted through the temporal bone. This phenomenon is known as ultrasonic hearing - sounds at frequencies exceeding the normal hearing range participate in audition. Mice are among the animals that possess one of the highest upper limits of the hearing range. Although ultrasonic hearing has been experimentally demonstrated in humans and guinea pigs, its existence in mice and interaction with ultrasound within the hearing range remain unknown. In this study, we found that ultrasound above the hearing range delivered through the temporal bone evokes the cochlear microphonic potential (CM) in mice. The CM synchronized with the applied single-tone ultrasound, and was actively amplified. Furthermore, the amplitudes of the CM were suppressed by sound with subharmonic frequencies of the applied frequencies. The results indicate that hair cells in mice can detect ultrasound stimuli with frequencies over 120 kHz and ultrasounds within and above the hearing range evoked hair cell currents at the close position along the cochlea.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482556","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":"Repetition-dependent acutecardiopulmonary responses during intensity-matched squats in males.","authors":"Johannes Lässing, Sonja Hummelmann, Maxi Kramer, Ulrich Laufs, Sven Fikenzer, Roberto Falz","doi":"10.1113/EP092363","DOIUrl":"https://doi.org/10.1113/EP092363","url":null,"abstract":"<p><p>The 'strength-endurance continuum' is a key concept in strength training (ST). Although cardiopulmonary responses have seldom been reported in conjunction with ST, this repeated-measurement study examined acute blood pressure and haemodynamic responses continuously depending on the number of repetitions but without changing the intensity. Fifteen healthy male participants (21.6 (2.0) years; mean (SD)) performed an incremental exercise test and a 3-repetition maximum test (3-RM) on a Smith machine. They were then randomly assigned to three ST sessions involving 10, 20 and 30 repetitions at 50% of their 3-RM. Blood pressure (vascular unloading technique) and cardiopulmonary responses (spirometry and impedance cardiography) were continuously monitored. Heart rate (121 (10) vs. 139 (22) vs. 153 (13) bpm, P = 0.001, respectively), cardiac output (10.4 (1.9) vs. 13.6 (3.8) vs. 14.6 (3.1) L/min, P = 0.001, respectively) and diastolic blood pressure (113 (8) vs. 116 (21) vs. 135 (22) mmHg, P = 0.001, respectively) increased in the training sessions with higher repetitions. Stroke volume, systolic blood pressure and end-diastolic volume indicated no change in peak values between training sessions. Total peripheral resistance (13.6 (2.8) vs. 11.3 (3.6) vs. 11.2 (3.1) mmHg min/L, P = 0.002, respectively) was significantly lower with 20 and 30 repetitions, while oxygen uptake ( <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <msub><mi>O</mi> <mn>2</mn></msub> </msub> <annotation>${dot V_{{{mathrm{O}}_{mathrm{2}}}}}$</annotation></semantics> </math> : 15.5 (1.9) vs. 20.5 (4.1) vs. 20.6 (4.4) mL/min/kg, P = 0.001, respectively) was significantly higher. ST of moderate intensity with an exhausting number (>20) of repetitions induces strong haemodynamic responses, especially high cardiac afterload and a compensatory heart rate acceleration, which may also create a strong stimulus for cardiopulmonary adaptation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476455","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":"Decoding the space integrome: Personalized countermeasures for a mission to Mars.","authors":"Damian M Bailey","doi":"10.1113/EP092629","DOIUrl":"https://doi.org/10.1113/EP092629","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466610","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}