{"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}
Jacob P Hartmann, Mathis B Mottelson, Rasmus H Dahl, Ronni R Plovsing, Ronan M G Berg
{"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}
Luiz Felipe Tavares, Ana Izabela Sobral de Oliveira-Souza, Vladimir Aron, Ana Beatriz Oliveira, Henrik Bjarke Vaegter, Susan Armijo-Olivo
{"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}
Jamal Khalilpour, Mohammad Reza Alipour, Parviz Shahabi
{"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":"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% O<sub>2</sub>) 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}
{"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}
Johannes Lässing, Sonja Hummelmann, Maxi Kramer, Ulrich Laufs, Sven Fikenzer, Roberto Falz
{"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}
Bonn Lee, Shiraz Ahmad, Charlotte E Edling, Fiona E N LeBeau, Kamalan Jeevaratnam
{"title":"Intact microdissection of stellate ganglia in a Parkinson's disease model reveals aggregation of mutant human α-synuclein in their cell bodies.","authors":"Bonn Lee, Shiraz Ahmad, Charlotte E Edling, Fiona E N LeBeau, Kamalan Jeevaratnam","doi":"10.1113/EP092261","DOIUrl":"https://doi.org/10.1113/EP092261","url":null,"abstract":"<p><p>Cardiac dysautonomia plays an important role in understanding Parkinson's disease (PD), with recent studies highlighting the presence of α-synuclein in cardiac tissue. We hypothesise that sympathetic dysregulation observed in PD may involve pathological changes caused by α-synuclein in stellate ganglia (SG). This study aimed to investigate α-synucleinopathy in SG of the genetic PD murine animal model. Mice overexpressing Ala30Pro (A30P) mutant α-synuclein were used. We here demonstrate a technique for meticulously dissecting SG. The collected SG from the transgenic mice were immunolabelled with neuronal markers, A30P human mutant α-synuclein and anti-α-synuclein aggregates. A30P mutant α-synuclein protein was expressed in the sympathetic neuronal (tyrosine hydroxylase (TH)-positive) cell bodies. Approximately 27% of the TH-positive cell bodies expressed the A30P mutant α-synuclein protein. The mutant protein was densely localised at the cardiopulmonary pole of the SG. Additionally, we observed that the A30P mutant protein formed fibril aggregation in the SG. Our findings suggest that α-synucleinopathy in the PD animal model can affect the sympathetic autonomic nervous system, providing insight for further research into targeting α-synuclein pathology in the SG as a potential link between cardiac dysautonomia and PD.</p>","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":"143476388","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}
Ronan M G Berg, Cody G Durrer, Jan Kyrre Berg Olsen Friis, Mathias Ried-Larsen
{"title":"The state of mechanistic research in the evidence-based medicine era: A sandwalk between triangulation and hierarchies.","authors":"Ronan M G Berg, Cody G Durrer, Jan Kyrre Berg Olsen Friis, Mathias Ried-Larsen","doi":"10.1113/EP092157","DOIUrl":"https://doi.org/10.1113/EP092157","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":"143467112","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}