Aymeric Paillisser, Julien Vincent Brugniaux, Florence Berquet, Jeremy De Abreu, Stephen Hogg, Emanuele Trucco, Martial Geiser, Tom Macgillivray, Aurélien Pichon, Paul Robach, Benoit Champigneulle, Samuel Verges, Christophe Chiquet
{"title":"Effect of chronic high-altitude hypoxia on retinal vascular phenotype, choroidal and retinal vasoreactivity in Peruvian highlanders.","authors":"Aymeric Paillisser, Julien Vincent Brugniaux, Florence Berquet, Jeremy De Abreu, Stephen Hogg, Emanuele Trucco, Martial Geiser, Tom Macgillivray, Aurélien Pichon, Paul Robach, Benoit Champigneulle, Samuel Verges, Christophe Chiquet","doi":"10.1113/EP093967","DOIUrl":"10.1113/EP093967","url":null,"abstract":"<p><p>High-altitude chronic hypoxia can induce excessive erythrocytosis (EE, defined as a haemoglobin concentration of ≥21 g/dL in men), leading to hyperviscosity and promoting endothelial dysfunction. We aimed to assess whether EE affects the retinal vascular phenotype and the ophthalmological vascular response to CO<sub>2</sub>. We conducted an ophthalmological cross-sectional study among highlanders permanently living at 5100 m (La Rinconada, Peru). The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and retinal vessel tortuosity were measured using semi-automatic imaging software (VAMPIRE) from the diameters of the six largest arteries and veins on fundus images. Choroidal blood flow was assessed using laser Doppler flowmetry. Measurements were performed at rest and during a hypercapnic challenge (+10.1 ± 1.4 mmHg end-tidal CO<sub>2</sub>)<sub>.</sub> Among the 62 included highlanders, 38 (61%) had EE. Compared with non-EE, highlanders with EE exhibited higher CRVE (278 ± 25 vs. 249 ± 24 µm, P < 0.001), with no other significant ophthalmological differences. Resting CRVE was significantly correlated (all P-values < 0.001) with haematocrit (r = 0.56), haemoglobin concentration (r = 0.65), blood volume (r = 0.55) and the arterial partial pressure of carbon dioxide (r = 0.46). Hypercapnia led to a moderate overall decrease in CRVE (-8.6 ± 22.0 µm, P = 0.02), without a specific effect of EE, and induced no other retinal vascular or choroidal blood flow changes in either group. We observed larger retinal vein diameters in EE highlanders compared with non-EE. Although hypercapnia is known to increase retinal vessel diameter in healthy lowlanders, it selectively decreased CRVE in highlanders, irrespective of EE status. These findings suggest a retinal vascular dysfunction in highlanders, probably induced by chronic exposure to severe hypoxia.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4814-4826"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758530","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}
Elya J Ritenis, Christos G Stathis, Matthew B Cooke, Stephen Keenan, Andrew Philp, Donny M Camera
{"title":"Effects of exercise in a fed or fasted state on mitochondrial dynamics regulators in the skeletal muscle of recreationally active males.","authors":"Elya J Ritenis, Christos G Stathis, Matthew B Cooke, Stephen Keenan, Andrew Philp, Donny M Camera","doi":"10.1113/EP093336","DOIUrl":"10.1113/EP093336","url":null,"abstract":"<p><p>Exercise and nutritional modulation favourably alter mitochondrial quantity and quality in skeletal muscle. Mitochondrial dynamics, the coordination of fission and fusion events, are poised to mediate key aspects of organelle adaptation that arise from exercise. However, the molecular basis by which exercise affects mitochondrial dynamics remains poorly understood. The objective of this work was to further elucidate the signalling response of mitochondrial dynamics regulators to exercise and explore the synergistic potential to combine exercise and nutritional modulation. In a randomized crossover design, eight healthy, recreationally active men (age 25.8 ± 5.3 years, BMI 24.4 ± 1.2 kg/m<sup>2</sup>, <math> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> </math> 39.2 ± 5.7 ml/kg/min) performed a 1-h bout of workload-matched aerobic exercise on a cycle ergometer at 50-70% of W<sub>max</sub>, either in a fasted or a fed (i.e., following a carbohydrate rich breakfast) state. Gas exchange was measured throughout, and blood samples were collected intermittently. Vastus lateralis muscle biopsies were collected pre-, post- and 3 h post-exercise. Western blotting was performed on cytosolic and mitochondrial fractions. Fasted exercise was accompanied by increased cytosolic acetyl-CoA carboxylase Ser79 phosphorylation (P ≤ 0.001), an effect not observed in the fed group (P > 0.05). The subcellular location of mitochondrial fission effector dynamin-related protein 1 (DRP1) was unchanged (P > 0.05) following exercise. However, group differences (i.e., Fed vs. Fasted) in DRP1 subcellular localization and phosphorylation at residues Ser616 and Ser637 were observed post-exercise. Substrate availability may potentially influence the mitochondrial dynamics signalling response in skeletal muscle to acute aerobic exercise.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4525-4540"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677672","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":"Multi-omics analysis of ion channels expressed by chicken embryo vestibular type I and type II hair cells.","authors":"Giulia Cheli, Roberta Giunta, Francesca Stella, Eleonora Guidi, Umberto Laforenza, Mariarosa Polimeni, Giancarlo Russo, Francesca Borgo, Lazarevic Dejan, Sergio Masetto","doi":"10.1113/EP094078","DOIUrl":"10.1113/EP094078","url":null,"abstract":"<p><p>Balance and gaze rely on the rapid and accurate detection and signalling of head movements by vestibular type I and type II hair cells. Signal transduction and transmission involve several types of ion channels, which are acquired progressively during hair cell differentiation and whose identity is known only in part. In the present study, we adopted a multi-omics approach to identify the molecular nature of ion channels expressed by chicken vestibular hair cells between embryonic day 15 and embryonic day 21, the day of hatching, when both type I and II hair cells appear functionally mature. Type I hair cells are characterized by the expression of a low-voltage-activated outward rectifying K<sup>+</sup> current, termed I<sub>KL</sub>. In adult mice, I<sub>KL</sub> is carried by the K<sub>V</sub>1.8 α-subunit, although it is still debatable whether the K<sub>V</sub>7.4 α-subunit contributes to I<sub>KL</sub> in immature mouse type I hair cells. In this study, no effect of linopirdine, a specific blocker of K<sub>V</sub>7 channels, was found in either immature or mature type I or II hair cells. Furthermore, whole-organ RT-PCR and transcriptome analysis showed no expression of the K<sub>V</sub>7.4 α-subunit transcript, while detecting the transcript for the K<sub>V</sub>1.8 subunit. Its expression in type I and II hair cells was finally confirmed by patch-sequencing experiments. Further analysis of the transcriptomes of individual hair cells revealed the presence of transcripts for several other α and auxiliary subunits of Na<sup>+</sup>, K<sup>+</sup> and Ca<sup>2+</sup> channels, which are, presumably, responsible for the ionic currents recorded in both birds and mammals.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4894-4914"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967137","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}
Rie Skovly Thomsen, Iben Elmerdahl Rasmussen, Stine Buus Nymand, Anna Agnes Lytzen, Jacob Peter Hartmann, Milan Mohammad, Malte Lund Adamsen, Birgitte Hanel, Jann Mortensen, Ronan M. G. Berg
{"title":"Effect of an acute exercise bout on alveolar–capillary membrane permeability and interstitial fluid accumulation in COPD","authors":"Rie Skovly Thomsen, Iben Elmerdahl Rasmussen, Stine Buus Nymand, Anna Agnes Lytzen, Jacob Peter Hartmann, Milan Mohammad, Malte Lund Adamsen, Birgitte Hanel, Jann Mortensen, Ronan M. G. Berg","doi":"10.1113/EP094018","DOIUrl":"10.1113/EP094018","url":null,"abstract":"<p>Exertional dyspnoea is a debilitating symptom in chronic obstructive pulmonary disease (COPD) and often persists after the cessation of exercise. The underlying mechanisms are not fully understood, and a potential contributing factor that has not previously been investigated is alveolar–capillary membrane breaching with extravasation of fluid into the lungs. Sixteen individuals with COPD and 16 age- and sex-matched healthy controls were included. Alveolar–capillary membrane permeability was quantified using the pulmonary clearance index (PCI), calculated from scintigraphically determined alveolar clearance of <sup>99m</sup>Tc-labelled diethylenetriaminepentaacetic acid at rest and following an acute exercise bout performed at maximal exertion, as determined by a prior cardiopulmonary exercise test. In addition, lung tissue mass (LTM) was assessed using low-dose computed tomography, with rest-to-post-exercise changes interpreted as reflecting alterations in interstitial fluid accumulation. The mean change in PCI from rest-to-post-exercise was −0.01 [95% CI: −0.09, 0.06]%/min in the COPD group and −0.05 [95% CI: −0.12, 0.02]%/min in the healthy control group (Group × Time interaction, <i>P</i> = 0.446). The mean change in LTM from rest-to-post-exercise was 16.5 [95% CI: −7.0, 40.0]g/1.73 m<sup>2</sup> in the COPD group and 35.2 [95% CI: 11.7, 58.7]g/1.73 m<sup>2</sup> in the healthy control group (Group × Time interaction, <i>P</i> = 0.258). In conclusion, the present study found no evidence of alveolar–capillary membrane breaching following maximal exercise, neither in individuals with COPD nor in healthy matched controls.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4315-4327"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891265","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}
Abdulkerim Darendeli, Oscar Soto, Eugene Tunik, Mathew Yarossi
{"title":"Common inputs to motor units are modulated by force profile and muscle length.","authors":"Abdulkerim Darendeli, Oscar Soto, Eugene Tunik, Mathew Yarossi","doi":"10.1113/EP094031","DOIUrl":"10.1113/EP094031","url":null,"abstract":"<p><p>Groups of motor units receive common synaptic inputs from specialized networks of premotor neurons to produce movement. Here, we test whether common inputs received by motor units in the first dorsal interosseous are fixed or task-dependent during submaximal isometric contractions. Discharge times of motor units were identified and tracked across a set of conditions. Factor analysis identified a single motor unit mode that captured most of the covariation in the discharge rates of motor units, presumably reflecting common synaptic inputs. This was supported by the high correlation values between motor unit pairs from the same participant. Next, displacement analysis on the discharge rates of motor units was computed to capture the magnitude of departures from a monotonic control structure expected from fixed common inputs. For the same force profile, activity of motor units was limited to a set of discharge rate-time trajectories across trials, suggesting a constrained pattern of premotor inputs to motor units. Importantly, changes in force profile and muscle length modulated synaptic inputs to motor units, as observed in the divergent rate-time trajectories of motor units and high displacement values. These findings highlight that common input is a key feature in the neural control of motor units and is subject to substantial modulation. The composition of inputs to motor units depends on the force profile and muscle length, and the system relies on reusing a common input structure when performing the same task.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4876-4893"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857132","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":"S14G-humanin attenuates renal ischaemia-reperfusion injury, potentially through activation of STAT3 and ERK1/2 signalling pathways in rats.","authors":"Leyla Abueid, Ahmet Faruk Torun, Ezgi Golal, Nuray Acar, Filiz Basrali","doi":"10.1113/EP094006","DOIUrl":"10.1113/EP094006","url":null,"abstract":"<p><p>Renal ischaemia-reperfusion (I/R) injury leads to acute tubular necrosis and renal failure, triggering pathological mechanisms including inflammation, reactive oxygen species generation, apoptosis and mitochondrial dysfunction. The mitochondrial peptide humanin (HN), known to possess anti-apoptotic and anti-inflammatory properties, has been shown to counteract oxidative stress and restore mitochondrial function. This study aimed to investigate the effects of S14G-humanin (humanin G, HNG) on renal I/R injury. Sprague-Dawley male rats were divided into four groups (n = 48): (1) Sham, (2) I/R, (3) HNG-Sham, and (4) HNG-I/R. In I/R groups, renal artery ligation was performed for 45 min followed by 24-h reperfusion. HNG (2 mg/kg, i.v.) was administered 10 min before reperfusion. Urine was collected during reperfusion, and the experiment was terminated by collecting blood and tissue samples. Blood urea nitrogen and serum creatinine levels were elevated in the I/R group and were not affected by HNG treatment. Glutathione level and superoxide dismutase activity, which were diminished in the I/R group, were significantly restored following HNG administration. Myeloperoxidase activity and malondialdehyde levels were significantly decreased in HNG-I/R group compared to the I/R group. ATP levels and mitochondrial complex I activity were significantly increased in the HNG-I/R group compared to I/R. The percentage of apoptotic cells, markedly increased in I/R, was significantly reduced in HNG-I/R. Signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation also increased in HNG-I/R rats compared to I/R animals. HNG mitigates renal I/R injury by attenuating oxidative stress, inflammation and apoptosis while enhancing antioxidant capacity and mitochondrial function, through STAT3 and/or ERK1/2 activation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4915-4927"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863066","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}
Mahdiyeh Farahani, Abbas Ali Gaeini, Alireza Ghardashi Afousi, Mahboobeh Borjian Fard
{"title":"FGF21/sirtuin 1 axis mediates the cardioprotective effects of high-intensity interval training against doxorubicin-induced cardiotoxicity by reducing inflammatory and oxidative stress","authors":"Mahdiyeh Farahani, Abbas Ali Gaeini, Alireza Ghardashi Afousi, Mahboobeh Borjian Fard","doi":"10.1113/EP093527","DOIUrl":"10.1113/EP093527","url":null,"abstract":"<p>Doxorubicin (DOX) is a potent anthracycline chemotherapeutic agent, but its clinical use is limited by cumulative cardiotoxicity. Exercise, particularly high-intensity interval training (HIIT), has emerged as an effective non-pharmacological strategy to counteract chemotherapy-induced cardiac injury. However, the molecular mechanisms underlying the cardioprotective effects of HIIT remain unclear. This study aimed to determine whether HIIT attenuates DOX-induced cardiotoxicity via activation of the fibroblast growth factor 21 (FGF21)/sirtuin 1 (SIRT1) signalling pathway in rats. Thirty-three male Wistar rats (200–250 g) were randomly assigned to three groups (<i>n</i> = 11 each): control (CONTROL), DOX-treated sedentary (DOX-Sed) and DOX-treated HIIT (DOX-HIIT). DOX-induced cardiotoxicity was induced by intraperitoneal DOX injections (12 mg/kg cumulative dose over 12 days). After confirmation of cardiac dysfunction by echocardiography, the DOX-HIIT group completed an 8 week treadmill HIIT programme (three sessions per week, five intervals of 4 min at 85%–90% of maximal O<sub>2</sub> uptake separated by 2 min at 50%–60% of maximal O<sub>2</sub> uptake). Cardiac function, oxidative stress markers, inflammatory cytokines, plasma levels of FGF21 and protein expression of FGFR1 and the SIRT1/AMPK/Nrf2 pathway were assessed. HIIT improved survival (81.8% vs. 63.6% in DOX-Sed), prevented weight loss and ameliorated left ventricular systolic dysfunction, as evidenced by increased ejection fraction and fractional shortening (<i>P</i> < 0.05). HIIT reduced cardiac interleukin-6, tumor necrosis factor-α, interleukin-1β and malondialdehyde levels while elevating antioxidant enzyme activities. Mechanistically, HIIT increased plasma FGF21 and phosphorylated FGFR1 and upregulated SIRT1, LKB1 and phosphorylated AMPK, leading to activation of the Nrf2/HO-1 antioxidant pathway. Therefore, HIIT-induced FGF21 has a potential therapeutic effect on cardiac function in DOX-induced cardiotoxicity through activation of the FGF21/SIRT1/LKB1/AMPK/Nrf2/HO-1 signalling pathway.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4409-4420"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683910","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}
Alberto E. Minetti, Gaspare Pavei, Damian M. Bailey
{"title":"Celebrating Rodolfo Margaria and applied physiology in Milan","authors":"Alberto E. Minetti, Gaspare Pavei, Damian M. Bailey","doi":"10.1113/EP093979","DOIUrl":"10.1113/EP093979","url":null,"abstract":"<p>This Editorial celebrates the convergence in Milan of three events of special significance to the Italian physiology community and to The Physiological Society: the unveiling of a Blue Plaque honouring Professor Rodolfo Margaria's seminal contributions; the opening of celebrations marking the 150th Anniversary of The Physiological Society; and the biennial conference Lavori in Corso (Work in Progress) 2026, a meeting dedicated to applied physiology that has recently expanded its international reach.</p><p>Introduced by The Physiological Society, Blue Plaques ‘honour outstanding physiologists who have contributed to the advancement of the discipline through their discoveries while leaving a legacy beyond their lifetime’ (The Physiological Society, <span>2026</span>). They also create a lasting physical link between the scientist being celebrated and the place in which much of their most influential work was conceived and conducted. In this case, that place is the former Institute of Physiology at the University of Milan in Italy. It was therefore a fitting tribute to Italian physiology that, on 23 January 2026, the first international Blue Plaque awarded by The Physiological Society outside the UK and Ireland was unveiled in Milan (Figure 1).</p><p>Rodolfo Margaria (1901–1983) obtained his medical degree in 1924 and his Teaching Habilitation (Docenza) in (Human) Experimental Physiology in 1928. His intellectual training was unusually broad, spanning chemistry, biochemistry, biophysics, thermodynamics and physiology. His academic career began in Ferrara, where he was appointed Professor of Physiology in 1934, before moving to Milan, where most of his academic activity was based between 1938 and 1972. Extended periods at leading international laboratories, including at University College London, Harvard University, the Kaiser Wilhelm Institute in Heidelberg and Yale University, allowed him to interact with leading figures in physiology, including A. V. Hill, himself later honoured with a Blue Plaque by The Physiological Society.</p><p>The first decades of the 20th century were decisive in shaping Margaria's scientific interests and his distinctively multidisciplinary vision of applied physiology. The term had already appeared in textbooks by Samson Wright in the UK and Best and Taylor in the USA (Tipton, <span>2016</span>) and was defined by Dill (1939) as ‘muscular exercise being performed at the work or performance site, including fatigue and training, blood changes, effects of age, high environmental temperatures, and the influences of low and high partial pressures of oxygen’. Many of Margaria's own recurring themes, encompassing altitude, aviation, gravity, space, diving, swimming, walking, running, skiing, phonation, sport, ergonomics and ageing, map closely onto, and in some cases extend beyond, this early definition. They reveal a scientist willing to move across disciplinary boundaries while retaining a common physiological logic and met","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4266-4269"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721160","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}
Munevver Gizem Hekim, Nalan Kaya Tektemur, Mete Ozcan
{"title":"Humanin ameliorates diabetes-induced testicular damage in a streptozotocin-induced mouse model.","authors":"Munevver Gizem Hekim, Nalan Kaya Tektemur, Mete Ozcan","doi":"10.1113/EP093912","DOIUrl":"10.1113/EP093912","url":null,"abstract":"<p><p>Diabetes mellitus is a major metabolic disorder closely associated with oxidative stress and male reproductive dysfunction. Humanin, a mitochondria-derived peptide, has been reported to exert cytoprotective, anti-apoptotic and antioxidant effects in various disease models; however, its role in diabetes-induced testicular damage remains unclear. This study aimed to investigate the effects of humanin on oxidative stress parameters in seminal vesicle fluid and histopathological alterations in testicular tissue in a streptozotocin (STZ)-induced diabetic mouse model. A total of 40 adult male Balb/C mice were randomly assigned into four groups: Control, Humanin (HN), STZ, and STZ+HN (n = 10 per group). Diabetes was induced via intraperitoneal administration of STZ (150 mg/kg). Humanin (4 mg/kg) was administered intraperitoneally for 15 days following diabetes induction. Total antioxidant status (TAS), total oxidant status (TOS), and glutathione (GSH) levels in seminal vesicle fluid were measured using ELISA. Testicular tissues were evaluated histopathologically and histomorphometrically. STZ-induced diabetes resulted in a significant decrease in TAS and GSH levels and an increase in TOS levels in seminal vesicle fluid (P < 0.05). Humanin treatment significantly increased TAS and GSH levels while reducing TOS levels compared to the STZ group (P < 0.05). Histopathological analysis demonstrated seminiferous tubule degeneration, germ cell loss, interstitial oedema, and vascular congestion in diabetic mice, whereas these alterations and associated histomorphometric abnormalities were significantly ameliorated following humanin treatment. Humanin attenuated diabetes-induced oxidative imbalance and testicular histopathological damage in STZ-induced diabetic mice. These findings suggest that humanin may exert protective effects against diabetes-associated testicular injury. Further studies are required to elucidate the underlying molecular mechanisms and validate these findings in broader experimental settings.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4498-4506"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430289","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}
Veera Puumalainen, Anni Maja, Tia-Marje Korhonen, Tuuli A Nissinen, Eero Hulkko, Janne A Ihalainen, Maarit Lehti, Sira Karvinen
{"title":"Ovarian hormone loss modifies the nucleic acid cargo of circulating extracellular vesicles and skeletal muscle metabolism after acute exercise in rats.","authors":"Veera Puumalainen, Anni Maja, Tia-Marje Korhonen, Tuuli A Nissinen, Eero Hulkko, Janne A Ihalainen, Maarit Lehti, Sira Karvinen","doi":"10.1113/EP094085","DOIUrl":"10.1113/EP094085","url":null,"abstract":"<p><p>Loss of ovarian hormones (i.e., menopause) leads to negative effects on metabolic health. While exercise offers significant benefits, it seems to be insufficient to completely reverse these changes. The mechanisms by which exercise conveys the effects throughout the body are still poorly understood. Extracellular vesicles (EVs) are released into circulation during exercise. EVs carry small non-coding RNAs (sRNAs), such as microRNAs (miRs), which are proposed as mediators of the effects of exercise. We have previously shown that the miR response to acute exercise of EVs and high-density lipoprotein (HDL) is diminished in postmenopausal women with low oestrogen levels, which we were able to replicate here also in a rat model. In this study, we examined the effect of loss of ovarian hormones and acute exercise in the sRNA cargo of EV and HDL particles in female rats. We show for the first time that loss of ovarian hormones affects specifically the nucleic acid cargo of circulating EVs. We further show that the oestrogen responsive miRs regulate anaerobic glycolytic pathway. Finally, we demonstrate that the loss of ovarian hormones leads to higher anaerobic energy production during an acute bout of exercise, implicating an inferior ability to sustain aerobic energy production during exercise.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4578-4619"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705948","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}