Helia G Megowan, Madeline Luu, Adam Shuaib, Kaitlyn B Augienello, Adam C Fries, Jake Searcy, Hans C Dreyer
{"title":"A semi-automated pipeline for quantitation of Pax7+, myonuclei, and cross-sectional area by fiber type.","authors":"Helia G Megowan, Madeline Luu, Adam Shuaib, Kaitlyn B Augienello, Adam C Fries, Jake Searcy, Hans C Dreyer","doi":"10.14814/phy2.71097","DOIUrl":"10.14814/phy2.71097","url":null,"abstract":"<p><p>Manual analysis of skeletal muscle cross-sections is time-consuming and subject to error and user bias. To overcome these limitations, we developed and validated a semi-automated, quantitative, and reproducible image-analysis pipeline specifically tailored to quantify Pax7+ satellite cells, myonuclei, and cross-sectional area by fiber type. The workflow combines Fiji/ImageJ-based image preprocessing with CellProfiler, Cellpose, and a custom Python script to process and analyze immunohistological images of muscle tissue cross-sections. Outcomes include Pax7+ satellite cells and myonuclei quantified per fiber by fiber type, along with cross-sectional area, perimeter, and fiber type classification. This semi-automated approach provides a robust and efficient platform for high-throughput analysis of muscle tissue cross-sections from large datasets.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 18","pages":"e71097"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behnaz Afrashteh, Steafan Khan, Rabeya Zinnat Adury, Damiano Angoli, Zachary C Danziger
{"title":"Early urodynamic profiles predict lower urinary tract recovery after spinal cord injury in female rats.","authors":"Behnaz Afrashteh, Steafan Khan, Rabeya Zinnat Adury, Damiano Angoli, Zachary C Danziger","doi":"10.14814/phy2.71101","DOIUrl":"10.14814/phy2.71101","url":null,"abstract":"<p><p>Bladder dysfunction is a major complication after spinal cord injury (SCI) and effective treatment remains challenging. Neurogenic bladder can be difficult to treat because of its heterogeneous and dynamic symptoms. We aimed to (1) characterize heterogeneity in bladder recovery from acute to chronic phases and (2) predict chronic urinary function using early urodynamic parameters. We performed continuous longitudinal urodynamic monitoring in 10 complete T9 SCI and 10 control rats over 4 weeks. A novel metabolic cage system enabled 24/7 tracking of voiding behavior. Key parameters, including voiding efficiency (VE), post-void residual (PVR), and ureter flow rate (UFR), were measured continuously throughout recovery. Unsupervised clustering identified three distinct spinally mediated reflexive voiding phenotypes in the chronic phase (days 20-30), defined by VE and PVR: good (robust efficient voiding), moderate (partial voiding efficiency), and poor (minimal voiding efficiency). No single acute-phase urodynamic parameter (3-10 days post-injury) differed significantly between phenotypes. In contrast, multivariate generalized linear models incorporating parameter interactions, particularly VV × VE and UFR × VE<sup>2</sup>, predicted chronic phenotype with high accuracy (R<sup>2</sup> = 0.90, p < 0.001). These findings underscore the prognostic importance of interactions among early urodynamic features in determining the severity of long-term neurogenic bladder outcomes after SCI and identify a critical window for individualized intervention.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 17","pages":"e71101"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Vaping causes an acute BMI-dependent change in pulmonary blood flow\".","authors":"","doi":"10.14814/phy2.71109","DOIUrl":"10.14814/phy2.71109","url":null,"abstract":"","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 18","pages":"e71109"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saloni Agrawal, Kenneth M Fifer, Samira S Farouk, Joshua L Rein
{"title":"Urine electrolytes guide treatment of Gitelman syndrome and recurrent syncope-A case report.","authors":"Saloni Agrawal, Kenneth M Fifer, Samira S Farouk, Joshua L Rein","doi":"10.14814/phy2.71043","DOIUrl":"10.14814/phy2.71043","url":null,"abstract":"<p><p>Syncope is a common reason for inpatient admission. Few case studies describe an association between syncope and Gitelman syndrome (GS). Herein, we present a case of a woman with hypokalemia and recurrent syncope which eventually led to a diagnosis of GS. A physiologic approach to urine electrolyte interpretation informed clinical decisions to diagnose and manage complications associated with GS. Genetic testing for renal electrolyte transport-related gene mutations among patients with recurrent syncope and electrolyte abnormalities may be diagnostic.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 18","pages":"e71043"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Armando J Aguero, Connor J Doherty, Paolo B Dominelli
{"title":"Greater muscle mass does not affect peripheral hypercapnic chemosensitivity during exercise in healthy adults.","authors":"Armando J Aguero, Connor J Doherty, Paolo B Dominelli","doi":"10.14814/phy2.71102","DOIUrl":"10.14814/phy2.71102","url":null,"abstract":"<p><p>Peripheral hypercapnic chemosensitivity (PHC) is the ventilatory response to a brief rise in arterial carbon dioxide tension. PHC is known to increase at the onset of exercise, with no further increases with progressive exercise intensity. The mechanisms for this augmentation remain unclear but may involve central command. We examined whether PHC scales with active muscle mass by comparing small-muscle (rhythmic handgrip, RHG), intermediate-muscle (single-leg extension, SLE), and large/whole-body (cycling, BIKE) exercise. Twenty-two healthy adults (n = 11 females) performed RHG, SLE, and BIKE exercise. PHC was measured before and during exercise using four trials, each consisting of two inhalations of 10% carbon dioxide. All exercise modalities produced a significant increase in PHC from rest. During exercise, SLE and BIKE (0.895 ± 0.388 and 1.028 ± 0.460 L·min<sup>-1</sup>·mmHg<sup>-1</sup>, respectively) elicited significantly greater PHC than RHG (0.683 ± 0.247 L·min<sup>-1</sup>·mmHg<sup>-1</sup>) (p = 0.037 and 0.015, respectively), while SLE and BIKE were not different (p = 0.263). Exercise sensitizes PHC regardless of recruited muscle mass, but augmentation does not scale linearly with muscle mass. As PHC increased with recruitment up to SLE, with no further increase during BIKE. These findings suggest that the augmentation of PHC is more closely associated with the transition to exercise, although the present exploratory study cannot determine the mechanism(s) responsible.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 17","pages":"e71102"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ASXL1 in proinflammatory macrophages attenuates inflammatory activation and macrophage-mediated renal tubular epithelial cell damage in acute kidney injury.","authors":"Yoshiyasu Ogura, Takehito Sugasawa, Masaomi Nangaku, Imari Mimura","doi":"10.14814/phy2.71119","DOIUrl":"https://doi.org/10.14814/phy2.71119","url":null,"abstract":"<p><p>Macrophages are major contributors to inflammatory responses in acute kidney injury (AKI) and rapidly alter their gene expression through epigenetic regulation. This study focused on ASXL1, a chromatin modifier regulating histone marks consisting of H3K27me3 (repressive) and H3K4me3 (activating) in M1 macrophages. We found that ASXL1-positive M1 macrophages were significantly increased in the unilateral ischemia-reperfusion injury kidneys of male mice in the acute phase. In cultured M1 macrophages, RNA sequencing revealed that Asxl1 knockdown upregulated inflammatory response genes such as Il6 and Il1b. Conversely, the expression of anti-apoptotic genes Csf3 and Lcn2 was suppressed, and pathways related to interleukin-17 signaling and Fcγ receptor-dependent phagocytosis were downregulated. In co-culture experiments, Asxl1 silencing in M1 macrophages induced more severe apoptosis and reduced proliferation of mouse renal cortical tubular cells. Mechanistically, chromatin immunoprecipitation analysis demonstrated that Asxl1 knockdown significantly decreased H3K27me3 levels at the Il6 and Il1b promoter regions and H3K4me3 levels at the Csf3 and Lcn2 promoter regions in M1 macrophages. These findings indicate that ASXL1 suppresses excessive inflammatory cytokine expression and preserves anti-apoptotic activity through histone modifications, while maintaining phagocytic capacity in M1 macrophages. ASXL1 in M1 macrophages thus attenuates inflammatory activation and macrophage-mediated renal tubular cell damage in AKI.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 19","pages":"e71119"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electroacupuncture pretreatment alleviates myocardial ischemia/reperfusion-induced lung injury by inhibiting the expression of HMGB1/RAGE in male rats.","authors":"Chenlong Xie, Jiaojiao Zhang, Yujiao Zhang, Hao Chi, Yue Yong, Jiangang Song","doi":"10.14814/phy2.71066","DOIUrl":"10.14814/phy2.71066","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion (MI/R)-induced lung injury is a major pulmonary complication after cardiac surgery. We aimed to verify this phenomenon in rats and to investigate whether electroacupuncture (EA) pretreatment at bilateral Feishu (BL13) and Zusanli (ST36) acupoints (once daily for 3 days) exerts protective effects. In an MI/R-induced lung injury model in SD rats, EA pretreatment significantly improved lung function and reduced pathological damage (p < 0.05 and p < 0.01, respectively). It also attenuated the pulmonary inflammatory response and decreased the expression of high mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) (p < 0.05 or p < 0.01). Intratracheal administration of recombinant HMGB1 (rHMGB1) to upregulate lung HMGB1/RAGE signaling impaired the pulmonary protective effect of EA (p < 0.05, p < 0.01). Together, these findings demonstrate that EA pretreatment mitigates MI/R-induced lung injury by inhibiting HMGB1/RAGE signaling.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 18","pages":"e71066"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine Kiely, Eamonn O'Connor, Donal O'Shea, Simon Green, Mikel Egaña
{"title":"Exercise training improves cardiorespiratory fitness and oxygen uptake kinetics to a similar extent in early and late middle-aged adults with type 2 diabetes.","authors":"Catherine Kiely, Eamonn O'Connor, Donal O'Shea, Simon Green, Mikel Egaña","doi":"10.14814/phy2.71107","DOIUrl":"10.14814/phy2.71107","url":null,"abstract":"<p><p>To determine the exercise training-induced changes in peak oxygen uptake (V̇O<sub>2peak</sub>) and oxygen uptake kinetics in early and late middle-aged adults with uncomplicated type 2 diabetes (T2D). Fifty inactive adults with T2D (16 females) were stratified into late middle-aged (60-70 years) and early middle-aged (37-59 years) cohorts and assigned to exercise training or control groups: late middle-aged training (TR-LMA, n = 12), late middle-aged control (CON-LMA, n = 9), early middle-aged training (TR-EMA, n = 17), or early middle-aged control (CON-EMA, n = 12). Training groups completed a supervised 12-week aerobic and resistance programme. V̇O<sub>2peak</sub> was assessed during incremental cycling while the time constant of the primary phase of oxygen uptake kinetics (τV̇O<sub>2p</sub>), blood pressure, and cardiac output (inert gas rebreathing) were measured during submaximal cycling before and after the intervention. V̇O<sub>2peak</sub> increased and τV̇O<sub>2</sub>p decreased (p < 0.001) in both training groups: TR-LMA (25.6 ± 5.7 to 28.2 ± 5.3 mL·kg<sup>-1</sup>·min<sup>-1</sup>; 39.8 ± 6.5 to 35.0 ± 7.3 s) and TR-EMA (25.3 ± 5.3 to 28.1 ± 5.3 mL·kg<sup>-1</sup>·min<sup>-1</sup>; 43.3 ± 9.0 to 33.8 ± 8.2 s), with no between-group differences. No changes occurred in CON-LMA or CON-EMA, and cardiovascular responses remained unchanged following training. Combined aerobic and resistance training similarly improved V̇O<sub>2peak</sub> and τV̇O<sub>2p</sub> in early and late middle-aged adults with T2D. The improvements in V̇O<sub>2</sub> kinetics appear to occur independently of systemic cardiovascular adaptations.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 18","pages":"e71107"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influence of lactate on the active force produced in skinned psoas and soleus muscle fibers from female rabbits.","authors":"Shiho Kunimatsu, Atsuki Fukutani, Tadao Isaka","doi":"10.14814/phy2.71140","DOIUrl":"https://doi.org/10.14814/phy2.71140","url":null,"abstract":"<p><p>Lactate has been recognized as an energy source, suggesting its potential use as an ergogenic supplement. However, its effect on muscle contraction remains unclear. This study examined the effect of lactate on muscle active force using skinned fibers. Rabbit psoas (N = 8) and soleus (N = 5) fibers were activated using three activating solutions as follows: (1) activating solution, pH 7.0 (Normal); (2) activating solution with lactate, pH 6.0 (Lactate pH 6.0); (3) activating solution with lactate, pH 7.0 (Lactate pH 7.0). Under these conditions, the fibers were isometrically activated at an average sarcomere length of 2.4 μm, and their length was subsequently shortened by 20%. Statistical test revealed that although the muscle active force (both isometric and concentric force) in Lactate pH 6.0 was smaller than in Normal and Lactate pH 7.0, no significant difference in muscle force was observed between Normal and Lactate pH 7.0. These patterns were consistent in both psoas and soleus fibers. These findings indicate that lactate ions do not affect muscle active force whereas a low-pH environment (acidosis) induces significant muscle force depression.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 19","pages":"e71140"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monika Lucia Bayer, Kenneth Hudlebusch Mertz, Asta Skovgaard Eriksen, Michael Kjaer, Stig Peter Magnusson, Frederik Hvid Linden, Rene Brüggebusch Svensson
{"title":"Early and persisting increase in fat content after human muscle strain injuries in adults.","authors":"Monika Lucia Bayer, Kenneth Hudlebusch Mertz, Asta Skovgaard Eriksen, Michael Kjaer, Stig Peter Magnusson, Frederik Hvid Linden, Rene Brüggebusch Svensson","doi":"10.14814/phy2.71086","DOIUrl":"10.14814/phy2.71086","url":null,"abstract":"<p><p>Acute muscle strain injuries belong to the most frequent sports injuries with high recurrence rates. Biopsies obtained from previously strain-injured muscles showed fat intra- and intermuscular, but quantification of fat content in the entire muscle volume following a strain injury has not been performed previously. The aim of the study was to evaluate fat fraction in the injured and the contralateral, uninjured muscle acutely, and 3- and 12-months after a strain injury. DIXON fat fraction was analyzed acutely after the injury, 3- and 12-months post injury in the injured and the contralateral, healthy muscle in 29 individuals with an ultrasound verified strain injury in either the calf or the hamstrings. There was a significant increase in fat content 3 and 12 months post injury in the injured, but not in the contralateral, uninjured muscles. There was a significant negative correlation between the increase in fat fraction and loss of muscle mass, and a significant positive correlation between the enlargement of the aponeurosis and the amount of fat in the injured muscles. Strain injuries lead to a rise in fat fraction in muscles from healthy, sports active individuals. The increased fat fraction appears permanent as fat accumulation in the muscle after the injury was not reversed after 12 months.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"14 17","pages":"e71086"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}