Pub Date : 2025-12-17eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1741426
Amjad Islam Amjad, Bisma Sajjad Sheikh, Sarfraz Aslam
{"title":"Biological resilience as a crucial determinant in preventing age-associated chronic diseases.","authors":"Amjad Islam Amjad, Bisma Sajjad Sheikh, Sarfraz Aslam","doi":"10.3389/fphys.2025.1741426","DOIUrl":"10.3389/fphys.2025.1741426","url":null,"abstract":"","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1741426"},"PeriodicalIF":3.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12753462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1651151
Jiaqi Zou, Riya Yerramilli, Tolunay Beker Aydemir
This review provides a comprehensive analysis of manganese (Mn) metabolism and its regulatory roles across multiple biological levels. By examining Mn homeostasis mechanisms, including Mn absorption, excretion, distribution, and transport across the intestines, liver, and brain, this work highlights the integrative nature of Mn physiology. Additionally, it explores routes of Mn overexposure and the consequences of Mn dysregulation on various organ systems, with a focus on neurotoxicity, as well as the genetic and environmental factors that contribute to Mn homeostasis. This review synthesizes insights into metal transporters to advance our understanding of their roles in maintaining systemic and brain Mn homeostasis under healthy conditions and their contribution to Mn dysregulation in disease states, particularly neurological disorders. By focusing on Mn transport and regulation across multiple physiological systems and its impact on health and disease, we aim to bridge the gap between molecular-level processes and whole-body physiology.
{"title":"Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.","authors":"Jiaqi Zou, Riya Yerramilli, Tolunay Beker Aydemir","doi":"10.3389/fphys.2025.1651151","DOIUrl":"10.3389/fphys.2025.1651151","url":null,"abstract":"<p><p>This review provides a comprehensive analysis of manganese (Mn) metabolism and its regulatory roles across multiple biological levels. By examining Mn homeostasis mechanisms, including Mn absorption, excretion, distribution, and transport across the intestines, liver, and brain, this work highlights the integrative nature of Mn physiology. Additionally, it explores routes of Mn overexposure and the consequences of Mn dysregulation on various organ systems, with a focus on neurotoxicity, as well as the genetic and environmental factors that contribute to Mn homeostasis. This review synthesizes insights into metal transporters to advance our understanding of their roles in maintaining systemic and brain Mn homeostasis under healthy conditions and their contribution to Mn dysregulation in disease states, particularly neurological disorders. By focusing on Mn transport and regulation across multiple physiological systems and its impact on health and disease, we aim to bridge the gap between molecular-level processes and whole-body physiology.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1651151"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12747974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1703100
Kang Ren, Zhendong Zhao, Lu Wu, Liyu Luo
Introduction: This randomized controlled trial aimed to compare the acute and sustained effects of tissue flossing (TF) versus dynamic stretching (DS) on hamstring muscle stiffness and flexibility in light volleyball (LVB) enthusiasts.
Methods: Thirty-seven participants were randomly assigned to TF, DS, or placebo groups. Muscle stiffness was evaluated using shear-wave elastography, measuring Young's modulus at the distal and proximal regions of the biceps femoris long head and semitendinosus. Flexibility was assessed via passive knee extension (KE), straight leg raise (SLR), and forward flexion distance (FFD) at baseline, immediately post-intervention, and 30 min post-intervention.
Results: The results demonstrated that TF significantly reduced muscle stiffness compared to DS at the 30-min mark, particularly in the semitendinosus [distal: mean difference = -43.40 kPa, 95% CI (-80.65, -6.16), p = 0.007; proximal: -51.13 kPa, (-101.20, -1.05), p = 0.040]. However, no significant differences were observed between the TF and DS groups in flexibility outcomes (KE, SLR, or FFD) at any time point.
Discussion: These findings indicate that while TF offers a prolonged reduction in hamstring stiffness-suggesting potential benefits in injury prevention and prolonged performance-its effect on functional flexibility remains comparable to that of dynamic stretching. TF may serve as an effective warm-up intervention for athletes requiring sustained decreases in muscle stiffness during activities.
简介:本随机对照试验旨在比较组织牙线(TF)和动态拉伸(DS)对轻型排球(LVB)爱好者腘绳肌僵硬和柔韧性的急性和持续影响。方法:37名参与者被随机分为TF组、DS组和安慰剂组。使用剪切波弹性成像评估肌肉刚度,测量股骨二头肌长头和半腱肌远端和近端区域的杨氏模量。在基线、干预后立即和干预后30分钟,通过被动膝关节伸展(KE)、直腿抬高(SLR)和前屈距离(FFD)评估灵活性。结果:结果表明,在30分钟时,与DS相比,TF显著降低了肌肉僵硬度,尤其是半腱肌[远端:平均差值= -43.40 kPa, 95% CI (-80.65, -6.16), p = 0.007;近端:-51.13 kPa, (-101.20, -1.05), p = 0.040]。然而,在任何时间点,TF组和DS组在灵活性结果(KE, SLR或FFD)方面均未观察到显著差异。讨论:这些研究结果表明,虽然TF可以长期降低腘绳肌僵硬度,这表明在预防损伤和延长运动表现方面有潜在的好处,但它对功能柔韧性的影响仍然与动态拉伸相当。对于需要在活动中持续降低肌肉僵硬度的运动员来说,TF可以作为有效的热身干预。
{"title":"Effects of tissue flossing and dynamic stretching on hamstring stiffness and flexibility in light volleyball enthusiasts: a randomized controlled trial.","authors":"Kang Ren, Zhendong Zhao, Lu Wu, Liyu Luo","doi":"10.3389/fphys.2025.1703100","DOIUrl":"10.3389/fphys.2025.1703100","url":null,"abstract":"<p><strong>Introduction: </strong>This randomized controlled trial aimed to compare the acute and sustained effects of tissue flossing (TF) versus dynamic stretching (DS) on hamstring muscle stiffness and flexibility in light volleyball (LVB) enthusiasts.</p><p><strong>Methods: </strong>Thirty-seven participants were randomly assigned to TF, DS, or placebo groups. Muscle stiffness was evaluated using shear-wave elastography, measuring Young's modulus at the distal and proximal regions of the biceps femoris long head and semitendinosus. Flexibility was assessed via passive knee extension (KE), straight leg raise (SLR), and forward flexion distance (FFD) at baseline, immediately post-intervention, and 30 min post-intervention.</p><p><strong>Results: </strong>The results demonstrated that TF significantly reduced muscle stiffness compared to DS at the 30-min mark, particularly in the semitendinosus [distal: mean difference = -43.40 kPa, 95% CI (-80.65, -6.16), p = 0.007; proximal: -51.13 kPa, (-101.20, -1.05), p = 0.040]. However, no significant differences were observed between the TF and DS groups in flexibility outcomes (KE, SLR, or FFD) at any time point.</p><p><strong>Discussion: </strong>These findings indicate that while TF offers a prolonged reduction in hamstring stiffness-suggesting potential benefits in injury prevention and prolonged performance-its effect on functional flexibility remains comparable to that of dynamic stretching. TF may serve as an effective warm-up intervention for athletes requiring sustained decreases in muscle stiffness during activities.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1703100"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12747938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1690915
Beatrice De Maria, Luca Ranucci, Clara Gino, Aida Zulueta, Monica Parati, Azzurra Cesoni Marcelli, Lorenza Chiara Zingale, Riccardo Sideri, Laura Adelaide Dalla Vecchia, Francesca Perego
Background: Regulation of vascular permeability in hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is key to understanding the disease, but the role of the autonomic nervous system (ANS) in this mechanism remains unclear.
Purpose: The aim of this study was to compare the cardiovascular autonomic response to the head-up tilt test (HUTT) in HAE-C1INH patients and matched healthy controls (HCs).
Methods: HAE-C1INH patients were evaluated during a 1-week symptom-free period. Electrocardiogram (ECG) and beat-to-beat non-invasive arterial blood pressure (BP) were recorded in the supine position (REST) and during 70° tilt (TILT). Heart rate and systolic BP (SBP) variability indices were derived. Variance (σ2SBP) and low-frequency power (LFSBP) of SBP variability were used as markers of sympathetic vascular control.
Results: Twenty-five HAE-C1INH patients [13 male individuals, 44 (28.8-57.5) years] and 25 HCs [13 male individuals, 44 (30.8-54.3) years] were enrolled and divided into <45 and ≥45 age groups. Eighteen patients were on long-term prophylaxis (LTP). In the younger group, LFSBP increased from REST to TILT in both groups, with no differences. In older subjects, HAE-C1INH patients showed higher σ2SBP [21.2 (9.3-59.2) vs. 7.5 (1.9-14.6) mmHg2] and a greater LFSBP increase [9.4 (4.6-22.4) vs. 0.9 (0.2-7.6) mmHg2] than HCs during TILT, suggesting sympathetic hyperactivation. No significant group differences in cardiac autonomic control were observed during REST or TILT, regardless of age. Findings in the LTP subgroup mirrored those of the full cohort.
Conclusion: Older HAE-C1INH patients display altered vascular autonomic regulation, with an exaggerated sympathetic response during orthostatic stress. Further studies are needed to assess the role of LTP in these alterations.
{"title":"Cardiac and vascular autonomic control in patients with hereditary angioedema.","authors":"Beatrice De Maria, Luca Ranucci, Clara Gino, Aida Zulueta, Monica Parati, Azzurra Cesoni Marcelli, Lorenza Chiara Zingale, Riccardo Sideri, Laura Adelaide Dalla Vecchia, Francesca Perego","doi":"10.3389/fphys.2025.1690915","DOIUrl":"10.3389/fphys.2025.1690915","url":null,"abstract":"<p><strong>Background: </strong>Regulation of vascular permeability in hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is key to understanding the disease, but the role of the autonomic nervous system (ANS) in this mechanism remains unclear.</p><p><strong>Purpose: </strong>The aim of this study was to compare the cardiovascular autonomic response to the head-up tilt test (HUTT) in HAE-C1INH patients and matched healthy controls (HCs).</p><p><strong>Methods: </strong>HAE-C1INH patients were evaluated during a 1-week symptom-free period. Electrocardiogram (ECG) and beat-to-beat non-invasive arterial blood pressure (BP) were recorded in the supine position (REST) and during 70° tilt (TILT). Heart rate and systolic BP (SBP) variability indices were derived. Variance (σ<sup>2</sup> <sub>SBP</sub>) and low-frequency power (LF<sub>SBP</sub>) of SBP variability were used as markers of sympathetic vascular control.</p><p><strong>Results: </strong>Twenty-five HAE-C1INH patients [13 male individuals, 44 (28.8-57.5) years] and 25 HCs [13 male individuals, 44 (30.8-54.3) years] were enrolled and divided into <45 and ≥45 age groups. Eighteen patients were on long-term prophylaxis (LTP). In the younger group, LF<sub>SBP</sub> increased from REST to TILT in both groups, with no differences. In older subjects, HAE-C1INH patients showed higher σ<sup>2</sup> <sub>SBP</sub> [21.2 (9.3-59.2) vs. 7.5 (1.9-14.6) mmHg<sup>2</sup>] and a greater LF<sub>SBP</sub> increase [9.4 (4.6-22.4) vs. 0.9 (0.2-7.6) mmHg<sup>2</sup>] than HCs during TILT, suggesting sympathetic hyperactivation. No significant group differences in cardiac autonomic control were observed during REST or TILT, regardless of age. Findings in the LTP subgroup mirrored those of the full cohort.</p><p><strong>Conclusion: </strong>Older HAE-C1INH patients display altered vascular autonomic regulation, with an exaggerated sympathetic response during orthostatic stress. Further studies are needed to assess the role of LTP in these alterations.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/study/NCT06408805?cond=Hereditary%20Angioedema&term=autonomic&rank=1.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1690915"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12747905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Accurately predicting sports injuries remains a significant challenge due to the complexity of factors involved, including anatomical structures and movement mechanics. Traditional approaches often rely on single data sources and fail to provide personalized risk assessments, limiting their effectiveness.
Methodology: This study introduces a multimodal approach to predicting sports injuries by combining high resolution computed tomography (CT) scans with biomechanical data from motion capture systems, wearable inertial measurement units (IMUs), and force-sensitive insoles. CT images were denoised and contrast-enhanced before being analyzed with the Swin-UNet architecture, which captures both fine structural details and broader spatial patterns. At the same time, biomechanical signals such as joint movement, ground reaction forces, and loading patterns were processed using orthogonal component decomposition and analyzed with a Long Short-Term Memory (LSTM) network to capture changes over time. The results from both models were combined through a decision level fusion method, producing a single injury-risk score. By integrating anatomical and functional data, the framework provides a more accurate and timely assessment of injury risk, supporting early intervention and improved athlete safety.
Results: The proposed model demonstrated strong predictive performance, achieving an accuracy of 94%, precision of 91%, recall of 92%, and an F1 score of 91%. These results highlight the advantage of combining high resolution imaging with biomechanical measurements through an advanced deep learning framework, outperforming traditional methods.
Conclusion: By integrating CT imaging and biomechanical data within a Swin Unet based framework, this study offers a precise and personalized approach to sports injury prediction. The inclusion of real-time monitoring further enhances the practical value of the model, supporting early intervention and improving athlete safety and training efficiency.
{"title":"Multi modal fusion of medical imaging and biomechanical data using attention based swin-unet and LSTM for sports injury prediction.","authors":"Siyuan Li, Ziyu Hou, Kamran Amjad, Husnain Mushtaq","doi":"10.3389/fphys.2025.1687895","DOIUrl":"10.3389/fphys.2025.1687895","url":null,"abstract":"<p><strong>Background: </strong>Accurately predicting sports injuries remains a significant challenge due to the complexity of factors involved, including anatomical structures and movement mechanics. Traditional approaches often rely on single data sources and fail to provide personalized risk assessments, limiting their effectiveness.</p><p><strong>Methodology: </strong>This study introduces a multimodal approach to predicting sports injuries by combining high resolution computed tomography (CT) scans with biomechanical data from motion capture systems, wearable inertial measurement units (IMUs), and force-sensitive insoles. CT images were denoised and contrast-enhanced before being analyzed with the Swin-UNet architecture, which captures both fine structural details and broader spatial patterns. At the same time, biomechanical signals such as joint movement, ground reaction forces, and loading patterns were processed using orthogonal component decomposition and analyzed with a Long Short-Term Memory (LSTM) network to capture changes over time. The results from both models were combined through a decision level fusion method, producing a single injury-risk score. By integrating anatomical and functional data, the framework provides a more accurate and timely assessment of injury risk, supporting early intervention and improved athlete safety.</p><p><strong>Results: </strong>The proposed model demonstrated strong predictive performance, achieving an accuracy of 94%, precision of 91%, recall of 92%, and an F1 score of 91%. These results highlight the advantage of combining high resolution imaging with biomechanical measurements through an advanced deep learning framework, outperforming traditional methods.</p><p><strong>Conclusion: </strong>By integrating CT imaging and biomechanical data within a Swin Unet based framework, this study offers a precise and personalized approach to sports injury prediction. The inclusion of real-time monitoring further enhances the practical value of the model, supporting early intervention and improving athlete safety and training efficiency.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1687895"},"PeriodicalIF":3.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12740555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1683389
Shuaipeng Ma, Qing Liu, Qianqian Chen, Songqing Nie, Yulin Zhang, Gang Wu, Xuesong Wang
Objective: To investigate whether grape seed powders (GSP) contribute to growth-promoting in aquaculture, a comprehensive analysis of the effects of GSP on grass carp (Ctenopharyngodon idella) was performed.
Methods: Six hundred grass carp were divided into four groups, including the control and the low (100 mg/kg), middle (500 mg/kg), and high (1000 mg/kg) GSP-supplemented groups. The material composition, growth parameters, physiological/biochemical indexes, and muscle nutrition were analyzed.
Results: After feeding of 60 days, the weight gain rate, specific growth rate, and condition factor of grass carp significantly increased with GSP supplementation at low and middle levels in comparison to the blank control (P < 0.05). Additionally, the catalase activities in the gill and gut significantly elevated as dietary supplementation with GSP at the low and middle levels in comparison to the blank control (P < 0.05), while the interleukins' (IL-1β, IL-4, IL-6, IL-10, and IL-12) contents in the spleen significantly decreased (P < 0.05), suggesting an enhancement in antioxidant capacity activities and a reduction in inflammation levels after supplemental feeding with GSP. The total amino acids and total fatty acids in the blank control were equivalent to these in the low GSP-supplemented group, which were inconsistent with the upregulation of total amino acids and downregulation of total fatty acids in the middle and high GSP-supplemented groups. Furthermore, pathogenic bacteria in the gut (e.g., Enterobacter hormaechei and Enterobacter cloacae) were effectively inhibited in the GSP-supplemented groups, with significant correlations to the increased amino acid (Pro) and the decreased fatty acids (e.g., C16:1n7, C18:1n9c, C20:2n6, and C22:6n3) (P < 0.05).
Conclusion: Based on the results, we confirmed that dietary supplementation with procyanidin-rich GSP at a relative low level (100 mg/kg) was beneficial for the healthy aquaculture of grass carp.
{"title":"Effects of dietary supplementation with grape seed powders on growth performance and muscle nutrition of grass carp (<i>Ctenopharyngodon idella</i>) by gut microbiota mediation.","authors":"Shuaipeng Ma, Qing Liu, Qianqian Chen, Songqing Nie, Yulin Zhang, Gang Wu, Xuesong Wang","doi":"10.3389/fphys.2025.1683389","DOIUrl":"10.3389/fphys.2025.1683389","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether grape seed powders (GSP) contribute to growth-promoting in aquaculture, a comprehensive analysis of the effects of GSP on grass carp (<i>Ctenopharyngodon idella</i>) was performed.</p><p><strong>Methods: </strong>Six hundred grass carp were divided into four groups, including the control and the low (100 mg/kg), middle (500 mg/kg), and high (1000 mg/kg) GSP-supplemented groups. The material composition, growth parameters, physiological/biochemical indexes, and muscle nutrition were analyzed.</p><p><strong>Results: </strong>After feeding of 60 days, the weight gain rate, specific growth rate, and condition factor of grass carp significantly increased with GSP supplementation at low and middle levels in comparison to the blank control (<i>P</i> < 0.05). Additionally, the catalase activities in the gill and gut significantly elevated as dietary supplementation with GSP at the low and middle levels in comparison to the blank control (<i>P</i> < 0.05), while the interleukins' (IL-1<i>β</i>, IL-4, IL-6, IL-10, and IL-12) contents in the spleen significantly decreased (<i>P</i> < 0.05), suggesting an enhancement in antioxidant capacity activities and a reduction in inflammation levels after supplemental feeding with GSP. The total amino acids and total fatty acids in the blank control were equivalent to these in the low GSP-supplemented group, which were inconsistent with the upregulation of total amino acids and downregulation of total fatty acids in the middle and high GSP-supplemented groups. Furthermore, pathogenic bacteria in the gut (e.g., <i>Enterobacter hormaechei</i> and <i>Enterobacter cloacae</i>) were effectively inhibited in the GSP-supplemented groups, with significant correlations to the increased amino acid (Pro) and the decreased fatty acids (e.g., C16:1n7, C18:1n9c, C20:2n6, and C22:6n3) (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Based on the results, we confirmed that dietary supplementation with procyanidin-rich GSP at a relative low level (100 mg/kg) was beneficial for the healthy aquaculture of grass carp.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1683389"},"PeriodicalIF":3.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12740752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: The efficacy of nonsteroidal mineralocorticoid receptor blockers (MRBs) in inhibiting the progression of diabetic kidney disease (DKD) is well-known. However, MRB therapy often leads to hyperkalemia and remains a major concern. Recent studies suggest that combining potassium-retaining diuretics, renin-angiotensin system inhibitors, and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduces the incidence of hyperkalemia. However, how SGLT2i, specifically affecting the proximal tubule (PT), suppresses hyperkalemia is unclear. This study aimed to elucidate the interaction between the aldosterone (Ald)/mineralocorticoid receptor (MR) signaling pathway and SGLT2i specifically in the PT, focusing on the synergistic effects on PT sodium (Na+) and potassium (K+) transport activity.
Methods: We investigated the effects of Ald and SGLT2i on PT Na+ and K+ transporters. For PT Na+ transport function analysis, freshly isolated PTs were used to analyze luminal NHE activity and basolateral NBCe1 activity using 2',7'-bis(carboxyethyl)-5 (6)-carboxyfluorescein acetoxymethyl ester. A DKD model was established using spontaneously diabetic Torii (SDT) fatty rats. The model rats were randomly assigned to the following groups: esaxerenone (Esx) monotherapy and Esx + dapagliflozin (Dapa) therapy. We then evaluated histological parameters, K+ channel expression, and various biological parameters.
Results: Ald increased not only the activity of NBCe1 and NHE3 but also the expression of TWIK-1/Kcnk1 and TASK-2/Kcnk5. These stimulatory effects were completely suppressed by ESX. Rats treated with Ald alone exhibited hypertension, hyperinsulinemia, and severe kidney injury, which were ameliorated by ESX; however, these rats also presented with hyperkalemia. The ESX + Dapa therapy reduced the incidence of hyperkalemia and improved kidney injury compared to ESX alone. The expression of TWIK-1 and TASK-2 increased in rats continuously treated with Ald compared with that in control rats, whereas their expression decreased to control levels in rats continuously treated with ESX alone. TWIK-1 expression did not significantly decrease in rats continuously treated with ESX and Dapa compared with that in rats treated with ESX alone.
Discussion: The findings indicate that Ald stimulates Na+ transport via the MR in the PT and regulates the expression of K+ channel genes. The MRB and SGLT2i combination may mitigate MRB-induced hyperkalemia, potentially by regulating TWIK-1 expression and maintaining K+ homeostasis.
{"title":"Combined effect of esaxerenone and dapagliflozin on aldosterone-mediated sodium reabsorption and potassium excretion.","authors":"Motonobu Nakamura, Nobuhiko Satoh, Tomohito Mizuno, Mayuko Takagi, Shoko Horita, Masaomi Nangaku","doi":"10.3389/fphys.2025.1677518","DOIUrl":"10.3389/fphys.2025.1677518","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of nonsteroidal mineralocorticoid receptor blockers (MRBs) in inhibiting the progression of diabetic kidney disease (DKD) is well-known. However, MRB therapy often leads to hyperkalemia and remains a major concern. Recent studies suggest that combining potassium-retaining diuretics, renin-angiotensin system inhibitors, and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduces the incidence of hyperkalemia. However, how SGLT2i, specifically affecting the proximal tubule (PT), suppresses hyperkalemia is unclear. This study aimed to elucidate the interaction between the aldosterone (Ald)/mineralocorticoid receptor (MR) signaling pathway and SGLT2i specifically in the PT, focusing on the synergistic effects on PT sodium (Na<sup>+</sup>) and potassium (K<sup>+</sup>) transport activity.</p><p><strong>Methods: </strong>We investigated the effects of Ald and SGLT2i on PT Na<sup>+</sup> and K<sup>+</sup> transporters. For PT Na<sup>+</sup> transport function analysis, freshly isolated PTs were used to analyze luminal NHE activity and basolateral NBCe1 activity using 2',7'-bis(carboxyethyl)-5 (6)-carboxyfluorescein acetoxymethyl ester. A DKD model was established using spontaneously diabetic Torii (SDT) fatty rats. The model rats were randomly assigned to the following groups: esaxerenone (Esx) monotherapy and Esx + dapagliflozin (Dapa) therapy. We then evaluated histological parameters, K<sup>+</sup> channel expression, and various biological parameters.</p><p><strong>Results: </strong>Ald increased not only the activity of NBCe1 and NHE3 but also the expression of TWIK-1/<i>Kcnk1</i> and TASK-2/<i>Kcnk5</i>. These stimulatory effects were completely suppressed by ESX. Rats treated with Ald alone exhibited hypertension, hyperinsulinemia, and severe kidney injury, which were ameliorated by ESX; however, these rats also presented with hyperkalemia. The ESX + Dapa therapy reduced the incidence of hyperkalemia and improved kidney injury compared to ESX alone. The expression of TWIK-1 and TASK-2 increased in rats continuously treated with Ald compared with that in control rats, whereas their expression decreased to control levels in rats continuously treated with ESX alone. TWIK-1 expression did not significantly decrease in rats continuously treated with ESX and Dapa compared with that in rats treated with ESX alone.</p><p><strong>Discussion: </strong>The findings indicate that Ald stimulates Na<sup>+</sup> transport via the MR in the PT and regulates the expression of K<sup>+</sup> channel genes. The MRB and SGLT2i combination may mitigate MRB-induced hyperkalemia, potentially by regulating TWIK-1 expression and maintaining K<sup>+</sup> homeostasis.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1677518"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12738813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1709093
Wolfgang Schobersberger, Maarit Valtonen, Anika Köck, Sebastien Racinais, Yannis Pitsiladis, Panagiotis Verdoukas, Borja Muniz-Pardos, Rikhard Mäki-Heikkilä, Johanna K Ihalainen, Dominique Gagnon, Tobias Dünnwald
Background: The aim of this study was to describe the thermoregulatory responses of elite athletes during competitions and training of the international cross-country skiing FIS Scandinavian Cup in Finland, held under cold (subzero) ambient conditions.
Methods: The core and skin temperatures were continuously recorded during two competition formats-a 10-km race (n = 18; 10 m, 8 f) and a 20-km race (n = 14; 9 m, 5 f)-and during training (n = 11; 7 m, 4 f) using electronic temperature pills and temperature sensors fixed on the chest, arm, hand, and thigh, respectively. The heart rate and skiing speed were continuously recorded using heart rate monitors with integrated GPS technology. Ambient temperatures during the measuring period ranged from -13.0 °C to -1.3 °C.
Results: The mean core temperature (Tcore) increased significantly during the 10-km classic (39.0 °C ± 0.4 °C) and the 20-km freestyle (39.2 °C ± 0.7 °C) races (all p < 0.001) and during trainings (38.3 °C ± 0.5 °C). In contrast, skin temperature decreased in all four body parts (all p < 0.001), with the greatest decreases measured on the thigh [18.7 °C ± 4.1 °C (10-km race), 20.7 °C ± 4.6 °C (20-km race), and 18.5 °C ± 3.2 °C (training)]. During both races, the heart rate significantly increased over time while the racing speed decreased (p < 0.001, respectively). The mean skin temperature of the thigh correlated with skiing speed in the 10-km (r = 0.573, p = 0.041) and the 20-km (r = 0.682, p = 0.021) races.
Conclusion: In summary, despite low ambient temperatures under real competition and training conditions, the athletes exhibited high heat generation, which enabled them to maintain a high core temperature. In contrast, the skin temperature dropped sharply during competitions and trainings. The association between the low mean skin temperature and the lower racing speed should be investigated further.
{"title":"Thermoregulatory responses in elite cross-country skiers during international competitions and training.","authors":"Wolfgang Schobersberger, Maarit Valtonen, Anika Köck, Sebastien Racinais, Yannis Pitsiladis, Panagiotis Verdoukas, Borja Muniz-Pardos, Rikhard Mäki-Heikkilä, Johanna K Ihalainen, Dominique Gagnon, Tobias Dünnwald","doi":"10.3389/fphys.2025.1709093","DOIUrl":"10.3389/fphys.2025.1709093","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to describe the thermoregulatory responses of elite athletes during competitions and training of the international cross-country skiing FIS Scandinavian Cup in Finland, held under cold (subzero) ambient conditions.</p><p><strong>Methods: </strong>The core and skin temperatures were continuously recorded during two competition formats-a 10-km race (n = 18; 10 m, 8 f) and a 20-km race (n = 14; 9 m, 5 f)-and during training (n = 11; 7 m, 4 f) using electronic temperature pills and temperature sensors fixed on the chest, arm, hand, and thigh, respectively. The heart rate and skiing speed were continuously recorded using heart rate monitors with integrated GPS technology. Ambient temperatures during the measuring period ranged from -13.0 °C to -1.3 °C.</p><p><strong>Results: </strong>The mean core temperature (T<sub>core</sub>) increased significantly during the 10-km classic (39.0 °C ± 0.4 °C) and the 20-km freestyle (39.2 °C ± 0.7 °C) races (all p < 0.001) and during trainings (38.3 °C ± 0.5 °C). In contrast, skin temperature decreased in all four body parts (all p < 0.001), with the greatest decreases measured on the thigh [18.7 °C ± 4.1 °C (10-km race), 20.7 °C ± 4.6 °C (20-km race), and 18.5 °C ± 3.2 °C (training)]. During both races, the heart rate significantly increased over time while the racing speed decreased (p < 0.001, respectively). The mean skin temperature of the thigh correlated with skiing speed in the 10-km (r = 0.573, p = 0.041) and the 20-km (r = 0.682, p = 0.021) races.</p><p><strong>Conclusion: </strong>In summary, despite low ambient temperatures under real competition and training conditions, the athletes exhibited high heat generation, which enabled them to maintain a high core temperature. In contrast, the skin temperature dropped sharply during competitions and trainings. The association between the low mean skin temperature and the lower racing speed should be investigated further.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1709093"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12738875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1656980
Gabriele Marinari, Darren S DeLorey
<p><strong>Introduction: </strong>Aerobic fitness and oxygen uptake kinetics (τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub>) at the onset of exercise appear to be inversely correlated, however, the mechanisms underlying changes in τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> across different levels of aerobic fitness have not been elucidated. The purpose of this study was to investigate the relationship between maximal <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> ( <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub>) and τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> and determine whether the capacity to deliver or to utilize O<sub>2</sub> limits τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> in an aerobic fitness dependent manner.</p><p><strong>Methods: </strong>Twenty-three healthy, young males (25 ± 4 years) with a <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> classified as superior (S; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> > 60 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 7), good (G; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> = 45-55 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 8) or poor (P; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> < 40 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 8) performed two moderate-intensity knee-extension (KE) exercise transitions (80% of gas exchange threshold) on a custom-built KE ergometer. <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> was measured breath-by-breath. Leg blood flow (BF) was measured by doppler ultrasound at the femoral artery, and leg vascular conductance (LVC) was calculated as BF·mean arterial pressure (MAP)<sup>-1</sup>. Near-infrared spectroscopy derived-[HHb] was measured on the vastus lateralis muscle. τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub>, τLVC, and τ[HHb] data were averaged and fit with a mono-exponential function.</p><p><strong>Results: </strong>τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> was faster in the S (<i>P</i> < 0.01) and G (<i>P</i> < 0.05) fitness groups compared with the P fitness group. τ[HHb] was faster in the S (<i>P</i> < 0.05) compared with the P fitness group. <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> was inversely correlated to τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> (<i>r</i> = -0.71; <i>P</i> < 0.001) and τ[HHb] (<i>r</i> = -0.55; <i>P</i> < 0.01), but not with τLVC (<i>r</i> = -0.12; <i>P</i> > 0.05). τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub
在运动开始时,有氧适应度和氧摄取动力学(τ V˙O2)似乎呈负相关,然而,在不同的有氧适应度水平上,τ V˙O2变化的机制尚未阐明。本研究的目的是研究最大V˙O2 (V˙O2max)和τ V˙O2之间的关系,并确定输送或利用O2的能力是否以有氧适应度依赖的方式限制τ V˙O2。方法:23名健康的年轻男性(25±4岁),V˙O2max分为优等(S; V˙O2max > 60 mL·kg-1·min-1, n = 7)、良好(G; V˙O2max = 45-55 mL·kg-1·min-1, n = 8)和差(P; V˙O2max < 40 mL·kg-1·min-1, n = 8),在定制的KE测力仪上进行两次中等强度膝关节伸展(KE)运动转换(80%气体交换阈值)。按呼吸测量V˙O2。用多普勒超声在股动脉处测量腿部血流量(BF),用BF·平均动脉压(MAP)-1计算腿部血管导度(LVC)。近红外光谱衍生-[hbb]测量股外侧肌。对τ V˙O2、τ lvc和τ[hbb]数据进行平均,并用单指数函数拟合。结果:S健身组τ V˙O2比P健身组快(P < 0.01), G健身组τ V˙O2比P健身组快(P < 0.05)。与P适应度组相比,S组τ[hbb]更快(P < 0.05)。V˙O2max与τ V˙O2呈负相关(r = -0.71, P < 0.001),与τ[hbb]呈负相关(r = -0.55, P < 0.01),与τ lvc无显著相关(r = -0.12, P < 0.05)。τ V˙O2与τ[hbb]呈正相关(r = -0.57, P < 0.01),与τ lvc无显著正相关(r = -0.25, P < 0.05)。结论:V˙O2max与τ V˙O2在不同健康水平间呈负相关。这些发现表明,在健康的年轻人中,无论有氧适能如何,细胞内利用O2的能力可能是τ V˙O2的主要限制因素。
{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\"><ns0:math> <ns0:mrow><ns0:mover><ns0:mi>V</ns0:mi> <ns0:mo>˙</ns0:mo></ns0:mover> </ns0:mrow> </ns0:math> O<sub>2max</sub> and the kinetics of <ns0:math> <ns0:mrow><ns0:mover><ns0:mi>V</ns0:mi> <ns0:mo>˙</ns0:mo></ns0:mover> </ns0:mrow> </ns0:math> O<sub>2</sub>, muscle oxygen delivery, and muscle deoxygenation.","authors":"Gabriele Marinari, Darren S DeLorey","doi":"10.3389/fphys.2025.1656980","DOIUrl":"10.3389/fphys.2025.1656980","url":null,"abstract":"<p><strong>Introduction: </strong>Aerobic fitness and oxygen uptake kinetics (τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub>) at the onset of exercise appear to be inversely correlated, however, the mechanisms underlying changes in τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> across different levels of aerobic fitness have not been elucidated. The purpose of this study was to investigate the relationship between maximal <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> ( <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub>) and τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> and determine whether the capacity to deliver or to utilize O<sub>2</sub> limits τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> in an aerobic fitness dependent manner.</p><p><strong>Methods: </strong>Twenty-three healthy, young males (25 ± 4 years) with a <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> classified as superior (S; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> > 60 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 7), good (G; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> = 45-55 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 8) or poor (P; <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> < 40 mL<b>·</b>kg<sup>-1</sup> <b>·</b>min<sup>-1</sup>, n = 8) performed two moderate-intensity knee-extension (KE) exercise transitions (80% of gas exchange threshold) on a custom-built KE ergometer. <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> was measured breath-by-breath. Leg blood flow (BF) was measured by doppler ultrasound at the femoral artery, and leg vascular conductance (LVC) was calculated as BF·mean arterial pressure (MAP)<sup>-1</sup>. Near-infrared spectroscopy derived-[HHb] was measured on the vastus lateralis muscle. τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub>, τLVC, and τ[HHb] data were averaged and fit with a mono-exponential function.</p><p><strong>Results: </strong>τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> was faster in the S (<i>P</i> < 0.01) and G (<i>P</i> < 0.05) fitness groups compared with the P fitness group. τ[HHb] was faster in the S (<i>P</i> < 0.05) compared with the P fitness group. <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2max</sub> was inversely correlated to τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub>2</sub> (<i>r</i> = -0.71; <i>P</i> < 0.001) and τ[HHb] (<i>r</i> = -0.55; <i>P</i> < 0.01), but not with τLVC (<i>r</i> = -0.12; <i>P</i> > 0.05). τ <math> <mrow><mover><mi>V</mi> <mo>˙</mo></mover> </mrow> </math> O<sub","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1656980"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12738168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11eCollection Date: 2025-01-01DOI: 10.3389/fphys.2025.1636766
Mia Levite, Nili Ilouz, Avi Harazi, Hadassa Goldberg-Stern, Eithan Galun, Stella Mitrani-Rosenbaum
Background: Glutamate is the major excitatory neurotransmitter in the nervous system, common in neuromuscular junctions, and with abnormally reduced levels in several muscle diseases. Glutamate receptor AMPA GluR3, encoded by the GRIA3 gene, has important neurophysiological roles in regulation of neural networks, sleep, and breathing. GluR3 deletion or abnormal function increases the susceptibility to seizures and disrupts oscillatory networks of sleep, breathing, exploratory activity, and motor coordination.
Questions: Do human skeletal muscle cells express GluR3? Are they activated by glutamate? Do autoimmune GluR3B antibodies of Nodding Syndrome (NS) patients, and/or other intractable epilepsy patients, that bind and damage neural cells, also bind and affect skeletal muscle cells?
Results: We discovered several original findings: 1) Human primary skeletal muscle cells (myoblasts) express GluR3 RNA and protein, evident by PCR and immunostaining, 2) glutamate (10-8-10-5M) increases intracellular sodium in human skeletal muscle cells and increases muscle cell number (probably by inducing muscle cell proliferation), 3) AMPA and NMDA increase intracellular sodium in skeletal muscle cells, 4) GluR3B monoclonal antibody binds skeletal muscle cells and increases their number, 5) autoimmune affinity-purified GluR3B antibodies of epileptic NS patients, suffering from nodding due to loss of muscle tone and muscle wasting, bind skeletal muscle cells, 6) purified IgGs rich in autoimmune GluR3B antibodies of intractable epilepsy patients bind and kill skeletal muscle cells.
Possible implications: Together, the novel findings in this study may have various important implications on muscle physiology and pathology and call for continuation studies on diverse physiological, pathological and therapeutic topics. Meanwhile, we raise few hypotheses: 1) GluR3 has an important physiological role in muscle cells and motor function, 2) impaired GluR3 function (due to genetic/epigenetic/autoimmune/infectious/inflammatory factors?) can cause muscle impairments and motor problems, 3) glutamate, by direct activation of GluR3 and/or other GluRs expressed in skeletal muscle cells, can beneficially affect muscle cell survival, growth, and function, 3) Glutamate, iGluR agonists, and/or GluR3B mAb may have therapeutic effects for muscle diseases, injuries, and age-related sarcopenia, 4) autoimmune GluR3B antibodies of NS patients and/or other epilepsy patients may bind GluR3 in muscle cells, damage these cells, and induce muscle dysfunction and motor problems.
{"title":"Human primary skeletal muscle cells express glutamate receptor GluR3, are activated by glutamate, and are affected by autoimmune GluR3B antibodies of epilepsy patients.","authors":"Mia Levite, Nili Ilouz, Avi Harazi, Hadassa Goldberg-Stern, Eithan Galun, Stella Mitrani-Rosenbaum","doi":"10.3389/fphys.2025.1636766","DOIUrl":"10.3389/fphys.2025.1636766","url":null,"abstract":"<p><strong>Background: </strong>Glutamate is the major excitatory neurotransmitter in the nervous system, common in neuromuscular junctions, and with abnormally reduced levels in several muscle diseases. Glutamate receptor AMPA GluR3, encoded by the GRIA3 gene, has important neurophysiological roles in regulation of neural networks, sleep, and breathing. GluR3 deletion or abnormal function increases the susceptibility to seizures and disrupts oscillatory networks of sleep, breathing, exploratory activity, and motor coordination.</p><p><strong>Questions: </strong>Do human skeletal muscle cells express GluR3? Are they activated by glutamate? Do autoimmune GluR3<b>B</b> antibodies of Nodding Syndrome (NS) patients, and/or other intractable epilepsy patients, that bind and damage neural cells, also bind and affect skeletal muscle cells?</p><p><strong>Results: </strong>We discovered several original findings: 1) Human primary skeletal muscle cells (myoblasts) express GluR3 RNA and protein, evident by PCR and immunostaining, 2) glutamate (10<sup>-8</sup>-10<sup>-5</sup>M) increases intracellular sodium in human skeletal muscle cells and increases muscle cell number (probably by inducing muscle cell proliferation), 3) AMPA and NMDA increase intracellular sodium in skeletal muscle cells, 4) GluR3<b>B</b> monoclonal antibody binds skeletal muscle cells and increases their number, 5) autoimmune affinity-purified GluR3<b>B</b> antibodies of epileptic NS patients, suffering from nodding due to loss of muscle tone and muscle wasting, bind skeletal muscle cells, 6) purified IgGs rich in autoimmune GluR3<b>B</b> antibodies of intractable epilepsy patients bind and kill skeletal muscle cells.</p><p><strong>Possible implications: </strong>Together, the novel findings in this study may have various important implications on muscle physiology and pathology and call for continuation studies on diverse physiological, pathological and therapeutic topics. Meanwhile, we raise few hypotheses: 1) GluR3 has an important physiological role in muscle cells and motor function, 2) impaired GluR3 function (due to genetic/epigenetic/autoimmune/infectious/inflammatory factors?) can cause muscle impairments and motor problems, 3) glutamate, by direct activation of GluR3 and/or other GluRs expressed in skeletal muscle cells, can beneficially affect muscle cell survival, growth, and function, 3) Glutamate, iGluR agonists, and/or GluR3<b>B</b> mAb may have therapeutic effects for muscle diseases, injuries, and age-related sarcopenia, 4) autoimmune GluR3<b>B</b> antibodies of NS patients and/or other epilepsy patients may bind GluR3 in muscle cells, damage these cells, and induce muscle dysfunction and motor problems.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"16 ","pages":"1636766"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}