Acta Physiologica最新文献

{"title":"Is Predisposition to T2D Impacted by Polymorphisms in Genes Involved in Insulin Signaling and Cellular Bioenergetics?","authors":"Benudhara Pati,&nbsp;Martin Jastroch,&nbsp;Naresh Chandra Bal","doi":"10.1111/apha.70122","DOIUrl":"10.1111/apha.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes (T2D) represents a growing global health challenge, with its prevalence and associated metabolic complications rising sharply over the past two decades. Although the pathogenesis of T2D is complex and influenced by lifestyle and (micro)environmental factors, genetic constituents have been considered major predisposing factors. Recent literature shows significant individual variations in both the progression of T2D and the efficacy of antidiabetic drugs. These individual variations are expected to emanate from the inherent genetic make-up and potential epigenetic modifications by environmental factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>It has been proposed that altered metabolism (including cellular bioenergetic mechanisms) provides protection from T2D. Moreover, several researchers have proposed that proteins regulating cellular bioenergetics, for example, involved in adaptive thermogenesis, represent good targets to counter T2D. Therefore, we thoroughly searched the literature on genetic variability associated with T2D in this review.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We could only find genes involved in (1) insulin secretion (<i>INS</i>, <i>PDX1</i>, <i>ABCC8</i>, <i>KCNJ11</i>, <i>KCNQ1</i>, <i>CDKAL1</i>, <i>IGFBP2</i>) and (2) cellular bioenergetics in insulin-responsive tissues (<i>INSR</i>, <i>IRS</i>, <i>AKT</i>, <i>SLC2A4</i>, <i>TBC1D4</i>, <i>PPP1R3A</i>, <i>LEP</i>, <i>LEPR</i>, <i>ADIPOQ</i>, <i>TCF7L2</i>, <i>PPAR-γ</i>, <i>SLC30A8</i>). Specific attention is given to diverse ethnic populations, in particular Indian subgroups where these genetic factors may display clearer association to T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By emphasizing genetic predispositions, this review highlights the lack of studies on the genetic association of cellular bioenergetics proteins in T2D pathogenesis. It also underscores the potential for early detection, personalized management, and the development of targeted therapies for individuals with T2D across different genetic profiles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty-Four Hour Rhythms in Cardiovascular Physiology","authors":"Morten B. Thomsen","doi":"10.1111/apha.70116","DOIUrl":"10.1111/apha.70116","url":null,"abstract":"<p>Many physiological parameters, such as heart rate and blood pressure, display pronounced daily rhythms, with significant differences between day and night levels. The ability to anticipate the 24 h cycle of ambient light confers an adaptive advantage, allowing organisms to prepare for periods of activity and rest. Considering chronophysiology is essential when designing, conducting, and interpreting laboratory experiments because of the often considerable amplitude of the rhythms. This review introduces a straightforward mathematical tool to detect 24 h rhythms in physiological datasets. Next, the review examines 24-h diurnal rhythms in heart rate, QT interval, and blood pressure, based on telemetry recordings from conscious, freely moving mice. These examples illustrate how long-term, continuous monitoring of physiological parameters enables precise characterization of daily cycles when present. Furthermore, the large datasets obtained through methods such as telemetry make it possible to determine whether the observed rhythms are dependent on heart rate. Circadian and diurnal rhythms play an essential role in cardiovascular physiology, influencing key parameters such as heart rate and blood pressure. Considering chronophysiology is therefore essential when designing, conducting, and interpreting physiological studies.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyocyte-Specific Deletion of Sirtuin 5 Accelerates the Development of Heart Failure Upon Dysregulating Purine Metabolism","authors":"Nikole J. Byrne,&nbsp;Christoph Koentges,&nbsp;Katharina Pfeil,&nbsp;Julia C. Lueg,&nbsp;Sayan Bakshi,&nbsp;Aleksandre Tarkhnishvili,&nbsp;Ivan Vosko,&nbsp;Johannes Gollmer,&nbsp;Laura C. Birkle,&nbsp;Thomas Rathner,&nbsp;Stephan Birkle,&nbsp;Sibai Tang,&nbsp;Clara Rau,&nbsp;Michael M. Hoffmann,&nbsp;Katja E. Odening,&nbsp;Stephen Barnes,&nbsp;Landon Shay Wilson,&nbsp;Senka Ljubojevic-Holzer,&nbsp;Markus Wallner,&nbsp;Dirk von Lewinski,&nbsp;Peter Rainer,&nbsp;Simon Sedej,&nbsp;Harald Sourij,&nbsp;Christoph Bode,&nbsp;Adam R. Wende,&nbsp;Andreas Zirlik,&nbsp;Heiko Bugger","doi":"10.1111/apha.70120","DOIUrl":"10.1111/apha.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sirtuin 5 (SIRT5), a mitochondrial NAD⁺-dependent deacylase, regulates fundamental cellular pathways, including energy substrate metabolism. The current study is designed to better elucidate the role of SIRT5 in the development of heart failure (HF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice with cardiomyocyte-specific deletion (<i>cSirt5</i>^−/−) or overexpression (c<i>Sirt5</i>-Tg) of SIRT5 were generated and subjected to chronic pressure overload by transverse aortic constriction (TAC) or Sham surgery. Cardiac structure and function were assessed by echocardiography, isolated heart perfusions, and histology. MS-based metabolomics and bulk RNA sequencing were used to explore metabolic and molecular signatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>c<i>Sirt5</i>-Tg mice had similar cardiac structure and function compared to control mice, whereas c<i>Sirt5</i>^−/− mice displayed exacerbated cardiac dilation and dysfunction following TAC, measured both in vivo by echocardiography and ex vivo in isolated heart perfusions. Metabolomics revealed accumulation of inosine and hypoxanthine, and depletion of adenosine, adenine, AMP, and ADP in c<i>Sirt5</i>^−/− hearts and following TAC, indicating dysregulation of purine metabolism. RNA-sequencing uncovered upregulation of purine-nucleoside phosphorylase and 5′ nucleotidase, and downregulation of adenosine kinase (ADK) in c<i>Sirt5</i>^−/− hearts following TAC, indicating dysregulation at the interface of adenosine nucleotide salvage and purine degradation in the absence of SIRT5. Analyses of left ventricular tissue of patients with HF revealed reduced SIRT5 expression correlating with reduced ADK expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Loss of SIRT5 in cardiomyocytes aggravates cardiac remodeling and dysfunction in response to chronic pressure overload, involving ATP precursor depletion due to transcriptional dysregulation of cardiac purine metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical Remodeling of Pressure Overloaded Rat Heart Is Attenuated if Imposed During Proliferative Cardiac Growth","authors":"Eva Nekvindova,&nbsp;Jaroslav Hrdlicka,&nbsp;Almos Boros,&nbsp;Michaela Slegrova,&nbsp;Alena Kvasilova,&nbsp;Vojtech Skop,&nbsp;Jan Halberstat,&nbsp;Kristyna Holzerova,&nbsp;Jan Neckar,&nbsp;David Sedmera,&nbsp;Veronika Olejnickova","doi":"10.1111/apha.70118","DOIUrl":"10.1111/apha.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Left ventricular pressure overload (LVPO) in adults is associated with adverse electrical remodeling, characterized by reduced conduction velocity (CV). However, the progression of LVPO differs when imposed during the proliferative phase of cardiac development. It remains unknown how increased cardiomyocyte proliferation affects LVPO electrical remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CV maturation from rat postnatal day (PD) 1 to PD90 and analyzed underlying connexin 43 (Cx43) profile. Pressure overload was induced by abdominal aortic constriction (AAC) in rats during the proliferative phase of cardiac growth (PD2). Animals subjected to AAC during the non-proliferative heart growth (AAC-PD6) and Sham-operated rats served as controls. Electrical remodeling was assessed at PD21 using ECG, optical mapping, western blots, immunofluorescence, and lipidomic analysis, complemented by functional analyses through echocardiography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pressure overload led to a 2.5-fold increase in heart weight compared to Sham in both AAC groups. A significant increase in relative left ventricular wall thickening was observed in AAC-PD2 rats only. Optical mapping and ECG showed preserved conduction properties in AAC-PD2 animals, whereas the AAC-PD6 group displayed prolonged QRS and significantly reduced longitudinal CV. While total and phosphorylated Cx43 levels were comparable between the AAC groups, AAC-PD2 animals demonstrated higher intercalated disc localization. Furthermore, lipidomic profiling revealed maintained long-chain acylcarnitine (LCAC) levels in AAC-PD2, whereas AAC-PD6 tended toward LCAC accumulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides new insights into the remodeling upon pressure overload during cardiac proliferative growth, demonstrating attenuated electrical alteration by preserved CV and highlighting the role of Cx43 localization and preserved levels of LCACs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fentanyl Disrupts Vagal Control of Airway Tone to Induce Transient Obstruction","authors":"Riley R. Parks,&nbsp;Marissa J. Andersen,&nbsp;Mackenna L. Hatfield,&nbsp;Nicholas J. Burgraff","doi":"10.1111/apha.70119","DOIUrl":"10.1111/apha.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Opioid-induced respiratory depression (OIRD) is the primary cause of death in opioid overdose, resulting from both suppressed respiratory rhythm and increased airway and thoracic rigidity that compromise ventilation and resuscitation. While the effect(s) of opioids on central rhythm-generating circuits are well documented, the mechanisms leading to airway obstruction remain poorly understood. Here, we investigated the hypothesis that enhanced vagal parasympathetic output contributes to fentanyl-induced airway disruption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In urethane-anesthetized mice, diaphragm electromyography (EMG), respiratory airflow, and vagus nerve activity were recorded in-vivo before and after intraperitoneal fentanyl administration (500 μg/kg). The effects of bilateral vagotomy, atropine administration, and intracisternal naloxone were evaluated to determine the contribution of vagal pathways and central opioid receptor mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fentanyl caused a characteristic slowing of respiratory rate accompanied by a compensatory increase in tidal volume, but also produced a transient delay between diaphragm activation and airflow onset, consistent with airway obstruction. This delay was abolished by bilateral vagotomy or atropine and reversed by intracisternal naloxone, implicating central vagal mechanisms. Vagal electroneurograms showed increased tonic multiunit activity and enhanced large-amplitude single-unit firing, particularly within efferent fibers, together with a loss of normal inspiratory phase-locking. The magnitude of tonic vagal activation strongly correlated with the severity of airway disruption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fentanyl disrupts respiratory-autonomic integration by enhancing parasympathetic vagal drive, producing a central, opioid receptor-mediated mechanism of airway constriction. Targeting vagal pathways may therefore represent a promising adjunctive strategy for improving airway patency and ventilatory recovery during opioid overdose reversal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Nitrate Prevents Cardiac Dysfunction in HFrEF by Improving Hemodynamics, Ameliorating Remodeling, and Resolving Inflammation","authors":"Miho Shimari,&nbsp;Gaia Picozzi,&nbsp;Ariela Boeder,&nbsp;Drielle Dantas Guimarães,&nbsp;Zhengbing Zhuge,&nbsp;Jon O. Lundberg,&nbsp;Mattias Carlstrom,&nbsp;Lars H. Lund,&nbsp;Daniel C. Andersson,&nbsp;Gianluigi Pironti","doi":"10.1111/apha.70115","DOIUrl":"10.1111/apha.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Impaired cardiac function, reduced nitric oxide (NO) bioavailability, and inflammation are key contributors to the pathogenesis and progression of heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate whether dietary inorganic nitrate supplementation can attenuate cardiac dysfunction and adverse remodeling in HFrEF by enhancing NO signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two mouse models of HFrEF, induced by myocardial infarction (MI) or transverse aortic constriction (TAC), were treated with dietary nitrate or a control diet for 4–6 weeks, initiating the treatment on day 3 after myocardial injury. Echocardiography and pressure volume (PV) loop analysis were employed to assess cardiac function and hemodynamics. Histology staining was performed to assess the degree of cardiac fibrosis. Myograph experiments were conducted to assess aortic vasorelaxation. Biomarkers related to hypertrophy, fibrosis, and inflammation were analyzed in cardiac tissues through Q-PCR analysis and immunofluorescence staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In HFrEF mice, long-term inorganic nitrate treatment increased systolic and diastolic function, enhanced vascular relaxation, and reduced both replacement and reactive fibrosis. In the nitrate group, cardiac gene expression showed downregulation of hypertrophy-, fibrosis-, and inflammation-related markers, alongside upregulation of anti-inflammatory markers associated with M1-to-M2 macrophage polarization. Immunofluorescence confirmed reduced fibrosis and increased anti-inflammatory protein biomarkers associated with increased serum nitrate and cardiac cGMP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early initiation of dietary nitrate supplementation after myocardial injury enhances cardiac and vascular function, reduces fibrosis and inflammation, and holds promise as a cardioprotective strategy to reduce the progression of HFrEF through NO-signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transduction Mechanisms for Cold Temperature in Mouse Trigeminal and Vagal Ganglion Neurons Innervating Different Peripheral Organs","authors":"Katharina Gers-Barlag,&nbsp;Ana Gómez del Campo,&nbsp;Pablo Hernández-Ortego,&nbsp;Eva Quintero,&nbsp;Félix Viana","doi":"10.1111/apha.70111","DOIUrl":"10.1111/apha.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To elucidate the molecular mechanism of cold sensing by visceral sensory endings, a side-by-side characterization of cold-sensitive (CS) neurons in adult mouse trigeminal (TG) and vagal ganglia (VG) was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A combination of physiological, pharmacological, molecular, and genetic tools was employed on trigeminal and vagal neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CS neurons are more abundant in VG, and the majority co-express TRPA1. Cold-evoked responses are severely blunted in <i>Trpa1</i> KO mice. In contrast, TRPM8 deletion or pharmacological TRPM8 blockade had little impact on VG cold sensitivity. In <i>Trpm8</i>^<i>eYFP</i> reporter mice, VG TRPM8 expression was restricted to the rostral jugular ganglion. In vivo labeling of airway-innervating VG neurons demonstrated their enhanced cold sensitivity and higher TRPA1 expression compared to neurons innervating the stomach wall. In contrast, the majority of CS TG neurons co-express TRPM8 markers, and their cold sensitivity is reduced after TRPM8 deletion or blockade. However, pharmacological or genetic ablation of TRPA1 confirmed its contribution to high-threshold cold sensitivity in TG, suggestive of a role in noxious cold sensing. In both ganglia, a fraction of CS neurons responded to cooling by a mechanism independent of TRPA1 or TRPM8. Blocking potassium channels enhanced cold sensitivity independently of the specific transducer mechanism, suggestive of a common excitability brake mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study highlights the differential contribution of TRPM8 and TRPA1 channels to cold sensitivity in somatic and visceral ganglia, establishing a critical role of TRPA1 channels in visceral cold transduction. Finally, cold sensitivity seems fine-tuned to the specific physiological needs of different organs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-126-5p Derived From Bone Marrow Mesenchymal Stem Cell Exosomes Promotes Skeletal Muscle Regeneration by Regulating FBXO32/MyoD Signaling","authors":"Yi Yan,&nbsp;Minxing Zheng,&nbsp;Xuanjing Wang,&nbsp;Tingting Fu,&nbsp;Jiahui Qi,&nbsp;Xiaofang Wei,&nbsp;Yaqin Sun,&nbsp;Jiayin Lu,&nbsp;Xiaomao Luo,&nbsp;Ying Wang,&nbsp;Haidong Wang","doi":"10.1111/apha.70114","DOIUrl":"10.1111/apha.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In the process of muscle growth and repair, microRNAs (miRNAs) serve as a critical factor in spatiotemporal regulation. Nevertheless, the molecular regulatory mechanisms underlying muscle regeneration remain largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Exosomes from control and miR-126-knockdown BMSCs were isolated via ultracentrifugation. A mouse muscle injury model was established using 1.2% barium chloride in gastrocnemius muscles. Injured tissues received local injections of BMSC exosomes or AAV-miR-126. Gene expression was analyzed by qRT-PCR/Western blot. Tissue morphology and repair were assessed via H&amp;E staining, while regeneration markers were evaluated through immunostaining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we identified miR-126-5p in BMSC-derived exosomes as a positive regulator of muscle regeneration. These exosomes promoted the proliferation and maturation of myoblasts and facilitated the regeneration of skeletal muscle in male C57BL/6J mice. FBXO32 was confirmed as the downstream target of exosomal miR-126-5p to regulate skeletal muscle regeneration, and it ubiquitinated and degraded myogenic differentiation 1 (MyoD). Notably, miR-126-5p knockdown from BMSC-derived exosomes significantly inhibited proliferation and differentiation of Pax7⁺ SCs and muscle regeneration, whereas adeno-associated virus (AAV)-mediated overexpression of miR-126-5p accelerated these processes. Specifically, the BMSC-derived exosomes delivered miR-126-5p to skeletal muscle, thus decreasing the expression of FBXO32, in turn increasing MyoD expression, finally significantly promoting satellite cell differentiation and skeletal muscle regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BMSC-derived exosomes could promote skeletal muscle injury repair through miR-126-5p, and thus miR-126-5p may act as a molecular therapeutic target of skeletal muscle diseases. Elucidating functional mechanisms of exosomes and miRNA is of great significance for developing new biotherapy strategies for skeletal muscle disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Preeclampsia and Gestational Diabetes on Future Maternal Cardiometabolic Health","authors":"Alice M. Barrell,&nbsp;Amanda N. Sferruzzi-Perri","doi":"10.1111/apha.70113","DOIUrl":"10.1111/apha.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Pregnancy is a time of significant maternal physiological change to meet the metabolic demands of the feto-placental unit. In cases of pregnancy complications, mal-adaptive physiological responses may occur, potentially impacting the health of both mother and fetus. Moreover, some maternal changes may persist beyond delivery. Although the clinical symptoms of preeclampsia (PE) and gestational diabetes mellitus (GDM) usually resolve post-partum, growing evidence suggests that these conditions confer a lifelong increased risk of cardiometabolic disease in affected women. This review aimed to summarize epidemiological evidence linking PE and GDM to future maternal cardiometabolic disorders, explore potential underlying mechanisms based on animal and small-scale human studies, and discuss implications for future research and postpartum clinical care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Targeted PubMed searches were conducted to search for relevant publications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data suggest that pregnancy complications may both reveal an underlying predisposition to cardiometabolic disease and induce lasting physiological changes that contribute to future health risks. Notably, women with a history of PE may have a 3–4-fold increased risk of cardiovascular disease, while those with prior GDM may face up to a 10-fold higher risk of developing type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pregnancy offers a valuable window into a woman's future health, presenting a unique opportunity for preventative medicine for up to half of the world's population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Differences of GABAergic Polarization and Shunting During Dendritic Integration","authors":"Yulia Dembitskaya,&nbsp;Artem Kirsanov,&nbsp;Yu-Wei Wu,&nbsp;Alexey Brazhe,&nbsp;Alexey Semyanov","doi":"10.1111/apha.70112","DOIUrl":"https://doi.org/10.1111/apha.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In the adult brain, GABA exerts either depolarizing or hyperpolarizing effects on neuronal membranes, depending on neuron type, subcellular location, and neuronal activity. Depolarizing GABA typically inhibits neurons through shunting, which is mediated by increased membrane conductance upon GABA_A receptor activation; however, it can also excite neurons by recruiting voltage-dependent conductances. The net influence of these opposing actions of depolarizing GABA on glutamatergic synaptic inputs remains incompletely understood. We aimed to examine the spatiotemporal characteristics of membrane polarization and shunting mediated by GABA_A receptors and assess their functional impact on the integration of GABAergic and glutamatergic inputs along dendrites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using whole-cell current-clamp recordings in CA1 pyramidal neurons and dentate gyrus granule cells (GCs) from rat hippocampal slices, we mimicked GABAergic and glutamatergic inputs with local GABA puff and glutamate spot-uncaging, respectively. A mathematical model further quantified the relative effects of local shunting and polarization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Depolarizing GABAergic postsynaptic responses (GPSRs) exhibited biphasic actions, exerting inhibitory effects at the synapse through shunting, and excitatory effects distally, where depolarization predominated. The excitatory component also persisted longer than the shunting inhibition. In contrast, hyperpolarizing GPSRs remained consistently inhibitory across both spatial and temporal dimensions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the complex spatiotemporal interplay between shunting and membrane polarization mediated by GABAergic inputs, providing new insights into dendritic computation and neuronal network dynamics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}