Acta Physiologica最新文献

{"title":"Acute Hypoxia Inhibits K2P3/9 (TASK1/3) Independently of Cytosolic ATP in Carotid Body Type 1 Cells","authors":"Dawon Kang, Jiaju Wang, Donghee Kim","doi":"10.1111/apha.70294","DOIUrl":"https://doi.org/10.1111/apha.70294","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia stimulates ventilation through a chemosensory reflex that is initiated by inhibition of the O<sub>2</sub>-sensitive K<sup>+</sup> channels such as K<sub>2P</sub>3/9 in carotid body Type 1 glomus (CB) cells. Because K<sub>2P</sub>3/9 activity is sensitive to cytosolic ATP concentration ([ATP]<sub>cyt</sub>, K<sub>1/2</sub> ≈ 2.5 mM), it has been proposed that hypoxia suppresses mitochondrial ATP production and thereby reduces [ATP]<sub>cyt</sub> to inhibit K<sub>2P</sub>3/9 activity. To test this hypothesis, we developed a K<sub>ATP</sub> channel-based bioassay using a patch-cramming approach to measure [ATP]<sub>cyt</sub> in living cells. Co-expression of Kir6.2(ΔC36-R50G) and SUR1(G1485D) in HEK293 cells formed a functional K<sub>ATP</sub> channel (designated R50G*) with markedly reduced ATP sensitivity. In inside-out patches, normalized R50G* (<span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msubsup>\u0000 <mrow>\u0000 <mi>R</mi>\u0000 <mn>50</mn>\u0000 <mi>G</mi>\u0000 </mrow>\u0000 <mi>NL</mi>\u0000 <mo>*</mo>\u0000 </msubsup>\u0000 </mrow>\u0000 <annotation>$$ mathrm{R}50{mathrm{G}}_{mathrm{NL}}^{ast } $$</annotation>\u0000 </semantics></math>) activity showed ~100-fold lower ATP sensitivity (K<sub>1/2</sub> ≈ 2.0 mM) than that of the wild-type K<sub>ATP</sub> (K<sub>1/2</sub> ≈ 20 μM). Inside-out patches from HEK293 cells containing R50G* were crammed into CB cells under normoxia (21% O<sub>2</sub>), exposing the patch to the CB cell cytoplasm. Based on <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msubsup>\u0000 <mrow>\u0000 <mi>R</mi>\u0000 <mn>50</mn>\u0000 <mi>G</mi>\u0000 </mrow>\u0000 <mi>NL</mi>\u0000 <mo>*</mo>\u0000 </msubsup>\u0000 </mrow>\u0000 <annotation>$$ mathrm{R}50{mathrm{G}}_{mathrm{NL}}^{ast } $$</annotation>\u0000 </semantics></math> activity in crammed CB cells, [ATP]<sub>cyt</sub> was estimated to be ~4.9 mM in normoxia. In CB cells, hypoxia (1% O<sub>2</sub>, 15 s) did not affect <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msubsup>\u0000 <mrow>\u0000 <mi>R</mi>\u0000 <mn>50</mn>\u0000 <mi>G</mi>\u0000 </mrow>\u0000 <mi>NL</mi>\u0000 <mo>*</mo>\u0000 </msubsup>\u0000 </mrow>\u0000 <annotation>$$ mathrm{R}50{mathrm{G}}_{mathrm{NL}}^{ast } $$</annotation>\u0000 </semantics></math> activity, indicating that [ATP]<sub>cyt</sub> remained stable during hypoxia. FCCP (1 μM), a mitochondrial uncoupler, increased <span></span><math>\u0000 ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784192","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":"Written in the Stars: Astrocyte Biology From Evolution to Disease","authors":"Carmen Falcone,&nbsp;Lutgarde Arckens,&nbsp;Monica Baiula,&nbsp;Andrea Bedini,&nbsp;Riccardo Bocchi,&nbsp;Matthew J. Broadhead,&nbsp;Marco Caprini,&nbsp;Fabio Cavaliere,&nbsp;Fabrizia Cesca,&nbsp;Helena H. Chowdhury,&nbsp;Katarzyna Ciuba,&nbsp;Laura Civiero,&nbsp;Carole Escartin,&nbsp;Stefano Ferroni,&nbsp;Francesco Formaggio,&nbsp;Angelisa Frasca,&nbsp;Rossella Gratton,&nbsp;Matthew Holt,&nbsp;Nunzio Iraci,&nbsp;Marko Kreft,&nbsp;Loredana Leggio,&nbsp;Annamaria Lia,&nbsp;Anna R. Malik,&nbsp;Rogier Min,&nbsp;Franziska E. Müller,&nbsp;Cahuê Murat,&nbsp;Maria João Pereira,&nbsp;Aleksandra Pekowska,&nbsp;Francesco Petrelli,&nbsp;Paula Ramos-Gonzalez,&nbsp;Maria V. Sanchez-Mico,&nbsp;Zala Smole,&nbsp;Dimitra Sokolova,&nbsp;Maite Solas,&nbsp;Alessia Soldano,&nbsp;Lukasz Mateusz Szewczyk,&nbsp;Carola Torazza,&nbsp;Francesco Paolo Ulloa Severino,&nbsp;Nerea Urrestizala-Arenaza,&nbsp;Andre Zeug,&nbsp;Jiafeng Zhou,&nbsp;Micaela Zonta,&nbsp;Robert Zorec,&nbsp;Alexei Verkhratsky,&nbsp;Nilhan Gunhanlar","doi":"10.1111/apha.70289","DOIUrl":"10.1111/apha.70289","url":null,"abstract":"<div>\u0000 \u0000 <p>In the 21st century, neuroglial research has entered a period of Renaissance, extending the views of prominent neuroanatomists and neurologists of the 19th and early 20th centuries, who assigned to glial cells numerous physiological functions and highlighted their fundamental role in the pathophysiology of nervous system diseases. Astrocytes are highly diversified in structure and function; they control brain homeostasis, support synaptic connectivity, and enable information processing in neural networks. Evolutionary diversification of astrocytes, initially emerging as supportive cells of primitive sensory organs, drove a continuous expansion of astroglial complexity and functional versatility, ultimately making them indispensable neuroprotectors and homeostatic regulators. The large, morphologically elaborate astrocytes of the human brain arguably reflect an evolutionary response to increased neuronal homeostatic demands. Astrocytes are indispensable for synaptic function, serving as the principal regulators of neurotransmitter turnover and neuronal excitability. Astrocytes also govern brain energy metabolism, mitochondrial dynamics, and calcium signaling, thereby actively shaping cortical plasticity and circuits. Astrocytes are fundamental elements of the pathophysiology of neurological, neuropsychiatric, and neurodegenerative diseases, including Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Rett syndrome, genetic astrocytopathies, and neurotrauma, where they demonstrate complex reactive changes directed at tissue preservation and regeneration, but which can also contribute to disease progression. Advances in single-cell transcriptomics, calcium imaging, chemogenetics, and iPSC-based models have transformed our understanding of astrocyte diversity and disease-specific dysfunction, opening new avenues of investigation. Given that no CNS disorder is known to occur without astrocyte involvement, multiple astrocyte-specific molecules represent compelling targets for cell-directed therapeutic strategies.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759472","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 Neurovascular Niche: A Gathering Venue for Neuroinflammation and Remyelination in Multiple Sclerosis","authors":"Ilias Kazanis,&nbsp;Maria Elena Silva,&nbsp;Alerie G. de la Fuente,&nbsp;Fernando de Castro,&nbsp;Francisco J. Rivera","doi":"10.1111/apha.70285","DOIUrl":"10.1111/apha.70285","url":null,"abstract":"<p>In the central nervous system (CNS), the tissue microenvironment is continuously monitored and regulated to secure the unobstructed function of neurons and of their networks. This is a key function of the neurovascular niche (NVN), which is the interface between the cells of the nervous tissue and the cells and the content of blood vessels. It is enabled by the Blood–Brain Barrier, a structure formed by endothelial and perivascular cells, extracellular matrix, and astrocytes, and is manifested by the limited surveillance of the CNS from blood-derived cells. Multiple sclerosis (MS) is a devastating degenerative disorder, in which the myelin sheaths that enwrap neuronal axons are destroyed, leading, over time, to neurological symptoms. MS has a strong immunological component which is targeted in most of the current disease-modifying treatments. Nevertheless, regenerative interventions aiming at enhancing and restoring the endogenous remyelination potential of the CNS, driven by the abundant Oligodendrocyte Progenitor Cells (OPCs), have not been successfully developed so far. Here, we will review key information on the structure of the NVN, and we will summarize the evidence on the role of inflammation in the emergence and the progress of MS, with a focus on the active response of OPCs. We will also present recent experimental evidence on the role of less investigated cellular elements of the NVN, such as pericytes and platelets, in the regulation of OPCs. Finally, we will discuss current and future treatments for MS.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719577","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":"Protective Arm of Renin-Angiotensin System: Evidence of Nephroprotective Effects Against Acute Kidney Injury","authors":"María Fernanda Fussi,&nbsp;Sara María Molinas","doi":"10.1111/apha.70292","DOIUrl":"10.1111/apha.70292","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute kidney injury (AKI) is a global health problem due to its high and increasing incidence, morbidity and mortality. Despite progress in understanding its pathophysiology, there are currently no pharmacological therapies that improve survival, limit damage, or accelerate recovery, except for supportive interventions and renal replacement therapies. Cumulative knowledge indicates that during AKI, the dynamic balance between the two arms of renin-angiotensin system (RAS) is disturbed, activating the classical and reducing the protective arm. This imbalance determines pathophysiological outcomes, so the modulation of protective arm emerges as a key therapeutic strategy. This arm offers several pharmacological targets such as angiotensin II type 2 receptor (AT2R), angiotensin converting enzyme 2 (ACE2), angiotensin (1–7) and its receptor Mas (MasR), and alamandine and its receptor, Mas-related G protein–coupled receptor D (MrgD). This review presents current evidence on the modulation of the protective arm of the RAS, its role in AKI pathophysiology, and its potential as a therapeutic target, presenting literature-based evidence that such modulation exerts beneficial effects in experimental models of ischemia–reperfusion, septic and nephrotoxic AKI. This evidence emphasizes the potential of these targets for drug development in the context of AKI. Further investigation of this RAS axis may expand our understanding of AKI pathophysiology and open new avenues for the development of targeted, effective, and safer therapeutic strategies.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710581","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":"MicroRNA-Driven Regulation of β-Cell Function in Type 2 Diabetes: Molecular Mechanisms, Network Insights, and Translational Perspectives","authors":"Lena Eliasson,&nbsp;Alexandros Karagiannopoulos,&nbsp;Mototsugu Nagao,&nbsp;Anna Wendt","doi":"10.1111/apha.70288","DOIUrl":"10.1111/apha.70288","url":null,"abstract":"<p>MicroRNAs (miRNAs) have emerged as central regulators of pancreatic islet biology, influencing β-cell development, proliferation, and function. In type 2 diabetes (T2D), both adaptive and maladaptive miRNA responses shape β-cell compensation and progressive secretory dysfunction. Here, we review current insights into the regulation of insulin secretion, with a focus on exocytosis and the autocrine and paracrine regulation of β-cells, and discuss the involvement of miRNAs in these processes. We describe miRNA biogenesis and the regulation of miRNAs in β-cells, focusing on glucose- and cAMP-responsive miRNAs and epigenetic control. We summarize mechanistic evidence linking individual miRNAs to the regulation of β-cell function during T2D development, including effects on metabolic signaling and the exocytotic machinery, and compare results from humans, rodents, and cell lines, while emphasizing both the need for and difficulties of performing these investigations in β-cells from human donors. Moreover, recent network-level analyses reveal that T2D is characterized not by isolated miRNA changes but by coordinated changes in miRNA–mRNA regulatory pathways that converge on reduced and/or compensatory insulin secretion. Beyond cell-intrinsic actions, we discuss how circulating miRNAs transported via extracellular vesicles (EVs) mediate crosstalk between β-cells and peripheral tissues, influencing insulin resistance, β-cell function, and systemic glucose homeostasis. Finally, we highlight the potential of circulating miRNAs as diagnostic and predictive biomarkers, as well as the use of EVs and miRNAs for therapeutic applications, while underscoring the technical challenges that currently limit clinical translation. Nevertheless, advances in technical, network, and inter-organ analyses position miRNAs as promising biomarkers and therapeutic targets in T2D.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688264","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":"Potassium Channels of the Airway Epithelium","authors":"Sandra Villanueva,&nbsp;Erwin Vera,&nbsp;Tábata Apablaza,&nbsp;Marcelo A. Catalán,&nbsp;Carlos A. Flores","doi":"10.1111/apha.70287","DOIUrl":"10.1111/apha.70287","url":null,"abstract":"<div>\u0000 \u0000 <p>Maintenance of potassium (K⁺) homeostasis across cell membranes is essential for life. While systemic K⁺ balance is primarily regulated by the kidneys and intestines, ion channels, pumps, and transporters govern K⁺ movement across epithelial barriers at the cellular level. Despite the prevalence of diseases caused by disrupted K⁺ homeostasis, the role of K⁺ channels in the lungs has received comparatively little attention. The airway epithelium expresses a diverse array of K⁺ channels that regulate key functions such as transepithelial ion transport, ciliary beating, and mucus secretion. These processes are fundamental components of mucociliary clearance (MCC), the primary innate defense mechanism of the lungs. Dysfunction of MCC is central to muco-obstructive diseases, including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma. While K⁺ channels were once considered therapeutic targets for enhancing anion secretion in CF, initial interest waned. However, it has been reinvigorated by recent findings showing that drugs targeting CFTR can also modulate airway epithelial K⁺ channels and facilitate MCC. In this review, we compile current evidence on targeting K⁺ channels to treat muco-obstructive diseases. We discuss therapeutic opportunities offered by K⁺ channel modulators, highlight emerging functions of these channels in the airways, and outline priorities for future research.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667631","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":"Impaired Renal Base Excretion in Secretin Receptor Knock-Out Mice During Prolonged Base-Loading","authors":"Tobias Jensen,&nbsp;Jesper Frank Andersen,&nbsp;Laura Woidemann Trans,&nbsp;Ida Marie Modvig,&nbsp;Helga Vitzthum,&nbsp;Jens Juul Holst,&nbsp;Bolette Hartman,&nbsp;Samuel L. Svendsen,&nbsp;Mads Vaarby Sørensen,&nbsp;Jens Leipziger,&nbsp;Peder Berg","doi":"10.1111/apha.70286","DOIUrl":"10.1111/apha.70286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Secretin was recently found to play a pivotal role in the renal adaptation to acute base excess. Here, secretin increases pendrin-dependent HCO₃⁻ secretion from the beta-intercalated cells in the cortical collecting ducts. Whether secretin and its receptor play a role during prolonged base-loading remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Urine and blood acid–base analyses were carried out in secretin receptor (SCTR) KO and WT mice at baseline and after 1 and up to 8 days of base-loading with NaHCO₃-enriched drinking water. Changes in pendrin protein abundance and function were assessed by immunoblotting and isolated tubule perfusion experiments. Plasma secretin levels and renal SCTR expression were assessed after 24 h of acid/base-loading by radioimmunoassay and qPCR, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SCTR KO mice responded with diminished urine alkalization and a lesser reduction of urinary acid excretion when base-loaded for 48 h. Concordantly, SCTR KO mice presented with increased blood base retention compared with WTs. Base-loaded SCTR WT and KO mice showed comparable total pendrin protein abundance. Despite this, pendrin function was markedly lower in SCTR KO mice. Base-loaded mice had higher plasma secretin and renal SCTR levels compared with acid-loaded mice. Higher arterial HCO₃⁻ associated with higher renal SCTR mRNA expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Loss of the SCTR diminishes renal base excretion capacity and exacerbates systemic base accumulation during prolonged base-loading. Further, plasma secretin and renal SCTR mRNA levels are modulated by acid–base intake. These findings further support a central role of secretin and its receptor in the regulation of both acute and prolonged base excess.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628893","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":"From the Perspective of the Peripheral Sensory Nervous System: The Role of Vitamin D in Neurogenic Inflammatory Skin Disorders","authors":"Sarah A. Commaroto,&nbsp;Richard D. Granstein","doi":"10.1111/apha.70262","DOIUrl":"10.1111/apha.70262","url":null,"abstract":"<div>\u0000 \u0000 <p>Vitamin D (VD) is a secosteroid hormone with critical physiologic roles in calcium homeostasis and bone mineralization. Recently, studies have uncovered VD's broader effects on immune system and nervous system function. VD receptors (VDRs) and enzymes responsible for the metabolism of VD have been discovered in dorsal root ganglion (DRG) neurons and nociceptive sensory neurons, implicating VD as a potential regulator of neurogenic inflammation. Neurogenic inflammation is a phenomenon in which sensory nerve fibers in the peripheral nervous system (PNS) are activated and release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), resulting in vasodilation, cytokine production, and immune cell infiltration. This process has been shown to drive chronic inflammatory skin disorders, including atopic dermatitis (AD) and psoriasis. VD has been recognized as a key factor in the pathogenesis and management of both conditions; however, the mechanism underlying its clinical benefits remains unclear. Emerging evidence has shown VD to influence CGRP signaling, interleukin-6 (IL-6) production, and TRPV1 channel activity—pathways that are integral to nociception and pruritus, as well as the Th17- and Th2-driven inflammation seen in psoriasis and AD, respectively. Thus, this review provides an overview of VD's possible mechanistic role in neurogenic skin inflammation and the implications of these pathways for identifying new therapeutic targets for psoriasis and AD.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589690","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":"Human Islet miR-199a-5p and miR-214-3p Associate With Donor Age, BMI, and Sex and Mediate Cellular Aging in Islet-Derived Cells","authors":"Wilson K. M. Wong,&nbsp;Isabelle El-Azzi,&nbsp;Aditya Nachanekar,&nbsp;Ehsan Alvandi,&nbsp;Nhan Ho Trong Pham,&nbsp;Hrishikesh P. Hardikar,&nbsp;Mya Polkamp,&nbsp;Vijit Saini,&nbsp;Feifei Cheng,&nbsp;Guozhi Jiang,&nbsp;Anja E. Sørensen,&nbsp;Yi Vee Chew,&nbsp;Helen E. Thomas,&nbsp;Thomas Loudovaris,&nbsp;Ronald C. W. Ma,&nbsp;Wayne J. Hawthorne,&nbsp;Louise T. Dalgaard,&nbsp;Mugdha V. Joglekar,&nbsp;Anandwardhan A. Hardikar","doi":"10.1111/apha.70277","DOIUrl":"10.1111/apha.70277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Human islets are widely researched to understand pathophysiological mechanisms leading to diabetes. Sex, age, and body mass index (BMI) are key donor traits influencing islet function, which is also regulated by an intricate network of microRNAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we profiled 754 microRNAs and 58 191 gene transcripts (19 919 protein-coding) in up to 131 different human islet donor preparations (without diabetes) and assessed their association with donor traits. Additionally, the effect of the age-associated key microRNAs on relative telomere length in human islet-derived cells was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MicroRNA discovery analyses identified miR-199a-5p and miR-214-3p to be associated (adjusted <i>p</i>-value ≤ 0.05) with all three traits (i.e., sex, age, and BMI); miR-147b-3p with sex and age; miR-378a-5p with sex and BMI; miR-542-3p, miR-34a-3p, miR-34a-5p, miR-497-5p and miR-99a-5p with age and BMI. After adjusting for covariates, 612 protein-coding gene transcripts associated with sex (excluding those from sex-chromosomes), 902 with age, and 250 with BMI. MicroRNA-199a-5p and miR-214-3p levels negatively correlated with mRNAs critical in islet function, metabolic regulation, and senescence. In vitro validation studies verified that inhibition of two common microRNAs (miR-199a-5p/-214-3p) slowed down telomere length shortening in human islet-derived cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our analyses identify human islet microRNAs associated with donor traits and provide evidence that these microRNAs can potentially modulate cellular aging phenotype (reflected by relative telomere length) in human islet-derived cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589720","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":"We Do Not Know Whether Head-Up Sleep Enhances Erythropoiesis","authors":"Meihan Guo,&nbsp;David Montero","doi":"10.1111/apha.70282","DOIUrl":"10.1111/apha.70282","url":null,"abstract":"&lt;p&gt;Red blood cells fill the “holy grail” of endurance performance. The more red blood cells in the circulation, the greater the capacity to deliver O&lt;sub&gt;2&lt;/sub&gt; to active muscle fibers, which determines peak O&lt;sub&gt;2&lt;/sub&gt; consumption (VO&lt;sub&gt;2peak&lt;/sub&gt;). Elite endurance athletes, without exception, present with a higher number of red blood cells per unit of body weight than untrained individuals. Beyond genetics, what increases the production of red blood cells, that is, erythropoiesis? Two main stimuli are established to date, chronic hypoxia and endurance training. We hypothesized an additional stimulus: chronic low circulating blood volume (BV) in the thoracic cavity, leading to neurohumoral reflexes increasing the production of erythropoietin (EPO) [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We tested the hypothesis that head-up sleep (HUS, 40 cm elevation of bed head, 12° head-up tilt) for 12 weeks would increase intravascular volumes, including plasma volume, total red blood cell volume (RBCV), and hemoglobin mass (Hb&lt;sub&gt;mass&lt;/sub&gt;) in healthy nonobese and nonsmoking women and men (42 ± 18 years, 51% women) [&lt;span&gt;2&lt;/span&gt;]. The participants were randomly allocated to (1) increased fluid (water) intake (IFI, 42 mL of water·kg&lt;sup&gt;−1&lt;/sup&gt;) (&lt;i&gt;n&lt;/i&gt; = 24), or (2) HUS + IFI (&lt;i&gt;n&lt;/i&gt; = 11). The IFI condition was intended to control for the placebo effect: the potential belief that the intervention elicited beneficial effects. Both groups were matched by sex, age, body composition, physical activity, and VO&lt;sub&gt;2peak&lt;/sub&gt;. Three individuals withdrew from the IFI intervention due to a busy working schedule or dislike of increased urination. Two individuals withdrew from the HUS + IFI intervention due to travel or sleep disturbance. Water intake was similar in IFI and HUS + IFI interventions (46.8 ± 4.8 vs. 44.5 ± 6.1 mL·kg&lt;sup&gt;−1&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.248). Heart rate, monitored at night, was elevated during the initial hours of sleep in the HUS + IFI group. Intravascular volumes and Hb&lt;sub&gt;mass&lt;/sub&gt; were unchanged with IFI or HUS + IFI (&lt;i&gt;p&lt;/i&gt; ≥ 0.246). At rest, cardiac filling and output per heart beat (stroke volume) were increased with both interventions (&lt;i&gt;p&lt;/i&gt; ≤ 0.007); the effect on resting stroke volume was larger with HUS + IFI than IFI alone (&lt;i&gt;p&lt;/i&gt; = 0.037). During exercise, peak cardiac output and VO&lt;sub&gt;2peak&lt;/sub&gt; were not altered with IFI or HUS + IFI, due to reduced left ventricular emptying (&lt;i&gt;p&lt;/i&gt; ≤ 0.003). The main results of this study are outlined in Figure 1. Our hypothesis was disproved. Could the control condition for the placebo effect (increased water intake) prevent the enhancement of erythropoiesis with HUS? We do not know, but to date, there is no evidence of increased water intake leading to reduced Hb&lt;sub&gt;mass&lt;/sub&gt;, rather the opposite [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;A recent study, not manipulating water intake, assessed the effects of 5 weeks of HUS (6° head-up tilt) on Hb&lt;sub&gt;mass&lt;/sub&gt; in healthy young men (&lt;i&gt;n&lt;/i&gt; = 9, 24 ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589641","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}