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        <title>Frontiers in Physiology | Cell Physiology section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/physiology/sections/cell-physiology</link>
        <description>RSS Feed for Cell Physiology section in the Frontiers in Physiology journal | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-05-12T19:43:19.377+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2026.1740128</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2026.1740128</link>
        <title><![CDATA[Walras modulates sex-dependent endoplasmic reticulum stress in cardiomyopathy]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Francisco J. Martinez-Amaro</author><author>Carlos Garcia-Padilla</author><author>Fernando Bonet</author><author>Elena Alonso-Villa</author><author>Rocio Toro</author><author>Houria Daimi</author><author>Eva Vargas</author><author>Ivan Hernandez</author><author>Borja Vilaplana-Martí</author><author>Ignacio Perez de Castro</author><author>Laetitia Bouchard</author><author>Fabien Hubert</author><author>Francesca Rochais</author><author>Antoine Muchir</author><author>Michaela Veliova</author><author>José Antonio Enriquez</author><author>Alejandro Salguero</author><author>Jose Luis De La Pompa</author><author>Estefania Lozano-Velasco</author><author>Diego Franco</author>
        <description><![CDATA[IntroductionCardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year. Most heart cardiomyopathies result in an increased need for protein production that translates into an increased endoplasmic reticulum stress and therefore in the activation of the unfolded protein response pathway (UPR). The sustained activation of this pathway produces cell death and worsens the course of the disease. The role of lncRNAs in UPR signalling and their impact in several cardiomyopathies is beginning to be addressed.MethodsTo conduct our study we have performed real time PCR (qPCR), immunochemistry (IMQ), SeaHorse mithocondrial activity, Western blot (WB), Mass spectrometry (MS) and cell viability analysis.ResultsOur results demonstrate a sex-dependent regulation of Walar, Walaa, Wallrd, Walrad and Walras lncRNAs in different dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) murine experimental models. Functional assays demonstrated that Walras overexpression leads to unfolded protein response (UPR) pathway activation and increased apoptosis, and additionally it also impairs mitochondrial function. Mechanistically, Walras physically interacts with calumenin (CALU), repressing its protein levels by promoting proteosomal degradation. Finally, we proved that APO02340.1, a Walras human homologue exerts a similar role.DiscussionOur data demonstrate that Walras and APO02340.1 modulate UPR associated apoptosis by regulating CALU protein turnover and thus acting as deletereous factors in several cardiomyophaties.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2026.1768672</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2026.1768672</link>
        <title><![CDATA[Mechanistic insights and challenges in mitochondrial regulation of macrophage polarization and inflammatory responses]]></title>
        <pubdate>2026-04-10T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Xinran Liu</author><author>Renping Liu</author>
        <description><![CDATA[Inflammation has a dual nature; excessive or uncontrolled inflammation can trigger metabolic inflammatory diseases, in which immune cells, especially macrophages, play a crucial role. Mitochondria, as the core of cellular energy metabolism, are closely related to macrophage polarization and inflammation regulation. Mitochondrial dysfunction can trigger inflammatory responses through the activation of multiple signaling pathways, involving multiple signaling pathways, including Cyclic GMP-AMP Synthase – Stimulator of Interferon Genes 1, inflammasomes, and Retinoic acid-Inducible Gene I (RIG-I). Currently, the role of mitochondria in regulating inflammatory responses is increasingly prominent; however, current research still faces many challenges, such as a lack of mechanistic connections, unclear details of key molecules, insufficiently refined experimental strategies, and difficulties in clinical translation. Future research needs to leverage advanced technologies to delve deeper into the mechanisms, improve the bioavailability and tissue-specific delivery of mitochondrial-targeted drugs, establish personalized evaluation criteria, and promote interdisciplinary innovation to facilitate the transition of mitochondrial-targeted therapy from basic research to clinical application.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2026.1783943</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2026.1783943</link>
        <title><![CDATA[From mechanical force to cellular response: the role of autophagy in orthodontic tooth movement]]></title>
        <pubdate>2026-03-25T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Yuan Dong</author><author>Yangyu Liu</author><author>Zhiqiang Hu</author><author>Chongxiao Qu</author>
        <description><![CDATA[Orthodontic tooth movement (OTM) is a process responding to orthodontic forces, which converts mechanical stresses into biochemical events to reconstruct the periodontal ligament and alveolar bone. As a lysosome-dependent catabolic process induced by various cellular stress conditions, autophagy maintains the homeostasis of cells, tissues, and organs and is widely involved in different physiologic or pathologic processes in the tooth. Recently, accumulating studies have investigated the role of autophagy in OTM. In this review, we focus on the autophagy induced by orthodontic forces, discuss the multifaceted effects of autophagy in bone remodeling, inflammation, and complications in OTM, which may reveal the potential clinical implications of autophagy in OTM and provide potential therapeutic targets for future orthodontic clinical treatment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1681290</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1681290</link>
        <title><![CDATA[Predictive value of matrix metalloproteinase-9 combined with magnetic resonance spectroscopy for delayed cerebral edema after spontaneous intracerebral hemorrhage]]></title>
        <pubdate>2026-02-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jing Sun</author><author>Lei Chen</author>
        <description><![CDATA[ObjectiveThe aim of this paper was to evaluate the predictive value of matrix metalloproteinase (MMP)-9 combined with magnetic resonance spectroscopy (MRS) for delayed cerebral edema after spontaneous intracerebral hemorrhage (SICH).MethodsPatients with head computed tomography (CT) suggestive of SICH were retrospectively included. Serum MMP-9 levels were measured within 24 h of the onset of the disease, and MRS was performed on day 3 after admission; N-acetylaspartate/creatine (NAA/Cr) values of edematous areas in MRS were measured and calculated separately. Delayed cerebral edema was defined as a 1-cm increase in the diameter of the peripheral edema around an intracerebral hematoma within 14 days compared with the peripheral diameter of the edema at 7 days, as confirmed by dynamic CT. Demographics of the delayed cerebral edema group were compared with those of the control group, along with baseline clinical data. Multivariate logistic regression analysis was applied to evaluate independent predictors of delayed cerebral edema. The predictive value of MMP-9 and MRS-related indices for delayed cerebral edema was assessed using receiver operating characteristic (ROC) curves.ResultsEighty SICH patients were included: 27 in the delayed cerebral edema group and 53 in the non-delayed cerebral edema group (control group). Univariate analysis revealed higher MMP-9 levels and NAA/Cr values in the delayed cerebral edema group relative to the control group (both P < 0.05). Multivariate logistic regression analysis disclosed that increased MMP-9 levels (OR = 1.041, 95% CI: 1.019–1.064, P < 0.001) and decreased NAA/Cr values (OR = 0.095, 95% CI: 0.015–0.586, P = 0.011) were independent predictive factors for the development of delayed cerebral edema after SICH. ROC curve analysis reflected that the area under the curve (AUC) of serum MMP-9 and NAA/Cr values alone and the area under the curve of the combination of the two indices for predicting the development of delayed cerebral edema after SICH were 0.835, 0.734, and 0.874, respectively.ConclusionThe combination of serum MMP-9 detection and MRS has a high efficacy in predicting the occurrence of delayed cerebral edema in SICH, providing guidance for subsequent clinical diagnosis and treatment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1734886</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1734886</link>
        <title><![CDATA[Long noncoding RNA X-inactive-specific transcript promotes hepatic fibrosis by suppressing ferroptosis in hepatic stellate cells via the miR-663a/GPX4 axis]]></title>
        <pubdate>2026-02-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jing Dai</author><author>Guo-Hui Zhong</author><author>Jun-Xing Yang</author><author>Xiao-Yu Tan</author><author>Dong Dai</author><author>Ming-Yi Li</author>
        <description><![CDATA[AimHepatic fibrosis (HF) is a critical pathological stage in the progression of chronic liver diseases, where hepatic stellate cell (HSC) activation is a key event. Ferroptosis regulates the fate of HSCs and represents a potential anti-fibrotic target. Long non-coding RNA XIST (lncRNA-XIST) is involved in fibrosis-related diseases. This study investigated how lncRNA-XIST promotes HF by regulating ferroptosis through the microRNA-663 (miR-663a)/GPX4 axis.MethodsLX-2 HSCs were activated using ethanol at varying concentrations for different durations to determine optimal conditions. HSCs were intervened with small interfering RNA against lncRNA-XIST, and Liproxstatin-1 was applied. RT-qPCR, Western blotting, CCK-8, colony formation, LDH release, and biochemical assays assessed gene/protein expression, cell viability, proliferation, ferroptosis markers (Fe2+, MDA, GSH), and cell death. Dual-luciferase assays validated interactions among lncRNA-XIST, miR-663a, and GPX4. In vivo, an HF mouse model was established and treated with sh-XIST or miR-663a antagonists. Liver fibrosis was evaluated by histology, immunohistochemistry, and serum liver injury markers (ALT, AST, HYP).ResultsEthanol promoted LX-2 activation and upregulated lncRNA-XIST in a time- and dose-dependent manner (optimal: 100 mM, 24 h). LncRNA-XIST knockdown reduced α-SMA, CoL1A1, GPX4 levels, and cell proliferation while increasing ferroptosis markers (indicative of enhanced ferroptosis) and miR-663a expression. Mechanistically, lncRNA-XIST was found to act as a competing endogenous RNA (ceRNA) to sponge miR-663a, thereby upregulating GPX4 and inhibiting ferroptosis. In vivo, lncRNA-XIST was shown to promote HF progression via the miR-663a/GPX4 axis.ConclusionLncRNA-XIST promotes HF by acting as a ceRNA for miR-663a, regulating GPX4, and suppressing ferroptosis to activate HSCs.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2026.1772233</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2026.1772233</link>
        <title><![CDATA[Correction: Single-cell transcriptome analysis profiles cellular dynamics and transcriptional changes in diabetic wound tissues following ESWT treatment]]></title>
        <pubdate>2026-02-09T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Dongyu Li</author><author>Yu Wang</author><author>Yunlong Wang</author><author>Changhai Shao</author><author>Lei Wang</author><author>Shijie Xin</author><author>Yuewen Ma</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1636766</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1636766</link>
        <title><![CDATA[Human primary skeletal muscle cells express glutamate receptor GluR3, are activated by glutamate, and are affected by autoimmune GluR3B antibodies of epilepsy patients]]></title>
        <pubdate>2025-12-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Mia Levite</author><author>Nili Ilouz</author><author>Avi Harazi</author><author>Hadassa Goldberg-Stern</author><author>Eithan Galun</author><author>Stella Mitrani-Rosenbaum</author>
        <description><![CDATA[BackgroundGlutamate 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.QuestionsDo 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?ResultsWe 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 implicationsTogether, 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1731863</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1731863</link>
        <title><![CDATA[Structural integrity of RyR2 clusters controls cardiac calcium leak]]></title>
        <pubdate>2025-12-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Andrew Noren</author><author>Yohannes Shiferaw</author>
        <description><![CDATA[BackgroundCalcium (Ca) leak from the sarcoplasmic reticulum contributes to cardiac arrhythmias, yet the structural mechanisms regulating spontaneous Ca release from ryanodine receptor type 2 (RyR2) clusters remain poorly understood.MethodsWe developed a computational model in which each RyR2 channel comprises four interacting subunits embedded within spatially organized clusters. This framework captures both cooperative gating within individual channels and coupling between neighboring channels.ResultsOur simulations reveal that spontaneous Ca spark timing depends exponentially on RyR2 cluster structural integrity. This exponential sensitivity means that modest disruptions in cluster structure, such as partial fragmentation, can increase spontaneous Ca spark frequency by 100–1,000 fold.ConclusionsCluster structural integrity provides a powerful control mechanism for Ca leak and represents a promising therapeutic target for restoring Ca homeostasis in cardiac myocytes.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1613917</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1613917</link>
        <title><![CDATA[Tracking hemopexin intracellularly and defining hemopexin protein “interactomes” in human immune and liver cell models]]></title>
        <pubdate>2025-11-20T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Bryan Rose</author><author>David Moore</author><author>Jeff Eskew</author><author>Roberto Vanacore</author><author>Steve D. Hartson</author><author>Dennis Province</author><author>D. Andrew Skaff</author><author>Ann Smith</author>
        <description><![CDATA[Maintaining hemopexin (HPX) plasma levels protects against heme-activated inflammation as well as the toxicity of heme and its iron during hemolysis. Plasma heme regulates HPX turnover in hepatocytes, thus controlling plasma HPX concentration. Heme from heme–HPX is delivered to the liver, and apo-HPX recycles without degradation. The scavenger receptor, low-density lipoprotein-related protein 1 (LRP1), binds heme–HPX and targets it for lysosomal degradation. Nevertheless, heme–HPX endocytosis also occurs in mouse embryonic fibroblast LRP1−/−PEA 13 cells. Therefore, the cell biology of heme–HPX endocytosis requires elucidation. We have identified candidate HPX receptors and human proteins that bind to heme–HPX, i.e., HPX “interactomes,” in a human neutrophil model (promyelocytic HL-60 cells), in hepatoma HepG2 cells, and in primary human hepatocytes. Immunoblots revealed that HL-60 cells lack LRP1, and immunocytochemistry established that HPX trafficked with transferrin and transferrin receptor 1 (TfR1) in Rab5-positive early endosomes, supporting a clathrin-mediated endocytotic pathway used by TfR1s. TfR1 was isolated by heme–HPX affinity chromatography of HL-60 and HepG2 extracts, and similarly, LRP1 from HepG2 cells. These receptors and novel HPX interactome proteins were identified by their peptide sequences. TfR1 downregulation in HL-60 cells in response to holo-human transferrin (Tf) decreased surface binding and intracellular HPX, implicating TfRs in heme–HPX endocytosis. In LRP+/+ HepG2 cells, HPX trafficked in endosomes with LRP1 and TfR1, or with TfR1 alone. HPX co-localized with TfR2, supporting that TfR2 potentially provides liver targeting of heme–HPX in vivo. TfR1 and 2 could both account for apo-HPX recycling. Heme–HPX affinity isolates from primary human hepatocytes contain LRP1 and TfR1. This HPX “interactome” also included proteins associated with hemostasis, inflammation control, coagulation regulation, wound healing, iron transport, and body fluid regulation. The overlapping and distinct roles of TfR1, TfR2, and LRP1 with HPX are reviewed. TfR1 is a scavenger receptor like LRP1; nevertheless, specific hepatic HPX receptors may exist. Increasing knowledge of HPX biology will elucidate the causes that regulate plasma HPX, thus improving clinical and veterinary care. Interestingly, increased understanding of the hematological adaptations to weightlessness that lead to anemia, termed “space anemia,” in astronauts and space tourists may provide new insights into HPX’s role in maintaining iron homeostasis and red cell biology under microgravity conditions as well as upon recovery from space and other anemias.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1693937</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1693937</link>
        <title><![CDATA[Single-cell transcriptome analysis profiles cellular dynamics and transcriptional changes in diabetic wound tissues following ESWT treatment]]></title>
        <pubdate>2025-11-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Dongyu Li</author><author>Yu Wang</author><author>Yunlong Wang</author><author>Changhai Shao</author><author>Lei Wang</author><author>Shijie Xin</author><author>Yuewen Ma</author>
        <description><![CDATA[IntroductionDiabetic wounds (DWs) remain a major complication of diabetes mellitus, characterized by impaired healing and limited therapeutic options. Extracorporeal shock wave therapy (ESWT), a non-invasive physical modality, has recently shown promise in accelerating chronic wound repair, yet the underlying cellular mechanisms remain poorly understood.MethodsHere, we employed single-cell RNA sequencing (scRNA-seq) to construct a comprehensive cellular atlas of DW tissues treated with ESWT, profiling approximately 39,475 cells.ResultsOur analysis identified 12 major cell populations, including macrophages, fibroblasts, endothelial cells, keratinocytes, and immune subsets, and revealed widespread transcriptional reprogramming associated with ESWT treatment. ESWT promoted the expansion of reparative macrophages, activated proregenerative fibroblast states, and restored angiogenic programs in endothelial cells. Moreover, cell–cell communication analysis revealed that ESWT not only attenuates pro-inflammatory signaling but also activates immune cell communication networks, thereby enhancing T cell, NK cell, and dendritic cell interactions. These changes collectively promote immune regulation and tissue repair, contributing to the restoration of a balanced wound microenvironment.DiscussionTogether, these findings provide a high-resolution single-cell map of ESWT mediated cellular and molecular alterations in DWs and uncover key cellular pathways contributing to improved tissue repair. This study offers new insights into the mechanisms of ESWT and supports its translational potential as a therapeutic strategy for chronic wound management.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1676701</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1676701</link>
        <title><![CDATA[Calcium arrhythmogenicity of Purkinje fibers: importance of the animal model]]></title>
        <pubdate>2025-10-30T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Bruno D. Stuyvers</author>
        <description><![CDATA[Ventricular tachycardias (VTs) and fibrillations (VFs) are frequent complications of ischemic myocardial infarction (MI). Because their initiation mechanism remains unknown, these arrhythmias are virtually unpredictable and often degenerate into cardiac arrest and syncope without immediate medical assistance. Electrical mapping and ablation techniques have located the origin of ischemic arrhythmias in the terminal arborizations of the cardiac conduction system, the Purkinje fibers. A classical model of MI in the dog has demonstrated that abnormal calcium (Ca2+) cycling in the Purkinje cells (Pcells) is the source of non-driven depolarizations (DADs) in the conduction tissue and is likely to create the pro-arrhythmic conditions of human ischemic heart. A better understanding of Ca2+ abnormalities in Pcells post infarction is an evident prerequisite for elucidating the mechanism of ischemic arrhythmias. Nevertheless, a unique Ca2+ handling system was discovered in Pcells, exhibiting fundamental differences compared with the well-known model of Excitation-Contraction coupling of ventricular cardiomyocytes. This cellular specificity of Purkinje fibers was observed in large mammalian species but not in murine hearts, where Purkinje cells are comparable to ventricular myocytes and designed to respond to 400–600 stimulations/min. The present report reviews the mechanism of Ca2+ arrhythmogenicity in Pcells of large mammalian hearts and documents the need for animal models that simulate the size and function of human hearts to study ischemic arrhythmias.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1693112</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1693112</link>
        <title><![CDATA[Residue 39 of Kir6.2 drives a difference in ATP sensitivity in human and canine beta-cell KATP channels]]></title>
        <pubdate>2025-10-17T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Natascia Vedovato</author><author>Frances M. Ashcroft</author><author>Brian Catchpole</author><author>Lucy J. Davison</author>
        <description><![CDATA[ATP-sensitive potassium (KATP) channels link beta-cell metabolism to electrical activity. By modulating the beta-cell membrane potential, they finely regulate glucose-stimulated insulin secretion. KATP channels are hetero-octameric complexes composed of four pore-forming subunits (Kir6.2, encoded by KCNJ11) and four regulatory subunits (SUR1, encoded by ABCC8). A multi-species alignment of the KCNJ11 gene revealed that, although the sequence is highly conserved, residue 39 varies among different mammals. Previous studies have shown that this residue plays a critical role in regulating KATP channel activity and its mutation results in neonatal diabetes in humans. We therefore explored whether the canine and human KATP channel show different ATP sensitivities as a result of their sequence variation. We used patch-clamp electrophysiology to investigate species variation in the ATP sensitivity of the KATP channel. Functional studies showed that canine KATP channels exhibit reduced ATP sensitivity compared to human channels. However, stimulation by MgADP was unaffected. We next compared the ATP sensitivity of hybrid channels (human Kir6.2 with canine SUR1, and vice versa), as well as KATP channels in which residue 39 was swapped between human and canine Kir6.2. In each case, ATP sensitivity was mainly determined by the identity of the residue at position 39. Our study suggests that the ATP sensitivity of the pancreatic KATP channel differs between human and dog. This suggests that the beta-cell membrane potential and potentially insulin release may be fine-tuned differently across species.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1641653</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1641653</link>
        <title><![CDATA[RARRES1 attenuates H2O2-induced RPE cell injury and inhibits choroidal neovascularization]]></title>
        <pubdate>2025-10-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yimeng Li</author><author>Caixia Wang</author><author>Tao Deng</author><author>Xuejing Li</author><author>Renhao Xu</author><author>Qingli Shang</author>
        <description><![CDATA[IntroductionNeovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in the elderly, yet its underlying molecular mechanisms remain incompletely understood, and novel biomarkers and therapeutic targets are urgently needed. This study aimed to identify and functionally characterize potential biomarkers and therapeutic candidates for nAMD, with a focus on retinoic acid receptor responder protein 1 (RARRES1). MethodsTandem mass tag (TMT)–based proteomic analysis was performed on aqueous humor samples from patients with nAMD and age-related cataracts. RARRES1 expression was examined in aqueous humor, laser-induced choroidal neovascularization (CNV) model mice, and human ARPE-19 cells exposed to H2O2. Functional studies assessed the effects of RARRES1 on oxidative stress, cell death, inflammatory and angiogenic factor expression, and signaling pathways in ARPE-19 cells. Its effects on proliferation, migration, and tube formation were tested in HUVECs. In vivo, a RARRES1-overexpressing AAV2 vector was injected intraocularly into CNV model mice, and lesion size and vascular leakage were evaluated using fundus fluorescein angiography, hematoxylin and eosin staining, and isolectin B-4 fluorescence staining. ResultsRARRES1 was significantly reduced in the aqueous humor of nAMD patients, in CNV model mice, and in H2O2-treated ARPE-19 cells. Overexpression of RARRES1 in ARPE-19 cells mitigated oxidative stress–induced damage, suppressed inflammatory and angiogenic factor expression, inhibited JNK phosphorylation, and increased Sirtuin 1 and Nrf2 expression. In HUVECs, RARRES1 reduced proliferation, migration, and tube formation. In vivo, intraocular delivery of RARRES1 significantly reduced CNV lesion size and vascular leakage. ConclusionRARRES1 protects retinal pigment epithelial cells from oxidative stress, inhibits choroidal neovascularization, and modulates inflammatory and angiogenic pathways. These findings identify RARRES1 as a potential biomarker and therapeutic target for nAMD.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1641445</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1641445</link>
        <title><![CDATA[Metabolomic profiling reveals novel biomarkers and therapeutic targets in Legg-Calvé-Perthes disease: a comprehensive analysis of peripheral blood and endothelial function]]></title>
        <pubdate>2025-10-01T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Shaoneng Zi</author><author>Chengyong Wang</author><author>Tong Zhang</author><author>Qian Lv</author><author>Zhiying Wan</author><author>Pengju He</author><author>Yong Hang</author><author>Yongqing Xu</author>
        <description><![CDATA[IntroductionLegg-Calvé-Perthes disease (LCPD) is juvenile idiopathic femoral head avascular necrosis with unclear pathophysiology. We aimed to identify circulating metabolic biomarkers and clarify the roles of peripheral inflammation and vascular/endothelial dysfunction in LCPD, and to evaluate the protective potential of 3-ketoglucose (3-KG) and sanguinarine (SANG).MethodsPeripheral blood from children with LCPD (n=36) and healthy controls (n=6) underwent untargeted LC-MS metabolomics with differential and pathway analyses. Candidate metabolites (3-KG, SANG) were tested in LPS-challenged HUVECs for effects on viability, ROS, IL-1β/IL-6/TNF-α, and NF-κB/eNOS/VCAM-1 (RNA-seq, qPCR, Western blot, immunofluorescence). In vivo validation used a steroid/LPS-induced rat model of femoral head osteonecrosis assessing histology, adipogenesis, serum ALP/TG, and Nos3/Vcam1/Nfkb1 expression.ResultsThirty-eight metabolites differed significantly between LCPD and controls; 3-KG and SANG were upregulated, whereas several metabolites including N-methyl-D-aspartate were downregulated, mapping to inflammatory and oxidative-stress pathways. Both 3-KG and SANG dose-dependently mitigated LPS-induced HUVEC injury by restoring viability, lowering ROS and pro-inflammatory cytokines, and normalizing NF-κB/eNOS/VCAM-1 at mRNA and protein levels, with SANG showing greater potency. In rats, both compounds ameliorated bone loss and adipogenesis, increased ALP, reduced TG, and reversed MPS-induced changes in Nos3, Vcam1 and Nfkb1.DiscussionThis work defines a peripheral “metabolomic fingerprint” of LCPD and links systemic metabolic alterations to endothelial inflammation/dysfunction. 3-KG and SANG exhibit endothelial-protective activity in vitro and in vivo, supporting their promise as diagnostic biomarkers and therapeutic candidates. Larger, longitudinal cohorts are needed to validate these signatures and clarify stage-specific dynamics.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1633251</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1633251</link>
        <title><![CDATA[Activation of Piezo1 and TRPV4 channels contributes to hCMEC/D3 cell mechano-sensing]]></title>
        <pubdate>2025-09-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Wenhan An</author><author>Min Sun</author><author>Xiulin Zhang</author><author>Laigang Huang</author><author>Hanwen Liu</author><author>Baojuan Cui</author>
        <description><![CDATA[IntroductionTRPV4 and Piezo1 channels have been considered two important mechanical sensors. To examine the role of these two channels in blood brain barrier (BBB) mechano-sensing, the expression and function of TRPV4 and PIEZO1 in hCMEC/D3, an in vitro model for human BBB endothelial cells, were investigated.MethodsTRPV4 and PIEZO1 mRNA and protein expression were analysed by RT-PCR, immunofluorescence and western blot, respectively, while their mechano-sensing function was investigated by calcium imaging.ResultsAmong the four mechano-sensing channels examined (TRPV2, TRPV4, PIEZO1 and Piezo2), TRPV4 and PIEZO1 were the two most abundantly expressed in hCMEC/D3 cells at the mRNA level. TRPV4 and PIEZO1 proteins were detected by immunofluorescence, western blot. The calcium imaging using channel-specific agonists/antagonists provided evidence of their function. Mechanical stimuli (poke or flow shear stress) induced a prominent increase in intracellular Ca2+([Ca2+]i) in hCMEC/D3 cells, which was significantly inhibited by application of selective TRPV4 or Piezo1 antagonists. Activation of PIEZO1 and TRPV4 using selective agonists resulted in the release of adenosine triphosphate (ATP) but not nitric oxide (NO). Extracellular ATP hydrolysis with apyrase, or blocking of P2X and P2Y purinoceptors with PPADS, significantly reduced mechanical stimulus-induced increases in [Ca2+]i in both the stimulated cell and neighboring cells.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1641323</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1641323</link>
        <title><![CDATA[Targeting ferroptosis for neuroprotection: potential therapeutic avenues in neurodegenerative and neuropsychiatric diseases]]></title>
        <pubdate>2025-08-28T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Muhammad S. Khan</author><author>Qichan Hu</author><author>Kendrix Okeibunor</author><author>Liang Ma</author><author>Jean C. Bopassa</author>
        <description><![CDATA[Ferroptosis is an iron-dependent programmed cell death that plays an important role in neurodegenerative and neuropsychiatric diseases. In the present study, we have highlighted how different risk factors are involved in the induction of ferroptosis in brain cells. In addition, we also demonstrated how ferroptosis plays an important role in different brain diseases. In our study why we focused and elaborated on the mechanisms of ferroptosis only in brain cells (Neurons, oligodendrocytes, and microglia) because they are particularly vulnerable to such kind of cell death. Additionally, brain cells are more dependent on mitochondrial function, iron regulation, and high levels of polyunsaturated fatty acids (PUFAs) as compared to peripheral body cells. Highlighting ferroptosis is more important because it has demonstrated several important mechanisms of neuronal injury and dysfunction which provides a deep understanding of the etiology of various brain diseases that were not sufficiently described by other programmed cell death pathways. Therefore, it has led to the exploration of new therapeutic strategies against various brain diseases and thus targeting ferroptosis-related proteins opens a new therapeutic window for several incurable brain diseases, and various ferroptosis regulators are now under clinical trials. However, their validation as a preclinical therapeutic agent is needed. Interestingly, here in our study we also summarize the most recent potential therapeutic targets and promising interventions which will provide a beam of light for future therapies against major brain diseases.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1647865</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1647865</link>
        <title><![CDATA[Advancements in macrophage research for cardiovascular disease]]></title>
        <pubdate>2025-08-14T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Meiling Cao</author><author>Yu Sun</author><author>Xinyue Zhang</author><author>Jiahui Zou</author><author>Mingyue Shi</author><author>Lei Li</author><author>Hongkun Jiang</author>
        <description><![CDATA[Cardiovascular disease is a major cause of human morbidity and mortality. With the rising prevalence of cardiovascular diseases and their increasing economic impact on individuals and society, a deeper understanding of their pathogenesis is essential. Macrophages play the crucial role in this regulatory network as key cell types in the innate immune system. This review provides an overview of the subpopulations, heterogeneity, and ontogenetic diversity of macrophages. It emphasizes how various cellular metabolic processes influence the biological functions of macrophages. Additionally, it explores the mechanisms through which macrophages function in different cardiovascular diseases (e.g., atherosclerosis, hypertension, or myocardial infarction) and examines their potential therapeutic applications. The review also addresses the current limitations and future directions for research and therapeutic strategies involving cardiac macrophages in cardiovascular diseases.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1617215</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1617215</link>
        <title><![CDATA[Exploring the potential anti-apoptotic effects of traditional Chinese medicine in intervertebral disc degeneration: mechanisms and therapeutic prospects]]></title>
        <pubdate>2025-08-04T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Kuaixiang Zhang</author><author>Lei Wan</author><author>Malik Ihsan Ullah Khan</author><author>Feifei Pu</author><author>Man Liu</author><author>Zhiqiang Zhao</author><author>Jitian Li</author>
        <description><![CDATA[Intervertebral disc degeneration (IDD) stands as one of the primary culprits behind low back pain and disability, imposing substantial burdens on individual health, families, and societal wellbeing. The multifactorial etiology and complex pathology of IDD pose significant challenges, with molecular mechanisms still not fully elucidated. A key aspect of the pathogenesis of IDD involves programmed cell death, specifically apoptosis, which exacerbates the condition by fostering the apoptosis of intervertebral disc (IVD) cells and accelerating the degradation of the extracellular matrix (ECM). Conversely, inhibiting apoptosis signalling pathways has emerged as a promising therapeutic strategy for IDD. Recent research has highlighted the potential of traditional Chinese medicine (TCM) to alleviate IDD at the genetic level by modulating apoptotic pathways. This review integrates the intricate mechanisms of IDD-induced cell apoptosis, the relevant targets implicated in IVD cell apoptosis, and the latest advancements in TCM-based treatments, drawing from a comprehensive analysis of literature sourced from the PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science databases. This study aims to offer fresh perspectives and innovative concepts for pharmacological interventions and to serve as a valuable reference for ongoing and future research endeavors. As the field of antiapoptotic research progresses, there is increasing urgency to identify safe, effective, and economically viable compounds from the vast array of natural resources, including plants and animals, to support the prevention and management of IDD. This approach not only aligns with the principles of sustainable development but also holds the promise of enriching the therapeutic armamentarium against IDD.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1636931</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1636931</link>
        <title><![CDATA[Ultrastructural insights into early myoblast differentiation induced by shockwave stimulation]]></title>
        <pubdate>2025-07-23T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Larisa Ryskalin</author><author>Federica Fulceri</author><author>Paola Soldani</author><author>Maria Cristina D’Agostino</author><author>Gabriele Morucci</author><author>Stefania Moscato</author><author>Marco Gesi</author>
        <description><![CDATA[IntroductionExtracorporeal shockwave therapy (ESWT) is a non-invasive therapeutic modality that uses high-energy acoustic waves (shockwaves, SW) to restore local homeostasis and stimulate tissue healing and regeneration through mechanotransduction. ESWT has gained popularity in treating numerous musculoskeletal indications such as tendinopathies, plantar fasciitis, bony non-unions, and stress fractures, with proven benefits in reducing pain, enhancing recovery, and in some cases preventing recurrence. In contrast, SW application in muscle injuries remains less investigated. Some clinical studies have shown promising results of ESWT for treating muscle injuries. Preclinical animal studies suggest that SW can improve muscle microcirculation, reduce inflammation, and accelerate tissue regeneration. In vitro studies, however, reported conflicting data regarding the effects of SW on muscle cells, with little data on ultrastructural changes supporting clinical results.Methods This study aimed to evaluate the ultrastructural effects of SW on C2C12 myoblasts. We applied 500 pulses with an Energy Flux Density of 0.1 mJ/mm2, 4 Hz, at a distance of 5 cm between the SW applicator and cell culture in a 37°C water bath. Evaluations were conducted at 24 h, 72 h, and up to 7 days post-treatment, including cell viability, Western blot, histomorphometry, and ultrastructural analysis. Immunocytochemistry for Myoblast Determination Protein 1 (MyoD) and Myogenin (MyoG) was performed to characterize subcellular distribution.ResultsLight and electron microscopy revealed that SW stimulation induced significant morphological changes, including increased cell elongation and ultrastructural features suggesting early fusion events. These changes correlated with a rise in the percentage of multinucleated cells, indicative of early myoblast differentiation. Despite this, Western blot analysis showed no significant differences in total MyoD and MyoG levels. However, immunogold electron microscopy demonstrated a marked increase in nuclear localization of both markers in treated cells, aligning with their roles in myogenic differentiation.DiscussionThese findings suggest SW promotes early myogenic progression through enhanced nuclear translocation of key regulatory proteins, rather than altering expression levels. Exploring SW-induced ultrastructural changes may offer new perspectives on early steps of myogenesis and holds promise for disclosing novel hypotheses on SW biological underpinning and expanding translational ESWT application in muscle injuries and sports medicine.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fphys.2025.1627164</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fphys.2025.1627164</link>
        <title><![CDATA[Multiple roles of ALDH1 in health and disease]]></title>
        <pubdate>2025-07-10T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Wenqi Zhao</author><author>Yu Xia</author><author>Zhiqi Gao</author><author>Jian Chen</author><author>Erlong Zhang</author>
        <description><![CDATA[Aldehyde dehydrogenase 1 (ALDH1) is an important aldehyde-metabolizing enzyme that plays a key role in various biological processes, such as regulating cellular growth, modulating retinoic acid (RA) signaling pathways, and contributing to stem cell function. It is recognized as a crucial biomarker not only because of its significant involvement in the occurrence and development of various cancers but also because it is an important prognostic indicator for cancer progression. Furthermore, recent research has provided substantial evidence that the multiple roles of ALDH1 extend beyond cancer, with significant progress in understanding its mechanisms in other diseases and its clinical applications. These findings provide potential therapeutic targets for the future treatment of other diseases. In this review, we summarize the current understanding of the biological functions of ALDH1, the molecular mechanisms of its transcription and regulation, and the progress in cancer research related to the ALDH1 family. We not only discuss the mechanisms of ALDH1 in cancer but also its research development and potential pathological mechanisms in other diseases. The role of ALDH1 in various diseases is complex, and its expression levels are highly important for disease diagnosis, treatment, and prognosis. Future in-depth studies on ALDH1 functions are expected to provide new strategies and directions for the treatment of related diseases.]]></description>
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