Biomolecules最新文献

{"title":"Valproic Acid Promotes the Differentiation of Satellite Glial Cells into Neurons via the pH-Dependent Pathway.","authors":"Dongyan Wang, Wenrun Kang, Jinhui Zhang, Jianwei Xu, Ruyi Wang, Xiangdan Xiao, Chao Wei, Wenfeng Yu, Junhou Lu","doi":"10.3390/biom15070986","DOIUrl":"10.3390/biom15070986","url":null,"abstract":"<p><p>Valproic acid (VPA) is a widely prescribed antiepileptic agent whose teratogenic potential has been recognized. In recent years, VPA has been shown to promote neuronal regeneration; however, the exact molecular mechanisms are not fully understood. This study elucidates the pH-dependent pathway through which VPA promotes the differentiation of satellite glial cells (SGCs) into neurons. We observed sustained intracellular pH elevation during the VPA-induced neural differentiation of SGCs, and the modulation of intracellular pH was shown to influence this differentiation process. Then, we found that VPA regulates intracellular pH through NHE1 (sodium-hydrogen exchanger 1), and that the pharmacological inhibition of NHE1 not only attenuated intracellular pH elevation but also substantially impaired VPA-induced neuronal differentiation. Finally, our results showed that the elevated intracellular pH promoted the neuronal differentiation of SGCs by activating β-catenin signaling. These findings provide novel insights into the mechanisms of VPA-induced neurogenesis, advancing our understanding of its pharmacological profile and informing its potential therapeutic application in neuronal regeneration strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.","authors":"Yan Chen, Kaiwen Lei, Yanglong Liu, Jianshen Liu, Kunhua Wei, Jiao Guo, Zhengquan Su","doi":"10.3390/biom15070990","DOIUrl":"10.3390/biom15070990","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive accumulation of triglycerides and other lipids within liver cells and is closely associated with cardiovascular disease and metabolic syndrome. Very low-density lipoprotein (VLDL) is a lipoprotein synthesized and secreted by the liver and is primarily responsible for transporting triglycerides from the liver to peripheral tissues. Therefore, there is a strong association between MASLD and VLDL. Studies have found that excess production and abnormal metabolism of VLDL can lead to elevated blood triglyceride levels, which in turn promote fat deposition in the liver, leading to MASLD. During the pathophysiological process of MASLD, adipokines and inflammatory mediators secreted by adipose tissue can affect the metabolic network of the liver, further aggravating VLDL metabolic disorders. This paper reviews the effects of VLDL synthesis and metabolism on the development of MASLD, including the changes in VLDL structure and composition, the biosynthesis of VLDL, and the mechanism of underlying VLDL-associated damage, in an attempt to elucidate the intricate crosstalk between MASLD and VLDL, in order to provide new perspectives and methods for the prevention and treatment of related diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A.","authors":"Xuemeng Shi, Shuaiwu Chen, Mingyang Liu, Yali Fan, Xin Wen, Jingyi Wang, Xiaoling Li, Huimin Liu, Lin Mao, Li Yu, Yuxin Hu, Jun Xu","doi":"10.3390/biom15070992","DOIUrl":"10.3390/biom15070992","url":null,"abstract":"<p><p>The broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how ABHD17A regulates the dynamic S-palmitoylation modification of IFITM1 remains unknown. Here, we demonstrated that ABHD17A physically interacts with IFITM1 and increases the S-palmitoylation level of IFITM1. Sequence alignment revealed that ABHD17A lacked the DHHC motif, which is capable of catalyzing the S-palmitoylation modification. Thus, we screened multiple candidate palmitoylating and depalmitoylating enzymes that may contribute to ABHD17A-induced upregulation of IFITM1 S-palmitoylation. The recently discovered depalmitoylase ABHD16A was significantly downregulated by ABHD17A, which counteracted the palmitate-removing reactions of ABHD16A on IFITM1 and subsequently upregulated the S-palmitoylation level and antiviral activity of IFITM1. Our work therefore elucidated the unconventional role of depalmitoylase ABHD17A in elevating the S-palmitoylation modification, expanded the biological functions of ABHD17A in innate immunity, and provided potential targets for viral disease therapy.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Differentiation Factor 15 Predicts Cardiovascular Events in Peripheral Artery Disease.","authors":"Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin, Mohammad Qadura","doi":"10.3390/biom15070991","DOIUrl":"10.3390/biom15070991","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Peripheral artery disease (PAD) is associated with an elevated risk of major adverse cardiovascular events (MACE). Despite this, few reliable biomarkers exist to identify patients at heightened risk of MACE. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine implicated in inflammation, atherosclerosis, and thrombosis, has been broadly studied in cardiovascular disease but remains underexplored in PAD. This study aimed to evaluate the prognostic utility of GDF15 for predicting 2-year MACE in PAD patients using explainable statistical and machine learning approaches. We conducted a prospective analysis of 1192 individuals (454 with PAD and 738 without PAD). At study entry, patient plasma GDF15 concentrations were measured using a validated multiplex immunoassay. The cohort was followed for two years to monitor the occurrence of MACE, defined as stroke, myocardial infarction, or death. Baseline GDF15 levels were compared between PAD and non-PAD participants using the Mann-Whitney U test. A machine learning model based on extreme gradient boosting (XGBoost) was trained to predict 2-year MACE using 10-fold cross-validation, incorporating GDF15 and clinical variables including age, sex, comorbidities (hypertension, diabetes, dyslipidemia, congestive heart failure, coronary artery disease, and previous stroke or transient ischemic attack), smoking history, and cardioprotective medication use. The model's primary evaluation metric was the F1 score, a validated measurement of the harmonic mean of the precision and recall values of the prediction model. Secondary model performance metrics included precision, recall, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). A prediction probability histogram and Shapley additive explanations (SHAP) analysis were used to assess model discrimination and interpretability. The mean participant age was 70 ± SD 11 years, with 32% (&lt;i&gt;n&lt;/i&gt; = 386) female representation. Median plasma GDF15 levels were significantly higher in PAD patients compared to the levels in non-PAD patients (1.29 [IQR 0.77-2.22] vs. 0.99 [IQR 0.61-1.63] pg/mL; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). During the 2-year follow-up period, 219 individuals (18.4%) experienced MACE. The XGBoost model demonstrated strong predictive performance for 2-year MACE (F1 score = 0.83; precision = 82.0%; recall = 83.7%; LR+ = 1.88; LR- = 0.83). The prediction histogram revealed distinct stratification between those who did vs. did not experience 2-year MACE. SHAP analysis identified GDF15 as the most influential predictive feature, surpassing traditional clinical predictors such as age, cardiovascular history, and smoking status. This study highlights GDF15 as a strong prognostic biomarker for 2-year MACE in patients with PAD. When combined with clinical variables in an interpretable machine learning model, GDF15 supports the early identification of patients at high risk for systemic cardiovascular events, facilitating personalized treatment","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12293086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytocompounds in Precision Dermatology: COX-2 Inhibitors as a Therapeutic Target in Atopic-Prone Skin.","authors":"Muhammad Suleman, Abrar Mohammad Sayaf, Chiara Moltrasio, Paola Maura Tricarico, Francesco Giambuzzi, Erika Rimondi, Elisabetta Melloni, Paola Secchiero, Annalisa Marcuzzi, Angelo Valerio Marzano, Sergio Crovella","doi":"10.3390/biom15070998","DOIUrl":"10.3390/biom15070998","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease characterized by persistent pruritus, immune system dysregulation, and an increased expression of cyclooxygenase-2 (COX-2), an enzyme that plays a central role in the production of prostaglandins and the promotion of inflammatory responses. In this study, we employed a comprehensive computational pipeline to identify phytocompounds capable of inhibiting COX-2 activity, offering an alternative to traditional non-steroidal anti-inflammatory drugs. The African and Traditional Chinese Medicine natural product databases were subjected to molecular screening, which identified six top compounds, namely, Tophit1 (-16.528 kcal/mol), Tophit2 (-10.879 kcal/mol), Tophit3 (-9.760 kcal/mol), Tophit4 (-9.752 kcal/mol), Tophit5 (-8.742 kcal/mol), and Tophit6 (-8.098 kcal/mol), with stronger binding affinities to COX-2 than the control drug rofecoxib (-7.305 kcal/mol). Molecular dynamics simulations over 200 ns, combined with MM/GBSA binding free energy calculations, consistently identified Tophit1 and Tophit2 as the most stable complexes, exhibiting exceptional structural integrity and a strong binding affinity to the target protein. ADMET profiling via SwissADME and pkCSM validated the drug-likeness, oral bioavailability, and safety of the lead compounds, with no Lipinski rule violations and favorable pharmacokinetic and toxicity profiles. These findings underscore the therapeutic potential of the selected phytocompounds as novel COX-2 inhibitors for the management of atopic-prone skin and warrant further experimental validation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12294077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Glucose in Diabetic Hyperglycemia Perturbs Lymphocyte SERCA-Regulated Ca²⁺ Stores with Accompanying ER Stress and Signaling Dysfunction.","authors":"Md Nasim Uddin, James L Graham, Peter J Havel, Roshanak Rahimian, David W Thomas","doi":"10.3390/biom15070987","DOIUrl":"10.3390/biom15070987","url":null,"abstract":"<p><p>It is well recognized that patients with type 2 diabetes mellitus (T2DM) exhibit significant impairment of immune function resulting in a higher frequency of infections. We hypothesize in this study that a likely contributor to immune dysfunction in T2DM is alteration of T lymphocyte signaling functions induced by chronic hyperglycemia. In this study we have utilized the established UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model of human T2DM to investigate whether progressive hyperglycemia diminishes T cell receptor (TCR)-releasable endoplasmic reticulum (ER) Ca²⁺ stores, an essential early antigen-stimulated signal driving T cell activation. Furthermore, results from this study demonstrate that chronic hyperglycemia markedly alters the expression profile of the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) Ca²⁺ ion pumps, which are the major enzymatic ion transporters maintaining replenished TCR-sensitive Ca²⁺ pools. We conducted companion experiments using Jurkat T lymphocytes exposed to high glucose which allowed finer resolution of early disruptions to ER Ca²⁺ store integrity and greater clarity on SERCA isoform-specific roles in diabetes-induced Ca²⁺ signal dysregulation. In summary, these experiments suggest that hyperglycemia in T2DM drives an ER stress state manifesting in reduced expression of the SERCA pumps, erosion of ER Ca²⁺ stores and culminating in T cell and immune dysfunction.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting miR-200a-3p Increases Sirtuin 1 and Mitigates Kidney Injury in a Tubular Cell Model of Diabetes and Hypertension-Related Renal Damage.","authors":"Olga Martinez-Arroyo, Ana Flores-Chova, Marta Mendez-Debaets, Laia Garcia-Ferran, Lesley Escrivá, Maria Jose Forner, Josep Redón, Raquel Cortes, Ana Ortega","doi":"10.3390/biom15070995","DOIUrl":"10.3390/biom15070995","url":null,"abstract":"<p><p>Hypertension and diabetes mellitus are key contributors to kidney damage, with the renal tubule playing a central role in the progression of kidney disease. MicroRNAs have important regulatory roles in renal injury and are among the most abundant cargos within extracellular vesicles (EVs), emerging as novel kidney disease biomarkers and therapeutic tools. Previously, we identified miR-200a-3p and its target SIRT1 as having a potential role in kidney injury. We aimed to evaluate miR-200a-3p levels in EVs from patient's urine and delve into its function in causing tubular injury. We quantified miR-200a-3p urinary EV levels in hypertensive patients with and without diabetes (<i>n</i> = 69), 42 of which were with increased urinary albumin excretion (UAE). We analysed miR-200a-3p levels in EVs and cellular pellets, as well as their targets at mRNA and protein levels in renal tubule cells (RPTECs) subjected to high glucose and Angiotensin II treatments, and observed their influence on apoptosis, RPTEC markers and tubular injury markers. We conducted microRNA mimic and inhibitor transfections in treated RPTECs. Our findings revealed elevated miR-200a-3p levels in increased UAE patient urinary EVs, effectively discriminating UAE (AUC of 0.75, <i>p</i> = 0.003). In vitro, miR-200a-3p and renal injury markers increased, while RPTEC markers, SIRT1, and apoptosis decreased under treatments. Experiments using miR-200a-3p mimics and inhibitors revealed a significant impact on SIRT1 and decrease in tubular damage through miR-200a-3p inhibition. Increased levels of miR-200a-3p emerge as a potential disease marker, and its inhibition provides a therapeutic target aimed at reducing renal tubular damage linked to hypertension and diabetes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a Potent Antimicrobial Peptide Through Rational Design: A New Frontier in Pathogen Control.","authors":"Bruna Agrillo, Monica Ambrosio, Rosa Luisa Ambrosio, Marta Gogliettino, Marco Balestrieri, Alessandra Porritiello, Maria Francesca Peruzy, Andrea Mancusi, Luigi Nicolais, Gianna Palmieri","doi":"10.3390/biom15070989","DOIUrl":"10.3390/biom15070989","url":null,"abstract":"<p><p>The increasing circulation of multi-drug-resistant pathogens, coupled with the sluggish development of new antibiotics, is weakening our capacity to combat human infections, resulting in elevated death tolls. To address this worldwide crisis, antimicrobial peptides (AMPs) are viewed as promising substitutes or adjuvants for combating bacterial infections caused by multidrug-resistant organisms. Here, the antimicrobial activity and structural characterization of a novel 13-amino acid cationic peptide named RKW (RKWILKWLRTWKK-NH2), designed based on known AMPs sequences and the identification of a key tryptophan-rich structural motif, were described. RKW displayed a broad-spectrum and potent antimicrobial and antibiofilm activity against Gram-positive and Gram-negative pathogens, including ESKAPE bacteria and fungi with minimal inhibitory concentrations (MBC) ranging from 5 µM to 20 μM. Structural results by fluorescence and Circular Dichroism (CD) spectroscopy revealed that the peptide was folded into a regular α-helical conformation in a membrane-like environment, remaining stable in a wide range of pH and temperature for at least 48 h of incubation. Furthermore, RKW showed low toxicity in vitro against mammalian fibroblast cells, indicating its potential as a promising candidate for the development of new antimicrobial or antiseptic strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.","authors":"Xianrui Yang, Lexie Shannon Holliday","doi":"10.3390/biom15070997","DOIUrl":"10.3390/biom15070997","url":null,"abstract":"<p><p>Diabetes is a risk factor for periodontitis. Increasing evidence suggests that a central player in this link is the vacuolar H+-ATPase (V-ATPase), which provides a physical and functional core for regulation by the catabolic lysosomal AMP-activated protein kinase complex (L-AMPK) and the anabolic mammalian target of rapamycin complex 1 (mTORC1). These complexes detect levels of various cellular nutrients, including glucose at the lysosome, and promote cellular responses to restore homeostasis. The high-glucose conditions of diabetes foster anabolic mTORC1 signaling that increases inflammation and inflammatory bone resorption in response to periodontal infections. Here, we review the structure and composition of V-ATPase, L-AMPK, mTORC1, and other elements of the energy-sensing platform. Mechanisms by which V-ATPase passes signals to the complexes are examined and recent data are reviewed. Current anti-bone resorptive therapeutics, bisphosphonates and denosumab, enhance the risk of medicine-related osteonecrosis of the jaw (MRONJ) and are not used to treat periodontal bone loss. Accumulating data suggest that it may be possible to target inflammatory bone resorption through agents that stimulate L-AMPK, including metformin and glucagon-like peptide-1 agonists. This approach may reduce inflammatory bone resorption without major effects on overall bone remodeling or increased risk of MRONJ.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Colitis-Induced Atrial Electrophysiological Remodeling.","authors":"Hiroki Kittaka, Edward J Ouille V, Carlos H Pereira, Andrès F Pélaez, Ali Keshavarzian, Kathrin Banach","doi":"10.3390/biom15070982","DOIUrl":"10.3390/biom15070982","url":null,"abstract":"<p><p>Patients with ulcerative colitis exhibit an increased risk for supraventricular arrhythmia during the active disease phase of the disease and show signs of atrial electrophysiological remodeling in remission. The goal of this study was to determine the basis for colitis-induced changes in atrial excitability. In a mouse model (C57BL/6; 3 months) of dextran sulfate sodium (DSS)-induced active colitis (3.5% weight/volume, 7 days), electrocardiograms (ECG) revealed altered atrial electrophysiological properties with a prolonged P-wave duration and PR interval. ECG changes coincided with a decreased atrial conduction velocity in Langendorff perfused hearts. Action potentials (AP) recorded from isolated atrial myocytes displayed an attenuated maximal upstroke velocity and amplitude during active colitis, as well as a prolonged AP duration (APD). Voltage clamp analysis revealed a colitis-induced shift in the voltage-dependent activation of the Na-current (I_Na) to more depolarizing voltages. In addition, protein levels of Na_v1.5 protein and connexin isoform Cx43 were reduced. APD prolongation depended on a reduction in the transient outward K-current (I_to) mostly generated by K_v4.2 channels. The changes in ECG, atrial conductance, and APD were reversible upon remission. The change in conduction velocity predominantly depended on the reversibility of the reduced Cx43 and Na_v1.5 expression. Treatment of mice with inhibitors of Angiotensin-converting enzyme (ACE) or Angiotensin II (AngII) receptor type 1 (AT1R) prevented the colitis-induced atrial electrophysiological remodeling. Our data support a colitis-induced increase in AngII signaling that promotes atrial electrophysiological remodeling and puts colitis patients at an increased risk for atrial arrhythmia.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}