Current molecular medicine最新文献

{"title":"Innovative Therapeutic Potential of Herbal Extracts Containing Punicic and Ellagic Acid: Addressing Lower Urinary Tract Disorders.","authors":"Hrishav Das Purkayastha, Abhishek Bhattacharjee, Ranjit Prasad Swain","doi":"10.2174/0115665240378450250410073416","DOIUrl":"10.2174/0115665240378450250410073416","url":null,"abstract":"<p><p>This review highlights the new healing frontiers opened by herbal preparations rich in punicic acid, as well as ellagic acid, in the management of Lower Urinary Tract Disorders (LUTD). New data prove that these bioactive compounds possess strong anti-inflammatory, antioxidant, and antibacterial properties, and therefore, can be helpful in treating LUTD symptoms such as urgency, frequency, and dysuria. We conducted a comprehensive pharmacological assessment of punicic and ellagic acids aimed at determining their role in bladder health through modulation of inflammatory processes and both alteration and maintenance of urothelium integrity, in addition to obtaining some background information and chemical properties of these acids. Furthermore, we evaluated the findings of clinical and preclinical studies that demonstrated the ability of these formulations to improve the basic functions of the organs in the urinary system and the quality of life of patients. The review also reflects on the use of herbal extracts in combination with current therapies as a synergistic approach, particularly on the healing effects of such combinations and the need for solid clinical evidence to support such claims. This paper focuses on the concept of how LUTDs can be treated safely and effectively without the help of drugs by integrating modern scientific strategies with traditional approaches, which will thus increase the comprehensiveness of treatment in urological care. Future research should focus on improving how well these compounds are absorbed in the body and gathering long-term safety data, with the goal of incorporating them into treatment guidelines.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Analysis of CYP11B2 (Aldosterone Synthase) and Evaluation of the HISTALDO Classification in Patients with Primary Aldosteronism.","authors":"Mustafa Karadepe, Hande Yanar, Hülya Binokay, Şeyda Erdoğan, Gamze Akkus","doi":"10.2174/0115665240378395250416064732","DOIUrl":"https://doi.org/10.2174/0115665240378395250416064732","url":null,"abstract":"<p><strong>Objective: </strong>Primary Aldosteronism (PA) is the most common cause of secondary hypertension. Immunohistochemical analysis of PA is based on specific monoclonal antibodies targeting CYP11B1 and CYP11B2, which are enzymes responsible for the aldosterone production in the adrenal cortex. The recently proposed HISTALDO classification introduced CYP11B2 immunohistochemistry to define clinically relevant diagnostic categories. We aimed to investigate the relationship between clinical characteristics and immunohistochemistry of CYP11B2 in PA and also evaluate staining in cortisol-producing cells by comparing patients with Cushing's Syndrome (CS). Consecutive patients diagnosed with PA (n=21) and CS (n=20) were included between 2015-2022. All of them underwent unilateral adrenalectomy in our tertiary center.</p><p><strong>Methods: </strong>Following hematoxylin and eosin (H&E) staining of the pathological specimens, all slides were re-evaluated and immunostained for CYP11B2. A semiquantitative H-score was assessed for each patient and compared with staining intensity. Patients with PA were grouped and classified according to the HISTALDO classification.</p><p><strong>Results: </strong>The mean size of adenoma in patients with PA was much smaller compared to patients with CS (p=0.001). An increase in the immunohistochemical H-score of the patients with PA (121.36 ±81.04 vs 73.94±57.70, p=0.045) was observed in comparison to the patients with CS. When comparing the patients with PA according to HISTALDO criteria, the H-score of the patients with Aldosterone Producing Adenoma (APA, n=10) was 136.6±78.86 compared to the non-APA group, which was 86.81±85.3 (n=11, p=0.05). Moreover, mean preoperative aldosterone levels (p=0.06) and aldosterone-to-renin ratio (ARR, p=0.03) were higher in patients with APA compared to non-APA patients. Response to surgical therapy was more favorable in patients with APA than the patients with non-APA.</p><p><strong>Conclusion: </strong>CYP11B2 is a key enzyme responsible for the synthesis of aldosterone. CYP11B2 expression, as assessed by immunostaining, was associated with the clinical characteristics, severity of PA, and response to the treatment. Hence, immunohistochemical analysis of CYP11B2 should be incorporated into the routine clinical workup to better localize aldosterone-producing cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Cytokine mRNA Expression During Zika Virus Infection In Mesocricetus auratus.","authors":"Wailla Rafaela Barroso Mendes, Karla Fabiane Lopes de Melo, Francisco Canindé Ferreira de Luna, Carolina Ramos Dos Santos, Edna Cristina Dos Santos Franco, Arnaldo Jorge Martins Filho, Pedro Fernando da Costa Vasconcelos, Samir Mansour Moraes Casseb","doi":"10.2174/0115665240344536250319054657","DOIUrl":"https://doi.org/10.2174/0115665240344536250319054657","url":null,"abstract":"<p><strong>Background: </strong>The Orthoflavivirus zikaense (ZIKV), a member of the Flaviviridae family, has been associated with severe neurological issues, particularly microcephaly, due to its ability to infect neural progenitor cells. This study investigates the mRNA expression of cytokines involved in the inflammatory response during ZIKV infection in Mesocricetus auratus. The research aims to understand the immune response to ZIKV in the context of sexual transmission.</p><p><strong>Methods: </strong>The study utilized hamsters of the species Mesocricetus auratus, divided into four groups: three infected with ZIKV and one control group. The animals were euthanized according to ethical guidelines, and renal tissues were collected. Total RNA was extracted and quantified, and both viral load and cytokine mRNA levels were measured using RT-qPCR. The study targeted cytokines such as TNF-A, RIG-I, RANTES, MDA5, IFN-A, and IFN-B. Statistical analysis was performed using Jamovi v 1.6.</p><p><strong>Results: </strong>The study found that the viral load peaked between 3 and 5 days postinfection and then significantly decreased. The expression of cytokine mRNAs showed distinct patterns, with peaks and declines at various time points post-infection. These patterns differed between male and female subgroups. Pearson correlation analysis revealed negative correlations between mRNA expression and days post-infection in most groups.</p><p><strong>Conclusion: </strong>The study concludes that ZIKV infection in hamsters induces a robust inflammatory response in the kidneys, with dynamic cytokine expression profiles that could serve as markers for monitoring infection and related pathologies. Genderspecific immune responses highlight the complexity of ZIKV pathogenesis, suggesting potential therapeutic targets for Zika-related complications.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemolysis Analysis and Hemolysis-related MicroRNA Candidates for Serum/Plasma Samples.","authors":"Rongxin He, Yuntao Zhou","doi":"10.2174/0115665240375969250421020452","DOIUrl":"https://doi.org/10.2174/0115665240375969250421020452","url":null,"abstract":"<p><p>Hemolysis is a major challenge in the screening and validation of serum or plasma miRNA biomarkers for human diseases. Over the past decade, numerous studies have focused on hemolysis detection at both the pre-analytical and postanalytical stages to minimize bias in miRNA quantification. Both conventional and advanced hemolysis determination methods have played important roles in quality control in hemolysis assessment and risk prediction during the plasma or serum miRNA quantification process. This review discusses the advantages of these methods and provides an interactive summary of prior knowledge on hemolysissensitive miRNAs and their potential applications in disease diagnosis. Furthermore, the review highlights the advancements in machine learning technologies that enhance classifier predictions and hemolysis risk model evaluations, particularly during the post-analytical stage. Finally, it discusses the ongoing development, standardization, and potential applications of these approaches, which will contribute to a more comprehensive and interpretable framework for the discovery and validation of plasma or serum miRNA biomarkers.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise Alleviates Atherosclerosis Through the Modulation of the NLRP3 Inflammasome.","authors":"Xuan Liu, Shujuan Hu, Xianwang Wang, Yuqing Ding","doi":"10.2174/0115665240368171250419113225","DOIUrl":"https://doi.org/10.2174/0115665240368171250419113225","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses, can exacerbate the progression of AS when activated. Growing evidence suggests that exercise, as a non-pharmacological intervention, can alleviate the progression of AS by modulating the activity of NLRP3 inflammasome. This review discusses how exercise influences the development of AS through the regulation of NLRP3 inflammasome and the underlying molecular mechanism. This study introduces the structure and activation mechanisms of NLRP3 inflammasome, as well as its role in AS. And summarizes how exercise can ameliorate endothelial dysfunction, regulate lipid metabolism, and suppress oxidative stress and inflammation by affecting the expression and activity of NLRP3 inflammasome, thereby exerting a beneficial impact on AS. Additionally, we explore the effects of exercise on the downstream inflammatory cytokines of NLRP3 inflammasome and how this regulation could help to slow the progression of AS. These findings underscore the therapeutic relevance of exercise in the prevention and treatment of AS. It provides new insights into the role of exercise interventions in the management of AS and lays a theoretical foundation for the development of innovative treatment strategies for cardiovascular disease. Given that the NLRP3 inflammatome plays an important role in the pathogenesis and treatment of AS, exercise therapy strategies targeting the NLRP3 inflammatome will help promote the development of precision medicine for AS.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value and Immunological Role of CBX7 in Lung Adenocarcinoma.","authors":"Lingzheng Yang, Yutang Huang, Wenlu Mo, Lanxiang Wu, Chunjie Wen","doi":"10.2174/0115665240374044250416021616","DOIUrl":"https://doi.org/10.2174/0115665240374044250416021616","url":null,"abstract":"<p><strong>Background: </strong>Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.</p><p><strong>Methods: </strong>CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune microenvironment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.</p><p><strong>Results: </strong>CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.</p><p><strong>Conclusion: </strong>We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation.","authors":"Xu He, Yan Li, Jun Chen, Li Zhang, Yan Huang, Ying Zhou, Jing Li","doi":"10.2174/0115665240355315250414051525","DOIUrl":"https://doi.org/10.2174/0115665240355315250414051525","url":null,"abstract":"<p><strong>Background: </strong>Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction.</p><p><strong>Methods: </strong>C2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated.</p><p><strong>Results: </strong>Hyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor.</p><p><strong>Conclusion: </strong>Ginsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroorotate Dehydrogenase as a Modulator of Ferroptosis in Myocardial Ischemia-Reperfusion Injury.","authors":"Mihribangvl Alip, Ziao Guo, Siwei Yang, Anikezi Wuji, Aikebaier Yasen, Bingjie Han, Munawaer Muaibati, Hongfu Wu, Xiaojun Cui","doi":"10.2174/0115665240305282241219144313","DOIUrl":"10.2174/0115665240305282241219144313","url":null,"abstract":"<p><strong>Introduction: </strong>Ferroptosis is increasingly acknowledged as a pivotal contributor to myocardial cell injury in ischemia-reperfusion (I/R). As a central enzyme in the pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH) is implicated in maintaining redox homeostasis and is thought to act as a protective agent against ferroptosis. Despite this association, the specific contributions of DHODH to myocardial ischemia-reperfusion injury (MIRI) and its cardioprotective potential remain inadequately elucidated.</p><p><strong>Aim: </strong>This study aimed to delineate the role of DHODH in MIRI and assess its capacity to modulate ferroptosis in cardiomyocytes.</p><p><strong>Methods: </strong>We utilized AC16 cardiomyocytes to establish an in vitro MIRI model to investigate the role of DHODH in ferroptosis. We quantitatively analyzed DHODH expression during I/R injury, along with its distribution in cytoplasmic and mitochondrial compartments. Cells pretreated with dihydroorotate (DHO) and orotate (OA)-the substrate and product of DHODH, respectively-provided a basis for assessing their susceptibility to ferroptosis. By employing siRNA to suppress DHODH expression, we delved into the underlying mechanisms of DHODH's protective role against I/Rinduced ferroptosis, focusing on oxidative stress and mitochondrial dysfunction.</p><p><strong>Results: </strong>Our findings reveal a significant induction of DHODH expression during ferroptosis in the AC16 I/R model. DHO pretreatment conferred resistance to ferroptosis, while OA pretreatment rendered cells more susceptible. Notably, DHODH silencing aggravated ferroptosis indicators, mainly through increased oxidative stress and mitochondrial dysfunction.</p><p><strong>Conclusion: </strong>DHODH emerges as a key modulator of ferroptosis in the context of MIRI, offering protection predominantly through its antioxidative functions and maintenance of mitochondrial integrity.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protease-Activated Receptor 2 Promotes Crohn's Disease-Associated Colonic Fibrosis through Fibroblast Activation.","authors":"Zhaohui Wang, Bin Liu, Chenghao Chu, Fubao Liu","doi":"10.2174/0115665240351860250403112214","DOIUrl":"https://doi.org/10.2174/0115665240351860250403112214","url":null,"abstract":"<p><strong>Aims: </strong>To clarify the roles of PAR-2 (protease-activated receptor 2) in Crohn's disease-associated colonic fibrosis.</p><p><strong>Background: </strong>G protein-coupled receptor, termed PAR-2, is triggered after serine proteases. Through activating genes encoding extracellular matrix proteins and proinflammatory cytokines, PAR-2 triggering promotes inflammatory / pro-fibrotic pathways. Although PAR-2 is highly expressed within the digestive system, its significance within colonic fibrosis (CF) has not yet been probed.</p><p><strong>Objective: </strong>The role of PAR-2 in Crohn's disease-related colonic fibrosis and its possible regulatory mechanisms has been investigated.</p><p><strong>Methods: </strong>PAR-2 expression was assessed variably in the colon of human and model mice. Immunofluorescence assay was used to analyze the phenotypic changes of fibroblasts after PAR-2 activation in the lamina propria. In in vitro assays, we explored the roles of PAR-2 in CCD-18Co fibroblasts treated with PAR-2 inhibitor ENMD-1068 and PAR-2 agonist SLIGRL-NH2.</p><p><strong>Results: </strong>PAR-2 was highly expressed in the subepithelial layer surrounding colonic crypts of CD patients or murine fibrosis cohort. Colonic PAR-2 expression was consistent with collagen deposition. Decreasing PAR-2 in experimental colon fibrosis caused a decrease in the amount of colonic collagen and histological fibrosis, followed by a reduction in colonic fibroblast activation. PAR-2 activation enhanced CF by showing a profibrogenic phenotype and collagen synthesis within CCD-18Co fibroblasts.</p><p><strong>Conclusion: </strong>Our results show that PAR-2 activation could upregulate extracellular matrix (ECM) proteomic levels, encourage CF, and cause a pro-fibrogenic phenotype within human colonic myofibroblasts.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of S100A12 Attenuates LPS-Induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway.","authors":"Ye Shen, Xiangming Ye, Lingzhi Jiang, Hengjie Li, Yanli Zhang, Wenmin Wang, Hui Mao","doi":"10.2174/0115665240338945250317082242","DOIUrl":"https://doi.org/10.2174/0115665240338945250317082242","url":null,"abstract":"<p><strong>Background: </strong>The calcium-binding protein S100A12 plays a pivotal role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the underlying mechanisms are yet to be fully elucidated.</p><p><strong>Objective: </strong>This study aimed to investigate the role of S100A12 in LPS-induced injury of human pulmonary microvascular endothelial cells (HPMECs) and its molecular regulatory mechanism.</p><p><strong>Methods: </strong>An in vitro model of ALI/ARDS was established by lipopolysaccharide (LPS)-induced HPMECs. CCK-8, flow cytometry assay, and ELISA were used to detect the cell viability, apoptosis, and inflammation. The integrity of the endothelial barrier was assessed by tube formation assay and VE-cadherin and occludin protein levels. The molecular mechanism of S100A12 was analyzed by transcriptomics and validated using qRT-PCR and western blotting analyses.</p><p><strong>Results: </strong>S100A12 expression was significantly elevated in LPS-stimulated HPMECs, and S100A12 knockdown alleviated LPS-induced apoptosis, inflammation, and endothelial barrier dysfunction in HPMECs. Transcriptomic analysis revealed the potential gene network mapping regulated by LPS stimulation and S100A12 knockdown. Differentially expressed genes were significantly enriched in the JAK2/STAT3 signaling pathway as verified by western blotting analysis.</p><p><strong>Conclusion: </strong>Our results suggested S100A12 to be significantly upregulated in LPSinduced HPMECs; inhibiting S100A12 can alleviate endothelial cell barrier dysfunction through the JAK2/STAT3 signaling pathway and thereby improve LPS-induced HPMECs injury.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}