Current molecular medicine最新文献

{"title":"Exploring the Therapeutic Role of Pregnane X Receptor Activation in Acute Kidney Injury: Mechanisms and Clinical Implications.","authors":"Qiming Fan, Huihui Song, Kexin Zhang, Chengxia Kan, Sufang Sheng, Yujie Ma, Xiaodong Sun, Ruiyan Pan, Zhentao Guo","doi":"10.2174/0115665240381768250607064429","DOIUrl":"https://doi.org/10.2174/0115665240381768250607064429","url":null,"abstract":"<p><p>Acute Kidney Injury (AKI) is a critical condition characterized by a rapid decline in kidney function, often resulting from ischemia-reperfusion, nephrotoxicity, or inflammation. Current treatments primarily rely on renal replacement therapies, which remain limited and controversial. The pregnane X receptor (PXR), a nuclear receptor involved in drug metabolism, immune regulation, and cellular homeostasis, has emerged as a promising target for AKI therapy. Preclinical studies suggest that PXR activation demonstrates protective effects in AKI through multiple mechanisms, including reducing inflammation, oxidative stress, and mitochondrial dysfunction. Specifically, PXR modulates nuclear factor-κB (NF-κB) signaling, supports mitochondrial function, regulates apoptosis, and enhances renal hemodynamics, thus mitigating AKI progression. Furthermore, PXR's role in the gut-liver-kidney axis strengthens intestinal barrier integrity and bile acid homeostasis, contributing to renal protection. Recent advances in research on the PXR agonists rifampicin and tanshinone IIA (TanIIA) highlight the potential of PXR-targeted therapies to mitigate nephrotoxicity and promote kidney recovery. This review provides a comprehensive analysis of PXR's protective mechanisms in AKI, underscoring its therapeutic potential and paving the way for new treatment strategies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282808","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":"Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics.","authors":"Farhan Ikhtiar, Adil Jamal, Amina Arif, Muhammad Naveed Shahid, Syed M Safeer Mehdi Bokhari","doi":"10.2174/0115665240371495250505054101","DOIUrl":"https://doi.org/10.2174/0115665240371495250505054101","url":null,"abstract":"<p><p>Hemochromatosis is an autosomal recessive iron overload disorder. It occurs due to a failure in the hepcidin response, leading to systemic iron overload. The high iron levels in the plasma stored in various organs cause injury and permanent damage. There are two types of hemochromatosis: primary and secondary. In non- HFE hemochromatosis, mutations in the HJV, HAMP, TRF2, and SLC40A1 genes are implicated, with the associated condition classified as type I hemochromatosis. In contrast, juvenile hemochromatosis (type II hemochromatosis/ HFE II) is linked to mutations in the hemojuvelin gene or the antimicrobial peptide hepcidin. In this study, relevant literature in databases, including PubMed, MEDLINE records, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and Embase, was searched. Our study inclusion criteria encompassed both experimental and observational studies or a combination of both, with data derived from the human population. The exclusion criteria included animal models, observational studies, and unpublished data. Hepcidin is usually up-regulated in response to high serum iron, but it is unexpectedly low in patients with hemochromatosis because of mutations in HFE, hemojuvelin (JH), and transferrin receptor 2 (TfR2). TfR2, expressed by hepatocytes, is mutated in hemochromatosis type III. Future research directions include exploring the molecular mechanisms underlying the effects of the TFR2 gene variant on iron homeostasis and liver damage and investigating potential therapeutic targets for treating hemochromatosis-related liver disease. Additionally, further epidemiological and modern genetic engineering studies are needed to better understand the prevalence and impact of hemochromatosis on liver health in different populations.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224643","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":"Metabolomic Profiling of Leukemic Hematopoiesis: Effects of BNT162b2 mRNA COVID-19 Vaccine Administration.","authors":"Batuhan Erdoğdu, Ozan Kaplan, Bilge Başak Fidan, Mustafa Çelebier, Ümit Yavuz Malkan, Ibrahim C Haznedaroglu","doi":"10.2174/0115665240361878250601074746","DOIUrl":"https://doi.org/10.2174/0115665240361878250601074746","url":null,"abstract":"<p><strong>Background: </strong>Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiological effects. This study investigates metabolomic alterations in leukemic bone marrow potentially associated with BNT162b2 vaccination.</p><p><strong>Objective: </strong>To compare the bone marrow metabolomic profiles of leukemia patients with and without BNT162b2 vaccination, and healthy unvaccinated controls, to explore potential metabolic differences.</p><p><strong>Methods: </strong>Bone marrow samples were obtained from three groups: vaccinated leukemia patients (n=7), unvaccinated leukemia patients without COVID-19 history (n=2), and unvaccinated healthy controls (n=7). Untargeted metabolomics was performed using LC-QTOF-MS. Data were analyzed using XCMS and MetaboAnalyst 5.0 to identify statistically significant metabolite differences and affected pathways. Fold change >1.5 and p<0.05 were considered significant.</p><p><strong>Results: </strong>Distinct metabolic profiles were observed between the leukemia and control groups. Increased glycolysis, pentose phosphate pathway activity, and altered tryptophan, lipid, and heme metabolism were noted in leukemia samples. Metabolic changes in vaccinated patients (ASL) were more similar to unvaccinated leukemia patients (LO) than to healthy controls, with minor vaccine-associated variations. Notable metabolites included 5-methoxyindoleacetate, phosphorylcholine, and tetrahydrofolic acid.</p><p><strong>Conclusion: </strong>This preliminary study identified altered metabolic pathways in leukemia bone marrow and suggests metabolomic differences associated with BNT162b2 vaccination. While the findings do not support a causal link between mRNA vaccination and leukemia development, they highlight the need for further studies to understand vaccine-induced metabolic modulation in hematological contexts.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215197","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":"Oxidized HDL as a Novel Predictive Biomarker in Conjunction with Selected Inflammatory Variables in Severe Dengue Fever Patients from Lahore, Pakistan.","authors":"Muhammad Sarwar, Rizwan Ashraf, Hassaan B Sohail, Rehan Majeed, Zara Khan, Maira Rehan, Saba Arif, Noor Kamil, Raahim Ali","doi":"10.2174/0115665240365589250519221441","DOIUrl":"https://doi.org/10.2174/0115665240365589250519221441","url":null,"abstract":"<p><strong>Background: </strong>Dengue fever is a deadly disease and represents one of the biggest threats to global health, with persisting uncertainty surrounding its prognosis and treatment standards. The onset of severe dengue fever, characterized by intense inflammation and the production of pro-inflammatory molecules, is currently the only well-established association with disease severity. Therefore, identifying and assessing both new and established biomarkers that can accurately predict the outcome of severe dengue fever is essential.</p><p><strong>Methods: </strong>In this study, 100 age-matched healthy controls and 100 hospitalized dengue patients positive for NS1 and IgM, with a mean age of 45 years (range: 22- 65), were examined. Potential biomarkers were analyzed using a Coulter counter, spectroscopy, and ELISA to determine their prognostic value in assessing dengue fever severity.</p><p><strong>Results: </strong>Triglycerides and very-low-density lipoproteins (VLDL) were significantly higher in severe dengue fever patients compared to controls (P<0.001). Conversely, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol levels were significantly lower in patients compared to controls (P<0.001). Albumin levels were 40.9% lower, lactate dehydrogenase (LDH) was 422.1% higher, and C-reactive protein (CRP) levels were 435.6% higher in severe dengue fever patients compared to controls. Unlike HDL, oxidized HDL (oxHDL) levels were 160.4% higher in patients with severe dengue fever compared to controls. Still, the absolute levels of oxHDL did not exceed total HDL levels, as confirmed by corrected data.</p><p><strong>Conclusion: </strong>Oxidized HDL, combined with other lipoproteins, may provide an ideal panel of prognostic indicators that could guide the treatment of severe dengue fever and serve as reliable biomarkers for predicting disease outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215198","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":"Association Between Blood Lead Levels and Diabetic Kidney Disease: A Cross-sectional Analysis of NHANES Data (1999-2018).","authors":"Yaxian Ning, Jianqin Wang, Xiaochun Zhou, Gouqin Wang, Lili Zhang","doi":"10.2174/0115665240293441250312133508","DOIUrl":"https://doi.org/10.2174/0115665240293441250312133508","url":null,"abstract":"<p><strong>Background: </strong>The relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between blood Pb levels and DKD risk using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018.</p><p><strong>Methods: </strong>A total of 1,343 participants were included, with 508 diagnosed with DKD. Baseline characteristics were compared between DKD and non-DKD groups. Multivariate generalized linear models (GLMs) and weighted logistic regression were used to assess correlations between blood Pb levels and DKD risk. A nomogram was developed to evaluate the predictive power of significant clinical characteristics.</p><p><strong>Results: </strong>Key clinical characteristics, including age, marital status, and serum Pb levels, differed significantly between DKD and non-DKD groups. Serum Pb was identified as a significant risk factor (ORs: 1.18-1.39, p < 0.01). The nomogram demonstrated good predictive accuracy (AUC = 0.717).</p><p><strong>Conclusion: </strong>Elevated blood Pb levels are significantly associated with DKD, with a non-linear relationship and a defined threshold. These findings highlight the potential role of Pb exposure in DKD pathogenesis and suggest the utility of blood Pb monitoring in diabetic patients.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198374","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":"Urinary CFHR2 as a Biomarker for Early Diagnosis and Disease Progression Prediction in Diabetic Kidney Disease.","authors":"Tao Du, Qing Zhang","doi":"10.2174/0115665240350524250524065114","DOIUrl":"https://doi.org/10.2174/0115665240350524250524065114","url":null,"abstract":"<p><strong>Aim: </strong>The pathogenesis of diabetic kidney disease (DKD) is complex, and the specific biomarkers for detecting early diagnosis and monitoring kidney function deterioration are insufficient, which affects the prognosis of patients. The complement activation in glomeruli and renal interstitium contributes to the aggravation of DKD. Several key complement proteins, such as complement factor 3 (C3), CD59, and complement factor H-related protein 2 (CFHR2) were reported to be potential biomarkers for early diagnosis and prognosis for DKD.</p><p><strong>Methods: </strong>In the current study, we focus on CFHR2, to investigate its capability and sensitivity as a DKD biomarker. As a non-invasive detection sample, urine has the characteristic of convenient sampling. In the current study, the urine samples were collected from three groups: diabetic patients without albuminuria, with microalbuminuria, and macroalbuminuria, to analyze whether CFHR2 was associated with albuminuria concentration and declined renal function. Meanwhile, the urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and C3 were also examined by enzyme-linked immunosorbent assay (ELISA) to compare with CFHR2 to determine whether CFHR2 had an advantage in predicting the early detection and progression of DKD. The Spearman correlation analysis was performed for the correlation analysis. The receiver operating characteristic curve was used to analyze the diagnostic efficacy.</p><p><strong>Results: </strong>CFHR2 had superior diagnostic power to predict the early occurrence of DKD and disease progression, compared with NGAL, microalbumin, and C3 in urine.</p><p><strong>Conclusion: </strong>CFHR2 has satisfactory potential to be a biomarker for early diagnosis and risk of progression of DKD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180945","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":"CD82 Methylation Patterns in Inflammatory Arthritis and their Clinical Association with Hypertension in Rheumatoid Arthritis.","authors":"Yiming Shi, Hongliang Hu, Mi Zhou, Cen Chang, Jianan Zhao, Yu Shan, Yixin Zheng, Fuyu Zhao, Yunshen Li, Shicheng Guo, Xiaolei Fan, Wukai Ma, Dongyi He","doi":"10.2174/0115665240371789250425113320","DOIUrl":"https://doi.org/10.2174/0115665240371789250425113320","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to compare CD82 methylation patterns in peripheral blood among patients with rheumatoid arthritis [RA], inflammatory arthritis, and healthy controls [HC] and to assess their clinical associations with hypertension in RA.</p><p><strong>Methods: </strong>In this cross-sectional study, CD82 methylation at positions 44596705- 44596865 on chromosome 11 was analyzed using targeted methylation techniques in peripheral blood from patients with RA, psoriatic arthritis [PsA], ankylosing spondylitis [AS], gout, and HC.</p><p><strong>Results: </strong>CD82 cg22143324 methylation levels were significantly different between RA patients and healthy controls [P<0.0001], PsA [P=0.0281], and AS [P=0.0360]. In RA subgroups, individuals negative for both rheumatoid factor [RF] and cyclic citrullinated peptide [CCP] [RA-DN], as well as those positive for both [RA-DP], exhibited significantly different methylation levels compared to HC [P=0.0355 and P<0.0001, respectively]. ROC analysis indicated a promising diagnostic potential for CD82 cg22143324 methylation, especially with the TTT haplotype. Correlation analysis revealed significant associations between CD82 methylation and CCP levels, as well as hypertension in RA patients.</p><p><strong>Conclusion: </strong>The analysis conducted revealed altered CD82 cg22143324 methylation in RA, with potential utility in distinguishing seronegative patients from healthy controls. An association between lower methylation levels and comorbid hypertension in RA patients was also observed, warranting further investigation.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110013","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":"SMAC/DIABLO: A Guardian Angel in Boosting Anticancer Drug-Induced Apoptosis.","authors":"Anuja Mishra, Swaroop Kumar Pandey","doi":"10.2174/0115665240380871250518032318","DOIUrl":"https://doi.org/10.2174/0115665240380871250518032318","url":null,"abstract":"<p><p>Apoptosis is an established hallmark of cancer. In normal conditions, apoptosis is strictly controlled; however, when it is not properly managed, it causes several complications, including cancer progression and drug resistance. SMAC/ Diablo (SMAC) is a mitochondrial protein that is released into the cytosol upon activation of BAX/BAK channels with apoptotic signals. SMAC protein interacts and neutralizes inhibitors of apoptosis (IAP) proteins and initiates the caspase cascade, which leads to apoptosis. SMAC is downregulated in several types of cancer, which led to the design of small-molecule inhibitors known as SMAC mimetics as new cancer therapeutics, and some of these molecules are in the clinical phase. It has also been shown that a combination of SMAC with standard anti-cancer drugs could be beneficial to drug-resistant cancer. Despite being a pro-apoptotic protein, it has been found that SMAC/Diablo is overexpressed in several types of cancers like lung, breast, bladder, cervix, pancreas, prostate, and colon, as well as in melanoma and glioma, and in cancer cells. Recently, we have reported that the overexpression of SMAC in cancers is essential for cell and tumor growth due to non-apoptotic regulation of phospholipid synthesis. The current review is focused on apoptotic and non-apoptotic functions of SMAC and its role in drug resistance.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109927","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":"miRNA-29b-3p: An Important Target for Ameliorating Liver Fibrosis in Wilson Disease by Inhibiting Autophagy.","authors":"Peng Huang, Yuzhe Huang, Ting Dong, Yulong Yang, Wei He, Meixia Wang, Han Wang, Wenming Yang","doi":"10.2174/0115665240373925250510072405","DOIUrl":"https://doi.org/10.2174/0115665240373925250510072405","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is an important pathological feature of Wilson disease (WD). The miRNA-29b-3p level decreased in liver fibrosis, while the mechanism of miRNA-29b-3p in liver fibrosis has not been reported, and was elucidated in the work.</p><p><strong>Methods: </strong>The miRNA-29b-3p levels were evaluated by q-PCR. The effect of miRNA- 29b-3p on the activity of hepatic stellate cells was detected by cell activity assay. The protein levels were checked by western blot. The interaction between miRNA-29b-3p and ULK1 mRNA with base complementary sequences was detected by double luciferase assay. The autophagosomes were observed by TEM. The cell fibrosis-like change was evaluated with an anti-α-smooth muscle actin (α-SMA) antibody by IF.</p><p><strong>Results: </strong>The results showed that miRNA-29b-3p mimics down-regulated the α-SMA and Col1 protein levels, and miRNA-29b-3p inhibitors upregulated the α-SMA and Col1 protein levels. The dual-luciferase assay result revealed that miRNA-29b-3p interacted with ULK1. The miRNA-29b-3p mimics inhibited the protein expression of ULK1, beclin1, and LC3, whereas miRNA-29b-3p inhibitors promoted the protein expression of ULK1, beclin1, and LC3.</p><p><strong>Conclusion: </strong>The miRNA-29b-3p blocked HSCs trans-differentiation into myofibroblasts by inhibiting autophagy, and further inhibiting liver fibrosis in WD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076588","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":"Boosting Antiviral Defenses: stat3 Inhibition Enhances Type I Interferon Response to Respiratory Syncytial Virus by Silencing KAP1.","authors":"Huagui Chen, Dongmei Ding, Zimeng Teng, Ran Zhang","doi":"10.2174/0115665240351066250330235743","DOIUrl":"https://doi.org/10.2174/0115665240351066250330235743","url":null,"abstract":"<p><strong>Introduction: </strong>The antiviral effects of type I interferons [IFNs] on respiratory syncytial virus [RSV]-infected airway epithelial cells have been identified. We aim to further reveal the mechanism of stat3 and kruppel-associated box-associated protein 1 [KAP1] in RSV-infected airway epithelial cells.</p><p><strong>Methods: </strong>Using the A549 cell line, we investigated the impact of RSV infection, KAP1 overexpression, and stat3 inhibition with Stattic. Cell counting kit 8 assay was used to determine the viability, and enzyme-linked immunosorbent assay was applied to measure the levels of IL-6, IL-8, IL-1β, IFN-α, and IFN-β. Viral replication was tested via plaque assay. Meanwhile, quantitative real-time reverse transcription polymerase chain reaction or/and western blot were applied to measure the expressions of p-stat3 and KAP1 in the cells.</p><p><strong>Results: </strong>RSV infection repressed the viability, upregulated p-stat3 and KAP1 expressions, elevated levels of inflammation-related factors [IL-6, IL-8, IL-1β], and type I IFN immune response-associated factors [IFN-α, IFN-β], and promoted viral replication in A549 cells. Stattic attenuated the promoting effect of RSV on inflammation-related factors and viral replication, but enhanced its impact on IFN-α and IFN-β levels in the cells. More importantly, KAP1 overexpression reversed the effects of Stattic on viability, inflammation [IL-6, IL-8, IL-1β], type I IFN immune response [IFN-α, IFN-β], and viral replication in RSV-infected A549 cells.</p><p><strong>Conclusion: </strong>Our findings unveil the pivotal role of stat3 inhibition in potentiating type I IFN-mediated antiviral responses against RSV in lung epithelial cells, revealing KAP1 as a potential therapeutic target for combating respiratory viral infections.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076587","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}