Journal of Inflammation Research最新文献

{"title":"Awareness of the Risk of Paradoxical Psoriasis in Patients with SAPHO Syndrome Undergoing Treatment with Secukinumab: A Case Series.","authors":"Cheng Xu, Xiayan Xu, Yongmei Han","doi":"10.2147/JIR.S510006","DOIUrl":"https://doi.org/10.2147/JIR.S510006","url":null,"abstract":"<p><p>SAPHO syndrome is a systemic inflammatory disease characterized by skin lesions and inflammatory changes in the bones and joints. There is no consensus on the treatment strategy of SAPHO syndrome. For patients with refractory SAPHO syndrome, biological agents can be considered. We report three patients who responded poorly to conventional therapy, all of whom had paradoxical recurrence of pustulosis after receiving secukinumab, and whose paradoxical pustulosis resolved after adjustment to tofacitinib. We reviewed the literature and concluded that secukinumab may be potentially risky for the treatment of SAPHO syndrome. This paradoxical aggravation of the rash may be related to paradoxical psoriasis. The specific pathogenesis is not clear, and tofacitinib may be a remedy for this situation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3705-3712"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Zofenopril and Thymoquinone in Cyclophosphamide-Induced Urotoxicity and Nephrotoxicity in Rats; The Value of Their Anti-Inflammatory and Antioxidant Properties.","authors":"Neveen Nawzad Mahmood, Ban Mousa Rashid, Sakar Karem Abdulla, Bushra Hassan Marouf, Karmand Salih Hamaamin, Hemn Hassan Othman","doi":"10.2147/JIR.S500375","DOIUrl":"https://doi.org/10.2147/JIR.S500375","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to investigate whether zofenopril (ZOF), thymoquinone (TQ), or their co-administration effectively ameliorates urotoxicity and nephrotoxicity following cyclophosphamide (CPH) treatment.</p><p><strong>Methods: </strong>A total of 48 Wister Albino female rats were divided into six groups each of eight rats; negative control (NC), positive control (PC), mesna (MS), ZOF, TQ, and ZOF+TQ groups. Normal saline, mesna, ZOF-15mg/kg, TQ-80mg/kg, and their combination were given orally for 19 days to the groups NC, MS, ZOF, TQ, and ZOF+TQ respectively. On the 17^th day, a single dose of CPH 200 mg/kg was given intraperitoneally for all the groups except the NC group. Urine was collected over 24 hours before animal scarification for urinalysis. After scarification, blood, and kidney tissue were obtained for assessment of conventional kidney function parameters, novel kidney injury biomarkers, pro-inflammatory cytokines, oxidative status, complete blood count (CBC), and histopathological examination.</p><p><strong>Results: </strong>CPH disturbed the urinary excretion of urea, creatinine, and protein, and significantly elevated novel biomarkers for kidney injury including cystatin-C (Cys-C) (p=0.019) and markedly kidney injury molecule-1 (KIM-1) (p=0.27), the semiquantitative measurement of hematuria revealed significant elevation of hematuria score (p=0.0002), urine pus and protein (p=0.0005). Additionally, CBC-derived inflammatory biomarkers including neutrophil-lymphocyte ratio (NLR) (p=0.001), neutrophil-monocyte ratio (NMR) (p=0.0004), pro-inflammatory cytokine interleukin (IL)-6 (p=0.016) and tumor necrosis factor (TNF)-α (p<=0.007), total antioxidant capacity (TAC) (p<0.0001) were significantly increased. Evidence of obvious histopathological structural alteration was noticed in kidney tissue and bladder urothelium in CPH-treated animals. ZOF, TQ, and their co-treatment significantly prevented these deleterious effects associated with CPH treatment.</p><p><strong>Conclusion: </strong>This study demonstrated that ZOF and TQ provided uroprotective and nephroprotective effects against CPH-induced nephrotoxicity by reducing kidney injury biomarkers, and CBC-derived inflammatory markers, restoring antioxidant capacity, and improving histopathological outcomes. The suggested mechanism involves the anti-inflammatory and antioxidant activity of TQ and the sulfhydryl-angiotensin converting enzyme inhibitor ZOF.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3657-3676"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordination of Neutrophil and Apoptosis-Inducing Ligand in Inflammatory Diseases.","authors":"Hanyu Xue, Ran Xie, Zhiwei Wang, Wenqian Fan, Yinxiang Wei, Lijie Zhang, Dan Zhao, Zhiming Song","doi":"10.2147/JIR.S506807","DOIUrl":"10.2147/JIR.S506807","url":null,"abstract":"<p><p>As the most abundant innate immune cells, neutrophils play a key role in host's anti-infective activity and tissue damage/repair process of sterile inflammation. Due to the restriction of apoptosis and other regulatory mechanisms, neutrophils have a short survival time in vivo. Because of the death domain of cytoplasmic regions, some members of tumor necrosis factor receptor superfamily (TNFRSF) are defined as death receptors, such as TNFR-I, Fas and DR4/DR5. TNF-α, FasL and TRAIL, which are known as apoptosis-inducing ligand, can bind to death receptors and activate intracellular apoptosis pathways to induce apoptosis. Accumulating studies found that these three apoptosis-inducing ligands play an important role in the immune system by coordinating with neutrophil, which including neutrophil recruitment/infiltration and function performing. In this review, we summarize existing studies targeting neutrophils as diagnosis and treatment for diseases, and focus on the involvement of neutrophils which regulated by apoptosis-inducing ligands in inflammatory diseases under current cognition.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3607-3621"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights From m6A RNA Methylation: Biomarkers for Diagnosis of Acute Myocardial Infarction.","authors":"Wenjun Fan, Wenbin Zhao, Renjie Hu, Chen Wei, Lixian Sun, Tong Hou, Ran Li, Qinghua Sun, Cuiqing Liu","doi":"10.2147/JIR.S512476","DOIUrl":"https://doi.org/10.2147/JIR.S512476","url":null,"abstract":"<p><strong>Purpose: </strong>Acute myocardial infarction (AMI) is a major contributor to death. The purpose of this study is to explore circulating biomarkers for AMI diagnosis from the perspectives of immunological microenvironment and N6-methyladenosine (m6A) RNA methylation regulation.</p><p><strong>Patients and methods: </strong>The GSE59867 dataset was used to download platform and probe data for conducting differential analysis of m6A regulators. A diagnostic nomogram was created utilizing the random-forest method and evaluated for predictive power. m6A-related gene patterns were identified, and their immune microenvironment characteristics were analyzed. Peripheral blood samples were obtained for validation in patient-based investigations using RT-qPCR. The association between m6A regulators and clinical parameters was examined via Spearman correlation analysis.</p><p><strong>Results: </strong>With a predictive nomogram model developed using key m6A regulators, two distinct m6A subtypes were identified, showing significant variations in infiltrating immunocyte abundance. In confirmation of the model prediction, examination of patient blood identified METTL3, WTAP, RBM15, ALKBH5, FTO, and FMR1 as novel circulating biomarkers for AMI diagnosis. METTL3 and FTO were identified as promising biomarkers for AMI given that they showed a positive correlation with left ventricular ejection fraction.</p><p><strong>Conclusion: </strong>The study identified six m6A regulators as circulating biomarkers for AMI diagnosis and suggested a potential role for m6A-mediated immune cell infiltration in the pathogenesis of AMI.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3589-3605"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplementation of Glucosamine Selenium Ameliorates DSS-Induced Chronic Colitis in Mice via Affecting Gut Microbiota, Inhibiting Pyroptosis and Inactivating Chemokine Signaling Pathway.","authors":"Tingting Zhao, Zhiyue Wen, Li Cui","doi":"10.2147/JIR.S486751","DOIUrl":"https://doi.org/10.2147/JIR.S486751","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative colitis (UC) is a chronic disease that requires pharmacological therapy to achieve remission. This study aimed to evaluate the effect of glucosamine selenium (GASe) on chronic colitis and reveal the underlying regulatory mechanisms.</p><p><strong>Methods: </strong>We evaluated the cumulative toxicity of GASe by gavage in mice for 40 days. Dextran sulfate sodium (DSS; 2.5%) was added to drinking water to induce chronic colitis, and GASe was administered to mice with chronic DSS colitis. 16S rRNA sequencing was performed to investigate the influence of GASe on gut microbiota, followed by diversity and LDA Effect Size (LEfSe) analyses. Differentially expressed genes (DEGs) associated with chronic DSS colitis were identified based on the expression profiling from the Gene Expression Omnibus (GEO) database and were subjected to functional enrichment analysis. Next, the effects of GASe on pyroptosis and chemokine signaling pathways were studied in vitro and in vivo.</p><p><strong>Results: </strong>GASe had no significant toxicity in mice, and administration of low-GASe and high-GASe increased the length of the colon, inhibited the expression of IL-12, IL-6, and TNF-α, and improved colonic tissue structure. Low-GASe improved the diversity of the gut microbiota and mainly affected the <i>Burkholderiaceae</i> family, <i>Paenalcaligenes</i> genus, and <i>Erysipelatoclostridium</i> genus. Low-GASe and high-GASe suppressed the pyroptosis-related proteins NLRP3, GSDMD, and caspase-1. Furthermore, we identified 114 DEGs from the GSE87466 and GSE53306 datasets and these DEGs were mainly enriched in the chemokine signaling pathway and some inflammatory pathways. Further experiments showed that administration of GASe inhibited the chemokine signaling pathway in chronic DSS colitis mice and NCM460 cells.</p><p><strong>Discussion: </strong>This study reveals abnormalities in the gut microbiota, pyroptosis, and chemokine signaling pathways involved in chronic colitis and may provide GASe as an alternative supplement for chronic colitis management.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3571-3588"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corn Silk Polysaccharides Before and After Selenization Reduced Calcium Oxalate Crystal-Induced HK-2 Cells Pyroptosis by Inhibiting the NLRP3-GSDMD Signaling Pathway.","authors":"Jin Han, Xin-Yi Tong, Yu-Yun Zheng, Jia-Hui Cheng, Jian-Ming Ouyang, Ke Li","doi":"10.2147/JIR.S506093","DOIUrl":"https://doi.org/10.2147/JIR.S506093","url":null,"abstract":"<p><strong>Objective: </strong>Pyroptosis is a new type of programmed cell death associated with many inflammatory diseases. Polysaccharides have anti-inflammatory effects. In this study, we investigated whether corn silk polysaccharides (DCSP) before and after selenization (Se-DCSP) can reduce the renal tubule pyroptosis induced by calcium oxalate crystals.</p><p><strong>Methods: </strong>HK-2 cells were exposed to calcium oxalate monohydrate with a size of 3 µm (COM-3μm) to establish a pyroptosis model. The degree of cell damage was determined by detecting cell viability, reactive oxygen species (ROS), and lactate dehydrogenase (LDH) content. The proportion of pyroptosis cells was quantitatively detected by Caspase-1/PI double staining. The expression levels of NLRP3, GSDMD, IL-18, and IL-1β were detected by confocal microscopy and Western blot analyses.</p><p><strong>Results: </strong>DCSP and Se-DCSP can reduce the secretion of inflammatory factors IL-1β/18 related to pyroptosis by reducing cell damage and oxidative stress, as well as down-regulate the expression of Caspase-1, NLRP3, GSDMD, and TNF-α, repair damaged cells, and inhibit pyroptosis in HK-2 cells. The inhibitory effect of selenized polysaccharide was significantly enhanced compared with that before selenification.</p><p><strong>Conclusion: </strong>Se-DCSP can inhibit pyroptosis through the NLRP3/Caspase-1/GSDMD/IL-1β/IL-18 signaling pathway to reduce the risk of kidney-stone formation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3623-3638"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Gene to Intervention: NLRC4 and WIPI1 Regulate Septic Acute Lung Injury Through Autophagy.","authors":"Xinyi Yang, Zhijian Sun, Zhuohui Liu, Hui Chen, Yang Fang, Wenqiang Tao, Ning Zhao, Xiufang Ouyang, Fen Liu, Kejian Qian","doi":"10.2147/JIR.S510691","DOIUrl":"https://doi.org/10.2147/JIR.S510691","url":null,"abstract":"<p><strong>Background: </strong>Septic Acute Lung Injury (SALI)-induced severe respiratory dysfunction has been established to significantly increase patient mortality rates and socioeconomic costs. To mitigate cellular damage, autophagy -a conserved biological process in organisms -degrades damaged cellular components, such as proteins and organelles. Although autophagy is crucially involved in the inflammatory response, its precise molecular mechanisms in SALI remain unclear, forming the basis of this study.</p><p><strong>Methods: </strong>Herein, two microarray datasets (GSE33118 and GSE131761) and three single-cell sequencing datasets (SCP43, SCP548, and SCP2156) derived from human samples were used to ascertain the interrelationship between Differentially Expressed Autophagy-Related Genes (DEARGs) and SALI. The relationship between key DEARGs and SALI was validated both in vitro and in vivo using various techniques, including flow cytometry, Immunofluorescence (IF), Quantitative Polymerase Chain Reaction (qPCR), Western Blotting (WB), and small interfering RNA (siRNA).</p><p><strong>Results: </strong>Herein, we found that autophagy activation attenuated SALI, with NLRC4 and WIPI1 as the two key DEARGs involved. Specifically, NLRC4 and WIPI1 downregulation mitigated SALI via autophagy activation. Compared to NLRC4, WIPI1 was more closely associated with noncanonical autophagic flux in SALI. Furthermore, immune infiltration analysis and single-cell data showed a close relationship between NLRC4, WIPI1, and immune cells.</p><p><strong>Conclusion: </strong>Our findings revealed that SALI correlated strongly with autophagy, with the downregulation of the two key DEARGs, NLRC4 and WIPI1, attenuating sepsis lung injury via autophagy regulation, highlighting their therapeutic significance in SALI.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3639-3656"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG-Associated Hypocomplementemia in Neonatal Lupus: A Retrospective Multicenter Study.","authors":"Wenqiang Sun, Yihui Li, Xinyun Jin, Xue Liu, Huiwen Li, Jingtao Bian, Lili Li, Jinhui Hu, Jie Huo, Zexi Sun, Huawei Wang, Mengzhao Li, Changchang Fu, Xueping Zhu","doi":"10.2147/JIR.S510816","DOIUrl":"https://doi.org/10.2147/JIR.S510816","url":null,"abstract":"<p><strong>Background: </strong>Hypocomplementemia, defined as a complement C3 or C4 level below the normal lower limit, is strongly associated with an unfavorable prognosis in patients with autoimmune diseases. This study aimed to explore the clinical features and outcomes of patients with neonatal systemic lupus erythematosus (NLE) with hypocomplementemia.</p><p><strong>Methods: </strong>This retrospective clinical study was conducted across four tertiary hospitals in Eastern China on January 1, 2011, and December 31, 2023. This study included 91 patients with NLE. Patients were classified into hypocomplementemic and non-hypocomplementemic groups according to their serum C3 and/or C4 levels. Risk factors for the development of hypocomplementemia were explored using univariate/multifactorial analyses, organ involvement, and follow-up outcomes were compared between groups.</p><p><strong>Results: </strong>The number of NLE patients with hypocomplementemia was 36 (39.56%). Hypocomplementemia group had a significantly lower proportion of fish oil supplementation during pregnancy, a higher proportion of cesarean deliveries, mothers with systemic lupus erythematosus, double antibody positivity for anti-SSA and anti-SSB, and higher serum IgG levels. Multivariate analyses showed that maternal allergic diseases, double antibody positivity, and serum IgG levels were risk factors for hypocomplementemia. Baseline IgG levels negatively correlated with complement C3 and C4 levels. NLE Patients with hypocomplementemia are more likely to have thrombocytopenia, hypoproteinemia, or gastrointestinal involvement than those without hypocomplementemia. Systemic application of glucocorticoids was significantly more prevalent in the hypocomplementemia group. Long-term follow-up revealed that allergy-associated disorders were common in patients with NLE and hypocomplementemia, followed by developmental delay, severe infections, attention- deficit hyperactivity disorder, and anxiety/depression, respectively. Log-rank analysis revealed that these patients had significantly higher frequencies of allergic diseases and developmental delays later in life.</p><p><strong>Conclusion: </strong>Maternal allergic diseases, double antibody positivity, and serum IgG levels were associated with the development of hypocomplementemia in children with NLE. Patients with hypocomplementemia-associated NLE typically exhibit a more severe disease course.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3419-3429"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Comments on The Association of Inflammatory Indexes Derived From Peripheral Blood Cell Count and Clinical Signs with Response to Treatment with Dupilumab in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis [Response to Letter].","authors":"Lingzhao Zhang, Jiangshan Pi, Jinsong Wang, Jingsi Chen, Yunxuan Zhang, Jie Li, Lingling Wang, Yue Li, Anwei Chen, Xiaoyan Luo, Hua Wang","doi":"10.2147/JIR.S523947","DOIUrl":"https://doi.org/10.2147/JIR.S523947","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3551-3553"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring The Role of TOP2A in the Intersection of Pathogenic Mechanisms Between Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis Based on Bioinformatics.","authors":"Shoujie Shi, Xin Hong, Yue Zhang, Shuilin Chen, Xiangfei Huang, Guihao Zheng, Bei Hu, Meifeng Lu, Weihua Li, Yanlong Zhong, Guicai Sun, Yulong Ouyang","doi":"10.2147/JIR.S497734","DOIUrl":"https://doi.org/10.2147/JIR.S497734","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF) share a common pathogenic mechanism, but the underlying mechanisms remain ambiguous. Our study aims at exploring the genetic-level pathogenic mechanism of these two diseases.</p><p><strong>Methods: </strong>We carried out bioinformatics analysis on the GSE55235 and GSE213001 datasets. Machine learning was employed to identify candidate genes, which were further verified using the GSE92592 and GSE89408 datasets, as well as quantitative real-time PCR (qRT-PCR). The expression levels of TOP2A in RA and IPF in vitro models were confirmed using Western blotting and qRT-PCR. Furthermore, we explored the influence of TOP2A on the occurrence and development of RA and IPF by using the selective inhibitor PluriSIn #2 in an in vitro model. Finally, an in vivo model of RA and IPF was constructed to assess TOP2A expression levels via immunohistochemistry.</p><p><strong>Results: </strong>Our bioinformatics analysis suggests a potential intersection in the pathogenic mechanisms of RA and IPF. We have identified 7 candidate genes: CXCL13, TOP2A, MMP13, MMP1, LY9, TENM4, and SEMA3E. Our findings reveal that the expression level of TOP2A is significantly elevated in both in vivo and in vitro models of RA and IPF. Additionally, our research indicates that PluriSIn #2 can effectively restrain inflammatory factors, extracellular matrix deposition, migration, invasion, the expression and nuclear uptake of p-smad2/3 protein in RA and IPF in vitro models.</p><p><strong>Conclusion: </strong>There is a certain correlation between RA and IPF at the genetic level, and the molecular mechanisms of their pathogenesis overlap, which might be the reason for the progression of RA. Among the candidate genes we identified, TOP2A may influence the occurrence and development of RA and IPF through the TGF-β/Smad signal pathway. This could be beneficial to the study of the pathogenesis and treatment of RA and IPF.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3449-3468"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}