Journal of Inflammation Research最新文献

{"title":"Analysis and Validation of Mitophagy-Related Genes in Diabetic Foot Ulcers.","authors":"Shaoyihan Fang, Huijuan Zhang, Wenjian Liu, Shuangyan Li, Zhenzhen Chen, Jingjie Min, Chengyu Dai, Jingwen An, Hongxiao Zhang, Dewu Liu","doi":"10.2147/JIR.S504001","DOIUrl":"10.2147/JIR.S504001","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to identify hub genes associated with mitophagy involved in the pathogenesis and progression of diabetic foot ulcer (DFU), and to characterize their immune cell infiltration features and single-cell expression profiles.</p><p><strong>Methods: </strong>DFU-related datasets (GSE80178, GSE68183) were retrieved from the GEO database. Subsequently, differentially expressed genes (DEGs) were identified via limma analysis, followed by gene set enrichment analysis (GSEA) to assess gene function enrichment. Identified DEGs were intersected with mitophagy-related genes. Machine learning (ML) algorithms were further employed to identify hub genes. Additionally, immune cell infiltration was examined via the CIBERSORT algorithm, and the correlation between the identified genes and immune infiltration was investigated. Finally, hub genes identified were validated via the single-cell RNA sequencing dataset GSE165816, and further validated using RT-PCR and Western blot (WB) assays.</p><p><strong>Results: </strong>Two hub genes, ANO6 and ALDH2, were identified and found to be significantly downregulated in the skin tissues of patients with DFU. Receiver operating characteristic (ROC) analysis demonstrated robust diagnostic potential (ANO6, AUC = 0.833, ALDH2, AUC = 0.806). Immune cell infiltration analysis demonstrated notable differences between the DFU and normal groups in naïve B cells, monocytes, resting mast cells, γδT cells, and regulatory T cells (Tregs). The findings were further validated through single-cell RNA sequencing (scRNA-seq) analysis and experimental studies, which confirmed the downregulation of ANO6 and ALDH2 in DFU tissues.</p><p><strong>Conclusion: </strong>Two mitophagy-related hub genes, ANO6 and ALDH2, were identified and validated as being significantly downregulated in DFU. Both genes demonstrated diagnostic potential and showed an association with immune cell infiltration. These findings suggest that mitophagy dysfunction may contribute to the pathophysiology of DFU, potentially through the dysregulation of inflammatory pathways and immune responses. While the results provide valuable insights into DFU and its management, further studies with larger cohorts and deeper exploration of mechanistic links to inflammation are necessary to translate these findings into therapeutic strategies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4367-4379"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753063","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":"The Association of Peripheral Blood Immunoinflammatory Markers with PE and Adverse Outcomes in Preeclampsia: A Retrospective Study.","authors":"Yunting Zhuang, Yanxuan Xiao, Ruiyan Bai, Yao Song, Zeshan Lin, Yiqi Yu, Qian Chen, Zhijian Wang","doi":"10.2147/JIR.S504552","DOIUrl":"10.2147/JIR.S504552","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is a syndrome exclusive to pregnancy, presenting substantial risks to maternal and fetal health. Systemic immune-inflammatory response is a prominent feature of PE.</p><p><strong>Methods: </strong>A retrospective study was conducted involving 749 pregnant women in Guangzhou, China from September 2018 to September 2024. Three hundred and seventy participants were diagnosed with PE, 166 of which had adverse pregnancy outcomes (APOs). Immuno-inflammatory markers expressed in peripheral blood were evaluated during the second-trimester. APOs included postpartum haemorrhage (PPH), premature rupture of membranes (PROM), placental abruption, fetal growth restriction, neonatal intensive care unit (NICU) transfer, and fetal distress. The relationship between immune-inflammatory markers and PE and APOs was analyzed.</p><p><strong>Results: </strong>Women with PE were at higher risk of APOs and had higher levels of neutrophil-to-lymphocyte ratio (NLR), systemic immunoinflammatory index (SII) and systemic inflammatory response index (SIRI). The AUC values for NLR, SII, and SIRI with PE were 0.594, 0.649, and 0.646 (P < 0.001), with cut-off values of 4.389, 994.863, and 2.406, respectively. For APOs in PE, the AUC values were 0.632, 0.627 and 0.669, with cut-off values of 4.959, 1070.408 and 3.346, respectively. Analysis indicated higher SII levels with increased incidences of fetal growth restriction, NICU transfer and fetal distress, and SIRI levels with NICU transfer and fetal distress (P < 0.05).</p><p><strong>Conclusion: </strong>Elevated levels of immune-inflammatory markers including NLR, SII, and SIRI are associated with PE and APOs. Our findings underscored the different optimal cut-off values of immune-inflammatory markers in the pregnant women between PE and the APOs.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4359-4366"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752331","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":"A Matrigel-Free 3D Chondrocytic Spheroid Model for Rheumatoid Arthritis-Associated Synoviocytes Invasion Studies.","authors":"Yingjie Zhao, Xuezhi Yang, Feng Yao, Ziwei Ouyang, Weirong Hu, Lin Li, Juan Cheng, Ke Wang, Jie Ding, Liang Zheng, Biao Qu, Cheng Sun, Shufang Li, Chen Jiang, Yanan Chen, Renpeng Zhou, Wei Hu","doi":"10.2147/JIR.S504701","DOIUrl":"10.2147/JIR.S504701","url":null,"abstract":"<p><strong>Background: </strong>The primary pathology of rheumatoid arthritis (RA) involves the invasion of the extracellular matrix (ECM) of articular cartilage by inflammation-activated fibroblast-like synoviocytes (FLS), a process targeted by most RA therapeutic drugs. However, the absence of an efficient in vitro model for evaluating FLS invasion hinders relevant drug screening and mechanism research. To address this, a novel three-dimensional (3D) chondrocytic spheroid model that mimics cartilage ECM has been developed, along with corresponding indices to quantify synoviocytes invasion.</p><p><strong>Methods: </strong>The matrigel-free 3D chondrocytic spheroid model was developed using an ultra-low attachment plate. The model was characterized using transcriptome sequencing, immunofluorescent staining. To explore the feasibility of this 3D chondrocytic spheroid model for evaluating the invasive capacity of synoviocytes, multi-interference strategies, including <i>ADAMTS5</i> gene overexpression, inflammatory cytokine stimulation, and anti-inflammatory drug (Etanercept) treatment were involved. Additionally, specific indices-Invasion Depth Ratio (IDR), Invasion Counts (IC), Invasion Ratio (IR), and Invasion Area Ratio (IAR)-were designed to quantify synoviocytes invasion.</p><p><strong>Results: </strong>The 3D culture environment is more suitable for cartilage ECM synthesis by increasing cartilage anabolism-related gene (<i>COL2A1</i>) and reducing catabolism-related genes (<i>ADAMTS5, MMP3, CCL2 and CDKN2A</i>) expression. Moreover, the optimal conditions for developing the 3D chondrocytic spheroid model were identified. This model was sensitive to gene, inflammation and drug interference. Increased IDR, IC, IR and IAR was observed in <i>ADAMTS5</i> overexpressed- and IL-1β-treated chondrocytic spheroid. Further, Etanercept could inhibit TNF-α induced synoviocytes invasion of chondrocytic spheroid.</p><p><strong>Conclusion: </strong>This matrigel-free 3D chondrocytic spheroid model offers an ideal platform for innovative drug screening and pathogenesis studies focused on synoviocytes invasion of cartilage.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4319-4334"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753061","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":"The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy.","authors":"Shuguang Zhang, Wenying Chen, Jihong Zhou, Qi Liang, Yu Zhang, Ming Su, Zilong Zhang, Jian Qu","doi":"10.2147/JIR.S499403","DOIUrl":"10.2147/JIR.S499403","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) have transformed cancer treatment by providing highly targeted and effective therapies that specifically attack cancer cells, thus reducing the likelihood of adverse events (AEs) in patients. mAbs exert their action through various mechanisms, such as receptor blockade, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and inhibition of immune checkpoints (eg, PD-1, PD-L1, and CTLA-4). These therapies have led to significant improvements in the treatment of several cancers, including HER2-positive breast cancer, non-small cell lung cancer (NSCLC), and melanoma. The efficacy of mAb therapy in cancer treatment is influenced by various intrinsic and extrinsic factors, such as environmental exposures, psychosocial factors, infection status, ways of life, and tumor microenvironment (TME), all of which can impact immune responses and treatment outcomes. Notably, the therapeutic benefits of mAbs are often accompanied by immune-related AEs (irAEs), which can vary from mild to severe and affect multiple organ systems. The dual nature of mAbs-stimulating antitumor immune responses while also inducing immune-related side effects-presents a notable challenge in clinical practice. This review highlights the importance of proactive strategies for managing irAEs, such as early detection, corticosteroid use, targeted immunosuppressive treatments, and the urgent need for reliable predictive biomarkers to improve treatment outcomes. Advancements in the prevention, prediction, and management of irAEs are essential to enhance the safety and effectiveness of mAb-based therapies, ultimately aiming to improve cancer patient outcomes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4335-4357"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752811","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":"Recurrence of Histiocytic Necrotizing Lymphadenitis in Children: A 10-year Multicenter Retrospective Study.","authors":"Yong-Ping Xie, Yan-Wen Xu, Yan Li, Hu Zhang, Shan-Shan Xu, Mei-Na Lu, Yi-Ping Chen, Jian-Mei Tian, Xin-Fang Huang, Zhi-Feng Liu, Zhi-Gang Gao, Li-Su Huang","doi":"10.2147/JIR.S504413","DOIUrl":"10.2147/JIR.S504413","url":null,"abstract":"<p><strong>Purpose: </strong>Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi-Fujimoto disease, is prone to recurrence in children. However, the frequency and risk factors associated with recurrence remain unclear.</p><p><strong>Patients and methods: </strong>This study included all children with pathology-confirmed HNL from five hospitals over ten years (2013-2023). This study employed STROBE analysis to investigate the association between clinical characteristics and HNL, which was subsequently verified through in both a derivation group and a validation group. Initial clinical features were collected, and data were randomly divided into derivation and validation sets (3:2 ratio). Cox regression analysis identified risk factors, and receiver operating characteristic curves were used to develop a prediction model. Flow cytometry focused on assessing CD4⁺ T-lymphocytes in lymphoid tissue.</p><p><strong>Results: </strong>Of the 593 HNL cases, 88 (14.8%) experienced recurrence during a median follow-up of 3 years. Cumulative recurrence rates at the first, fifth, and ninth years were 8.7%, 20.0%, and 32.2%, respectively. Factors associated with recurrence included age ≤ 6-year-old (Hazard ratio [HR] 3.6, 95% confident interval [CI], 2.0-6.4), C-reactive protein > 16 mg/L (HR, 1.9, 95% CI, 1.0-3.6), blood CD4⁺ T-lymphocytes ≤ 30% (HR, 4.4, 95% CI, 1.0-18.7), ferritin > 150 μg/L (HR, 2.3, 95% CI, 1.1-5.3) and platelets ≤ 200×10⁹/L (HR 1.8, 95% CI, 1.0-3.2). The prediction model demonstrated areas under the curve of 0.81 for the derivation dataset and 0.77 for the validation dataset, classifying patients into low, medium, and high-risk categories, with corresponding recurrence rates of 5.2%, 19.0%, and 42.9%. Lower lymphoid CD4⁺ T-lymphocyte counts were also observed in the recurrent group.</p><p><strong>Conclusion: </strong>The recurrence of HNL increases over time. Key factors, including C-reactive protein (CRP) levels, CD4⁺ T-lymphocyte counts, ferritin, platelets, and age at diagnosis may contribute to recurrence risk.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4307-4318"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753111","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":"The Dual Roles of STAT3 in Ferroptosis: Mechanism, Regulation and Therapeutic Potential.","authors":"Jinghui Xie, Dan Luo, Pengfei Xing, Weijun Ding","doi":"10.2147/JIR.S506964","DOIUrl":"10.2147/JIR.S506964","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent programmed mechanism of cell death that is driven by lipid peroxidation, is an important pathogenic factor in oncological and non-oncological disorders. Dysregulation of iron and lipid metabolism profoundly influences disease progression through ferroptosis modulation. Signal transducer and activator of transcription 3 (STAT3), a transcriptional regulator, regulates ferroptosis by binding to promoters of key molecules such as solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1). In this review, we described the role of STAT3 in supporting tumors survival by suppressing ferroptosis in malignancies, and bidirectionally regulating ferroptosis in non-tumors to regulate the development of the disease. We also reported emerging therapeutic strategies that target STAT3-mediated ferroptosis, including natural phytochemicals, inhibitors, and nanotechnology-enabled drug delivery systems. These advancements deepen the mechanistic understanding of ferroptosis regulation, and provide new theoretical bases and strategies to treat ferroptosis-related diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4251-4266"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719826","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":"Understanding the Mode of Action of Several Active Ingredients from the Micro-Immunotherapy Medicine 2LZONA^®.","authors":"Camille Jacques, Flora Marchand, Mathias Chatelais, Adrien Brulefert, Ilaria Floris","doi":"10.2147/JIR.S498930","DOIUrl":"10.2147/JIR.S498930","url":null,"abstract":"<p><strong>Introduction: </strong>Varicella-zoster virus (VZV) affects over 90% of the global population. The initial encounter with VZV, often in the early years of childhood, results in varicella. From latency, VZV can reactivate in later stages of life, leading to the development of herpes zoster. Considering the importance of host immune responses in preventing reactivation and clinical manifestations associated with VZV infection, a therapy that sustains the immune system could be of great interest.</p><p><strong>Objective: </strong>The present work aimed to set the basis of the possible mode of action of 2LZONA^®, a micro-immunotherapy medicine composed of five different capsules. Thus, the effects of several active substances employed in this medicine were assessed in human primary immune-related cells.</p><p><strong>Results and discussion: </strong>Our results showed that DNA (8 CH) and RNA (8 CH), two active substances used in 2LZONA, displayed phagocytosis-enhancing capabilities in granulocytes and contained sub-micron particles that could explain, at least partially, the observed effect. These two active substances tested singularly and together with other actives of 2LZONA's capsules, modulated the proliferation of immature, transitory, and mature subsets of natural killer (NK) cells in an IL-15-like pattern, suggesting an enhancement of their activation levels. Moreover, the tested items of 2LZONA increased the secretion of IL-2, IL-6, IL-13, and TNF-α in human peripheral blood mononuclear cells (PBMCs). Furthermore, the proliferation of PBMCs-derived NK cells, intermediate monocytes, and neutrophils was slightly increased by this treatment. In CD3 and CD3/CD28 pre-primed conditions, actives present in one capsule of 2LZONA enhanced the secretion of IL-6 and TNF-α. Finally, one capsule of 2LZONA reduced the expression of human leukocyte antigen (HLA) in IFN-inflamed endothelial cells. Overall, these data provide, for the first time, preliminary experimental evidence of the mechanisms of action of some of the active ingredients employed in 2LZONA capsules.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4267-4290"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710222","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":"Identification and Validation of the Potential Key Biomarkers for Atopic Dermatitis Mitochondrion by Learning Algorithms.","authors":"Junhao Xu, Xinyu Pan, Miao Zhang, Kairong Sun, Zihan Li, Juan Chen","doi":"10.2147/JIR.S507085","DOIUrl":"10.2147/JIR.S507085","url":null,"abstract":"<p><strong>Purpose: </strong>Atopic dermatitis (AD) is a common inflammatory skin condition characterized by erythema and pruritus. Its precise pathogenesis remains unclear, though factors such as genetic predisposition, autoantigen response, allergen exposure, infections, and skin barrier dysfunction are involved. Research suggests a correlation between AD and mitochondrial dysfunction, as well as oxidative stress in skin tissues.</p><p><strong>Methods: </strong> Skin sample datasets related to AD (GSE36842, GSE120721, GSE16161, and GSE121212) were retrieved from the GEO database. Differential gene analysis identified differentially expressed genes (DEGs) in AD. Three potential biomarkers-COX17, ACOX2, and ADH1B-were identified using LASSO and Support Vector Machine (SVM) algorithms. These biomarkers were validated through ROC curve analysis, nomogram modeling, calibration curves, and real-time PCR. Immune infiltration analysis assessed correlations of the biomarkers. Additionally, single-cell analysis of the GSE153760 dataset identified nine cell clusters and confirmed expression patterns of the three hub genes.</p><p><strong>Results: </strong>Differential analysis identified 150 upregulated and 367 downregulated genes. Enrichment analysis revealed significant pathways related to mitochondrial function, oxidative stress, and energy metabolism in skin samples from AD patients. Area under the curve (AUC) values for biomarkers COX17, ACOX2, and ADH1B were 1.000, 0.928, and 0.895, respectively, indicating strong predictive capacity. qPCR results showed COX17 was highly expressed in AD lesions, while ACOX2 and ADH1B were higher in normal skin, consistent with previous findings. Correlation analysis indicated ACOX2 and ADH1B were positively correlated with resting mast cells but negatively with activated T cells and NK cells, while COX17 showed a positive correlation with activated T cells and a negative correlation with resting mast cells.</p><p><strong>Conclusion: </strong>This study suggests that the hub genes COX17, ACOX2, and ADH1B may serve as potential biomarkers in the pathogenesis of AD. These findings could provide insights for the treatment and prognosis of AD and related inflammatory skin conditions.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4291-4306"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719823","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":"FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression.","authors":"Maoting Hu, Kunlin Yu, Chunlin Wang, Wuling Liu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Giulio Sartori, Francesco Bertoni, Xiao Xiao, Yaacov Ben-David","doi":"10.2147/JIR.S500822","DOIUrl":"10.2147/JIR.S500822","url":null,"abstract":"<p><strong>Plaque psoriasis: </strong>Plaque psoriasis is an inflammatory skin disorder affecting nearly 2% of the world population. Despite recent advances in psoriasis treatment, there is still a need for more effective therapies. The ETS transcription factor FLI1 plays critical roles in hematopoiesis, angiogenesis, immunity, and cancer. Emerging evidence suggests that FLI1 is intricately involved in inflammatory processes underlying psoriasis pathogenesis.</p><p><strong>Methods: </strong>RNAseq and bioinformatic analysis were used to identify the correlation between FLI1 levels and the expression of inflammatory genes associated with psoriasis. Over-expression of FLI1 in skin cells determined FLI1's role in inducing transcription of psoriasis-related inflammatory genes, including IL6, IL1A, IL1B, IL23, and TNFα. Inhibitors such as chelerythrine (CLT) were tested for their suppressive effects on these genes. Mouse models of plaque psoriasis were employed to assess the therapeutic potential of CLT and tacrolimus (TAC).</p><p><strong>Results: </strong>Over-expression of FLI1 in skin cells upregulated 24 psoriasis-associated genes, which were identified through RNAseq. Inhibitors of FLI1, such as CLT, suppressed these inflammatory genes in skin cells. In mouse models of plaque psoriasis induced by imiquimod (IMQ) or phorbol ester (TPA), treatment with the anti-FLI1 inhibitor CLT, administered either peritoneally or topically, significantly downregulated inflammatory genes and alleviated psoriasis symptoms. Similarly, TAC, a common immunosuppressive agent, effectively attenuated IMQ-induced psoriasis by acting as a potent anti-FLI1 compound.</p><p><strong>Conclusion: </strong>These findings demonstrate that FLI1 plays a central role in psoriasis development and highlight it as a potential therapeutic target for this skin disorder.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4213-4231"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700516","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":"Systemic Lupus Erythematosus Stimulates Chondrocyte Pyroptosis to Aggravate Arthritis via Suppression of NRF-2/KEAP-1 and NF-κB Pathway.","authors":"Shuchao Shen, Xuliang Fang, Helou Zhang, Tingting Lang, Fangda Fu, Yu Du, Taotao Xu, Hongting Jin, Peijian Tong, Chengliang Wu, Changfeng Hu, Hongfeng Ruan","doi":"10.2147/JIR.S502800","DOIUrl":"10.2147/JIR.S502800","url":null,"abstract":"<p><strong>Purpose: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by diverse clinical manifestations, including joint symptoms. Arthritis represents one of the earliest manifestations of SLE, profoundly affecting the quality of life for affected individuals, yet the underlying mechanisms of SLE-associated arthritis remain insufficiently investigated. The study aimed to investigate the impact of SLE exacerbation on arthritis using the MRL/<i>lpr</i> mouse model, which closely mimics human SLE manifestations.</p><p><strong>Methods: </strong>In the present study, we evaluated the impact of SLE onset on knee joint degeneration by comparing arthritic phenotype and complex molecular alterations between 6 female 14-week-old MRL/<i>lpr</i> mice, which manifest SLE, and MRL/<i>MpJ</i> mice, which remain unaffected.</p><p><strong>Results: </strong>Our results demonstrated that MRL/<i>lpr</i> mice exhibited a more severe arthritic phenotype compared to MRL/<i>MpJ</i> mice, characterized by elevated Osteoarthritis Research Society International (OARSI) scores (<i>P</i> < 0.01), disrupted extracellular matrix metabolism, impaired chondrocyte proliferation and increased apoptosis. Notably, inflammatory cytokines proteins such as IL-1β and TNF-α (both <i>P</i> < 0.01), IL-18 and IL-6 (both <i>P</i> < 0.05), were significantly increased in articular cartilage of MRL/<i>lpr</i> mice, accompanied by increased expression of calcitonin gene-related peptide (CGRP) (<i>P</i> < 0.05), NETRIN-1, and NESTIN (both <i>P</i> < 0.01), indicating that SLE promotes inflammation response and sensory nerve ingrowth in the knee joint, contributing to the progression of arthritis. Mechanistic analysis revealed that SLE exacerbation intensified chondrocyte pyroptosis by upregulating pyroptotic-related proteins, including NLRP3, CASPASE-1, and gasdermin D (all <i>P</i> < 0.01), through the regulation of the nuclear factor erythroid 2-related factor (NRF-2)/KEAP-1 and nuclear factor kappa-B (NF-κB) pathway.</p><p><strong>Conclusion: </strong>Collectively, our findings underscore the mechanistic connection between chondrocyte pyroptosis and arthritis exacerbation in SLE, suggesting potential therapeutic targets for mitigating arthritis progression in the context of SLE.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4233-4250"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700530","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}