Inflammation Research最新文献

{"title":"International comparison of neutrophil surface markers after severe trauma is feasible using point of care flowcytometry - results from a pilot study.","authors":"Christian Thomas Hübner, Emma de Fraiture, Nathalie Piaz, Louise Virginie Duebel, Roman Pfeifer, Sanne Brands, Felix Karl-Ludwig Klingebiel, Yannik Kalbas, Paolo Cinelli, Leo Koenderman, Falco Hietbrink, Hans-Christoph Pape, Michel Paul Johan Teuben","doi":"10.1007/s00011-026-02335-1","DOIUrl":"10.1007/s00011-026-02335-1","url":null,"abstract":"<p><strong>Introduction: </strong>The dynamics of cell surface marker expression on systemic neutrophils provide valuable insights into the post-traumatic immune response. Recent advances in point-of-care (PoC) technologies allow for rapid on-site neutrophil analysis. The current study aimed to proof, if results of PoC measurements are comparable between two study centers.</p><p><strong>Methods: </strong>A well-established laboratory protocol for fully automated PoC flowcytometry analysis of neutrophils was applied inside the trauma bay of two level 1 trauma centers. We analyzed the neutrophil surface patterns CD16, CD11b, CD62L, CD10 and CD64 and compared the results between two centers both in heathy controls and patients.</p><p><strong>Results: </strong>28 Polytrauma patients were included. The measurements at both centers revealed similar results with respect to the expression neutrophil activation markers in patients with different trauma severities. Particularly the expression of CD16, CD11b and CD10 were very comparable between both centers in both healthy controls and trauma patients.</p><p><strong>Conclusion: </strong>This study demonstrates the successful implementation of a fully automated PoC neutrophil analysis infrastructure from one trauma center to another facilitating multicenter flow cytometry studies. This paves the way for advanced immune monitoring that could significantly improve personalized clinical decision-making.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.","authors":"Mohamed Alsabbagh, Satanay Z Hubrack, Lara Gamgoum, Maryiam J A Osman, Katherine E Ford, Alya Al Shakaki, Amal Robay, Housam Sarakbi, Samar Al Emadi, Rafah Mackeh, Khalid A Fakhro, Bernice Lo","doi":"10.1007/s00011-026-02326-2","DOIUrl":"10.1007/s00011-026-02326-2","url":null,"abstract":"<p><strong>Background: </strong>A20 is an anti-inflammatory protein that suppresses nuclear factor-κB (NF-κB)-mediated inflammatory gene expression and inhibits cell death. Disruption of A20 function results in defective suppression of the NF-κB pathway, manifesting in diverse autoimmune and autoinflammatory conditions. While autosomal dominant A20 mutations have been identified to cause autoinflammatory disease, recessive A20 mutations causing disease have not been previously described.</p><p><strong>Methods: </strong>We utilized whole exome sequencing to identify the variant of interest. In silico structural modeling as well as immunoprecipitation were used to ascertain A20's interaction with linear ubiquitin, coupled with flow cytometric analysis and western blotting to measure the expression of NF-κB activation markers. We quantified NF-κB pathway activity using NF-κB reporter assay.</p><p><strong>Results: </strong>Here, we report a novel homozygous mutation in the A20 protein responsible for early-onset lupus-like disease starting at four years of age. We show that the A20 E781K variant, situated in the seventh zinc finger domain of A20, compromises the protein's ability to bind linear ubiquitin, resulting in a functional hypomorph with a reduced capacity to inhibit NF-κB activation and downstream gene expression in HEK293 cells.</p><p><strong>Conclusion: </strong>Our findings characterize a critical mutation associated with early-onset lupus-like disease in its recessive form and continue to highlight the important role of A20 in maintaining immune homeostasis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.","authors":"Nan Gao, Song Yang, Wei-Jian Zhang, Hao-Tian Lu, Zheng-Nan Zhang, Yi-Xin Qian, Guo-Qiang Zhang","doi":"10.1007/s00011-026-02310-w","DOIUrl":"10.1007/s00011-026-02310-w","url":null,"abstract":"<p><strong>Objective and design: </strong>This narrative review synthesizes current evidence on the role of SERPINE1/PAI-1 in acute respiratory distress syndrome (ARDS), with particular emphasis on inflammation-coagulation-fibrinolysis crosstalk.</p><p><strong>Material or subjects: </strong>Published experimental, translational, genetic, and clinical studies addressing SERPINE1/PAI-1 in ARDS and related critical illnesses were summarized.</p><p><strong>Treatment: </strong>Not applicable.</p><p><strong>Methods: </strong>We summarized evidence on the pathobiological functions, cellular sources, biomarker potential, genetic associations, and therapeutic implications of SERPINE1/PAI-1.</p><p><strong>Results: </strong>SERPINE1 limits tissue-type and urokinase-type plasminogen activator activity, thereby promoting hypofibrinolysis and persistent fibrin deposition in the injured lung. Experimental and clinical evidence further links elevated PAI-1 to inflammatory amplification, endothelial injury, pulmonary microvascular thrombosis, greater disease severity, and adverse outcomes, although the strength of evidence and the degree of causal support vary across these processes. High-expression SERPINE1 variants may also influence clinical outcomes in selected critical illness settings. Pharmacological PAI-1 inhibition is biologically plausible, but its translation to ARDS remains limited by disease heterogeneity, uncertainty regarding treatment timing, and the risk of bleeding.</p><p><strong>Conclusions: </strong>SERPINE1 is a potentially important integrative regulator and biomarker of dysregulated inflammation, coagulation, and fibrinolysis in ARDS. Future studies should clarify its causal, cell-specific, and phenotype-dependent roles to facilitate the development of targeted therapeutic strategies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niflumic acid suppresses NLRP3 inflammasome activation by limiting chloride efflux and mitochondrial ROS production.","authors":"Yuanhao Li, Qianqian Xie, Tianyin Sun, Jiwei Lu, Mengmeng Li, Renan Bai, Ronghua Lv, Fei Li, Haoqi Wang, Jingjing Cong, Wenwei Yin, Jing Li, Xuefu Wang","doi":"10.1007/s00011-026-02328-0","DOIUrl":"10.1007/s00011-026-02328-0","url":null,"abstract":"<p><strong>Background and aims: </strong>Aberrant activation of the NLRP3 inflammasome contributes to the development of multiple inflammatory disorders, but clinically approved inhibitors targeting this pathway are still lacking. We investigated whether niflumic acid (NFA), a clinically used nonsteroidal anti-inflammatory drug, regulates NLRP3 inflammasome activation and explored the underlying mechanism.</p><p><strong>Methods: </strong>NLRP3 inflammasome activation was induced in murine bone marrow-derived macrophages and PMA-differentiated THP-1 cells using nigericin, ATP, and monosodium urate crystals. Inflammasome activation, chloride efflux, mitochondrial injury, and mitochondrial ROS production were evaluated by immunoblotting, ELISA, flow cytometry, confocal microscopy, co-immunoprecipitation, and ASC speck analysis. TMEM16F was examined by molecular docking, cellular thermal shift assay, siRNA-mediated silencing, and pharmacological inhibition. The anti-inflammatory effects of NFA were further assessed in mouse models of LPS-induced endotoxemia, MSU-induced peritonitis, and acetaminophen-induced liver injury.</p><p><strong>Results: </strong>NFA preferentially inhibited NLRP3 inflammasome activation, as evidenced by reduced caspase-1 cleavage and decreased IL-1β and IL-18 maturation and secretion, without significantly affecting TNF-α production or the activation of the AIM2 and NLRC4 inflammasomes. Mechanistically, NFA suppressed ASC speck formation and disrupted NLRP3-ASC interaction, indicating impaired inflammasome assembly. NFA also blocked chloride efflux, alleviated mitochondrial damage, and reduced mitochondrial reactive oxygen species (mtROS) generation, while having minimal effects on K⁺ efflux and Ca²⁺ influx. Moreover, TMEM16F was found to contribute to NFA-mediated inhibition of NLRP3 inflammasome activation, and genetic depletion of TMEM16F or pharmacological inhibition of Ca²⁺-activated chloride channel activity mimicked the effects of NFA on chloride efflux, mtROS production, and NLRP3 inflammasome activation. In vivo, NFA reduced inflammatory injury and inflammasome-associated readouts in multiple inflammatory models.</p><p><strong>Conclusion: </strong>NFA suppresses NLRP3 inflammasome activation through a mechanism associated, at least in part, with TMEM16F-related chloride efflux and mtROS production. These findings suggest an anti-inflammatory mechanism of NFA that is not fully explained by canonical COX inhibition and support further investigation of NFA as a potential modulator of inflammasome-associated inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid PKM2 deficiency alleviates allergic airway inflammation and promotes macrophage efferocytosis via SLC13A3.","authors":"Lingli Chen, Yile Liu, Yating Chen, Yue Zhang, Lei Yu, Yantong Zhu, Wang Peng, Maolan Wu, Xiangrong Zheng","doi":"10.1007/s00011-026-02329-z","DOIUrl":"10.1007/s00011-026-02329-z","url":null,"abstract":"<p><strong>Background: </strong>Allergic asthma is characterized by chronic airway inflammation that fails to resolve efficiently. Defective efferocytosis and metabolic reprogramming of macrophages are crucial factors in allergic diseases. While PKM2 is known to participate in phagocytosis and metabolism, its specific role in modulating asthma remains unclear.</p><p><strong>Objective: </strong>To delineate the underlying mechanisms of PKM2 in allergic asthma.</p><p><strong>Methods: </strong>We generated myeloid cell-specific LysM^crePKM2^fl/fl mice, with littermate PKM2^fl/fl mice serving as controls, and challenged them with ovalbumin (OVA) extract to induce allergic airway inflammation. In vivo, we assessed airway hyperresponsiveness, pulmonary inflammation, Th2 cytokine levels, apoptosis, and efferocytosis-related receptor expression. Primary bone marrow-derived macrophages(BMDMs) were isolated for in vitro evaluation of efferocytic activity under distinct polarization conditions. To investigate underlying mechanisms, we performed RNA-seq to identify PKM2 downstream targets, followed by lentiviral-mediated overexpression of the candidate molecule SLC13A3 in THP-1 cells, with validation through molecular docking, immunoprecipitation, and functional assays.</p><p><strong>Results: </strong>We found that PKM2 is upregulated in macrophages during asthma. Myeloid cell-specific PKM2 deficiency mitigated OVA-induced Th2 inflammation and eosinophilic apoptosis while reducing airway hyperresponsiveness (AHR). Mechanistically, PKM2-expressing macrophages exhibited decreased SLC13A3 transcription, which drove activation of the PI3K-AKT and redistributed STAT6/1 ratio to impair efferocytosis. This impairment disturbed the M2/M1 balance. In vitro experiments confirmed that SLC13A3 overexpression enhanced efferocytic capacity and promoted a shift toward M2/M1 balance. Conversely, PKM2 overexpression in macrophages impaired efferocytosis and exacerbated chronic airway inflammation.</p><p><strong>Conclusion: </strong>Our study reveals a novel role for myeloid cell-specific PKM2 and SLC13A3 in asthma, linking efferocytosis to immune metabolism during allergic inflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review.","authors":"Leah Elson, Niels Eijkelkamp, J Henk Coert","doi":"10.1007/s00011-026-02317-3","DOIUrl":"10.1007/s00011-026-02317-3","url":null,"abstract":"<p><strong>Objective and design: </strong>This systematic review synthesized evidence for a conserved lipopolysaccharide (LPS)-mediated pathogenic mechanism across diverse tissues and evaluated its potential relevance to peripheral neuropathy.</p><p><strong>Methods: </strong>Studies were identified in which LPS was the independent exposure and pro-inflammatory, M1-like macrophage activation/polarization was an outcome. Structured evidence mapping was used to code in-vivo studies for direct measurement of prespecified steps along a proposed pathway: gut perturbation→barrier disruption→circulating LPS→systemic inflammation→tissue interface disruption→innate immune activation→M1-like macrophage skew→tissue dysfunction. Conditional concordance and downstream chain completeness scores were calculated.</p><p><strong>Results: </strong>Mechanistic patterns were conserved between pulmonary, cardiac, renal, lymphatic, gastrointestinal, central nervous, adipose, osseous, urologic, dental, hepatic, uterine, and pancreatic tissues. Conditional concordance with the proposed pathway was high (mean 0.984 ± 0.053). Eleven studies assessed all downstream steps from LPS exposure to tissue dysfunction, each demonstrating full chain completeness. M1 macrophage skew (87%), innate immune activation (87%), and circulating LPS (82.6%) were the most frequently reported steps.</p><p><strong>Conclusions: </strong>These findings demonstrate conservation of LPS-driven M1-like macrophage polarization and tissue injury across systems, supporting the need to further investigate the biological plausibility of a gut-immune-nerve axis contributing to peripheral neuropathy.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.","authors":"Yang Shao, Rui Feng Zhang, Zhonghe Wang, Jiali Gan, Xi Juan Jiang, Lin Yang, Zhi Jie Song","doi":"10.1007/s00011-026-02313-7","DOIUrl":"10.1007/s00011-026-02313-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Autoimmune diseases (AIDs) are characterized by disrupted immune tolerance, chronic inflammation, and organ-specific tissue injury. Their pathogenesis involves the interplay between genetic susceptibility and environmental factors. Although current biological agents and glucocorticoid therapies have improved clinical outcomes, long-term remission rates remain limited, with persistent risks including infection, organ toxicity, and immunogenicity. Emerging evidence indicates that copper homeostasis imbalance, mitochondrial dysfunction, redox stress, and immunometabolic remodeling coexist in multiple systemic and organ-specific AIDs. Cuproptosis, a newly identified form of regulated cell death, provides a potential mechanistic framework to understand the convergence of these pathological processes. However, direct in vivo evidence of canonical cuproptosis in autoimmune lesions remains scarce, and most relevant studies rely on transcriptomic associations, public dataset mining, or model-dependent experiments. There is an urgent need to clarify conceptual boundaries and the hierarchy of evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This review aims to systematically distinguish the conceptual differences among copper dysregulation, copper-associated mitochondrial/redox stress, cuproptosis-related vulnerability, and canonical cuproptosis. It seeks to summarize the hierarchical levels and limitations of existing evidence, evaluate the translational potential of copper-modulating strategies in AIDs, and provide references for future research directions and clinical translation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;1. A hierarchical evidence grading system for cuproptosis was established, categorizing existing evidence into six levels: bioinformatic inference (e.g., transcriptomic differential expression, immune infiltration correlation), disease-associated phenotypic evidence, functional perturbation evidence, rescue-based evidence, direct biochemical validation, and in vivo disease validation. It was clarified that canonical cuproptosis can only be confirmed when copper dependence, involvement of the Ferredoxin 1 (FDX1)-lipoylation axis, aggregation of lipoylated proteins, destabilization of Fe-S clusters, and functional rescue are demonstrated. 2. The characteristics of copper metabolism disorders and cuproptosis related molecular remodeling in systemic AIDs (e.g., systemic lupus erythematosus, rheumatoid arthritis) and organ-specific AIDs (e.g., inflammatory bowel disease, ankylosing spondylitis) were summarized. Findings mostly reflected copper-associated metabolic stress or susceptibility markers rather than definitive functional activation. 3. The immunometabolic regulatory roles of cuproptosis in immune cells-including macrophages, dendritic cells, and T cells-were analyzed, highlighting that their effects are cell-type and context dependent. 4. The limitations of copper-modulating strategies, such as copper chelators and","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP1 modulates ZDHHC5-mediated NLRP3 inflammasome activation to promote mitochondrial damage and foam cell formation of vascular smooth muscle cells.","authors":"Yunqing Zhang, Qian Yang, Zheng Sui, Zheng Wan, Kuang Peng, Panyang Feng, Liping Liu","doi":"10.1007/s00011-026-02324-4","DOIUrl":"10.1007/s00011-026-02324-4","url":null,"abstract":"<p><strong>Background: </strong>Smooth muscle-derived foam cell formation is a key to atherosclerosis (AS) development. Mitochondrial damage is involved in AS pathogenesis S. Here, effects of ZDHHC5 on mitochondrial damage and foam cell formation of vascular smooth muscle cells were evaluated.</p><p><strong>Methods: </strong>Expressions of mRNA and protein were determined by RT-qPCR and Western blot. ORO and Nile red staining evaluated foam cell formation. Mito tracker Green and Mito Tracker Red probes evaluated mitochondrial integrity. Electron microscopy observed mitochondrial morphology. Cytoplasmic mtDNA was quantified by mtDNA release assay. Acyl-biotin exchange assay tested palmitoylation level. Co-immunoprecipitation (Co-IP) detected interaction between ZDHHC5 and NLRP3. RNA immunoprecipitation (RIP) and RNA pull down verified interaction between ZDHHC5 and IGF2BP1. Methylated RNA immunoprecipitation (MeRIP) assessed m6A level on ZDHHC5. ApoE^-/- mouse model of AS was constructed. Histological analysis of atherosclerotic lesions was performed. Levels of IL-1β and IL-18 in serum were detected by ELISA.</p><p><strong>Results: </strong>NLRP3 depletion reduced damage to mitochondria within foam cells derived from smooth muscle. Inhibiting NLRP3 palmitoylation hindered NLRP3 inflammasome activation. ZDHHC5 triggered NLRP3 activation through enhancing NLRP3 palmitoylation. ZDHHC5 exacerbated mitochondrial damage via activating NLRP3 inflammasome. IGF2BP1 enhanced stability and expression of ZDHHC5 mRNA in a m6A-dependent way. IGF2BP1 triggered NLRP3-mediated mitochondrial damage and amplified AS by upregulating ZDHHC5 in ApoE^-/- mice. IGF2BP1, ZDHHC5, and NLRP3 function as biomarkers for early detection of AS.</p><p><strong>Conclusions: </strong>IGF2BP1 regulates ZDHHC5-mediated NLRP3 inflammasome activation, thereby enhancing mitochondrial damage and foam cell formation in vascular smooth muscle cells, which provides new therapeutic targets for AS.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics identifies CYP1B1 as a candidate molecular link between toxicant exposure and ferroptosis-related epithelial stress in COPD.","authors":"Lingfeng Liu, Mingjun Jiang, Muzi Lei, Kun Du, Xiangyang Ye, Dafei Wei, Xiaowu Tan, Zhuang Mi, Yao Tang, Ruiting Sun, Sha Liu","doi":"10.1007/s00011-026-02294-7","DOIUrl":"10.1007/s00011-026-02294-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation, chronic airway inflammation, and epithelial remodeling. Although oxidative stress and lipid peroxidation are increasingly recognized as important contributors to COPD pathobiology, the epithelial biomarkers and regulatory pathways linking cigarette-smoke exposure to ferroptosis-related injury remain incompletely defined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to identify COPD-associated biomarkers and pathways by integrating bulk transcriptomics, single-cell RNA sequencing, machine-learning analysis, and experimental validation, with a particular focus on the potential association between CYP1B1 and ferroptosis-related epithelial stress.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Public transcriptomic cohorts, including GSE47460, GSE76925, and GSE37768, were analyzed using differential expression analysis, weighted gene co-expression network analysis, functional enrichment analysis, and machine-learning-based feature prioritization. Single-cell RNA-seq datasets, including GSE196341 and GSE135893, were used to explore cell-type localization of candidate genes. A cigarette-smoke-exposed mouse model and cigarette-smoke extract-treated 16HBE cells were used for experimental validation, and small-scale proteomic data were incorporated as orthogonal supporting evidence. Molecular docking was performed as an exploratory analysis to predict putative interactions between CYP1B1 and candidate compounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-four candidate genes were identified by intersecting COPD-associated co-expression modules with differentially expressed genes. Machine-learning analysis prioritized BHLHE22, DPP6, DHRS9, and CYP1B1 as candidate diagnostic biomarkers. The combined model showed high discrimination in the training cohort, with reduced but retained performance in an external validation cohort. Single-gene ROC analysis in an independent dataset suggested moderate discriminatory performance, with CYP1B1 showing relatively consistent performance across analyses. Single-cell analysis indicated that CYP1B1 expression was enriched in airway secretory cell-related populations, and CYP1B1-high airway secretory cells were associated with ferroptosis-related pathway signatures. In cigarette-smoke-exposed mice and CSE-treated 16HBE cells, CYP1B1 expression was increased, accompanied by inflammatory and epithelial injury-related changes. Knockdown of CYP1B1 attenuated CSE-induced alterations in ferroptosis-related markers, including GPX4, MDA, 4-HNE, and GSH/GSSG. Exploratory molecular docking identified several compounds with predicted CYP1B1-binding potential, although experimental validation is required.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Integrative multi-omics and experimental analyses identified CYP1B1 as a candidate COPD-associated epithelial stress biomarker linked to ferroptosis-related signatures in airway secre","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophil cationic protein-driven type 2 inflammation impairs olfactory function in a murine model.","authors":"Zhong Zheng, Liufeiyan Fan, Haofei Bai, Silyu Jing, Chunyang Zhang, Yubin Lai, Min Xu, Jian Wang, Tao Xue, Dingjun Zha, Fuquan Chen","doi":"10.1007/s00011-026-02273-y","DOIUrl":"10.1007/s00011-026-02273-y","url":null,"abstract":"<p><strong>Objective and design: </strong>Eosinophilic chronic rhinosinusitis (ECRS) is characterized by the infiltration of eosinophils and is frequently associated with olfactory dysfunction (OD). The underlying mechanisms of OD related to ECRS remain poorly understood. This study aims to develop a murine model of eosinophil-induced OD (EIOD) within a brief timeframe by administering eosinophil cationic protein (ECP) intranasally. The efficacy of the model was assessed through a series of behavioral, morphological, and molecular biology experiments.</p><p><strong>Methods: </strong>Male mice received intranasal ECP for durations of 10 and 20 days to induce EIOD. The established mouse model was subsequently subjected to olfactory behavior assessments, histological examinations, cytokine analysis of nasal lavage fluid, and gene expression profiling to confirm its validity.</p><p><strong>Results: </strong>Behavioral assessments conducted on the mice substantiated the presence of OD and revealed a thinning of the olfactory epithelial mucosa, accompanied by a reduction in the number of olfactory sensory neurons. Concurrently, an increase in type 2 inflammatory cytokines was detected in the nasal lavage fluid. Upon cessation of ECP administration, both olfactory function and the olfactory mucosa exhibited signs of recovery. Furthermore, RNA sequencing analysis revealed alterations in certain inflammatory immune pathways.</p><p><strong>Conclusion: </strong>This study effectively established and validated an EIOD murine model, thereby offering valuable tools for investigating the pathogenesis and potential therapeutic interventions for this disease.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}