Inflammation Research最新文献

{"title":"Ethyl ferulate attenuates allergic asthma via inhibiting macrophage M2 polarization through STAT6/IRF4 pathway.","authors":"Longlong Ge, Weizhen Chen, Shuguang Han, Huan Yang, Mingchen Du, Shengpeng Li, Xinran Bai, Peilin Zhao, Dan Chen, Qingfeng Pang, Yaxian Wu","doi":"10.1007/s00011-026-02309-3","DOIUrl":"10.1007/s00011-026-02309-3","url":null,"abstract":"<p><strong>Objective: </strong>Allergic asthma is a chronic airway inflammatory disease with limited therapeutic options in clinical practice. Ethyl ferulate (EF), a natural compound commonly found in Chuanxiong, Danggui and grains, has been shown to possess multiple biological activities. However, the effect of EF on allergic asthma and its underlying mechanisms remains unclear. This study aimed to investigate the therapeutic potential and mechanism of EF in allergic asthma.</p><p><strong>Methods: </strong>The house dust mite (HDM)-induced allergic asthma mouse model was used to evaluate the effects of EF on airway inflammation and macrophage M2 polarization. Adoptive transfer experiments were used to confirm the critical role of M2 polarization in the attenuation of allergic asthma by EF. Mechanistic studies were performed by using IL-4-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs).</p><p><strong>Results: </strong>EF significantly attenuated HDM-induced airway inflammation, eosinophil infiltration, mucus secretion, and airway remodeling. EF suppressed M2 macrophage markers (CD206, Arg1, Ym1, Fizz1) in lung tissues and IL-4-stimulated macrophages. Mechanistically, EF blocked STAT6 phosphorylation and nuclear translocation, thereby inhibiting the STAT6/IRF4 pathway.</p><p><strong>Conclusions: </strong>EF alleviates allergic asthma by inhibiting M2 macrophage polarization via disruption of the STAT6/IRF4 signaling pathway, supporting its potential as a therapeutic agent derived from traditional medicine.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345160","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":"Endothelial cell-specific knockout of ATG5 ameliorates inflammation and renal fibrosis by regulating pyroptosis.","authors":"Yu Huang, Shu Wen, Li Chen, Yujiu Gao, Shufan Xu, Chen Fang, Jian Tang, Yue Yuan, Ying Feng, Shinan Ma, Shan Luo, Qinghong Zhang, Xiuyan Shi, Xuzhi Ruan, Xingrong Guo","doi":"10.1007/s00011-026-02272-z","DOIUrl":"10.1007/s00011-026-02272-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;ATG5, a key regulator of autophagy-associated inflammation, is markedly upregulated under inflammatory conditions. In this study, we observed significantly elevated ATG5 expression in the kidneys of patients with renal fibrosis and in mouse kidneys after unilateral ureteral obstruction (UUO), particularly in renal tubules and glomeruli. Recent studies suggest that enhanced ATG5-mediated autophagy in tubular epithelial cells targets the NF-κB pathway to alleviate renal injury. The glomerulus is a dense capillary network primarily composed of endothelial cells, which represent a key immune cell population in the kidney. However, whether endothelial ATG5 exerts a function similar to that of tubular ATG5 during the progression of renal fibrosis remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;First, Sirius red staining, immunohistochemistry staining and other and pathological methods were used to analyze the expression of ATG5 in relation to the progression of renal fibrosis in patients and UUO model mice. We next observed the effects of endothelial-specific knockout of ATG5 in mice with renal fibrosis induced by the UUO model by ultrasound image assessment, HE staining, and Masson staining. Human umbilical vein endothelial cells (HUVECs) were isolated, and their regulation of inflammation and promotion of renal fibrosis were analyzed by overexpression and knockdown of ATG5 using in vitro synthetic mRNA and siRNA interference techniques. Transmission electron microscopy (TEM), qPCR and Western blotting were used to determine the effect of endothelial ATG5 on promoting inflammation-dependent pyroptosis in vitro and in vivo. Finally, the expression of GSDMD, a key pyroptosis gene, was examined in the kidneys of clinical renal fiber patients by immunohistochemistry staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We successfully generated endothelial-specific ATG5 knockout (Tek-Cre ATG5 KO) mice and found that endothelial cell deletion of ATG5 attenuated UUO-induced renal fibrosis. Mechanistically, endothelial-specific ATG5 knockout suppressed pyroptosis and the release of inflammatory factors in the UUO model, primarily by inhibiting GSDMD expression and its cleavage into the N-GSDMD fragment during canonical NLRP3 inflammasome activation. Electron microscopy results showed that ATG5 mainly caused pyroptosis independent of plasma membrane pores in endothelial cells. Conditioned medium from human umbilical vein endothelial cells with ATG5 knockdown inhibited the expression of the key fibrotic marker TGF-β1 in renal tubular epithelial HK-2 cells. Consistent results were obtained when HK-2 cells were cocultured with serum from UUO mice with endothelial-specific ATG5 knockout. Furthermore, GSDMD expression was positively correlated with the degree of fibrosis in patients with renal fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Collectively, our findings demonstrate that ATG5 modulates the inflammatory response by mediating pyroptos","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345202","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":"Trichomonas vaginalis-induced inflammation is associated with Th17 differentiation and tumor-intrinsic IL-17R signaling in prostate cancer progression.","authors":"Ik-Hwan Han, Seobo Sim, Juri Kim, Soon-Jung Park, Jae-Sook Ryu","doi":"10.1007/s00011-026-02312-8","DOIUrl":"10.1007/s00011-026-02312-8","url":null,"abstract":"<p><strong>Objective: </strong>Chronic inflammation associated with infection has been implicated in prostate cancer (PCa) progression, yet the immunological mechanisms linking sexually transmitted pathogens to tumor development remain incompletely understood. Trichomonas vaginalis (Tv), the most prevalent nonviral sexually transmitted parasite worldwide, has been associated with prostatic inflammation and increased PCa risk. However, how Tv-induced inflammation influences tumor progression has not been clearly defined. Here, we investigated whether Tv-induced epithelial inflammation promotes Th17 differentiation and drives prostate tumor progression through intratumoral IL-17 receptor (IL-17R) signaling.</p><p><strong>Methods: </strong>Conditioned media of prostate epithelial cells (PECs, RWPE-1 cell line) was prepared by infection without (CM) and with Tv (TCM). Human CD4⁺ T cells were isolated using the CD4⁺ isolation kit from human peripheral blood. Conditioned medium of CD4⁺ T cells was prepared by incubation with CM (T-CM) or TCM (T-TCM).</p><p><strong>Results: </strong>Conditioned media from Tv-stimulated PECs induced robust production of IL-6 and IL-1β, which promoted IL-6/IL-1R-dependent differentiation of human CD4⁺ T cells into Th17 cells. Conditioned media from these Th17 cells enhanced proliferation and migration of prostate epithelial and cancer cells and activated IL-17R-TRAF6-NF-κB signaling pathways. Using a syngeneic mouse prostate cancer model in C57BL/6 mice, we found that IL-17R neutralization significantly reduced tumor growth without affecting Th17 cell abundance, supporting the involvement of tumor-intrinsic IL-17R signaling in Tvs-associated tumor progression. Spatial transcriptomic analysis further revealed enrichment of IL-17R-associated proliferative and invasive gene programs in Tvs-treated tumors. Consistently, analysis of prostate adenocarcinoma datasets showed that IL17RA expression was associated with proliferative and invasive signatures and poorer clinical outcomes.</p><p><strong>Conclusion: </strong>Collectively, these findings identify a Tv-Th17-IL-17R signaling axis linking infection-induced inflammation to tumor-intrinsic oncogenic signaling in prostate cancer, highlighting IL-17R signaling as a potential therapeutic target in inflammation-associated PCa.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345138","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":"Mechanism-centered target discovery across glomerulonephritis phenotypes: an integrative multi-omics study.","authors":"Jiachen Liu, Xiaorui Qiu, Dianjie Zeng, Yue Li, Yuxi Wang, Jiashu Gu, Yashpal S Kanwar, Leyi Chen, Chenming Wei, Yinhuai Wang, Wenpeng Wang, Liya Sun","doi":"10.1007/s00011-026-02299-2","DOIUrl":"10.1007/s00011-026-02299-2","url":null,"abstract":"<p><strong>Background: </strong>Glomerulonephritis (GN) comprises a heterogeneous group of immune-mediated kidney disorders with substantial biological and clinical diversity. Current treatment still relies largely on broad immunosuppression, underscoring the need for mechanism-informed target discovery across GN phenotypes.</p><p><strong>Methods: </strong>We performed a program-guided integrative multi-omics study by combining cis-expression quantitative trait loci and cis-protein quantitative trait loci with GN genome-wide association datasets from UK Biobank, the GWAS Catalog, and FinnGen. Candidate genes were organized into four predefined mechanistic programs: cytokine/TNF signaling, cell-cycle/senescence-repair balance, complement/innate immune activation, and regulated cell-death/redox stress. Six GN-related outcomes were analyzed. Bayesian colocalization, cross-dataset meta-analysis, mouse knockout annotation, drug-repurposing assessment, network pharmacology, and rule-based evidence scoring were used to refine target prioritization.</p><p><strong>Results: </strong>Integrative screening identified 42 transcriptomic and 12 proteomic putative targets, with the strongest enrichment in non-proliferative glomerulonephritis and primary membranoproliferative glomerulonephritis. Bayesian colocalization supported PPP2R1B in non-proliferative glomerulonephritis, SOD1 in IgA nephropathy, and CDK4 in primary membranoproliferative glomerulonephritis. Among 42 transcriptomic gene-outcome pairs taken forward, 11 were supported by cross-dataset meta-analysis. Proteomic meta-analysis supported several cross-dataset signals, including protective associations of ANXA5, GSR, and TNFRSF1B with glomerulonephritis. Across outcomes, complement/innate immunity and cytokine/TNF signaling formed the dominant shared backbone. After separating MHC-region signals for cautious interpretation, 31 non-MHC targets were retained for primary prioritization, with PPP2R1B, CDK4, and SOD1 comprising the top tier.</p><p><strong>Conclusions: </strong>This mechanism-centered integrative multi-omics study delineates shared and phenotype-enriched biological programs across the GN spectrum and identifies a prioritized set of candidate targets for future validation and therapeutic development.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345141","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":"Re-evaluation of the prognosis of patients with IgA nephropathy and mild proteinuria: a longitudinal study with unexpected results.","authors":"Xiuhua Ma, Sen Zhang, Wenhui Chen, Xiaoling Zhou","doi":"10.1007/s00011-026-02308-4","DOIUrl":"10.1007/s00011-026-02308-4","url":null,"abstract":"<p><strong>Background: </strong>IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a major cause of chronic kidney disease. Mild proteinuria (< 0.5 g/24 h) is generally considered to indicate a favorable prognosis in IgAN. This study aimed to explore the clinicopathological features and prognostic factors of such patients.</p><p><strong>Method: </strong>We performed a retrospective analysis of IgAN patients who had renal biopsies at our hospital from 2008 to 2023. We included patients with 24-hour proteinuria < 0.5 g, age ≥ 15 years, and follow-up ≥ 12 months. Risk factors were assessed using logistic regression and Cox proportional hazards models.</p><p><strong>Results: </strong>Over a mean follow-up of 90.75months, 27 patients(10.19%) experienced endpoint events. The overall eGFR slope was - 2.07mL/min/1.73 m² per year. Greater eGFR decline correlated with lower 10-year renal survival. Multivariate analysis showed severe tubulointerstitial damage, lower baseline eGFR and steeper eGFR decline were independent risk factors for renal endpoint events. Renal arteriolar lesions, lower baseline eGFR, steeper eGFR decline, and lower TyG-BMI were risk factors for poor renal prognosis.</p><p><strong>Conclusions: </strong>Our study challenges the assumption that IgAN patients with mild proteinuria have a favorable prognosis. Over 90.75 months, 10.19% of patients experienced endpoint events, with an eGFR decline of 2.07 mL/min/1.73 m² per year. These findings indicate significant disease progression risk in IgAN patients with mild proteinuria. In addition to traditional risk factors, metabolic factors such as TyG-BMI are important prognostic predictors.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345180","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":"Reconceptualizing chorioamnionitis as an immune-mediated inflammatory disorder at the maternal-fetal interface.","authors":"Tzu-Ming Wang, Chung-Min Shen, Shih-Chang Lin, Wu-Shiun Hsieh, Yi-Li Hung, Jiun-Wen Guo","doi":"10.1007/s00011-026-02286-7","DOIUrl":"10.1007/s00011-026-02286-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chorioamnionitis has long been regarded as an infection-driven obstetric disorder, yet converging clinical, pathological, and mechanistic evidence demonstrates that host-derived inflammatory pathways, together with microbial factors, critically shape placental injury, fetal involvement, and neonatal outcomes. Histological inflammation of the chorioamniotic membranes correlates more strongly with adverse outcomes than microbial detection alone, underscoring the importance of host immune responses even in the context of microbial invasion.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This review aims to synthesize current insights into the immune landscape of the maternal-fetal interface, the coordinated contributions of multiple immune pathways, the interplay between microbial and non-microbial triggers, and the downstream consequences for fetal and neonatal health. Rather than replacing the infection-based paradigm, we aim to extend it by integrating immunological mechanisms that account for disease heterogeneity and variable clinical outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A narrative review was conducted using a structured literature identification strategy. Relevant peer-reviewed original studies, review articles, clinical investigations, and translational studies were identified through targeted literature searches and synthesized according to their mechanistic and clinical relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sterile intra-amniotic inflammation can produce overlapping responses with infection, arising from partially distinct mechanisms and representing a context-dependent extension within infection-associated processes, without constituting a separate primary pathway. Advances in maternal-fetal immunology identify the maternal-fetal interface as a dynamic immune environment in which disrupted tolerance, heightened pattern-recognition signaling, and amplified cytokine and chemokine networks lower the threshold for pathological activation. Multiple pathways including interleukin-1 and interleukin-6 signaling, macrophage activation, and neutrophil-mediated responses collectively drive this process. In this context, neutrophil extracellular traps formation represents an important effector mechanism linking microbial and non-microbial cues to tissue-destructive inflammation. Fetal exposure to these pathways results in immune programming consistent with the fetal inflammatory response syndrome, contributing to pulmonary, intestinal, and neurodevelopmental sequelae. Although antibiotics remain essential for infection control, they do not directly target downstream immune circuits sustaining placental inflammation or fetal injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Reframing chorioamnionitis as an immune-mediated disorder, while preserving the central role of infection, supports endotype-based classification and targeted immunomodulation. It also highlights the potential of microbiota-informed strategies beyond pathogen e","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148329183","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":"Methylmalonic acid as a ferroptosis-derived danger signal: activation of the PI3K-NF-κB pathway drives M1 macrophage polarization in renal ischemia-reperfusion injury.","authors":"Huimeng Wang, Jiajia Sun, Xiaohu Li, Hongxuan Ma, Yongsheng Luo, Minghui Qin, Hao Zhang, Haodong Bian, Jinfeng Li","doi":"10.1007/s00011-026-02300-y","DOIUrl":"10.1007/s00011-026-02300-y","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis and macrophage activation are key contributors to the development of acute kidney injury (AKI). Ferroptosis is accompanied by metabolic reprogramming and the release of soluble mediators, including metabolites, cytokines, and extracellular signals, which can propagate tissue damage and modulate immune responses. However, the metabolic profile of ferroptotic tubular epithelial cells and its impact on the immune microenvironment during ischemia-reperfusion injury (IRI) remains largely unexplored.</p><p><strong>Methods: </strong>Using untargeted metabolomics, we found that ferroptotic cells secreted abnormally elevated levels of methylmalonic acid (MMA), and investigated the physiological role of MMA in acute kidney injury in mice. Furthermore, through transcriptomics and Western blotting, we explored the mechanism by which the ferroptosis-associated metabolite MMA promotes macrophage polarization.</p><p><strong>Results: </strong>Here, untargeted metabolomics revealed a distinct metabolic secretome of ferroptotic tubular epithelial cells, with the level of MMA markedly elevated after IRI. Mechanistic studies demonstrated that MMA activated the PI3K/ Akt /NF-κB pathway in macrophages, driving M1 polarization and increasing the secretion of proinflammatory cytokines such as IL-6 and TNF-α, ultimately exacerbating acute kidney injury.</p><p><strong>Conclusion: </strong>These findings reveal the mechanism of metabolite-immune crosstalk in AKI, and suggest that targeting the ferroptosis-macrophage axis may represent a therapeutic strategy to disrupt the vicious cycle of inflammation and tissue injury.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294743","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":"Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.","authors":"Yanqi Lei, Min Tang, Huilan Deng, Yanqun Li, Jidi Wu, Li Luo, Yulin Mou, Qianshi Wu, Qifu Li, Yong Xu, Wei Huang","doi":"10.1007/s00011-026-02302-w","DOIUrl":"10.1007/s00011-026-02302-w","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is associated with oxidative stress, systemic immune dysregulation and chronic low-grade inflammation, which contributes to a wide spectrum of microvascular and macrovascular complications. Efferocytosis, the phagocytic clearance of apoptotic cells by macrophages and dendritic cells, is essential for inflammation resolution and tissue repair. Defective efferocytosis has been increasingly implicated in the progression of diabetes and several of its major complications, including atherosclerosis, nephropathy, retinopathy, impaired wound healing, and osteoporosis.</p><p><strong>Objectives: </strong>This narrative review is prepared through a focused literature search of studies investigating efferocytosis in diabetes, elucidates how its disruption contributes to the progression of diabetic complications, and further highlight emerging therapeutic strategies aimed at regulating efferocytosis. This paper is expected to provide direction and outlook for the research on efferocytosis and diabetes.</p><p><strong>Results: </strong>Efferocytosis regulation involves a coordinated cascade of find-me signals, engulfment receptors, intracellular cytoskeletal remodeling, and metabolic reprogramming. This review summarizes the key molecular changes of defective efferocytosis and pathological changes in diabetic complications. Importantly, emerging preclinical studies have demonstrated that restoring efferocytosis ameliorate inflammation, promote tissue regeneration, and interrupt the progression of diabetic complications.</p><p><strong>Conclusions: </strong>Efferocytosis not only illuminates fundamental aspects of immune regulation but also opens up new therapeutic possibilities. As the field continues to evolve, integrating efferocytosis-based interventions into the broader therapeutic landscape of diabetes may represent a paradigm shift in the management of its chronic complications.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294954","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":"Endoglin is not a mediator in 7-ketocholesterol-induced endothelial activation in liver sinusoidal endothelial cells in vitro.","authors":"Petra Fikrova, Katarina Tripska, Samira Eissazadeh, Martina Vasinova, Adela Diepoltova, Jana Urbankova Rathouska, Ivana Nemeckova, Radim Havelek, SeyedehNiloufar Mohammadi, Ivone Cristina Igreja Sa, Petr Nachtigal","doi":"10.1007/s00011-026-02307-5","DOIUrl":"10.1007/s00011-026-02307-5","url":null,"abstract":"<p><strong>Background: </strong>Endoglin (ENG) is expressed in liver sinusoidal endothelial cells (LSECs), where it regulates endothelial activation and inflammation. The 7-ketocholesterol (7-K), a cholesterol oxidation product, accumulates in the liver and induces endothelial dysfunction. ENG has been shown to play an important role in adhesion processes in other endothelial models but its role in LSECs upon 7-K exposure remains unclear. We hypothesized that 7-K treatment of LSECs would confirm the critical role of ENG in endothelial activation, potentially outweighing the contributions of the cell adhesion molecules VCAM-1 and ICAM-1.</p><p><strong>Methods: </strong>Human LSECs were exposed to 25 µM 7-K. Protein expression and monocyte adhesion were assessed by flow cytometry, and soluble ENG was measured by ELISA.</p><p><strong>Results: </strong>7-K reduced ENG expression, while ICAM-1 was markedly upregulated. 7-K increased monocyte adhesion to LSECs, which was abrogated by ICAM-1, but not by ENG neutralization.</p><p><strong>Conclusion: </strong>We showed that 7-K promotes a pro-inflammatory phenotype defined by ICAM-1, rather than ENG. Thus, we propose that individual roles of ENG, ICAM-1, and VCAM-1 must be carefully considered when studying endothelial dysfunction.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294920","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":"Recombinant human diamine oxidase prevents histamine-induced hypoxia, shock and death in guinea pigs.","authors":"Felix Kosta, Matthias Weiss-Tessbach, Elisabeth Gludovacz, Birgit Reiter, Martin Murauer, Bernd Jilma, Marlene Rager-Resch","doi":"10.1007/s00011-026-02297-4","DOIUrl":"10.1007/s00011-026-02297-4","url":null,"abstract":"<p><strong>Background and objective: </strong>Histamine is the principal effector of anaphylaxis, and circulating levels correlate well with symptom severity in Hymenoptera venom-induced anaphylaxis. Adrenaline, the recommended first-line therapy, does not neutralize histamine and may cause relevant adverse effects. Recombinant human diamine oxidase (rhDAO), engineered with a mutated heparin-binding motif, exhibits improved pharmacokinetics and rapid histamine-degrading activity. The primary aim of this study was to evaluate whether prophylactic or particularly therapeutic rhDAO prevents or reduces histamine-induced shock compared with adrenaline in guinea pigs.</p><p><strong>Methods: </strong>Guinea pigs received subcutaneous histamine (1 mg/kg) with or without intramuscular adrenaline or intravenous rhDAO (2-8 mg/kg). Mean arterial pressure, heart rate, and arterial oxygen partial pressure (PaO₂) were monitored. Plasma histamine and rhDAO levels were measured.</p><p><strong>Results: </strong>Histamine injection raised plasma levels above 200 ng/ml and consistently induced shock with 42% mortality. Prophylactic and therapeutic rhDAO completely degraded circulating histamine, reduced shock incidence from 100% to 0% at the highest doses, shortened tachycardia, improved PaO₂ and decreased mortality. Intramuscular adrenaline (0.005 or 0.01 mg/kg) did not improve hemodynamics, oxygenation or survival.</p><p><strong>Conclusion: </strong>Recombinant hDAO prevented and treated histamine-induced shock and hypoxia, whereas adrenaline was ineffective. These findings support clinical development of rhDAO for life-threatening histamine-mediated conditions, including anaphylaxis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294857","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}