Inflammation Research最新文献

{"title":"BGP-15 ameliorates sepsis-induced cardiomyopathy via SIRT3/SOD2-associated antioxidant signaling and suppression of myocardial inflammation.","authors":"Yanxue Zhao, Xinpei Liu, Zining Wu, Xiaocui Wang, Guotao Ma, Xingrong Liu, Jun Zheng, Sheng Yang, Chaoji Zhang","doi":"10.1007/s00011-026-02353-z","DOIUrl":"10.1007/s00011-026-02353-z","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis-induced cardiomyopathy is a serious complication of sepsis characterized by acute myocardial dysfunction and substantial mortality. This study evaluated the therapeutic effects of BGP-15 and the potential involvement of SIRT3/SOD2-associated signaling in a mouse model of cecal ligation and puncture (CLP)-induced sepsis.</p><p><strong>Materials and methods: </strong>BGP-15 (20 or 40 mg/kg) was administered intravenously once at 6 h after CLP surgery. Survival, cardiac function, myocardial injury, oxidative stress, and inflammatory responses were evaluated. Myocardial SIRT3 expression, SOD2 Lys68 acetylation, and total SOD2 protein were assessed. The SIRT3 inhibitor 3-TYP was co-administered to investigate the potential involvement of SIRT3-related signaling in the effects of BGP-15.</p><p><strong>Results: </strong>Sepsis was associated with cardiac dysfunction, increased mortality and myocardial injury, reduced myocardial SIRT3 expression, increased SOD2 Lys68 acetylation, and decreased total SOD2 protein. BGP-15 treatment improved survival and cardiac function, reduced serum CK-MB and LDH levels, and attenuated myocardial oxidative and inflammatory injury. High-dose BGP-15 increased SIRT3 expression, both BGP-15 doses reduced the Acetyl-SOD2/SOD2 ratio, and total SOD2 protein was increased. Co-administration of 3-TYP attenuated several cardiac, oxidative, and inflammatory effects associated with BGP-15 treatment, whereas its apparent attenuation of the 14-day survival benefit did not reach statistical significance (log-rank P = 0.1103).</p><p><strong>Conclusion: </strong>These findings support the involvement of SIRT3-related signaling in the cardioprotective effects associated with BGP-15 in experimental sepsis and support further preclinical investigation of BGP-15 for septic cardiomyopathy. SIRT3 and SOD2 enzymatic activities were not measured directly.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897166","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":"Itaconate alleviates LPS-induced septic liver injury by regulating ROS-PAD4-mediated macrophages extracellular traps through Nrf2.","authors":"Liwu Zeng, Yaxin Wang, Gan Mao, Yisong Gao, Kaixiong Tao, Ruidong Li","doi":"10.1007/s00011-026-02359-7","DOIUrl":"10.1007/s00011-026-02359-7","url":null,"abstract":"<p><p>Activated macrophages release macrophage extracellular traps (METs), which are a major cause of tissue damage in sepsis. However, the molecular mechanisms governing their production remain poorly characterized. In this study, we demonstrate that MET levels are markedly elevated in both the liver and circulation in a lipopolysaccharide (LPS)-induced sepsis model. The immunometabolite itaconate-a product of the enzyme aconitate decarboxylase 1 (Acod1)-emerged as a critical suppressor of this pathway. Genetic ablation of immune responsive gene 1 (Irg1) resulted in heightened MET release, exacerbated hepatic injury, and decreased survival in septic mice. In contrast, the itaconate derivative 4-octyl itaconate (4-OI) robustly suppressed MET formation and ameliorated liver damage. Mechanistically, 4-OI activated the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in scavenging of intracellular reactive oxygen species (ROS), which suppressed ROS-dependent activation of peptidylarginine deiminase 4 (PAD4), thereby inhibiting histone citrullination and subsequent MET release. The suppression of MET formation by 4-OI is mediated through an Nrf2-dependent mechanism, as its absence abolishes this suppression, revealing the Nrf2-ROS-PAD4 axis's key role. The findings reveal a new metabolic-immune pathway: itaconate reduces sepsis-linked liver injury by using Nrf2 to suppress METs, suggesting a novel clinical treatment approach.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897180","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":"Mast cell-derived extracellular vesicles in lung diseases: roles in pulmonary inflammation, immune regulation, and microenvironmental remodeling.","authors":"Yu Wang, Caopei Zheng, Yuqing Sun, Yulin Zhang","doi":"10.1007/s00011-026-02349-9","DOIUrl":"10.1007/s00011-026-02349-9","url":null,"abstract":"<p><strong>Objective: </strong>This review summarizes the biological characteristics of mast cell-derived extracellular vesicles (EVs) and their roles in lung diseases involving mast cell activation and immune dysregulation, focusing on asthma, neonatal lung injury, and lung adenocarcinoma.</p><p><strong>Material: </strong>Published studies involving mast cell lines, animal models, and patient-derived biospecimens on mast cell-derived EVs in pulmonary inflammation were summarized.</p><p><strong>Treatment: </strong>Not applicable.</p><p><strong>Methods: </strong>We synthesized evidence on EV biogenesis, cargo composition, target-cell interactions, immunomodulatory functions, and disease-specific roles.</p><p><strong>Results: </strong>Mast cells are key effector cells in pulmonary inflammation whose functions extend beyond classical degranulation. They communicate with epithelial, stromal, and immune cells via EVs carrying proteins, lipids, mRNAs, and microRNAs. These vesicles modify recipient-cell function and mediate inflammatory amplification, epithelial injury, airway remodeling, and immune-cell activation. Mast cell-derived EVs exert disease- and context-dependent effects by regulating epithelial-immune crosstalk, type 2 inflammation, tissue remodeling, and tumor microenvironmental interactions.</p><p><strong>Conclusions: </strong>Mast cell-derived EVs are key mediators of intercellular communication in pulmonary inflammation. However, most evidence comes from cell and animal models, and the clinical relevance of specific EV cargoes remains unclear. Further studies are needed to clarify their disease-specific mechanisms and evaluate their potential as biomarkers and therapeutic targets.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897184","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":"FOXP1 exacerbates allergic rhinitis progression by mediating ferroptosis in nasal mucosal epithelial cells via transcriptional regulation of SDHAF2.","authors":"Liqiang Deng, Debao Luo, Xiaowen Zhang","doi":"10.1007/s00011-026-02333-3","DOIUrl":"10.1007/s00011-026-02333-3","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of the transcription factor FOXP1 and its target gene SDHAF2 in allergic rhinitis (AR), as well as their regulatory effects on ferroptosis in nasal epithelial cells.</p><p><strong>Methods: </strong>An AR mouse model and IL-4/IL-13-induced human nasal epithelial cells (HNEpCs) were used. Gene and protein expression, cytokine secretion, ferroptosis markers, nasal pathology, and AR symptoms were assessed via transcriptome sequencing, qRT-PCR, Western blot, ELISA, dual-luciferase reporter assay, co-immunoprecipitation, detection of Fe²⁺, ROS, GSH, MDA and lipid peroxides (LPO), and transmission electron microscopy. The biological functions of FOXP1 and SDHAF2 were explored through gene knockdown or overexpression, combined with the intervention of ferroptosis activator Erastin or inhibitor Ferrostatin-1.</p><p><strong>Results: </strong>Sdhaf2 was significantly upregulated in AR models and closely associated with mitochondrial function and ferroptosis. Knockdown of SDHAF2 inhibited IL-4/IL-13-induced ferroptosis and inflammation in HNEpCs, whereas overexpression of SDHAF2 aggravated these phenotypes. The above changes could be modulated by Erastin or Ferrostatin-1. FOXP1 was highly expressed in AR models and transcriptionally regulated SDHAF2, which was verified by dual-luciferase reporter assays. SDHAF2 interacted with ALOX15 to increase ALOX15 expression and promote ferroptosis. Additional overexpression of ALOX15 reversed the inhibitory effect of SDHAF2 knockdown on ferroptosis. In OVA-induced AR mice, Sdhaf2 knockdown relieved nasal symptoms, reduced inflammatory cytokines, improved nasal pathological lesions and suppressed ferroptosis, and these protective effects were partially abolished by Erastin.</p><p><strong>Conclusion: </strong>FOXP1 upregulates SDHAF2. The encoded SDHAF2 protein interacts with ALOX15 to facilitate ferroptosis in nasal epithelial cells, thereby aggravating AR progression. The FOXP1/SDHAF2/ALOX15/ferroptosis axis may serve as a novel therapeutic target for AR.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897191","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":"Exercise as a modulator of purinergic signaling and inflammation in cancer-associated sarcopenia: a narrative review.","authors":"Emeline Moraes de Oliveira, Vitor Mariano Gonçalves Dockhorn, João Victor Garcia de Souza, Francini Franscescon, Débora Tavares de Resende E Silva","doi":"10.1007/s00011-026-02331-5","DOIUrl":"10.1007/s00011-026-02331-5","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength, is highly prevalent among cancer patients and is strongly associated with poor prognosis. Increasing evidence indicates that overactivation of the purinergic system contributes to a chronic inflammatory state that promotes tumor progression and exacerbates muscle wasting.</p><p><strong>Purpose: </strong>This narrative review examines how physical exercise may modulate purinergic signaling and inflammation, potentially improving the quality of life of cancer patients with sarcopenia.</p><p><strong>Methods: </strong>A literature search was conducted in the MEDLINE database via PubMed, including articles published between 2008 and 2025, using descriptors such as \"purinergic signaling\", \"CD39\", \"CD73\", \"P2X7 receptor\", \"adenosine\", \"sarcopenia\", \"skeletal muscle metabolism\", \"cancer\", \"inflammation\", and \"extracellular ATP\".</p><p><strong>Results: </strong>Original studies and review articles in English addressing the relationship between purinergic pathways, inflammation, muscle metabolism, and cancer were included.</p><p><strong>Conclusions: </strong>Findings suggest that cancer-related sarcopenia is closely linked to systemic inflammation mediated by purinergic pathways, and evidence indicates that exercise may play a pivotal role in mitigating muscle loss and improving patient outcomes.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897174","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":"Theaflavin attenuates atherosclerosis by targeting GSK-3β to suppress pyroptosis and Promote Autophagy in macrophages.","authors":"Sha Yang, Liping Liao, Qin Yang, Tianqin Xia, Shihan Qin, Qingrui Tang, Mingzhu Li, Jiaojiao Bian, Yu Du, Xi Yong, Xiaochun Fan, Zhengmin Xu","doi":"10.1007/s00011-026-02343-1","DOIUrl":"10.1007/s00011-026-02343-1","url":null,"abstract":"<p><strong>Objective and design: </strong>This experimental study investigated theaflavin (TF) as a potential treatment for atherosclerosis (AS), focusing on its regulation of macrophage pyroptosis and autophagy via GSK-3β.</p><p><strong>Material or subjects: </strong>Human aortic tissues from controls and subjects with AS, twelve male ApoE^-/- mice, and ox-LDL-induced Ana-1 mouse macrophages, including Gsdmd/Caspase-1-overexpressing and Gsdmd-deficient cells, were studied.</p><p><strong>Treatment: </strong>After 6 weeks of high-fat feeding, mice received TF (10 mg/kg/day, intraperitoneally) or PBS for 6 weeks; macrophages were stimulated with ox-LDL (20 μg/mL) and treated with TF for 48 h.</p><p><strong>Methods: </strong>Oil Red O staining, immunofluorescence, Western blotting, ELISA, CRISPR/Cas9, molecular docking, cellular thermal shift assay, and co-immunoprecipitation were performed. Data were expressed as mean ± SD and analyzed using unpaired two-tailed t-tests or ANOVA with Dunnett's test.</p><p><strong>Results: </strong>TF attenuated aortic plaque formation and reduced GSDMD-N, C-CASP1, NLRP3, and IL-1β. In vitro, TF suppressed lipid uptake in Gsdmd- or Caspase-1-overexpressing macrophages but showed no effect in Gsdmd-deficient cells. TF interacted with GSK-3β, reduced p-GSK-3β(Tyr216), promoted autophagy, and enhanced GSK-3β-cathepsin B interaction.</p><p><strong>Conclusions: </strong>TF attenuates AS progression by suppressing pyroptosis-mediated foam cell formation and promoting autophagy through modulation of GSK-3β activity.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897261","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 omics profiling of CRELD2 in ccRCC: a nexus of genetics, prognosis, and tumor microenvironment.","authors":"Shouyong Liu, Yulin Zhou, Li Fan, Yi Wang, Le Qu, Wenquan Zhou","doi":"10.1007/s00011-026-02354-y","DOIUrl":"10.1007/s00011-026-02354-y","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive form of renal malignancy. Although therapeutic strategies such as targeted agents and immune checkpoint inhibitors have progressed, the prognosis for patients with advanced ccRCC remains unsatisfactory. Cysteine-rich epidermal growth factor-like domain 2 (CRELD2), a protein localized to the endoplasmic reticulum, is involved in several biological processes, yet its function in ccRCC has not been clearly characterized.</p><p><strong>Methods: </strong>We conducted an integrative multi-omics study to investigate the role of CRELD2 in ccRCC. The study incorporated mendelian randomization (MR), bulk and single-cell RNA sequencing, immunohistochemistry, immune infiltration analysis, and spatial transcriptomics to explore expression patterns, prognostic value, cellular distribution, and potential biological implications of CRELD2.</p><p><strong>Results: </strong>MR and summary-data-based MR analyses identified CRELD2 as a genetically supported candidate associated with RCC susceptibility. Elevated CRELD2 expression was confirmed at both mRNA and protein levels in ccRCC and correlated with worse overall survival independently. Single-cell analysis revealed preferential CRELD2 enrichment in endothelial and B-cell compartments, with CRELD2-high subsets showing shared enrichment of TNFA/NFκB, MTORC1, ROS, and oxidative phosphorylation pathways. Immune infiltration analysis linked CRELD2 expression to a B-cell-related immune infiltration profile, while spatial transcriptomics showed CRELD2 enrichment in tertiary lymphoid structure (TLS)-associated regions. Across single-cell and spatial analyses, TNFA/NFκB-related immune-inflammatory signaling represented a recurrent CRELD2-associated pathway feature.</p><p><strong>Conclusion: </strong>This study pointed out the CRELD2-centered TLS-associated immune-inflammatory conceptual axis, linking CRELD2 expression, endothelial/B-cell cellular contexts, B-cell-related immune infiltration, TLS-associated spatial localization, and recurrent TNFA/NFκB pathway enrichment via multi-omics and supporting it as a candidate therapeutic biomarker in ccRCC for further functional investigations.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897164","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":"CCL5 mRNA-enriched small extracellular vesicles from renal tubular epithelial cells enhance macrophage inflammatory responses in diabetic nephropathy.","authors":"Luyang Xie, Jian Ye, Shan He, Lan Yang, Qinkai Chen, Jiayan Huang, Qing Zhao, Yu Wang","doi":"10.1007/s00011-026-02356-w","DOIUrl":"10.1007/s00011-026-02356-w","url":null,"abstract":"<p><strong>Background: </strong>Small extracellular vesicles (sEVs) derived from tubular epithelial cells (TECs) are important mediators of tubular-immune cell communication in diabetic nephropathy (DN). However, the RNA cargo involved in TEC-macrophage inflammatory communication remains incompletely understood. This study investigated whether sEV-associated CCL5 mRNA contributes to inflammatory communication between TECs and macrophages in DN.</p><p><strong>Methods: </strong>Urinary sEV transcriptomic analysis and clinical association analysis were performed to identify DN-associated RNA cargo. In vitro, sEVs released from TECs exposed to high glucose were incubated with macrophages, and macrophage migration, inflammatory cytokine expression, and TLR4/MyD88/NF-κB-related signaling were evaluated. Ccl5 knockdown in TECs and actinomycin D experiments were used to examine sEV-associated Ccl5 mRNA enrichment, transfer, and function.</p><p><strong>Results: </strong>CCL5 mRNA was increased in urinary sEVs in DN and was associated with tubulointerstitial injury in clinical samples. High-glucose-treated TECs released sEVs enriched in Ccl5 mRNA that were internalized by macrophages and enhanced macrophage migration, inflammatory cytokine expression, and TLR4/MyD88/NF-κB-related signaling. Ccl5 knockdown attenuated these effects, while actinomycin D experiments further supported the transfer of vesicle-associated Ccl5 mRNA. Activated macrophages also promoted injury-related responses in glomerular cells.</p><p><strong>Conclusion: </strong>These findings suggest that TEC-derived sEV-associated Ccl5 mRNA may contribute to TEC-to-macrophage inflammatory communication in DN, with activated macrophages potentially propagating injury-related responses to glomerular cells.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897230","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":"Depleting luminal cysteine with engineered bacteroides vulgatus alleviates experimental colitis by suppressing Th17 differentiation through an ATF6-dependent mechanism.","authors":"Jianghao Wang, Zhe-Xian Tian, Shanwen Chen, Grace Y Chen, Yi-Ping Wang, Pengyuan Wang","doi":"10.1007/s00011-026-02341-3","DOIUrl":"10.1007/s00011-026-02341-3","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by dysregulated immune responses, particularly the aberrant activation of T helper 17 (Th17) cells. While microbiome-based therapies show promise, wild-type probiotics often lack specific mechanisms to target the metabolic and immunological drivers of inflammation.</p><p><strong>Methods: </strong>In this study, we engineered a cysteine-auxotrophic strain of Bacteroides vulgatus (BV1608) by chromosomally integrating the E. coli cyuP gene to enhance cysteine uptake. We evaluated its colonization capability, safety, and therapeutic efficacy in dextran sulfate sodium (DSS)-induced acute and chronic colitis murine models.</p><p><strong>Results: </strong>BV1608 exhibited superior colonization and cysteine assimilation compared to the wild-type strain. Oral administration of BV1608 significantly alleviated colitis symptoms, reduced pro-inflammatory cytokines, and restored intestinal barrier integrity. Mechanistically, BV1608 created a localized cysteine-restricted microenvironment in the gut and suppressed pathogenic Th17 differentiation. Under cystine-restricted conditions, ATF6 was activated in CD4⁺ T cells, and its inhibition partially restored IL-17A⁺ CD4⁺ T cell differentiation, indicating a functional role for ATF6. Meanwhile, cystine restriction was associated with increased BATF2 expression and enhanced ATF6 binding at the BATF2 promoter, suggesting BATF2 as a potential downstream node.</p><p><strong>Conclusion: </strong>Our findings demonstrate that metabolically engineered B. vulgatus BV1608 ameliorates colitis by coupling microbial cysteine sequestration with host immune modulation via the ATF6-dependent suppression of Th17 differentiation, while implicating BATF2-associated transcriptional regulation as a potential downstream mechanism. This study provides a novel synbiotic strategy for treating UC by targeting the immunometabolic interface.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897208","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":"An NLRP3 inflammasome-anchored Astragalus mechanistic prior yields a mortality-associated transcriptomic signal in ICU sepsis: a secondary analysis with exploratory cross-cohort assessment.","authors":"Xiaojuan Yang, Tiantian Hu, Jiali Wang, Zhiyuan Gao, Wei Yuan, Biao Gao","doi":"10.1007/s00011-026-02352-0","DOIUrl":"10.1007/s00011-026-02352-0","url":null,"abstract":"<p><strong>Objective and design: </strong>We developed ASTRA, a literature-informed, author-defined Astragalus mechanistic prior, and examined whether integrated and node-level whole-blood transcriptomic scores were associated with 28-day mortality in ICU sepsis.</p><p><strong>Methods: </strong>The primary analysis included 479 adults with sepsis from GSE65682; an exploratory cross-cohort directional assessment included 51 Day-1 patients with septic shock from GSE95233. Mean-Z scores were evaluated using age-adjusted logistic regression with false-discovery-rate correction. Sensitivity analyses included singscore, restricted cubic splines, label permutation, leave-one-gene-out analysis, correlations with IL1B and IL6 mRNA, and adjustment for transcriptome-derived myeloid-cell composition.</p><p><strong>Results: </strong>The integrated ASTRA score showed a nominal inverse association with mortality but did not survive false-discovery-rate correction. The NLRP3-related three-gene score showed the strongest association in GSE65682 (OR per 1-SD increase, 0.70; 95% CI 0.57-0.86; q = 0.0072) and remained directionally stable in leave-one-gene-out analyses. It correlated positively with IL1B and IL6 mRNA and with MCP-counter monocytic-lineage and neutrophil scores. Joint MCP-counter adjustment attenuated the association to an OR of 0.79 (95% CI 0.58-1.06), whereas xCell neutrophil adjustment strengthened it to an OR of 0.64 (95% CI 0.50-0.83), indicating method-sensitive dependence on estimated cell composition. In GSE95233, the age-adjusted NLRP3 estimate was directionally concordant but imprecise (OR 0.68; 95% CI 0.37-1.23).</p><p><strong>Conclusions: </strong>ASTRA provides a reproducible framework for mechanism-guided transcriptomic scoring in sepsis. The NLRP3-linked signal represents an observational whole-blood transcriptomic state that partly tracks estimated myeloid-cell composition and concurrent inflammatory transcription. It does not establish protective inflammasome activity, Astragalus efficacy, or pharmacological target engagement.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897188","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}