Inflammation Research最新文献

{"title":"Identification of immune cell mitochondrial dysfunction characteristics and clinical predictive biomarkers in sepsis via multi-cohort machine learning and single-cell RNA sequencing.","authors":"Xin Le, Youfen Fan, Sida Xu, Jiliang Li, Shengyong Cui, Guoying Jin, Neng Huang, Yaohua Yu, Pei Xu","doi":"10.1007/s00011-026-02366-8","DOIUrl":"10.1007/s00011-026-02366-8","url":null,"abstract":"<p><strong>Background: </strong>Sepsis involves dysregulated host responses with mitochondrial dysfunction as a key mechanism, yet its immune cell landscape and clinical utility are unclear.</p><p><strong>Methods: </strong>We integrated five GEO datasets (GSE65682, GSE95233, GSE54514, GSE26440, GSE26378) comprising 1,256 samples. Mitochondrial dysfunction-related genes were identified through differential expression analysis and WGCNA. Ten machine learning algorithms were compared to construct an optimal diagnostic model. NMF clustering defined sepsis subtypes, and a mitochondrial dysfunction score (MAS) was developed. Single-cell RNA sequencing (GSE167363, 59,731 cells) validated cell-type-specific expression patterns. Furthermore, Western blotting was performed to confirm the protein-level expression of selected hub genes in PBMC samples.</p><p><strong>Results: </strong>438 differentially expressed genes were identified (224 upregulated, 214 downregulated), with upregulated genes enriched in oxidative phosphorylation and downregulated genes in T cell receptor signaling. Elastic net achieved optimal diagnostic performance (AUC = 0.9156), yielding a 12‑gene signature with robust external validation (AUC up to 0.918). NMF stratified patients into two subtypes (Cluster 1, n = 412; Cluster 2, n = 511) with distinct immune profiles; Cluster 2 exhibited elevated NLRP3/IL1B expression and enhanced innate immune infiltration. MAS significantly correlated with sepsis status (p = 7.56e‑27) and showed superior diagnostic performance (AUC up to 0.969). Single‑cell analysis revealed MAS enrichment in monocytes and dendritic cells, with positive correlation to monocyte function (rho = 0.443). Notably, protein-level validation confirmed that TXN, CTSZ, SLPI, PSMC5, and DNM2 were significantly upregulated, while FLI1 was downregulated in sepsis patients, consistent with the transcriptomic findings. Furthermore, clinical correlation analysis revealed that the signature score was significantly positively correlated with SOFA and APACHE II scores, and patients with high signature scores exhibited significantly worse 28-day survival. Pseudotime trajectories showed distinct differentiation patterns (P < 0.001).</p><p><strong>Conclusions: </strong>This comprehensive multi-omics analysis, further supported by experimental protein-level validation and clinical correlation with severity scores and survival outcomes, establishes mitochondrial dysfunction-immunity crosstalk as a central axis in sepsis pathogenesis. The identified 12-gene signature and MAS score provide robust diagnostic tools with translational potential for clinical sepsis management.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008419","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":"Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.","authors":"Jinfei Fan, Yue Jiang, Xinchi Luan, Xuezhe Wang, Xin Wang, Xiaolei Zhang, Jingwen Tian, Xiaofei Xin, Wensheng Qiu, Weiwei Qi","doi":"10.1007/s00011-026-02360-0","DOIUrl":"10.1007/s00011-026-02360-0","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal motility disorders are closely associated with dysfunction of smooth muscle cells (SMCs), and phenotypic switching of SMCs serves as a critical pathological basis for this process. Under a chronic inflammatory microenvironment, SMCs can transform into a synthetic phenotype and contribute to complications such as intestinal fibrosis. Macrophages, as the predominant immune cell population in the gastrointestinal tract, have an unclear role in regulating the phenotypic switching of SMCs, and the underlying mechanisms remain poorly understood.</p><p><strong>Findings: </strong>This article systematically reviews the regulatory mechanisms underlying gastrointestinal smooth muscle phenotypic switching, and highlights the potential role of macrophages in regulating gastrointestinal smooth muscle phenotypic switching and summarizes the underlying mechanisms, including inflammatory responses, microbial interactions, and neural regulation.</p><p><strong>Conclusions: </strong>The macrophage‑smooth muscle axis provides new perspectives for understanding the pathogenesis of inflammatory bowel disease (IBD) and may serve as a reference for exploring potential therapeutic strategies for gastrointestinal motility disorders.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008455","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":"STAT1: a central hub linking ferroptosis and inflammation in hepatic ischemia-reperfusion injury.","authors":"Chenxi Li, Yan Chen, Zhengye Wang, Yuchen Ni, Lei Yan","doi":"10.1007/s00011-026-02370-y","DOIUrl":"10.1007/s00011-026-02370-y","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion injury (HIRI) remains an intractable perioperative complication of liver transplantation and hepatectomy, driven by two interdependent but historically segregated pathological cascades: iron-dependent ferroptotic parenchymal death and amplified sterile inflammatory signaling. A critical unmet gap in the field is identification of a single upstream molecular node capable of synchronously coordinating both injury programs. Building upon the foundational murine experimental work published by Wu et al. (2025) defining the STAT1-miR-497-5p-HDAC7 linear signaling cascade, this Perspective advances three exclusive, integrative conceptual frameworks original to our group: (1) STAT1 functions as a convergent master transcriptional hub that epigenetically couples ferroptosis and inflammation via one unified epigenetic axis; (2) the STAT1-miR-497-5p-HDAC7 module represents a conserved universal pathogenic cassette across all solid organ ischemia-reperfusion injury (IRI); (3) a tiered tri-modal translational pipeline integrating combinatorial circulating biomarkers, selective small-molecule HDAC7/JAK inhibitors, and tissue-targeted miR-497-5p RNA therapeutics enables dual-action liver graft protection. Beyond synthesizing published mechanistic data, we reframe field-wide generic HIRI research bottlenecks into STAT1-axis-specific testable hypotheses, including compartmentalized cell-type synergistic injury loops, estrogen-driven sexual dimorphism of STAT1 epigenetic activity, and closed bidirectional feedback circuits between STAT1 and canonical IRI pathways (NF-κB, Nrf2, HIF-1α). We further outline a cell-specific knockout and single-cell transcriptomic experimental roadmap to validate our novel predictions, and contextualize near-term clinical translation of this axis for perioperative liver protection. Targeted disruption of this STAT1-centered regulatory hub represents a uniquely promising strategy to simultaneously block both ferroptotic and inflammatory liver damage, with broad translatable implications for multi-organ IRI treatment.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989923","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":"The role of mTORC2/RICTOR in immune cells and inflammatory diseases.","authors":"Jingting Xu, Wenxin Zhong, Fei Xin, Fei Xu, Zehang Zheng, Fengjing Guo","doi":"10.1007/s00011-026-02365-9","DOIUrl":"10.1007/s00011-026-02365-9","url":null,"abstract":"<p><strong>Background: </strong>mTORC2, defined by its core component RICTOR, is a key regulator of immune cell function and inflammation, yet its roles have long been underappreciated due to lack of specific inhibitors and in vivo tools.</p><p><strong>Objective: </strong>This review summarizes the current understanding of mTORC2-specific signaling (via AKT, SGK1, and PKC) in regulating the development, differentiation, and effector functions of diverse immune cells, and discusses its emerging roles in immune cell inflammation and tissue-specific inflammation.</p><p><strong>Method: </strong>We synthesized findings from recent studies using conditional knockout mouse models, pharmacological inhibitors, and clinical samples.</p><p><strong>Conclusion: </strong>mTORC2 controls Th1/Th2 differentiation, Treg stability, and memory T cell formation; regulates BCR signaling and plasma cell survival; and modulates macrophage M2 polarization, DC maturation, and NK cell function. In tissue inflammation, mTORC2 plays context-dependent roles-exacerbating osteoarthritis and pancreatitis but restraining pro-inflammatory polarization in colorectal cancer. Dual mTORC1/2 inhibitors (e.g., AZD2014) have shown early promise, though challenges remain regarding efficacy, toxicity, and immunomodulatory complexity.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989934","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":"Single-cell RNA profiling suggests goflikicept-mediated immune modulation in idiopathic recurrent pericarditis.","authors":"A Golovkin, E Markelova, E V Ignatieva, O Kalinina, O A Ivanova, D Antonets, Y Medvedeva, A Minin, D Shtokalo, V Ramensky, I Kudryavtsev, O Moiseeva, V Myachikova, Y Vyatkin, Y Lavrovsky, M Samsonov, A Maslyanskiy, A Kostareva, E Shlyakhto","doi":"10.1007/s00011-026-02347-x","DOIUrl":"10.1007/s00011-026-02347-x","url":null,"abstract":"<p><strong>Objective: </strong>Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disorder characterized by NLRP3 inflammasome overactivation, resulting in excessive IL-1β and IL-1α production. Although IL-1 blockade shows promise as a therapeutic strategy, the underlying molecular mechanisms remain incompletely understood. We investigated the effect of goflikicept, a novel heterodimeric fusion protein that inhibits both IL-1β and IL-1α, on peripheral blood mononuclear cell (PBMC) transcriptomes from patients with IRP.</p><p><strong>Methods: </strong>Single‑cell RNA sequencing was performed on PBMCs from patients with IRP before and during goflikicept treatment. Treatment‑related transcriptomic signatures were analyzed across innate and adaptive immune cell subsets.</p><p><strong>Results: </strong>Goflikicept induced temporal transcriptional reprogramming, with a particularly pronounced downregulation of IL-1-related inflammatory pathways in classical monocytes by day 35 of treatment. Furthermore, goflikicept was associated with coordinated transcriptional changes in adaptive immune compartments, including naïve B cells, circulating plasma cell precursors, and unconventional T cell subsets (γδ T and MAIT cells).</p><p><strong>Conclusions: </strong>Goflikicept effectively normalized dysregulated immune responses in IRP, supporting the broader therapeutic potential of IL-1 blockade in NLRP3-mediated inflammatory diseases. This study provides the first single-cell resolution insights into the molecular mechanisms of IL-1 blockade, informing the development of targeted therapies for autoinflammatory conditions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968103","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":"Discovery and validation of novel plasma protein biomarkers for severe tuberculosis patients.","authors":"Yifan Hu, Yu Xue, Wei Shu, Weicong Ren, Rui Li, Zichun Ma, Ruichao Liu, Yu Pang, Liang Li","doi":"10.1007/s00011-026-02362-y","DOIUrl":"10.1007/s00011-026-02362-y","url":null,"abstract":"<p><strong>Objective: </strong>Severe tuberculosis (STB) imposes a substantial disease burden, yet reliable biomarkers for distinguishing STB from mild/moderate tuberculosis (MTB) remain scarce. This study aimed to identify and independently validate plasma protein biomarkers associated with tuberculosis severity.</p><p><strong>Methods: </strong>In this multicenter prospective study, 298 adults with confirmed pulmonary tuberculosis were enrolled into screening (n = 128) and independent validation (n = 170) cohorts. Plasma samples were analysed using data-independent acquisition proteomics. Differentially expressed proteins were screened via Limma and four machine-learning algorithms, with candidate proteins measured by enzyme-linked immunosorbent assays. Receiver operating characteristic analysis assessed individual and combined diagnostic performance.</p><p><strong>Results: </strong>STB patients were older and presented with lymphopenia, hypoalbuminemia, neutrophilia, and elevated lactate dehydrogenase. Among 166 differentially expressed proteins, HSPA5, HSP90B1, EEF1D, and SULT1A1 were selected for validation. In STB patients, HSPA5, HSP90B1, and EEF1D were upregulated, whereas SULT1A1 was downregulated. The four-protein panel achieved an AUC of 0.908 (95% CI 0.864-0.952), with 87.5% sensitivity and 83.8% specificity, modestly outperforming HSPA5 alone (AUC = 0.894). Functional enrichment implicated cholesterol metabolism, immune-inflammatory pathways, and endoplasmic reticulum stress.</p><p><strong>Conclusions: </strong>The four-protein panel effectively discriminated STB from MTB; however, its marginal improvement over HSPA5 alone suggests that an HSPA5-based assay may offer a simpler, more practical, and potentially cost-effective strategy for severity stratification.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968048","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":"Autoimmune processes and production of catalytically active antibodies-abzymes in prone to amyotrophic lateral sclerosis FUS(1-359) mice.","authors":"Andrey E Urusov, Marina A Gorobets, Kseniya S Aulova, Anna M Timofeeva, Ludmila B Toporkova, Irina A Orlovskaya, Aleksey A Ustyugov, Georgy A Nevinsky","doi":"10.1007/s00011-026-02358-8","DOIUrl":"10.1007/s00011-026-02358-8","url":null,"abstract":"<p><strong>Objective: </strong>It was shown previously that the development of not only many autoimmune (AIDs) but also neurological and neurodegenerative diseases (NDDs) including multiple sclerosis, tick-borne encephalitis, and schizophrenia in humans and experimental mice models occurs due to a specific destruction of the immune system. This error in the immune system leads to the formation of B lymphocytes producing adverse antibodies-abzymes possessing different catalytic activities.</p><p><strong>Methods: </strong>One of the earliest and statistically reliable index of developments of autoimmune reactions is the appearance in the blood abzymes that are absent in conditionally healthy donors. We investigated the in time changes catalytic activities of Abs-abzymes using standard methods of enzymology.</p><p><strong>Results: </strong>It was shown for the first time that, as in the case of various AIDs and NDDs, the early stages of ALS development in FUS(1-359) mice are also associated with the production of catalytic antibodies. CD-1 mice utilized for obtaining FUS(1-359) mice were also used. IgG samples were isolated from the blood of transgenic FUS(1-359) mice and their non-transgenic siblings (CD1) at different times. The first signs of ALS-like symptoms develop at the age of ≥ 2 months of life in FUS(1-359) mice, which was taken as zero time point, and then by ≥ 80 days of age, deep pathology was observed. It was shown for the first time that antibodies from the blood of FUS(1-359) mice exhibit DNase, amylase, phosphatase, and catalase catalytic activities beginning from 2 months of age. However, unlike non-transgenic siblings, the relative activity of mice IgGs was higher in FUS(1-359) mice. All activities of FUS(1-359) mice IgGs began to increase significantly starting from 20 to 30 days after beginning of experiments and achieved maximum upon reaching deep pathology.</p><p><strong>Conclusions: </strong>The data obtained indicate that in the early stages of ALS development in FUS(1-359) mice containing genes associated with this pathology in humans, there is a disruption of the immune system and production of abzymes that destroy components of blood, cells and tissues. One cannot exclude that such autoimmune reactions are important for development of ALS in FUS(1-359) mice.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967917","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":"Old drug with new application: spironolactone suppresses Panx 1-mediated Ca²⁺ influx to attenuate inflammation-driven neutral lipid accumulation in early atherosclerosis.","authors":"Yang Yang, Tianyi Gu, Mengxue Zheng, Qiushi Huang, Jiahao Lu, Jiang Chen, Yaqin Tang, Xue Zhang, Yuexia Liao, Yan Sun","doi":"10.1007/s00011-026-02361-z","DOIUrl":"10.1007/s00011-026-02361-z","url":null,"abstract":"<p><strong>Rationale: </strong>Atherosclerosis (AS) is a chronic inflammatory disease of the arterial walls, initiated by endothelial dysfunction and subendothelial lipid deposition. Even though treatments to lower lipids have improved, there are still not many options that specifically tackle inflammation-caused endothelial dysfunction in the early stage of AS. Spironolactone (SP) has been shown to be beneficial in reducing cardiovascular complications, and while it acts as a pharmacological inhibitor of pannexin 1 (Panx 1), the mechanism by which SP modulates Panx 1 in endothelial cells (ECs) during inflammation remains unclear.</p><p><strong>Objective: </strong>To identify Panx 1 on ECs is a key mediator through which SP ameliorates vascular inflammation, lowers oleic acid (OA)-induced intracellular neutral lipid accumulation, and sustains the function of ECs, thereby attenuating early AS.</p><p><strong>Methods and results: </strong>In vivo, SP administration significantly ameliorated plasma biochemical parameters, mitigate aortic inflammation and reduced lipid deposition, thereby reducing endothelial activation and alleviating endothelium damage in an early AS model established by feeding ApoE^-/- mice a high-fat diet. Non-targeted metabolomic profiling revealed that SP profoundly remodeled the plasma metabolome, indicating systemic metabolic restoration. In vitro, SP reversed TNF-α induced activation of ECs and attenuated OA-induced neutral lipid accumulation in human umbilical vein ECs. However, no significant difference of Panx 1 expression in ECs was observed between normal and abnormal endothelial function in AS mouse models or clinical subjects. Mechanistically, SP targeted Panx 1 as a pivotal mediator of the inflammatory response, not only inhibiting TNF-α induced Panx 1 expression but also significantly blocking the functional opening of Panx 1 channels, thereby preventing subsequent Ca²⁺ influx. This attenuation of intracellular Ca²⁺ overload was essential for the protective effects of SP against both endothelial dysfunction and inflammation-mediated OA to induce intracellular neutral lipid accumulation. Furthermore, we demonstrated that SP suppresses NFκB signaling activation by inhibiting the Panx 1-dependent intracellular Ca²⁺ rise, revealing a mechanistic Panx 1/Ca²⁺/NFκB axis that regulates inflammation-driven intracellular neutral lipid accumulation.</p><p><strong>Conclusion: </strong>Taken together, these findings indicate that SP mitigates early AS by reduced endothelial activation and attenuating inflammation-driven intracellular neutral lipid accumulation via suppression of the Panx 1/Ca²⁺/NFκB signaling axis. This study establishes Panx 1 as a promising therapeutic target for early vascular intervention in AS and considers SP as a potential candidate for prevention of atherosclerotic cardiovascular disease.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968023","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":"Major cardiovascular event risk of advanced therapies in inflammatory bowel diseases: systematic review and meta-analysis.","authors":"Amirah H Alnahdi, Chelsea Salmon, Fanxing Du, Mikael Svensson, Naueen Chaudhry, Ellen M Zimmermann, Tianze Jiao","doi":"10.1007/s00011-026-02336-0","DOIUrl":"10.1007/s00011-026-02336-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD.</p><p><strong>Methods: </strong>Systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials identified 43 studies (36 RCTs, including 9 long-term follow-up (LTF) studies, and 7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratifying studies by drug class and length of follow-up. Sensitivity analyses were conducted using alternative methods to account for zero-event data.</p><p><strong>Results: </strong>Placebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR 0.60; 95% CI 0.24-1.51), with similar findings across sensitivity analyses accounting for sparse and zero-event data. Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR 0.35; 95% CI 0.05-2.21), JAK inhibitors (OR 0.57; 95% CI 0.16-2.06), and a potential increase with Anti-TNF agents (OR: 3.04; 95% CI 0.31-29.47), though none reached statistical significance. LTF studies showed consistent findings. Observational studies suggested lower MACE risk with Anti-TNF therapies (OR 0.29; 95% CI 0.21-0.40), but not with IL-12/IL-23 (OR 4.41; 95% CI 0.49-39.28) or JAK inhibitors (OR 1.57; 95% CI 0.86-2.84).</p><p><strong>Conclusion: </strong>Advanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968041","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":"Compartment-specific inflammation in tuberculous lymphadenitis: a case-control study.","authors":"Caian L Vinhaes, Samyra Almeida da Silveira, Beatriz Barreto-Duarte, Bruno B Andrade, Flávia Marinho Sant'Anna, Carolina Arana Stanis Schmaltz, Felipe M Ridolfi, Valeria C Rolla, Adriano Gomes-Silva","doi":"10.1007/s00011-026-02351-1","DOIUrl":"10.1007/s00011-026-02351-1","url":null,"abstract":"<p><p>Extrapulmonary tuberculosis (EPTB) represents a substantial proportion of tuberculosis cases, particularly among people living with HIV. Tuberculous lymphadenitis is one of the most common forms of EPTB and represents a condition in which the lymph node functions both as an immune-organizing site and a focus of Mycobacterium tuberculosis (Mtb) infection. Although peripheral blood biomarkers are frequently used to investigate immune responses in tuberculosis, they may not accurately reflect immunological processes occurring at the site of disease. In this study, we aimed to characterize and compare systemic and local inflammatory responses in individuals with suspected lymph node tuberculosis. We conducted a case-control study including 24 individuals undergoing lymph node biopsy for pathological lymphadenopathy at the National Institute of Infectious Diseases Evandro Chagas (Fiocruz), Brazil. Eleven participants were diagnosed with tuberculous lymphadenitis (45.8%) and thirteen served as non-TB controls (54.2%). Paired plasma and lymph node interstitial fluid samples were collected, and concentrations of 29 cytokines, chemokines, and growth factors were quantified using multiplex Luminex assays. Statistical analyses included non-parametric comparisons, hierarchical clustering, Spearman correlation-based network analysis, and canonical correlation analysis to evaluate inflammatory profiles and immune network organization. Plasma inflammatory profiles did not distinguish EPTB cases from controls. In contrast, lymph node samples from EPTB participants exhibited significantly higher concentrations of IL-8, IL-3, and IL-5 and reduced IL-10 levels. Network analyses of correlations between protein concentrations revealed dense and highly interconnected inflammatory networks in plasma, centered on IL-6, IFN-α2, and IL-12p70, whereas lymph node networks were sparser and dominated by TNF-α and IL-1 family cytokines. Cross-compartment analysis identified associations between systemic mediators, particularly TNF-β and IL-7, and pro-inflammatory signals in lymph nodes. Additionally, HbA1c levels were correlated with concentrations of multiple inflammatory mediators, particularly within lymph nodes. Together, these findings indicate that tuberculous lymphadenitis is characterized by marked compartmentalization of immune responses, emphasizing the importance of tissue-level immune profiling for understanding EPTB pathogenesis.</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/PMC13546146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897211","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}