Journal of Inflammation Research最新文献

{"title":"Evaluating Baricitinib for Severe Paediatric Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with Single-Cell Sequencing.","authors":"Danyang Yang, Xin Liu, Wenwen Jing, Xu Feng, Canying Lai, Chenyue Liu, Zhigang Xu, Yangang Zhang, Jiayi Han, Songmei Geng, Ruilian Li, Dan Li, Boyi Cheng, Yufei Wu, Zhuokun Liu, Jialin Lian, Zhenghui Wang, Yale Liu, Xiaoli Li","doi":"10.2147/JIR.S576383","DOIUrl":"https://doi.org/10.2147/JIR.S576383","url":null,"abstract":"<p><strong>Purpose: </strong>Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe type of drug reaction that has significant mortality rate. Traditional treatments, including glucocorticoids and immunosuppressants, are sometimes insufficient. We present a case of severe paediatric DRESS unresponsive to conventional therapies, in which baricitinib, guided by single-cell RNA sequencing (scRNA-seq), led to clinical improvement. Single-cell transcriptomics is a revolutionary technology that allows scientists to measure the activity of all genes in individual cells on a large scale and has emerged as a tool for personalized therapeutic targeting.</p><p><strong>Patient and methods: </strong>A 3-year-old male with DRESS triggered by phenobarbital presented with fever, skin rash, impaired liver function, eosinophilia, and cytomegalovirus infection. After failing high-dose corticosteroids, intravenous immunoglobulin, and etanercept, baricitinib was initiated. Peripheral blood mononuclear cells and skin biopsy samples underwent scRNA-seq to identify dysregulated pathways and potential therapeutic targets.</p><p><strong>Results: </strong>Baricitinib treatment led to resolution of skin lesions, normalization of eosinophil counts and liver function, and successful tapering of corticosteroids. Single-cell RNA sequencing uncovered that clusters of CD4+ and CD8+ T cells contain JAK2.</p><p><strong>Conclusion: </strong>Our findings suggest that baricitinib, a JAK1/2 inhibitor, is a safe and effective salvage therapy for corticosteroid-refractory paediatric DRESS. scRNA-seq can guide targeted treatment decisions in DRESS.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"576383"},"PeriodicalIF":4.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Neutrophils on the Tissue Microenvironment During Intestinal Inflammation.","authors":"Faiz Minhajuddin, Sean P Colgan, Ian M Cartwright","doi":"10.2147/JIR.S540855","DOIUrl":"https://doi.org/10.2147/JIR.S540855","url":null,"abstract":"<p><p>Neutrophils (polymorphonuclear leukocytes, PMN) are abundant innate immune cells that rapidly accumulate at mucosal surfaces during inflammation. While their antimicrobial functions are essential for host defense, sustained PMN activation profoundly alters the tissue microenvironment, driving epithelial barrier disruption, ECM remodeling, metabolic imbalance, and microbiome dysbiosis. In chronic inflammatory diseases such as inflammatory bowel disease (IBD), these processes contribute to persistent tissue injury and therapeutic resistance. In this review, we synthesize evidence from human mucosal biopsies, experimental models of intestinal inflammation, and emerging single-cell, spatial, and metabolic approaches to define how PMN shape the inflamed mucosal microenvironment. We highlight mechanisms governing PMN recruitment, retention, and survival; effector programs including reactive oxygen species production, protease release, and PMN extracellular trap formation; and bidirectional crosstalk with epithelial, stromal, and immune cell compartments. We further discuss how PMN-driven metabolic and microbiome alterations reinforce chronic inflammation and influence responses to biologic therapy. Collectively, these insights reframe PMN as context-dependent regulators of mucosal pathology and repair and identify PMN-centered pathways as promising targets for precision therapies aimed at restoring barrier function and promoting durable inflammatory resolution.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"540855"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Systemic Inflammation Response Index, Worsening of Left Ventricular Systolic Function and Prognosis in Patients with Coronary Artery Disease.","authors":"Huangtao Ruan, Xiaozhao Lu, Huan Lu, Haozhang Huang, Zuxian Huang, Shangyi Tang, Ziyao Yuan, Rengui Jiang, Jiazhen Xin, Tao Tang, Jin Liu, Yong Liu, Ning Tan","doi":"10.2147/JIR.S577895","DOIUrl":"https://doi.org/10.2147/JIR.S577895","url":null,"abstract":"<p><strong>Background: </strong>Inflammation contributes substantially to the progression and adverse prognosis of coronary artery disease (CAD). Worsening of left ventricular (LV) systolic function is a key contributor to poor prognosis in CAD patients. However, whether inflammation influences prognosis through worsening of left ventricular systolic function remains uncertain.</p><p><strong>Methods: </strong>This retrospective study enrolled patients from Cardiorenal Improvement-II who were initially hospitalised between 2007 and 2020 and had both baseline and follow-up echocardiographic information. Participants were stratified by systemic inflammation response index (SIRI) into 4 quartiles (Q1-Q4) for comparison. Worsening of LV systolic function served as the primary endpoint and was identified by an absolute decrease of 10% or more in LV ejection fraction from baseline to 12 months following hospital discharge. Secondary outcomes included cardiovascular and all-cause mortality. Logistic regression models were utilized to evaluate the association of SIRI with worsening of left ventricular systolic function. Mediation analysis was used to investigate the proportion of fatalities mediated by worsening of left ventricular systolic function.</p><p><strong>Results: </strong>Among the 6307 enrolled participants with CAD (62.0 ±10.7 years, 20.6% female), a total of 521 (8.3%) worsening of left ventricular systolic function occurred in 1 year, and 523 (8.3%) cardiovascular deaths and 1022 (16.2%) all-cause deaths were recorded with a median observation period of 4.2 years. After fully adjusting, the logistic regression analysis revealed that Q4 group patients (with SIRI ≥2.61) were associated with a higher risk of worsening of LV systolic function (adjusted odds ratio: 1.52, 95% confidence intervals: 1.15-2.01, P =0.003). Approximately 4.0% and 2.0% of the overall association of SIRI with cardiovascular and all-cause mortality were mediated by worsening of left ventricular systolic function (P <0.05), respectively.</p><p><strong>Conclusion: </strong>SIRI serve as a potential risk factor for worsening of LV systolic function in CAD patients, and further contributes to poor prognosis, indicating that anti-inflammatory treatment represents a viable approach to improve the prognosis for CAD patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"577895"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: The Predictive Value of Nomogram Model Based on Neutrophil-to-Lymphocyte Ratio (NLR) and Prothrombin Time-International Normalized Ratio (PT-INR)-to-Albumin Ratio (PTAR) for Early Bacterial Intra-Abdominal Infection After Orthotopic Liver Transplantation [Corrigendum].","authors":"","doi":"10.2147/JIR.S609436","DOIUrl":"https://doi.org/10.2147/JIR.S609436","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/JIR.S571498.].</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"609436"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid-Sparing Control of Bullous Pemphigoid with Dupilumab and Tripterygium Glycosides: A Real-World Cohort with Longitudinal Transcriptomics.","authors":"Si-Hang Wang, Si-Zhe Li, Yi-Ran Li, Jie Zhang, Yan Wang, Ya-Gang Zuo","doi":"10.2147/JIR.S596205","DOIUrl":"https://doi.org/10.2147/JIR.S596205","url":null,"abstract":"<p><strong>Background: </strong>Bullous pemphigoid (BP) often requires long-term corticosteroids with substantial adverse effects. Effective corticosteroid-sparing treatments could improve safety and quality of life for patients with BP.</p><p><strong>Objective: </strong>To evaluate the clinical efficacy, safety, and transcriptomic correlates of dupilumab combined with tripterygium glycoside (TG) in moderate-to-severe BP.</p><p><strong>Materials and methods: </strong>We conducted a clinical cohort study at Peking Union Medical College Hospital. Twelve consecutive BP patients (bullous pemphigoid disease area index [BPDAI] ≥20) who had received dupilumab combined with oral TG were retrospectively identified. Systemic corticosteroids were avoided whenever feasible; rescue initiation or dose escalation was permitted for relapse or inadequate control. Outcomes included BPDAI, pruritus Numeric Rating Scale (NRS), serum anti-BP180 antibody levels, and eosinophil percentage from baseline to week 12. Safety was monitored throughout follow-up. Longitudinal peripheral blood samples were collected before and after treatment for transcriptomic profiling.</p><p><strong>Results: </strong>Among 12 patients, 10 (83%) achieved complete remission within 3 months, including 9 (75%) without initiating systemic corticosteroids or dose escalation. Median time to disease control was 8 days (IQR, 7-9.75). Significant improvements were observed in BPDAI (-37.50; 95% CI, -62.65 to -30.65; <i>p</i> = 0.003), pruritus NRS (-7.58; 95% CI, -9.00 to -6.00; <i>p</i> = 0.002), anti-BP180 antibody (-33.00 U/mL; 95% CI, -62.00 to -7.00; <i>p</i> = 0.006), and eosinophil percentage (mean difference, -8.73%; 95% CI, -12.88% to -4.58%; <i>p</i> < 0.001). One patient reported transient cognitive symptom worsening. Transcriptomic analysis showed downregulation of C-X-C motif chemokine receptor 4 (CXCR4) and matrix metallopeptidase 9 (MMP-9), and reduced interleukin-8- and type I interferon-related inflammation.</p><p><strong>Conclusion: </strong>Dupilumab combined with TG is a promising corticosteroid-sparing treatment strategy for moderate-to-severe BP. Dupilumab likely contributed substantially to disease control, while TG may have provided adjunctive immunomodulatory effects. Transcriptomic findings point to CXCR4 and MMP-9 as candidate markers distinguishing pre- versus post-treatment samples, warranting external validation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"596205"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Prognostic Value of Nutritional and Inflammatory Indices for Predicting Functionally Significant Coronary Stenosis Verified by FFR: The PNI-SII-GINI Study.","authors":"Mehmet Zafer Aydın, Can Baba Arin, Mehmet Kamil Teber, Zülfiye Kuzu, Mustafa Gök, Ishak Ahmed Abdi","doi":"10.2147/JIR.S585010","DOIUrl":"https://doi.org/10.2147/JIR.S585010","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammatory and nutritional indices have been associated with coronary artery disease burden and prognosis; however, their ability to predict lesion-level functional ischemia remains uncertain. This study evaluated whether the Prognostic Nutritional Index (PNI), Systemic Immune-Inflammation Index (SII), and Global Inflammation-Nutrition Index (GINI) are associated with functionally significant coronary stenosis assessed by fractional flow reserve (FFR).</p><p><strong>Methods: </strong>In this single-center observational study, patients with angiographically intermediate coronary lesions who underwent FFR assessment were included. PNI, SII, and GINI were calculated from routine laboratory parameters. Functionally significant stenosis was defined as FFR ≤ 0.80. Discriminative performance was evaluated using receiver-operating-characteristic (ROC) analysis, and associations were assessed with binary logistic regression.</p><p><strong>Results: </strong>A total of 113 patients were analyzed, of whom 48 (42.5%) had FFR ≤ 0.80. Baseline clinical characteristics and inflammatory-nutritional indices were comparable between patients with FFR ≤ 0.80 and FFR > 0.80. ROC analysis demonstrated limited discriminative ability for all indices, with area under the curve values of 0.544 for PNI, 0.461 for SII, and 0.554 for GINI (all p > 0.05). In logistic regression analysis, none of the indices independently predicted FFR-defined ischemia.</p><p><strong>Conclusion: </strong>Systemic inflammatory and nutritional indices, including PNI, SII, and GINI, did not reliably identify functionally significant coronary stenosis defined by FFR. These findings highlight the distinction between global inflammatory-nutritional status and lesion-specific coronary physiology, reinforcing the continued importance of direct physiological assessment for ischemia-guided management.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"585010"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Outcomes of Tocilizumab Usage in Cryptogenic Febrile Infection-Related Epilepsy Syndrome at Both Acute and Chronic Phase: A Retrospective Study.","authors":"Xiaolu Deng, Shimeng Chen, Fei Yin, Fang He, Ciliu Zhang, Lifen Yang, Leilei Mao, Li Yang, Yang Han, Jing Peng","doi":"10.2147/JIR.S584971","DOIUrl":"https://doi.org/10.2147/JIR.S584971","url":null,"abstract":"<p><strong>Purpose: </strong>To provide more observational evidence for potential efficacy of tocilizumab (TCZ) in children with cryptogenic febrile infection-related epilepsy syndrome (FIRES) administered during acute and chronic phase.</p><p><strong>Methods: </strong>Data of 22 children with FIRES who received TCZ were collected retrospectively. Patients were categorized into two groups: acute group (TCZ used within 4 weeks post-onset; n = 12) and chronic group (TCZ used beyond 4 weeks post-onset; n = 10).</p><p><strong>Results: </strong>In both groups, patients experienced >50% reduction in seizure frequency, electroencephalogram (EEG) improvements, alleviation on cranial magnetic resonance imaging (MRI), and significantly decreased mRS scores (<i>P</i> < 0.05). In acute group, 6 patients became seizure-free by the last follow-up, and 7 patients reduced their number of antiseizure medications (ASMs). TCZ administration in acute phase shortened status epilepticus (SE) duration. At last follow-up, the acute group exhibited higher rates of seizure freedom and >50% seizure reduction (<i>P</i> < 0.05), lower incidences of motor and speech deficits (<i>P</i> < 0.05), and a greater likelihood of returning to school (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>TCZ treatment was associated with reduced seizure frequency, improved EEG and MRI findings, decreased reliance on antiseizure medications, and functional improvement as measured by mRS. Initiation of treatment during the acute phase may be associated with a shortened duration of status epilepticus and, compared to chronic-phase intervention, appears to correlate with more favorable long-term outcomes.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"584971"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant Strategies to Improve the Efficacy of Allergen Immunotherapy.","authors":"Kaissar Tabynov, Kairat Tabynov, Nikolai Petrovsky","doi":"10.2147/JIR.S546218","DOIUrl":"https://doi.org/10.2147/JIR.S546218","url":null,"abstract":"<p><p>Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for IgE-mediated allergy capable of inducing durable disease remission even after cessation of treatment. Conventional AIT delivered by subcutaneous injection is effective but requires long treatment courses and carries a risk of systemic reactions. Mucosal AIT strategies administered by oral, sublingual, or intranasal routes provide a safer, needle-free alternative, but are generally less immunogenic and hence less durable in their effects. Adjuvants have the potential to enhance the efficacy of AIT by improving antigen uptake, activating innate immune cells and/or by suppressing or redirecting pathogenic Th2 immune responses to allergens. This review synthesizes current evidence on how adjuvants might assist allergen immunotherapy, including by induction of regulatory T cells and regulatory B cells, augmentation of blocking IgG and IgA antibodies, and attenuation of IgE-driven effector responses. We survey major adjuvant classes and delivery platforms, including depot carriers, Toll-like receptor (TLR) agonists, nano-emulsions, liposomes, and polysaccharide-based nanoparticles, and summarize findings from preclinical models and early-phase clinical trials. Key translational challenges are considered, including issues of local and systemic safety, route-specific reactogenicity, manufacturing consistency, and regulatory evaluation. Finally, we outline design principles for next-generation adjuvanted AIT vaccines that aim for faster, safer, and more effective immunotherapy, with an emphasis on rational immune targeting and patient-centric delivery formats. Together, these insights highlight key design principles for adjuvanted allergen immunotherapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"546218"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor on Immune-Inflammatory Responses in the Acute Phase of Ischemic Stroke.","authors":"Zhenzhen Li, Cong Sun, Qing Zhang, Lifan Ji, Yiting Zhang, Shuo Li, Mengmeng Gu, Jie Gao, Zhihui Huang, Meng Wang, Junshan Zhou, Lin Zhu, Teng Jiang, Qing Zhou, Qiwen Deng","doi":"10.2147/JIR.S590179","DOIUrl":"https://doi.org/10.2147/JIR.S590179","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) triggers a complex systemic immune-inflammatory response. While proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide significant lipid-lowering and pleiotropic anti-inflammatory effects, their impact on early peripheral inflammatory and immune responses in AIS patients due to large artery atherosclerosis (LAA) remains underexplored.</p><p><strong>Methods: </strong>A total of 72 AIS patients attributed to LAA were included in the final analysis of this prospective study (the standard treatment group, n = 24; the intensive treatment group, n = 48). Fasting blood samples were obtained at admission and the 2-week follow-up. A comprehensive panel of laboratory parameters was assessed at baseline and the 2-week follow-up, encompassing lipid profiles, a spectrum of inflammatory biomarkers (including but not limited to high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and lymphocyte subsets.</p><p><strong>Results: </strong>The intensive treatment group achieved a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) compared to the standard treatment group (<i>P</i> < 0.001). Notably, the intensive treatment group also showed significant reductions in key pro-inflammatory cytokines IL-6 (<i>P</i> = 0.024) and TNF-α (<i>P</i> = 0.041). However, no significant between-group differences were observed in the changes of peripheral blood lymphocyte subsets (<i>P</i> > 0.050).</p><p><strong>Conclusion: </strong>In AIS patients, early adjunctive PCSK9 inhibitor therapy provides superior lipid-lowering and may modulate specific pro-inflammatory cytokines compared to statin monotherapy, without significantly altering peripheral lymphocyte subset distributions within 2 weeks. Further large-scale studies are warranted to validate its immunomodulatory role and long-term clinical outcomes.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT05410457. Registered May 24, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05410457; ClinicalTrials.gov NCT05397405. Registered May 23, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05397405.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"590179"},"PeriodicalIF":4.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel snoRNA, Gm24418 Attenuates Inflammation Injury After Acute TBI Through Regulating CCL2.","authors":"Ming Luo, Yang Wang, Xiaohang Guo, Weikang Luo, Zhiqiang Yuan, Xueping Yang, Xudong Fan, Zhaoyu Yang, Tao Tang","doi":"10.2147/JIR.S583983","DOIUrl":"https://doi.org/10.2147/JIR.S583983","url":null,"abstract":"<p><strong>Purpose: </strong>Traumatic brain injury (TBI) triggers profound neuroinflammatory responses; however, the regulatory role of small nucleolar RNAs (snoRNAs) in TBI-associated neuroinflammation remains poorly understood. This study evaluated its prognostic value in TBI.</p><p><strong>Mice and methods: </strong>A controlled cortical impact (CCI) model was established in male C57BL/6 mice and validated through modified neurological severity scoring (mNSS), hematoxylin-eosin (H&E) staining, and immunostaining for IgG leakage and Nissl substance. Cortical snoRNA expression profiles were assessed using microarray analysis, with differentially expressed candidates confirmed by quantitative real-time PCR (qRT-PCR). The spatial distribution of snoRNAs was determined via fluorescence in situ hybridization (FISH), while the anti-inflammatory effects of snoRNA Gm24418 were evaluated in vivo and vitro. Downstream molecular pathways were identified through transcriptomic sequencing combined with bioinformatics analysis.</p><p><strong>Results: </strong>Mice subjected to CCI exhibited significant motor and cognitive impairments (elevated mNSS), neuronal loss (as indicated by H&E and Nissl staining), and blood-brain barrier disruption (evidenced by IgG extravasation). Microarray analysis identified 47 dysregulated small nucleolar RNAs (snoRNAs), comprising 43 that were downregulated and 4 that were upregulated, with Gm24418 exhibiting the most significant downregulation. FISH confirmed the localization of Gm24418 predominantly in cortical neurons. Overexpression of Gm24418 in N₂A cells and mice significantly reduced the levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6, and suppressed the activation of Ccl2 and TNF signaling pathways. Mechanistic analyses indicated that Gm24418 overexpression is associated with downregulation of the TNF signaling pathway, thereby attenuating neuroinflammation and promoting the restoration of blood-brain barrier integrity following TBI.</p><p><strong>Conclusion: </strong>Gm24418 is identified as a neuron-specific snoRNA that ameliorates TBI-induced neuropathology through influencing the expression of key inflammatory mediators, including CCL2 and TNF-α, representing a promising novel therapeutic target for post-traumatic neuroinflammation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"583983"},"PeriodicalIF":4.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}