Journal of Inflammation Research最新文献

{"title":"Recurrence of Histiocytic Necrotizing Lymphadenitis in Children: A 10-year Multicenter Retrospective Study.","authors":"Yong-Ping Xie, Yan-Wen Xu, Yan Li, Hu Zhang, Shan-Shan Xu, Mei-Na Lu, Yi-Ping Chen, Jian-Mei Tian, Xin-Fang Huang, Zhi-Feng Liu, Zhi-Gang Gao, Li-Su Huang","doi":"10.2147/JIR.S504413","DOIUrl":"10.2147/JIR.S504413","url":null,"abstract":"<p><strong>Purpose: </strong>Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi-Fujimoto disease, is prone to recurrence in children. However, the frequency and risk factors associated with recurrence remain unclear.</p><p><strong>Patients and methods: </strong>This study included all children with pathology-confirmed HNL from five hospitals over ten years (2013-2023). This study employed STROBE analysis to investigate the association between clinical characteristics and HNL, which was subsequently verified through in both a derivation group and a validation group. Initial clinical features were collected, and data were randomly divided into derivation and validation sets (3:2 ratio). Cox regression analysis identified risk factors, and receiver operating characteristic curves were used to develop a prediction model. Flow cytometry focused on assessing CD4⁺ T-lymphocytes in lymphoid tissue.</p><p><strong>Results: </strong>Of the 593 HNL cases, 88 (14.8%) experienced recurrence during a median follow-up of 3 years. Cumulative recurrence rates at the first, fifth, and ninth years were 8.7%, 20.0%, and 32.2%, respectively. Factors associated with recurrence included age ≤ 6-year-old (Hazard ratio [HR] 3.6, 95% confident interval [CI], 2.0-6.4), C-reactive protein > 16 mg/L (HR, 1.9, 95% CI, 1.0-3.6), blood CD4⁺ T-lymphocytes ≤ 30% (HR, 4.4, 95% CI, 1.0-18.7), ferritin > 150 μg/L (HR, 2.3, 95% CI, 1.1-5.3) and platelets ≤ 200×10⁹/L (HR 1.8, 95% CI, 1.0-3.2). The prediction model demonstrated areas under the curve of 0.81 for the derivation dataset and 0.77 for the validation dataset, classifying patients into low, medium, and high-risk categories, with corresponding recurrence rates of 5.2%, 19.0%, and 42.9%. Lower lymphoid CD4⁺ T-lymphocyte counts were also observed in the recurrent group.</p><p><strong>Conclusion: </strong>The recurrence of HNL increases over time. Key factors, including C-reactive protein (CRP) levels, CD4⁺ T-lymphocyte counts, ferritin, platelets, and age at diagnosis may contribute to recurrence risk.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4307-4318"},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753111","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 Dual Roles of STAT3 in Ferroptosis: Mechanism, Regulation and Therapeutic Potential.","authors":"Jinghui Xie, Dan Luo, Pengfei Xing, Weijun Ding","doi":"10.2147/JIR.S506964","DOIUrl":"10.2147/JIR.S506964","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent programmed mechanism of cell death that is driven by lipid peroxidation, is an important pathogenic factor in oncological and non-oncological disorders. Dysregulation of iron and lipid metabolism profoundly influences disease progression through ferroptosis modulation. Signal transducer and activator of transcription 3 (STAT3), a transcriptional regulator, regulates ferroptosis by binding to promoters of key molecules such as solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1). In this review, we described the role of STAT3 in supporting tumors survival by suppressing ferroptosis in malignancies, and bidirectionally regulating ferroptosis in non-tumors to regulate the development of the disease. We also reported emerging therapeutic strategies that target STAT3-mediated ferroptosis, including natural phytochemicals, inhibitors, and nanotechnology-enabled drug delivery systems. These advancements deepen the mechanistic understanding of ferroptosis regulation, and provide new theoretical bases and strategies to treat ferroptosis-related diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4251-4266"},"PeriodicalIF":4.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719826","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":"Understanding the Mode of Action of Several Active Ingredients from the Micro-Immunotherapy Medicine 2LZONA^®.","authors":"Camille Jacques, Flora Marchand, Mathias Chatelais, Adrien Brulefert, Ilaria Floris","doi":"10.2147/JIR.S498930","DOIUrl":"10.2147/JIR.S498930","url":null,"abstract":"<p><strong>Introduction: </strong>Varicella-zoster virus (VZV) affects over 90% of the global population. The initial encounter with VZV, often in the early years of childhood, results in varicella. From latency, VZV can reactivate in later stages of life, leading to the development of herpes zoster. Considering the importance of host immune responses in preventing reactivation and clinical manifestations associated with VZV infection, a therapy that sustains the immune system could be of great interest.</p><p><strong>Objective: </strong>The present work aimed to set the basis of the possible mode of action of 2LZONA^®, a micro-immunotherapy medicine composed of five different capsules. Thus, the effects of several active substances employed in this medicine were assessed in human primary immune-related cells.</p><p><strong>Results and discussion: </strong>Our results showed that DNA (8 CH) and RNA (8 CH), two active substances used in 2LZONA, displayed phagocytosis-enhancing capabilities in granulocytes and contained sub-micron particles that could explain, at least partially, the observed effect. These two active substances tested singularly and together with other actives of 2LZONA's capsules, modulated the proliferation of immature, transitory, and mature subsets of natural killer (NK) cells in an IL-15-like pattern, suggesting an enhancement of their activation levels. Moreover, the tested items of 2LZONA increased the secretion of IL-2, IL-6, IL-13, and TNF-α in human peripheral blood mononuclear cells (PBMCs). Furthermore, the proliferation of PBMCs-derived NK cells, intermediate monocytes, and neutrophils was slightly increased by this treatment. In CD3 and CD3/CD28 pre-primed conditions, actives present in one capsule of 2LZONA enhanced the secretion of IL-6 and TNF-α. Finally, one capsule of 2LZONA reduced the expression of human leukocyte antigen (HLA) in IFN-inflamed endothelial cells. Overall, these data provide, for the first time, preliminary experimental evidence of the mechanisms of action of some of the active ingredients employed in 2LZONA capsules.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4267-4290"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710222","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":"Identification and Validation of the Potential Key Biomarkers for Atopic Dermatitis Mitochondrion by Learning Algorithms.","authors":"Junhao Xu, Xinyu Pan, Miao Zhang, Kairong Sun, Zihan Li, Juan Chen","doi":"10.2147/JIR.S507085","DOIUrl":"10.2147/JIR.S507085","url":null,"abstract":"<p><strong>Purpose: </strong>Atopic dermatitis (AD) is a common inflammatory skin condition characterized by erythema and pruritus. Its precise pathogenesis remains unclear, though factors such as genetic predisposition, autoantigen response, allergen exposure, infections, and skin barrier dysfunction are involved. Research suggests a correlation between AD and mitochondrial dysfunction, as well as oxidative stress in skin tissues.</p><p><strong>Methods: </strong> Skin sample datasets related to AD (GSE36842, GSE120721, GSE16161, and GSE121212) were retrieved from the GEO database. Differential gene analysis identified differentially expressed genes (DEGs) in AD. Three potential biomarkers-COX17, ACOX2, and ADH1B-were identified using LASSO and Support Vector Machine (SVM) algorithms. These biomarkers were validated through ROC curve analysis, nomogram modeling, calibration curves, and real-time PCR. Immune infiltration analysis assessed correlations of the biomarkers. Additionally, single-cell analysis of the GSE153760 dataset identified nine cell clusters and confirmed expression patterns of the three hub genes.</p><p><strong>Results: </strong>Differential analysis identified 150 upregulated and 367 downregulated genes. Enrichment analysis revealed significant pathways related to mitochondrial function, oxidative stress, and energy metabolism in skin samples from AD patients. Area under the curve (AUC) values for biomarkers COX17, ACOX2, and ADH1B were 1.000, 0.928, and 0.895, respectively, indicating strong predictive capacity. qPCR results showed COX17 was highly expressed in AD lesions, while ACOX2 and ADH1B were higher in normal skin, consistent with previous findings. Correlation analysis indicated ACOX2 and ADH1B were positively correlated with resting mast cells but negatively with activated T cells and NK cells, while COX17 showed a positive correlation with activated T cells and a negative correlation with resting mast cells.</p><p><strong>Conclusion: </strong>This study suggests that the hub genes COX17, ACOX2, and ADH1B may serve as potential biomarkers in the pathogenesis of AD. These findings could provide insights for the treatment and prognosis of AD and related inflammatory skin conditions.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4291-4306"},"PeriodicalIF":4.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719823","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":"FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression.","authors":"Maoting Hu, Kunlin Yu, Chunlin Wang, Wuling Liu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Giulio Sartori, Francesco Bertoni, Xiao Xiao, Yaacov Ben-David","doi":"10.2147/JIR.S500822","DOIUrl":"10.2147/JIR.S500822","url":null,"abstract":"<p><strong>Plaque psoriasis: </strong>Plaque psoriasis is an inflammatory skin disorder affecting nearly 2% of the world population. Despite recent advances in psoriasis treatment, there is still a need for more effective therapies. The ETS transcription factor FLI1 plays critical roles in hematopoiesis, angiogenesis, immunity, and cancer. Emerging evidence suggests that FLI1 is intricately involved in inflammatory processes underlying psoriasis pathogenesis.</p><p><strong>Methods: </strong>RNAseq and bioinformatic analysis were used to identify the correlation between FLI1 levels and the expression of inflammatory genes associated with psoriasis. Over-expression of FLI1 in skin cells determined FLI1's role in inducing transcription of psoriasis-related inflammatory genes, including IL6, IL1A, IL1B, IL23, and TNFα. Inhibitors such as chelerythrine (CLT) were tested for their suppressive effects on these genes. Mouse models of plaque psoriasis were employed to assess the therapeutic potential of CLT and tacrolimus (TAC).</p><p><strong>Results: </strong>Over-expression of FLI1 in skin cells upregulated 24 psoriasis-associated genes, which were identified through RNAseq. Inhibitors of FLI1, such as CLT, suppressed these inflammatory genes in skin cells. In mouse models of plaque psoriasis induced by imiquimod (IMQ) or phorbol ester (TPA), treatment with the anti-FLI1 inhibitor CLT, administered either peritoneally or topically, significantly downregulated inflammatory genes and alleviated psoriasis symptoms. Similarly, TAC, a common immunosuppressive agent, effectively attenuated IMQ-induced psoriasis by acting as a potent anti-FLI1 compound.</p><p><strong>Conclusion: </strong>These findings demonstrate that FLI1 plays a central role in psoriasis development and highlight it as a potential therapeutic target for this skin disorder.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4213-4231"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700516","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":"Systemic Lupus Erythematosus Stimulates Chondrocyte Pyroptosis to Aggravate Arthritis via Suppression of NRF-2/KEAP-1 and NF-κB Pathway.","authors":"Shuchao Shen, Xuliang Fang, Helou Zhang, Tingting Lang, Fangda Fu, Yu Du, Taotao Xu, Hongting Jin, Peijian Tong, Chengliang Wu, Changfeng Hu, Hongfeng Ruan","doi":"10.2147/JIR.S502800","DOIUrl":"10.2147/JIR.S502800","url":null,"abstract":"<p><strong>Purpose: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by diverse clinical manifestations, including joint symptoms. Arthritis represents one of the earliest manifestations of SLE, profoundly affecting the quality of life for affected individuals, yet the underlying mechanisms of SLE-associated arthritis remain insufficiently investigated. The study aimed to investigate the impact of SLE exacerbation on arthritis using the MRL/<i>lpr</i> mouse model, which closely mimics human SLE manifestations.</p><p><strong>Methods: </strong>In the present study, we evaluated the impact of SLE onset on knee joint degeneration by comparing arthritic phenotype and complex molecular alterations between 6 female 14-week-old MRL/<i>lpr</i> mice, which manifest SLE, and MRL/<i>MpJ</i> mice, which remain unaffected.</p><p><strong>Results: </strong>Our results demonstrated that MRL/<i>lpr</i> mice exhibited a more severe arthritic phenotype compared to MRL/<i>MpJ</i> mice, characterized by elevated Osteoarthritis Research Society International (OARSI) scores (<i>P</i> < 0.01), disrupted extracellular matrix metabolism, impaired chondrocyte proliferation and increased apoptosis. Notably, inflammatory cytokines proteins such as IL-1β and TNF-α (both <i>P</i> < 0.01), IL-18 and IL-6 (both <i>P</i> < 0.05), were significantly increased in articular cartilage of MRL/<i>lpr</i> mice, accompanied by increased expression of calcitonin gene-related peptide (CGRP) (<i>P</i> < 0.05), NETRIN-1, and NESTIN (both <i>P</i> < 0.01), indicating that SLE promotes inflammation response and sensory nerve ingrowth in the knee joint, contributing to the progression of arthritis. Mechanistic analysis revealed that SLE exacerbation intensified chondrocyte pyroptosis by upregulating pyroptotic-related proteins, including NLRP3, CASPASE-1, and gasdermin D (all <i>P</i> < 0.01), through the regulation of the nuclear factor erythroid 2-related factor (NRF-2)/KEAP-1 and nuclear factor kappa-B (NF-κB) pathway.</p><p><strong>Conclusion: </strong>Collectively, our findings underscore the mechanistic connection between chondrocyte pyroptosis and arthritis exacerbation in SLE, suggesting potential therapeutic targets for mitigating arthritis progression in the context of SLE.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4233-4250"},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700530","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":"Dynamic Trends of Albumin-to-C-Reactive Protein Ratio: A Prognostic Indicator in Elderly Patients with Community-Acquired Pneumonia.","authors":"Lei Miao, Chen Gong, Jingxian Liao, Chunhui Xie, Xiaozhu Shen, Yajuan Cheng","doi":"10.2147/JIR.S512632","DOIUrl":"10.2147/JIR.S512632","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of dynamic changes in the albumin-to-C-reactive protein ratio (ACR) in elderly patients with community-acquired pneumonia (CAP) has not been fully elucidated. This study aims to evaluate the utility of ACR as a dynamic biomarker for predicting 28-day mortality and enhancing risk stratification in this high-risk population.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on 437 elderly CAP patients (≥65 years). Serum albumin and C-reactive protein (CRP) levels were measured at admission (T0), 24 hours (T1), and 3 days (T2) post-admission. ACR was calculated for each time point, and its prognostic value was assessed using advanced statistical methods.</p><p><strong>Results: </strong>The 28-day mortality rate was 16.7%. ACR levels were consistently lower in non-survivors across all time points (P < 0.001). RCS analysis revealed a nonlinear relationship between ACR and mortality risk. Time-varying ROC analysis demonstrated that ACR consistently outperformed CRP in predicting mortality, with superior area under the curve (AUC) values at all time points. Random-effects modeling indicated minimal inter-individual variability in ACR (random effects variance: 0.030; standard deviation: 0.175). Time-varying Cox regression confirmed a strong negative association between dynamic ACR changes and mortality risk, with a C-statistic of 0.833 (P < 0.001).</p><p><strong>Conclusion: </strong>Dynamic monitoring of ACR is a robust and clinically applicable tool for predicting short-term mortality in elderly CAP patients. By integrating markers of inflammation and nutritional status, ACR facilitates early identification of high-risk patients and supports personalized treatment strategies. These findings highlight the potential of ACR as a novel biomarker for improving clinical outcomes in this vulnerable population.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4195-4211"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692561","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":"Identification of Disulfidptosis-Related Genes and Molecular Subgroups in Rheumatoid Arthritis for Diagnostic Model and Patient Stratification.","authors":"Xinyi Liu, Siyao Wang, Xinru Du, Yulu Wang, Lingfei Mo, Hanchao Li, Zechao Qu, Xiaohao Wang, Jian Sun, Yuanyuan Li, Jing Wang","doi":"10.2147/JIR.S505746","DOIUrl":"10.2147/JIR.S505746","url":null,"abstract":"<p><strong>Introduction: </strong>Cell death contributes to the pathogenesis of rheumatoid arthritis (RA) through various pathways. Disulfidptosis is a recently discovered novel form of cell death characterized by the abnormal accumulation of intracellular disulfide bonds. It remains unclear for the association between RA and disulfidptosis.</p><p><strong>Methods: </strong>A comprehensive analysis of three GEO datasets was presented in this study. First, the analysis involved the use of weighted gene co-expression network analysis (WGCNA) and differential analysis and were employed to identify the key module genes related to RA and disulfidptosis-related genes. The machine learning algorithms were used to identify the hub genes. Second, a diagnostic model was constructed for RA based on the hub genes. The nomogram and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic value of the model. Third, two RA subtypes were identified based on hub genes by using consensus clustering analysis. Then, the disease activity scores, clinical markers, and immune cells were compared between the two RA subgroups. Finally, the differential expression of hub genes was validated between healthy controls and RA patients by qPCR.</p><p><strong>Results: </strong>Four hub genes (KLHL2, POLK, CLEC4D, NXT2) were identified. The expression of the four hub genes was verified to be significantly higher in RA patients compared with healthy controls. The superior diagnostic value of the model was validated, which demonstrated that the model outperforms each hub gene individually. Two subtypes of RA were determined. Patients in cluster A exhibited relatively lower levels of DAS28-CRP, DAS28-ESR, CDAI, SDAI, RF, CRP, and MMP3. In contrast, patients in cluster B had significantly higher levels of the above markers.</p><p><strong>Conclusion: </strong>Four hub genes were identified to provide unique insights into the role of disulfidptosis in RA. Additionally, a promising diagnosis model and patient stratification were established based on the hub genes to assess the risk of RA onset and RA disease activity.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4157-4175"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692591","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":"Differential Diagnosis Value of Neutrophil Gelatinase Associated Lipocalin as a Noninvasive Biomarker in Perianal Fistulizing Crohn's Disease.","authors":"Kai Ma, Yikun Li, Jingwen Wu, Yi Fu, Lu Yin, Simin Xu, Feiyang Weng, Yibo Yao, Chen Wang","doi":"10.2147/JIR.S504213","DOIUrl":"10.2147/JIR.S504213","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing perianal fistulizing Crohn's disease (pfCD) typically depends on costly and time-intensive endoscopic and radiographic procedures. Compelling evidence indicates that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the pathophysiology of Crohn's disease (CD) and may serve as a noninvasive biomarker for its diagnosis. This study aimed to evaluate NGAL's potential as a noninvasive diagnostic biomarker between pfCD and cryptoglandular (CG) perianal fistula, and its correlation with disease severity in pfCD.</p><p><strong>Methods: </strong>Serum, fecal, and fistula tissue samples were collected from 96 patients with pfCD and 97 patients with CG perianal fistula as controls. Serum NGAL levels were quantified through ELISA and fistula tissue NGAL levels were quantified through immunohistochemical staining, while pfCD disease severity was evaluated using the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI). Additional laboratory parameters, including NGAL, fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were analyzed, and their correlations were assessed. Receiver operating characteristic (ROC) analysis was conducted to evaluate NGAL's diagnostic potential for pfCD.</p><p><strong>Results: </strong>Levels of serum NGAL, FC, CRP, and ESR in patients with pfCD were significantly elevated compared to the control group (<i>p</i> < 0.001); Spearman correlation analysis indicated a positive correlation between serum NGAL and FC, CRP, ESR, CDAI, and PDAI scores. The area under the ROC curve (AUC) for serum NGAL in diagnosing pfCD was 0.927 (95% <i>CI</i>: 0.890-0.964). The AUC for FC in diagnosing pfCD were 0.887 (95% <i>CI</i>: 0.839-0.935). Additionally, serum and fistula tissue NGAL levels were positively correlated with disease complexity in pfCD according to the Montreal classification.</p><p><strong>Conclusion: </strong>These findings suggest that serum NGAL is associated with pfCD severity and may offer a promising noninvasive biomarker for diagnosing and assessing pfCD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4075-4086"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692495","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":"LT-α Facilitates the Aerobic Glycolysis and M1 Polarization of Macrophages by Activating the NF-κB Signaling Pathway in Intervertebral Disc Degeneration.","authors":"Chensheng Qiu, Zhu Guo, Junhua Yuan, Hongfei Xiang, Bohua Chen, Yuanxue Yi, Yongsheng Zhao","doi":"10.2147/JIR.S506162","DOIUrl":"10.2147/JIR.S506162","url":null,"abstract":"<p><strong>Purpose: </strong>Injury and inflammatory activate and polarize macrophages in intervertebral disc degeneration (IVDD). Further research needs to be carried to explore the mechanisms that regulate macrophage polarization, providing new insights and targets for IVDD treatment. The aim of our study was to evaluate the influence of LT-α on aerobic glycolysis (AG) and polarization in macrophages.</p><p><strong>Methods: </strong>M0 macrophages were achieved by stimulating THP-1 cells with PMA. M1 macrophages were obtained by IFN-γ and LPS stimulation in M0 macrophages. Energy metabolomics, AG and apoptosis related protein expression, migration and invasion measurement, proliferation was analyzed. Polarization of macrophages, AG associated genes expression, macrophage recruitment was evaluated. NF-κB signaling was ascertained by laser confocal and Western blotting.</p><p><strong>Results: </strong>The propanoate metabolism pathway was enriched in LT-α overexpressing M0 macrophages, and various energy metabolites were detected. Glucose absorption, lactic acid production, and levels of AG proteins were strikingly increased in LT-α overexpression macrophages and remarkably repressed in LT-α knockdown macrophages, accompanied by activated and inactivated NF-κB signaling, respectively. Suppressed migration and invasion ability, restrained proliferation, activated AG, and enhanced apoptosis were observed in nucleus pulposus (NP) cells treated by LT-α overexpressed macrophages, accompanied by reduced macrophage recruitment, with opposite results when treated by LT-α knockdown macrophages. The enhanced M1 polarization and activated AG in LT-α overexpression macrophages were abolished by co-culturing with NF-κB inhibitor.</p><p><strong>Conclusion: </strong>LT-α facilitates the AG and M1 polarization of macrophages via activating the NF-κB signaling pathway.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"4103-4120"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692540","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}