Journal of Inflammation Research最新文献

Objective: This study aimed to analyze the differential expression patterns of serum cytokines across severity-stratified pediatric adenovirus pneumonia cases and evaluate their clinical utility as predictive biomarkers for disease severity.

Methods: This retrospective study included 88 pediatric adenovirus pneumonia cases and 54 healthy children between January 2021 and December 2024. Cases were stratified by disease severity into mild (n = 59) and severe (n = 29) pneumonia groups. We collected baseline clinical characteristics and measured pretreatment levels of 12 serum cytokines. Comparative analyses of cytokine profiles were performed across different severity groups (mild and severe) and healthy controls. The diagnostic performance of these cytokines for severe pneumonia detection was evaluated using receiver operating characteristic (ROC) curve analysis, with particular focus on the area under the curve (AUC) values.

Results: Severe pneumonia cases exhibited a more pronounced clinical course, characterized by significantly longer hospitalization, fever duration, and cough persistence, a higher incidence of wheezing and tachypnea, and marked elevations in inflammatory markers (CRP, ESR, LDH, fibrinogen, D-dimer). Of the 12 cytokines elevated versus controls, only interleukin (IL)-6, IL-8, and IL-10 exhibited statistically significant, severity-dependent increases (p < 0.05) and were correlated with longer hospitalization and persistent cough. ROC analysis revealed IL-6 and IL-10 as superior predictors for disease severity, with AUC reaching 0.88 (95% CI: 0.83-0.94). At optimal cutoffs, IL-6 showed 93% sensitivity and 71% specificity, while IL-10 demonstrated 90% sensitivity and 83% specificity. IL-8 showed moderate diagnostic value (AUC = 0.79, with 69% sensitivity and 83% specificity).

Conclusion: These findings demonstrate distinct cytokine expression patterns across varying severity levels of pediatric adenovirus pneumonia. The robust performance of IL-6 and IL-10 underscores their potential as biomarkers for early severity stratification in clinical practice.

Background: Temporal lobe epilepsy (TLE), the predominant drug-resistant focal epilepsy, involves neuroinflammation and neuronal hyperexcitability. Cuproptosis-a copper-dependent cell death pathway triggered by mitochondrial copper overload and lipoylated protein aggregation-remains unexplored in epilepsy. This study investigates its molecular basis, neuroinflammatory crosstalk, and therapeutic implications in TLE.

Methods: Bulk RNA-seq and single-cell RNA-seq datasets from GEO were analyzed using weighted gene co-expression network analysis (WGCNA) and consensus clustering to stratify cuproptosis-associated TLE subtypes. Ten machine learning algorithms identified hub genes linked to cuproptosis-immune crosstalk. Experimental validation in a pilocarpine-induced TLE mouse model confirmed gene expression changes via Western blot and immunohistochemistry.

Results: Two TLE subtypes were stratified: cuproptosis-related gene (CRG) -high with upregulated cuproptosis drivers, heightened macrophage/T-cell infiltration, and NF-κB-mediated neuroinflammation, and CRG-low exhibiting disrupted copper homeostasis. Hub genes (CD44, PDE5A, TUBA1A) linked cuproptosis to astrocyte-driven immune interactions, endothelial dysfunction, and neuronal stress. Single-cell analysis localized CD44 to astrocytes interacting with microglia, while PDE5A and TUBA1A correlated with blood-brain barrier leakage and neuronal hyperexcitability. Experimental validation confirmed decreased CD44 and elevated PDE5A/TUBA1A in TLE mice, aligning with seizure severity.

Conclusion: This study firstly establishes cuproptosis as a mechanistic bridge between copper dysregulation and TLE pathology, driving neuroinflammation via NF-κB and neuronal-glial dysfunction. The CRG-based subtyping offers novel disease classification, while CD44, PDE5A, and TUBA1A emerge as therapeutic targets to mitigate copper-mediated neurotoxicity. These findings reposition cuproptosis as a key pathway in epilepsy, providing a roadmap for precision therapy in drug-resistant TLE.

Background: Research on the connection between serum ferritin levels and the neutrophil-to-lymphocyte ratio (NLR) in individuals with osteoporotic fractures (OPF) are currently limited. This study aims to investigate the relationship between the NLR and serum ferritin levels, with the goal of offering a more convenience method for assessing iron stores and inflammatory response in clinical settings.

Methods: A retrospective cross-sectional analyzed 4782 patients with OPF. Initial measurements included serum ferritin and NLR. The analysis accounted for various confounders. Furthermore, techniques such as multivariable linear regression, smooth curve fitting, and threshold analysis techniques were utilized.

Results: A strong association was observed between serum ferritin levels and the NLR in patients with OPF (β = 6.36, 95% CI, 2.02, 10.65, P-value < 0.01). The recognized threshold was 5.31. When levels dropped below this point (< 5.31), there was a notable rise in serum ferritin (β= 32.08; 95% CI, 12.97, 51.20, P-value < 0.01). This study discovered a threshold effect between serum ferritin and NLR.

Discussion: Recognizing this threshold effect holds substantial clinical importance, as it could provide a novel approach for assessing inflammation levels and iron reserves in patients with OPF. Higher or lower NLR may be relevant for identifying iron status. Clinicians may assess the iron status of patients with OPF by monitoring NLR, which may serve as an indicator of their iron reserves. This information can facilitate the formulation of targeted strategies for diagnosis and treatment. Nevertheless, further detailed studies are needed to confirm the current results.

Conclusion: The study reveals a threshold effect between serum ferritin and NLR in patients with OPF, showing a positive correlation, particularly when NLR is below 5.31. This discovery reveals that NLR may serve as a biomarker for rapidly evaluating iron reserves in patients with OPF. Therefore, clinicians may incorporate NLR as a potential biomarker for quick iron evaluation to determine the next step of comorbidity screening and treatment plan.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD), the most common chronic liver disease worldwide, is characterized as a chronic inflammatory disease within an altered immune microenvironment. Investigating the relationship between peripheral blood parameters and intrahepatic immune remodeling is significant for developing non-invasive diagnostic tools and targeted immunotherapies for early MAFLD. This study aimed to investigate the causal relationships and underlying mechanisms between peripheral blood cell indices and intrahepatic immune microenvironment remodeling in early-stage MAFLD.

Methods: We performed bidirectional mendelian randomization analyses to assess the causal effects of peripheral blood cell traits on MAFLD risk. Mediation mendelian randomization was applied to identify key inflammatory mediators. Hepatic immune cell recruitment pathways were explored by integrating mendelian randomization findings with bulk RNA sequencing data. Single-cell RNA sequencing of mouse models that replicate metabolic syndrome-associated MAFLD pathology was employed to characterize lymphocyte-driven pathways. Key findings were validated using an independent public single-cell RNA sequencing dataset derived from human peripheral blood mononuclear cells and an independent public single-cell RNA sequencing dataset from a non-genetically modified murine model.

Results: (1) Bidirectional Mendelian randomization revealed a unidirectional causal effect of elevated peripheral lymphocyte count on disease risk. (2) Mediation analysis implicated Cd5-mediated inflammatory pathways in this association. (3) Integration of mendelian randomization and bulk transcriptomic data linked lymphocytes to hepatic recruitment pathways. (4) Single-cell RNA sequencing of MAFLD models identified a novel Itgb1⁺Cd5⁺Cd4⁺T cell subset enriched in diseased livers. These cells interact with hepatic Vcam1^highMmp12⁺Kupffer cells via Vcam1-Itgb1 signaling, initiating inflammation. (5) This pathogenic cell subset and interaction were conserved in an independent, non-genetically modified murine model. Furthermore, a corresponding Itgb1⁺Cd5⁺Cd4⁺T cell population was identified in the peripheral blood mononuclear cells of human MAFLD patients.

Conclusion: We innovatively established that peripheral T lymphocytes exhibit a positive causal relationship with MAFLD development, mediated by Cd5 expression levels. Furthermore, liver-resident Vcam1^highKupffer cells may facilitate immune microenvironment remodeling in early MAFLD by recruiting Itgb1⁺Cd5⁺Cd4⁺T cells through the Vcam1-Itgb1 adhesion pathway.

Purpose: To evaluate the predictive value of baseline and preoperative blood parameters for treatment efficacy and prognosis in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy (nCIT) followed by radical surgery.

Patients and methods: This retrospective study analyzed clinical data from patients with LA-ESCC patients treated with nCIT followed by surgery (October 2019-November 2024). Patients were categorized based on pathological response (pathological complete response [pCR] and major pathological response [MPR]). Univariate and multivariate analyses identified factors associated with pCR and MPR. Cox regression and Kaplan-Meier methods were used to evaluate overall survival (OS) and disease-free survival (DFS). Nomograms and Receiver Operating Characteristic (ROC) curves were created for prognostic prediction.

Results: Among 236 patients, the pCR rate was 31.8%, and the MPR rate was 51.7%. pCR was associated with improved DFS (Hazard Ratio [HR] = 0.27, 95% CI: 0.16-0.43, p < 0.0001) but not OS (p = 0.058). MPR was significantly correlated with both DFS (HR=0.27, 95% CI: 0.17-0.44, p < 0.0001) and OS (HR=0.38, 95% CI: 0.21-0.71, p = 0.0023). Identified predictors of treatment response included baseline and preoperative platelet indices (mean platelet volume [MPV], platelet distribution width [PDW], platelet-large cell ratio [P-LCR]) for both pCR and MPR, along with preoperative Apolipoprotein A1 (ApoA1) specifically for MPR (all identified as independent predictors on univariate and multivariate analysis, p < 0.05), reflecting their role in modulating the inflammatory response. A predictive model combining MPV (HR = 0.86, 95% CI: 0.61-1.22) and ApoA1 (HR = 0.24, 95% CI: 0.07-0.81) demonstrated good accuracy in forecasting DFS (30 months: AUC = 0.71, 95% CI: 0.60-0.81).

Conclusion: Baseline and preoperative blood parameters (MPV, PDW, P-LCR) and preoperative ApoA1 are valuable predictors of treatment response and prognosis in LA-ESCC. Nomograms incorporating these markers offer reliable prognostic insights for DFS.

Purpose: This study aimed to investigate the association between serum high mobility group box 1 (HMGB1) levels and stroke through the long-term follow-up of patients with paroxysmal atrial fibrillation (AF).

Patients and methods: The study was a prospective cohort study. A total of 304 patients with paroxysmal AF were enrolled, including 66 who underwent radiofrequency ablation (RFA). Serum HMGB1 levels were measured using an enzyme-linked immunosorbent assay. The primary endpoint was the first occurrence of a major adverse cerebrovascular event (MACE), defined as an acute ischemic stroke or all-cause mortality.

Results: During the median follow-up of 81.5 months, 76 MACEs were recorded. Patients were categorized into MACE and no-MACE groups based on the occurrence of MACE. The MACE group showed significantly higher age, CHA₂DS₂-VASc scores, and serum HMGB1 levels than the non-MACE group (p<0.05). The areas under the curve (AUC) for HMGB1 and CHA₂DS₂-VASc were 0.779 [95% (confidence interval, CI): 0.728-0.824)] and 0.818 (95% CI: 0.770-0.860), respectively. The combination of HMGB1 and CHA₂DS₂-VASc yielded an AUC of 0.895 (95% CI: 0.855-0.927), which was significantly higher than that of either metric alone (P < 0.05). Kaplan-Meier analysis showed that patients with high HMGB1 levels had a significantly lower event-free survival rate for MACE than those with low HMGB1 levels (P < 0.05). Multivariate Cox regression analysis identified HMGB1 level [(Hazard ratio, HR), 4.161; 95% CI, 2.518-6.878)] as an independent predictor of MACE in paroxysmal AF, along with the CHA₂DS₂-VASc score (HR: 5.567, 95% CI: 3.089-10.032).

Conclusion: Elevated serum HMGB1 level was identified as a significant predictor of stroke or mortality in patients with paroxysmal AF, and may enhance the predictive capacity of current risk stratification tools while supporting more personalized anticoagulation strategies.

Purpose: Modulation of the AKT signaling pathway can effectively regulate endoplasmic reticulum stress (ERS) and inhibit ischemia-induced cardiomyocyte apoptosis in myocardial ischemia-reperfusion injury (MIRI). The present study was designed to investigate the role of AKT and ERS in the modulation of MIRI by Huanglian Jiedu Decoction (HLJDD) through in vitro and in vivo experiments.

Methods: In vivo studies employed a rat model of MIRI with three HLJDD dosage groups and a nicorandil control group. Comprehensive evaluations were conducted, including assessments of cardiac function, histopathological analysis, apoptosis detection, and immunohistochemical examination of ERS markers. For in vitro validation, H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation conditions, and cellular viability assays were combined with ultrastructural and molecular analyses. Investigations guided by network pharmacology focused on the PERK/eIF2α/CHOP signaling pathway and AKT phosphorylation.

Results: HLJDD demonstrated dose-dependent cardioprotective effects through attenuation of myocardial apoptosis and ERS activation. Mechanistic studies revealed its ability to restore AKT phosphorylation and suppress the PERK/eIF2α/CHOP signaling cascade. The cardioprotective effects were abolished upon AKT inhibition, thereby confirming the specificity of this pathway.

Conclusion: HLJDD may serve as a potential therapeutic candidate for ischemia-induced cardiomyocyte apoptosis during MIRI. HLJDD exerts its effects by inhibiting the AKT-mediated PERK/eIF2α/CHOP signaling pathway, attenuating ERS and thereby reducing MIRI-induced apoptosis.

Objective: To explore the X-ray, CT, and MRI imaging features of Brucellar spondylodiscitis (BS) across different stages and evaluate their diagnostic value.

Methods: Retrospective analysis of imaging features in 137 BS patients (early stage: 40; advanced: 52; recovery: 45) classified by the 2023 Chinese Medical Association Consensus. Diagnostic performances of X-ray, CT, and MRI were compared.

Results: Lumbar involvement predominated (98.5%), with 73.7% single-segment cases. X-ray missed 90% of early-stage BS but detected intervertebral stenosis/bone destruction better in advanced/recovery stages (P<0.05). CT excelled in identifying bone destruction (83.9%), sequestration (5.1%), and fractures (6.6%). MRI detected granulomas (85.4%) and abscesses (3.6%) effectively, especially granulomas in advanced-stage (p < 0.05, compared with early stage and recovery stage). CT+MRI synergistically improved staging accuracy for early/advanced BS.

Conclusion: CT and MRI are critical for BS staging, with combined use recommended to minimize misdiagnosis and guide treatment.

Background: Ulcerative colitis (UC) is a debilitating inflammatory condition with growing global prevalence. While immune dysregulation is a known hallmark, the specific molecular drivers and their link to fibrosis remain incompletely characterized. To address this, we conducted a study combining bioinformatic analyses of public datasets with experimental validation to identify and validate key biomarker candidates involved in UC pathogenesis.

Methods: Three publicly available ulcerative colitis gene expression datasets (GSE38713, GSE87466, GSE119600) were retrieved from the Gene Expression Omnibus (GEO). Immune cell infiltration was evaluated using ssGSEA, with significant cell types identified by Wilcoxon test and LASSO regression. DEGs were screened and analyzed using GO, KEGG, and PPI networks. Hub genes were identified using cytoHubba and validated via ROC curves. RT-qPCR, WB, and IHC validated findings in UC rat models and clinical samples.

Results: The differentially expressed genes (DEGs) were evaluated using ten distinct algorithms, resulting in the identification of eight common DEGs following an intersection analysis. 4 hub genes were further identified through validation using the GSE119600 dataset, namely Cluster of Differentiation 274 (CD274), Matrix Metallopeptidase 1 (MMP1), neutrophil cytosolic factor 2 (NCF2), Plasminogen Activator Urokinase (PLAU). Notably, NCF2 demonstrated the highest specificity and sensitivity for diagnosing ulcerative colitis (UC), suggesting its potential utility as a diagnostic biomarker. Additionally, a distinct immune cell type exhibited significant differences between UC patients and healthy controls (HC). Correlation analyses utilizing bioinformatics techniques revealed that the hub genes CD274, MMP1, NCF2, and PLAU were positively associated with macrophage infiltration, highlighting their potential role in the immune response in UC.

Conclusion: CD274, MMP1, NCF2, PLAU can serve as hub genes associated with UC. Among these, NCF2 stands out as a particularly promising target for further research into the underlying mechanisms of UC. Additionally, NCF2 may play a role in the development and progression of UC by modulating macrophage infiltration.