Journal of Inflammation Research最新文献

Objective: This study aimed to elucidate the functional role of Kininogen-1 (KNG1) in traumatic brain injury (TBI) and evaluate its potential as a therapeutic target.

Methods: A TBI rat model was established using a controlled cortical impact method. Neurological deficits were assessed via modified neurological severity scores (mNSS). Brain tissues were analyzed for edema, inflammation, and neuronal damage using histopathology (HE/Nissl staining), RT-qPCR, and transcriptomics. An in vitro oxidative stress model was constructed using H₂O₂-treated PC-12 cells. KNG1 knockdown was achieved via siRNA transfection, followed by analysis of oxidative stress markers (ROS, SOD, CAT) and MAPK pathway activation (Western blot).

Results: TBI rats exhibited significant neurological impairment. Transcriptomics identified 1,655 differentially expressed genes (DEGs), including upregulated KNG1, associated with inflammation and MAPK signaling. In vitro, KNG1 knockdown reduced oxidative stress (↑SOD/CAT, ↓ROS) and suppressed MAPK-p38/ERK phosphorylation.

Conclusion: Our transcriptomic analysis of TBI rat brain tissue identified KNG1 as a significantly upregulated gene functionally linked to the MAPK pathway, suggesting its potential role as an upstream regulator. Subsequently, in vitro functional validation demonstrated for the first time that KNG1 knockdown concurrently alleviated oxidative stress and suppressed MAPK hyperactivation. Therefore, this study not only defines a critical role for KNG1 in TBI pathology but also supports its potential as a therapeutic target that modulates multiple injury cascades.

Doxorubicin (DOX) is one of the most effective and widely used anthracycline chemotherapeutic agents, yet its clinical utility is severely limited by cumulative, dose-dependent cardiotoxicity. Currently, clinical management of DOX-induced cardiotoxicity is largely limited to dose adjustment, cardiac monitoring, and nonspecific cardioprotective agents, underscoring the lack of targeted anti-inflammatory strategies in current practice. A growing body of evidence indicates that inflammation is a central driver of DOX-induced cardiotoxicity, synergistically exacerbating oxidative stress, mitochondrial dysfunction, and cardiomyocyte death. These pathological processes not only compromise myocardial contractility, but also accelerate adverse cardiac remodeling, ultimately increasing the risk of heart failure in cancer survivors. Over the past decade, the discovery of non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), and extracellular vesicles such as exosomes has reshaped our understanding of the molecular regulation of cardiac inflammation. These molecules act as crucial modulators of intercellular communication and inflammatory signaling, influencing key pathways such as those involving nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and apoptosis-related cascades. Experimental studies have demonstrated that specific miRNAs and circRNAs suppress the production of inflammatory cytokines, reduce oxidative damage, and enhance survival in DOX-exposed cardiomyocytes and animal models. Similarly, exosome-mediated delivery of protective RNAs or proteins has emerged as a promising approach to mitigate DOX-induced myocardial injury. This review amasses current evidence on the anti-inflammatory functions of miRNAs, circRNAs, and exosomes in DOX-induced cardiac inflammation, highlighting their mechanistic roles, therapeutic potential, and the challenges that must be addressed to move these strategies toward clinical application.

Objective: To investigate whether monocyte CD11c (mCD11c) can serve as a promising biomarker for the diagnosis and prognosis of sepsis, distinguishing it from non-infectious inflammatory conditions.

Methods: A prospective, observational cohort study was conducted using a discovery cohort (sepsis, mild infection, patients after cardiovascular surgery, recovered sepsis patients, and healthy controls) and a validation cohort (sepsis, mild infection, and patients after cardiovascular surgery). Peripheral blood samples were analyzed using Cytometry by Time-of-Flight (CyTOF), single-cell RNA sequencing, and flow cytometry to assess the immune cell composition and mCD11c expression. Clinical data and outcomes were collected for analysis.

Results: The discovery cohort showed a significant downregulation of mCD11c in patients with sepsis. The validation cohort confirmed a lower mCD11c% in sepsis than in the other groups. Receiver operating characteristic (ROC) curve analysis showed that mCD11c had a higher AUC (0.939, P < 0.001) than traditional markers in distinguishing sepsis from non-infectious inflammation. mCD11c% was an independent prognostic factor for 7-day mortality (P < 0.05), with significant differences in survival rates between patients with mCD11c% above and below 96.445%.

Conclusion: mCD11c is a promising biomarker for early sepsis diagnosis and short-term survival prediction, outperforming the traditional markers. Larger multicenter studies are needed to validate these findings and to explore their potential as intervention targets.

Background: Sepsis and acute-on-chronic liver failure (ACLF) constitute a severe clinical interaction, resulting in alarmingly high short-term mortality rates. Current prognostic models, such as the Sequential Organ Failure Assessment (SOFA) score, lack specificity for this distinct patient group. The pathophysiology of both conditions is critically influenced by immune dysfunction, systemic inflammation, and nutritional deficits. This study sought to develop and validate a novel prognostic model that integrates immune-inflammatory-nutritional indicators to enhance the prediction of 28-day mortality in sepsis patients with ACLF.

Methods: A retrospective cohort study was conducted involving 246 sepsis patients with ACLF admitted to Shaanxi Provincial People's Hospital. Participants were randomly divided into a training cohort (n=185) and a validation cohort (n=61). Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses were utilized to identify independent predictors and construct a prognostic nomogram. The model's efficacy was thoroughly evaluated based on its discriminative capacity (area under the receiver operating characteristic curve, AUC), calibration (calibration curves), and clinical utility (decision curve analysis, DCA).

Results: The 28-day mortality rate was observed to be 37.0%. Six independent predictors were identified and integrated into the nomogram: hepatic encephalopathy, D-dimer levels, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), ALBI grade, and the systemic inflammation response index (SIRI). The nomogram exhibited exceptional discriminative ability, with AUC values of 0.907 and 0.862 in the training and validation cohorts, respectively, significantly surpassing the performance of the SOFA score (AUCs: 0.651 and 0.624). Calibration curves indicated excellent concordance between predicted and observed outcomes, while DCA confirmed a substantial clinical net benefit across a broad range of threshold probabilities.

Conclusion: We have successfully developed and validated a robust nomogram that utilizes routinely available immune-inflammatory-nutritional indicators to provide individualized risk estimation of 28-day mortality in sepsis patients with ACLF. This model represents an advanced prognostic instrument when compared to traditional scoring systems, with the potential to enable early detection of high-risk patients and inform individualized therapeutic interventions.

Objective: To assess the prognostic utility of the preoperative neutrophil percentage-to-albumin ratio (NPAR) for short-term complications and long-term survival in colorectal cancer patients receiving robot-assisted laparoscopic radical surgery.

Methods: This retrospective study included 230 patients with stage I-III colorectal cancer who underwent Da Vinci robot-assisted laparoscopic radical resection at the Department of Gastrointestinal Surgery, Second Xiangya Hospital of Central South University, between June 2016 and December 2024. Laboratory indicators were collected within 7 days prior to surgery, and NPAR was calculated. The optimal cutoff value of NPAR (14.75) was determined using restricted cubic spline (RCS) analysis and receiver operating characteristic (ROC) curve. Based on a cutoff value of 14.75, patients were categorized into high (≥14.75) and low (<14.75) NPAR groups. Multivariate logistic regression was employed to examine the relationship between NPAR levels and postoperative complications. Additionally, Kaplan-Meier survival analysis was conducted to evaluate its influence on overall survival (OS).

Results: A significant non-linear positive association was observed between NPAR and the risk of postoperative complications (P for non-linearity = 0.008). The high NPAR group exhibited a markedly higher incidence of complications (OR = 138.53, 95% CI: 12.79-1500.47, P < 0.001). Kaplan-Meier analysis demonstrated significantly reduced overall survival among patients with elevated NPAR (log-rank P = 6.2 × 10⁻⁷). Furthermore, subgroup analyses confirmed the consistent predictive performance of NPAR across diverse clinical subsets.

Conclusion: Elevated preoperative NPAR significantly predicts higher risks of complications and poorer survival following robotic surgery for colorectal cancer. As a straightforward and clinically applicable biomarker, it shows great promise for preoperative risk stratification and outcome evaluation, supporting its broader adoption in clinical practice.

Objective: Neutrophil extracellular traps (NETs) are involved in the pathogenesis of gouty arthritis (GA). This study aimed to investigate whether standardized extract of flavonoids from Smilax glabra Roxb. (SFSG) alleviates GA by targeting NETs formation and to elucidate its underlying mechanisms involving neutrophil-driven inflammation and signaling pathways.

Methods: SFSG's effects were evaluated in a monosodium urate (MSU)-induced GA model. Neutrophil depletion (via mAb 1A8 antibody) validated their pathogenic role. SFSG was administered for 7 days to assess joint swelling, histopathology (HE staining), neutrophil infiltration (immunohistochemistry), and inflammatory cytokines (IL-1β and IL-8, measured by ELISA). In MSU and PMA-stimulated neutrophils, SFSG (0-200 μg/mL, non-toxic by CCK8) was tested for NETs formation (immunofluorescence, transmission electron microscopy), oxidative stress (ROS), lactate dehydrogenase (LDH) activity, Raf/ERK signaling, and citrullinated histone H3 (CitH3) (Western blotting).

Results: Neutrophil depletion significantly alleviated MSU-induced joint inflammation, confirming neutrophils as key drivers of GA pathology. SFSG treatment dose-dependently suppressed MSU-induced joint inflammation in vivo. Notably, the high dose inhibited ankle swelling by ~66% (reducing it from 58.36% to 19.75%), matching the efficacy of colchicine. Concomitant reductions in neutrophil infiltration and IL-1β/IL-8 levels were also observed. Additionally, SFSG attenuated PADI4 and NOX2 gene expression. In vitro, SFSG inhibited NETs formation, ROS production, and LDH release while downregulating Raf/ERK signaling and CitH3 expression.

Conclusion: SFSG alleviates GA progression by targeting neutrophil-driven inflammation and NETs formation through suppression of Raf/ERK signaling and CitH3 expression, thereby demonstrating its potential as a phytotherapeutic agent for neutrophil-associated pathologies.

Objective: This study explored the therapeutic effects and mechanisms of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on postoperative ileus (POI) and their potential in preventing or treating POI.

Methods: A murine model of postoperative ileus (POI) and an in vitro macrophage inflammation model were employed. Analyses included the assessment of intestinal injury, motility, inflammatory cytokines, macrophage infiltration, and polarization. RNA sequencing implicated the JAK2/STAT3 pathway, which was validated through immunohistochemistry and Western blot. Subsequent STAT3 knockout and overexpression experiments in macrophages further elucidated the underlying mechanism.

Results: ω-3 PUFAs alleviated intestinal damage, restored motility, and reduced local pro-inflammatory cytokine levels in POI mice, along with reduced macrophage infiltration. In vitro, ω-3 PUFAs suppressed M1 polarization. RNA-seq implicated the JAK/STAT pathway, and further experiments confirmed that ω-3 PUFAs markedly suppressed the phosphorylation of JAK2, STAT3, and p65 in both macrophages and ileal tissue. Genetic manipulation of STAT3 established that ω-3 PUFAs attenuate inflammation primarily through modulating macrophage polarization.

Conclusion: ω-3 PUFAs alleviate POI by inhibiting the JAK2/STAT3 signaling pathway in macrophages, thereby suppressing their polarization toward the pro-inflammatory M1 phenotype and reducing local intestinal inflammation. These findings indicate that ω-3 PUFAs may be a promising prophylactic or therapeutic agent for POI.

Purpose: Predicting postoperative nasal polyp recurrence (PR) remains challenging because existing approaches rely on single clinical samples and thus fail to capture the complex, multi-compartment biology of the disease. This study aims to determine whether nasal fluid (NF) and serum protein concordance, reflecting the degree of coupling between local nasal and systemic inflammation, provides a more integrated prognostic signature for PR.

Patients and methods: Using the proximity extension assay (PEA), we quantified 92 proteins in NF and serum from 54 nasal polyps (NPs) patients (including 18 PR and 36 non-PR). In this prospective study, with PR assessed after a minimum follow-up of 6 months, NF-serum protein concordance was comprehensively assessed for associations with disease features and PR. Kaplan-Meier analysis and univariate Cox regression identified PR-predictive biomarkers, validated via bulk RNA-seq, single-cell RNA-seq (scRNAseq), immunofluorescence, and public database analysis.

Results: Proteomic analysis of NF and serum revealed distinct protein profiles between PR and non-PR groups. Elevated NF-serum concordance was observed in current smokers and asthmatics, and positively correlated with eosinophil counts (r=0.26), pre-surgery Lund-Mackay (LM) scores (r=0.34), nasal VAS (r=0.26) and SNOT-22 scores (r=0.46) (Pearson's test, all P<0.05). Survival analysis demonstrated that higher NF-serum concordance predicted increased PR risk (HR=7.9, 95% CI=2.4-25.6, P<0.001). Univariate Cox regression identified leukemia inhibitory factor receptor (LIFR) as a novel PR biomarker (HR=2.1, 95% CI=1-4.2, P<0.05). Bulk RNA-seq confirmed LIFR upregulation in PR (P<0.05), while scRNA-seq localized predominant LIFR expression to CRSwNP endothelial cells. Immunofluorescence verified LIFR-CD31 colocalization with stronger LIFR signals in PR (P<0.05). Transcriptional (Twist1/NR2F2) and post-transcriptional (miRNA-mediated) regulatory mechanisms were implicated in LIFR-driven pathogenesis.

Conclusion: Our study first investigated NF-serum proteomic concordance as a predictor of PR and demonstrated the potential of integrated multi-compartment analysis for predicting recurrence.

Introduction: Allergic contact dermatitis (ACD) is a common T cell-mediated delayed hypersensitivity reaction characterized by chronic skin inflammation. Coral calcium carried hydrogen (CCH), a novel solid-phase hydrogen carrier, enables sustained hydrogen release and demonstrates superior stability compared to conventional hydrogen delivery methods. However, its therapeutic potential in ACD remains unexplored.

Methods: ACD was induced in female BALB/c mice (8-week-old) using 2,4-dinitrochlorobenzene (DNCB). Mice were divided into four groups: Control, DNCB model, CCH-treated (oral CCH), and dexamethasone (DEX)-treated (oral DEX). Disease severity was assessed through dermatitis scores, scratching frequency, spleen coefficient, and histopathological analysis. Serum cytokine levels and peripheral blood immune cell profiles were evaluated to elucidate the underlying mechanisms.

Results: CCH treatment significantly ameliorated ACD symptoms, comparable to DEX, as evidenced by reduced dermatitis scores, scratching behavior, and spleen enlargement. Histologically, CCH promoted ulcer healing and more effectively suppressed epidermal hyperplasia and skin inflammation than DEX. Mechanistically, CCH selectively reduced serum IgE and IL-17 levels while decreasing lymphocyte counts and proportions. In contrast, DEX primarily inhibited monocytes and neutrophils.

Conclusion: CCH exerts its therapeutic effects by modulating lymphocyte-mediated immune responses and suppressing pro-inflammatory cytokines, offering a promising therapeutic alternative with efficacy comparable to glucocorticoids.