Journal of Inflammation Research最新文献

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, lacks effective treatments targeting its pervasive immune dysregulation. Despite growing interest in neuroimmune interactions, there remains a fragmented understanding of how distinct brain regions integrate peripheral immune signals and orchestrate systemic immune responses in sepsis. Emerging evidence highlights the brain as a master regulator of systemic immunity in sepsis through the neuro-immune-endocrine network. This review summarizes recent advances in understanding how distinct brain regions, including the hypothalamus, brainstem, cortex and cerebellum, sense peripheral inflammation and feedback-regulate systemic immune responses via dedicated neural circuits, neurotransmitters, and autonomic outputs. We also highlight the therapeutic potential of neuromodulation techniques designed to target these central circuits and discuss their implications for developing future precision medicine strategies in sepsis management.

Background:  To elucidate the therapeutic mechanism of polydatin against lung ischemia-reperfusion injury (LIRI), this study adopted an integrated strategy combining network pharmacology with experimental verification.

Methods: Potential targets of polydatin were retrieved from TCMSP, PubChem, SwissTargetPrediction, and Herb. LIRI-related targets were were collected from GeneCards, OMIM, and TTD. Venn analysis was used to identify common targets. A protein-protein interaction (PPI) network was constructed using STRING and analyzed with Cytoscape (CytoNCA plugin).Enrichment analyses (GO/KEGG) were performed to identify key pathways. For experimental validation, an in vitro LIRI model was established in human alveolar epithelial A549 cells undergoing hypoxia/reoxygenation (H/R). The protective effects and associated mechanisms of polydatin were then evaluated through multiple assays, including CCK-8 assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), ELISA, TUNEL staining, and reactive oxygen species (ROS) detection. Meanwhile, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were quantified.

Results: Network pharmacology identified 199 potential common targets, with top 10 core ones including AKT1, IL6, TNF, ALB, TP53, INS, IL1B, STAT3, EGFR, and BCL2. GO/KEGG analyses indicated polydatin's protective effects may relate to inflammatory response modulation, apoptotic signaling regulation, and NF-κB pathway involvement. Experimentally, polydatin enhanced H/R-injured A549 cell viability, reduced apoptosis, increased SOD activity, and decreased MDA, ROS, and inflammatory cytokines (IL-6, IL-1β, TNF-α). It also upregulated AKT1 and ALB mRNA and downregulated TP53 mRNA.

Conclusion: Collectively, our results indicate that polydatin alleviates LIRI by attenuating oxidative stress, inflammation, and apoptosis, likely via multi-target and multi-pathway mechanisms centered on key hubs such as AKT1, IL6, TNF, ALB, TP53, and the NF-κB pathway. This study provides a theoretical and experimental basis for further exploration of polydatin as a potential LIRI treatment.

Aim of study: The objective of this research is to clarify the mechanism by which FZJDF mitigates lipopolysaccharide (LPS)- ALI through the enhancement of short-chain fatty acids (SCFAs) production by Clostridium butyricum (C. butyricum), and the modulation of the gut microbiota-gut-lung axis.

Materials and methods: The mice were treated with FZJDF for 7 days and then treated with LPS. The therapeutic efficacy of FZJDF against LPS-induced ALI was evaluated through lung-to-weight ratio, Inflammatory factor, pathological changes. Additionally, the intestinal barrier function was evaluated by analyzing tight junction protein expression levels. 16S rRNA gene sequencing was employed to monitor alterations in the intestinal microbiome and pulmonary microbiota, while gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography (UPLC) were utilized to quantify the concentrations of SCFAs. Ultimately, the necessity of C. butyricum for FZJDF's therapeutic influence was confirmed through antibiotic-mediated gut microbiota depletion.

Results: FZJDF significantly decreased lung-to-weight ratio and reducing inflammatory cell infiltration of neutrophils. Furthermore, it significantly elevated the expression levels of tight junction proteins. It is plausible that FZJDF may improve intestinal and lung microecological imbalance and stimulate the synthesis of SCFAs. Notably, we determine C. butyricum as the crucial bacterium for the role of FZJDF in gut barrier repair and suppression of lung inflammation in ALI mice. The use of antibiotics led to the repair of the intestinal barrier and a failure in SCFAs production, whereas C. butyricum colonization restores the therapeutic effect of FZJDF in ALI mice, further confirming that FZJDF attenuates ALI.

Conclusion: Our results imply that FZJDF could exert its palliative effect in ALI by regulating the intestinal microbiota to increase the production of SCFAs, which in turn inhibits neutrophil-mediated inflammatory responses. These findings support microbiota-targeted traditional medicine as a translational strategy for acute lung injury.

Background: Non-atherosclerotic vascular aging (NAVA) contributes to cardiovascular risk through progressive arterial stiffening and endothelial dysfunction. Colchicine, best known for anti-inflammatory activity, has been proposed to protect vascular structure and function. We evaluated whether chronic colchicine mitigates NAVA in a smooth-muscle-specific ERCC1 knockout (SMC-KO) mouse model of DNA-damage-driven vascular aging.

Methods: We performed experiments in the SMC-KO treated with colchicine (0.1mg/kg/day) or vehicle from the age of 10 to 22 weeks. Endothelial function was assessed by acetylcholine-induced vasorelaxation, and vascular structure by pulse-wave velocity (PWV), carotid intima-media thickness (cIMT), and elastin integrity.

Results: SMC-KO mice developed increased arterial stiffness and impaired acetylcholine-mediated relaxation. Chronic colchicine significantly (p<0.01) lowered PWV, preserved elastin architecture, and improved endothelium-dependent relaxation, while sodium-nitroprusside responses and systemic cytokine levels remained unchanged.

Conclusion: Chronic colchicine treatment preserves endothelial function and vascular elastin structure and reduces arterial stiffness in a DNA-damage-driven model of non-atherosclerotic vascular aging. These findings highlight colchicine's pleiotropic vascular benefits beyond anti-inflammation, supporting its potential repurposing for primary prevention in vascular aging and cardiovascular health or the development of colchicine-mimicking drugs with greater selectivity and improved safety profiles.

Purpose: Intracranial hypertension is the most common symptom of cerebral venous sinus thrombosis. Recent studies have indicated that both the coagulation and inflammation systems play roles in the occurrence and development of cerebral venous sinus thrombosis. Therefore, this study aimed to explore the individual and combined effects of coagulation-related biomarker [fibrinogen (FIB)] and inflammation-related biomarker [C-reactive Protein (CRP)] in predicting intracranial hypertension.

Patients and methods: We retrospectively and consecutively included 157 cerebral venous sinus thrombosis patients, who were divided into four groups according to the cut-offs of CRP and FIB by the receiver operating characteristics curves: low CRP low FIB, high CRP low FIB, low CRP high FIB and high CRP high FIB. Logistic regression models were used to compute the odds ratios and 95% confidence intervals for intracranial hypertension across the four subgroups.

Results: Cerebral venous sinus thrombosis patients with intracranial hypertension had much higher CRP and FIB levels than those without intracranial hypertension did (all P<0.05). After adjusted by gender, age, modified Rankin scale, duration, headache, seizure, smoking, history of thrombosis and other risk factors, white blood cell, systemic immune-inflammation index and estimated glomerular filtration rate, patients in high CRP high FIB group were 5.286 (95% CI: 2.04-13.701, P=0.001) times more frequent to experience intracranial hypertension than those in low CRP low FIB group did. The addition of CRP and FIB to the basic model significantly improved discriminatory power for intracranial hypertension, as area under the curve increased from 0.692 (95% CI: 0.609-0.775, P<0.001) to 0.767 (95% CI: 0.692-0.843, P<0.001).

Conclusion: Higher levels of both CRP and FIB are associated with an increased risk of intracranial hypertension following cerebral venous sinus thrombosis. The combination of CRP and FIB has a better predictive ability for intracranial hypertension in patients with cerebral venous sinus thrombosis than either CRP or FIB alone.

Objective: This study aimed to develop a prognostic model for patients with sepsis complicated by autoimmune diseases using machine learning methods and validate the model.

Methods: Data on patients with sepsis and autoimmune diseases were extracted from the MIMIC-IV database. Participants were randomly divided into training set and validation set according to the ratio of 7:3. The predictors were selected by using LASSO regression analysis and the Boruta algorithm which affect the 28-day prognosis of patients. A nomogram was developed based on independent risk factors identified by logistic regression for 28-day prognosis and was internally and externally validated using calibration curves and DCA. Based on nomogram scores, patients were stratified into high- and low-score groups, with KM analysis demonstrating significant differences in mortality between the cohorts.

Results: A total of 1,481 patients from the MIMIC-IV database met inclusion criteria and an external validation set included 57 patients from the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University. Ten overlapping predictors (Age, Gender, BMI, WBC, BUN, PT, APTT, history of cerebrovascular disease, history of liver disease, and CRRT) were identified by LASSO and Boruta algorithms and were subsequently confirmed as statistically significant independent risk factors through logistic regression. The prediction model built by the ten predictors showed superior predictive performance compared to the SOFA score in training (AUC=0.772), internal validation (AUC=0.771), and external validation cohorts (AUC=0.787). Hosmer-Lemeshow tests and calibration curves indicated strong agreement between predicted outcomes and actual observations across all cohorts, and DCA suggested significant clinical utility. The KM curve shows that the mortality rate of the high-score group is significantly higher than that of the low-score group.

Conclusion: A prognostic model for predicting 28-day mortality in sepsis patients with autoimmune diseases demonstrated robust predictive performance and clinical applicability upon internal and external validation.

Background: Pouchitis is the most common complication following ileal pouch-anal anastomosis for ulcerative colitis. Antibiotics remain the cornerstone of therapy for acute and chronic antibiotic dependent pouchitis, though evidence guiding their optimal use is limited.

Material and methods: A comprehensive literature search of PubMed, MEDLINE, Embase, and Google Scholar was conducted from database inception through October 2025 to identify studies evaluating antibiotic therapy for acute pouchitis. Eligible studies included randomized controlled trials, cohort studies, and observational series reporting clinical, endoscopic, or histologic outcomes. Data were extracted from 10 studies on study design, antibiotic regimen, efficacy, safety, and recurrence.

Results: Data on the optimal selection of antibiotics for pouchitis is limited. Ciprofloxacin and metronidazole are the most extensively studied and commonly prescribed antibiotics. In a randomized clinical trial, ciprofloxacin demonstrated superior efficacy and tolerability compared with metronidazole. Rifaximin and vancomycin show potential benefit in selected cases.

Conclusion: Antibiotic therapy provides rapid and effective symptom control in most patients with acute pouchitis. Ciprofloxacin should be considered first-line, with metronidazole or combination therapy reserved for non-responders.

Objective: We aimed to explore the correlation between the inflammatory burden index (IBI) and the development of sepsis in critically ill patients with extensive burns.

Methods: This retrospective cohort study included extensively burned patients who were admitted to the First Affiliated Hospital of Army Medical University from January 1, 2014, to December 31, 2023. These patients were divided into two groups based on the presence or absence of sepsis within 28 days after burns (the sepsis group and the nonsepsis group). Furthermore, the patients' basic information, burn severity, blood parameters in the early post-burn period (within 48h after burns), mechanical ventilation, ICU length of stay and the outcome were collected. Independent samples Mann-Whitney U-tests and chi-square tests were performed with respect to the indicators between the groups. Univariate and multivariate logistic regression analyses were conducted on the basis of indicators that exhibited statistically significant differences to identify independent risk factors pertaining to sepsis occurrence. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of indicators such as the IBI and determine optimal cutoff values.

Results: A total of 178 critically ill patients with extensive burns were enrolled in this study. Significant differences were observed in the total body surface area (TBSA), burn index (BI), C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR), IBI, revised Baux score (rBaux), mechanical ventilation and ICU length of stay between the sepsis group and the nonsepsis group (P <0.05). Logistic regression analysis identified the IBI in the early post-burn period as an independent risk factor for sepsis (P <0.05), and its predictive performance surpassed that of the CRP level. The optimal cut-off value of the IBI was 695.01, and combination of the IBI with the BI led to further improvements in predictive performance.

Conclusion: The IBI in the early post-burn period offers good predictive value for the development of sepsis in critically ill patients with extensive burns, which is helpful for formulating treatment strategies, including early surgical intervention, antibiotic application, and early enteral nutrition, etc. to reduce the incidence of sepsis.