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.

Purpose: Mycoplasma pneumoniae (MP)-segmental/lobar pneumonia represents a growing proportion of Mycoplasma pneumoniae pneumonia (MPP) in children. We aimed to identify the clinical characteristics and risk factors for MP-segmental/lobar pneumonia in children to facilitate early diagnosis and intervention.

Methods: We conducted a retrospective cohort study at a tertiary pediatric center in Chongqing, China, involving 1406 children hospitalized for MPP from January to December 2023. Based on imaging findings, patients were categorized into MP-ordinary pneumonia group and MP-segmental/lobar pneumonia group. Clinical data were compared, and univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The predictive performance was assessed using receiver operating characteristic (ROC) curves.

Results: The MP-segmental/lobar pneumonia group exhibited a significantly longer duration of pre-admission fever, longer hospital stays, and higher rates of bronchoscopy, respiratory failure, and pulmonary complications. (all P < 0.05). Logistic regression analysis identified the following independent risk factors for MP-segmental/lobar pneumonia: sex, days with fever prior to admission, C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), platelet-lymphocyte ratio (PLR), and platelet (PLT). ROC curve analysis identified five primary predictive indicators (days with fever prior to admission >5.5 days, D-dimer >0.539mg/L, CRP >11.33mg/L, LDH >309.5U/L, PLR >155.815) and two secondary predictive indicators (PLT >340.5×10⁹/L, female sex) based on predicted efficacy. The combined use of these seven indicators further enhanced predictive performance (AUC = 0.741, 95% CI: 0.715-0.766).

Conclusion: MP-segmental/lobar pneumonia exhibits more pronounced clinical symptoms and elevated inflammatory markers. The seven clinical indicators-days with fever prior to admission, CRP, D-dimer, LDH, PLR, PLT and female sex-serve as useful predictive markers for segmental/lobar pneumonia caused by MP. These indicators aid clinicians in the early diagnosis and intervention of MPP, thereby preventing its progression to segmental/lobar pneumonia.

Purpose: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Delayed diagnosis and treatment elevate the risk of coronary artery complications. This study aims to investigate metabolic disorders associated with its potential pathophysiology and to explore novel diagnostic biomarkers.

Patients and methods: Untargeted metabolomics was used to identify significantly dysregulated metabolic pathways in patients with KD. Targeted lipidomic analysis was performed to detect differentially expressed lipid metabolites. Candidate plasma biomarkers were quantified using ELISA. Single-cell RNA sequencing was used to analyze the expression of lipid metabolism-related genes and cellular heterogeneity.

Results: Sphingolipid metabolism was confirmed to be dysregulated in patients with KD. Twelve differentially expressed lipid species were identified: 20:5-carnitine, sphingomyelin 32:2;O2, ceramide d16:0/24:0, glucosylceramide d18:1/26:0, lysophosphatidylcholine (LPC) O-16:0, LPC 17:0, LPC 18:0, and phosphatidylcholine (PC) 32:2, PC 36:3, PC 40:3, PC 40:4, and PC 40:7. ELISA validation confirmed the lipidomics-identified alterations in LPC. As a diagnostic biomarker, LPC achieved an area under the curve (AUC) of 0.768, with 64.7% sensitivity and 88.2% specificity. Single-cell RNA sequencing data revealed a marked accumulation of monocytes in KD, along with upregulated expression of lipid metabolism-associated genes. Notably, the expression levels of inflammatory genes were altered along with those of LPC degradation-related genes in monocytes from patients with KD.

Conclusion: This study demonstrated significant dysregulation of lipid metabolism in KD, potentially driven by inflammatory responses in monocytes. LPC has emerged as a potential biomarker of KD and provides new insights into its early diagnosis.

Background: Dupilumab is generally considered safe and effective for treating bullous pemphigoid (BP). We report the first case of recurrent hypoperfusion-induced cerebral infarction temporally associated with dupilumab administration in an elderly patient.

Case presentation: A 96-year-old male with BP, type 2 diabetes, and a history of stroke developed acute hypotension, depressed consciousness, and reduced oral intake within 24-72 hours after three separate dupilumab injections. Initial neuroimaging revealed watershed infarcts. Proactive volume expansion during one administration successfully averted new infarction, whereas lack of prophylactic hydration on another occasion precipitated a transient ischemic attack (TIA).

Observations & analysis: A significant temporal association was documented. The Naranjo Adverse Drug Reaction Probability Scale score was 8, indicating a probable association. The patient's advanced age, compromised cerebrovascular reserve, and mandatory discontinuation of antithrombotics created a hypervulnerable substrate. The hypotensive mechanism is hypothesized to involve IL-4/IL-13 pathway blockade, potentially disrupting endothelial function and vascular tone regulation.

Conclusion & clinical implications: This case report describes a potential, albeit rare, serious adverse effect associated with dupilumab in an elderly individual at high risk. Based on this single experience, we suggest at least 72 hours of post-injection blood pressure monitoring for high-risk patients. Management could include administering prophylactic fluid replacement based on the patient's actual condition and critically reassessing concomitant antihypertensive regimens. This finding highlights the need for heightened clinical vigilance and suggests that the drug's safety profile in advanced-age patients may warrant further investigation.

Background: Lumbar infectious spondylodiscitis is a severe spinal condition traditionally managed with antibiotics, though some patients require surgical intervention. The heterogeneity in infection sites, causative pathogens, and clinical presentations leads to significant variability in surgical approaches, and optimal surgical strategies remain controversial. This study aims to evaluate the feasibility, safety, and preliminary efficacy of endoscopic retroperitoneal debridement combined with posterior percutaneous pedicle screw fixation for the treatment of lumbar infectious spondylodiscitis.

Methods: This retrospective study analyzed patients diagnosed with lumbar infectious spondylodiscitis and treated with endoscopic retroperitoneal debridement at our institution from June 2023 to June 2024. Baseline patient characteristics, operative time, intraoperative blood loss, postoperative lesion clearance, changes in inflammatory markers (eg, C-reactive protein[CRP] and erythrocyte sedimentation rate[ESR]), complication rates, Visual analog scale (VAS) scores for back pain, Oswestry Disability Index (ODI) scores, kyphotic angle changes at the infected level, and radiological follow-up outcomes were recorded.

Results: Of the 30 patients, 28 (28/30, 93.33%) showed improvement in clinical symptoms. During follow-up, all patients demonstrated significant improvements in VAS scores and ODI scores compared to preoperative values (p<0.05). At the final follow-up, all patients exhibited a kyphotic angle change of less than 8°, and no spinal instability was observed. Computed tomography (CT) at the 12-month follow-up demonstrated intervertebral bone fusion in 27 cases (27/29, 93.10%). Postoperative inflammatory markers showed improved compared with preoperative levels (p<0.001). No infection recurrence or serious surgery-related complications were observed during the postoperative follow-up period.

Conclusion: Endoscopic retroperitoneal debridement combined with posterior percutaneous pedicle screw fixation appears to be a safe and effective minimally invasive approach for treating lumbar infectious spondylodiscitis. However, long-term efficacy requires further validation through prospective studies with larger sample sizes and extended follow-up periods.

Background: Lactylation has emerged as a novel post-translational modification, and genes linked to both lactylation and macrophage polarization may play a role in inflammatory bowel disease (IBD). However, the connection between these genes and TNF-α inhibitor response in IBD remained unclear.

Methods: This study used bioinformatic tools including weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, and machine learning algorithms to identify correlations between lactylation and macrophage-related genes and TNF-α inhibitor response in IBD.

Results: Significant differential expression of MNDA, CALD1, RECQL, and RBM10 was identified between the remission and non-remission groups in the pre-treatment data. Based on these findings, we established a predictive model for TNF-α inhibitor response, achieving an ROC performance with training AUC reaching 0.894 and validation AUC reaching 0.883. Furthermore, MNDA, LGALS1, ZYX, ADAR, and WAS were significantly elevated in the non-remission group 4-6 weeks after initial treatment. Immune infiltration analysis further indicated strong correlations between hub genes expression and immune cell proportions. In addition, GSEA identified signaling pathways associated with TNF-α inhibitor response. To validate these observations, TNF-α inhibitor was administered to mice with TNBS-induced colitis, and the expression of hub genes was confirmed by RT-qPCR. Importantly, combination therapy with lactate supplementation enhanced the efficacy of TNF-α inhibitor treatment compared with monotherapy. Finally, analysis of lactylation levels indicated intergroup differences associated with TNF-α inhibitor treatment in IBD.

Conclusion: Overall, we identified lactylation and macrophage-related genes as potential biomarkers for TNF-α inhibitor response. Lactate supplementation was found to enhance the efficacy of TNF-α inhibitor based on animal experimental validation. Nevertheless, the findings were based on secondary analyses of public datasets, and the animal experiments remained preliminary. Further studies should be conducted to validate these findings and explore the molecular pathways involved.

Purpose: Atrial fibrillation (AF) is a leading cause of stroke, heart failure, and mortality, yet the molecular mechanisms remain incompletely defined.

Patients and methods: We integrated bulk transcriptomes from GEO with weighted gene co-expression network analysis, consensus clustering, and a 12-algorithm machine-learning pipeline (66 model combinations) to map programmed cell death (PCD) pathways and pinpoint diagnostic genes. Immune infiltration was profiled by CIBERSORT, xCell, and ssGSEA. Hub-gene expression was validated in an HL-1 atrial pacing model and in peripheral blood mononuclear cells (PBMCs) from patients with persistent AF.

Results: Four hub genes-SGPL1, NPC2, PTGDS, and RCAN1-were identified and incorporated into a nomogram and a PCD-based risk score (PCDscore). The nomogram showed robust discrimination in the training cohort and two independent validation datasets. Patients with a high PCDscore exhibited markedly increased immune-cell infiltration and dysregulated immune modulators, with macrophages consistently enriched across algorithms. qRT-PCR confirmed up-regulation of SGPL1, NPC2, and RCAN1 and down-regulation of PTGDS in AF cell models; NPC2 and SGPL1 were further elevated in PBMCs from AF patients.

Conclusion: Our integrative framework reveals PCD-linked remodeling in AF and nominates SGPL1, NPC2, PTGDS, and RCAN1 as candidate diagnostic biomarkers, providing a PCD-based nomogram and risk score that may inform patient stratification and hypothesis-generating targeted interventions.