Journal of Inflammation Research最新文献

Objective: Chronic unresolved inflammation is a core driver of diabetic kidney disease (DKD) progression, with gut microbiota dysbiosis and metabolite imbalance (via gut-kidney axis) as key pathogenic triggers. This review systematically elucidates the pathological link between gut microbiota-metabolite-axis dysfunction and DKD-related inflammation (centered on NF-κB/NLRP3 pathways) and summarizes multi-target intervention strategies-including traditional Chinese medicine (TCM), SGLT2 inhibitors, probiotics/prebiotics-targeting this axis.

Methods: Literature search was conducted on PubMed using keywords ["Gut microbiota" or "Gut microflora" or "Gut microbiota metabolites"], ["Diabetic kidney disease" or "Diabetic nephropathy" or "DKD"], ["immune regulation"], ["intestinal barrier"], [inflammation"], ["Traditional Chinese Medicine" or "TCM"], without date restrictions. Articles that do not meet the requirements are excluded.

Results: Gut microbiota dysbiosis in DKD is characterized by reduced SCFA-producing bacteria (Ruminococcaceae, Lachnospiraceae) and enriched pathogenic Proteobacteria, leading to metabolite imbalance: insufficient beneficial metabolites (SCFAs, IPA) and accumulation of harmful metabolites (TMAO, phenyl sulfate, BCAAs). This imbalance impairs intestinal barrier (ZO-1/Occludin downregulation), promotes endotoxin (LPS) translocation, and activates NF-κB (p65 phosphorylation) and NLRP3 inflammasome (NLRP3/ASC/caspase-1 complex), exacerbating renal inflammation via pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). Intervention strategies (including TCM) suppress this cascade: TCM (eg, Astragalus membranaceus, Xiaoyaosan) reshapes microbiota, strengthens intestinal barrier, and inhibits NF-κB/NLRP3; SGLT2 inhibitors and probiotics/prebiotics complement via SCFA elevation and TMAO reduction. Clinically, these interventions lower UACR, improve eGFR, and correlate with reduced serum IL-1β/TNF-α.

Conclusion: Gut microbiota-metabolite-intestinal barrier axis dysfunction is a pivotal pathological mechanism of DKD inflammation, mediated by NF-κB/NLRP3 pathways. Multi-pronged interventions targeting this axis effectively resolve inflammation, providing promising therapeutic approaches for DKD.

Introduction: Bone marrow mesenchymal stem cells (BMSCs) are effective in treating a variety of chronic pain conditions, including bone cancer pain (BCP); however, the underlying mechanism remains unclear. Microglia are the main cells involved in hyperalgesia and maintenance of BCP. Hence, their activation and polarization are key signs of neuroinflammation. The Toll-like receptor 4/ nuclear factor-kappa B (TLR4/ NF-κB) signaling pathway plays an essential role in microglial activation and neuroinflammation. Nonetheless, whether BMSCs can be used to treat BCP by regulating the TLR4/NF-κB signaling pathway and microglial activation requires further research. In this study, a series of experiments were conducted to explore the specific mechanisms underlying the beneficial effects of BMSCs on BCP.

Methods: Initially, this study demonstrated the therapeutic effect of BMSCs on BCP through behavioral and pathological evaluations. Subsequently, the effects of BMSCs on microglia and related mechanisms were detected by Western blotting, immunofluorescence, ELISA, and RNA sequencing. Finally, based on the microglia BV2-BMSCs co-culture model, the mechanism of BMSCs regulation of microglia was further verified through in vitro experiments.

Results: Intrathecal injection of BMSCs was found to alleviate BCP by inhibiting the activation of microglia in the spinal dorsal horn and the release of cytokines, which involves the regulation of the TLR4/NF-kB signaling pathway. In addition, BMSCs inhibited the nuclear transport of NF-κB in vitro.

Discussion: These results revealed that the TLR4/NF-κB signaling pathway in microglia is one of the targets of BMSCs in BCP treatment.

Allergic bronchopulmonary aspergillosis (ABPA) is a severe asthma endotype arising from dysregulated immune responses to Aspergillus fumigatus in susceptible individuals. ABPA is characterized by exaggerated type 2 immune responses, markedly elevated serum total IgE and A. fumigatus-specific IgE and IgG levels, peripheral blood eosinophilia, and imaging abnormalities, including bronchiectasis and mucus impaction. Genetic predisposition involving HLA genotypes and immune-related polymorphisms contributes to disease susceptibility. The 2024 International Society of Human and Animal Mycology guidelines provide standardized criteria that integrate clinical, immunological, and radiological parameters to identify ABPA and distinguish it from overlapping diagnoses. Management employs a dual approach: anti-inflammatory therapy with systemic corticosteroids targets dysregulated immunity, while antifungal therapy with triazoles reduces airway fungal burden. The relapsing-remitting disease course necessitates systematic monitoring using clinical assessment, total IgE levels, and serial imaging to detect relapses, distinguish them from asthma exacerbations or infections, and optimize treatment intensity. Despite substantial progress in understanding the pathobiology of ABPA, high-quality evidence for optimal management strategies remains limited. Future research should focus on precision medicine approaches, novel biomarkers, and inhaled antifungal therapies to improve outcomes in this severe asthma phenotype. This review provides clinicians with comprehensive information on the pathobiology, diagnosis, classification, and evidence-based management strategies for ABPA, aiming to improve outcomes for patients with this severe asthma endotype.

Purpose: Cathepsin C (CTSC) has been identified as a key pathogenic gene in chronic rhinosinusitis. This study aimed to investigate the specific function and subcellular localization of CTSC within the nasal mucosal epithelium.

Patients and methods: A total of 34 patients with eosinophilic chronic rhinosinusitis with nasal polyps (eNP), 32 with non-eosinophilic chronic rhinosinusitis with nasal polyps (neNP), and 16 control subjects were enrolled. Airway epithelial morphology was examined by scanning electron microscopy. The expression, localization, and function of CTSC in epithelial cells were assessed using single-cell RNA sequencing (scRNA-seq), immunohistochemistry, quantitative real-time PCR, Western blot, and an siRNA-mediated knockdown approach in an IL-4/IL-13-stimulated 16HBE cell line model.

Results: scRNA-seq revealed that CTSC was primarily localized to goblet cells and basal cells within the nasal epithelium, with its expression significantly upregulated in eNP patients compared with those in control subjects and neNP. These findings were confirmed at both the RNA and protein levels in clinical tissue samples. CTSC mRNA expression showed a significant positive correlation with the expression of T-helper 2 cytokines, including IL-4 and IL-13. In vitro experiments demonstrated that CTSC expression was induced in 16HBE cells upon IL-4/IL-13 stimulation. siRNA-mediated knockdown of CTSC led to pronounced suppression of IL-4/IL-13-induced release of CCL26, IL-25, and TNF-α, underscoring its functional involvement in inflammatory responses.

Conclusion: This study identifies CTSC as a novel regulator of type 2 inflammation like eNP. It is specifically upregulated in nasal epithelial goblet and basal cells, highlighting its potential as a therapeutic target for airway diseases.

Corticosteroids have long been a cornerstone in the management of many pediatric neurological disorders. However, their broad immunomodulatory effects raise concerns in the era of precision medicine, where more targeted approaches are increasingly favored, warranting a critical reappraisal of their roles in pediatric neurology. Of particular importance is the possibility that corticosteroids may potentiate components of the innate immune responses and thereby exacerbate neuroinflammation. Accordingly, disease-specific immunopathogenesis should be considered in therapeutic decision-making. The potential for adverse effects, especially with long-term use, remains a major consideration and underscores the need for careful risk-benefit analysis. Several therapeutic innovations, including selective glucocorticoid receptor modulators (such as vamorolone) and intra-erythrocyte dexamethasone delivery, have shown promising safety profiles in Duchenne muscular dystrophy and ataxia telangiectasia, respectively. Beyond the well-established role of corticosteroids in infantile epileptic spasms syndrome, recent evidence suggests that corticosteroids may benefit a substantial proportion of patients with various forms of epilepsy that are resistant to conventional antiseizure medications. Further research is warranted to define the optimal use of corticosteroids with respect to dosing, formulation, timing, and route of administration in various pediatric neurological disorders.

Background: The Platelet-to-HDL-cholesterol ratio (PHR), an emerging inflammatory biomarker, shows promise as a predictor in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). However, the association between PHR and glycemic metabolism status and their combined effects on the prognosis of CAD patients undergoing percutaneous coronary intervention (PCI) remains unclear.

Methods: A total of 31,761 CAD patients hospitalized for PCI were included. The primary endpoint was defined as major adverse cardiovascular events (MACEs). According to the median PHR levels, patients were grouped into higher levels of PHR (PHR-H) and lower levels of PHR (PHR-L) and further divided by glycemic status into four groups: PHR-H/T2DM, PHR-H/Non-T2DM, PHR-L/T2DM, PHR-L/Non-T2DM.

Results: During the 1-year follow-up, 2258 (7.1%) MACEs occurred. Elevated PHR conferred 17% excess risk for MACEs. A 1-unit increase in LnPHR was associated with a 26% increased risk of MACEs in the T2DM cohort, and a 27% increase of MACEs risks in the non-T2DM cohort. Compared to those in PHR-H/T2DM group, patients in PHR-L/T2DM, PHR-H/Non-T2DM, PHR-L/Non-T2DM had significantly decreased risk of MACEs [adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.73-0.96, P =0.009; aHR: 0.81, 95% CI: 0.69-0.95, P =0.009; aHR: 0.70, 95% CI: 0.60-0.83, P <0.001; respectively]. Cox regression analysis also indicated the highest risk of MACEs among patients in PHR-H/T2DM group than in other groups (P for trend <0.001). Restricted cubic spline analyses revealed positive linear associations of PHR with MACEs, all-cause death, and unplanned target vessel revascularization, while a significant non-linear relationship between PHR and myocardial infarction. Additionally, subgroup analysis indicated consistent effects on MACEs within diverse subsets.

Conclusion: Elevated PHR levels combined with T2DM were associated with worse clinical outcomes after PCI at 1-year follow-up. The PHR may serve as a valuable predictor for identifying high-risk patients post-PCI, particularly in diabetic cohorts.

Purpose: Recurrence of atrial fibrillation (AF) following catheter ablation (CA) is a common clinical challenge in AF management. Chronic inflammation plays a crucial role in the mechanism of AF recurrence. Although preliminary studies have explored the predictive value of composite inflammatory markers for AF recurrence, there remains a notable lack of research that directly compares multiple composite markers simultaneously. This study aims to investigate and compare the associations between nine composite inflammatory markers and the risk of AF recurrence after CA in patients with AF.

Patients and methods: This study prospectively included 744 AF patients who underwent their first CA at the Second Affiliated Hospital of Xi'an Jiaotong University between October 2017 and July 2024.We calculated nine composite inflammatory markers from pre-procedure peripheral blood cell counts. After adjusting for confounders, Cox regression, restricted cubic splines (RCS), and receiver operating characteristic (ROC) curves assessed their association with AF recurrence. Sensitivity analysis verified result robustness.

Results: Higher levels of the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Systemic Immune-Inflammation Response Index (SIRI), and Pan-Immune-Inflammation Value (PIV) were significantly associated with increased recurrence risk. After full model adjustment, Q4 vs Q1 HRs [95% CIs] were: SII 1.88 (1.23-2.88), NLR 1.85 (1.21-2.84), SIRI 2.03 (1.31-3.14), PIV 1.58 (1.06-2.38), with risk rising as indices increased. The Neutrophil-to-Platelet Ratio (NPR) Q3 risk was higher than Q1 (HR=1.58; 95% CI:1.07-2.32). In terms of prognostic predictive efficacy, NLR demonstrated the best performance among the inflammatory indicators (AUC: 0.62). Sensitivity analysis confirmed each index's robustness.

Conclusion: The SII, NLR, SIRI, NPR, and PIV may serve as valuable biomarkers for AF recurrence, among which NLR exhibits superior predictive capability compared to the other indices. These markers should be considered in clinical risk stratification and hold promise for providing new strategies and directions to reduce the recurrence rate.

Purpose: While melatonin is known to suppress pyroptosis in various cell types, its role and mechanisms in alveolar epithelial cells are not fully understood. Using lipopolysaccharide (LPS)-treated human pulmonary alveolar epithelial cells (HPAEpiC) as an in vitro model, this study aimed to investigate the anti-pyroptotic mechanism of melatonin.

Methods: HPAEpiC cells were treated with LPS to induce pyroptosis. Cell death was assessed by propidium iodide staining, and morphological changes were examined using transmission electron microscopy (TEM). Pyroptosis-related markers were analyzed by Western blot and immunofluorescence, while inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Chromatin immunoprecipitation (ChIP) assay and siRNA knockdown were performed to identify key targets and mechanisms involved in melatonin-mediated inhibition of pyroptosis.

Results: Melatonin significantly reduced LPS-induced pyroptosis in HPAEpiC cells. It downregulated the expression of E26 oncogene homolog 1 (ETS1), and overexpression of ETS1 reversed the anti-pyroptotic effect of melatonin. ChIP assays confirmed that ETS1 binds to the NLRP3 promoter, an interaction inhibited by melatonin. Additionally, melatonin upregulated sirtuin 1 (SIRT1), leading to ETS1 deacetylation. Knockdown of SIRT1 abolished the protective effect of melatonin against pyroptosis. Furthermore, siRNA targeting melatonin receptor 2 (MT2) attenuated melatonin-induced SIRT1 upregulation, ETS1 deacetylation, and pyroptosis inhibition.

Conclusion: Our findings indicate that melatonin alleviates LPS-induced pyroptosis in alveolar epithelial cells through the MT2/SIRT1/ETS1/NLRP3 signaling pathway.

Objective: To explore electroacupuncture (EA)'s effect and mechanism in alleviating prodromal Parkinson's disease (pPD) by targeting TLR2-mediated neuroinflammation.

Methods: Rat pPD models were established via striatal 10 μg/4 μL 6-OHDA injection. EA was applied at DU20, EX-HN3, LR2, and LR3 for 14 days. Behavioral tests, ELISA, immunohistochemistry, immunofluorescence, Western blot and qRT-PCR were used to assess non-motor symptoms, DA/TH levels, TLR2 expression, microglial activation, TLR2/NF-κB/NLRP3 pathway and pyroptosis.

Results: 6-OHDA induced 30-40% striatal DA reduction and typical pPD non-motor symptoms. EA significantly improved these symptoms, reduced TLR2 expression in key regions (substantia nigra, hippocampus, etc), inhibited M1 microglial activation (decreased CD86, increased CD206), and suppressed TLR2/NF-κB/NLRP3 pathway-related proteins, and inhibits microglial pyroptosis.

Conclusion: EA inhibited the neuroinflammation and microglial cell activation as well as pyroptosis mediated by TLR2, thereby alleviating the non-motor symptoms of PD. This provides a potential possibility for the intervention treatment of PD to prevent the progression of the disease.