Journal of Inflammation Research最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) in children is a clinically significant inflammatory disorder characterized by persistent symptoms and complex underlying mechanisms. This study used multi-omics approaches to investigate potential microbial and metabolic associations in pediatric CRSwNP.

Methods: Nasal secretions from 20 children with CRSwNP and 19 healthy controls were analyzed using metagenomics, untargeted metabolomics, and proteomics.

Results: CRSwNP patients showed higher microbial diversity and altered microbial communities, with increased Streptococcus abundance. Metabolomic sequencing revealed that 13'-Hydroxy-alpha-tocopherol was significantly upregulated in the CRSwNP group and exhibited a positive correlation with the abundance of Streptococcus. Proteomic sequencing revealed that proteins involved in glutathione metabolism were significantly downregulated in the CRSwNP group, with GCLM and GGCT showing a significant negative correlation with 13'-Hydroxy-alpha-tocopherol.

Conclusion: These associative findings suggest potential links among Streptococcus, 13'-Hydroxy-α-tocopherol, and glutathione metabolism, indicating that oxidative stress-related imbalance may contribute to pediatric CRSwNP. These results provide preliminary evidence that 13'-Hydroxy-α-tocopherol may serve as a potential biomarker for pediatric CRSwNP.

Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of the TNFSF superfamily, with the ability to associate to Death Domain Receptor 3 (DR3) but also to Decoy Receptor 3 (DcR3). Functional signaling affects several DR3-bearing cells and critically regulates diverse immunological processes such as adaptive lymphocytic responses, homeostatic mucosal pathways, as well as fibrotic mechanisms. The multifaceted pleiotropic nature of the TL1A/DR3 system appears to be critically involved in the pathogenesis of inflammatory and autoimmune diseases, particularly Inflammatory Bowel Disease (IBD) and allergic lung inflammation and may represent a novel therapeutic target for patients. In fact, several clinical programs with anti-TL1A monoclonal antibodies are currently underway and initial results from clinical trials in patients with IBD report positive effects on clinical and endoscopical outcomes with favorable safety profile. In this narrative review, we aim to link the immunological characteristics of the TL1A/DR3 cytokine: receptor system with the pathogenesis of IBD but also other immune-mediated conditions by critically revisiting mechanistic evidence from animal models and associations with human disease states. We also review available information on the use of anti-TL1A monoclonal antibodies and comment on future challenges that may be associated with the therapeutic potential of targeting the TL1A/DR3 pathway.

Purpose: Chronic inflammation of the lungs can affect pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD). The Bufei Yishen formula (BYF) and Effective-compound combination of BYF III (ECC-BYF III) ameliorate lung histopathological injury and remodeling, but the mechanism remains unclear. This study aimed to observe the effects of ECC-BYF III on pulmonary vascular inflammation in COPD and to elucidate its detailed mechanism.

Methods: In vivo, COPD rat model was established through cigarette smoke exposure (CSE) combined with repeated infections of Klebsiella pneumoniae. Rats were randomly treated with ECC-BYF III (5.5 mg/kg, once a day) or doxofylline (36 mg/kg, once a day) for eight weeks. In vitro, Human umbilical vein endothelial cells (HUVECs) and human monocyte leukemia cells (THP-1) were induced with 10 μg/mL LPS for 24h. The pulmonary function, histopathology, inflammatory factor levels, immunoblotting results were evaluated.

Results: Compared with the model group, ECC-BYF III significantly improved the lung function, alleviated pulmonary artery inflammation and relieved pulmonary vascular remodeling in COPD rats. At the molecular level, ECC-BYF III down-regulated VEGF₁₆₅/P38 MAPK signaling pathway. In the inflammatory model of HUVEC induced by LPS, 35 and 70μg/mL ECC-BYF III significantly decreased the levels of tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β) and Endothelin-1 (ET-1) mRNA, and increased the expression of endothelial nitric oxide synthase (eNOS) mRNA. In addition, ECC-BYF III also inhibited VEGF₁₆₅/P38 MAPK pathway in LPS-induced HUVEC and THP-1/HUVEC co-cultured inflammatory models.

Conclusion: Our findings demonstrate that ECC-BYF III can improve pulmonary vascular remodeling in COPD rats, and its key pharmacodynamic mechanism involves the inhibition of the VEGF₁₆₅/P38 MAPK pathway, thereby reducing inflammatory infiltration.

Objective: Lupus nephritis (LN) is a major cause of kidney failure in systemic lupus erythematosus, with podocyte injury being a key determinant of proteinuria and poor renal outcome. Ferroptosis, an iron-dependent form of regulated cell death, has been implicated in kidney diseases, but its role in LN remains unclear.

Methods: We integrated in vivo experiments using MRL/lpr mice, in vitro assays with immortalized podocytes (MPC5), and transcriptomic analysis of human glomerular datasets (GSE32591). Ferroptosis involvement was evaluated by ferrostatin-1 (Fer-1) treatment, measurement of ferroptosis markers, and assessment of podocyte proteins. Bioinformatic analyses (differential expression, WGCNA, LASSO regression, and FerrDb integration) identified candidate ferroptosis regulators, followed by functional validation of CYBB via siRNA knockdown and overexpression.

Results: Progressive nephritis in MRL/lpr mice showed iron overload, lipid peroxidation, glutathione depletion, and GPX4 downregulation, leading to podocyte loss and proteinuria. Fer-1 treatment markedly ameliorated renal pathology and preserved podocyte integrity. Human LN datasets identified CYBB as a ferroptosis-related hub gene upregulated in disease. CYBB expression correlated with renal dysfunction and oxidative injury, while in vitro assays confirmed that CYBB overexpression enhanced ROS generation and ferroptotic podocyte damage, whereas CYBB knockdown or Fer-1 reversed these effects.

Conclusion: These findings identify CYBB-mediated ferroptosis as a key driver of podocyte injury in LN. By promoting ROS generation and lipid peroxidation, CYBB serves as a mechanistic link between oxidative stress and ferroptotic cell death. Both pharmacological and genetic inhibition of CYBB mitigated ferroptosis, preserved podocyte integrity, and improved renal function, highlighting CYBB as a promising therapeutic target in lupus nephritis.

Objective: This research aimed to explore key glycosylation-related genes (signature genes) and associated molecular mechanism on chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which further providing new perspectives for disease prognosis and diagnose.

Patients and methods: The gene expression profiles were obtained from the public GEO database. The glycosylation-related genes were identified based co-DEGs from COPD vs normal samples and IPF vs normal samples, module genes by weighted gene co-expression network analysis (WGCNA), as well as glycosylation genes from database. Signature genes were screened using machine learning methods, followed by immune infiltration, function analysis, drug-gene and transcriptional regulatory network analysis. Finally, validation analysis based on tissue samples from COPD/IPF patients were performed to test the expression of signature genes.

Results: A total of 35 differentially expressed glycosylation-related genes for both COPD and IPF were explored. By three kinds of machine learning analyses, totally three signature genes including SULF1, ST8SIA1 and FCN3 were explored. In COPD, the AUC values for FCN3, ST8SIA1, and SULF1 were 0.643, 0.722, and 0.719, respectively; while in IPF, they were 0.955, 0.792, and 0.943, respectively. Immune infiltration and GSEA analysis showed that signature genes were dramatically correlated with activated B cell and extracellular matrix (ECM)-associated functions (P < 0.05). Bisphenol A and Valproic acid were common drugs for both three signature genes. Validation analysis found that the ST8SIA1 expression was related to the disease state (P < 0.001). Functional experiments revealed that it affected cell behaviors, including proliferation, apoptosis, migration, and invasion (all, P < 0.01), and drug treatments could regulate its expression and glycosylation levels (all, P < 0.05), providing crucial evidence for biomarker research and pathogenesis exploration of the two diseases.

Conclusion: We identified SULF1, ST8SIA1 and FCN3 as shared glycosylation-related biomarkers in COPD and IPF. These genes bridge fibrosis, inflammation, and immune dysregulation, offering potential diagnostic and therapeutic targets.

Background: The systemic immune-inflammation index (SII), a novel inflammatory index integrating neutrophil, platelet, and lymphocyte counts, predicts outcomes in several cardiovascular diseases, yet its role in heart failure with preserved ejection fraction (HFpEF) remains unclear. We therefore investigated the prognostic value of SII in HFpEF patients and compares its performance against other inflammatory markers, including systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP).

Methods: We retrospectively analyzed a cohort of 316 patients with HFpEF diagnosed between January 2017 and January 2021. All-cause mortality, cardiovascular mortality and HF rehospitalization were assessed over a median follow-up of 24 months. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were employed to evaluate the comparative prognostic performance of SII against SIRI, NLR and CRP.

Results: Logistic regression models revealed that each 100-unit increase in SII was independently associated with elevated risks of cardiovascular mortality (OR:1.321, 95% CI:1.191-1.467, P<0.001) and HF rehospitalization (OR:1.168, 95% CI:1.098-1.241, P<0.001), but not with all-cause mortality (P>0.05). SII demonstrated superior prognostic performance compared to SIRI, NLR and CRP both in cardiovascular mortality (NRI range: 0.798-1.097; IDI range: 0.094-0.142, all P<0.05) and HF rehospitalization (NRI range: 0.254-0.455; IDI range: 0.016-0.066, all P<0.05). However, SII provided no incremental utility for all-cause mortality (P>0.05).

Conclusion: SII emerges as a superior predictor of adverse cardiovascular outcomes in HFpEF compared to conventional inflammatory markers, supporting its use for risk stratification and as a potential therapeutic guide. Nevertheless, its association with all-cause mortality remains limited.

Background: Increasing evidence suggests that individuals with diabetic nephropathy (DN) are at a significantly higher risk of developing atherosclerosis (AS) compared to the general population. However, the precise mechanisms underlying this association remain unclear. This study aims to explore the shared pathways and potential biomarkers implicated in this complication.

Methods: Microarray data downloaded from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) in DN and AS. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression modules relevant to DN and AS. We conducted functional pathway enrichment analysis on the shared genes. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) methods were utilized to identify and validate potential diagnostic markers. Additionally, immunoinfiltration analysis was performed to examine the relationship between the core markers of DN and AS and the expression of immunoinfiltrating cells. Finally, blood samples from patients were collected to assess the diagnostic efficacy of PRCP.

Results: The results of common genes analysis showed that immune and inflammatory response particularly cytokine-cytokine receptor interactions may be a common feature in the pathophysiology of DN and AS. Three potential shared diagnostic markers-ID4, RNF213, and PRCP-were identified and validated using SVM and LASSO. Immunoinfiltration analysis revealed that the expressions of ID4, RNF213, and PRCP were associated with variations in immune cell populations. Differential analysis of peripheral blood microarray data indicated that only PRCP was significantly overexpressed in both AS and DN samples. Moreover, qRT-PCR confirmed the increased expression of PRCP in peripheral blood mononuclear cells (PBMCs) samples from patients.

Conclusion: The co-expression of RNF213, PRCP, and ID4 may contribute to the development of AS and DN. PRCP, particularly, shows promise as a diagnostic marker due to its detectability as a protein in peripheral blood.

Purpose: To elucidate the molecular mechanism by which ginsenoside Rg3 (G-Rg3) protects human bronchial epithelial (HBE) cells against lipopolysaccharide (LPS)-induced injury, focusing on its regulation of autophagic flux and the TLR4/NF-κB-mediated inflammatory pathway.

Methods: HBE cells were treated with LPS (1-100 ng/mL) to induce autophagy dysregulation and inflammation. G-Rg3 (2-16 μM) was administered to evaluate its protective effects. Western blotting was used to detect autophagy-related proteins (ATG4B, ATG7, PIK3C3, LC3B, p62) and TLR4/NF-κB signaling molecules; ELISA quantified proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, IL-8); PI staining and flow cytometry analyzed cell death and apoptosis.

Results: LPS dose-dependently upregulated the expression of autophagy-related proteins (ATG4B, ATG7, PIK3C3, p62, LC3B-II), with accumulated p62 and LC3B-II indicating impaired clearance of autophagic substrates. Additionally, G-Rg3 inhibited LPS-induced TLR4/NF-κB activation, suppressed proinflammatory cytokine secretion, and attenuated HBE cell apoptosis/necrosis.

Conclusion: G-Rg3 mitigates LPS-induced HBE cell injury by dual mechanisms: restoring impaired autophagic flux and inhibiting the TLR4/NF-κB inflammatory cascade. These findings identify G-Rg3 as a promising therapeutic agent targeting the crosstalk between autophagy and inflammation in respiratory diseases such as COPD and acute lung injury.