Journal of Inflammation Research最新文献

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.

Airway inflammation has traditionally been assessed using invasive or semi-invasive techniques, prompting growing interest in non-invasive biomarkers. Exhaled breath condensate (EBC) offers a repeatable and well-tolerated method to evaluate airway inflammation and oxidative stress, with hydrogen peroxide (H₂O₂) emerging as a biomarker with relevant translational potential for disease monitoring and treatment response. This narrative review aimed to evaluate the potential H₂O₂ in EBC as a non-invasive biomarker for disease monitoring and treatment response in inflammatory respiratory diseases. Key clinical studies investigating H₂O₂ in patients with asthma, COPD, bronchiectasis and acute lung conditions were analyzed. Exhaled H₂O₂ levels are elevated in several inflammatory respiratory diseases, reflecting airway oxidative stress and disease instability, with higher concentrations observed in untreated or exacerbated patients, which decline in response to therapy. These findings indicate that H₂O₂ appears to be a promising tool for assessing airway oxidative stress and inflammation. Further research is needed to validate its clinical relevance and support its integration into standard clinical management.

Background: Systemic lupus erythematosus (SLE) is characterized by immune dysregulation driven in part by aberrant CD4⁺ T cell activation and defective autophagy. Although exosomes are increasingly recognized as mediators of immune communication, the contribution of exosomal long non-coding RNAs (lncRNAs) to T cell dysfunction in SLE remains poorly defined. This study investigated the pathogenic role and mechanism of plasma exosomal lncRNA XIST in regulating CD4⁺ T cell autophagy and activation.

Methods: Quantitative reverse transcription PCR (qRT-PCR) was used to quantify lncRNA XIST levels in plasma exosomes, while Western blotting, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were employed to assess the effects of exosomes on CD4⁺ T cell function. Gain- and loss-of-function approaches were applied to elucidate the underlying molecular mechanisms.

Results: LncRNA XIST was significantly overexpressed in SLE plasma exosomes and positively correlated with disease activity. These exosomes enhanced lncRNA XIST expression in CD4⁺ T cells from healthy controls (HCs), leading to suppressed autophagy and increased activation. Similar effects were observed with engineered HC plasma exosomes overexpressing lncRNA XIST. Conversely, silencing lncRNA XIST in SLE CD4⁺ T cells promoted autophagy and reduced activation, although these changes were reversed upon treatment with autologous plasma exosomes. Mechanistically, exosomal XIST functioned as a molecular sponge for miR-98, upregulating RICTOR and activating the Akt/mTOR signaling pathway, thereby modulating CD4⁺ T cell function.

Conclusion: Plasma exosomal lncRNA XIST impairs CD4⁺ T cell autophagy and promotes activation through the miR-98/RICTOR/Akt-mTOR axis, representing a mechanistically defined candidate biomarker and potential therapeutic target in SLE.

Palmoplantar pustulosis (PPP) is a chronic inflammatory dermatosis often treated with IL-17 inhibitors like secukinumab. Paradoxical cutaneous reactions to such biologics, though rare, are increasingly recognized. We report a case of a 25-year-old woman with PPP who developed a biopsy-confirmed acute pityriasis lichenoides et varioliformis acuta (PLEVA) eruption following six weeks of secukinumab therapy. Upon switching treatment to tofacitinib, both the PPP and the paradoxical PLEVA showed significant improvement. This case highlights PLEVA as a potential paradoxical reaction to IL-17 inhibition and suggests JAK inhibitors may be an effective alternative in this scenario.

Introduction: Osteoarthritis (OA) represents a prevalent degenerative joint condition, in which chondrocyte dysfunction plays a key role in disease progression. Although accumulating evidence underscores the importance of cellular stemness regulation in OA development, systematic screening of related biomarkers has been insufficient. The current study sought to discover and validate potential biomarkers through bioinformatics and machine learning (ML), offering novel perspectives for early detection and therapeutic intervention in OA.

Methods: The present study examined six OA-related transcriptomic profiles from the Gene Expression Omnibus (GEO) to discover and validate stemness-associated biomarkers. Differentially expressed genes (DEGs) were selected and analyzed for enriched biological functions. OA-related modules were determined via weighted gene coexpression network analysis (WGCNA). Key stemness-related genes were selected using ML algorithms, including support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and the least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) analysis was implemented to determine diagnostic accuracy. Utilizing single-sample gene set enrichment analysis (ssGSEA), the link with immune cell infiltration was examined. Ultimately, immunohistochemistry was employed for experimental validation.

Results: Intersection analysis identified 56 stemness-related DEGs in OA cartilage. WGCNA analysis yielded 7 modules significantly associated with stemness genes, and a combined screening approach identified 60 candidate genes. Using four machine learning algorithms-SVM, LASSO, XGBoost, and RF-four feature genes were ultimately determined (WWP2, CDKN1A, IL11, and CRTAC1), among which WWP2, CDKN1A, and CRTAC1 showed significant differential expression between OA and normal samples and demonstrated good diagnostic performance in both the training and validation cohorts (AUC > 0.7). ssGSEA analysis revealed that the expression of these three genes was significantly correlated with specific immune cell subpopulations. Immunohistochemistry further confirmed that WWP2 and CDKN1A were downregulated in OA tissues, whereas CRTAC1 was upregulated.

Conclusion: Through bioinformatics analysis and IHC validation, we identified three stemness-associated biomarker genes (WWP2, CDKN1A, CRTAC1) in OA. These findings may provide meaningful implications for future clinical assessment, treatment, and research on OA.

Interleukin-23 (IL-23) inhibitors represent a major advance in the management of moderate-to-severe plaque psoriasis, grounded in the central pathogenic role of the IL-23/Th17 axis. By selectively targeting the p19 subunit, guselkumab, risankizumab, and tildrakizumab effectively suppress disease-driving inflammation while preserving IL-12-mediated host defence. Pivotal randomized trials have demonstrated high levels of skin clearance, durable efficacy, and favourable safety profiles. Nevertheless, such trials only partially reflect the heterogeneous and medically complex populations treated in everyday practice. Against this background, this narrative review focuses on the expanding body of real-world evidence, which has provided novel insights into the long-term durability, drug survival, performance in difficult-to-treat anatomical sites, and safety of IL-23 inhibitors in special and comorbid populations. Real-world studies consistently confirm high effectiveness in elderly patients, individuals with multiple comorbidities, and those with extensive prior biologic exposure, as well as in challenging disease localisations such as scalp, nails, palmoplantar, genital, and pretibial psoriasis. Across large observational cohorts, IL-23 inhibitors show excellent treatment persistence, largely driven by sustained efficacy and low rates of discontinuation for adverse events. Reassuring safety profiles have also been documented in patients with a history of malignancy, latent infections, or cardiometabolic disease, together with improvements in quality of life and systemic inflammatory burden. By integrating evidence from randomized trials with large real-world cohorts, this narrative review provides a clinically oriented synthesis of the efficacy, safety, and therapeutic positioning of IL-23 inhibitors in psoriasis. Although all three agents demonstrate high and durable effectiveness, real-world data suggest subtle intraclass differences, with guselkumab and risankizumab often achieving faster or deeper early responses, and tildrakizumab offering greater dosing flexibility with comparable long-term persistence in selected patient profiles. Overall, IL-23 blockade has evolved from a highly effective trial-based strategy into a versatile and reliable long-term therapeutic approach capable of addressing unmet needs in routine clinical practice.

Purpose: This study aimed to evaluate histopathological changes in the olfactory bulb and nasal mucosa, as well as olfactory outcomes, following treatment modalities in an rat model of experimental AR.

Methods: This experimental study included 49 female Sprague-Dawley rats, randomly allocated into seven groups (n = 7 per group). Allergic rhinitis was induced by ovalbumin sensitization and intranasal challenge. Study groups included negative and positive controls, and treatment groups receiving methylprednisolone, montelukast, levocetirizine, olopatadine, or fluticasone propionate between days 21 and 34. The primary outcome was histopathological evaluation of inflammatory and structural changes in the nasal mucosa and olfactory bulb at day 34. The secondary outcome was assessment of olfactory function using the food-finding latency test.

Results: All animals completed the study without mortality. Compared with the positive control group, all treatment modalities resulted in significant improvement in nasal mucosal histopathology, including vascular dilatation, goblet cell hyperplasia, inflammatory cell infiltration, plasma cell infiltration, mast cell infiltration, eosinophil infiltration, chondrocyte hypertrophy, and ciliary loss. Similarly, significant improvements were observed in most olfactory bulb parameters, including glomerular layer thickness, glomerular diameter, glomerular organization, neuronal degeneration, vascular congestion, perivascular edema, and microglial activation. No significant superiority was observed among treatment groups in histopathological outcomes. In olfactory testing, a significant reduction in food-finding latency at day 28 compared with day 21 was observed only in the methylprednisolone and olopatadine groups (p = 0.038 and p = 0.027). By day 34, significant reductions in food-finding latency compared with day 21 were observed within all treatment groups (p < 0.001 for methylprednisolone, olopatadine, and fluticasone propionate; p = 0.005 for levocetirizine; p = 0.026 for montelukast).

Conclusion: All treatment modalities improved olfactory mucosal and olfactory bulb histopathological parameters, with no clear superiority. Notably, methylprednisolone and olopatadine provided early improvement in olfactory function, highlighting their therapeutic potential.

Sepsis is a severe systemic inflammatory response syndrome, and macrophages play a crucial role in its pathogenesis. In recent years, more and more attention has been paid to the molecular signaling pathways of hypoxia, especially hypoxia-inducible factor 1-alpha (HIF-1α) and its related metabolic reprogramming, which have shown their importance in regulating the inflammatory response and functional state of macrophages. At present, although a large number of studies have explored the functional changes of macrophages in sepsis, there are still many unsolved mysteries about the specific mechanism and clinical significance of the effect of hypoxia signaling pathway on macrophage function and disease progression. In this review, the metabolic pathways regulated by HIF-1α, the activation of inflammasomes, the reprogramming of cell functions, and the effects of hypoxia-related signaling pathways on macrophage function and the pathological process of sepsis were summarized. Combined with the latest single-cell transcriptomics data and molecular mechanism research, we systematically explore the potential therapeutic targets and intervention strategies, which provide theoretical basis and research direction for the precise treatment of sepsis.