Journal of Inflammation Research最新文献

Introduction: This study aimed to identify biomarkers and develop a predictive model for distinguishing severe asthma (SA) from non-severe asthma (NSA) by integrating clinical data and extracellular vesicles (EVs) proteomics.

Methods: Plasma-derived EVs were isolated from 44 individuals, including 15 healthy controls, 15 SA patients, and 14 NSA patients. Proteomic profiling of EVs was performed using proximity barcoding assay (PBA). Clinical indicators such as FEV1/FVC ratio, DLCO% predicted, and blood neutrophil count were recorded. A multivariate model incorporating both clinical and EV-derived protein data was constructed and evaluated using ROC curve analysis. Candidate biomarkers were further validated in cell-based and murine SA models.

Results: Although total EV counts and protein load did not differ significantly across groups, specific EV proteins (eg, SELL, PECAM1, ITGB3, CD9) were consistently elevated. Notably, protein combinations such as ITGB3&CLDN1 and ESAM&ITGA6 showed strong discriminatory power between SA and NSA (AUC > 0.8). The integrative model combining clinical metrics and EV proteins (IL6, NGFR, NFASC, PCDHA1) achieved a high predictive accuracy (AUC = 0.97 ± 0.075). Expression of IL6, NGFR, and NFASC was significantly upregulated in SA cellular and animal models, aligning with patient data.

Conclusion: This study presents a reliable multi-parameter model for distinguishing severe from non-severe asthma, leveraging both clinical indicators and EV proteomics. These findings support the potential of EV-based biomarkers in early diagnosis and personalized management of SA.

Background: Endoscopic evaluation remains the gold standard for assessing Crohn's disease (CD) activity and mucosal healing (MH), but it is invasive, expensive and time consuming. Therefore, there is an urgent need for a non-invasive quantitative alternative method.

Aim: To develop a topological radiomics-based multi-task deep learning model for simultaneous prediction of MH status and endoscopic activity scores in CD.

Methods: A total of 81 CD patients were stratified into training (n=60) and validation (n=21) groups at a 7:3 ratio. Topological radiomic features were extracted from multiphase CT enterography. A multi-task model was trained to predict MH (classification) and SES-CD (regression), integrating feature selection and SHAP-based interpretability.

Results: Three discriminative topological features were identified across arterial and portal phases. For MH prediction, the multi-task model achieved an AUC of 0.938 for training set and 0.875 for validation set. For SES-CD prediction, it showed lower MSE and MAE, with higher R² and C-index than the single-phase models.

Conclusion: The multi-task topological radiomics framework enables accurate, non-invasive assessment of mucosal healing and endoscopic activity in CD, offering a clinically interpretable approach with strong translational potential. Future studies with larger cohorts are warranted to further validate its robustness.

Purpose: The syndemic of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) presents a growing global health challenge, particularly in high-burden countries. T2DM is known to impair immune responses, increasing susceptibility to TB. However, the cytokine dynamics underlying this interaction remain unclear. This study aimed to explore the differences in ex vivo cytokine responses between individuals with and without T2DM following TB antigen stimulation.

Patients and methods: In this cross-sectional study, we analyzed plasma samples from 110 individuals with T2DM and 38 without, collected as part of the TANDEM and INFECT cohort studies in Indonesia. Cytokine levels (IL-1β, IL-6, TNF-α, and IFN-γ) were measured using ELISA before and after TB antigen stimulation using the QuantiFERON-TB Gold assay. Demographic, clinical, and metabolic parameters were recorded. Statistical analyses included Mann-Whitney U-tests and Spearman correlation.

Results: Patients with DM showed a higher baseline levels of pro-inflammatory cytokines than non-DM individuals, particularly in IL-1β, IL-6 and TNF-α, suggesting a primed immune response even before TB antigen exposure. After TB antigen stimulation, no significant between-group differences were observed in cytokine levels. However, IL-1β showed a more pronounced median increase in T2DM (124 vs -54 pg/mL, p = 0.43), while IL-6, TNF-α, and IFN-γ changes were blunted in the T2DM group. Correlation analyses revealed that in T2DM individuals, IL-1β positively correlated with IL-6 and TNF-α both pre- and post-stimulation. IL-6 and IFN-γ showed significant associations with HbA1c and BMI in the non-DM group.

Conclusion: T2DM group exhibited altered immune patterns marked by heightened IL-1β response and disrupted regulation of IL-6, TNF-α, and IFN-γ, although no statistically significant cytokine differences were observed. These findings suggest an immune dysregulation in T2DM that may contribute to TB susceptibility, warranting further investigation using CD4/CD8-responsive assays in larger, more diverse populations.

Purpose: Inflammatory skin diseases, including psoriasis (PsO), atopic dermatitis (AD), hidradenitis suppurativa (HS), and alopecia areata (AA), are chronic immune-mediated disorders that substantially impair the quality of life and impose a growing socioeconomic burden. In Latin America (LA), these conditions unfold in the context of structural inequality, fragmented health systems, and limited epidemiological data. Our objective was to review the epidemiology, awareness, and treatment landscape of PsO, AD, HS, and AA in Latin America, highlighting regional guidelines, real-world studies, and unmet needs.

Methods: A narrative review was performed by integrating data from peer-reviewed publications, national and regional guidelines, registry analyses, and real-world studies published until 2025.

Results: The prevalence of PsO in LA ranges from 0.5% to 2%, AD affects 2-3% of adults, HS prevalence is estimated at 0.3-0.5%, and AA lifetime risk approximates 1-2%. Across conditions, awareness among patients and non-specialists remains low, contributing to delayed diagnosis and undertreatment. National guidelines, recently updated in Argentina, Brazil, Colombia, and Mexico, broadly align with international standards, adapting recommendations to local resource and reimbursement constraints. Biologic and targeted therapies have transformed disease management; however, access remains inequitable, limited by high costs, fragmented insurance systems, and slow regulatory approval processes. Emerging real-world evidence from registries such as MEASURE-AD, RENAAC (AA), and national HS cohorts confirms therapeutic benefit but highlights persistent disparities and data gaps.

Conclusion: Despite major advances in therapeutic innovation, LA faces continuing inequities in access and outcomes for inflammatory skin diseases. Coordinated regional registries, harmonized clinical guidelines, and policy reforms to accelerate drug approval and reimbursement are essential to achieve equitable dermatologic care.

Gastric ulcers remain a prevalent gastrointestinal disorder aggravated by physical and psychological stress, which disrupts the balance between mucosal defense and aggressive factors. Conventional treatments, though effective, often produce adverse effects and recurrence. This review consolidates the mechanistic insights into phytochemicals, particularly flavonoids, terpenoids, alkaloids, and saponins that exert anti-ulcer effects through antioxidant, anti-inflammatory, and cytoprotective pathways. Emphasis is placed on their roles in modulating prostaglandin synthesis, nitric oxide signaling, cytokine expression, and H⁺/K⁺-ATPase inhibition. Furthermore, recent experimental evidence from stress-induced gastric ulcer models (WIRS, CRS, HRS) is summarized to correlate specific phytochemical classes with protective outcomes. The review underscores phytomedicines as promising, safer alternatives for managing stress-induced gastric ulcers and encourages future standardization and molecular validation studies.

Purpose: Ustekinumab (UST) is effective for Crohn's disease (CD), yet reliable biomarkers for predicting long-term response remain scarce. This study aimed to identify novel plasma proteomic biomarkers and develop predictive models for long-term endoscopic response to UST therapy in patients.

Methods: Baseline plasma inflammatory proteins were profiled using the Olink platform in 40 CD patients treated with UST (20 responders, 20 non-responders). Differentially expressed proteins (DEPs) were identified after adjusting for age, age at diagnosis, and SES-CD scores. Stable DEPs were selected via bootstrap resampling and further validated in an independent patient group from the same center (n=20) using ELISA. Predictive models were constructed using logistic regression, random forest, and support vector machine (SVM) algorithms.

Results: Non-responders had elevated baseline interleukin-8 (IL8) and CD6 levels and reduced thymic stromal lymphopoietin (TSLP) compared to responders. ELISA confirmed differential expression of IL8, CD6, and TSLP, with CD6 showing the best diagnostic accuracy (AUC=0.800). The logistic regression model combining these markers achieved an AUC of 0.828 (95% CI: 0.701-0.954), outperforming random forest (AUC=0.745) and SVM (AUC=0.775).

Conclusion: Baseline plasma IL8, CD6, and TSLP are potential predictive biomarkers of long-term endoscopic response to UST in CD, providing a basis for personalized treatment strategies.

Background: Chronic pancreatitis (CP) is characterized by significant pancreatic exocrine dysfunction, with limited targeting therapeutic strategies. It has been reported that DCHD can effectively alleviate pancreatic injury in chronic pancreatitis; however, its effect and mechanism on pancreatic exocrine dysfunction remain unclear.

Objective: To investigate the therapeutic effects of Da-Chai-Hu Decoction (DCHD) on pancreatic exocrine dysfunction in CP and explore its underlying mechanisms.

Methods: Thirty male C57BL/6 mice were divided into control, CP model, and three DCHD dose groups (11, 22, 44 g/kg). CP was induced via repeated caerulein injections (50 μg/kg), followed by 3 weeks of DCHD treatment. Histopathological analysis of pancreatic tissue (via HE staining, IHC, IF), molecular assays (Western blot, RT-PCR), and RNA-seq were performed. LC-MS/MS identified chemical components in the serum of DCHD-treated mice, and network pharmacology predicted potential targets. Mouse pancreatic acinar cells (266-6) exposed to caerulein and PI3K inhibitor LY294002 were treated with DCHD serum to validate pathways.

Results: DCHD not only alleviated pancreatic fibrosis (α-SMA) and inflammation (IL-6), but also maintained the level of Amylase. RNA-seq revealed that DCHD treatment downregulated the expression of genes related to inflammation, fibrosis, apoptosis, and ERS. The bioactive compounds in DCHD serum were identified by LC-MS/MS, and further were linked to PI3K/AKT and ERS pathway through network pharmacology. In vivo validation experiment showed that the expression of PI3K/AKT pathway and ERS markers in pancreatic tissue was significantly reduced in the DCHD group compared with CP mice (P<0.05). In vitro, serum containing DCHD enhanced the mRNA level of Ptf1-α and Cpa1 which represent pancreatic exocrine function and inhibited ERS, apoptosis, and PI3K/AKT signaling activation in 266-6 cells stimulated with caerulein. Furthermore, the expression of ERS marker including GRP78 and DDIT3 in acinar cells was significantly inhibited by PI3K inhibitors (LY294002) (P<0.05). After treatment of LY294002, the effect of DCHD-containing serum alleviating ERS of acinar cells was abrogated.

Conclusion: DCHD suppress ERS by regulating the PI3K/AKT pathway in pancreatic acinar cells and further alleviates pancreatic exocrine dysfunction. This study confirms the therapeutic potential of DCHD in pancreatic exocrine dysfunction, and offers a new therapeutic option for CP with pancreatic exocrine dysfunction.

Purpose: Systemic inflammation plays a crucial role in the progression and prognosis of non-small cell lung cancer (NSCLC), yet the prognostic value of perioperative inflammatory markers remains underexplored.

Patients and methods: We retrospectively analyzed 243 patients who underwent resection (2015-2019) at The Second Xiangya Hospital. Five inflammatory indices-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV)-were calculated from pre- and postoperative blood counts, and their changes (Δ values) were derived. Prognostic markers were identified using receiver operating characteristic (ROC) curve analysis, Cox regression, least absolute shrinkage and selection operator (LASSO), and stepwise selection. A nomogram was developed in a training cohort and internally validated using a 70/30 hold-out split from the same center.

Results: Postoperative SII and PIV, along with their perioperative changes (ΔSII and ΔPIV), showed superior prognostic performance compared to preoperative values. The final nomogram (POST_SII, POST_PIV, clinical tumor-node-metastasis stage, smoking history, preoperative albumin, age, and gender) achieved a concordance index (C-index) of 0.85 in the training cohort, with area under the curve (AUCs) of 0.86, 0.89, and 0.94 at 1-, 3-, and 5-year, and a C-index of 0.80 with AUCs of 0.74, 0.85, and 0.90 in the validation cohort. The model surpassed TNM and clinical models and showed greater net clinical benefit in decision-curve analysis.

Conclusion: Postoperative SII and PIV are strong inflammatory predictors of survival after NSCLC resection. A nomogram integrating these markers with clinical variables provides accurate, individualized risk stratification.

The interleukin-4/its receptor (IL-4/IL-4R) axis has been identified as a pivotal driver of type 2 (Th2) inflammation. Biologics targeting this axis, particularly IL-4 receptor alpha subunit (IL-4Rα) monoclonal antibodies (such as dupilumab), provide revolutionary therapeutic options for multiple Th2 inflammatory diseases by simultaneously blocking IL-4 and interleukin-13 (IL-13) signaling. This review systematically evaluates the clinical application of IL-4/IL-4R-targeted therapies across a spectrum of indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and bullous pemphigoid. A substantial body of research, including randomized controlled trials and real-world studies, has demonstrated the efficacy of this therapy in improving disease-specific scores, enhancing lung function, and reducing the risk of acute exacerbations. However, the effectiveness of this treatment exhibits heterogeneity, with some patients developing primary resistance. With respect to safety, the therapy is generally well-tolerated; however, it is associated with a series of characteristic adverse events, including injection site reactions (incidence 8%-22%), disease-specific conjunctivitis (up to 14%-19% in patients with atopic dermatitis), nasopharyngitis, and transient eosinophilia. Future advancements in dynamic biomarker monitoring, bispecific antibody development, and precision dosing strategies hold promise for further optimizing the efficacy-safety balance and expanding therapeutic applications, including in neurodegenerative diseases. The objective of this review is to provide clinicians with a thorough, evidence-based synopsis of the current clinical value and prospects of IL-4/IL-4R-targeted therapies.

This comprehensive review aims to synthesize current evidence on sepsis-related skeletal muscle atrophy, with a focus on underlying mechanisms, diagnostic approaches, and therapeutic interventions. A systematic literature search was conducted in PubMed, Web of Science, and Cochrane Library up to October 2024, including clinical, translational, and animal studies. We critically analyzed the pathophysiological mechanisms linking sepsis to muscle wasting, including inflammatory signaling, mitochondrial dysfunction, and proteolytic pathways. Epidemiological data indicate a high incidence of muscle atrophy in sepsis patients, particularly among the elderly and those with comorbidities. Diagnostic modalities such as CT, MRI, ultrasound, and emerging biomarkers including urinary titin and myokines are discussed. Treatment strategies encompassing nutritional support, pharmacotherapy (eg, GLP-1RAs, myostatin inhibitors), and rehabilitation are evaluated. Controversies regarding etiology and treatment efficacy are highlighted. Future directions include the exploration of novel biomarkers, genomics-based personalized therapy, and long-term outcome studies. This review provides a structured and critical appraisal of the current state of knowledge, aiming to inform clinical practice and future research.