Journal of Inflammation Research最新文献

Background: Airway epithelial cells (AECs) and alveolar macrophages are involved in airway inflammation. The direct effects of atmospheric fine-particulate-matter (PM2.5) on airway cells, such as AECs and alveolar macrophages, have been widely investigated, but the effect of cell-cell interaction on inflammatory response remains unclear. Exosomes play a crucial role in intercellular communication. However, the cellular interaction of exosomes in PM2.5-induced airway inflammation is unclear.

Methods: The PM2.5-induced human bronchial epithelial (BEAS-2B) cells and phorbol 12-myristate 13-acetate-induced macrophages (Mφ) were co-cultured and then the expression of IL-6, IL-1β, TNF-α and miRNA-155-5p were detected. Exosomes from PM2.5-exposed BEAS-2B cells were then co-cultured with Mφ to detect the expression of miR-155-5p and inflammatory cytokines, as well as cytokine signaling inhibitor-1 (SOCS1)/NFκB, and to detect the effect of the exosome inhibitor GW4869.

Results: After the co-culture of PM2.5-induced BEAS-2B cells and Mφ, the expression of Mφ-derived IL-6, IL-1β, and TNF-α, as well as miRNA-155-5p were upregulated. The expression of miRNA-155-5p was upregulated in BEAS-2B and BEAS-2B cell-derived exosomes after exposure to PM2.5. Furthermore, co-culturing exosomes derived from PM2.5-exposed BEAS-2B cells with Mφ, upregulated miR-155-5p and inflammatory cytokines, decreased cytokine signaling inhibitor-1 (SOCS1) expression, and activated NF-κB. In addition, adding exosome inhibitor GW4869 to PM2.5-interfered BEAS-2B cells co-culture with Mφ downregulated miRNA-155-5p expression, inhibited NF-κB, and reduced the levels of inflammatory factors.

Conclusion: PM2.5 promotes Mφ inflammation by upregulating miRNA-155-5P in exosomes obtained from BEAS-2B cells through miR-155-5P/SOCS1/NF-κB pathway. Exosomal miRNAs mediate cellular communication between BEAS-2B cells and Mφ, which may be a new mechanism of PM2.5-stimulated pulmonary inflammatory response.

Purpose: This research sought to evaluate the clinical value of systemic immune-inflammation index and systemic inflammation response index in predicting the response to radioactive iodine (RAI) therapy in individuals diagnosed with differentiated thyroid cancer.

Patients and methods: This retrospective study included 406 patients with differentiated thyroid cancer who received initial RAI therapy and follow-up from December 2019 to December 2023. Patients were divided into two groups based on imaging and serum indicators to evaluate the response to radioactive iodine treatment: the ER group (excellent response) and the non-ER group (suboptimal response). Systemic immune-inflammation index and systemic inflammation response index were calculated based on peripheral blood cell counts before treatment. Multivariable logistic regression analysis was used to assess the independent associations of these indices with the therapeutic response to radioiodine treatment. Receiver operating characteristic (ROC) curves were graphed and the area under the curve (AUC) was calculated to evaluate their predictive ability.

Results: Compared to the ER group, patients in the non-ER group had significantly elevated systemic immune-inflammation index and systemic inflammation response index levels (p < 0.001). After adjusting for confounding factors, there was a significant association between these indices and the response to radioactive iodine treatment in patients with differentiated thyroid cancer. The optimal cutoff values for predicting the response to RAI treatment were 668.91 for systemic immune-inflammation index (AUC=0.692, sensitivity 58.2%, specificity 73.1%, 95% CI: 0.639-0.745, p < 0.001) and 0.47 for systemic inflammation response index (AUC=0.664, sensitivity 85.6%, specificity 42.7%, 95% CI: 0.612-0.717, p < 0.001).

Conclusion: Systemic immune-inflammation index and systemic inflammation response index could be valuable for predicting the response to RAI treatment in individuals diagnosed with differentiated thyroid cancer. Further research is needed to explore their practical utility, and these novel inflammation markers could serve as adjunct tools in clinical practice.

Background: Intracranial aneurysms (IA) frequently cause subarachnoid hemorrhage (SAH) and have poor prognosis. However, the molecular mechanisms and diagnostic biomarkers associated with IA and ruptured IA (rIA) remain poorly understood.

Methods: In this study, single-cell and transcriptome datasets were obtained from the GEO database. The cell populations were annotated to identify potential pathogenic subpopulations, followed by intercellular communication, pseudotime, and SCENIC analyses. Proteome-wide and transcriptome-wide Mendelian randomization (MR) analyses were conducted to identify risk factors for IA and SAH. The major pathological changes and diagnostic biomarkers of IA and SAH were identified based on the transcriptome datasets. A clinical cohort was established to identify the diagnostic biomarkers and validate the results.

Results: Macrophages and neutrophils were predominantly increased in IA and rIA tissues, and neutrophils were markedly upregulated in the blood of SAH patients. SPP1⁺ Macrophage was progressively elevated in aneurysms, promoting vascular smooth muscle cell (VSMC) phenotypic transformation and collagen matrix remodeling through the SPP1 and TGF-β pathways. Furthermore, HIF1α regulon was enriched in SPP1⁺ Macrophage, mediating inflammation and metabolic reprogramming, which contributed to IA progression. Integrated MR analysis identified CD36 as a risk factor for both IA and SAH, and it has been recognized as an effective blood biomarker for SAH. Neutrophils and their related indicators have emerged as excellent biomarkers of SAH in clinical cohorts.

Conclusion: This study highlighted the detrimental role of SPP1⁺ Macrophage in IA and SAH using single-cell sequencing and MR analyses. CD36 was identified as a risk factor for IA and SAH and was also an efficient blood biomarker for SAH. In a clinical cohort, neutrophils and related indicators were valuable for the early diagnosis of SAH.

Background: There is limited research on the long-term prognosis of percutaneous coronary intervention (PCI) in coronary chronic total occlusion (CTO) patients who have previously undergone coronary artery bypass grafting (CABG). Additionally, the prognostic value of a novel systemic immune inflammation index (SII) in this specific patient population remains unclear.

Methods: To adjust for differences in baseline features and minimize bias, 335 pairs of patients with or without prior CABG undergone PCI were obtained after probability score matching (PSM) in a single-center cohort. The clinical characteristics were collected, and the primary outcomes were major cardiovascular events (MACE), which included all-cause death, nonfatal MI and unplanned revascularization, were recorded during the follow-up period after discharge. The group with prior CABG were divided according to the median level of SII: Lower SII group (SII ≤ 570.10, N = 167) and higher SII group (SII ≥ 570.10, N = 168).

Results: The SII values were significantly higher in the prior CABG group than in the without prior CABG group [570.10 (444.60, 814.12) vs 519.65 (446.86, 565.84), P < 0.001, respectively]. The survival Kaplan-Meier analysis showed that patients with prior CABG was significantly associated with a higher risk of MACE than patients without prior CABG (P = 0.016) in the long-term follow-up. As SII levels increased, the cumulative risk of MACE became significantly higher in the patients with prior CABG (P = 0.023) stratified by the median value of SII. The Cox proportional hazards regression model analysis indicated that the level of SII (hazard ratio = 2.035, 95% CI, 1.103-3.753, P = 0.023) emerged as independent predictors of MACE. The restricted cubic spline (RCS) analysis illustrated that the HR for MACE increased with increasing SII.

Conclusion: SII is a reliable predictor of long-term cardiovascular events after PCI in CTO patients with prior CABG, suggesting that SII may be helpful in identifying high-risk patients who need more aggressive treatment and follow-up strategies.

Objective: To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS.

Methods: Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)).

Results: The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P<0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P<0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P<0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P<0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P<0.05).

Conclusions: In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.

Purpose: Understanding the role of systemic inflammation in the development of Metabolic Syndrome (MetS) is crucial for identifying individuals at a higher risk of this cluster of conditions that increase the risk of heart disease, stroke, and diabetes.

Patients and methods: A retrospective cohort study was conducted with 4,312 participants who were free from MetS at the study's onset and had high-sensitivity C-reactive protein (hsCRP) levels measured. Latent class trajectory modeling was utilized to identify distinct hsCRP trajectory patterns. Multivariable regression and proportional hazards analyses were employed to evaluate the predictive value of hsCRP trajectories for the development of MetS.

Results: During the 1.63-year follow-up period, 1,308 participants developed metabolic syndrome (MetS). Individuals with high hsCRP levels exhibited a significantly increased risk of developing MetS compared to those with low hsCRP levels (HR = 1.062, 95% CI 1.103-1.113). The hsCRP trajectory analysis identified three distinct groups: low-stable, increasing, and decreasing. The decreasing and increasing hsCRP trajectory groups demonstrated a 1.408-fold (95% CI 1.115-1.779) and a 1.618-fold (95% CI 1.288-2.033) increased risk of MetS, respectively.

Conclusion: This study suggests that participants with higher baseline hsCRP levels and increasing hsCRP trajectories are associated with a progression toward MetS. Long-term hsCRP trajectories may serve as useful tools for identifying individuals at higher risk of MetS who could benefit from targeted preventive and therapeutic interventions.

Background: Chronic atrophic gastritis (CAG) is a severe condition characterized by inflammation and loss of appropriate mucosal glands in the stomach. The underlying mechanisms of CAG development remain unclear. Exploring immune-related circular RNAs (circRNAs) could provide insights for potential diagnostic and therapeutic strategies.

Methods: Samples from 40 patients with CAG and non-CAG (CNAG) underwent high-throughput sequencing, and EdgeR analysis identified differentially expressed circRNAs and mRNAs. Gene Ontology (GO) analysis elucidated biological functions, while Immune Cell Abundance Identifier (ImmuCellAI) estimated immune cell abundance. Flow cytometry analyzed immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) identified hub genes related to the immune response in CAG. CircRNA-mRNA networks were constructed, and qRT-PCR validated findings.

Results: A total of 163 differentially expressed immune-related genes (DEIRGs) were identified between CAG and CNAG. The upregulated immune-related mRNAs in CAG were significantly enriched in antimicrobial humoral response, viral entry into host cells, neutrophil activation, and leukocyte migration. Conversely, downregulated immune-related mRNAs were linked to regulation of natural killer cell-mediated cytotoxicity, positive regulation of adaptive immune response, antigen receptor-mediated signaling pathway, and B cell activation. Immune Cell Abundance Identifier (ImmuCellAI) and flow cytometry confirmed increased neutrophil infiltration in CAG compared to CNAG. WGCNA identified 56 hub immune-related genes. Additionally, circRNA expression profiles in CNAG and CAG were explored, with 19 upregulated and 23 downregulated circRNAs identified in CAG. The upregulated circRNAs were associated with biological processes like carnitine metabolic process and regulation of B cell receptor signaling pathway. A circRNA-mRNA co-expression network was constructed based on five circRNAs highly related to hub immune-related genes. Furthermore, the expression of eight immune-related mRNAs and five circRNAs were validated in CAG.

Conclusion: This study is the first systematic analysis of circRNA profiles in CAG and provide important insights for potential immunotherapeutic strategies and early diagnostic biomarkers in CAG treatment.

Purpose: The objective of this study was to create a predictive model for the onset of persistent organ failure (POF) in individuals suffering from acute biliary pancreatitis (ABP) by utilizing indicators observed within 24 hours of hospital admission. Early detection of high-risk POF patients is crucial for clinical decision-making.

Patients and methods: Clinical data and laboratory indicators within 24 hours of admission from ABP patients diagnosed at The First Affiliated Hospital of Wenzhou Medical University between January 1, 2016, and January 1, 2024 were collected and retrospectively analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression (stepwise regression) methods were employed to identify variables for constructing the prediction model. The prediction model's performance was evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). It was compared with other scoring systems such as SIRS, BISAP, APACHE II, CTSI, and MCTSI. Additionally, a web-based calculator was created to simplify the calculation process.

Results: Out of 324 ABP patients, 25 developed POF. Initial screening identified 18 variables; through LASSO regression and multivariable logistic regression analysis, five variables including BMI, Hb, ALB, Ca, and LIP were determined as independent predictors of POF. According to these factors to build prediction model, draw the nomogram. The AUC's receiver operating characteristic curve analysis demonstrated a significantly higher value in comparison to other scoring systems. Calibration curve and DCA show that the established model to predict the accuracy of POF is higher, clinical decision of net benefit is also higher. A network calculator utilizing this predictive model was developed.

Conclusion: A predictive model incorporating five risk indicators has been established exhibiting high discriminatory power and accuracy which aids in early identification of ABP patients at risk for developing POF. This holds significant value in guiding clinical decision-making.

Background: Inflammatory bowel disease (IBD) is affected by interactions between intestinal microbial factors, abnormal inflammation, and an impaired intestinal mucosal barrier. Neutrophils (NE) are key players in IBD. Fusobacterium nucleatum (F. nucleatum) is reported to contribute to IBD progression. However, the relationship between F. nucleatum, abnormal inflammation, and intestinal barrier impairment should be interpreted to understand the role of F. nucleatum in IBD.

Methods: Dextran sulfate sodium (DSS)-induced colitis model was established and mice were orally administered with F. nucleatum. F. nucleatum colonization was confirmed by fluorescence in situ hybridization (FISH) and PCR. Intestinal barrier impairment was investigated by tight junction protein expression. Immuno-histochemistry (IHC) for Ly6G and flow cytometry detection to measure NE chemotaxis in mouse colon tissues. Caco-2 monolayers were used to evaluate epithelial integrity and permeability in vitro. A transwell model involving caco-2 cells and NE co-culture was used to assess NE chemotaxis. NE chemokines were measured by ELISA. A mouse model of NE exhaustion using an anti-Ly6G antibody was used to identify the role of NEs in F. nucleatum-induced colitis. Transcriptome sequencing and bioinformatics analysis were applied to screen cytokines and signaling pathways.

Results: Administration of F. nucleatum aggravated colitis in the DSS model. F. nucleatum infection downregulates ZO-1 and Occludin expression and increases intestinal permeability. Additionally, F. nucleatum-induced NE chemotaxis decreases the integrity and permeability of the caco-2 monolayer. F. nucleatum-induced NE chemotaxis is dependent on IEC-derived interleukin 8 (IL-8) secretion, mediated by the TLR2/ERK signaling pathway. In addition, NE exhaustion in mice inhibited F. nucleatum-induced intestinal barrier impairment and colitis.

Conclusion: F. nucleatum improves NE chemotaxis by infecting intestinal epithelial cells (IECs) to secrete IL-8 and aggravate intestinal barrier impairment, contributing to the progression of intestinal inflammation. Examining and eliminating F. nucleatum could be a valuable microbiome-based method for IBD surveillance and prevention.