Journal of Inflammation Research最新文献

Objective: Atherosclerosis(AS) is a vascular disease characterized by the development of plaque in the arteries, and atrial fibrillation (AF) is a common heart arrhythmia. These two conditions share several risk factors in common, such as aging, diabetes, obesity, and hypertension. Ferroptosis is a new mode of non-apoptotic cell death that plays a key role in cardiomyocyte death and has been associated with a variety of cardiac diseases. This study aimed to investigate the ferroptosis biomarkers and underlying biological mechanisms associated with AF and AS.

Materials and methods: The gene expression dataset was obtained from GEO database, differentially expressed genes (DEGs) and ferroptosis expressed genes (FDGs) were obtained by data processing and screening, and then functional enrichment, network construction, transcription factor prediction, identification of biomarkers by LASSO and SVM - RFE algorithms, and also immune infiltration analyses and cellular experiments were performed.

Results: In AF and AS, 1627 and 571 DEGs were identified respectively, and 128 were intersected, and 47 common FDGs were also identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs revealed that they were associated with biological processes and pathways such as leukocyte immunity, and FDGs were also involved in specific functions and pathways. Fifteen key genes were identified, CSF1R and ITGAM expression differences were verified, and seven transcription factors were predicted to be differentially expressed. Characterized genes were screened to construct models with good diagnostic efficacy, and immune infiltration showed that NUPR1 was associated with altered immune environments, and WB indicated that NUPR1 was highly expressed in the disease model.

Conclusion: Our study demonstrates that the ferroptosis gene NUPR1 plays a role in the pathogenesis of atrial fibrillation and atherosclerosis, and also provides valuable insights into their molecular mechanisms, which may contribute to the development of new targets and strategies for the treatment of these diseases.

Purpose: Spleen tyrosine kinase (Syk) is a widely-expressed cytoplasmic non-receptor tyrosine kinase involved in regulating various signaling pathways and plays an important role in chronic inflammation and autoimmune diseases. Gain-of-function SYK variants have been implicated in pediatric inflammatory bowel diseases. This study aimed to investigate the effects of gain-of-function SYK variants on the susceptibility to experimental colitis and macrophage function.

Methods: Colitis was induced using dextran sodium sulfate and dinitrobenzene sulfonic acid in mice harboring a gain-of-function variant in SYK (Syk^S544Y). Intestinal inflammation was assessed via disease activity index, histological analysis, and Western blotting. The frequencies of macrophages, phagocytosis, and reactive oxygen species (ROS) production in bone marrow-derived macrophages (BMDM) were measured via flow cytometry. Chemokines and BMDM chemotaxis were analyzed using real-time quantitative reverse transcription polymerase chain reaction and Transwell assays. The expression of nucleotide-binding domain leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome-related proteins were detected using immunohistochemistry, enzyme-linked immunoassay and Western blotting.

Results: Syk^S544Y mice exhibited increased susceptibility to experimental colitis, and macrophage infiltration in colon tissues significantly increased. We observed increased expression of macrophage chemokines in colon tissues and enhanced chemotaxis in Syk^S544Y BMDM. Additionally, we detected increased levels of fluorescent microspheres and 2.7-dichloride-hydro fluorescein diacetate-labeled ROS in Syk^S544Y BMDM. Moreover, enhanced levels of NLRP3 inflammasome-related proteins were observed in the colon tissues and BMDM from Syk^S544Y mice.

Conclusion: Gain-of-function variant in SYK may contribute to the pathogenesis of pediatric inflammatory bowel diseases by promoting macrophage migration, phagocytosis, ROS production and activation of NLRP3 inflammasomes.

Purpose: The predictive value of the Systemic Immune-Inflammation Index (SII) on mortality in patients with sepsis-associated acute kidney injury (S-AKI) remains unclear. This study aims to investigate the predictive value of SII levels at the Intensive Care Unit (ICU) on the 28-day mortality of S-AKI patients.

Patients and methods: S-AKI patients admitted to the ICU of Henan Provincial People's Hospital from January 1, 2023, to December 31, 2023. Patients who were diagnosed with S-AKI were divided into survival and death groups based on their 28-day outcome after ICU admission. Using receiver operating characteristic (ROC) curves to determine the best cut-off values and prognostic abilities of various parameters. Kaplan-Meier survival curves describe the 28-day survival of patients after ICU admission. Cox regression analysis identified the main risk factors associated with mortality in S-AKI patients, constructing a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability of this model.

Results: A total of 216 patients with S-AKI were included. ROC analysis showed that SII had the highest predictive value for mortality risk in S-AKI patients after ICU admission. Compared with the low-SII group, the high-SII group had higher 28-day (86.7% vs 32.4%, respectively, P <0.001) mortality rate. Based on Cox regression analysis, a nomogram predictive model was constructed, including age, respiratory failure, SII levels, number of organ dysfunctions at ICU admission, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHEII). The C-index for predicting the 28-day survival rate was 0.682. Decision curve analysis indicated a high level of clinical predictive efficacy.

Conclusion: SII serves as a potential biomarker for predicting the prognosis of S-AKI patients. The constructed nomogram prognostic model can aid in assessing the prognosis of S-AKI patients.

Purpose: Granulomatous lobular mastitis (GLM) has seen a rising incidence, though its pathogenesis remains unclear, posing challenges for treatment and contributing to high recurrence rates with conventional therapies. While the role of inflammatory and immune factors in GLM has been recognized, a comprehensive clinical evaluation of these markers is still lacking. This study aims to identify potential diagnostic markers and therapeutic targets by comparing immune markers and cytokine levels in GLM patients and healthy controls.

Methods: Conducted at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2023 to May 2024, this study enrolled 30 GLM patients and 15 healthy female controls in a 2:1 ratio. Serum levels of immune markers and cytokines were analyzed to explore their potential association with GLM.

Results: The study population comprised 30 GLM patients with a mean age of 33.40 ± 4.12 years and 15 healthy female controls with a mean age of 32.13 ± 6.19 years. Significantly elevated levels of C-reactive protein (CRP), Immunoglobulin A (IgA), Complement Component 3 (C3), Complement Component 4 (C4), Compliment Component 1q (C1q), Alpha1-antit-rypsin (AAT), α1-acidglycoprotein (AGP), Anti-histone antibodies (Anti-HIS), Anti-Ro52 antibodies (Anti-Ro52), Anti-double stranded DNA antibodies (Anti-dsDNA), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-α (TNF-α) were observed in GLM patients compared to controls (all P < 0.05). Subgroup analysis revealed higher levels of CRP, C3, C1q, AAT, and AGP in patients with larger mass areas and those with erythema nodosum (all P < 0.05). No significant differences were found in subgroups based on disease duration or recurrence (both P > 0.05).

Conclusion: Serum levels of CRP, IgA, AAT, AGP, Anti-HIS, Anti-Ro52, Anti-dsDNA, C3, C4, C1q, IL-6, IL-10, and TNF-α may serve as diagnostic and prognostic indicators for GLM, with CRP, AAT, AGP, and C1q being particularly indicative of disease severity. These markers offer potential therapeutic targets for GLM.

Purpose: Existing biomarkers including C-reactive protein (CRP) do not adequately distinguish active and inactive TAK. We compared serum p-glycoprotein (p-gp)/Multidrug Resistance Protein 1 (MDR1), monomeric CRP (mCRP), CRP, and mCRP:CRP ratio in Takayasu arteritis (TAK) and healthy controls and their relationship with disease activity.

Patients and methods: Serum p-gp mCRP (ELISA) and CRP (nephelometry) were compared between consecutive adults with TAK (>18 years) enrolled from a prospective cohort (n = 92) and healthy controls (n = 29), and between active vs inactive TAK (n = 46 each). In a subset of active immunosuppressive-naïve TAK (n = 29), correlation was assessed between serum p-gp and p-gp expression on circulating T helper lymphocyte populations: overall (CD4+), Th17 (CD4+IL-17+), Th17.1 (CD4+IL-17+IFN-γ+) lymphocytes [normalized to Tregs (CD4+CD25+FoxP3+)]. Changes in serum p-gp, mCRP, CRP, and mCRP:CRP were compared before and after immunosuppression (n = 29). Data was represented using median (Q1-Q3). Receiver operating characteristics (ROC) curves were generated for TAK vs controls, and active vs inactive TAK with serum p-gp, mCRP, CRP, and mCRP:CRP. Multivariable-adjusted linear regression was used to predict active disease with serum p-gp, mCRP, CRP, or mCRP:CRP.

Results: Serum p-gp (11.19 vs 8.05 ng/mL), mCRP (1.61 vs 1.25 µg/L), and CRP (5.40 vs 2.1 mg/L) were elevated in TAK vs controls (p <0.05 for all). CRP was higher and mCRP:CRP ratio was lower in active vs inactive TAK (p < 0.001). ROC curves identified moderate prediction for active disease with CRP and inactive disease with serum p-gp (area under ROC curve 0.705 and 0.392, respectively). Multivariable-adjusted linear regression confirmed association of CRP with active disease (p = 0.009) and serum p-gp with inactive disease (p = 0.041). In treatment-naïve TAK, serum p-gp negatively correlated with p-gp+Th17.1 lymphocytes (Spearman's rho=-0.39, p = 0.046). CRP and serum p-gp were significantly lowered following immunosuppressive therapy in treatment-naïve TAK (p < 0.05).

Conclusion: Serum p-gp and mCRP are elevated in TAK. Serum p-gp is associated with inactive disease.

Purpose: Prostate cancer (PCa) is seriously affecting men's health and quality of life. Existing studies indicate that PCa stem cells are responsible for promoting the growth and contributing to the high recurrence rate of PCa.

Methods: We retrieved and downloaded PCa-related datasets from both the GEO and TCGA database. These datasets were subsequently analyzed using single-cell analysis, difference analysis, WGCNA, and machine learning algorithms. WB was performed to detect the expression of Hedgehog interacting protein (HHIP), JAK1/STAT3 pathway-related protein, CD133 and CD44. Immunohistochemistry was conducted to assess the distribution of HHIP and Ki67. The levels of inflammatory factors were measured using ELISA. The tumor cell stemness was evaluated through spheroid formation assay and flow cytometry.

Results: Through bioinformatics analysis, we identified eight genes (ARHGAP24, HHIP, MITF, CBX7, PPP1R12B, PLEKHA1, ADGRA2, and PGR). Among these genes, we selected HHIP for follow-up experiments and confirmed its low expression in PCa tumor tissues. Primary cancer-associated fibroblasts (CAFs) were extracted, and to further explore the mechanism of HHIP, we overexpressed or knocked down HHIP in CAFs. Overexpression of HHIP was found to inhibit the JAK1/STAT3 pathway and the secretion of inflammatory factors, thus suppressing both the proliferation and stemness of PCa cells. Treatment of CAFs with the JAK1/STAT3 pathway inhibitor AG490 led to a decrease in inflammatory factor secretion, along with inhibition of PCa cell proliferation and stemness. On this basis, knockdown of HHIP partially reversed the inhibitory effects of AG490 on PCa cells. Finally, we constructed a mouse subcutaneous tumor model and found that HHIP inhibited tumor proliferation and densification.

Conclusion: In summary, HHIP in CAFs can regulate the JAK1/STAT3 pathway and affect the secretion of inflammatory factors, thus affecting the proliferation of PCa.

Aim: The interaction between inflammatory biomarkers (high-sensitivity C-reactive protein, hsCRP) and antioxidants (uric acid, UA) regarding prognosis after ischemic stroke or transient ischemic attack (TIA) remains inadequately explored. This study aimed to assess (1) the individual and joint effects of hsCRP and UA, and (2) the neuroprotective role of UA in patients with elevated hsCRP levels concerning poor functional outcomes at 90 days.

Methods: A prospective cohort study was conducted involving 2140 consecutive ischemic stroke or TIA patients with hsCRP and UA levels. The primary outcome was defined as a poor functional outcome, indicated by a modified Rankin Scale (mRS) score of 3-6 at 90 days, with a shift in the mRS score as a secondary outcome. Logistic regression and propensity score (PS) analyses were employed to ensure robustness.

Results: Poor functional outcome occurred in 345 (16.1%) patients. Individual effects found that the highest quartiles of hsCRP (adjusted OR = 3.090; 95% CI 2.150-4.442) and UA (adjusted OR = 0.671; 95% CI 0.551-0.883) were associated with increased or decreased risk of poor functional outcome, respectively. Joint effects (adjusted OR = 3.994; 95% CI 2.758-5.640) between hsCRP and UA on the primary outcome were more apparent in patients with high hsCRP levels (hsCRP > 1.60 mg/L) and low UA levels (UA ≤ 291.85 µmol/L). For the patients with high hsCRP levels, patients with low UA levels had a higher risk of primary and secondary outcomes, compared with those with high UA levels, after unadjusted or adjusted for hsCRP. Similar and reliable results were observed in PS-based models.

Conclusion: In patients with ischemic stroke or TIA, joint high levels of hsCRP and low UA levels significantly correlate with increased risk of poor functional outcome at 90 days. In addition, high UA levels could reduce the risk of poor functional outcome for patients with high hsCRP levels.

Purpose: Our study aimed to establish a prediction model for coronary artery disease (CAD) that integrates immune infiltration and a gene expression signature.

Methods: 613 differentially expressed genes (DEGs) and 12 hub genes were screened via the GSE113079 dataset. The pathway enrichment analysis indicated that these genes (613 DEGs and 12 hub genes) were closely associated with the inflammatory and immune responses. Based on the differentially expressed miRNA (DEmiRNA)-DEG regulatory network and immune cell infiltration, the Lasso algorithm constructed a CAD risk prediction model containing the risk score and immune score. Then, ROC-AUC and polymerase chain reaction (PCR) were performed for validation.

Results: Six hub genes (PTGER1, PIK3R1, ADRA2A, CORT, CXCL12, and S1PR5) had a high distinguishing capability (AUC > 0.90). In addition, the miRNAs targeting 12 hub genes were predicted and intersected with the DEmiRNAs, and the DEmiRNA-DEG regulatory network was then constructed. Two LASSO models and a novel CAD risk prediction model were constructed through LASSO regression analysis, and they both accurately obtained the risk of CAD. The CAD risk prediction model shows good performance (AUC = 0.988). We also constructed a valid nomogram, and PCR results verified three downregulation hub genes and one upregulation gene in the CAD risk model.

Conclusion: We demonstrated the molecular mechanism of the hub genes in CAD and provided a valuable tool for predicting the risk of CAD.

Neuregulin 4 (Nrg4), a novel adipokine produced primarily by brown adipose tissue (BAT), has been functionally characterized to exert beneficial effects on modulating energy homeostasis and glucolipid metabolism, and is closely associated with the development and progression of obesity and obesity-associated metabolic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Recently, there has been a growing focus on the relationship between circulating Nrg4 levels and T2DM-related vascular complications. In this review, we discussed the known and potential roles of Nrg4 in various physiological and pathological processes, and its association with vascular complications in T2DM, in the aim of finding a potential biomarker recommended for the clinical diagnosis, prognosis and follow-up of T2DM patients at high risk of developing vascular complications as well as providing new therapeutic approaches.

Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. Recent progress in comprehending AR has revealed the significant role played by type 2 cytokines, specifically interleukin (IL)-13, IL-4, and IL-5. These cytokines are released by helper T cells 2 (Th2) and innate lymphoid cells (ILC2s). ILC2s have the ability to interact with various immune cells and are essential in promoting both type 2 immune response and tissue repair, contributing to normal homeostatic functions within the body. This article presents a summary of the latest advancements in comprehending the activity of ILC2s, with particular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive understanding of ILC2s biology establishes a robust foundation for unraveling the pathogenesis of AR and devising innovative therapeutic approaches for its management.