Journal of Inflammation Research最新文献

Objective: This study evaluated the diagnostic value of plasma Neutrophil extracellular traps (NETs) levels and the index of cardiac electrophysiological balance (iCEB) in identifying silent myocardial ischemia (SMI) in maintenance hemodialysis (MHD) patients.

Methods: This cross-sectional observational study involved patients receiving MHD treatment. Data were collected on coronary angiography performed in our hospital from February 2023 to February 2024. Patients diagnosed with myocardial ischemia via coronary angiography but without obvious symptoms were grouped as the SMI group, while those without SMI were grouped as the control group. Plasma NETs levels were assessed using markers indicative of NETs components including double-stranded DNA (dsDNA), circulating free DNA (cfDNA) and myeloperoxidase, while iCEB (QT/QRS) and electrocardiographic findings were obtained. Additionally, echocardiographic parameters, inflammatory markers, and cardiac biomarkers were analyzed. Receiver operating characteristic (ROC) analysis were employed to evaluate the diagnostic accuracy of plasma NETs levels and iCEB in identifying SMI.

Results: A total of 114 patients were included, with 79 participants in the control group and 35 participants in the SMI group. The SMI group exhibited significantly elevated levels of NETs associated components (dsDNA(37.89±4.55 vs 31.64±5.32, P<0.001), cfDNA(11.27±2.03 vs 8.91±1.84, P<0.001), MPO-DNA(23.69±4.01 vs 17.52±3.41, P<0.001)), as well as higher iCEB compared to the control group(56.45±7.67 vs 45.89±6.23, P<0.001). Furthermore, electrocardiography findings, echocardiographic parameters, inflammatory markers, and cardiac biomarkers showed significant differences between the two groups. The ROC analysis demonstrated the potential diagnostic accuracies of NETs levels and iCEB, with an area under the curve (AUC) of 0.908, sensitivity of 0.987, and specificity of 0.829 for identifying SMI.

Conclusion: The study highlights the combined diagnostic value of plasma NETs levels and iCEB in identifying SMI in MHD patients, providing valuable insights into potential early detection and risk stratification strategies for this population.

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by inflammation of the sacroiliac joints and spine. Cuproptosis is a newly recognized copper-induced cell death mechanism. Our study explored the novel role of cuproptosis-related genes (CRGs) in AS, focusing on immune cell infiltration and molecular clustering.

Methods: By analyzing the peripheral blood gene expression datasets obtained from GSE73754, GSE25101, and GSE11886, we identified the expression patterns of cellular factors and immune infiltration cell related to cuproptosis. Subsequently, we employed weighted gene co-expression network analysis (WGCNA) to identify differentially expressed genes (DEGs) within each cluster and utilized the "GSVA" and "GSEABase" software packages to examine variations in gene sets enriched across various CRG clusters. Finally, we selected the best-performing machine learning model to predict genes associated with AS. Datasets (GSE25101 and GSE73754) and ELISA to assess the expression levels of the five genes and their corresponding proteins.

Results: Seven cuproptosis-related DEGs and four immune cell types were identified, revealing significant immune heterogeneity in the immune cell infiltration between the two cuproptosis-related molecular clusters in AS. The eXtreme Gradient Boosting (XGB) model showed the highest predictive accuracy, achieving an area under the receiver operating characteristic curve (AUC) of 0.725, and 5-gene prediction models were established. It showed satisfactory performance in the GSE25101 dataset (AUC = 0.812). According to the blood serum samples of AS patients and controls, PELI1 had a higher expression level (AUC = 0.703, p = 0.07), while ICAM2 and RANGAP1 had lower expression levels (AUC = 0.724, 0.745, and p = 0.011, 0.000, respectively) in AS patients.

Conclusion: We explored the correlation of cuproptosis in AS, and developed the optimal machine learning model to identify high-risk genes associated with AS. We also explored the pathogenesis and treatment strategies of AS, targeting PELI1, ICAM2, and RANGAP1.

Background: The phenomenon of "kidney-brain crosstalk" has stimulated scholarly inquiry into the correlations between kidney injury (KI) and Alzheimer's disease (AD). Nonetheless, the precise interactions and shared mechanisms between KI and AD have yet to be fully investigated. The primary goal of this study was to investigate the link between KI and AD, with a specific focus on identifying diagnostic biomarkers for KI-related AD.

Methods: The first step of the present study was to use Mendelian randomization (MR) analysis to investigate the link between KI and AD, followed by verification of in vivo and in vitro experiments. Subsequently, bioinformatics and machine learning techniques were used to identify biomarkers for KI-associated ferroptosis-related genes (FRGs) in AD, which were validated in following experiments. Moreover, the relationship between hub biomarkers and immune infiltration was assessed using CIBERSORT, and the potential drugs or small molecules associated with the core biomarkers were identified via the DGIdb database.

Results: MR analysis showed that KI may be a risk factor for AD. Experiments showed that the combination of D-galactose and aluminum chloride was found to induce both KI and AD, with ferroptosis emerging as a bridge to facilitate crosstalk between KI and AD. Besides, we identified EGFR and RELA have significant diagnostic value. These biomarkers are associated with NK_cells_resting and B_cells_memory and could be targeted for intervention in KI-related AD by treating gefitinib and plumbagin.

Conclusion: Our study elucidates that ferroptosis may be an important pathway for kidney-brain crosstalk. Notably, gefitinib and plumbagin may be therapeutic candidates for intervening in KI-associated AD by targeting EGFR and RELA.

Objective: Gastric cancer (GC) is a common malignant tumor of the digestive tract. Accumulating studies suggest that inflammation is linked with the pathogenesis of GC. The study delves into novel hematological inflammatory markers, such as systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and prognostic nutritional index (PNI), to explore their potential applications in early diagnosis of GC.

Methods: From October 2020 and August 2024, 1339 GC patients admitted to our hospital were enrolled in this study. The pre-treatment SII, SIRI, and PNI was calculated from peripheral blood samples. Univariate and multivariate logistic regression analyses were utilized to verify independent risk factors for patients, and constructed the nomograms. The correlation between hematological indicators and tumor-node-metastasis (TNM) stage was assessed through Spearman's analysis.

Results: Eligible patients and healthy controls were grouped by gender. The diagnostic ability of PNI was significantly superior to other indicators to diagnose male GC (area under the curve [AUC]=0.908, 95% CI: 0.892-0.925) and female GC (AUC=0.890, 95% CI: 0.865-0.914). Besides, the combination of hematological indicators is more effective in diagnosing GC patients, especially for male patients (AUC=0.916, 95% CI: 0.901-0.932, sensitivity: 84.98%, specificity: 84.29%). The C-statistic of Nomogram model was 0.917 for males and 0.875 for females. In both male and female cohorts, CEA, SII, and SIRI were positively correlated with TNM stage, while PNI was negatively correlated. The AUC of CEA, SII, SIRI, and PNI combined for the diagnosis in the early stage of male GC patients was 0.897 (95% CI: 0.875-0.918, sensitivity: 86.57%, specificity: 80.30%) is higher than that of in the advanced stage (AUC: 0.745, 95% CI: 0.710-0.780, sensitivity: 56.53%, specificity: 82.86%).

Conclusion: The combined CEA, SII, PNI, and SIRI could be used as screening biomarkers in diagnosing GC, especially in the early stage of male GC patients.

Coagulopathy in sepsis is common and is associated with high mortality. Although immunothrombosis is necessary for infection control, excessive thrombus formation can trigger a systemic thrombo-inflammatory response. Immunothrombosis plays a core role in sepsis-induced coagulopathy, and research has revealed a complex interplay between inflammation and coagulation. Different mechanisms underlying sepsis-related coagulopathy are discussed, including factors contributing to the imbalance of pro- and anticoagulation relevant to endothelial cells. The potential therapeutic implications of anticoagulants on these mechanisms are discussed. This review contributes to our understanding of the pathogenesis of coagulopathy in patients with sepsis. Recent studies suggest that endothelial cells play an important role in immunoregulation and hemostasis. Meanwhile, the non-anticoagulation effects of anticoagulants, especially heparin, which act in the pathogenesis of coagulopathy in septic patients, have been partially revealed. We believe that further insights into the pathogenesis of sepsis-induced coagulopathy will help physicians evaluate patient conditions effectively, leading to advanced early recognition and better decision-making in the treatment of sepsis.

Background: The common occurrence of atrial fibrillation (AF) as a cardiac arrhythmia, along with its link to sleep deprivation (SD), is gaining more acknowledgment. Even with progress in comprehending the development of AF, the molecular connections between SD and AF are still not well-defined. The objective of this research was to pinpoint the shared molecular routes responsible for SD-induced AF and investigate possible treatment targets.

Methods: Utilizing bioinformatics, we examined two transcriptome datasets from the Gene Expression Omnibus (GEO) database to pinpoint genes with differential expression (DEGs) common to SD and AF. Analyses focusing on functional enrichment, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted to pinpoint crucial biological mechanisms and pathways. Furthermore, we utilized immunofluorescence and Western blot techniques to evaluate YBX1 expression and its role in activating NLRP3 inflammasomes in a rat model induced by SD.

Results: A total of 540 common DEGs were precisely identified between the AF and SD data collections. Studies emphasizing functional enrichment have highlighted the significance of inflammation pathways, particularly the NOD-like receptor signaling route. The application of machine learning uncovered four crucial genes-CDC5L, MAPK14, RAB5A, and YBX1-with YBX1 becoming the predominant gene in diagnostic processes. Investigating immune penetration revealed significant connections between YBX1 expression and specific immune cell types, notably CD8+ T cells and M1 macrophages. Live studies have demonstrated that SD amplifies the atrial electrical rearrangement, structural changes, the infiltration of inflammatory cells, and the heightened presence of YBX1 along with inflammasome elements.

Conclusion: The research pinpoints YBX1 as a crucial gene in SD-related AF, possibly influencing its impact via the NOD-like receptor signaling route and the invasion of immune cells. The results offer crucial understanding of the molecular processes behind AF and propose YBX1 as a possible treatment focus to reduce the risk of AF caused by SD.

Background: Synovitis is one of the key pathological feature driving osteoarthritis (OA) development. Diverse programmed cell death (PCD) pathways are closely linked to the pathogenesis of OA, but few studies have explored the relationship between PCD-related genes and synovitis.

Methods: The transcriptome expression profiles of OA synovial samples were obtained from the Gene Expression Omnibus (GEO) database. Using machine learning algorithms, Hub PCD-related differentially expressed genes (Hub PCD-DEGs) were identified. The expression of Hub PCD-DEGs was validated in human OA samples by qRT-PCR. A diagnostic model for OA was constructed based on the expression levels of Hub PCD-DEGs. Unsupervised consensus clustering analysis and weighted correlation network analysis (WGCNA) were employed to identify differential clustering patterns of PCD-related genes in OA patients. The molecular characteristics of Hub PCD-DEGs, their role in synovial immune inflammation, and their association with the immune microenvironment were investigated through functional enrichment analysis and ssGSEA immune infiltration analysis. Single-cell RNA sequencing analysis provided insights into the characteristics of distinct cell clusters in OA synovial tissues and their interactions with Hub PCD-DEGs.

Results: We identified five Hub PCD-DEGs: TNFAIP3, JUN, PPP1R15A, INHBB, and DDIT4. qRT-PCR analysis confirmed that all five genes were significantly downregulated in OA synovial tissue. The diagnostic model constructed based on these Hub PCD-DEGs demonstrated diagnostic efficiency in distinguishing OA tissues as well as progression of OA. Additionally, a correlation was observed between the expression levels of Hub PCD-DEGs, immune cell infiltration, and inflammatory cytokine levels. We identified two distinct PCD clusters, each exhibiting unique molecular and immunological characteristics. Single-cell RNA sequencing further revealed dynamic and complex cellular changes in OA synovial tissue, with differential expression of Hub PCD-DEGs across various immune cell types.

Conclusion: Our study suggests that PCD-related genes may be involved in development of OA synovitis. The five screened Hub PCD-DEGs (TNFAIP3, JUN, PPP1R15A, INHBB and DDIT4) could be explored as candidate biomarkers or therapeutic targets for OA.

Background: Adenoid hypertrophy is a common disorder of childhood, and has an unclear pathogenesis. At the beginning of the COVID-19 pandemic, there was a significant reduction in the incidence of adenoid hypertrophy in children under long-term home quarantine, providing a rare research model to explore the pathogenesis and treatment targets of adenoidal hypertrophy in children.

Methodology: Before and during the home quarantine period, adenoids that underwent surgery were detected using label-free proteomics. Differences in protein expression were analyzed using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, Protein-protein interaction, and immunohistochemistry analysis.

Results: Long-term home quarantine had a profound impact on the proteomics of pediatric adenoids, with up-regulated and down-regulated proteins of 28 and 92 downregulated proteins, respectively. Functional enrichment analysis showed that the differentially expressed proteins were mainly enriched in pathways such as leukocyte activation, inflammatory response, IL-1 production, Th17 cell differentiation, and IL-17 signaling. In the home quarantine group, inflammation-related proteins (TNF-α, IL-6), CD36, and S100A2, were considerably reduced, whereas NQO1 levels increased significantly, potentially alleviating adenoid hypertrophy. NQO1, CD36, NDUFS8, and NDUFAF2 exhibited strong interactions.

Conclusion: This study identified some candidate differential proteins, such as NQO1, CD36, S100A2, and the inflammation pathways involved in adenoid hypertrophy in preschool children.

Purpose: Treatment of severe burn wound injury remains a significant clinical challenge as serious infections/complex repair process and irregulating inflammation response. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have a multidirectional differentiation potential and could repair multiple injuries under appropriate conditions. Poly(L-lysine)-graft-4-hydroxyphenylacetic acid (PLL-g-HPA) hydrogel is an enzyme-promoted biodegradable in hydrogel with good water absorption, biocompatibility and anti-bacterial properties. Therefore, the aim of this study was to evaluate the therapeutic effect of hUC-MSCs combined with PLL-g-HPA hydrogel on full thickness burn injury in rat model.

Methods: The PLL-g-HPA hydrogel was developed and characterized by Scanning Electron Microscopy (SEM), Fourier-Transform Infrared Spectroscopy (FTIR), Hydrogen-1 nuclear magnetic resonance (H-NMR). The cytotoxicity to human foreskin fibroblasts (HFF) were assessed by CCK-8 assay and live/dead quantification and antibacterial activity against Escherichia coli and Staphylococcus aureus was also detected by colony forming unit. A full-thickness burn wound injury model in 12 SD rats was established, and the therapeutic effect of PLL-g-HPA hydrogel combined with hUC-MSCs was detected by healing time/Histology/inflammation factor expression level.

Results: The findings from SEM, FTIR, and HFF analyses demonstrated the successful synthesis of PLL-g-HPA hydrogels. These hydrogels exhibited low cytotoxicity at minimal concentrations while maintaining excellent moisture retention and antibacterial properties. Compared to the control group, treatment with PLL-g-HPA hydrogel in conjunction with hUC-MSCs significantly enhanced wound healing, modulated inflammatory responses, and promoted angiogenesis as well as re-epithelialization in rat models.

Conclusion: The PLL-g-HPA hydrogel in conjunction with hUC-MSCs represents a promising therapeutic approach for the management of burn wounds.

Major Depressive Disorder (MDD) is a common and severe neuropsychiatric condition resulting in irregular alterations in affect, mood, and cognition. Besides the well-studied neurotransmission-related etiologies of MDD, several biological systems and phenomena, such as the hypothalamic-pituitary-adrenal (HPA) axis, reactive oxygen species (ROS) production, and cytokine signaling, have been implicated as being altered and contributing to depressive symptoms. However, the manner in which these factors interact with each other to induce their effects on MDD development has been less clear, but is beginning to be understood. Flavins are potent biomolecules that regulate many redox activities, including ROS generation and energy production. Studies have found that circulating flavin levels are modulated during stress and MDD. Flavins are also known for their importance in immune responses. This review offers a unique perspective that considers the redox-active cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), as vital substrates for linking MDD-related maladaptive processes together, by permitting stress-induced enhancement of microglial interleukin-1 beta (IL-1β) signaling.