Journal of Inflammation Research最新文献

Background: The protein known as Fatty Acid-Binding Protein 4 (FABP4), predominantly found in adipocytes, macrophages, and endothelial cells, has emerged as a pivotal biomarker linking inflammation and metabolism in the context of cardiovascular diseases.

Aim: The present investigation sought to elucidate the influence of FABP4 on the prognostic ramifications for patients experiencing ischemic vascular events, which encompass ischemic cerebrovascular occurrences, myocardial infarctions, and cardiovascular mortality.

Methods: A total of 1102 consecutive patients diagnosed with acute myocardial infarction (AMI) and aged over 55 years were prospectively enrolled from March 2017 to January 2020. Initially, participants were stratified into three groups according to the tertile levels of FABP4, followed by further categorization based on various lipid profiles and specific inflammatory markers.

Results: On follow-up (median 751 days, maximum 1506 days), a total of 158 ischemic events were recorded. 1) In multivariable models meticulously adjusted for age, gender, traditional coronary heart disease factors, Killip classification, and discharge medications, the association of elevated levels of FABP4 (Tertile 3 HR 1.618 [1.061 to 2.468], p=0.026), augmented concentrations of PTX3 (Tertile 3 HR 1.811 [1.211 to 2.710], p=0.004), or LL-37 (Tertile 3 HR 0.651 [0.433 to 0.981], p=0.040) with ischemic risk was markedly intensified. 2) Multivariate HRs associated with 1 standard deviation (SD) (mg/dL) increase in the FABP4 parameters were as follows in different subgroups. 1-SD difference in FABP4 was associated with a 23%, 23%, 21 and 29% increase in ischemic events over after fully adjusted the confounding risk factors among male, patients with hyperlipidemia, hypertension and diabetes respectively. 3) The Kaplan-Meier curve demonstrated significant differences between the tertiles of FABP4 index levels among all enrolled participants (p=0.0180).

Conclusion: This study reinforces the utility of FABP4 for enhancing risk stratification specifically among older patients diagnosed with ST-elevation myocardial infarction.

Objective: Type 2 diabetes mellitus (T2DM) is a serious, chronic metabolic disease globally and its pathogenesis is not completely understood yet. This study aimed to thoroughly investigate the fluctuation of inflammatory markers in the peripheral blood of patients with T2DM, which are rarely reported.

Methods: Peripheral blood samples from patients with T2DM and healthy individuals, as well as their clinical information, were collected at the Second Affiliated Hospital of Soochow University. Flow cytometry was used to analyse the immune cells and cytokines in the peripheral blood. CCK-8 assay was performed to detect the viability of THP-1 cell after treatment with 5 mΜ or 50 mΜ glucose. Flow cytometry, Western Blotting and qPCR were used to analyse the apoptosis of monocytes or THP-1 cells.

Results: The numbers of white blood cells, lymphocytes, and neutrophils substantially increased with elevated IL-6 levels. There was a significant decrease in monocytes due to increased cell apoptosis caused by sustained high glucose stimulation. Hyperglycemia reduced monocyte viability and altered monocyte subgroups by increasing the number of intermediate and non-classical monocytes.

Conclusion: In summary, our work reveals that patients with T2DM do have variations of peripheral inflammation biomarkers, especially monocytes.

Background: Associations between ulcerative colitis (UC) and ankylosing spondylitis (AS) have been reported in multiple studies, but the common etiologies of UC and AS remain unknown. Thus, in the current study, we aimed to investigate the shared genes and relevant mechanisms in UC and AS.

Methods: Using datasets for UC (GSE113079) and AS (GSE1797879), we initially identified differentially expressed genes (DEGs) through differential expression analysis. The DEGs from both datasets were intersected to identify common DEGs, relevant to both UC and AS, which were used in receiver operating characteristic (ROC) curve analysis to confirm key genes in the shared pathway. Gene set enrichment analysis (GSEA) was used to obtain information on key gene pathways and interactions with UC or AS-related diseases, followed by immune infiltration analysis. Finally, peripheral blood samples of AS and UC were used to verify the mRNA expression of the eight key genes using reverse transcription-polymerase chain reaction (RT-PCR).

Results: Our results revealed that GMFG, GNG11, CLEC4D, CMTM2, VAMP5, S100A8, S100A12 and DGKQ are potential diagnostic biomarkers of AS and UC. Rimegepant, eptinezumab, methotrexate, atogepant, and ubrogepant were identified as potential drugs for S100A12 and S100A8 in patients with UC and AS. GSEA showed that these key genes were associated with antigen processing and presentation, natural killer cell mediated cytotoxicity and the T cell receptor signaling pathway in AS and UC, and were significantly associated with immune cells in various immune-related pathways. Subsequent functional experiments revealed significant increases in the mRNA expressions of S100A12 and VAMP5 in patients with AS and UC. Additionally, CLEC4D mRNA expression was notably higher in patients with UC than in healthy controls.

Conclusion: Key genes and shared pathways were identified in UC and AS, which may improve understanding of their relationship and guide diagnosis and treatment strategies.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications which exerts detrimental effects on mothers and children. Emerging evidence has pointed to the important role of the fatty acid transporter protein CD36 in the pathogenesis of GDM. As a heavily glycosylated transmembrane protein, CD36 is widely expressed in diverse cell types, including placental trophoblasts, monocytes/macrophages, adipocytes, and pancreatic cells et al. CD36 plays a key role in lipid metabolism and signal transduction in the pathophysiological mechanism of GDM. The modified expression and functionality of CD36 may contribute to inflammation and oxidative stress in maternal tissues, interfere with insulin signaling, and subsequently influence maternal insulin sensitivity and fetal growth, increasing the risk for GDM. This review provides an overview of the current knowledge regarding the expression and function of CD36 in various tissues throughout pregnancy and explores how CD36 dysregulation can activate inflammatory pathways, worsen insulin resistance, and disrupt lipid metabolism, thereby complicating the necessary metabolic adjustments during pregnancy. Furthermore, the review delves into emerging therapeutic approaches targeting CD36 signaling to alleviate the impacts of GDM. Understanding the involvement of CD36 in GDM could yield crucial insights into its mechanisms and potential interventions for enhancing maternal and fetal health outcomes.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease and increasing evidence suggests that disturbances in the composition and function of gut microbiota are potentially implicated in the progression of RA. Further revealing the microbiota and related metabolic disorders in the preclinical stage of RA (pre-RA) is of great significance for exploration of disease mechanisms.

Methods: DBA/1 mice were injected with type II collagen on days 0 and 21 to establish collagen-induced arthritis (CIA) mouse model. Footpad thickness, serum autoantibodies, and joint histopathology were used to assess the progression of RA. A combination of 16S rRNA sequencing, untargeted metabolomics and targeted short-chain fatty acids (SCFAs) analysis were employed to comprehensively investigate the alterations of gut microbiota and fecal metabolites in CIA during the pre-RA stage.

Results: 20 days after the initial collagen immunization, CIA mice showed immune responses without joint symptoms, alongside gut microbiota disruption. Alterations were observed in 20 microbial taxa, including Oscillospira, Bifidobacterium, Ruminococcus, Allobaculum, Alistipes, Lactobacillus, and Candidatus_Arthromitus, etc. Untargeted and targeted metabolomics identified 33 altered fecal metabolites, mainly including sugars and their derivatives, amino acids, long-chain fatty acids and SCFAs, etc. Correlation analysis showed significant correlations between specific gut microbial abundances and fecal metabolite levels. Especially, SCFAs were strongly associated with Bifidobacterium, Alistipes, Ruminococcus, Anaerotruncus, and Allobaculum.

Conclusion: These findings suggest that collagen immunization leads to disruption of gut microbiome and induces changes of fecal metabolites in mice, which may play a key role in early development of RA in CIA mice.

Introduction: Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer's disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA.

Methods: We included 40 AD patients diagnosed based on clinical manifestations and AD biomarker levels in cerebrospinal fluid (CSF). Severe or nonsevere OSA (apnoea-hypopnea index ≥ 30/h and < 30/h, respectively) was diagnosed through overnight polysomnography (PSG). The expression levels of 136 inflammation-related and 84 redox-related genes were evaluated by whole blood targeted transcriptomics.

Results: Three inflammatory and six redox genes were upregulated in the blood of AD patients with severe OSA. Three of them correlated with PSG parameters. A pathway enrichment analysis showed a strong enrichment of the serotonergic synapse pathway in severe OSA AD patients.

Discussion: Our results show an upregulation of nine genes involved in NF-κB-mediated inflammation and redox metabolism in the blood of patients with mild AD with severe OSA. Therefore, severe OSA may worsen the inflammation and oxidative damage that are already altered in patients with AD.

Purpose: Baicalin is a flavonoid of Scutellaria baicalensis Georgi. It possesses antipyretic, analgesic, and anti-inflammatory effects. It has great potential to treat gout. A network pharmacology approach, molecular docking and experimental validation were applied to investigate the pharmacological mechanisms of baicalin in treating gout.

Methods: The potential targets of baicalin were retrieved from the TCMSP, PharmMapper, STITCH, and Swiss Target Prediction databases. The gout-related targets were retrieved from the DrugBank, TTD, and Genecards databases. Then, the potential targets and signaling pathways were acquired via protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, the key targets were selected to dock with baicalin based on molecular docking. Finally, in vitro experiments were conducted to further validate the predictions.

Results: A total of 318 potential targets of baicalin and 752 gout-related targets were screened. TNF, VEGFA, MMP9, PTGS2, and TLR4 might be the hub therapeutic target genes. The TLR4/NF-κB signaling pathway might be the foremost pathway in baicalin against gout. Moreover, molecular docking showed that baicalin combined well with TNF, VEGFA, MMP9, COX-2, and TLR4, respectively. The results of cell experiments suggested that baicalin could reduce the levels of inflammatory cytokines by inhibiting the TLR4/NF-κB signaling pathway in MSU-stimulated THP-1 cells and regulate the expression of these hub targets.

Conclusion: These results revealed that baicalin possesses "multitarget, multipathway, multilevel" regulatory effects. From a therapeutic standpoint, baicalin may be a promising anti-inflammatory agent for alleviating gout.

Introduction: Irritable bowel syndrome (IBS) is characterized by patients' high level of suffering. There is increasing evidence for involvement of the immune system in this disease. Adipokines have been reported to be critical immunoregulators in many clinical conditions, including gastrointestinal (GI) inflammatory diseases. Our study aimed to investigate associations of omentin-1 (a newly discovered adipokine) with IBS.

Methods: In the current study, serum levels of omentin-1 were measured in 209 patients with IBS (including three subtypes) and 188 healthy controls by enzyme-linked immunosorbent assay (ELISA). The somatic symptoms of IBS were determined by the 5-item IBS symptoms severity score (IBS-SSS), quality of life (QOL) by 34-item IBS-QOL questionnaire, and psychological disorders by Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Visceral Sensitivity Index (VSI). Therapeutic effect of omentin-1 for IBS was investigated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBS mouse model.

Results: We found that serum levels of omentin-1 were significantly decreased in patients with the diarrhea-predominant IBS (IBS-D) subtype (not the constipation or alternating subtype) compared to those in healthy subjects. Patients with lower serum omentin-1 levels suffered from higher severity of somatic symptoms (abdominal pain and distention, flatulence, rumbling), lower QOL, and worse psychological status. In a one-year follow-up, serum omentin-1 levels showed potential to reflect the disease progression. Additionally, lower omentin-1 levels were found to be accompanied with higher levels of serum pro-inflammatory cytokine concentrations in patients with IBS-D. Supplement of omentin-1 was protective against visceral hypersensitivity and mucosal inflammation in an IBS mouse model.

Discussion: Our findings highlight the potential value of serum omentin-1 levels as an innovative biomarker in IBS, emphasizing its significance in improving clinical treatment and management of the disease.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), as a common chronic liver condition globally, is experiencing an increasing incidence rate which poses significant health risks. Despite this, the detailed mechanisms underlying the disease's onset and progression remain poorly understood. In this study, we aim to identify effective diagnostic biomarkers for MASLD using microarray data combined with machine learning techniques, which will aid in further understanding the pathogenesis of MASLD.

Methods: We collected six datasets from the Gene Expression Omnibus (GEO) database, using five of them as training sets and one as a validation set. We employed three machine learning methods-LASSO, SVM, and Random Forest (RF)-to identify hub genes associated with MASLD. These genes were further validated using the external dataset GSE164760. Additionally, functional enrichment analysis, immune infiltration analysis, and immune function analysis were conducted. A TF-miRNA-mRNA network was constructed, and single-cell RNA sequencing was used to determine the distribution of key genes within key cell clusters. Finally, the expression of the key genes was further validated using the palmitic acid-induced AML-12 cell line and the MCD mouse model.

Results: In this study, through differential gene expression (DEGs) analysis and machine learning techniques, we successfully identified 10 hub genes. Among these, the key gene EGR1 was validated and screened using an external dataset, with an area under the curve (AUC) of 0.882. Enrichment analyses and immune infiltration assessments revealed multiple pathways involving EGR1 in the pathogenesis and progression of MASLD, showing significant correlations with various immune cells. Furthermore, additional cellular experiments and animal model validations confirmed that the expression trends of EGR1 are highly consistent with our analytical findings.

Conclusion: Our research has confirmed EGR1 as a key gene in MASLD, providing novel insights into the disease's pathogenesis and identifying new therapeutic targets for its treatment.

Objective: Hypertension development and progression are largely influenced by inflammation, which plays a critical role by activating the immune system and causing damage to the vascular endothelium. Metabolic dysfunction-associated fatty liver disease (MAFLD) is also associated with chronic low-grade inflammation, which drives disease progression via metabolic imbalances and adipose tissue dysfunction. This study investigates the relationship between inflammatory indices and MAFLD in hypertensive patients and assesses the predictive accuracy of these indices for MAFLD.

Methods: We performed a cross-sectional analysis involving 34,303 hypertensive patients from a Chinese hospital-based registry. The diagnosis of MAFLD was established using metabolic dysfunction criteria alongside evidence of hepatic steatosis confirmed through imaging. Complete blood counts were used to calculate inflammatory indices, including the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI). To assess the relationship between inflammatory indices and MAFLD, multivariable logistic regression was performed with adjustments for potential confounders. The diagnostic performance of these indices was analyzed using receiver operating characteristic (ROC) curves and area under the curve (AUC) calculations.

Results: Patients with MAFLD exhibited significantly elevated levels of all inflammatory indices compared to those without. After multivariable adjustment, each standard deviation increase in AISI, SIRI, and SII was associated with a 74%, 62%, and 58% increased odds of MAFLD, respectively. The AUC for AISI was 0.659, indicating moderate diagnostic accuracy. The AUCs for SIRI and SII were 0.626 and 0.619, respectively, while NLR, PLR, and MLR had lower AUCs of 0.593, 0.558, and 0.589, respectively.

Conclusion: In hypertensive patients, inflammatory indices, especially AISI, show a strong association with MAFLD, indicating their potential utility in risk stratification within clinical settings. Further research is needed to evaluate the effectiveness of these markers in the management of MAFLD.