Journal of Inflammation Research最新文献

Purpose: Chronic heart failure (CHF) is a major public health issue with high morbidity and mortality, where inflammation plays a key role in its progression. Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and NOD-like receptor protein 3 (NLRP3) regulate inflammatory responses, but their prognostic value in CHF remains unclear. This study aims to investigate the association between serum levels of TNFAIP3 and NLRP3 and the risk of major adverse cardiovascular events (MACEs) in patients with CHF.

Patients and methods: A cohort study was conducted involving 318 patients with CHF and 122 controls. Serum levels of TNFAIP3 and NLRP3 were measured using enzyme-linked immunosorbent assay method. Propensity score matching (PSM) was used to control for confounders. Multivariable logistic regression, restricted cubic spline, threshold effect, and receiver operating characteristic (ROC) analyses were employed to evaluate the associations between biomarker levels and MACEs over a 6-month follow-up.

Results: After PSM, patients with CHF had significantly higher TNFAIP3 and NLRP3 levels than controls (both p < 0.001). Compared to CHF patients without MACEs, those with MACEs exhibited significantly lower levels of TNFAIP3 and higher levels of NLRP3. Multivariable analysis confirmed TNFAIP3 as an independent protective factor [odds ratio (OR)= 0.61, 95% confidence interval (CI): 0.40-0.93) and NLRP3 as an independent risk factor (OR = 1.24, 95% CI: 1.17-1.31) for MACEs. ROC analysis demonstrated NLRP3 (AUROC = 0.756) had better predictive ability than TNFAIP3 (AUROC = 0.611).

Conclusion: TNFAIP3 and NLRP3 are significantly associated with the risk of MACEs in patients with CHF and NLRP3 demonstrates stronger predictive performance than TNFAIP3.

Purpose: Previous studies have highlighted a strong association between programmed cell death and ulcerative colitis (UC). Banxia Xiexin decoction (BXD) is a thoroughly validated formula with an extensive history of clinical application for treating UC. However, it remains unclear whether BXD regulates pyroptosis and necroptosis in UC. This study focused on pyroptosis and necroptosis to investigate the underlying mechanisms of BXD on UC.

Material and methods: The therapeutic effects of BXD were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. To identify key signaling pathways, transcriptomics and proteomics were performed, followed by the validation of these pathways using Western blotting, immunohistochemistry, and immunofluorescence in vivo and in vitro. The bioactive components of BXD were screened through pharmacodynamic experiments, molecular docking, and surface plasmon resonance (SPR) analysis.

Results: BXD significantly alleviated UC symptoms by reducing inflammatory levels and improving intestinal barrier function. Multi-omics analyses demonstrated a significant alteration in pyroptosis- and necroptosis-related signaling pathways following BXD intervention. BXD suppressed pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway in the colons of UC model mice and in LPS+TNF-α-induced NCM460 cells. The screening of active ingredients revealed that baicalin and glycyrrhizic acid significantly affected LDH release and IL-1β levels. Molecular docking and SPR analyses demonstrated that baicalin targeted P2RX7 with high affinity and that glycyrrhizic acid targeted TNFR1 with moderate affinity.

Conclusion: BXD ameliorates inflammation and intestinal barrier dysfunction in UC by suppressing pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway. Baicalin and glycyrrhizic acid are identified as the pharmacodynamic components responsible for these therapeutic effects. These findings can provide molecular mechanisms and a material basis for the clinical application of BXD in the treatment of UC.

Background: Early in-hospital mortality remains an important concern after coronary artery bypass grafting. Existing risk scores, such as EuroSCORE and STS, rely mainly on demographic and clinical parameters and do not adequately incorporate routine hematological markers. This study aimed to develop and validate the Hematological Inflammatory Gradient Score (HIGS), a novel model derived from routinely available hematological indices, to predict early postoperative mortality after coronary artery bypass grafting (CABG).

Methods: A retrospective, single-center cohort of 202 patients undergoing elective isolated CABG between January 2022 and March 2024 was analyzed. HIGS was calculated using standardized z-scores of red cell distribution width (RDW), platelet distribution width (PDW), and immature granulocyte percentage (IG%). Discrimination was assessed with ROC curve analysis, while logistic regression identified independent predictors of mortality.

Results: In-hospital mortality occurred in 10.9% (22/202) of patients. Compared with survivors, non-survivors had significantly higher HIGS values (1.02 ± 0.74 vs -0.12 ± 0.43, p < 0.001). HIGS demonstrated the highest discriminative ability for mortality prediction among tested parameters (AUC = 0.862, 95% CI: 0.794-0.931), with 86.4% sensitivity and 78.9% specificity at the optimal cut-off (>0.44). When added to the base model consisting of age, ejection fraction, and urea, HIGS provided a modest improvement in discrimination (AUC increase from 0.639 to 0.665). In multivariate analysis, lower ejection fraction, higher IG%, and elevated urea were independent predictors of mortality, and inclusion of HIGS improved model performance.

Conclusion: HIGS is a simple, inexpensive, and biologically plausible score derived from routine blood tests that reliably stratifies early mortality risk after CABG. If confirmed in larger, prospective multicenter studies, HIGS may serve as a practical adjunct to conventional risk models in perioperative decision-making. Given the retrospective, single-center design and limited event count, these findings should be interpreted cautiously, and external validation is required.

Background: Although increasing evidence implicates circular RNAs (circRNAs) in the pathogenesis of various autoimmune diseases, the potential role of circRNAs in rheumatoid arthritis (RA) remains poorly understood.

Methods: Utilizing a two-phase study design, we performed high-throughput RNA sequencing on peripheral blood mononuclear cells (PBMCs) from three treatment-naïve RA patients and three healthy controls (HCs), followed by validation in an independent cohort of 32 RA patients and 32 HCs using real-time quantitative polymerase chain reaction (RT-qPCR).

Results: A total of 157 circRNAs were differentially expressed between RA patients and HCs, including 91 upregulated and 66 downregulated circRNAs. Six circRNAs, including hsa_circ_0001394, hsa_circ_0001998, hsa_circ_0009172, hsa_circ_0006732, circRNA2842, and circRNA8330, were further confirmed to be upregulated in RA. Among them, hsa_circ_0001394 demonstrated perfect sensitivity (100%), and hsa_circ_0001998 exhibited perfect specificity (100%) in distinguishing RA from HCs. All six circRNAs showed considerable diagnostic performance, with area under the curve (AUC) values ranging from 0.794 to 0.993. Additionally, specific circRNAs correlated significantly with established serological markers: hsa_circ_0009172 expression was negatively associated with anti-cyclic citrullinated peptide (anti-CCP) antibody titers, whereas hsa_circ_0001998 expression correlated positively with rheumatoid factor (RF). Pathway enrichment analysis suggested that these differentially expressed circRNAs may participate in RA pathogenesis through key pathways like Wnt, calcium and VEGF signaling.

Conclusion: Our study identifies several novel circRNAs with high diagnostic utility for RA, highlighting their potential as promising biomarkers and therapeutic targets.

Background: The role of ITGB7 in pancreatic ductal adenocarcinoma (PDAC) remains unreported. This study aims to investigate the effects of ITGB7 on inflammation and immune microenvironment, and its correlation with the response to immune checkpoint inhibitors (ICIs).

Methods: The correlation between ITGB7 expression and the response to ICIs treatment was evaluated in our clinical cohort and in the TCGA dataset. TMT and PRM proteomic analysis identified ITGB7-associated proteins, biological processes, and signal pathways. The role of ITGB7 in macrophage polarization was explored both in vivo and in vitro. Additionally, ITGB7-associated immune and inflammatory regulatory molecules, and immune cells infiltration in PDAC were assessed using TCGA dataset. An ITGB7-associated ceRNA network was constructed to explore post-transcriptional regulation.

Results: Clinical sample analysis and TCGA analysis showed that ITGB7 was significantly overexpressed in PDAC compared to normal pancreatic tissue. Patients with high ITGB7 expression demonstrated a better response to ICIs blockade therapy and exhibited a favorable prognosis. Proteomic analysis indicated that ITGB7 regulates immune- and inflammation- related proteins. ITGB7 expressed in pancreatic tumor cells promoted M2 macrophage polarization. ITGB7 modulated immune-related signaling pathways and was positively correlated with expression of immune checkpoint molecules, inflammatory cytokines, and immune-stimulating molecules. ITGB7 correlated with increased immune cell infiltration.

Conclusion: We provide the first evidence that ITGB7 expression correlates with immune regulation, inflammatory modulation, and immune cell infiltration in PDAC. ITGB7 is associated with enhanced immunotherapy response and improved prognosis. This study provides novel insights into the regulation of PDAC immune responses.

Purpose: Benign prostatic hyperplasia (BPH) is a common condition in older men, but treatment is often associated with complications and high recurrence rates. Previous clinical studies have shown that Brain Awakening and Mind Opening (BAMO) acupuncture and Simiao Pill can improve lower urinary tract symptoms in patients with BPH. This study explores the potential mechanisms behind these treatment methods for BPH using a mice model.

Methods: Six-week-old ICR male mice were divided into 5 groups (n=10). The Mice were injected subcutaneously with TP (5mg/kg/d) / corn oil (equal volume) for 28 days to establish a BPH model and a control group. After successful modelling, the mice were treated with distilled water for 21 days, while the BAMO acupuncture group, the Simiao pill group, and the mixed group were treated accordingly (BAMO acupuncture at Neiguan (PC6), Sanyinjiao (SP6), and Guanyuan (CV4) acupoints for 30 minutes every other day, or Simiao pill once a day).

Results: BAMO acupuncture, Simiao pills, and their combination effectively reduced prostate hyperplasia in mice. The observed therapeutic effects likely involve multiple mechanisms: suppression of dihydrotestosterone (DHT) synthesis via reduced testosterone levels and downregulated SRD5A2 expression (P<0.01), promotion of prostate cell apoptosis (indicated by an increased BAX/BCL-2 ratio, P<0.05), and mitigation of inflammation through decreased levels of pro-inflammatory cytokines IL-6 and TNF-α (P<0.05).

Conclusion: BAMO acupuncture and Simiao pill can restore normal prostate tissue structure in mice through multiple mechanisms: (1) reducing DHT production; (2) promoting apoptosis; (3) reducing inflammatory responses. Future studies could further investigate the hormonal regulation and apoptosis of BAMO acupuncture in mice.

With 13% of global tumorigenesis related to pathogens and 2.2 million new tumour cases related to viral infections every year, the role played by viruses in tumorigenesis cannot be ignored. At present, the viruses that have been identified as carcinogenic substances are EB virus, hepatitis B virus, hepatitis C virus, Kaposi's sarcoma virus, human immunodeficiency virus type 1, human T-cell lymphotropic virus type 1, human papillomavirus, Merkel cell polyomavirus, and BK virus. There are also a number of viruses which have not been designated as carcinogens, but which are also closely related to the tumours' development, such as Simian virus 40, JC virus and human cytomegalovirus. Human oncolytic viruses are divided into DNA oncolytic viruses and RNA oncolytic viruses, which are highly diverse and have different tumorigenic mechanisms. This article focuses on these confirmed DNA tumor viruses and RNA tumor viruses, delving into the various tumor types they cause and the mechanisms behind them. Based on the comparative analysis of their oncogenic pathways, we conclude that common mechanisms, such as the disruption of tumor suppressor proteins, chronic inflammation, and immune evasion, presenting actionable targets for both prophylactic intervention and precision therapy against virus-associated cancers.

Background and purpose: Chronic atrophic gastritis (CAG), affecting approximately 20-30% in high-risk populations, contributes to significant morbidity and mortality due to its progression to gastric cancer. Despite two decades of research into its pathogenesis, the vast body of literature has not yet been systematically mapped. A comprehensive bibliometric analysis mapping the field's evolution, collaborative networks, and knowledge gaps remains lacking. Therefore, we conduct a 20-year bibliometric analysis (2005-2024) of research on the mechanism of CAG to identify seminal works, emerging themes, evaluate global collaboration networks, and highlight translational challenges and opportunities.

Patients and methods: Data were retrieved from the Web of Science Core Collection (WoSCC) spanning from January 1, 2005, to December 31, 2024. Bibliometric analysis was performed using CiteSpace and VOSviewer to analyze publication trends, influential authors and institutions, keyword clusters, and citation bursts.

Results: A total of 954 papers were identified, with China leading in publication output (41.51%), followed by the USA (15.20%). The USA demonstrated high centrality in international collaboration. Key journals included WORLD J GASTROENTERO and GASTROENTEROLOGY. Prolific authors such as Liu Yuetao and co-cited authors like CORREA P were identified. Keyword analysis revealed "Helicobacter pylori" as the most prominent term, with clusters focusing on traditional Chinese medicine, macrophage biology, and gastric intestinal metaplasia.

Conclusion: The study highlights the significant research output and collaboration in CAG, emphasizing the importance of interdisciplinary approaches and international partnerships. Future research should focus on integrating traditional knowledge with modern mechanistic studies and addressing emerging themes such as microbiome dysbiosis and precision medicine.

Purpose: Chronic low-grade inflammation is increasingly recognized as a contributing factor in the development of cardiovascular events. This study aimed to evaluate the association between time-weighted cumulative exposure to high-sensitivity C-reactive protein (cumhsCRP) and the risk of new-onset cardiac conduction block (CCB).

Patients and methods: A total of 48,703 participants from a prospective community-based cohort were included. The average exposure time for cumhsCRP was 6.36 years. Participants were stratified into two groups: cumhsCRP < 2 mg/L and cumhsCRP ≥ 2 mg/L. The incidence of new-onset cardiac conduction block and its subtypes was identified through standard 12-lead electrocardiograms. Cox proportional hazards models were used to assess the relationship between cumhsCRP levels and incident CCB risk, adjusting for potential confounders. A restricted cubic spline curve further explored the dose-response pattern.

Results: During a mean follow-up period of 9.24 years, 803 cases of new-onset CCB were documented (incidence rate: 1.65%). After full multivariable adjustment, individuals in the cumhsCRP ≥ 2 mg/L group exhibited a significantly higher risk of CCB compared to those with cumhsCRP < 2 mg/L (HR: 1.24, 95% CI: 1.07-1.44). The RCS analysis suggested a linear association between log-transformed cumhsCRP and CCB risk (p for non-linearity = 0.294).

Conclusion: Elevated cumulative exposure to high-sensitivity C-reactive protein is independently associated with an increased risk of developing CCB, especially left bundle branch block and left anterior fascicular block. This study will provide new insights into the prevention of CCB.

Purpose: To explore the mechanism of cuprotosis in psoriasis, screen cuprotosis related genes (PDCRGs) in psoriasis, and provide new targets for precise diagnosis and treatment of psoriasis.

Material and methods: Integrate bioinformatics analysis and experimental validation. Firstly, based on the GEO database (GSE161683, GSE166388, GSE277173), differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) in psoriasis were screened; Identification of differential cuprotosis related genes (PDCRGs) in psoriasis using a self built cuprotosis gene database (1098 CRGs); Screen key PDCRGs through PPI network, machine learning, and ROC analysis. Subsequently, a mouse model of psoriasis induced by imiquimod (IMQ) was constructed, and gene expression, copper ion levels, inflammatory factors, and oxidative stress factors were validated using qPCR, Western blot, immunohistochemistry, fluorescence, and ELISA.

Results: Thirty-four PDCRGs were identified, among which STAT1, DLD, GBP1, CXCL10, PDHB, and LIAS are Hub genes. Machine learning and ROC analysis further identified APOL6, CD274, and LIAS as key diagnostic biomarkers. PDCRGs are significantly enriched in the TCA cycle, copper ion transport, and glucose metabolism pathways. The levels of FDX1 and serum copper ions were increased in the skin lesions of psoriasis mice, accompanied by upregulation of TCA cycle key proteins and PDCRGs expression; Copper overload triggers oxidative stress and inflammation cascade.

Conclusion: APOL6, CD274, and LIAS were screened as cuprotosis markers in psoriasis. Overexpression of these PDCRGs in psoriasis model mice can promote copper ion accumulation and interfere with the TCA cycle, increase oxidative stress and inflammation levels, and ultimately lead to the occurrence of psoriasis. Therefore, targeted intervention of cuprotosis is of great significance for the clinical treatment of psoriasis.