Journal of Inflammation Research最新文献

Purpose: Sepsis is the 10th leading cause of death globally and the most common cause of death in patients with infections. Ubiquitination plays a key role in regulating immune responses during sepsis. This study combined bioinformatics and Mendelian randomization (MR) analyses to identify ubiquitin-related genes (UbRGs) with unique roles in sepsis.

Methods: Relevant genes were obtained from the GSE28750 dataset and GSE95233, weighted gene co-expression network analyses were performed to identify gene modules, and differentially expressed UBRGs (DE-UBRGs) were generated by differentially expressed genes (DEGs) crossover with key modular genes and UBRGs in sepsis and normal samples. Causal relationships between sepsis and UbRGs were analysed using MR, performance diagnostics were performed using subject work characteristics (ROC) curves, and an artificial neural network (ANN) model was developed. On this basis, immune infiltration was performed and the expression of key genes was verified in animal models.

Results: 3022 DEGs were found between sepsis and normal. A total of 2620 genes were obtained as key modular genes. Crossing DEGs, key modular genes and UBRGs yielded 93 DE-UBRGs. MR results showed WDR26 as a risk factor for sepsis (OR>1) and UBE2D1 as a protective factor for sepsis (OR<1), which was reinforced by scatterplot and forest plot. ROC curves showed that WDR26 and UBE2D1 could accurately differentiate between sepsis and normal samples. Confusion matrix and ROC curve results indicate that the artificial neural network model has strong diagnostic ability. The results of immune infiltration showed that.WDR26 was negatively correlated with plasma cells, while UBE2D1 was positively correlated with CD4 naïve T cells. Significant differences between sepsis and normal were obtained between UBE2D1 and WDR26 in the animal model.

Conclusion: There appeared to be a causal relationship between sepsis, WDR26 and UBE2D1. The insights were of value for effective clinical diagnosis and treatment in sepsis.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with chronic and recurrent characteristics caused by multiple reasons, including iron overload, intestinal inflammation, and barrier dysfunction. Here, we investigated the effects of chemical inhibition of NOXs and NLRP3 activity on colonic iron metabolism and inflammatory reactions in a murine model of dextran sodium sulfate (DSS)-induced ulcerative colitis.

Methods: The mice were randomly divided into five groups: normal control group, DSS-induced ulcerative colitis model group (DSS), DSS + Dapansutrile group, DSS + Diphenyleneiodonium chloride group, and DSS + Dapansutrile + Diphenyleneiodonium chloride group. On day 14, the mice were euthanized. Tissues were collected and analyzed to determine the effects of chemical inhibition of NOXs and NLRP3 activity on colonic iron metabolism and inflammatory reactions of dextran sodium sulfate-induced ulcerative colitis. Measurements such as weight, disease activity index, HE staining, Prussian blue staining, immunohistochemical and immunofluorescence, ELISA, flow cytometry detection, Western blot, and Quantitative Real-Time PCR were conducted.

Results: Chemical inhibition of NOXs and NLRP3 in vivo could significantly reduce colonic iron overload and macrophage infiltration, thus alleviating colonic inflammatory response and tissue damage. Notably, the inhibition of NOXs significantly inhibited the expression of NLRP3 and oxidative damage, but the inhibition of NLRP3 had no significant effect on the expression of NOXs and oxidative damage, suggesting NOXs may exert their effects other than oxidative damage through NLRP3.

Conclusion: To our knowledge, this work is the first to reveal that NLRP3 mediates NOXs-induced colonic iron overload and inflammation rather than oxidative damage in ulcerative colitis murine model, suggesting that the NOXs might promote ulcerative colitis by inducing colonic iron overload and macrophage infiltration dependent or partially dependent on NLRP3, as well as oxidative damage independent of NLRP3, which imply that both NOXs and NLRP3 are attractive targets for anti-colitis therapy.

Background and aims: Tuberculous pericarditis (TBP) is a severe, life-threatening complication, yet its diagnosis is highly challenging due to the lack of sufficient diagnostic tools. The aim of this study was to develop and validate a diagnostic prediction model suitable for primary healthcare institutions to predict the risk of TBP.

Methods: We collected detailed medical histories, imaging examination results, laboratory test data, and clinical characteristics of patients and used the Least Absolute Shrinkage and Selection Operator (LASSO) technique combined with logistic regression analysis to construct a predictive model. The diagnostic efficacy of the model was assessed using the Receiver Operating Characteristic (ROC) curve, calibration curve, and Decision Curve Analysis (DCA).

Results: A total of 304 patients were included in the study, with a median age of 64 years, of which 144 were diagnosed with tuberculous pericarditis. Patients were randomly assigned to the training and validation sets in a 7:3 ratio. LASSO logistic regression analysis revealed that weight loss (P=0.011), body mass index (BMI) (P=0.061), history of tuberculosis (P=0.022), history of dust exposure (P=0.03), moderate to severe kidney disease (P=0.005), erythrocyte sedimentation rate (ESR) (P=0.084), and B-type natriuretic peptide (BNP) (P<0.001) are independent risk factors for TBP. Based on these factors, we constructed a nomogram with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.757 in both the training and validation sets, indicating high discriminative ability of the model. Calibration curve analysis showed good consistency of the model. DCA results indicated that the model has significant clinical application value when the threshold probability is set between 1-100% (training set) and 30-100% (validation set).

Conclusion: We successfully developed a nomogram model for predicting tuberculous pericarditis, which can assist clinicians in improving diagnostic accuracy and reducing misdiagnoses and missed diagnoses in primary healthcare settings.

The Vacuolar Protein Sorting 35 (VPS35)-Retromer complex plays a pivotal role in intracellular protein trafficking and recycling. As an integral component of the Retromer complex, VPS35 selectively recognizes and retrogradely transports membrane protein receptors to the trans-Golgi network, thereby preventing the degradation of transmembrane proteins by lysosomes after they have fulfilled their physiological functions, and facilitating their continued activity. VPS35 regulates autophagy, mitophagy, mitochondrial homeostasis, and various other biological processes, including epidermal regeneration, neuronal iron homeostasis, and synaptic function. Studies have shown that mutations or dysfunctions in VPS35 disrupt the normal operation of Retromer, impair neuronal health and survival, and contribute to the onset of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Additionally, VPS35 modulates tumor growth and metastasis in cancers such as liver and breast cancer through the regulation of multiple signaling pathways. Targeting VPS35 might be a potential therapy in clinic treatment of neurodegenerative diseases and cancers.

Background: Oxygen supplementation is essential for patients with a multitude of diseases but can cause severe hyperoxia-induced lung injury (HLI), necessitating the identification of therapeutic targets to improve clinical outcomes. Cuproptosis, a novel copper-dependent form of cell death characterized by proteotoxic stress resulting from lipoylated protein aggregation and loss of iron-sulfur cluster proteins, is distinct from other forms of cell death. However, the role of cuproptosis in HLI remains unclear.

Methods: We established an HLI model in MLE-12 cells and C57BL/6 mice to investigate the involvement of cuproptosis in hyperoxia-induced toxicity.

Results: We observed a time-dependent increase in the cuproptosis-related gene Fdx1 under hyperoxia. Moreover, hyperoxia activated the membrane-associated copper transporter SLC31A1 and significantly elevated copper levels in MLE-12 cells, as well as in the serum and lung tissue of C57BL/6 mice. Further analysis revealed that hyperoxia significantly altered the expression of cuproptosis-related genes without affecting DLAT levels, but significantly increased lipoylated-DLAT levels. ELISA, CCK-8 assays, HE staining, lung wet-to-dry weight ratio, and bronchoalveolar lavage fluid analysis demonstrated that treatment with the cuproptosis inhibitor TTM reduced pro-inflammatory cytokines (TNF-α and IL-1β) and alleviated hyperoxia-induced injury in both MLE-12 cells and C57BL/6 mice.

Conclusion: Our study identifies the involvement of cuproptosis in HLI, providing new insights into the pathogenesis of hyperoxic lung injury and potential therapeutic strategies.

Objective: To analyze the clinical efficacy of combined minocycline hydrochloride and tinidazole therapy for chronic periodontitis (CP).

Methods: A retrospective analysis was conducted on clinical data from 93 CP patients admitted to our hospital from January 2021 to January 2023. All patients met the inclusion and exclusion criteria. They were divided into a control group (n=46) and an observation group (n=47). All patients received full-mouth ultrasonic debridement. On this basis, patients in the control group received weekly subgingival minocycline hydrochloride ointment (Sunstar^®) injections, while patients in the observation group received combined 500 mg tinidazole tablets twice daily ×4 weeks. Periodontal parameters and gingival crevicular fluid (GCF) biomarkers were assessed at baseline and 3-month follow-up.

Results: The results showed that the total effective rate of treatment in the observation group (91.49%) was significantly higher than that in the control group (73.91%) (P<0.05). The periodontal indicators (Plaque Index, Gingival Bleeding Index, Periodontal Pocket Depth), inflammatory factor indicators (C-reactive protein, Tumor Necrosis Factor-α, Interleukin-1β), Matrix Metalloproteinase-9 (MMP-9), and Secretory Immunoglobulin A (SIgA) levels of both groups decreased significantly after treatment. Moreover, these indicators in the observation group were significantly lower than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05).

Conclusion: The combination therapy of minocycline hydrochloride and tinidazole significantly improved the clinical efficacy for CP patients. Compared with minocycline hydrochloride alone, the addition of tinidazole further improved patients' periodontal health, reduced the inflammatory response and MMP-9, SIgA levels, and did not increase the risk of adverse reactions. This suggests good drug safety and clinical promotion value.

Purpose: To construct a risk nomogram model of ventilator-associated pneumonia (VAP) patients with mechanical ventilation in the intensive care unit (ICU) based on peripheral blood inflammatory indicators and to evaluate its diagnostic value.

Patients and methods: A matched 1:2 case: control study was conducted. Fifty-five mechanically ventilated patients with VAP and 113 patients without VAP were admitted to the ICU of Suzhou City Hospital with mechanical ventilation from January 2022 to June 2023 and were retrospectively included as study subjects. Clinical data and laboratory indicators of all patients were collected; the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic immunoinflammatory index (SII), and systemic inflammatory response index (SIRI) were calculated, and endotracheal aspirate (ETA) culture results of VAP patients were recorded.

Results: There were 61 pathogenic bacteria cultured in the ETA samples of 55 VAP patients, including 56 gram-negative bacilli, 4 gram-positive cocci, and 1 fungus. The proportions of hypoproteinemia, procalcitonin (PCT), NLR, PLR, SII, and SIRI in VAP patients were significantly higher than those in non-VAP patients, with statistical significance (P < 0.05). Univariate and multivariate logistic regression analyses showed that hypoproteinemia, PCT, NLR, PLR, and SIRI were independent influencing factors for VAP in ICU patients (P < 0.05). The ROC curve analysis results showed that the area under the curve of the model for diagnosing VAP in ICU patients was 0.894 [(95% CI = 0.844-0.945), P < 0.001], and the sensitivity and specificity were 87.3% and 74.3%, respectively. The calibration curve shows that the model has good accuracy, and the clinical decision curve indicates that the clinical net benefit rate is higher when the model is used to diagnose VAP.

Conclusion: Hypoproteinemia, PCT, NLR, PLR, and SIRI are the independent risk factors for VAP in ICU patients. The nomogram model constructed based on these easily accessible indicators may provide a promising tool for the early diagnosis of VAP in ICU patients, while requires further refinement for routine clinical use.

Rationale: The diagnostic value of endothelial-associated biomarkers in IgAN and their ability to differentiate it from other kidney diseases have not yet been clarified.

Objective: This study aimed to investigate the diagnostic value of endothelial-associated biomarkers in IgAN patients.

Methods and results: This is a cross-sectional study involving 96 participants, with IgAN, LN, MN, and healthy subjects recruited in a 1:1:1:1 ratio. Seventy-five percent of the sample was used for developing a classification model, and the remaining 25% was used for constructing a validation cohort. Plasma levels of 12 endothelial-associated biomarkers were detected using multiplex immunoassay technology. Among all the biomarkers evaluated, VLA-4 and VEGFD were prioritized for distinguishing IgAN from other groups (p<0.001), with 85% classification accuracy. These two biomarkers also showed significant correlation with eGFR (VLA-4: r = - 0.291, P = 0.021; VEGFD: r = - 0.271, P = 0.031) and Gd-IgA1 (VLA-4: r = 0.403, P = 0.003; VEGFD: r = 0.412, P = 0.002). These two biomarkers also showed superior diagnostic efficacy (AUC=0.952 and 0.945) compared to Gd-IgA1 (AUC=0.736). Subgroup analysis of IgAN patients revealed clinically relevant effect sizes for the IgA and IgA/C3 ratios between high- and low-VLA-4 and VEGFD groups, with Hedges' g values of 0.962 and 0.819, respectively. The diagnostic efficacy of VLA-4 and VEGFD levels in IgAN was further validated in an independent cohort comprising 24 participants.

Conclusion: VLA-4 and VEGFD emerge as robust, non-invasive biomarkers for IgAN diagnosis and may play significant roles in the pathogenesis of IgAN.

Stroke remains a leading cause of death and disability worldwide. Recent evidence suggests that stroke pathophysiology extends beyond vascular dysfunction to include complex interactions within the neurovascular unit (NVU), particularly involving fibrinogen. This blood-derived protein accumulates in the brain following blood-brain barrier (BBB) disruption and plays crucial roles in neuroinflammation and tissue repair. Through its unique structural domains, fibrinogen interacts with multiple cellular components, including astrocytes, microglia, and neural stem cells, thereby modulating inflammatory responses and neural repair mechanisms. This review examines fibrinogen's structure and its diverse functions in stroke pathophysiology, focusing on its interactions with vascular cells, glial cells, and peripheral immune cells. We also discuss emerging therapeutic strategies targeting fibrinogen-mediated pathways and the challenge of translating experimental results into effective clinical treatments.