Journal of Inflammation Research最新文献

Purpose: Angesinenolide B (ASB), a phthalide dimer with a peroxy bridge, is uniquely isolated from Chinese medicine Angelica sinensis radix and demonstrates significant anti-inflammatory properties. The objective of the current study was to evaluate the anti-inflammatory function of ASB and the potential mechanism in lipopolysaccharide (LPS)-stimulated macrophages and CuSO₄-induced zebrafish models.

Methods: The level of nitric oxide (NO), a proinflammatory mediator, in LPS-stimulated RAW264.7 cells was quantified using Griess method. ELISA was employed to investigate the generation of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while qRT-PCR was utilized to analyze the mRNA expressions of TNF-α, IL-6, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Fluorescence microscopy and flow cytometry were employed for the determination of ROS generation. Western blot and immunofluorescence techniques were utilized to assess the impact of ASB on iNOS and COX-2, and on the NF-κB, MAPK and STATs signaling pathways. Moreover, the affinities between ASB and the target proteins were verified by molecular docking analysis. In vivo, ROS generation was explored using fluorescent probe DCFH-DA, and the TNF-α and IL-6 mRNA expressions were also evaluated in CuSO₄-induced zebrafish inflammation model.

Results: ASB treatment was found to suppress the levels of NO, TNF-α, IL-6 and ROS, restrain the expressions of iNOS and COX-2 proteins and mRNA, as well as down-regulate MAPK and STATs signaling pathways in LPS-stimulated RAW264.7 cells. Furthermore, the administration of ASB effectively attenuated the overproduction ROS and the high mRNA expressions of TNF-α and IL-6 in a zebrafish model of inflammation induced by CuSO₄.

Conclusion: ASB has the potentiality to reduce the levels of proinflammatory mediators and cytokines, decrease ROS production, and also down-regulate the MAPK and STATs signaling pathways, thereby exerting an anti-inflammatory effect. This implies that ASB could potentially serve as a viable approach for addressing inflammatory conditions.

Objective: In primary healthcare, diagnosing rheumatoid arthritis (RA) is challenging due to a general lack of in-depth knowledge of RA by general practitioners (GPs) and the lack of effective tools, leading to high rates of missed diagnosis. This study focuses on a screening model for primary healthcare, aiming to improve early RA screening accuracy and efficiency at a relatively lower cost, reducing delays in GPs' recognition of RA.

Methods: We randomly selected 2106 participants from the RA group or combined control group (comprising healthy individuals and patients with non-RA rheumatic diseases) at Peking University Shenzhen Hospital as the developing cohort. Guided by experienced rheumatologists, we built a comprehensive database with 26 clinical features. Using 10 classical machine learning algorithms, we developed screening models. Evaluation metrics determined the best model. Employing multivariatelogistic regression results and the best-performing model to identify the least costly features, ensuring applicability in primary healthcare clinics. Subsequently, we retrained and validated our proposed model based on two primary healthcare validation cohorts.

Results: In experiments, the algorithms achieved over 88% accuracy on training and test sets. Random Forest (RF) excelled with 96.20% (95% CI 95.39% to 97.02%) accuracy, 96.22% (95% CI 95.40% to 97.03%) specificity, 96.18% (95% CI 95.37% to 97.00%) sensitivity, and 96.20% (95% CI 95.39% to 97.02%) Areas Under Curves (AUC). A meticulous feature selection identified 11 key features for RA screening. In an external test on two primary healthcare datasets with these features, RF demonstrated an accuracy of 88.435% (95% CI 85.55% to 91.32%), sensitivity of 98.55% (95% CI 97.47% to 99.63%), specificity of 85.56% (95% CI 82.39% to 88.73%), and an AUC of 92.055% (95% CI 89.62% to 94.49%).

Conclusion: The screening model excels in automating prompt identification of RA in primary healthcare, improving the early detection of RA, and reducing delays and associated costs. Our findings contribute positively and are poised to elevate prospective RA management, fostering improvements in healthcare sector responsiveness and resource efficiency.

Purpose: Traditional Mongolian Medicine Batri-7 (BT-7) is the key Mongolian Medicine (MM) for bacterial enteritis. BT-7 is a well-known clinical MM due to its antibacterial properties. BT-7 contains plant-derived bioactive compounds, but its molecular mechanism of action remains unclear. This study explores BT-7's antibacterial compounds and therapeutic mechanism in a Salmonella enteritis mouse model.

Methods: The active components of BT-7 were detected by liquid chromatography-tandem mass spectrometry assay and identified by UPLC/Q-TOF-MS. An enteritis mouse model induced by Salmonella typhimurium was used in this study. Pathological analysis of small intestine was conducted with hematoxylin and eosin staining. The macrophage recruitment in model mice's intestines was detected by flow cytometry. Simultaneously, the Minimum Inhibitory Concentration of BT-7 was evaluated against bacterial by microbroth dilution method, BT-7 regulation of Salmonella typhimurium gene was performed by RNA-Seq methods and verified by qRT-PCR.

Results: In the LC-MS/MS assay, negative and positive-ion modes are identified for 511 and 699 compounds from BT-7, respectively. Of them, we found multiple antibacterial and anti inflammation compounds including chrysin, oroxylin A and luteolin. In vivo, we observed that treatment of mouse Salmonella enteritis with BT-7 decreases inflammation score and macrophages on intestinal tenue. In vitro, BT-7 presented the highest antibacterial activities against tested strains with MIC was 2-4 mg/mL. Meanwhile, BT-7 significantly down regulated Salmonella infection genes.

Conclusion: Twenty key anti-bacterial components were identified in the BT-7. In vivo experiment shows that orally administered BT-7 effectively reduce the inflammation of intestine in model of Salmonella-induced mouse enteritis by down regulating the infection-related virulence genes of Salmonella. Through this study, we discovered the mechanism of BT-7's dual action on the host and pathogenic bacteria. This gives inspiration for anti-infective disease research in traditional medicine and also proves that traditional medicines still have good prospects for treating infectious diseases.

Sepsis is a critical condition characterized by organ dysfunction due to a dysregulated response to infection that poses significant global health challenges. Coagulation dysfunction is nearly ubiquitous among sepsis patients. Its mechanisms involve platelet activation, coagulation cascade activation, inflammatory reaction imbalances, immune dysregulation, mitochondrial damage, neuroendocrine network disruptions, and endoplasmic reticulum (ER) stress. These factors not only interact but also exacerbate one another, leading to severe organ dysfunction. This review illustrates the mechanisms of sepsis-induced coagulopathy, with a focus on tissue factor activation, endothelial glycocalyx damage, and the release of neutrophil extracellular traps (NETs), all of which are potential targets for therapeutic interventions.

Background: Recent interest has focused on the role of inflammatory markers in assessing coronary artery disease (CAD) severity, especially in the early stages. However, there remains a gap in identifying reliable biomarkers to predict postoperative mortality in patients undergoing coronary artery bypass grafting (CABG). Traditional markers such as C-reactive protein (CRP) and white blood cell (WBC) counts are commonly used but have limitations in specificity and prognostic value. The Delta Neutrophil Index (DNI), which reflects immature granulocyte levels, offers a promising alternative. Unlike CRP and WBC, DNI specifically measures the acute inflammatory response, providing a more targeted indicator of risk. This study evaluates the significance of postoperative DNI as a prognostic marker for early mortality in CABG patients, addressing the need for more accurate biomarkers in postoperative care.

Aim: The aim of this study is to determine the significance of the Delta Neutrophil Index (DNI), which reflects the proportion of immature granulocytes, as a prognostic marker for early postoperative mortality in patients undergoing coronary artery bypass grafting (CABG).

Methods: This rigorously designed retrospective cohort study was conducted at a high-volume tertiary care center specializing in cardiovascular surgery, including a robust patient cohort to ensure comprehensive data analysis and reliable conclusions. The study included a consecutive series of 446 patients who underwent coronary artery bypass grafting (CABG) between January 1, 2022, and August 1, 2023.

Results: Mortality was found to be associated with preoperative DNI (p<0.05). A 1-unit increase in pre-DNI measurement was associated with a 2.61-fold (95% Confidence Interval: 1.54-4.45) increase in the risk of death. Additionally, mortality was also associated with postoperative DNI (p<0.05). A 1-unit increase in postoperative DNI measurement was associated with a 10.21-fold (95% Confidence Interval: 5.08-20.05) increase in the risk of death.

Conclusion: Elevated DNI values are strong independent predictors of postoperative mortality, underscoring its critical role in perioperative risk assessment for CABG patients. Both preoperative and postoperative DNI levels are significantly linked to mortality, emphasizing DNI's value in improving patient outcomes and reducing complications. Integrating DNI into routine clinical practice can provide a more personalized approach to care, enhancing survival and optimizing postoperative management.

Background: The pathogenesis is of livedoid vasculopathy (LV)-a rare, chronic, and recurrent cutaneous vascular obstructive disease-is not fully understood. Conventional anticoagulant therapy sometimes exhibits limited efficacy, and although JAK inhibitors have demonstrated some efficacy in the treatment of refractory LV, the evidence remains insufficient.

Case presentation: This study reports a case of a 14-year-old girl who were failed to maintain remission following treatment with oral rivaroxaban combined with external use of heparin sodium cream. However, the symptoms improved significantly 2 weeks after treatment with baricitinib, and remission was maintained during its gradual reduction.

Conclusion: Successful treatment of this refractory patient with baricitinib provides another evidence for the potential therapeutic effect of JAK1/JAK2 inhibitors in LV, and also offers a reference for the dosage tapering regime of baricitinib in LV.

Purpose: Cucurbitacins have demonstrated anti-inflammatory effects and show promise for inflammatory bowel diseases. However, the underlying mechanisms by which cucurbitacins affect colitis remain largely unknown.

Methods: In this study, we investigated the impact of cucurbitacin IIa on dextran sulfate sodium (DSS)-induced colitis in rats and the alterations in intestinal extracellular vesicles (EVs). EVs were isolated and characterized, followed by analysis of the small RNAs and proteins encapsulated within them using small RNA sequencing and proteomics, respectively.

Results: Our results revealed that cucurbitacin IIa alleviated colitis symptoms in DSS-treated rats, along with changes in the morphology and composition of intestinal EVs. Notably, EVs from cucurbitacin IIa-treated rats also mitigated colitis symptoms in DSS-treated rats. Further analysis showed that cucurbitacin IIa modified the protein profiles and microRNA composition of EVs extracted from the feces of colitis rats. Specifically, microRNA-30b-5p, significantly increased by cucurbitacin IIa, was found to alleviate colitis symptoms in DSS-treated rats. In conclusion, cucurbitacin IIa appears to alleviate colitis by promoting the release of microRNA-30b-5p from host-derived extracellular vesicles.

Conclusion: These findings enhance our understanding of cucurbitacin IIa's effects on intestinal health and offer potential new therapeutic targets for inflammatory bowel disease treatment.

Introduction: The prevalence of osteoarthritis (OA), the most common chronic joint condition, is increasing due to the aging population and escalating obesity rates, leading to a significant impact on human health and well-being. Thus, analyzing the key targets of OA through bioinformatics can help discover new biomarkers to improve its diagnosis.

Methods: The microarray and RNA-seq results were screened from the Gene Expression Omnibus (GEO) database. Functional enrichment analyses, protein-protein interaction (PPI) analysis, and weighted gene co-expression network analysis (WGCNA) of the DEGs were performed. RT-qPCR and WB were further performed to verify the hub gene expression in OA rat.

Results: In this study, 35 key genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA) using the GSE169077 and GSE114007 datasets. Enrichment analysis revealed that these key genes were predominantly enriched in the HIF-1 signaling pathway, ECM-receptor interaction, and FoxO signaling pathway. Through the integration of protein-protein interaction (PPI) analysis, validation in animal models and ROC curve analysis, four pivotal genes (GADD45B, CLDN5, HILPDA and CDKN1B) were finally identified.

Conclusion: In conclusion, these identified key genes could serve as novel targets for predicting and treating OA, offering fresh insights into its etiology and pathogenesis.

Purpose: To determine the significance of lesion-pleura relationship in differentiating peripheral inflammatory lesions (PILs) and peripheral lung cancers (PLCs).

Patients and methods: From January 2017 to April 2022, a total of 743 patients with 501 PLCs and 292 PILs (≥1.5 cm) were retrospectively enrolled. The patients' clinical characteristics and CT features of lesions in these two groups were analyzed and compared, and the impact of the lesion-pleura relationship (broad or narrow basement and distance between lesion and pleura) on differentiation was specifically assessed.

Results: Lesions attached to pleura were more frequent in PILs (188, 64.4%) than in PLCs (244, 48.7%) (P < 0.001), and those with broad basement-to-pleura were also more common in PILs (133, 70.7%) than in PLCs (47, 19.3%) (P < 0.001). Among the 296 lesions with a lesion-pleura distance ≤16 mm, the optimal cutoff value of distance was ≤8.9 mm (area under curve [AUC], 0.733; sensitivity: 0.770; specificity: 0.623; P < 0.001) for predicting PLCs. Regarding the 728 lesions attached to pleura or with a lesion-pleura distance ≤16 mm, the AUC of the model based on the clinical and CT features for predicting PLCs significantly increased from 0.812 to 0.879 after including lesion-pleura relationship (narrow basement or lesion-pleura distance ≤ 8.9 mm) (P < 0.001). Additionally, the lesion-pleura relationship was one of independent indicators for differentiation (odds ratio, 9.433; P < 0.001).

Conclusion: When differentiating peripheral lesions (≥1.5 cm), it is crucial to consider the basement-to-pleura and lesion-pleura distance besides patients' clinical characteristics, laboratory parameters and morphological features.