Journal of Inflammation Research最新文献

Introduction: Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality.

Methods: Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL.

Results: Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL.

Discussion: This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research.

Background: Previous studies have demonstrated that neutrophil extracellular traps (NETs) are crucial in infectious diseases. This study aims to evaluate the clinical value of NET-related biomarkers in identifying the risk of COVID-19 and diagnosing the disease.

Methods: This study involved 32 patients who tested positive for COVID-19 via polymerase chain reaction (PCR) between April and August 2023. During the same period, 30 healthy volunteers were enrolled as a control group. The principal biomarkers related to NETs are citrullinated histone H3 (CitH3), double-stranded DNA (dsDNA), myeloperoxidase-DNA complex (MPO-DNA), and Nucleosome. Elevated levels in two or more of these biomarkers indicate raised NET concentrations. Multivariable logistic regression analysis was employed to assess whether NET-related biomarkers were the independent risk factor of COVID-19. The diagnostic value of NET-related biomarkers in COVID-19 was further evaluated using receiver operating characteristic (ROC) curve analysis. Statistical procedures were executed in SPSS software (version 24.0, USA).

Results: Compared with the control group, patients infected with COVID-19 had higher levels of dsDNA and nucleosomes (P < 0.001). Correlation analysis revealed a positive correlation between dsDNA levels and neutrophil count (r = 0.309, P = 0.015) as well as between nucleosome levels and neutrophil count (r = 0.446, P < 0.001). Further analysis showed that dsDNA and nucleosomes were independent risk factors for COVID-19 infection. ROC curve analysis showed that dsDNA area under the curve (AUC) = 0.777, 95% confidence interval (CI), 0.661-0.893, P < 0.001, and nucleosomes (AUC = 0.884, 95% CI, 0.778-0.991, P < 0.001) had well diagnostic value in the diagnosing COVID-19 infection.

Conclusion: NET-related biomarkers, dsDNA and nucleosomes, were independent risk factors of COVID-19 infection and potentially useful biomarkers in diagnosing COVID-19 infection in older patients.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent joint inflammation, pain, and tissue degradation. This study evaluates the therapeutic potential of Norisoboldine (NOR), an isoquinoline alkaloid from Lindera aggregata, in a rat model of RA.

Methods: Rats were divided into five groups: normal control (G1), RA model (G2), NOR-treated groups at 15 mg/kg (G3) and 30 mg/kg (G4), and methotrexate-treated group (G5). NOR's anti-arthritic effects were assessed by measuring clinical arthritis scores and inflammatory markers (RF, CRP, TNF-α, IL-6, IL-10). Oxidative stress markers (MDA, SOD, catalase, GPx) and pathways (NF-κB/IKKβ and Nrf2/Keap1) were also evaluated. Histopathology assessed synovial inflammation and tissue degradation.

Results: NOR treatment significantly reduced arthritis severity, as evidenced by decreased clinical arthritis scores and inflammatory markers in RA rats. NOR also exhibited strong antioxidant effects, demonstrated by decreased MDA levels and enhanced SOD, catalase, and GPx activities. NOR further downregulated matrix metalloproteinases (Mmp-2, Mmp-3), aggrecanases (Adamts-4, Adamts-5), and PCNA expression. Histopathology confirmed marked reductions in synovial inflammation and tissue damage in NOR-treated groups.

Discussion: These findings suggest that NOR's anti-inflammatory and antioxidant properties contribute to reducing both inflammation and the overall severity of RA. NOR's multifaceted actions support its potential as a novel therapeutic agent for RA.

Conclusion: NOR demonstrates protective effects in RA rats by reducing inflammation, oxidative stress, and extracellular matrix degradation, offering promise as a therapeutic option to manage RA pathology comprehensively.

Objective: Ferroptosis is intricately associated with the pathophysiology processes of myocardial ischemia. Cardamonin (CAR) has been shown to provide significant protection against tissue damage due to multiple ischemia/reperfusion. This study aimed to examine the cardioprotective properties of CAR in myocardial ischemia/reperfusion injury (MIRI) and provide insights into the possible mechanisms involved.

Methods: An MIRI mice model was conducted by coronary artery ligation, and the effects of CAR on myocardial tissue damage were evaluated by infarct size assessment, echocardiography, and H&E staining. The extent of ferroptosis was detected by examining the levels of ferroptosis-related proteins and lipid reactive oxygen species (ROS). The function pathway of CAR was analyzed by network pharmacology and verified using Western blotting. In addition, we induced hypoxia/reoxygenation (H/R) in cardiomyocytes to detect SLC7A11 expression, ROS level, mitochondrial iron content, and oxidative stress marker levels. The target protein of CAR was identified by Western blotting and molecular docking. We then evaluated the regulatory role of STAT3 on MIRI-induced ferroptosis by silencing STAT3.

Results: In our study, CAR demonstrated a reduction in myocardial histopathological damage and mitigation of ferroptosis in MIRI mice. Through network pharmacology analysis and Western blotting, our findings indicated that CAR modulates the AGE-RAGE signaling pathway, particularly impacting STAT3. Meanwhile, in vitro experiments revealed that advanced-glycation end products (AGEs) exacerbated H/R-induced ferroptosis, whereas CAR alleviated this ferroptosis in the presence of both AGEs and H/R. CAR was observed to enhance STAT3 expression in H/R+AGRs-treated cardiomyocytes. Molecular docking results demonstrated favorable binding interactions between CAR and STAT3. Our study confirmed that CAR mitigated MIRI-induced myocardial injury and ferroptosis through targeting STAT3 in mice.

Conclusion: In conclusion, CAR inhibited ferroptosis by activating the STAT3 signaling, thereby mitigating MIRI.

Background: Serpin B9 is highly expressed in breast cancer, melanoma, and various malignant cells and inhibits NK cell killing through the Serpin B9-GrB axle. However, the current studies have only validated the role of Serpin B9 in vivo and vitro, and lack of systematic studies on the expression of Serpin B9 in patients' tumor tissues and its prognostic implications. In this study, we propose to further validate the role of Serpin B9 by comparing its expression level in tissues of lung adenocarcinoma patients and its correlation with the efficacy of immunotherapy.

Methods: This study included 200 patients with LUAD between Feb 2022 and Feb 2023. IHC scoring assessed Serpin B9 expression in the tumor and adjacent tissues, with an H-score of 2 as the cutoff value. Patients were divided into high- and low-expression groups. T-tests were used to compare Serpin B9 expression and treatment efficacy between the tumor and adjacent tissues in both groups. Baseline characteristics were compared using X2 tests. Prognostic risk factors were identified using Cox regression and Kaplan-Meier survival curves.

Results: The expression level of Serpin B9 in LUAD tumor tissues are higher than adjacent tissues and positively correlated with the TNM stage and negative correlated with PFS in patients with LUAD. Additionally, immunotherapy efficacy was inversely correlated with Serpin B9 expression.

Conclusion: The increased expression of Serpin B9 in LUAD tumor tissues is negatively linked to prognosis and immunotherapy efficacy. This underscores their potential as prognostic and therapeutic targets.

Felty's syndrome (FS) is an uncommon disorder with a poor prognosis, and most patients die from infections caused by neutropenia. Currently, there is no standardized treatment strategy, and treatment options are based on case reports and clinical experience. To date, no cases of FS complicated by coronavirus disease-2019 (COVID-19) have been reported. This article reports a successful case of FS complicated by COVID-19. We emphasized treating rheumatic diseases with immunosuppressive therapy at appropriate doses based on strong and effective anti-infection when co-infected.

Purpose: The presence of T cells expressing TLR-2 and TLR-4 has been associated with relapsing-remitting multiple sclerosis (RRMS) pathogenesis. Here, we evaluated whether the effectiveness of DMT in controlling clinical activity of the disease would be associated with modulation of proportion of TLRs⁺ T cells.

Patients and methods: Whole peripheral blood mononuclear cells, purified CD4⁺ and CD8⁺ T cells from RRMS patients were cultured with different stimuli. The frequency of IL-17-secreting CD4⁺ and CD8⁺ T cells positive for TLR-2 and TLR-4 was determined by flow cytometry. The cytokine profile of these T cells following TLR-2 and TLR-4 stimulation was determined by Multiplex. Some of these T cell cultures were treated with hydrocortisone. The levels of LPS-binding protein (LBP) were dosed by ELISA. Clinical (occurrence of relapses) and radiological (number of active brain lesions) activity were evaluated during the 1-year follow-up.

Results: Despite DMT, high intensity of TLR-2 and TLR-4 expression on (CD4⁺ and CD8⁺) T-cells, as well as the frequency of IL-17-secreting (CD4⁺ and CD8⁺) T-cells, are predictive of future RRMS relapses. Moreover, higher cytokine production related to Th17/Tc-17 phenotypes in response to TLR-2 and TLR-4 agonists was observed in DMT-treated patients and displayed an elevated number of brain lesions. The hyperresponsiveness of MS-derived T-cells to TLR-2 and TLR-4 ligands, with high levels of IL-1β, IL-6, IL-17, IFN-γ and GM-CSF in response to both TLR agonists, positively correlated with plasma LBP levels. Interestingly, corticoid was less efficient in reducing Th17 and Tc-17 cytokine production induced by TLR-2 and TLR-4 ligands in DMT-treated patients who relapsed during follow-up.

Conclusion: Collectively, the data suggested that persistence of circulating Th17 and Tc17 cells expressing elevated levels of functional TLR-2 and TLR-4 could indicate high disease activity and lower therapeutic efficacy in RRMS patients.

Purpose: Sepsis can induce sepsis-associated encephalopathy (SAE), with Ulinastatin (UTI) serving a critical anti-inflammatory role. This study aimed to identify the hub genes in an SAE mouse model following UTI intervention and investigate the underlying molecular mechanisms.

Materials and methods: Through differential expression analysis to obtain differentially expressed genes (DEGs), ie, UTI vs CLP (DEGs1) and Con vs CLP (DEGs2). After taking the intersection of the genes with opposite differential trends in these two parts and immune-related genes (IRGs), DE-IRGs were obtained. Hub genes in the protein-protein interaction (PPI) network were then determined using six algorithms from the Cytohubba plugin in Cytoscape. Gene set enrichment analysis (GSEA) was employed to explore the functional relevance of these hub genes. Additionally, the immune microenvironment across the three groups was compared, and hub gene-related drugs were predicted using an online database. Finally, qRT-PCR was used to validate the expression of the hub genes in hippocampal tissue from CLP mice.

Results: RNA sequencing obtained 864 differentially expressed genes (DEGs) (CLP vs Con) and 279 DEGs (UTI vs CLP). Taking the intersection of DEGs with opposite expression trends yielded 165 DEGs. Six key genes (ICAM - 1, IRF7, IL - 1β, CCL2, IL - 6 and SOCS3) were screened by six algorithms. Immune infiltration analysis found that Treg cells were reversed after treatment with UTI in the diseased state. A total of 106 hub - gene - related drugs were predicted, among which BINDARIT - CCL2 and LIFITEGRAST - ICAM1 showed particularly high affinities. The qRT - PCR verification results were consistent with the sequencing results.

Conclusion: In conclusion, ICAM-1, IRF7, IL-1β, CCL2, IL-6, and SOCS3 were identified as potential therapeutic targets in SAE mice treated with UTI. This study offers theoretical support for UTI as a treatment option for SAE.

Background: High-grade cervical intraepithelial neoplasia (CIN2/3) is a precursor to invasive cervical cancer, necessitating effective management. While the Loop Electrosurgical Excision Procedure (LEEP) is a successful treatment, recurrence remains a significant concern. This study evaluates the predictive value of preoperative immune-inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), in assessing the risk of residual or recurrent CIN post-LEEP.

Methods: A retrospective analysis was performed on 423 women who underwent LEEP for CIN2/3 at Cangzhou Central Hospital between 2016 and 2020. Cox proportional hazards regression models with restricted cubic splines were used to evaluate linear and non-linear associations between immune-inflammatory indices and recurrence risk. Multivariate models were adjusted for confounding factors, and subgroup analyses were conducted to test the robustness of the associations. Threshold non-linear fitting and saturation effect analyses were also performed to identify inflection points influencing residual or recurrent disease risk.

Results: Significant differences in age, menopausal status, TCT results, HPV status, degrees of CIN and margin status were observed between recurrence and non-recurrence groups. NLR demonstrated a U-shaped relationship with recurrence risk, with a threshold effect. NLR values below 3.15 were associated with a reduced recurrence risk, while higher values increased the risk. PLR and SII showed a modest protective effect below their respective thresholds.

Conclusion: Systemic inflammation plays a key role in CIN recurrence following LEEP. NLR serves as a valuable prognostic marker, highlighting the potential for personalised follow-up strategies. Further research is needed to confirm these findings and elucidate the underlying mechanisms.

Purpose: Tuberculosis (TB) is a major global health threat and its diagnosis remains challenging. This study aimed to develop a nomogram that incorporated peripheral blood transcriptional signatures and other blood tests for the diagnosis of tuberculosis.

Patients and methods: Patients with TB, patients with other definite pulmonary diseases (OPD), individuals with latent tuberculosis infection (LTBI), and healthy controls (HC) were retrospectively enrolled between May 2017 and April 2018. The results of the interferon-γ release assay (IGRA) and blood counts were obtained from medical records, and the transcripts of 10 genes were detected using reverse transcription polymerase chain reaction (RT-PCR). Variable selection was performed using least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression was performed for the optimal prediction model with backward direction. The model was displayed as a nomogram, and its performance was evaluated for discrimination ability, calibration ability, and clinical usefulness. Internal validation of the prediction model was conducted using bootstrap resampling.

Results: A total of 185 participants were enrolled, including 84 patients with TB and 101 controls. A prediction nomogram composed of IGRA, percentage of neutrophils, and expression levels of CD64, granzyme A (GZMA), and PR/SET domain 1 (PRDM1) was established. The nomogram demonstrated good discrimination, with an unadjusted area under the curve (AUC) of 0.914 (95% CI: 0.875-0.954) and a bootstrap-corrected AUC of 0.914 (95% CI: 0.874-0.947). With a cutoff value of 0.519, the sensitivity and specificity for discriminating PTB from controls were 0.81 and 0.871, respectively. The nomogram also showed good calibration with the Hosmer-Lemeshow test (P=0.58) and good clinical practicality displayed by the decision curve analysis.

Conclusion: A nomogram composed of IGRA, percentage of neutrophils, and expression of CD64, GZMA, and PRDM1 was established. The nomogram demonstrated a sensitivity and specificity of 81% and 87%, respectively, for differentiating TB from controls.