Journal of Inflammation Research最新文献

Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations.

Methods: The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.

Results: MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.

Conclusion: Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.

Purpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.

Patient data and methods: Data from 448 consecutive patients with MS at the Third People's Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model's performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).

Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune-inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.

Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.

Background: Accurate prediction of treatment response in Crohn's disease (CD) patients undergoing infliximab (IFX) therapy is essential for clinical decision-making. Our goal was to compare the performance of the clinical characteristics, radiomics and deep learning model from computed tomography enterography (CTE) for identifying individuals at high risk of IFX treatment failure.

Methods: This retrospective study enrolled 263 CD patients from three medical centers between 2017 and 2023 patients received CTE examinations within 1 month before IFX commencement. A training cohort was recruited from center 1 (n=166), while test cohort from centers 2 and 3 (n=97). The deep learning model and radiomics were constructed based on CTE images of lesion. The clinical model was developed using clinical characteristics. Two fusion methods were used to create fusion model: the feature-based early fusion model and the decision-based late fusion model. The performances of the predictive models were evaluated.

Results: The early fusion model achieved the highest area under characteristics curve (AUC) (0.85-0.91) among all patient cohorts, significantly outperforming deep learning model (AUC=0.72-0.82, p=0.06-0.03, Delong test) and radiomics model (AUC=0.72-0.78, p=0.06-0.01). Compared to early fusion model, the AUC values for the clinical and late fusion models were 0.71-0.91 (p=0.01-0.41), and 0.81-0.88 (p=0.49-0.37) in the test and training set, respectively. Moreover, the early fusion had the lowest value of Brier's score 0.15-0.12 in all patient set.

Conclusion: The early fusion model, which integrates deep learning, radiomics, and clinical data, can be utilized to predict the response to IFX treatment in CD patients and illustrated clinical decision-making utility.

Aim: In this study, the predictive value of soluble growth stimulation expressed gene 2 protein (sST2) for long-term clinical outcomes in patients with acute heart failure (AHF) is assessed. In addition, the influence of a history of myocardial infarction on the levels of sST2 in patients with HF, as well as its impact on outcome events, is explored. We also aim to establish a specific standard for sST2 levels in this subgroup.

Methods: We conducted an ambispective cohort study involving hospitalized patients with AHF, measuring their sST2 levels and following their progress over three years. The primary endpoint was major adverse cardiovascular events (MACEs), encompassing heart failure readmission and all-cause mortality over three years. Cox regression analysis was used to evaluate the prognostic significance of sST2 levels, along with a subgroup analysis using propensity score matching (PSM) to adjust for confounding variables. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal sST2 threshold using Youden's J statistics, and a sensitivity analysis included Kaplan-Meier survival curves.

Results: The study included 149 patients with a median age of 68 years, of whom 57% were male. Both univariate and multivariate Cox regression analyses confirmed sST2 as an independent predictor of MACEs. Post-PSM analysis, 124 samples were grouped by MI history ROC curve analysis revealed an area under the curve of 0.726 for predicting MACEs in patients with MI, demonstrating a significant predictive value for sST2 levels above 34 ng/mL, which correlated with increased readmission and mortality rates. In contrast, sST2 levels in patients without MI history showed no significant predictive relevance.

Conclusion: sST2 has significant long-term predictive value for clinical outcomes in patients with AHF, particularly for those with a prior MI history, indicating a need for heightened clinical attention and thorough follow-up to mitigate long-term adverse cardiovascular outcomes.

Background: Sepsis-associated acute lung injury (SI-ALI) is triggered by various direct or indirect noncardiogenic factors affecting the alveolar epithelium and capillary endothelial cells. Menaquinone-4 (MK-4), a major component of vitamin K, plays a crucial role as an antioxidant by effectively neutralizing reactive oxygen species (ROS) and safeguarding critical biomolecules from oxidative harm within cells. However, the specific mechanisms and clinical implications of MK-4 in SI-ALI are unclear and require further study.

Methods: Cecal ligation and puncture (CLP) surgery is a commonly used method to induce sepsis in C57BL/6N wild-type mice, and the mice were administered MK-4 at a dosage of 200 mg/kg/day and 3-TYP at 5 mg/kg/day via intraperitoneal injection for 3 days, or erastin (5 mg/kg) 0.5 hours before CLP surgery. The mice were sacrificed 24 hours after CLP surgery, and blood and lung tissue samples were collected. Pathological changes in the lung tissue and oxidative stress levels were detected. The expression levels of Sirt3, acetylated lysine, p53, SLC7A11 ALOX12 and ferroptosis-related proteins were determined. ligation and puncture (CLP).

Results: In this study, we observed that the lung inflammation was associated with reduced Sirt3 expression and increased acetylated lysine levels. The progression of SI-ALI was mitigated by MK-4 through its role in upregulating Sirt3 expression. MK-4 achieved antioxidant effects by downregulating ROS and inflammatory factor levels. Mechanistically, MK-4 inhibited the p53/SLC7A11 signalling pathway in ferroptosis by inhibiting the acetylation of p53, independent of p53 levels. In addition, MK-4 inhibited ferroptosis independent of GPX4. These findings indicate that MK-4 is a promising novel therapeutic agent for treating SI-ALI and possibly sepsis.

Conclusion: These experiments revealed that MK-4 acts as a ferroptosis suppressor, increasing the expression of Sirt3, inhibiting the p53/SLC7A11 signalling pathway, and reducing oxidative stress and inflammatory responses, thereby exerting a protective effect against ALI in sepsis.

Purpose: The high mortality rate associated with the critical stages of severe fever with thrombocytopenia syndrome (SFTS) does not have effective treatment. We aimed to evaluate the 28-day mortality and potential impact of glucocorticoid therapy in these patients.

Patients and methods: This retrospective observational study included participants from the intensive care unit between July 2019 and April 2023. The participants were categorized into glucocorticoid (GC) and non-GC groups. Propensity score matching (PSM) was employed to ensure comparability between groups. We used Cox proportional hazard models to examine mortality risk associated with GC use, Kaplan-Meier survival analyses for overall survival, stratified Cox proportional hazard models for subgroup analyses, and likelihood ratio tests to examine interactions between subgroups.

Results: Of 218 patients with SFTS (median age, 71 years; male, 49.1%), 61.9% required mechanical ventilation, 58.3% received GC treatment, and the 28-day mortality rate was 61.5%. After PSM, there were 58 patients in each group; post-PSM analysis revealed improved 28-day mortality rates with GC treatment, particularly for patients with Glasgow coma scale (GCS) score <13 (hazard ratio [HR], 95% confidence interval [CI] for GCS score: 9-12: 0.39, 0.17-0.88, p=0.024 and for GCS score: 3-8: 0.09, 0.02-0.35, p=0.001); lactate levels >2 mmol/L (0.35, 0.15-0.83, p=0.017); and norepinephrine usage (0.26, 0.13-0.49, p<0.001). Combining antiviral (0.41, 0.22-0.78, p=0.006) or immunoglobulin therapy (0.22, 0.1-0.51, p<0.001) with GC treatment significantly decreased the 28-day mortality rates, compared with GC monotherapy.

Conclusion: Using GCs reduced the high 28-day mortality rate in the patients, especially with low GCS score, high lactate levels, norepinephrine intake, and on antiviral or immunoglobulin therapy.

Purpose: Bronchiectasis patients are prone to Pseudomonas aeruginosa infection due to decreased level of sphingosine in airway. Adiponectin receptor agonist AdipoRon activates the intrinsic ceramidase activity of adiponectin receptor 1 (AdipoR1) and positively regulates sphingosine metabolism. This study aimed to investigate the potential therapeutic benefit of AdipoRon against Pseudomonas aeruginosa infection.

Methods: A mouse model of Pseudomonas aeruginosa lung infection and a co-culture model of human bronchial epithelial cells with Pseudomonas aeruginosa were established to explore the protective effect of AdipoRon. Liquid chromatography-mass spectrometry was used to detect the effect of AdipoRon on sphingosine level in lung of Pseudomonas aeruginosa-infected mouse models.

Results: The down-regulation of adiponectin and AdipoR1 in airway of bronchiectasis patients was linked to Pseudomonas aeruginosa infection. By activating AdipoR1, AdipoRon reduced Pseudomonas aeruginosa adherence on bronchial epithelial cells and protected cilia from damage in vitro. With the treatment of AdipoRon, the load of Pseudomonas aeruginosa in lung significantly decreased, and peribronchial inflammatory cell infiltration was lessened in vivo. The reduced level of sphingosine in the airway of Pseudomonas aeruginosa infected mice was replenished by AdipoRon, thus playing a protective role in the airway. Moreover, AdipoRon activated P-AMPKα/PGC1α, inhibited TLR4/P-NF-κB p65, and reduced expression of pro-apoptotic bax. However, the protective effect of AdipoRon on resisting Pseudomonas aeruginosa infection was weakened when AdipoR1 was knocked down.

Conclusion: AdipoRon protects bronchial epithelial cells and lung by enhancing their resistance to Pseudomonas aeruginosa infection. The mechanism might be modulating sphingosine metabolism and activating P-AMPKα/PGC1α while inhibiting TLR4/P-NF-κB p65.

Rheumatoid arthritis (RA) is a chronically progressive autoimmune disease with increasing age-standardized prevalence and incidence of RA worldwide. Its pathological features are persistent synovitis of the joint, accompanied by the release of a large number of inflammatory cytokines and cartilage and bone destruction. RA can lead to progressive joint damage, stiffness and swelling, vascular and bone-related complications, and irreversible disability, which seriously affects patients' life treatment. Early diagnosis and treatment can enhance the quality of life of RA patients. Platelet-to-lymphocyte ratio (PLR), as a common indicator in routine blood tests, has been proposed as an indicator of systemic inflammation in recent years. Its clinical detection is less invasive, economical, rapid and simple, and has been applied to the clinical evaluation of a variety of diseases. Of note, this indicator is important in assessing disease activity in RA, co-diagnosing RA, detecting subclinical complications, and monitoring responses to anti-inflammatory therapy. Therefore, this review summarizes the relationship between PLR and RA and the relevant mechanisms, further advancing the understanding of the clinical value of PLR.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by sustained airflow limitation that represents one of the main causes of disability in modern society. Depression affects approximately 40% of COPD patients. Both COPD and depression are associated with chronic systemic inflammation and their comorbidity represents a critical unmet treatment need. N-methyl-D-aspartate glutamatergic receptors (NMDAR) are well characterized in the central nervous system (CNS) and widely expressed in lung tissue and inflammation-related cells. Accumulating evidence indicates that pathologic NMDAR up-regulation, leading to pro-inflammatory pathways activation and tissue damage, may play a crucial role in chronic lung injury as well as in depression. D-cycloserine, a bacteriostatic antibiotic used since the 1950's in tuberculosis, acts at therapeutic dosages also as a NMDAR functional antagonist and has antidepressant and anti-inflammatory effects. We hypothesize that NMDAR down-regulation may represent a unified molecular target for the treatment of COPD - depression comorbidity and may simultaneously alleviate both respiratory and depression symptomatology. We postulate that D-cycloserine treatment may achieve these dual - hit objectives and envisage that our hypotheses may apply to additional inflammation disorders that are frequently accompanied by depression.

Purpose: Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs.

Methods: This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann-Whitney U-tests, and multivariable regression models.

Results: This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (β: 17, 95% CI: -1.49 to 35.48), a smaller affected body surface area (BSA) (β: -40.68, 95% CI: -71.59 to -9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%.

Conclusion: This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.