Journal of Inflammation Research最新文献

Background: The combined effect of systemic immune-inflammation index (SII) and aortic valve calcification (AVC) on the risk of major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) remains unclear. This study aimed to investigate their combined association with MACE in CHD.

Methods: This retrospective cohort study included 846 CHD patients. SII was calculated as platelet count × neutrophil count / lymphocyte count, and AVC status was determined by echocardiography. Patients were divided into four groups based on median SII and AVC presence: Low SII + AVC (-), High SII + AVC (-), Low SII + AVC (+), and High SII + AVC (+). Cox regression, subgroup and sensitivity analyses assessed the association between SII + AVC and MACE.

Results: Multivariate Cox regression revealed that, compared to the Low SII + AVC (-), MACE risk increased 6.542-fold in the High SII + AVC (+) group and 1.605-fold in the High SII + AVC (-) group (P < 0.05). Subgroup analysis indicated that, compared to the Low SII + AVC (-), MACE risk was significantly elevated in the High SII + AVC (-) group for patients over 60, both genders, with hypertension, hyperlipidemia, or without diabetes (P < 0.05). In the Low SII + AVC (+) group, MACE risk was elevated only in males (P < 0.05). The High SII + AVC (+) group had increased MACE risk in all subgroups except those with diabetes (P < 0.05). After excluding patients with estimated glomerular filtration rate < 60 mL/min/1.73m², the high SII + AVC (+) group remained significantly associated with increased MACE risk (P = 0.001), as did the High SII + AVC (-) group (P = 0.031).

Conclusion: The combination of SII and AVC is significantly associated with MACE risk in patients with CHD.

The host glycosylation mechanism, with sialic acids as a key component, is essential for synthesizing carbohydrate components in viral glycoproteins. We hypothesize a correlation between the presence of the Neu5Gc on the host tissue and the development of infectious complications, adverse vaccine reactions, and autoimmune diseases. In certain mammals, including humans, the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene (negative-CMAH) prevents the synthesis of Neu5Gc, which acts as a Mammalian-associated Carbohydrate Antigen (MCA), (XeSiAs-Neu5Gc). When negative-CMAH species consume products from positive-CMAH mammals or are exposed to non-human cell-derived medicines, Neu5Gc can be integrated into their glycocalyx through a process called xenosialylation, eliciting an inflammatory response (xenosialitis) and prompting the production of circulating anti-Neu5Gc antibodies aimed at eliminating Neu5Gc. We hypothesize that in the case of xenosialylation, neutralizing antiviral antibodies from infections or vaccinations-including those for SARS-CoV-2-may cross-react with the XeSiAs-Neu5Gc glycans, as these resemble viral envelope antigens produced by the host's glycosylation. Additionally, circulating anti-Neu5Gc antibodies may also react with other circulating antibodies, including newly formed antiviral ones with a XeSiAs-Neu5Gc-contaminated Fc region. This can lead to the serum removal of the anti-inflammatory antibodies, leaving only hyperinflammatory IgG agalactosylated antibodies. Such conditions are also seen in various inflammatory and autoimmune diseases. We hypothesize that the combination of antibody cross-reaction and the removal of the XeSiAs-Neu5Gc-contaminated Fc region anti-inflammatory antibodies may intensify severe inflammatory responses like cytokine storms and coagulopathies in COVID-19 patients and those vaccinated. Assessing serum levels of total XeSiAs-Neu5Gc antibodies could be a valuable method for identifying patients at risk of severe complications from viral infections and vaccinations, including SARS-CoV-2. This strategy may also deepen our understanding of the pathogenesis of autoimmune diseases linked to post-infectious and post-vaccination complications, particularly for viruses utilizing the host glycosylation machinery, such as SARS-CoV-2, IAV, EBV, and others.

Purpose: Severe fever with thrombocytopenia syndrome (SFTS) is an acute viral infection disease with a high mortality, but there are no specific effective drugs or vaccines available for use. To develop effective treatment methods, more basic researches are urgently needed to elucidate the response mechanisms of patients.

Patients and methods: Here, we conducted the transcriptomic analysis of peripheral immunity in 14 SFTS patients, ranging from moderate infection to severe and fatal disease.

Results: The results showed orderly cytokine signaling pathway modulation in moderate patients, cellular immunosuppression in severe patients, and significant dysregulation of the inflammatory response and coagulation dysfunction characteristic of deceased patients. In addition, WGCNA further showed a significant positive correlation between fatal outcomes and B cell and immunoglobulin mediated immune function modules, as well as a significant negative correlation with coagulation function modules.

Conclusion: Overall, our research findings systematically observed potential immune mechanisms underlying clinical symptom heterogeneity and noteworthily revealed multiple signaling pathways leading to coagulation dysfunction in fatal outcomes, not just related to decreased platelet count, which can further elucidate the interaction between viruses and hosts and contribute to clinical treatment.

Purpose: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with significant poor prognosis. Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Eosinophil-to-Lymphocyte Ratio (ELR), Basophil-to-Lymphocyte Ratio (BLR), Platelet-to-Lymphocyte Ratio (PLR), and Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) are vital indicators for inflammation, immune status, and nutritional condition. This study evaluated the predictive value of these indicators in AECOPD and developed predictive models to assess the prognosis of AECOPD based on these indicators.

Patients and methods: We retrospectively collected data from 2609 AECOPD patients. The outcomes assessed included occurrence of respiratory failure (RF), intensive care unit (ICU) stay, mechanical ventilation (MV), and 30-day readmission. We evaluated the predictive ability of LMR, NLR, PLR, BLR, ELR, and HALP for predicting the prognosis of AECOPD patients. Furthermore, based on these indicators, we utilized LASSO regression and multivariable analysis to develop models for predicting the prognosis of AECOPD patients. The predictive value of these indicators and the performance of the models were assessed using AUCs.

Results: LMR exhibited AUCs of 0.612 for RF, 0.715 for ICU stay, 0.714 for MV, and 0.624 for 30-day readmission. Other indicators, including NLR, PLR, BLR, EMR, and HALP, showed AUCs ranging from 0.621 to 0.699 for predicting these outcomes in AECOPD. The models developed using LASSO regression and multivariable analysis yielded AUCs of 0.717 for RF, 0.773 for ICU stay, 0.780 for MV, and 0.682 for 30-day readmission. Incorporating LMR, NLR, PLR, BLR, ELR, and HALP into the models individually further enhanced predictive performance, particularly with LMR (AUCs of 0.753 for RF, 0.797 for ICU stay, 0.802 for MV, and 0.697 for 30-day readmission), NLR (AUCs of 0.753 for RF, 0.796 for ICU stay, 0.802 for MV, and 0.698 for 30-day readmission), and HALP (AUCs of 0.752 for RF, 0.790 for ICU stay, 0.797 for MV, and 0.697 for 30-day readmission).

Conclusion: Indicators of LMR, NLR, PLR, BLR, ELR, and HALP showed good performance in predicting outcomes for AECOPD patients. The integration of these indicators into prognostic models significantly enhances their predictive efficacy.

Osteoarthritis (OA) is a prevalent degenerative disease in elderly people that is characterized by cartilage loss and abrasion, leading to joint pain and dysfunction. The aetiology of OA is complicated and includes abnormal mechanical stress, a mild inflammatory environment, chondrocyte senescence and apoptosis, and changes in chondrocyte metabolism. Ferroptosis is a regulated cell death modality characterized by the excessive accumulation of lipid peroxidation and mitochondrial dysfunction. The role of ferroptosis in OA pathogenesis has aroused researchers' attention in the past two years, and there is mounting evidence indicating that ferroptosis is destructive. However, the impact of ferroptosis on OA and how the regulators of ferroptosis affect OA development are unclear. Here, we reviewed the current understanding of ferroptosis in OA pathogenesis and summarized several drugs and compounds targeting ferroptosis in OA treatment. The accumulation of intracellular iron, the trigger of Fenton reaction, the excessive production of ROS, the peroxidation of PUFA-PLs, and mitochondrial and membrane damage are involved in chondrocyte ferroptosis. System X_c ^- and GPX4 are the most important regulators that control ferroptosis. Several compounds, such as DFO and Fer-1, have been proven effective in preventing ferroptosis and slowing OA progression on animal models. Collectively, targeting ferroptosis shows great potential in treating OA.

Microglial polarization refers to the ability of microglia to exhibit different functional states under various conditions. As the resident immune cells of the brain, changes in the functional state of microglia play a crucial role in the progression of postoperative cognitive dysfunction. Recent studies have indicated that CD200-CD200R signaling is associated with microglial polarization. This review focuses on the latest advancements regarding whether CD200-CD200R signaling can regulate microglial polarization and thereby influence postoperative cognitive dysfunction.

Colorectal cancer (CRC) commonly metastasizes to the liver, and this poses a significant clinical challenge. Tumor-associated macrophages (TAMs), key players within the TME, play a significant role in promoting CRC metastasis by secreting various chemokines, growth factors, and cytokines. This review not only aims to enhance our knowledge of TAMs' functions in CRC progression and metastasis but also examines innovative therapeutic strategies to address the clinical problem of colorectal liver metastasis (CLM). By targeting TAMs, we may be able to develop more effective treatments and offer hope to patients suffering from this devastating disease.

Background: Patients with lymphoma who present with fever of unknown origin (FUO) as an initial symptom lack specific clinical feature analysis, prognostic factor analysis, and existing prognostic models. We aim to create a prognostic model for these patients to improve prognosis and risk assessment.

Methods: A total of 555 lymphoma patients with FUO as initial symptom studied at Huadong Hospital affiliated with Fudan University. Univariable Cox regression identified outcome predictors, analyzed by LASSO Cox. Multifactorial Cox on screened coefficients determined independent prognostic factors and nomogram model. The validity of the nomogram was evaluated through bootstrap sampling, calibration curves for model calibration, time-dependent ROC curve analysis for discrimination assessment, and decision curve analysis for evaluating clinical usefulness. Further validation involved utilizing Kaplan-Meier curves and Log rank tests. Lastly, X-tile software determined the optimal cutoff point for the nomogram score by comparing it with the traditional International Prognostic Index (IPI) scoring system.

Results: The entire cohort was divided into a training cohort (n=388) and a validation cohort (n=167). These risk factors (cell pathologic type, performance status score, Ann Arbor staging, thrombocytopenia, and raised direct bilirubin) were used to construct a web-based dynamic survival rate calculator for lymphoma patients initially presenting with FUO. The lymphoma-specific nomogram demonstrated good consistency and efficacy in predicting the model's risk stratification. Compared to the IPI scoring system, the nomogram model had higher AUC values for different clinical endpoints. The new nomogram prognostic model showed better differentiation of risk groups compared to traditional IPI scoring.

Conclusion: Our study developed and validated a prognostic nomogram for lymphoma patients initially presenting with FUO, demonstrating robust predictive efficacy and risk stratification ability. Furthermore, we have successfully implemented this model into a web-based dynamic survival rate calculator.

Background: The Systemic Inflammation Response Index (SIRI) and N-terminal Pro-B-type natriuretic peptide (NT-proBNP) have been proposed as reliable predictors of poor prognosis in cardiovascular disease and all-cause mortality, However, their validity has not been extensively evaluated in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA).

Patients and methods: 259 patients diagnosed with MINOCA were enrolled in this study from January 2015 to December 2022, and serum levels of SIRI and NT-proBNP were detected. The primary endpoints were major adverse cardiovascular events (MACE). According to the occurrence of MACE during the follow-up period, patients were grouped into MACE and Non-MACE groups, and divided by the median values for SIRI and NT-proBNP into groups: low SIRI, high SIRI, low NT-proBNP, and high NT-proBNP.

Results: A statistically significant difference in the levels of SIRI and NT-proBNP was observed between the MACE group and the non-MACE group. Kaplan-Meier survival curve analysis revealed that patients with high SIRI and high NT-proBNP had a significantly higher risk of MACE (log-rank P < 0.001). Furthermore, even after adjusting for covariates, the high SIRI and high NT-proBNP were associated with an increased risk of MACE (P<0.001, HR: 3.188, 95% CI 1.940-5.241; P<0.001, HR: 2.245, 95% CI 1.432-3.519). Additionally, the combined prognosis prediction of SIRI and NT-proBNP was superior to a single prediction, and adding SIRI and NT-proBNP to the traditional risk factor model improved the model's predictive value.

Conclusion: High levels of SIRI and NT-proBNP exhibit a significant correlation with an increased risk of MACE, thereby suggesting that SIRI can be used as a reliable inflammatory indicator for predicting the risk in MINOCA patients, with significantly improved prognostic value when combined with NT-proBNP.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by active polyarthritis, which leads to functional loss and joint deformities. Natural compounds derived from marine organisms are considered valuable immune-modulating agents. This study aimed to assess the anti-inflammatory effect of sinulariolide, a soft coral-derived compound, on RA fibroblast-like synoviocytes and its therapeutic efficacy against collagen-induced arthritis (CIA).

Methods: To determine the effects of sinulariolide on tumor necrosis factor-alpha (TNF-α)-induced inflammation, MH7A cells pre-treated with 10 ng/mL TNF-α for 24 h were treated with sinulariolide. The effect of sinulariolide on proinflammatory cytokine expressions at both the mRNA and protein levels in the MH7A cells was assessed using real-time-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Further, we analyzed the effect of sinulariolide on the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways using Western blotting and the TransAM NF-κB p65 kit. To comprehensively evaluate the potential application of sinulariolide in the treatment of inflammatory diseases, we used a well-established collagen-induced arthritis (CIA) mouse model. We examined the tissue sections of the ankle joints of the mice, assessed synovial hyperplasia, inflammatory cell infiltration, and cartilage damage, and used ELISA to analyze changes in cytokine expression in the hind paw tissues.

Results: MH7A cells treated with sinulariolide showed a notable reduction in the expression of proinflammatory cytokines, which could be due to decreased activation of the MAPK and NF-kB pathways. Additionally, sinulariolide-treated mice showed significantly reduced joint swelling and lower clinical arthritis scores than those in the normal and control groups. Significant reductions in synovial hyperplasia, inflammatory cell infiltration, and cartilage damage were observed in the tissue sections of the ankle joints of the mice treated with sinulariolide. Furthermore, the expression of inflammatory cytokines in the hind paw tissue of the mice treated with sinulariolide was significantly decreased.

Conclusion: Sinulariolide inhibited the progression of inflammation in MH7A cells. Sinulariolide treatment significantly reduced clinical arthritis symptoms and histological inflammatory responses in mice with CIA. Sinulariolide may serve as a potential therapeutic agent for RA.