Journal of Inflammation Research最新文献

Background: Endometriosis is frequently treated with Paeoniae Radix. It contains Tellimagrandin II, which has the role of modulating immunity and anti-tumor. Therefore, we will explore the effects of Tellimagrandin II on the apoptosis and invasion/migration of ectopic endometrial cells (EECs).

Methods: Tellimagrandin II was used to treat EECs, and transcriptomics and bioinformatics techniques were used to identify its main pathways and targets of Tellimagrandin II. Western blotting was used to confirm the expression of essential targets. Flow cytometry was applied, the impact of tellimagrandin II on EECs apoptosis was identified. Transwell assays were conducted the effects of Tellimagrandin II on EECs invasion and migration. Finally, the binding of tellimagrandin II to key targets was confirmed using molecular docking techniques.

Results: Tellimagrandin II may inhibit pathways like beta-alanine metabolism and ECM-receptor interaction while activating JAK-STAT, NF-κB, and apoptotic pathways, according to transcriptomics and GSEA enrichment analysis. Tellimagrandin II can inhibit ALDH7A1 expression in EECs as well as increase SMOX expression, which may facilitate the accumulation of 3-Aminopropanal. This action becomes more pronounced as the dosage is increased. By upregulating the expression of NLRP3, TIMP-1, Caspase-3, BAX, and Caspase-1 in EECs while decreasing the expression of β-catenin and MMP2, tellimagrandin II can prevent EECs invasion and migration and encourage EECs apoptosis. Tellimagrandin II exhibited good docking with ALDH7A1 and SMOX, according to molecular docking.

Conclusion: Tellimagrandin II may stimulate inflammasomes by encouraging 3-aminopropanal accumulation within EECs. The increase in inflammasomes may promote EECs apoptosis and inhibit EECs invasion and migration. However, its in vivo inhibitory effects on endometriosis require further investigation.

Background: ANCA-associated vasculitis (AAV) is a group of autoimmune diseases characterized by necrotizing inflammation and fibrinoid necrosis of small- and medium-sized blood vessels. Renal involvement is common in AAV; however, renal hemorrhage is extremely rare, particularly in cases of eosinophilic granulomatosis with polyangiitis (EGPA). Spontaneous renal hemorrhage often presents as acute abdomen.

Case presentation: We report a 51-year-old male with a prior diagnosis of EGPA who presented to the emergency department with acute left-sided abdominal pain and signs of hypovolemic shock. Imaging revealed a massive left perirenal hematoma without active contrast extravasation, suggestive of renal rupture. Initial management focused on hemostasis and stabilization, but recurrent contralateral renal hemorrhage occurred during hospitalization. Further immunological, histopathological, and bone marrow evaluations confirmed EGPA complicated by renal involvement. The patient was treated with corticosteroids, cyclophosphamide, and rituximab, but recurrent hemorrhage indicated rapid disease progression or insufficient therapeutic response. Due to financial constraints, the patient was discharged prematurely, precluding long-term follow-up.

Discussion: This case highlights the complexity of diagnosing and managing AAV-associated renal hemorrhage, particularly in EGPA patients. While the renal vascular changes observed, such as inflammation and potential necrosis, may be linked to the underlying vasculitis in EGPA, causality should be interpreted with caution, as other factors like coagulopathy, concurrent infections, or iatrogenic effects could contribute. Current literature suggests that ANCA-associated mechanisms, including NETs formation, play a role in vascular damage, but direct causation in rare complications like renal hemorrhage remains uncertain and requires further investigation. While EGPA treatment primarily involves immunosuppressive therapy targeting vasculitis and eosinophilia, spontaneous renal hemorrhage requires an integrated approach, including conservative management, interventional embolization, or surgical exploration in life-threatening cases. Reports of AAV-associated renal hemorrhage are rare, and large-scale studies are lacking, necessitating further research to optimize treatment strategies.

Purpose: Sepsis continues to pose a significant threat to global health, characterized by elevated mortality rates. Pulmonary complications frequently develop in septic patients, with endothelial dysfunction correlating with adverse clinical outcomes. While overproduction of neutrophil extracellular traps (NETs) is implicated in vascular damage, their specific influence on the regenerative potential of pulmonary endothelial cells requires further elucidation. Our investigation aims to address this critical knowledge gap.

Patients and methods: Clinical samples from sepsis patients and healthy controls were analyzed to establish the correlation between NETs and pulmonary endothelial injury. An in vivo sepsis model was generated through cecal ligation and puncture (CLP) in mice, with sham surgery animals serving as reference group. Human umbilical vein endothelial cells (HUVECs) were employed for in vitro assessment of NETs-mediated cell cycle modulation.

Results: Elevated NETs formation was observed in septic patients, showing positive association with inflammatory damage. CLP-induced mice demonstrated substantially increased NETs levels, pronounced pulmonary vascular permeability, and notable endothelial cell depletion. DNase I-mediated NETs degradation alleviated pulmonary inflammation and promoted endothelial recovery. Both experimental models revealed that excessive NETs release during sepsis compromises endothelial proliferation via polo-like kinase 1 (PLK1) pathway inhibition and subsequent G2/M phase arrest.

Conclusion: This study establishes that NETs accumulation in septic pulmonary injury hinders endothelial regeneration and vascular repair through PLK1 signaling suppression and G2/M cell cycle blockade.

Background: To assess whether baseline serum high density lipoprotein (HDL) levels predict the effectiveness of infliximab in patients with Crohn's disease (CD).

Methods: This was a retrospective single-center study evaluating CD patients baseline data and effectiveness of infliximab at the Xiangya Hospital, Central South University, between January 2016 and September 2021. The primary endpoint was composite adverse outcome during 52 weeks, defined as clinical activity, changes in treatment, surgical treatment, or unexpected readmission.

Results: Among the 166 enrolled patients, 37 (22.3%) experienced adverse events within the 52-week follow-up period. HDL was identified as a predictor of adverse outcomes at 52 weeks (AUC 0.661, p < 0.05), with an optimal cut-off value of 0.85. Patients with higher HDL levels not only exhibited elevated total cholesterol but were also associated with better nutritional status and lower inflammatory burden. HDL was negatively correlated with white blood cell count and C-reactive protein, and positively correlated with albumin level (p < 0.05). Baseline HDL level was an independent risk factor for adverse events within 52 weeks in CD patients treated with infliximab (p = 0.022). Moreover, the high-HDL group demonstrated a significantly lower risk of developing adverse events (p = 0.0017).

Conclusion: The identification of HDL as an independent risk factor for 52-week adverse events in infliximab-treated CD patients suggests its potential utility as a predictive biomarker.

Trial registration: The study adhered to the Declaration of Helsinki. All participants provided written informed consent, and the study was approved by the Ethics Committee of Xiangya Hospital, Central South University with approval No. 202108158.

Purpose: Sepsis is a life-threatening condition, and early detection remains a challenge. While bile acids have been implicated in various diseases, their role as biomarkers for sepsis is underexplored. This study aims to identify metabolites associated with sepsis and assess the potential of bile acids for early diagnosis and prognosis of pediatric sepsis.

Methods: We enrolled 100 participants in the discovery phase and 141 participants in the validation phase. Non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analyses were performed to identify differential metabolites between sepsis patients and healthy controls. Targeted quantitative analysis of 12 plasma bile acids (BA) was conducted to assess their concentrations. Machine learning algorithms, including Recursive Feature Elimination (RFE), Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), Support Vector Machine-RFE (SVM-RFE), and Gradient Boosting Decision Tree (GBDT), were employed to identify key BAs for sepsis diagnosis.

Results: Untargeted metabolomics revealed bile acid pathway dysregulation, validated by targeted quantification showing elevated primary bile acids-cholic acid (CA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA)-and taurine-conjugated secondary bile acid TDCA (p<0.05). Conversely, secondary bile acids deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), and lithocholic acid (LCA) were significantly reduced (p<0.05). Univariate logistic regression identified TCA, TDCA, GCA, TCDCA, GCDCA, and TDCA/DCA as risk factors for sepsis, while LCA, DCA, UDCA, GUDCA, and DCA/CA were protective factors. Five machine learning models identified four bile acid indicators-UDCA, GUDCA, GCA, DCA-as key predictors for sepsis diagnosis, with a combined model area under the curve (AUC) of 0.880. Additionally, DCA/CA and GCDCA were important predictors for septic shock, with risks increasing by 4.5% (OR = 1.045, 95% CI: 1.009-1.081) and 30% (OR = 0.700, 95% CI: 0.526-0.932), respectively. LCA was a risk factor for respiratory failure in sepsis, with an OR of 2.154 (95% CI: 1.022-4.540).

Conclusion: Our results highlight the potential of bile acid profiling as a diagnostic and prognostic biomarker for pediatric sepsis. These findings suggest a path toward early intervention, improving patient outcomes by enabling timely detection and treatment.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which intense pruritus and eczematous lesions arise from tightly coupled disturbances of the nervous and immune systems. Emerging evidence indicates that a dysregulated neuroimmune axis-as reflected by peripheral neuronal sensitization, epidermal barrier dysfunction, and central itch processing-plays a central role in disease onset, persistence, and clinical heterogeneity. In this review, we synthesize current knowledge on the neuroimmune mechanisms that drive AD, focusing on how cytokines such as IL-31, IL-4/IL-13, TSLP and IL-33, together with neuropeptides including substance P, CGRP and VIP, establish self-reinforcing itch-scratch and inflammation loops at the level of the skin and the central nervous system. We then highlight recent multi-omics and systems biology approaches, including single-cell and spatial transcriptomics, neuroimaging, and microbiome profiling, that have reshaped the understanding of neuroimmune "neighbourhoods" and the gut-skin-brain axis in AD. Building on these mechanistic insights, we summarize key neuroimmune biomarkers-such as NGF, IL-31, TARC/CCL17, S100 proteins, barrier-related lipids, neurofunctional readouts from fMRI, and microbial signatures-and discuss their potential for improving diagnosis, patient stratification, and treatment monitoring within a precision medicine framework. Finally, we review established and emerging neuroimmune-targeted therapies, including IL-4/IL-13 and IL-31 pathway inhibitors, JAK inhibitors, OX40/OX40L-directed biologics, TRP and NK1R antagonists, phototherapy, and microbiome-based interventions, with a particular emphasis on biomarker-guided sequencing and combination strategies. Overall, we propose that positioning the neuroimmune axis at the core of AD pathogenesis provides a conceptual basis for developing stratified, durable, and patient-centred neuroimmunotherapy, while also outlining the remaining challenges regarding clinical validation of biomarkers, long-term safety, accessibility, and implementation across diverse patient populations.

Background: Robust biomarkers are needed to address the prognostic heterogeneity in colorectal cancer (CRC). The pan-immune-inflammation value (PIV) and prognostic nutritional index (PNI) are biomarkers of systemic inflammation and immunonutritional status, respectively. This study aimed to develop and validate a novel combined PIV-PNI score to predict survival in CRC patients undergoing curative resection.

Methods: This study included a total of 2116 CRC patients who underwent surgical treatment. The PIV and PNI were evaluated and cut-off values were determined. The PIV-PNI value range was 0 to 2, where 2 represented high PIV (≥ 208.9) and low PNI (≤ 49.05), with high PIV or low PNI indicated by 1 and neither is represented by a 0, respectively. The Cox regression model was used to determine the independent risk factors affecting the prognosis of the patients. A nomogram based on PIV-PNI was constructed, and its performance was evaluated using the C-index, calibration curve, ROC curve, and DCA curve. Finally, the nomogram model was compared with the existing staging models.

Results: Patients with higher PIV-PNI scores had a poorer prognosis. In the multivariate analysis, it was found that the PIV-PNI score was an independent predictor for the overall survival rate and disease-free survival rate of CRC patients. The nomogram based on PIV-PNI demonstrated excellent discrimination, calibration, and clinical net benefit. The proposed nomogram performed better than other existing staging systems, as evidenced by its higher AUC value.

Conclusion: The PIV-PNI score is a potent, non-invasive prognostic biomarker. The developed nomogram facilitates accurate risk stratification, potentially guiding personalized postoperative surveillance and adjuvant therapy decisions for CRC patients.

Beyond glycemic control, hypoglycemic agents exhibit multifaceted effects that may influence pulmonary health in patients with diabetes mellitus. This narrative review synthesizes available evidence from preclinical and clinical studies on the impact of major hypoglycemic drug classes-including biguanides, sulfonylureas, thiazolidinediones, α-glucosidase inhibitors, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists, and insulin-on pulmonary diseases. Evidence suggests that these agents exert class-specific, and often conflicting, effects: preclinical studies support their protective potential in acute lung injury, while clinical data indicate variable efficacy in asthma, COPD, and respiratory infections including COVID-19. Conversely, some agents may be associated with increased risks of lung cancer or COPD exacerbations, underscoring the need for context-specific prescribing. Mechanistic insights from animal models primarily involve modulation of inflammatory, oxidative, and immune pathways. This narrative review aims to provide a clinical framework for personalizing hypoglycemic therapy in patients with comorbid pulmonary conditions, while underscoring the need for well-designed prospective studies to resolve existing controversies.

Ferroptosis, a iron-dependent programmed cell death characterized by iron-dependent accumulation of lipid peroxidation to lethal levels, is closely related to the pathogenesis of hypertriglyceridemic acute pancreatitis, a condition marked by lipid metabolism disorders. This paper summarizes the latest research progress in understanding the mechanistic contributions on the mechanisms of ferroptosis in HTG-AP, with a particular focus on the roles of lipid peroxidation and iron-catalyzed reactive oxygen species generation in the pathogenesis and progression of HTG-AP. It further elaborates on critical molecules-including the GPX4, ACSL4, SLC7A11 and FSP1-CoQ10-NAD(P)H and key cellular signaling pathways-including the HIF pathways, JAK-STAT pathways, PI3K/ Akt pathways closely linked to ferroptosis in HTG-AP. Understanding the pathophysiological role of hypertriglyceridemia in pancreatic injury is essential for unraveling the complex interplay between lipid and iron metabolic homeostasis. Additionally, by integrating evidence from preclinical models and human studies, this review emphasizes the importance of ferroptosis mechanisms in the treatment of HTG-AP, with the goal of identifying potential therapeutic targets and proposing innovative intervention strategies aimed at mitigating ferroptosis, potentially improving outcomes in HTG-AP.

Background: Multiple Organ Dysfunction Syndrome (MODS) is a lethal complication of acute pancreatitis (AP), making early identification of high-risk patients crucial for improving outcomes.

Aim: To develop and validate a clinically applicable nomogram for predicting MODS risk in acute pancreatitis patients based on clinical and laboratory variables collected within the first 24 hours of admission.

Methods: We conducted a single-center retrospective cohort study using routinely collected electronic health records from Shanxi Bethune Hospital (Taiyuan, China), including 693 adult patients with acute pancreatitis admitted between January 1, 2019 and December 31, 2021. From 29 candidate indicators obtained within 24 hours of admission, key predictors were selected via LASSO regression, and three machine-learning models - generalized linear model (GLM), random forest (RF), and support vector machine (SVM) - were constructed and compared.

Results: Among the candidate models, the GLM-based nomogram showed the best overall performance. Using a parsimonious variable selection strategy, we derived a final 7-variable model. This model demonstrated good discrimination, with areas under the curve of 0.829 in the training cohort and 0.846 in the validation cohort, and showed satisfactory calibration, a high negative predictive value, and clinical net benefit.

Conclusion: Our internally validated 7-variable nomogram, based on a generalized linear model, showed good discrimination and a high negative predictive value for early prediction of multiple organ dysfunction syndrome in patients with acute pancreatitis, and may assist clinicians in early risk stratification and resource allocation. Further external validation and prospective studies are warranted to confirm its generalizability and clarify its impact on clinical decision-making and patient outcomes.