Mediators Of Inflammation[JOURNAL]
Sun
200 papers
SPP1 May Play an Important Role in the Carcinoid Nature of PAH.
Huang Y, Yan S, Zhu J … +1 more , Zhang W
Mediators Inflamm · 2025 · PMID 41498045 · Full text
OBJECTION: Pulmonary arterial hypertension (PAH) was a cancer-like disease. It shared several mechanisms, including perivascular inflammation. But the genes common and different between cancer and PAH was still unclear....
OBJECTION: Pulmonary arterial hypertension (PAH) was a cancer-like disease. It shared several mechanisms, including perivascular inflammation. But the genes common and different between cancer and PAH was still unclear. We aimed to analyze the genes common in the two diseases, especially the N7-methylguanosine (m7G) genes. METHODS: We acquired dataset GSE1519, GSE113439, and GSE81089 and recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. m7G-related genes were identified using a online tool RMvar. The extent of immune cell infiltration in the normal and PAH tissues, nonsmall cell lung cancer (NSCLC) tissues was determined using ImmuneCellAI and CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. Single cell analysis and Cellchat were used to analyze the role of SPP1 in the PAH. RESULTS: Among five DEGs overlapped by the differently datasets about NSCLC, CD163, and SPP1 were m7G genes. The immune cell infiltration results suggested that PAH and NSCLC shared different immune cell infiltration. SPP1 was significantly correlated to the macrophage cells and activated mast cells in NSCLC. Higher expression of CD163 and SPP1 might be related to the progression of monocrotaline (MCT) induced rats in the dataset GSE229361. The KM survival analysis suggested that higher expression of CD163 and SPP1 related to poor prognosis of NSCLC. The important role of SPP1 in PAH was verified using single cell anslysis. CONCLUSION: Different T cells infiltration contributed to the development of PAH and NSCLC. SPP1 might be vital for the cancer-like characteristics of PAH.
Integrative Genomic and Single-Cell Insights Into Efferocytosis-Mediated Immune Regulation in Clear Cell Renal Cell Carcinoma.
Shi B, Deng M, Ma J … +8 more , Chen C, Peng A, Zhu A, Yang R, Jin Z, Zhu J, Zhang M, Shen S
Mediators Inflamm · 2025 · PMID 41498044 · Full text
BACKGROUND: Efferocytosis, the phagocytic clearance of apoptotic cells, plays a key role in tumor progression and immune regulation, but its prognostic significance and molecular mechanisms in clear cell renal cell carci...
BACKGROUND: Efferocytosis, the phagocytic clearance of apoptotic cells, plays a key role in tumor progression and immune regulation, but its prognostic significance and molecular mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear. METHODS: Four efferocytosis-related pathways were curated, and the pathway activities were quantified in ccRCC. Prognostic genes were identified by univariate Cox regression and used to construct linear survival models with multiple algorithms, with the optimal model selected by cross-validation. Associations between the risk score and tumor mutational burden (TMB), mutation profiles, and copy number variation (CNV) were subsequently evaluated. Multiomics integration highlighted RAC1 as a key risk gene, which was further examined using single-cell and spatial transcriptomics (ST) to characterize expression patterns, tumor microenvironment interactions, and pathway enrichments. Protein-level validation was performed using immunohistochemistry (IHC) data from the Human Protein Atlas. RESULTS: Efferocytosis pathway activity was upregulated in ccRCC, increased with disease stage, and correlated with poorer survival. The ridge regression-based prognostic model demonstrated consistent predictive performance across independent datasets and was associated with higher TMB, specific mutation patterns, and increased CNV. Notably, RAC1, identified as the top weighted gene in the model, was overexpressed in association with copy number amplification, showing preferential enrichment in malignant core regions and strong links to oncogenic signaling. CONCLUSION: Efferocytosis activation characterizes aggressive ccRCC. The developed prognostic model and identification of RAC1 as a central effector link efferocytosis-related risk to immune remodeling and oncogenic signaling, providing potential biomarkers and therapeutic targets.
Gut-Bone Axis Mediates Exercise Modality-Dependent Suppression of Inflammatory Osteoclastogenesis in Ovariectomy-Induced Bone Loss.
Gao Y, Wang H, Shi L … +11 more , Cao M, Liu X, Zhang Y, Chen X, Rong Y, Han B, Lu P, Dai G, Fan W, Rui Y, Li Y
Mediators Inflamm · 2025 · PMID 41498043 · Full text
Exercise is crucial for postmenopausal osteoporosis (PMOP) management, yet the comparative efficacy of different exercise modalities and the underlying mechanisms remain unclear. This study investigated the differential...
Exercise is crucial for postmenopausal osteoporosis (PMOP) management, yet the comparative efficacy of different exercise modalities and the underlying mechanisms remain unclear. This study investigated the differential effects of distance-matched high-intensity interval training (HIIT) and moderate-intensity continuous exercise (MICE) on ovariectomy (OVX)-induced osteoporosis (OP) in mice. After 12 weeks of training, micro-CT analysis revealed that MICE, but not HIIT, significantly attenuated OVX-induced bone loss and microstructural deterioration. Crucially, only MICE suppressed osteoclastogenesis and reduced proinflammatory factors (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) expression in the femur, serum, and colon. Mechanistically, MICE uniquely restored gut microbiota (GM) diversity, mitigated dysbiosis, and enhanced intestinal barrier integrity by upregulating the expression of tight junction proteins (TJPs; ZO-1, occludin, and claudin-1), thereby reducing systemic inflammation. In contrast, HIIT failed to ameliorate GM imbalance and intestinal permeability. Our findings demonstrate that the protective effect of MICE on OVX-induced OP is mediated through the gut-bone axis by modulating GM, repairing the intestinal barrier, and suppressing inflammatory osteoclast activation. This study provides novel evidence that the benefits of exercise on PMOP are modality-dependent, highlighting MICE as a superior strategy and offering mechanistic insights for optimizing exercise prescriptions.
A Multicenter Study on the Prognostic Value of Indicators Derived From Complete Blood Count in Glioblastoma.
Hou S, Gu Q, Yang T … +5 more , Hou Y, Wang M, Pan Y, Jin C, Lin N
Mediators Inflamm · 2025 · PMID 41498042 · Full text
BACKGROUND: Previous studies have found that some indices derived from preoperative complete blood count (CBC) are closely related to the prognosis of glioma, but the results are inconsistent. This study comprehensively...
BACKGROUND: Previous studies have found that some indices derived from preoperative complete blood count (CBC) are closely related to the prognosis of glioma, but the results are inconsistent. This study comprehensively discussed the prognostic significance of the preoperative CBC index in patients with glioblastoma (GBM) through a multicenter study. METHODS: In this multicenter study, we retrospectively analyzed clinical data from 143 GBM patients to evaluate the prognostic value of 12 preoperative CBC-derived indicators: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), red cell distribution width (RDW), platelet distribution width (PDW), RDW-to-PDW (RPR), systemic inflammation index (SII), systemic inflammation response index (SIRI), hemoglobin-to-red cell distribution width ratio (HRR), platelet-to-basophil ratio (PBR), lymphocyte-to-basophil ratio (LBR), and eosinophil-to-lymphocyte ratio (ELR). Optimal cut-off values for each indicator were determined using maximally selected rank statistics (MSRS). Survival outcomes were assessed by Kaplan-Meier analysis, and univariate and multivariate Cox regression were employed to identify independent prognostic factors. Furthermore, a nomogram was developed by integrating significant prognostic indicators to facilitate individualized prediction of survival in GBM patients. RESULTS: The results showed that higher levels of NLR, PLR, MLR, RDW, PDW, and RPR were associated with shorter survival in GBM patients. In contrast, lower levels of ELR were associated with shorter survival in GBM patients. Among these, RDW (HR 1.905, 95% CI 1.114-3.258, = 0.019), MLR (HR 1.603, 95% CI 1.029-2.496, = 0.037), and ELR (HR 0.380, 95% CI 0.193-0.747, = 0.005) emerged as an independent prognostic factors. The prognostic nomogram was constructed according to the three independent factors, which improved the accuracy of prognosis prediction (AUC = 0.702). CONCLUSION: Routine preoperative CBC parameters, particularly RDW, MLR, and ELR, serve as valuable complementary prognostic indicators for GBM patients. These accessible biomarkers warrant further validation through large-sample, multicenter studies to solidify their clinical utility.
RETRACTION: Inhibiting HMGB1 with Glycyrrhizic Acid Protects Brain Injury after DAI via Its Anti-Inflammatory Effect.
Inflammation MO
Mediators Inflamm · 2025 · PMID 41498041 · Full text
[This retracts the article DOI: 10.1155/2016/4569521.].
[This retracts the article DOI: 10.1155/2016/4569521.].
Rongbei Maimendong Decoction Promotes Radiosensitivity of Non-Small Cell Lung Cancer Cells by Inhibiting SOD1 Expression.
Liu S, Pang X, Wang L … +8 more , Zhan N, Wu S, Deng J, Jin K, Bai Y, Jiang D, Qi L, Li Z
Mediators Inflamm · 2025 · PMID 41498040 · Full text
Some natural remedies in traditional Chinese medicine (TCM) inhibit tumor progression and increase sensitivity in the treatment of patients who have received radiation therapy. However, the specific synergistic effect of...
Some natural remedies in traditional Chinese medicine (TCM) inhibit tumor progression and increase sensitivity in the treatment of patients who have received radiation therapy. However, the specific synergistic effect of the active ingredients in the traditional Chinese therapeutic Rongbei Maimendong decoction (RBMD) on sensitivity to radiation therapy for non-cell lung cancer (NSCLC) is still unclear. RBMD inhibited transplanted tumor cell growth in mice, showing a dose-dependent effect in tumor growth inhibition following radiotherapy. Our study utilized bioinformatics analysis and liquid chromatography with tandem mass spectrometry to identify the presence of β-thymidine (β-thy) in bark, the primary component of RBMD. This compound modulated mRNA and protein levels of SOD1 by interacting with SOD1, inhibiting the malignant characteristics (proliferation, apoptosis, migration, and invasion) of NSCLC cells. Furthermore, apoptosis assays demonstrated that β-thy attenuated tumor growth in mice following radiotherapy. Single-cell gel electrophoresis assays demonstrated the ability of SOD1 to mitigate DNA damage in irradiated (IR) NSCLC cells, suppressing apoptosis, and that β-thy attenuated this SOD1 protective effect, mitigating NSCLC cells resistance to radiation. We propose that the consumption of RBMD, which is rich in β-thy, may enhance NSCLC radiosensitivity by hindering DNA repair mechanisms and facilitating apoptosis through DNA damage augmentation.
Mitochondrial Dysfunction and Immune Cell Infiltration in Diabetic Kidney Disease: A Mendelian Randomization and Multiomics Study.
Zhang T, Wu J, Zhang J … +7 more , Hu Y, Zhao Y, Mao G, Jiao J, Wang J, Chen R, Zheng C
Mediators Inflamm · 2025 · PMID 41498039 · Full text
BACKGROUND: Diabetic kidney disease (DKD) is a multifactorial complication of diabetes involving mitochondrial dysfunction and immune cell infiltration. However, the causal relationships remain unclear. METHODS: We appli...
BACKGROUND: Diabetic kidney disease (DKD) is a multifactorial complication of diabetes involving mitochondrial dysfunction and immune cell infiltration. However, the causal relationships remain unclear. METHODS: We applied Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to investigate the roles of mitochondrial gene expression and immune cells in DKD. Additionally, peripheral blood mononuclear cells (PBMCs) from DKD patients were analyzed for differential gene expression. RESULTS: Higher expression of mitochondrial genes PCCB, ACADM, ADHFE1, OCIAD1, and FIS1 increased DKD risk, while genes like NT5DC2, ATP5MC3, and GLYCTK decreased risk. Immune traits, including human leukocyte antigen (HLA)-DR + plasmacytoid dendritic cells (pDCs), mediated the effects of mitochondrial dysfunction on DKD. scRNA-seq revealed significant downregulation of ATP5MC3, GLYCTK, and NT5DC2 in podocytes (PODOs) and tubular cells in DKD kidneys, alongside increased infiltration of helper T cells, B cells, dendritic cells (DCs), and plasma cells. PBMC analysis highlighted the upregulation of proinflammatory genes (CXCL2, CXCL3, and others) in DKD patients. CONCLUSION: This study highlights the complex interplay between mitochondrial dysfunction and immune cell infiltration in DKD pathogenesis. Key mitochondrial genes and immune traits identified here offer novel therapeutic targets such as ATP5MC3, GLYCTK, and DC pathways.
RETRACTION: Interleukin-10-Modified Adipose-Derived Mesenchymal Stem Cells Prevent Hypertrophic Scar Formation via Regulating the Biological Characteristics of Fibroblasts and Inflammation.
Inflammation MO
Mediators Inflamm · 2025 · PMID 41498038 · Full text
[This retracts the article DOI: 10.1155/2022/6368311.].
[This retracts the article DOI: 10.1155/2022/6368311.].
Single-Cell Transcriptomic Analysis Reveals an Inflammatory Antigen-Presenting Macrophages Subtype Drive Vitiligo Pathogenesis Through STAT1-Mediated Dual Mechanisms.
Qi R, Huang M, Lin Z … +5 more , Deng H, Sa R, Chen Y, Chen G, Duan X
Mediators Inflamm · 2025 · PMID 41498037 · Full text
BACKGROUND: Vitiligo is a common depigmentary disorder characterized by progressive melanocyte (MEL) loss. While T-cell activation is central to its pathogenesis, the role of macrophages remains poorly understood. This s...
BACKGROUND: Vitiligo is a common depigmentary disorder characterized by progressive melanocyte (MEL) loss. While T-cell activation is central to its pathogenesis, the role of macrophages remains poorly understood. This study characterizes macrophage heterogeneity and function in vitiligo using single-cell transcriptomic analysis and experimental validation. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data from healthy and vitiligo-affected skin to identify macrophage subpopulations. Computational analyses included cell subpopulation clustering, pseudotime trajectory inference, cell-cell communication, and high-dimensional weighted gene coexpression network analysis (hdWGCNA). In vivo and in vitro experiments examined the effects of STAT1 suppression on the macrophage inflammatory phenotype and antigen presentation capacity. RESULTS: scRNA-seq analysis identified macrophages and T cell subsets enriched in vitiligo. Macrophage subclustering identified five subpopulations, with inflammatory antigen-presenting macrophages (Mac-InflamAP) significantly enriched in vitiligo lesions and M1-polarized. Pseudotime analysis revealed Mac-InflamAP as a terminal differentiation state. Cell-cell communication analysis showed Mac-InflamAP exerts TNF-mediated inhibitory effects on MELs while enhancing T-cell antigen presentation, thereby promoting MEL loss. hdWGCNA identified STAT1 as a key regulator highly expressed in Mac-InflamAP. In vivo, STAT1 inhibition by fludarabine ameliorated vitiligo progression by suppressing T cell activation and macrophage M1-polarization. In vitro experiments confirmed STAT1 suppression reduced macrophage M1 polarization, inflammatory phenotype, and antigen presentation capabilities. CONCLUSIONS: This study reveals an uncharacterized inflammatory macrophage subpopulation crucial to vitiligo pathogenesis through dual mechanisms: direct MEL inhibition and enhanced T-cell activation. The identification of STAT1 as a key regulatory molecule provides a novel therapeutic target for vitiligo. These findings advance our understanding of immune-mediated mechanisms in vitiligo.
Neutrophils in Intracerebral Hemorrhage: Roles, Mechanisms, and Therapeutic Implications.
Chu J, Qiu Y, Zhou Q … +1 more , Yu J
Mediators Inflamm · 2025 · PMID 41498036 · Full text
Nontraumatic intracerebral hemorrhage (ICH), characterized by bleeding into the brain parenchyma, is a major cause of adult disability and mortality. The pathophysiology of ICH involves complex processes, including mass...
Nontraumatic intracerebral hemorrhage (ICH), characterized by bleeding into the brain parenchyma, is a major cause of adult disability and mortality. The pathophysiology of ICH involves complex processes, including mass effect and subsequent inflammatory responses, which cause severe primary and secondary brain damage. As the first responders in neuroinflammatory reactions, neutrophils are rapidly recruited to the hemorrhage site. They interact with other immune cells, release cytotoxic molecules, and significantly exacerbate neuroinflammation. In the acute phase, neutrophils secrete cytokines, chemokines and neutrophil extracellular traps (NETs), which are particularly detrimental to brain tissue. However, in later stages, infiltrated neutrophils can adopt an immunosuppressive phenotype, exerting beneficial effects. Emerging evidence reveals that neutrophils play a multifaceted role in ICH progression, shifting between anti-inflammatory or pro-inflammatory phenotypes depending on brain tissue niche. Hence, tuning neutrophils into a beneficial phenotype represents a promising therapeutic strategy for ICH. We conducted a comprehensive literature search in PubMed and Web of Science databases for relevant studies published up to July 2025, using keywords including "intracerebral hemorrhage (ICH)," "neutrophil," "inflammation," "neuroinflammation," " neutrophil extracellular traps (NETs)," "treatment," "therapy," and "therapeutics." In this article, we explore the roles of neutrophils in ICH, encompassing their recruitment, activation mechanisms, interactions with other immune cells, and impact on neuroinflammation and neuronal injury. Furthermore, we discuss therapeutic strategies targeting neutrophil-mediated pathways in ICH, highlighting potential avenues for future research and clinical intervention.
Foxj2 Attenuates LPS-Induced Inflammatory Response in Macrophages.
Huang P, Fu J, Hu J … +4 more , Lei Y, Dai C, Wu T, Liu J
Mediators Inflamm · 2025 · PMID 41498035 · Full text
BACKGROUND: Macrophages are central to innate immune responses and are crucial in maintaining homeostasis and managing inflammatory diseases. Forkhead box J2 (Foxj2) is a member of the forkhead/hepatocyte nuclear factor...
BACKGROUND: Macrophages are central to innate immune responses and are crucial in maintaining homeostasis and managing inflammatory diseases. Forkhead box J2 (Foxj2) is a member of the forkhead/hepatocyte nuclear factor 3 transcription factor family and is essential for multiple biological functions. However, the involvement of Foxj2 in the inflammatory process in macrophages remains unclear. OBJECTIVE: The present study aimed to explore the role of Foxj2 in the inflammatory processes of macrophages activated through lipopolysaccharide (LPS) stimulation. METHODS: The modulation of Foxj2 expression in macrophages in response to LPS stimulation was investigated via reverse-transcription quantitative (RT-q) PCR, Western blot, and immunofluorescence staining assays. Macrophages were infected with adenovirus vectors to upregulate the expression of the Foxj2 gene. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP)-PCR analysis were used to determine the regulatory relationship between Foxj2 and Tak1 (transforming growth factor-β-activated kinase 1). RESULTS: LPS stimulation of peritoneal macrophages led to a significant decrease in Foxj2 expression. In addition, LPS treatment led to Foxj2 depletion in several mouse tissues, including the heart, liver, spleen, lungs, kidneys, adipose tissue, blood vessels, and peritoneal macrophages. Furthermore, Foxj2 overexpression ameliorated the mRNA expression of TNF, IL-1β, IL-6, IL-12, IFN-stimulated gene 15, and IFN-β in macrophages treated with LPS. Additionally, Foxj2 overexpression attenuated phosphorylation of Stat1, p65, Erk1/2, Jnk, and p38. Subsequent experiments confirmed the binding of Foxj2 to the promoter region of Tak1, led to the suppression of Tak1's transcriptional activity. Moreover, a reduction in Foxj2 levels was observed during the pathological processes of numerous diseases characterized by inflammation, including high-fat diet (HFD)-induced obesity, HFD-induced nonalcoholic fatty liver disease (NAFLD), doxorubicin-induced cardiomyopathy, acute myocardial infarction (AMI) and D-galactose induced aging conditions. CONCLUSION: The present findings indicated that Foxj2 is crucial in mitigating macrophage inflammation induced by LPS and might be considered a target for treating sepsis and other inflammatory diseases.
Targeting the Inflammation-Metabolism Axis in MGUS: Causal Roles of CXCL10 Mediated by Blood Metabolites.
Gu S, Wang Z, Wen Z … +4 more , Fang M, Ye L, Jiang J, Hua H
Mediators Inflamm · 2025 · PMID 41498034 · Full text
BACKGROUND: Inflammatory cytokines have been implicated in monoclonal gammopathy of undetermined significance (MGUS), but their causal mechanisms remain unclear. Metabolites play pivotal roles in plasma cell dysregulatio...
BACKGROUND: Inflammatory cytokines have been implicated in monoclonal gammopathy of undetermined significance (MGUS), but their causal mechanisms remain unclear. Metabolites play pivotal roles in plasma cell dysregulation, however, their potential mediation effects between cytokines and MGUS are unexplored. We aimed to elucidate causal relationships between inflammatory cytokines and MGUS and identify metabolite-mediated pathways. METHODS: Using genome-wide association study (GWAS) summary statistics, we performed bidirectional two-sample Mendelian randomization (MR) to assess causality between 91 inflammatory cytokines and MGUS. A two-step MR approach was employed to investigate metabolite mediation using data from 1400 blood metabolites. Sensitivity analyses addressed pleiotropy and reverse causality (IVs: < 1 × 10, -statistic > 10). RESULTS: MR analysis identified CXCL10 (OR = 2.12, 95% CI: 1.06-4.23, = 0.034) and IL-6 (OR = 3.61, 95% CI: 1.22-10.65, = 0.020) as causal risk factors for MGUS. We also found Threonate (OR = 2.24, 95% CI: 1.06-4.75, = 0.035), X-22776 (OR = 3.45, 95% CI: 1.37-8.67, = 0.009) and glucose to sucrose ratio (OR = 2.89, 95% CI: 1.18-7.07, = 0.020) were associated with increased MGUS risk, while N-acetylputrescine to (N(1) + N(8))-acetylspermidine ratio (OR = 0.65, 95% CI: 0.43-0.98, = 0.039) showed protective effects. Mediation analysis revealed 2 metabolites Threonate and X-22776 mediating CXCL10's effect on MGUS. Threonate mediated 11.2% ( = 0.08, = 0.014) and X-22776 mediated 17.7% ( = 0.13, = 0.028) of CXCL10's total effect. Sensitivity analyses confirmed robustness (no pleiotropy: MR-Egger intercept > 0.05; Cochran's > 0.05). CONCLUSION: This study deeply reveals the mechanism by which inflammatory cytokines affect the pathogenesis of MGUS through metabolite-mediated pathways, providing new potential targets for the early diagnosis and treatment of MGUS. In the future, other inflammatory cytokines and metabolites that may be related to the pathogenesis of MGUS can be further explored, and the interactions and potential mechanisms between them can be further studied to provide a more comprehensive theoretical basis and practical guidance for the prevention and treatment of MGUS.
Comprehensive Single-Cell Characterization of LDL in the Ovarian Cancer Microenvironment and Its Prognostic Implications.
Tian K, Liu J, Zhou L … +2 more , Gao Y, Wei S
Mediators Inflamm · 2025 · PMID 41498033 · Full text
BACKGROUND: Low-density lipoprotein (LDL) is a critical regulator of lipid metabolism and has been implicated in the development and progression of various malignancies. However, its specific roles and mechanisms in the...
BACKGROUND: Low-density lipoprotein (LDL) is a critical regulator of lipid metabolism and has been implicated in the development and progression of various malignancies. However, its specific roles and mechanisms in the ovarian cancer tumor microenvironment (TME) remain unclear. This study aimed to comprehensively elucidate the distribution, functional pathways, and prognostic value of LDL in ovarian cancer using single-cell transcriptome analysis. METHODS: Single-cell transcriptome data from ovarian cancer patients were analyzed. The AUCell algorithm was used to score LDL-related gene expression in different cell subsets, dividing cells into high and low LDL score groups. Functional pathway enrichment (Gene Set Variation Analysis [GSVA]) and cell-cell communication (CellChat) analyses were performed. Differentially expressed genes (DEGs) identified between the two groups were combined with bulk RNA-seq data from eight cohorts to construct the LDL-related ovarian cancer prognostic signature (LDLOCPS) using machine learning. Prognostic performance and immune landscape differences were evaluated between high and low LDLOCPS groups. RESULTS: LDL was predominantly highly expressed in myeloid cells (macrophages and monocytes) and stromal cells (fibroblasts, smooth muscle cells, and endothelial cells) within the ovarian cancer TME. GSVA revealed that the high LDL score group was significantly enriched for pathways including epithelial-mesenchymal transition (EMT), inflammatory response, coagulation, and angiogenesis. CellChat analysis demonstrated enhanced cell-cell communication involving IL6, CSF, and tenascin in the high LDL score group, with SPP1+ macrophages and monocytes showing stronger incoming and outgoing signals. The LDLOCPS model, constructed from bulk transcriptomic data and validated across eight cohorts, effectively stratified patients by risk; the high LDLOCPS group exhibited significantly worse overall survival. Receiver operating characteristic (ROC) and principal component analysis (PCA) analyses confirmed the robust predictive performance of LDLOCPS. Moreover, patients in the high LDLOCPS group showed reduced immune cell infiltration and lower expression of immune-related genes, suggesting an immunosuppressive microenvironment. CONCLUSION: This study systematically reveals the spatial distribution of LDL within the ovarian cancer microenvironment and uncovers its regulatory roles in tumor progression through multiple signaling pathways. The LDLOCPS model provides a valuable tool for risk stratification and prognosis prediction in ovarian cancer. LDL-mediated microenvironmental and immunosuppressive effects may offer novel insights for developing targeted and immunomodulatory therapies in ovarian cancer.
Non-Responders to Biologic Disease Modifying Antirheumatic Treatment for Inflammatory Bowel Diseases.
Gadzhanova S, Roughead E
Mediators Inflamm · 2025 · PMID 41498032 · Full text
BACKGROUND AND AIM: Biologic disease-modifying antirheumatic drugs (bDMARDs) are effectively used to relieve symptoms in inflammatory bowel diseases (IBD). The study aimed to examine the rate of non-responders to bDMARD...
BACKGROUND AND AIM: Biologic disease-modifying antirheumatic drugs (bDMARDs) are effectively used to relieve symptoms in inflammatory bowel diseases (IBD). The study aimed to examine the rate of non-responders to bDMARD treatment in Australian population. METHOD: Cohort studies using a 10% random sample of the population dispensing medicines under the Australian Pharmaceutical Benefits Scheme (PBS). People aged 18 years and over who initiated bDMARD for IBD in 2019 or 2020 were followed for 12 months. The proportion of non-responders (people who discontinued initial therapy by Week 16 and 40) was determined using Kaplan-Meier survival analysis. RESULTS: There were 522 initiators of bDMARD for Crohn's disease (mean age of 42 years). By Week 16, 15% discontinued initial therapy (primary non-responders); 22% of initial responders discontinued bDMARD by Week 40 (secondary non-responders). The primary non-responder rate was lowest amongst infliximab initiators (6%), and highest for ustekinumab (24%). Infliximab had the lowest (17%) secondary non-responder rate compared to the other biologics, suggesting less loss of response over time.There were 390 initiators of bDMARD for ulcerative colitis (UC) (mean age of 44 years). By Week 16, 25% discontinued initial therapy; 21% of people with initial response discontinued by Week 40. The non-responder rates were lowest amongst vedolizumab initiators (5% for primary and 8% for secondary) and highest amongst adalimumab (50% for primary and 48% for secondary). CONCLUSION: Comparison between bDMARD agents showed lowest initial non-response and lowest loss of sustained response in infliximab initiators with Crohn's disease and in vedolizumab initiators with UC.
Comprehensive Analysis of the Correlation Between Immune-Inflammatory Biomarkers and Intestinal Necrosis in Patients With Acute Intestinal Ischemia.
Tian Y, Wang F, Zhang M … +2 more , Ding R, Wang Y
Mediators Inflamm · 2025 · PMID 41498031 · Full text
BACKGROUND: The relationship between immune-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) and intestinal necrosi...
BACKGROUND: The relationship between immune-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) and intestinal necrosis in different types of acute intestinal ischemia remains unclear. METHODS: A total of 138 patients with acute intestinal ischemia were divided into a nonnecrosis group ( = 65) and a necrosis group ( = 73). Least absolute shrinkage and selection operator (Lasso)-logistic regression model was used to identify independent risk factors for intestinal necrosis. Multivariate logistic regression was conducted to assess the associations between NLR and SII levels and intestinal necrosis. Sensitivity analyses were performed using smooth curve fitting, threshold effect analysis, subgroup analysis, and propensity score matching (PSM). . RESULTS: The optimal thresholds of NLR and SII for differentiating intestinal necrosis were 8.85 and 1492.11, respectively, while PLR showed no significant association. In Lasso-logistic regression analysis, vascular intestinal ischemia, NLR ≥ 8.85, SII≥ 1492.11, C-reactive protein (CRP), and D-dimer > 0.5 mg/L were independent risk factors for intestinal necrosis. After adjusting for potential confounding variables, the multivariate logistic regression analysis showed a positive correlation between natural logarithm (Ln)-NLR (OR = 20.187, 95% CI = 3.788-107.578, < 0.001) and Ln-SII (OR = 5.375, 95% CI = 1.141-25.313, < 0.033) and intestinal necrosis. Subgroup analysis showed a significant interaction between NLR, intestinal necrosis, and coronary heart disease ( interaction = 0.016). Smooth curve fitting indicated the relationship between Ln-NLR and Ln-SII and intestinal necrosis was nonlinear, with inflection points at 1.78 (NLR = 5.93) and 7.32 (SII = 1510.20), respectively. When NLR > 5.93 or SII < 1510.20, the risk of intestinal necrosis significantly increased. The associations remained robust after PSM. CONCLUSION: This study demonstrates that elevated levels of NLR and SII are significantly associated with intestinal necrosis, suggesting that these biomarkers may help identify patients at higher risk of intestinal necrosis in acute intestinal ischemia. However, prospective studies are needed to validate their predictive value.
RETRACTION: A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation.
Inflammation MO
Mediators Inflamm · 2025 · PMID 41498030 · Full text
[This retracts the article DOI: 10.1155/2019/8709583.].
[This retracts the article DOI: 10.1155/2019/8709583.].
Immunomodulatory Mechanisms of Rehmanniae Radix Praeparata-Achyranthes Root-Chinese Angelica Root Combination in Nontraumatic Osteonecrosis of the Femoral Head: A Comprehensive Network Pharmacology and Molecular Docking Study Focusing on Immunological Pathways.
Li X, Ng L, Liu C … +7 more , Qin L, Xiao P, Liu C, Liu Y, Zhang Q, Huang W, Zhou Y
Mediators Inflamm · 2025 · PMID 41498029 · Full text
OBJECTIVE: Nontraumatic osteonecrosis of the femoral head (NONFH) is a devastating condition characterised by immune dysregulation and sterile inflammation, which are increasingly acknowledged as central pathogenic mecha...
OBJECTIVE: Nontraumatic osteonecrosis of the femoral head (NONFH) is a devastating condition characterised by immune dysregulation and sterile inflammation, which are increasingly acknowledged as central pathogenic mechanisms. This study aims to identify the core herbal combination for NONFH and systematically explore its immunomodulatory effects and underlying pharmacological mechanisms, with a focus on immune system interactions. METHODS: The core combination 'Rehmanniae radix praeparata (SDH)-achyranthes root (NX)-Chinese angelica root (DG)' (SND) was identified via data mining of clinical literature using the Traditional Chinese Medicine Inheritance Support System (TCMISS) V2.5 platform. Its chemical constituents were characterised by ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technology, yielding 127 identified compounds, 47 of which were selected as bioactive components based on drug-likeness screening. The potential molecular targets of SND and NONFH were predicted and intersected, with a focus on immune-related targets. Subsequent comprehensive enrichment analysis was performed, emphasising immune pathway involvement, along with immune infiltration profiling. A support vector machine (SVM) model was constructed to identify key immune-related targets, and interactions were validated via molecular docking and molecular dynamics (MD) simulations. RESULTS: SND shared 46 candidate targets with NONFH. Enrichment analysis revealed these targets were significantly enriched in immune-inflammatory pathways, especially those related to immune cell activation and regulation. Notably, pathways involved in neutrophil extracellular trap (NET) formation and other innate immune responses were prominent. Machine learning identified five key targets: ACP1, NDUFAF3, haematopoietic cell kinase (HCK), CXCR2 and platelet-activating factor receptor (PTAFR)-all of which play critical roles in the modulation, signalling and activation of immune cells, particularly neutrophils and macrophages. Subsequent immune infiltration analysis demonstrated a strong correlation between these key targets (e.g. HCK, CXCR2 and PTAFR) and neutrophil abundance in NONFH. Molecular docking (MD) and molecular dynamics simulations (MDS). MD confirmed stable binding between the active components and these targets, with the HCK-chrysophanic acid complex exhibiting the strongest affinity (binding energy: -8.7 kcal/mol). CONCLUSION: Our integrated analysis suggests that SND alleviates NONFH primarily through multi-target immunomodulation, explicitly involving suppression of NET formation and regulation of immune cell activity, especially neutrophils and osteoclasts. This study presents a novel, immunologically explicit hypothesis for the mechanism of SND against NONFH, providing a solid theoretical foundation for future experimental validation and clinical application.
Interplay Between Key Molecular Signaling Pathways and Immune Players Following Brain Irradiation.
Richard SA
Mediators Inflamm · 2025 · PMID 41498028 · Full text
Irradiation (IRT) has been used extensively for the diagnosis and treatment of primary as well as metastatic brain tumors. Although the susceptibility of the radiation-induced brain injury or damage (RIBI) is partially a...
Irradiation (IRT) has been used extensively for the diagnosis and treatment of primary as well as metastatic brain tumors. Although the susceptibility of the radiation-induced brain injury or damage (RIBI) is partially associated with the sensitivity of particular cell types, pathways of injury in other types of brain disease or damage implicate the significance of the interaction between cell compartments. IRT-induced double-strand breaks (DSBs) are the utmost detrimental kind of DNA damage, which result in cell death as well as sustainable chromosomal reconfigurations following IRT exposure to the brain. It is worth noting that IRT-induced DSBs, and stimulation of interplay of key signaling pathways such as mitogen-activated protein kinases (MAPK), JAK/STAT, phosphoinositide-3-kinase/protein kinase B/AKT (PI3K-PKB/AKT), protein 53 (p53), mammalian target of rapamycin (mTOR), NF-kB, transforming growth factor beta (TGF-), tumor necrosis factor (TNF), as well as reactive oxygen species (ROS) to either trigger radiosensitization or radioresistance as well as RIBI mechanisms. Also, IRT is capable of influencing fundamental immune players like cluster of differentiation markers, the complement cascade, T cells, B cells, interleukins, as well as chemotactic cytokines. Thus, the aim of this review is to explicate the key molecular signaling and immune mechanisms associated with IRT-induced neurological deficits following brain IRT.
Correction to "Seven Immune-Related Genes' Prognostic Value and Correlation with Treatment Outcome in Head and Neck Squamous Cell Carcinoma".
Mediators Inflamm · 2025 · PMID 41498027 · Full text
[This corrects the article DOI: 10.1155/2023/8533476.].
[This corrects the article DOI: 10.1155/2023/8533476.].
Risk Assessment of Venous Thromboembolism in Neurocritical Patients: Construction and Validation of a Clinical Prediction Model.
Zhou M, Wang R, Zhu L … +3 more , Wang C, Hu W, Shi J
Mediators Inflamm · 2025 · PMID 41498026 · Full text
BACKGROUND/OBJECTIVE: Venous thromboembolism (VTE) remains a significant challenge in neurocritical care, with limited tailored risk assessment tools available for clinical practice. This study aimed to develop and valid...
BACKGROUND/OBJECTIVE: Venous thromboembolism (VTE) remains a significant challenge in neurocritical care, with limited tailored risk assessment tools available for clinical practice. This study aimed to develop and validate a practical prediction model to support VTE prevention strategies in neurocritical patients. METHODS: A total of 605 neurocritical patients were retrospectively enrolled in the neurologic intensive care unit (NICU) from May 2022 to April 2024. The eligible patients were randomly divided into a training dataset and a testing dataset in a ratio of 7:3. Variables with significant univariate effects in the training dataset were selected for multivariable stepwise regression analysis. The model fitting goodness was tested using the Hosmer-Lemeshow test, the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the model discrimination, and decision curve analysis (DCA) was used to test the clinical value of the model. RESULTS: The final model identified age, length of stay in the NICU, activated partial thromboplastin time (APTT), D-dimer, tracheotomy duration, pulmonary infection, antibiotic use, and dehydrating agents as key predictors. The nomogram demonstrated excellent discrimination (AUC 0.763, 95% CI: 0.714-0.811 in the training dataset; AUC 0.809, 95% CI: 0.732-0.885 in the testing cohort), strong calibration (Hosmer-Lemeshow test: = 0.126 [training]; = 0.823 [testing]) and consistent clinical net benefit across prevention thresholds (10%-40% risk probability). CONCLUSIONS: The risk prediction model developed in this study can effectively predict VTE occurrence in neurocritical patients with good discrimination and clinical utility, providing a valuable tool for identifying high-risk individuals and performing early prevention and treatment measures.
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