Mediators Of Inflammation[JOURNAL]
Sun
200 papers
lncRNA NKILA Promotes Warburg Effect and Immune Escape in Intrahepatic Cholangiocarcinoma by Regulating the MTX1/TOMM40 Axis.
Zhu M, Zhu H, Zhou Z … +4 more , Zheng H, Dong Z, Dong W, Wan X
Mediators Inflamm · 2025 · PMID 41498025 · Full text
BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with high heterogeneity and poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis through dysregulated e...
BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with high heterogeneity and poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis through dysregulated expression. We explored the effects and mechanisms of nuclear transcription factor NF-κB interacting lncRNA (NKILA) in ICC. METHODS: Bioinformatic analysis was performed to determine the expression and relationship of NKILA with metaxin 1 (MTX1), and translocase of outer mitochondrial membrane 40 (TOMM40) expression in ICC tissue samples. Cholangiocarcinoma cell lines were cultured in vitro and the transplanted tumor model was constructed in vivo to study the role of NKILA in ICC. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the effects of NKILA on the Warburg effect, autophagy, programed cell death 1 ligand 1 (PD-L1) expression, and CD8 T cytotoxicity in ICC cells. RNA immunoprecipitation (IP) (RIP) assay and RNA-RNA pull down assays were utilized to detect the binding of NKILA and MTX1, and CO-IP was performed to assess the interaction between MTX1 and TOMM40. RESULTS: We found that NKILA, MTX1, and TOMM40 were substantially upregulated in ICC tissues, and NKILA silencing reduced MTX1-TOMM40 binding in ICC cells. NKILA facilitated proliferation, invasion, Warburg effects, and autophagy of ICC cells by regulating mammalian target of rapamycin (mTOR) pathway, PD-L1 expression, and CD8 T cytotoxicity, while dichloroacetate (DCA) could reverse these effects. Mechanistically, NKILA binds directly to MTX1 mRNA, which stabilizes MTX1 mRNA and thereby promotes the expression of MTX1 protein. NKILA silencing could inactivate MTX1/TOMM40 axis to inhibit Warburg effect and autophagy-associated immune escape. CONCLUSIONS: LncRNA NKILA promotes Warburg effect and immune escape in ICC by regulating the MTX1/TOMM40 axis.
Glioblastoma Prognosis and Therapeutic Response Predicted by a Cancer-Associated Fibroblasts Risk Score.
Zhou H, Yang X, Zhao W … +6 more , Huang Y, Zhang Z, Jiang J, Jiang X, Ren B, Yang K
Mediators Inflamm · 2025 · PMID 41498024 · Full text
BACKGROUND: Cancer-associated fibroblasts (CAFs), as a key component of the tumor microenvironment, have not been systematically elucidated in glioblastoma (GBM). Our study aims to develop a prognostic model integrating...
BACKGROUND: Cancer-associated fibroblasts (CAFs), as a key component of the tumor microenvironment, have not been systematically elucidated in glioblastoma (GBM). Our study aims to develop a prognostic model integrating CAFs-related features, with the goal of providing new insights for precise stratification and optimized treatment strategies for GBM patients. METHODS: Utilizing GBM-related data from reputable public databases, we utilized the Seurat package in R to analyze single-cell RNA sequencing (scRNA-seq) data for the characterization of CAFs in GBM. We identified CAFs phenotypes and screened for key CAFs-related genes significantly associated with patient prognosis. Using regression analysis, we constructed a CAFs-based risk score, which was subsequently validated in multiple independent cohorts. A nomogram integrating the risk score and clinicopathological features was also developed. Furthermore, we systematically evaluated the prognostic and therapeutic relevance of the model in GBM patients through multi-dimensional analyses, including gene mutation profiling, pathway enrichment analysis, immune infiltration, immunotherapy response, and drug sensitivity analysis. RESULTS: A total of six CAFs-related genes (FAM241B, LSM2, IGFBP2, LOXL1, OSMR, and STOX1) were identified as significantly associated with GBM prognosis. We used it to construct the CAFs-based risk score model, which demonstrated robust prognostic performance across multiple cohorts and served as an independent predictor of overall survival in GBM patients, efficiently categorizing groups into high and low risk. By integrating clinical features, the nomogram model significantly increased predictive accuracy and reliability. Analytical results indicated a statistically significant association between the computed risk score and the level of immune cell infiltration. Furthermore, the established prognostic model exhibited robust efficacy in predicting patient outcomes following conventional targeted treatments as well as immunotherapeutic interventions. CONCLUSIONS: This study introduces a GBM risk profiling framework and accompanying nomogram, offering exceptional accuracy in prognostic prediction for GBM. The framework and nomogram provide valuable insights into the roles of CAFs and key genes in GBM progression and immunity, and extend beyond classification by offering promising avenues for deciphering tumor mutations, mapping immune landscapes, refining drug predictions, and forecasting the efficacy of immunotherapeutic interventions. These findings have the potential to significantly improve personalized treatment strategies and patient outcomes.
Single-Cell Transcriptomics Reveal Microenvironment Alterations in Canine Peri-Implantitis.
Wang M, Zhang D, Liao C … +6 more , Wu D, Geng N, Xia Y, Chen Y, Chen S, Peng W
Mediators Inflamm · 2025 · PMID 41498023 · Full text
BACKGROUND: Peri-implantitis, a major contributor to dental implant failure, lacks comprehensive insights into tissue-specific heterogeneity as current researches predominantly focus on the whole peri-implant tissue rath...
BACKGROUND: Peri-implantitis, a major contributor to dental implant failure, lacks comprehensive insights into tissue-specific heterogeneity as current researches predominantly focus on the whole peri-implant tissue rather than distinct molecular and cellular dynamics in gingiva and alveolar bone microenvironments. Furthermore, ethical challenges hinder the acquisition of healthy peri-implant tissues, limiting our understanding of peri-implantitis progression and the development of targeted therapies. METHODS: We established a controlled peri-implantitis model in beagle dogs, enabling ethical collection of healthy control tissues. Single-cell RNA sequencing (scRNA-seq) transcriptomics profiling was conducted on gingiva and alveolar bone tissues from diseased and healthy controls. Additionally, flow cytometry was utilized to further verify the identified subclusters and their involvement in peri-implantitis. RESULTS: Single-cell transcriptomic profiling unveiled a pronounced expansion of inflammation-associated cellular subsets in both gingival and alveolar bone microenvironments during peri-implantitis. Gingival tissues exhibited marked expansions in IL6/IL18BP endothelial cell and CXCL8 fibroblast, whereas APOD fibroblast dominated in peri-implantitis bone tissues. Gene-level profiling further identified upregulated pro-inflammatory chemokines (, , ) within gingiva IL18BP endothelial cells. Notably, we discovered a unique ligand-receptor interaction C3 (APOD fibroblast)-C3AR1 (monocyte/macrophage) in alveolar bone tissue, implicating complement-dependent signaling in immune crosstalk. CONCLUSIONS: Our study provides the first comparative atlas of soft/hard tissue remodeling in peri-implantitis at single-cell resolution. The expansion of IL6/IL18BP endothelial cell and CXCL8 fibroblast in gingiva, alongside APOD fibroblast-driven C3-C3AR1 signaling in alveolar bone, highlights distinct microenvironmental reprogramming between soft and hard tissues. These findings not only identify potential therapeutic targets but also validate the translational relevance of the canine model for peri-implantitis research.
Development and Evaluation of an Innovative Inflammatory Prognostic Score for Predicting Long-Term Mortality in Patients With Pulmonary Embolism.
Zhu N, Zhang L, Wu J … +4 more , Ye F, Yu N, Cao C, Chen L
Mediators Inflamm · 2025 · PMID 41498022 · Full text
BACKGROUND: Systemic inflammation is closely associated with adverse outcomes in pulmonary embolism (PE). This study aimed to develop and evaluate a novel inflammatory prognostic score (IPS) derived from multiple inflamm...
BACKGROUND: Systemic inflammation is closely associated with adverse outcomes in pulmonary embolism (PE). This study aimed to develop and evaluate a novel inflammatory prognostic score (IPS) derived from multiple inflammation-related biomarkers to predict long-term all-cause mortality in patients with acute PE. METHODS: This retrospective cohort study included 1642 patients with confirmed acute PE admitted between January 2016 and January 2024 at the First Affiliated Hospital of Ningbo University and the Affiliated People Hospital of Ningbo University. The primary outcome was all-cause mortality. Follow-up was conducted in January 2025. Fifteen inflammatory biomarkers were analyzed, including C-reactive protein (CRP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), monocyte count (MON), red cell distribution width (RDW), platelet count (PLT), and eight derived indices: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-MLR (NMLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and inflammatory burden index (IBI). IPS was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression. Prognostic performance was assessed using Kaplan-Meier survival analysis, multivariable Cox regression, time-dependent receiver operating characteristic (ROC) analysis, and random survival forest (RSF). RESULTS: During a median follow-up of 43.87 months, 262 patients (16.0%) died. The IPS was calculated as: IPS = 0.395 × IBI + 0.236 × RDW + 0.208 × SIRI + 0.115 × MLR + 0.040 × CRP. Patients with high IPS (≥0.55) had a significantly higher risk of all-cause mortality compared to those with low IPS (adjusted hazard ratio [HR] = 2.55, 95% confidence intervals [CI]: 1.92-3.38; < 0.001). Time-dependent area under the curve (AUC) for IPS were 0.756, 0.768, and 0.773 at 1, 3, and 5 years, respectively. When added to the baseline clinical model-including age, length of hospital stay, deep vein thrombosis, diastolic blood pressure, body mass index (BMI), lactate, log-transformed serum creatinine, blood urea nitrogen (BUN), log-transformed D-dimer, left ventricular ejection fraction (LVEF), pulmonary artery systolic pressure (PASP), and computed tomography pulmonary angiography (CTPA)-based embolism location (main pulmonary artery)-IPS improved the AUC from 0.820 to 0.886 at 3 years ( < 0.001, DeLong test). RSF analysis further identified IPS as the most informative inflammatory predictor of mortality. CONCLUSIONS: The IPS, derived from five routinely available inflammatory biomarkers, was independently associated with long-term mortality and significantly enhanced risk stratification beyond traditional clinical predictors in patients with acute PE. This score may support early prognostic assessment and individualized management.
Emerging Topics and Trends in Neutrophil Extracellular Traps in ARDS: A Bibliometric and Visual Analysis.
Wang Y, Luo Z, Fu S … +5 more , Li Q, Zhang Z, Huang N, Zou K, Zou L
Mediators Inflamm · 2025 · PMID 41498021 · Full text
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a critical illness with significant impacts on human respiratory health. Neutrophil extracellular traps (NETs), secreted by neutrophils, play dual roles in immune...
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a critical illness with significant impacts on human respiratory health. Neutrophil extracellular traps (NETs), secreted by neutrophils, play dual roles in immune defense and tissue inflammation. Recent studies have highlighted the association between NETs and ARDS, yet no comprehensive bibliometric analysis has been conducted in this field. This study aims to analyze the research progress and evolving hot spots related to NETs in ARDS through bibliometric methods. METHODS: Articles published between 2011 and 2024 were retrieved from the Web of Science Core Collection (WoSCC), PubMed, and Embase. Data analysis was performed using visualization tools such as VOSviewer, CiteSpace, and Microsoft Office Excel 2021. RESULTS: A total of 328 articles were analyzed. The annual publication trend in this field has shown a steady increase, with China and the United States leading in research output. Frontiers in Immunology stands out for its high publication volume and citation count, indicating strong reference value. The most prolific author is Zhang, Hao from Zhongshan Hospital, Fudan University, while Egeblad, Mikala from Cold Spring Harbor Laboratory holds the highest citation count. Inflammatory response is a research focus in this field, and the association between NETs and thrombus formation represents an emerging research hotspot within the domain. Research and development of NETs-targeted therapies for acute lung injury (ALI) and ARDS is an important direction for future research. CONCLUSION: This bibliometric analysis comprehensively summarizes research progress and hotspot evolution in NETs-related ARDS studies, providing valuable insights for researchers and inspiring future research directions.
TMOD2 and DOCK4 as Novel Gut Microbiota-Associated Biomarkers for Colorectal Adenoma: Integrated Transcriptomic Analysis and Therapeutic Target Identification.
Liu C, Wang L, Huai J … +4 more , He S, Su Q, Min Q, An Z
Mediators Inflamm · 2025 · PMID 41378121 · Full text
Colorectal adenomas (CRA) represent critical precursors to colorectal cancer (CRC), yet reliable transcriptomic biomarkers for early detection and therapeutic targeting remain limited. Integration of gut microbiota (GM)...
Colorectal adenomas (CRA) represent critical precursors to colorectal cancer (CRC), yet reliable transcriptomic biomarkers for early detection and therapeutic targeting remain limited. Integration of gut microbiota (GM) genetics with transcriptomics offers a novel approach to identify disease-associated molecular signatures. We sought to identify GM-associated molecular signatures that could serve as early intervention targets. We integrated transcriptomic data with Mendelian randomization (MR) analysis to establish causal relationships between GM and CRA development. Machine learning algorithms identified robust biomarkers, which we validated through expression analysis and receiver operating characteristic (ROC) analysis to construct predictive nomogram models. Comprehensive molecular characterization included Gene Set Enrichment Analysis (GSEA), immune profiling, and regulatory network analysis. Single-cell RNA sequencing (scRNA-seq) analysis further validated biomarker expression patterns across distinct cell populations in the tumor microenvironment. We discovered 12 GM species with significant causal relationships to CRA risk. Two biomarkers, TMOD2 and DOCK4, emerged as powerful predictive indicators with strong correlation ( = 0.66, < 0.001). These biomarkers demonstrated excellent diagnostic performance in ROC analysis and revealed previously unrecognized connections to cell adhesion pathways critical for adenoma progression. Single-cell analysis revealed TMOD2 expression across multiple cell clusters with notable exclusion in mast cells, while DOCK4 expression was predominantly restricted to fibroblasts, myeloid, and epithelial cells. Notably, we identified distinct immune cell infiltration patterns, including altered naive B cells and macrophage populations, suggesting immune dysregulation as a key mechanism. GSEA revealed enrichment in cell adhesion molecule (CAM) pathways. Regulatory network analysis uncovered complex control by 18 microRNAs (miRNAs), 40 long noncoding RNAs (lncRNAs), and 10 transcription factors (TFs), with EIF3A emerging as a key m6A reader protein. Drug screening identified 22 potential therapeutic compounds, with trichostatin A showing optimal binding affinity. These findings establish TMOD2 and DOCK4 as novel biomarkers linking GM dysbiosis to CRA development, opening new avenues for microbiome-targeted early intervention strategies.
The Role of Inflammatory Cytokines in the Causal Pathway From Gut Microbiota to Sjögren's Syndrome: Evidence From Mendelian Randomization.
Zhao J, Han J, Fan X … +7 more , Kang J, Wu R, Zhao Y, Bai L, Gao X, Ma D, Zhang L
Mediators Inflamm · 2025 · PMID 41368219 · Full text
PURPOSE: Evidence is accumulating that links gut microbiota, a crucial component of the immune environment, to Sjogren's syndrome (SS). The mechanisms underlying the influence of gut microbiota on the onset and developme...
PURPOSE: Evidence is accumulating that links gut microbiota, a crucial component of the immune environment, to Sjogren's syndrome (SS). The mechanisms underlying the influence of gut microbiota on the onset and development of SS are still not completely understood. To this end, we applied a Mendelian randomization (MR) framework to investigate whether inflammatory cytokines mediate the association of gut microbiota with SS. METHODS: Our MR analysis leveraged publicly available GWAS data, including information on 211 gut microbiota taxa sourced from the MiBioGen consortium (18,340 participants), summary statistics for 91 inflammatory cytokines obtained from a study of 14,824 individuals, and genetic data for SS derived from the UK Biobank (407,746 participants). To investigate causal associations between gut microbiota and SS, we primarily employed the inverse variance weighted method, supported by additional techniques such as MR-Egger, simple mode, weighted median, and weighted mode for validation. The potential mediating effect of inflammatory cytokines in the gut microbiota-SS relationship was investigated using both mediation MR and multivariable MR (MVMR) analyses. RESULTS: MR analysis identified five microbiota taxa causally associated with SS. Particularly, class Gammaproteobacteria (OR = 3.468, 95% CI = 1.139-10.557, =0.029) and genus Peptococcus (OR = 1.722, 95% CI = 1.082-2.471, =0.022) were significantly associated with an increased risk of developing SS. Six inflammatory cytokines were identified as potentially causal, with Axin-1 (OR = 2.556, 95% CI = 1.072-6.096, =0.034) and C-X-C motif chemokine 10 levels (CXCL10) (OR = 3.049, 95% CI = 1.428-6.513, =0.004) being the most critical contributors. Mediation MR analysis showed that Axin-1 levels mediated 16.96% of the causal effect of class Gammaproteobacteria on SS, CXCL10 levels mediated 36.78% of the causal effect of genus Coprococcus3 on SS. CONCLUSION: The findings suggest that certain gut microbiota is sociated with an increased risk of SS, mediated by specific inflammatory cytokines.
Changes in Nucleus Pulposus Cell Atlas and the Role of SPP1 During Intervertebral Disc Degeneration: Single-Cell Sequencing Analysis.
Liu C, Jiao K, Li X … +6 more , Deng Z, Wang S, Cheng Y, Li M, Zhou X, Wei X
Mediators Inflamm · 2025 · PMID 41357134 · Full text
BACKGROUND: The nucleus pulposus (NP) plays a central role in the pathogenesis of intervertebral disc degeneration (IVDD); however, its internal cellular heterogeneity and molecular mechanisms have not yet been elucidate...
BACKGROUND: The nucleus pulposus (NP) plays a central role in the pathogenesis of intervertebral disc degeneration (IVDD); however, its internal cellular heterogeneity and molecular mechanisms have not yet been elucidated. METHODS: ScRNA-seq was used to evaluate the structure of the NP at different degenerative stages in the same individual with IVDD. Unsupervised clustering of cells based on gene expression profiles was performed using the Seurat package and passed to uniform manifold approximation and projection (UMAP) for cluster visualization. A rat disc degeneration model and an in vitro human NP cell degeneration model were established to validate the scRNA-seq identification results. RESULTS: Six NP subclusters and immune cells were identified and their distribution and functional differences between healthy and degenerative states were investigated. Immune cells were present only in degenerated NPs and may trigger NP degeneration. Cellular communication within the NP was altered by the intervention of immune cells. Secreted phosphorylated protein 1 (SPP1), secreted by immune cells, plays a major role and is a key molecule in NP degeneration. The results of in vivo animal experiments and in vitro cellular experiments showed that the expression of SPP1 was increased in degenerating NPs. High expression of SPP1 promoted NP degeneration, whereas inhibition of its expression attenuated degeneration. CONCLUSIONS: Cytoarchitectural changes in NP were revealed by scRNA-seq. SPP1 is involved in the pathogenesis of disc degeneration and may be a new target for intervention in IVDD.
Telomere Length and Clear Cell Renal Cell Carcinoma: Unraveling Causal Mechanisms Through Integrative Genetic and Single-Cell Transcriptomic Analysis.
Zhang K, Huang C, Zhou J … +3 more , Fan K, Ruan M, Xiao Y
Mediators Inflamm · 2025 · PMID 41357133 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) presents significant clinical challenges. This study investigates the causal relationship between telomere length (TL) and ccRCC risk using a comprehensive multicohort...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) presents significant clinical challenges. This study investigates the causal relationship between telomere length (TL) and ccRCC risk using a comprehensive multicohort genetic approach. METHODS: We conducted a rigorous two-sample Mendelian randomization (MR) analysis using independent discovery (UK Biobank, = 472,174) and validation (genome-wide association studies [GWAS] Catalog, = 438,351) cohorts. Multivariable MR (MVMR) adjusted for chronic kidney disease (CKD), hypertension, and smoking. Colocalization analysis and single-cell RNA sequencing (scRNA-seq) were employed to validate genetic associations and explore cellular mechanisms. RESULTS: In the discovery cohort, inverse variance weighted (IVW) MR analysis revealed a significant positive association between TL and ccRCC risk (odds ratio [OR]: 1.604, 95% confidence interval [CI]: 1.358-1.895, < 0.001). The validation cohort consistently confirmed these findings (OR: 1.470, 95% CI: 1.290-1.674, < 0.001). MVMR analysis using IVW method, adjusting for key risk factors, demonstrated a significant association (OR: 2.072, 95% CI: 1.724-2.491, < 0.001). Colocalization analysis showed strong evidence of shared causal variants (posterior probability > 98% in both discovery and validation sets). scRNA-seq revealed that proximal tubule cells (PTCs) with telomerase-associated genes and exhibited complex senescence dynamics, characterizing distinct cellular communication patterns in the tumor microenvironment. CONCLUSION: Our comprehensive multiomics study provides robust evidence of a causal relationship between TL and ccRCC risk. By integrating genetic epidemiology and single-cell transcriptomics, we unveil novel molecular mechanisms underlying ccRCC pathogenesis and identify potential therapeutic targets.
A Machine Learning-Derived Taurine Metabolism Signature Predicts Prognosis and Immune Landscape in Lung Adenocarcinoma via Integrative Single-Cell Analysis.
Wang M, Mu Q, Jiang Y … +3 more , Jing Y, Zhao Y, Han X
Mediators Inflamm · 2025 · PMID 41341805 · Full text
BACKGROUND: Lung adenocarcinoma (LUAD) represents a biologically diverse tumor type, often associated with unfavorable prognosis and unsatisfactory therapeutic outcomes. Over the past few years, increasing attention has...
BACKGROUND: Lung adenocarcinoma (LUAD) represents a biologically diverse tumor type, often associated with unfavorable prognosis and unsatisfactory therapeutic outcomes. Over the past few years, increasing attention has been given to metabolic alterations as key contributors to cancer development. Nevertheless, the specific contribution of taurine-related metabolic pathways in LUAD remains unclear. By constructing a model from taurine metabolism-associated genes, we aimed to elucidate its mechanistic basis and evaluate its relevance to clinical outcomes. METHODS: Transcriptomic profiles and clinical annotations from TCGA along with five LUAD datasets from the GEO repository were comprehensively integrated. A risk score indicative of taurine metabolism-associated signature (taurine-related signature [TRS]) was constructed by integrating LASSO regression, stepwise Cox modeling, and SuperPC algorithm. Its predictive capability was systematically evaluated using Kaplan-Meier survival analysis, ROC curves, and DCA. To further investigate the relationship between TRS and both cellular heterogeneity and tumor microenvironmental context, single-cell RNA-seq data were integrated into the analysis. Moreover, the tumorigenic role of the hub gene was experimentally validated via in vitro functional assays. RESULTS: The TRS signature was validated for its predictive relevance using six LUAD datasets from independent sources, showing its ability to categorize patients based on survival variations. Elevated TRS levels were strongly linked to increased tumor cell proliferation, immune evasion characteristics, and impaired response to immunotherapy. Findings from single-cell RNA sequencing indicated that epithelial subpopulations with higher TRS expression displayed intensified metabolic activity and reduced antigen presentation efficiency. In particular, -a key component of the TRS gene set-was highly expressed in LUAD tissues and associated with less favorable prognostic profiles. Functional silencing of led to decreased proliferation and invasive capacity of LUAD cells, supporting its potential role as a tumor-promoting factor. CONCLUSION: We established a taurine metabolism-related prognostic model (TRS) and investigated its function in LUAD by combining transcriptomic information from both bulk tissues and single-cell datasets. The TRS effectively categorizes patients according to their prognosis and reflects immune-related features. , identified as a crucial gene within the TRS, could be explored as a potential therapeutic candidate, offering insights into LUAD metabolism and informing the development of metabolism-based therapeutic strategies.
Causal Gene Identification and Biomarker Prioritization in Periodontitis via Integrative Multiomics and Mendelian Randomization.
Mo H, Chen L, Ren S … +2 more , Wu Y, Tian A
Mediators Inflamm · 2025 · PMID 41333919 · Full text
INTRODUCTION: Periodontitis is a common inflammatory disease that compromises oral and systemic health. This study aimed to elucidate its molecular mechanisms and identify potential biomarkers for early diagnosis and pre...
INTRODUCTION: Periodontitis is a common inflammatory disease that compromises oral and systemic health. This study aimed to elucidate its molecular mechanisms and identify potential biomarkers for early diagnosis and precision treatment. METHODS: We integrated genome-wide association study (GWAS) and transcriptomic data from periodontitis patients and healthy controls. Summary data-based Mendelian randomization (SMR) and the heterogeneity in dependent instruments (HEIDI) test were used to identify genetically associated genes. Differentially expressed genes (DEGs) were identified using LIMMA, and weighted gene co-expression network analysis (WGCNA) revealed disease-related gene modules. Candidate biomarkers were prioritized through intersection analysis and evaluated using five machine learning algorithms. Causal relationships were further validated by two-sample Mendelian randomization (TSMR). Functional enrichment was assessed via gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA), and immune infiltration was analyzed using CIBERSORT. RESULTS: SMR identified 360 gene-trait associations, with 320 passing the HEIDI test, corresponding to 294 unique genes. DEGs were enriched in immune and neuronal development pathways. WGCNA uncovered nine gene modules associated with periodontitis. Intersection and machine learning analyses identified five key biomarkers-GPX2, IGKV2D-30, CD34, GSTA4, and NYNRIN-with strong predictive performance, validated by MR analysis ( < 0.05). Immune infiltration analysis revealed increased regulatory T cells, activated mast cells, and neutrophils, and decreased memory B cells and resting mast cells in periodontitis, with biomarker expression levels showing significant immune correlations. CONCLUSION: This integrative multiomics analysis uncovers causal genes and robust biomarkers involved in periodontitis pathogenesis, providing new insights for early detection and individualized treatment strategies. Further experimental validation is needed to confirm their functional roles in disease progression and therapeutic potential.
The Impact of the hsCRP/BMI Ratio on Cardiovascular Outcomes in CAD Patients: A Population-Based Study.
Liu D, Wang X, Zhang K … +13 more , Meng X, Wang J, Yang J, Gao J, Wang Y, Wen J, Li C, Zheng M, Liu G, Ma Y, Wang W, Tang YD, Shao C
Mediators Inflamm · 2025 · PMID 41333918 · Full text
BACKGROUND: It remains uncertain whether a novel composite indicator, the high sensitivity C-reactive protein (CRP) (hsCRP)-to-body mass index (BMI) ratio (CBR), is associated with unfavourable events in subjects who hav...
BACKGROUND: It remains uncertain whether a novel composite indicator, the high sensitivity C-reactive protein (CRP) (hsCRP)-to-body mass index (BMI) ratio (CBR), is associated with unfavourable events in subjects who have undergone drug-eluting stent (DES) implantation. Therefore, we conducted a prospective cohort study to evaluate the associations between the CBR and adverse outcome occurrences. METHODS: From January 2013 to December 2013, a total of 9810 subjects who underwent DES implantation were enrolled in the study. The participants were divided into three groups on the basis of the CBR. We defined the primary endpoint as the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), and the secondary endpoints included the occurrence of all-cause death, myocardial infarction(MI), stroke or target vessel revascularization (TVR). Kaplan‒Meier (K‒M) analysis and Cox regression analysis were performed to assess the discrepancy in the risk of adverse outcomes between the different CBR groups. RESULTS: Over an average follow-up period of 26.7 months, 1022 MACCEs were recorded, which included 122 deaths, 392 MIs, 156 strokes and 461 instances of TVR. The results from the K‒M analysis suggested that the rates of MACCEs and MI increased with increasing tertiles of the CBR. Furthermore, Cox regression analysis demonstrated that there were significant associations between a high CBR and increased MACCE and MI risk. CONCLUSION: In subjects who underwent DES implantation, a higher CBR was significantly related to increased long-term MACCE and MI risk.
Role of Dendritic Cells in Mediating the Effect of Growth Differentiation Factor 15 on Nonalcoholic Fatty Liver Disease: Insights From Causal Inference and Single-Cell Profiling.
Yao T, Zheng P, Wang ZN … +3 more , Fang LX, Wu YH, Lin YN
Mediators Inflamm · 2025 · PMID 41333917 · Full text
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents one of the most prevalent chronic liver conditions worldwide. Previous studies have highlighted an association between circulating growth differentiation fa...
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents one of the most prevalent chronic liver conditions worldwide. Previous studies have highlighted an association between circulating growth differentiation factor 15 (GDF-15) levels and NAFLD, as well as the involvement of immune cells in its pathogenesis and progression. However, the causal relationships remain unclear. METHODS: We obtained summary-level data for circulating GDF-15 levels, NAFLD, and 731 immune cell phenotypes from large-scale genome-wide association studies (GWAS) and the FinnGen database. Mendelian randomization (MR) analysis was employed to explore the causal relationship between circulating GDF-15 levels and NAFLD. Additionally, a two-step MR approach was utilized to identify and assess the mediatory role of immune cells in this association. Finally, single-cell RNA sequencing analysis (scRNA-seq) was performed to validate the proportions of CD123 dendritic cell (DC) subsets in NAFLD progression. RESULTS: Two-sample MR analysis revealed that elevated levels of GDF-15 are associated with an increased risk of NAFLD (OR = 1.16; 95% confidence interval [CI] = 1.03-1.30; =0.017), and replication analysis further confirmed the stability of these findings (OR = 1.10; 95% CI = 1.01-1.20; =0.037). Mediation analysis identified that CD123 on plasmacytoid DCs (DCs), CD123 on CD62L+ plasmacytoid DCs, CD80 on plasmacytoid DCs, and CD80 on CD62L+ plasmacytoid DCs mediate the causal effect of GDF-15 on NAFLD. Sensitivity analyses and bidirectional MR further ensured the robustness of these findings. Single-cell analysis further validated these results. CONCLUSIONS: Our findings propose a causal relationship between GDF-15 and NAFLD mediated by DCs, offering novel insights for potential therapeutic and preventive strategies for NAFLD.
Gut Microbes Secretions May Trigger Mononuclear Cell Migration and Offer Comorbidity Mechanism Between Inflammatory Bowel Disease and Diabetic Retinopathy.
Xu B, Wu S, Huang J … +6 more , Lin M, Liu Q, Li X, Fu M, Xia Z, Yi G
Mediators Inflamm · 2025 · PMID 41333916 · Full text
BACKGROUND: Researches have found that the gut microbiota stimulate inflammation by releasing proinflammatory chemicals, including bile acids (BAs) and L-kynurenine. In the present study, our purpose is to investigate th...
BACKGROUND: Researches have found that the gut microbiota stimulate inflammation by releasing proinflammatory chemicals, including bile acids (BAs) and L-kynurenine. In the present study, our purpose is to investigate the potential functional roles of gut microbes and their secretions in the comorbidity mechanism between inflammatory bowel disease (IBD) and diabetic retinopathy (DR). METHODS: Specific existing gut microbes among IBD and diabetes mellitus (DM) patients were gained and analyzed to figure out the proinflammatory chemicals secreted by specific existent microbes. The expression data of peripheral blood mononuclear cells (PBMCs) were obtained and underwent differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) to find out potential effects of microbes secretions on PBMCs. Single-cell analysis was conducted to elucidate the underlying cytological comorbidity mechanisms. RESULTS: The results of the study showed that the secretions of abnormal gut microbes in IBD and DM patients, such as BAs and L-Kynurenine, can stimulate abnormal immune response. PBMCs can be activated, mobilized, and disrupt vascular endothelial barriers upon exposure to proinflammatory substances generated by and , the dysbiotic gut microbiota in IBD, which exacerbate retinal inflammation and worsening DR pathological conditions. Furthermore, genes related to PBMC migration, such as RSU1, FN1, and CD9, are activated in PBMCs after exposure to pro-inflammatory chemicals from abnormal gut microbes, offering a genetic comorbidity mechanism for IBD and DR. We also unraveled that IBD can promote the proliferation and activation of effector memory T (Tem) cells, which also showed elevation in DR patients, thereby providing a cellular basis for the comorbidity between IBD and DR. CONCLUSION: The aberrant gut bacteria in IBD patients might secrete proinflammatory substances, such as L-kynurenine and BAs, which may activate mononuclear cells, especially the Tem. The mononuclear cells subsequently migrated into the retina, exacerbating the situation of DR. This finding underscores the potential of comorbidity mechanism for better treatment of DR in the future.
Alleviation of Inflammatory Conditions Caused by Extremely Low-Frequency Electromagnetic Field Exposure by .
Choi JY, Lee JS, Lee SA … +3 more , Moon HW, Park SY, Hwang KW
Mediators Inflamm · 2025 · PMID 41321590 · Full text
BACKGROUND: Electronic devices such as cellphones, microwaves, and other household devices are known to emit electromagnetic waves. As such, it creates an environment that may disrupt homeostasis. Ginsenosides in red gin...
BACKGROUND: Electronic devices such as cellphones, microwaves, and other household devices are known to emit electromagnetic waves. As such, it creates an environment that may disrupt homeostasis. Ginsenosides in red ginseng is a Korean herb that is known for their anticancer, anti-inflammatory, and antidiabetic properties. This study aims to assess the therapeutic properties of ginsenosides in extremely low-frequency electromagnetic field exposure (ELF-EMF) environment. MATERIALS AND METHODS: To observe the anti-inflammatory effects of ginsenosides, lipopolysaccharide (LPS) and ELF-EMF-induced RAW 264.7 cells were treated with 14 ginsenosides. Here, the production and gene expression of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, and nitric oxide (NO) were determined. Furthermore, neuronal apoptosis was examined as this may be induced by excessive secretion of pro-inflammatory cytokines and increased calcium influx. RESULTS: RAW264.7 cells exposed to ELF-EMF showed an increase in NO production and pro-inflammatory cytokines. Moreover, under ELF-EMF exposure, translocation of NF-kB increased and NFAT2, due to elevated calcium influx, increased as well. These inflammatory responses were alleviated by the ginsenosides and among the 14 ginsenosides, ginsenoside Rd had the most potent anti-inflammatory effect. CONCLUSION: Ginsenosides alleviate inflammation induced by ELF-EMF by downregulating inflammatory-related cytokines and proteins. It also had an effect on decreasing nerve cell apoptosis by reducing inflammatory response.
Velutin Inhibits IL-1β-Induced Nucleus Pulposus Inflammatory and Extracellular Matrix Degradation Attenuating Mouse Intervertebral Disc Degeneration via the NF-κB and MAPK Pathways.
Zhang Y, Xu R, Wang K … +5 more , Li X, Lou Y, Cao L, Yang W, Qian Y
Mediators Inflamm · 2025 · PMID 41321589 · Full text
Intervertebral disk degeneration (IVDD) usually causes lower back pain (LBP). Mechanical stress, trauma, aseptic inflammation, infection, and genetic susceptibility can accelerate the development of IVDD. Reportedly, pro...
Intervertebral disk degeneration (IVDD) usually causes lower back pain (LBP). Mechanical stress, trauma, aseptic inflammation, infection, and genetic susceptibility can accelerate the development of IVDD. Reportedly, proinflammatory cytokines and extracellular matrix (ECM) degradation play significant roles in IVDD progression. Therefore, anti-inflammatory treatments and ECM inhibition can potentially delay the progression of IVDD. Velutin, a natural flavonoid, has the vigorous effects of suppressing inflammation. In this study, we researched the protective effects of velutin and the underlying mechanisms. Additionally, we evaluated its validity in a mouse IVDD model. The results indicated that velutin effectively suppressed interleukin-1β-induced inflammatory mediators. Moreover, our findings revealed the mechanisms of velutin's anti-inflammatory effects. Our results indicate that velutin is a potential therapeutic agent for IVDD.
Lipopolysaccharide Sensitizes Steroid-Induced Brain Injury in Neonatal Rat Pups.
Chang YS, Yang TM, Hsu YL … +2 more , Kuo YM, Lin CH
Mediators Inflamm · 2025 · PMID 41321588 · Full text
BACKGROUND: Infection is a pathogenetic factor for bronchopulmonary dysplasia (BPD), and corticosteroids are often used for its prevention or treatment. However, few studies have examined their combined effects on brain...
BACKGROUND: Infection is a pathogenetic factor for bronchopulmonary dysplasia (BPD), and corticosteroids are often used for its prevention or treatment. However, few studies have examined their combined effects on brain injury in the context of infection. METHODS: Rat pups received lipopolysaccharide (LPS) on postnatal Day 1 (P1), followed by tapering doses of dexamethasone (Dex) or hydrocortisone (HC) from P2 to P4. We measured body and brain weights, TUNEL-positive cell counts, synaptic protein levels, and mRNA expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in six brain regions at P5. RESULTS: The LPS-HC and LPS-Dex groups showed more TUNEL-positive cells in the hippocampus, cerebellum, and brain stem compared to LPS-naïve controls. Oligodendrocyte precursor cells were the predominant TUNEL-positive cells in the hippocampus and brain stem. Additionally, the LPS-Dex or LPS-HC group showed significantly reduced levels of postsynaptic density protein 95 (PSD95), a postsynaptic protein, in these regions, while treatment with Dex or HC alone did not impact PSD95 expression. GR mRNA was significantly reduced in cortex, striatum, hippocampus, and cerebellum in LPS-HC group, with MR mRNA reduction limited primarily to the striatum. CONCLUSIONS: LPS sensitized the immature brain to Dex or HC-related cell death to possible apoptosis and augmented the LPS-induced disruption of synaptic integrity in certain brain regions, potentially via altered GR and MR expression that may modulate corticosteroid receptor signaling.
The Systemic Inflammation Response Index as an Independent Predictor of Acute Kidney Injury in Critically Ill Patients With Acute Myocardial Infarction: Insights From a Large-Scale Cohort Study.
Li X, Ruan L, Zhang S … +7 more , Qin Y, Pu Y, Yang J, Xu S, Tang H, Tang C, Qiao Y
Mediators Inflamm · 2025 · PMID 41321587 · Full text
BACKGROUND: Acute kidney injury (AKI) is a critical risk factor for adverse outcomes in acute myocardial infarction (AMI) patients admitted to the intensive care unit (ICU). Early identification of high-risk patients is...
BACKGROUND: Acute kidney injury (AKI) is a critical risk factor for adverse outcomes in acute myocardial infarction (AMI) patients admitted to the intensive care unit (ICU). Early identification of high-risk patients is essential for personalized treatment. The systemic inflammation response index (SIRI), a marker of systemic inflammation, has not been fully explored for its predictive role in AKI. METHODS: This study included 6936 critically ill AMI patients from the MIMIC-III and MIMIC-IV databases Lasso regression, multivariate logistic regression, restricted cubic spline (RCS) models, and subgroup analyses were employed to explore the association between SIRI and AKI risk. Then, we constructed a predictive model based on these findings internally validated using bootstrapping (1000 repetitions). Discrimination was assessed by the optimism-corrected area under the receiver operating characteristic (ROC) curve (areas under the curve [AUC]), and calibration was evaluated by the calibration curve and the Hosmer-Lemeshow test. The optimal cutoff value for SIRI was determined using the Youden index and propensity score matching (PSM; 1:1) was performed. Conditional logistic regression was used to validate the robustness of this association. Additionally, Cox regression and Kaplan-Meier survival analyses were conducted to assess the relationship between SIRI and in-hospital mortality in the overall cohort. RESULTS: Elevated SIRI levels independently predicted AKI, showing a nonlinear relationship. Subgroup and propensity-matched analyses confirmed this association. Furthermore, the predictive performance of the model was robust upon internal validation. The optimism-corrected AUC was 0.767 (95% CI: 0.755-0.781) and the calibration curve showed excellent agreement, the Hosmer-Lemeshow test indicated good fit (=0.539). Kaplan-Meier curves revealed higher in-hospital mortality in higher SIRI quartiles (log-rank < 0.001). Multivariate Cox regression further supported SIRI as a significant predictor of in-hospital mortality. CONCLUSION: SIRI is an independent risk factor for AKI and in-hospital mortality in critically ill AMI patients, offering valuable clinical utility for early AKI prediction and risk stratification.
Research on the Antiaging Activity of Licorice Water Extract in Aging Mice via Antioxidation, Neuronal Protection, Gut Microbiota Restoration, and PI3K/AKT/mTOR Modulation.
Yu Y, Xue B, Liu T … +6 more , Yue X, Liu D, Yu X, Xu Y, Zhao X, Li X
Mediators Inflamm · 2025 · PMID 41311553 · Full text
BACKGROUND: Aging is a multifaceted physiological process characterized by progressive multiorgan dysfunction, oxidative stress, neuronal injury, cognitive impairment, and alterations in gut microbiota composition. Licor...
BACKGROUND: Aging is a multifaceted physiological process characterized by progressive multiorgan dysfunction, oxidative stress, neuronal injury, cognitive impairment, and alterations in gut microbiota composition. Licorice, a widely used traditional medicinal herb, contains diverse bioactive constituents; however, its overall antiaging properties and mechanistic basis in aging models have not been systematically elucidated. METHODS: Aging mice model was established using D-galactose (D-Gal). Body weight, organ indices, senescence markers, antioxidant activity, neuronal integrity, and behavioral performance were assessed to evaluate the protective role of licorice water (LW) extract. Further, gut microbiota profiling, network pharmacology, and western blotting were employed to investigate further the potential mechanisms underlying the antiaging effects of LW. RESULTS: LW administration significantly improved body weight gain, organ indices, and hippocampal structure in aging mice, increased antioxidant enzyme activity, and decreased the proportion of SA-β-Gal-positive cells. Moreover, LW treatment reshaped gut microbiota composition by lowering the (F/B) ratio and increasing the relative abundance of beneficial bacterial taxa. Network pharmacology analysis identified 66 licorice-associated antiaging genes, with quercetin, kaempferol, naringenin, formononetin, and licochalcone A as key active components. The principal molecular targets included AKT1, TP53, ESR1, CASPASE3, and BCL2, while the major enriched pathways involved PI3K-Akt, lipid and atherosclerosis, AGE-RAGE, MAPK, and IL-17 pathway. Furthermore, Western blot analysis revealed that LW significantly downregulated the expression of p-PI3K, p-AKT, and p-mTOR in brain tissue. CONCLUSION: These findings demonstrate that LW exerts protective antiaging effects in D-Gal-induced mice by enhancing antioxidant activities, safeguarding neuronal function to improve cognition, restoring gut microbiota balance, and modulating the PI3K/AKT/mTOR pathway, supporting its promise as a candidate for antiaging interventions.
Paeoniflorin Alleviates LPS-Induced Inflammation and Acute Myocardial Injury by Inhibiting PI3K/Akt/ERK-Mediated HIF-1α and TLR4/MyD88/NF-κB Inflammatory Signaling.
Guo X, Han Z, Sun J … +7 more , Liu S, Zhang C, Xu G, Wang X, Song Q, Yang H, Li A
Mediators Inflamm · 2025 · PMID 41311552 · Full text
Sepsis-induced myocardial injury (SIMI) greatly increases the mortality rate of sepsis. Although paeoniflorin (PF) has been proven to improve survival in sepsis, the detailed mechanism of PF on SIMI remains elusive. In t...
Sepsis-induced myocardial injury (SIMI) greatly increases the mortality rate of sepsis. Although paeoniflorin (PF) has been proven to improve survival in sepsis, the detailed mechanism of PF on SIMI remains elusive. In this study, network pharmacology revealed 90 overlapping targets between PF- and SIMI-related targets. Analysis using the molecular complex detection (MCODE) method identified a significant module with scores exceeding 30, comprising the top 10 targets: Akt1, STAT3, CASP3, BCL2, TP53, PTGS2, CXCL8, TLR4, CCL2, and ICAM1. These targets are involved in tissue repair during inflammatory response, apoptosis, immunity, and lipopolysaccharide (LPS) immune receptor activity. The enriched pathways in inflammatory signaling, include NF-κB signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. Molecular docking further verified the strong binding abilities of PF to PI3K, Akt1, ERK1, ERK2, HIF-1α, TLR4, and NF-κB. In LPS-induced sepsis rat model, PF pretreatment inhibited PI3K/Akt/ERK-mediated HIF-1α and TLR4/MyD88/NF-κB signaling, thereby reducing inflammation by decreasing the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and cardiac tissue. Ultimately, PF ameliorated SIMI by improving cardiac pathological and functional changes and mitigating myocardial injury markers, such as lactate dehydrogenase (LDH), CK-MB, cTnT/TNNT2, TNNI3/cTn-I, and aspartate aminotransferase (AST). Collectively, the PI3K/Akt/ERK-mediated HIF-1α and TLR4/MyD88/NF-κB inflammation signaling appear to be the primary mechanisms through which PF exerts its beneficial effects on SIMI.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe