Mediators Of Inflammation[JOURNAL]
Sun
200 papers
Uncovering the Independent Role of Lipid Peroxidation in Osteoporosis Through an Integrated Bibliometric and Bioinformatics Analysis.
Li X, Ng L, Dong W … +5 more , Li M, Bai Y, Liu Y, Wu C, Zhou Y
Mediators Inflamm · 2026 · PMID 41710265 · Full text
OBJECTIVE: This study, utilising bibliometric analysis combined with bioinformatics approaches, systematically analysed research trends in the fields of osteoporosis (OP) and autophagy (ATG) over the past two decades, wi...
OBJECTIVE: This study, utilising bibliometric analysis combined with bioinformatics approaches, systematically analysed research trends in the fields of osteoporosis (OP) and autophagy (ATG) over the past two decades, with a focus on the emerging frontier of lipid peroxidation (LP). The aim was to reveal its independent role in the OP network, distinct from the ferroptosis framework. METHODS: CiteSpace.6.4.R1 was utilised to perform visualisation analysis on 588 relevant articles from the Web of Science Core Collection, examining countries, institutions, authors, and keywords. Common targets between OP and key burst terms were screened via the Gene Expression Omnibus (GEO) database, followed by the construction of a protein-protein interaction (PPI) network and gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Subsequently, we constructed 113 models using 12 machine learning algorithms to screen for feature genes, and the diagnostic value of key targets was validated using receiver operating characteristic (ROC) curves. RESULTS: Bibliometric analysis indicated that the field entered a period of rapid development from 2018, with China dominating in terms of publication volume and the United States leading in academic influence. Keyword burst detection identified 'LP' as an emerging frontier since 2023. Bioinformatics analysis identified 127 common OP-LP targets, which are enriched in pathways such as NF-κB, eestrogen signalling, and mitophagy. Through machine learning and MCODE module analysis, five key targets were ultimately screened: Amyloid beta precursor protein (APP), Forkhead Box O1 (FOXO1), Forkhead Box O3 (FOXO3), Jun Proto-Oncogene (JUN), and Synuclein Alpha (SNCA). ROC curves demonstrated their good diagnostic efficacy. CONCLUSION: This study is the first to integrate bibliometric and bioinformatics methods, revealing the macro-level trends in OP-ATG research and the molecular mechanisms underlying OP-LP crossover. It successfully identified five key OP-LP targets, providing a new perspective for understanding OP mechanisms and developing targeted therapies.
Taohong Siwu Decoction Regulates MSC-Mediated H-Type Angiogenesis to Accelerate Bone Fracture Healing Through VHL/HIF-1α Ubiquitination.
Li W, Ma Z, He P … +6 more , Xu W, Liu X, Yao J, Wu Q, Zou P, Li T
Mediators Inflamm · 2026 · PMID 41710264 · Full text
BACKGROUND: Bone fracture healing is a multifaceted process that involves different stages and intercellular interactions. In this study, we aimed to investigate the effect of Taohong Siwu decoction (TSD) on bone fractur...
BACKGROUND: Bone fracture healing is a multifaceted process that involves different stages and intercellular interactions. In this study, we aimed to investigate the effect of Taohong Siwu decoction (TSD) on bone fracture healing and the underlying mechanisms. METHODS: First, a mouse model of femur fracture was constructed, and TSD intervention was administered for durations of 7, 14, and 21 days. Following this, immunofluorescence (IF) was employed to evaluate the expression of CD90 (a marker for mesenchymal stem cells [MSCs]), endomucin (Emcn), and CD31. We also treated MSCs with normal serum and 10% TSD-containing serum to investigate the effects of TSD. Molecular docking was applied to verify the binding of active compounds in TSD to pVon Hippel-Lindau (VHL). Additionally, MSCs were treated with paeoniflorin and 2-methoxyestradiol (2-ME2) to explore the effects of paeoniflorin. Subsequently, mouse aortic endothelial cells were extracted and identified. Furthermore, normally cultured MSCs were cocultured with endothelial cells. MSCs were exposed to control serum, 10% TSD-containing serum, and a combination of 10% TSD-containing serum with 2-ME2. Finally, we administered a combination of 2-ME2 over 21 days to evaluate its effects on the fractured mice. RESULTS: TSD significantly influenced H-type angiogenesis during the healing process of fractured mice. Compared to the sham group, the model group exhibited lower levels of Emcn, CD90, hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF), while there was an increase in pVHL expression. After 7, 14, and 21 days of TSD intervention, the levels of Emcn, CD90, HIF-1α, VEGF, and pVHL gradually increased, whereas HIF-1α expression decreased. In vitro experiments revealed that TSD enhanced the proliferation and migration of MSCs while inhibiting the ubiquitination of pVHL/HIF-1α. Moreover, ferulic acid, amygdalin, hydroxysafflor yellow A, and paeoniflorin demonstrated a strong affinity for binding with pVHL. Notably, paeoniflorin promoted the proliferation and migration of MSCs through the pVHL/HIF-1α pathway to promote angiogenesis. Furthermore, TSD was found to enhance endothelial angiogenesis in MSCs. In summary, TSD affects H-type angiogenesis and MSCs homing during the healing process of fractured mice through the HIF-1α axis. CONCLUSIONS: TSD regulated MSC-mediated H-type angiogenesis to accelerate fracture healing through VHL/HIF-1α ubiquitination.
Mitochondria Pathway Signature Predicts Prognosis and Therapeutic Response and Identifies REXO2 as a Crucial Regulator in Breast Cancer.
Guo Z, Cao H, Lei C … +6 more , Ma D, Wu J, Xing Z, Zhao C, Wang X, Cui J
Mediators Inflamm · 2026 · PMID 41710263 · Full text
BACKGROUND: Mitochondrial-related pathways (MRPs) play a crucial role in cancer metabolism and progression; however, their prognostic value in breast cancer (BC) is still poorly understood. METHODS: We integrated multiom...
BACKGROUND: Mitochondrial-related pathways (MRPs) play a crucial role in cancer metabolism and progression; however, their prognostic value in breast cancer (BC) is still poorly understood. METHODS: We integrated multiomics data to investigate the landscape of MRPs in BC. A mitochondria pathways-associated signature (MPAS) was established using multimachine learning framework and interpreted by SHAP analysis across independent BC cohorts. Additionally, a series of functional experiments were employed to explore the role of RNA exonuclease 2 (REXO2) in BC cells. RESULTS: MRPs are extensively activated in BC at multiomics level. MPAS demonstrates outstanding predictive performance across multiple BC cohorts, with high scores indicating poor clinical outcomes. Moreover, it was observed that high MPAS scores are closely associated with immunosuppressive states and inflammatory microenvironments. SHAP analysis identified REXO2 as a hub factor of MPAS. Cell-based work confirmed that silencing REXO2 greatly inhibited cell proliferation and induced apoptosis in BC. CONCLUSIONS: Our proposed MPAS could effectively evaluate the prognosis and treatment response of BC patients, providing new reference for clinical decision-making. Furthermore, REXO2 regulates cell proliferation and apoptosis, making it a promising potential therapeutic target for inhibiting BC progression.
Correction to "Association Between Dietary Inflammatory Index and NAFLD: A Cross-Sectional Study of the National Health and Nutrition Examination Survey".
Mediators Inflamm · 2026 · PMID 41704747 · Full text
[This corrects the article DOI: 10.1155/mi/4954551.].
[This corrects the article DOI: 10.1155/mi/4954551.].
Macrophage-Mediated Cellular Communication Networks in Lung Squamous Cell Carcinoma and Adenocarcinoma Revealed by Single-Cell Sequencing.
Zhang X, Zhao Y, Wang Y … +4 more , Yu X, Xia H, Li M, Yang XA
Mediators Inflamm · 2026 · PMID 41704746 · Full text
BACKGROUND: Lung cancer, particularly the non-small cell lung cancer (NSCLC) subtypes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), exhibits high heterogeneity and high mortality. This study aimed t...
BACKGROUND: Lung cancer, particularly the non-small cell lung cancer (NSCLC) subtypes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD), exhibits high heterogeneity and high mortality. This study aimed to explore their tumor microenvironment (TME) features, cellular interactions, and potential therapeutic targets. METHODS: Using scRNA-seq datasets (GSE200972, GSE117570, and GSE127465) and TCGA bulk RNA-seq data, we performed cell clustering, pseudotime trajectory, cell-cell communication, and survival analyses. Batch correction and quality control were applied first, followed by cell type annotation with SingleR, copy number variation inference with InferCNV, and intercellular signaling investigation with CellChat. RESULTS: Four epithelial signatures (S1-S4) with distinct gene expression profiles were identified, with S3 specific to LUSC and correlated with high malignancy. Pseudotime analysis revealed distinct differentiation trajectories: S2→S1→S3/S4 in LUSC and S4→S1→S2 in LUAD. In LUSC, S3 interacted with macrophages via the and ligand-receptor pairs, involving the PI3K-Akt pathways; in LUAD, S4 communicated with neutrophils through , linked to interferon-related pathways. Macrophages played a central role in the TME, with as a key ligand-receptor pair in LUSC and in LUAD. Additionally, and expression correlated with prognosis in LUSC and LUAD, respectively. CONCLUSION: This study highlights subtype-specific epithelial signatures, identifies key signaling pathways (e.g., ), and pinpoints candidate therapeutic targets (, ). These discoveries shed new light on the distinct pathogenic mechanisms of LUSC and LUAD and provide actionable insights to facilitate the clinical translation of subtype-specific personalized immunotherapies.
Integrated Multiomics Elucidates Molecular Mechanisms of Bisphenol A in Exacerbating Crohn's Disease.
Dai L, Qiu C
Mediators Inflamm · 2026 · PMID 41695600 · Full text
BACKGROUND: Bisphenol A (BPA), a widespread environmental endocrine-disrupting chemical, has been associated with the development and progression of Crohn's disease (CD), yet its precise molecular mechanisms remain uncle...
BACKGROUND: Bisphenol A (BPA), a widespread environmental endocrine-disrupting chemical, has been associated with the development and progression of Crohn's disease (CD), yet its precise molecular mechanisms remain unclear. We aimed to systematically elucidate the potential molecular mechanisms by which BPA exacerbates CD and to identify key biomarkers and therapeutic targets. METHODS: BPA-related targets and CD transcriptomic datasets (GSE36807, GSE75214, and GSE95095) were retrieved from public databases. Overlapping genes were identified and subjected to functional enrichment and protein-protein interaction (PPI) network analysis. Multiple machine learning algorithms were employed to screen for core genes, and molecular docking was used to validate the binding affinity between BPA and core proteins. Immune infiltration analysis and regulatory network construction were performed to explore the roles of core genes in the immune microenvironment and post-translational regulation. RESULTS: A total of 65 overlapping genes between BPA and CD were identified, primarily enriched in pathways related to inflammation, apoptosis, and immune regulation. Machine learning screened five core genes (HGF, IL1R1, MMP1, MMP2, and NTRK2), which demonstrated strong diagnostic performance in independent datasets. Molecular docking revealed strong binding affinity between BPA and these proteins, with the lowest binding energy observed for MMP2 (-8.4 kcal/mol). Immune infiltration analysis indicated significant correlations between core genes and immune cell subsets such as Tr1, Th17, and Tfh cells. Regulatory network analysis identified key transcription factors (e.g., STAT3) and E3 ubiquitin ligases (e.g., SYVN1) involved in gene regulation. CONCLUSION: BPA may exacerbate CD progression by dysregulating core genes, such as HGF, IL1R1, MMP1, MMP2, and NTRK2, thereby disrupting inflammatory balance, extracellular matrix remodeling, and immune homeostasis.
The Impact of White Blood Cell Count Trajectories on Prognosis and Secondary Acute Kidney Injury in Sepsis Patients.
Yan J, Abudurexiti A, Yibubula G … +2 more , Li W, Liang J
Mediators Inflamm · 2026 · PMID 41695599 · Full text
BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, yet the prognostic value of longitudinal white blood cell (WBC) dynamics remains underexplored. M...
BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, yet the prognostic value of longitudinal white blood cell (WBC) dynamics remains underexplored. Most studies rely on single-timepoint measurements, potentially overlooking important dynamic information for risk stratification. OBJECTIVES: This study aimed to identify distinct WBC trajectory patterns during the first 7 days of ICU admission and evaluate their associations with mortality and secondary AKI in sepsis patients. METHODS: This retrospective cohort study analyzed 15,328 adult sepsis patients from the MIMIC-IV database (version 3.1) between 2008 and 2019. Group-based trajectory modeling (GBTM) was applied to daily WBC counts to identify trajectory subgroups. The primary outcome was 28-day mortality, with secondary outcomes including 90-day mortality and secondary AKI occurring after day 7. Cox proportional hazards regression was used to estimate hazard ratios with 95% confidence intervals. Subgroup analyses evaluated effect consistency across clinically relevant characteristics. RESULTS: Four distinct WBC trajectory groups were identified: high ( = 812, 5.3%), medium-high ( = 2,830, 18.5%), medium-low ( = 7,121, 46.5%), and low ( = 4,565, 29.8%), with overall mean WBC counts of 24.13, 16.60, 11.24, and 6.64 × 10/L, respectively. The 28-day mortality rates were 31.2%, 20.7%, 14.8%, and 12.9% for high, medium-high, medium-low, and low groups, respectively (log-rank < 0.001). Compared with the high group, the low trajectory demonstrated significantly reduced mortality risk (HR: 0.36, 95% CI: 0.31-0.42, < 0.001). The high-trajectory group exhibited higher secondary AKI incidence (21.8% vs. 13.0%, < 0.001) and greater disease severity. A significant interaction was observed for AKI status ( for interaction = 0.003). CONCLUSIONS: Longitudinal WBC trajectory patterns provide superior prognostic information compared to single-timepoint measurements in sepsis patients, with persistently high WBC levels associated with increased mortality and secondary AKI risk.
PSMA4 as a Druggable Target in Hidradenitis Suppurativa: Evidence From Mendelian Randomization and Single-Cell Transcriptomics.
Guo S, Gao L, Sun Y … +4 more , Yin L, Li P, Sun B, Lu J
Mediators Inflamm · 2026 · PMID 41685341 · Full text
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendel...
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendelian randomization (MR) analysis using blood cis-expression quantitative trait locus (eQTL) and HS genome-wide association study (GWAS) data. Colocalization, transcriptomic validation, single-cell RNA sequencing, and cell-cell communication analyses were integrated to explore gene function and cell-type specificity. We identified eight genes that showed significant associations with HS through MR analysis. Colocalization analysis further prioritized PSMA4 and MAST3 as the most promising druggable targets for HS. Specifically, PSMA4 (single nucleotide polymorphisms [SNPs] = 10; inverse-variance weighted [IVW] OR = 1.912, 95% CI: 1.492-2.450, < 0.001; PP.H4 = 0.975) and MAST3 (SNPs = 15; IVW OR = 0.557, 95% CI: 0.453-0.686, < 0.001; PP.H4 = 0.832) exhibited strong statistical associations. Transcriptomic validation revealed that PSMA4 was upregulated and MAST3 was downregulated in HS lesions. Further single-cell analysis revealed that PSMA4 was predominantly enriched in CD4 T cells and involved in pro-inflammatory signaling, particularly the tumor necrosis factor (TNF) pathway. PSMA4 and MAST3 are potential therapeutic targets for HS. PSMA4 may promote inflammation via CD4 T cell-mediated signaling, offering a novel avenue for treatment development.
Causal Association Between Plasma Proteins and Pericarditis: A Mendelian Randomization Study With Therapeutic Target Identification.
Chen Z, Chen Z, Peng L … +1 more , Zhang H
Mediators Inflamm · 2026 · PMID 41674924 · Full text
BACKGROUND: Observational studies demonstrate that pro-inflammatory cytokines play a critical role in pericarditis. However, the causal association between circulating plasma proteins and pericarditis remains unestablish...
BACKGROUND: Observational studies demonstrate that pro-inflammatory cytokines play a critical role in pericarditis. However, the causal association between circulating plasma proteins and pericarditis remains unestablished. OBJECTIVE: This research aimed to assess the causal association between plasma proteins and pericarditis and to investigate potential therapeutic targets. METHODS: A genome-wide association study (GWAS) involving 35,559 individuals of European ancestry was conducted using 4907 plasma proteins as instrumental variables (IVs). The causal relationship between plasma proteins and pericarditis was examined using inverse weighted median, variance weighting, and Mendelian randomization (MR)-Egger methods. Horizontal pleiotropy was evaluated via MR-Egger regression, and heterogeneity was quantified by Cochran's Q statistic. In addition, enrichment analyses, construction of a protein-protein interaction (PPI) network, and single-cell RNA sequencing (scRNA-seq) analysis were performed. Molecular docking was used to predict potential drug targets. RESULTS: MR analyses identified 67 plasma proteins with potential causal relationships with pericarditis, such as NEU1, GDNF, LAT, CASP8, ZFYVE27, and NAPA. Among them, elevated levels of NEU1, GDNF, and LAT increased the risk of pericarditis, whereas higher levels of CASP8, ZFYVE27, and NAPA decreased the risk of pericarditis. Pleiotropy tests and sensitivity analyses confirmed the stability of the findings. Moreover, scRNA-seq analysis revealed that genes such as , and were specifically expressed in cardiac progenitor cells (CPCs). Molecular docking further identified compounds with anti-inflammatory, antioxidant, or immunomodulatory potential, including phorbol 12-myristate 13-acetate (PMA), cerivastatin, and melatonin. CONCLUSION: This research examined the causal association between plasma proteins and pericarditis by MR analysis and identified several potential therapeutic targets. These findings provide theoretical evidence for targeted drug development and clinical prevention strategies for pericarditis.
Gut Microbiota-Derived Metabolites Regulate CASP3 and Neuroimmune Pathways in Multiple Sclerosis: An Integrative Multiomics Study.
Li Li, Liu H, Ye Z … +1 more , Xu W
Mediators Inflamm · 2026 · PMID 41674923 · Full text
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, closely associated with neuroinflammation, immune dysregulation, and gut microbiota imbalance. Gut microbiota-derived met...
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, closely associated with neuroinflammation, immune dysregulation, and gut microbiota imbalance. Gut microbiota-derived metabolites may modulate key targets involved in MS pathogenesis. METHODS: This study integrated network pharmacology, machine learning (ML), and single-cell transcriptome analysis to identify MS-related differentially expressed genes (DEGs) and potential targets of gut microbial metabolites. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) method, and causal relationships were validated via Mendelian randomization (MR). Single-cell analysis, molecular docking, and assessments of drug-likeness and toxicity were also performed. RESULTS: Caspase-3 (CASP3) was identified as a core target interacting with multiple gut microbial metabolites, including L-isoleucine, aromatic lactic acid derivatives, 3-hydroxyphenethyl alcohol, and D-xylose, potentially regulating neuroimmune responses via TNF, MAPK, IL-17, and galectin pathways. Specific microbial taxa, such as , , and , were closely associated with these metabolites. The metabolites exhibited favorable drug-likeness and low predicted toxicity, indicating potential therapeutic value. CONCLUSION: Gut microbial dysbiosis and its metabolites play a significant role in MS onset and progression, providing a theoretical basis for identifying therapeutic targets and gut-CNS axis interventions. Experimental validation is needed to confirm mechanisms and translational potential.
Bone Marrow Mesenchymal Stem Cell-Derived Exosomal Let-7b-5p Reduces High Glucose-Induced Microglial Activation and Inflammation Through TLR4/ATF4.
Zhang Y, Luo Y, Han J … +5 more , Wang L, Xu H, Zhang L, Chen P, Luo H
Mediators Inflamm · 2026 · PMID 41674922 · Full text
BACKGROUND AND OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision loss in patients with diabetes mellitus (DM), and its pathogenesis is closely associated with aberrant microglial activation. Although bone...
BACKGROUND AND OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision loss in patients with diabetes mellitus (DM), and its pathogenesis is closely associated with aberrant microglial activation. Although bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) and the miRNAs that they carry show therapeutic potential for DR, the specific roles and molecular mechanisms through which let-7b-5p regulates microglial activation after it is delivered by BMSC-Exo remain unclear. This study aimed to elucidate the function and underlying mechanism of BMSC-Exo let-7b-5p in DR. METHODS: A DR mouse model was established by intraperitoneal injection of streptozotocin (STZ), and BV-2 microglia were stimulated with high glucose (HG) to induce activation in vitro. The morphological characteristics of the BMSC-Exo were identified using transmission electron microscopy (TEM). Protein and gene expression levels, as well as microglial activation, were assessed by Western blot, RT-qPCR, and immunofluorescence, respectively. Retinal tissue damage and apoptosis were evaluated using HE staining and TUNEL assays. RESULTS: BMSC-Exo treatment significantly suppressed the expression of activation markers (Iba1 and TSPO) and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in HG-induced BV-2 cells and DR mouse retinas while alleviating retinal tissue damage and apoptosis. Bioinformatics analysis revealed the downregulation of let-7b-5p in DR. Functional experiments demonstrated that let-7b-5p overexpression enhanced the inhibitory effects of BMSC-Exo on microglial activation, inflammation, and retinal damage, whereas let-7b-5p knockdown attenuated these therapeutic benefits. Mechanistically, BMSC-Exo let-7b-5p inhibited excessive microglial activation and inflammatory responses by targeting the TLR4/ATF4 signaling pathway. CONCLUSION: BMSC-Exo deliver let-7b-5p to suppress the TLR4/ATF4 pathway, thereby mitigating microglial activation and inflammation and ultimately delaying DR progression. These findings support the potential of this novel therapeutic strategy for targeted DR treatment.
Inflammatory Factors Derived From Metabolic Dysfunction-Alcoholic Fatty Liver Disease: Inducers of Anxiety and Spatial Memory Impairment.
Peng TT, Shi Y, Yu R … +8 more , Nie YX, Mu Y, Jin T, Zhang JN, Wang X, Hua Q, Tan Y, Devkar RV
Mediators Inflamm · 2026 · PMID 41674921 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global epidemic, with growing evidence suggesting its adverse impact on brain function. However, the underlying mechanisms linking hepatic...
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global epidemic, with growing evidence suggesting its adverse impact on brain function. However, the underlying mechanisms linking hepatic metabolic dysfunction to neurodegeneration remain unclear. In this study, we systematically investigated the liver-brain axis by integrating genetic epidemiology, experimental neuroscience, and transcriptomics techniques. Two-sample Mendelian randomization (MR) analysis revealed a potential causal relationship between MASLD and cognitive decline. These findings were validated in a high-fat diet (HFD)-induced MASLD mouse model, which exhibited hallmark features of metabolic dysfunction, including significant body fat accumulation and elevated serum levels of pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α[TNF-α]). Behavioral assays demonstrated pronounced anxiety-like behaviors and impaired spatial memory. Neuropathological analysis revealed neuronal loss and structural alterations in the hippocampal dentate gyrus (DG), accompanied by astrocyte remodeling and M1 microglial polarization, indicating neuroinflammation-driven disruption of hippocampal circuits. At the molecular level, MASLD altered the expression of key hippocampal genes-including , , and -impacting immune response, lipid metabolism, and apoptotic pathways, which collectively contributed to cognitive deficits. Dual immunofluorescence staining, combined with Sholl and 3D analysis quantitatively characterized neuroglial morphological and functional changes, providing structural-level evidence for MASLD-related brain dysfunction. Taken together, our findings identify MASLD as a modifiable risk factor for neurodegeneration, with systemic inflammation playing a pivotal role in the liver-brain axis. This study highlights key genes and pathways underlying MASLD-induced cognitive impairment, advances understanding of metabolic-neural cross talk, and offers potential therapeutic targets for mitigating cognitive decline through intervention in the liver-brain axis, developing intervention strategies and highlight the therapeutic promise of targeting the liver-brain axis.
Correction to "mTOR Modulates the Endoplasmic Reticulum Stress-Induced CD4+ T Cell Apoptosis Mediated by ROS in Septic Immunosuppression".
Mediators Inflamm · 2026 · PMID 41669542 · Full text
[This corrects the article DOI: 10.1155/2022/6077570.].
[This corrects the article DOI: 10.1155/2022/6077570.].
Evaluating the Link Between High-Density Lipoprotein-Related Inflammatory Indices and Gallstone Disease in U.S. Adults.
Fu C, Chen J, Liu K … +2 more , Dong H, Li X
Mediators Inflamm · 2026 · PMID 41659897 · Full text
BACKGROUND: Gallstone disease is a condition affecting the digestive system, strongly linked to inflammation and lipid metabolism. Inflammatory markers derived from high-density lipoprotein (HDL), incorporating both immu...
BACKGROUND: Gallstone disease is a condition affecting the digestive system, strongly linked to inflammation and lipid metabolism. Inflammatory markers derived from high-density lipoprotein (HDL), incorporating both immune cells and HDL-C, play a crucial role in assessing inflammatory responses. This study aims to explore the relationship between these HDL-related inflammatory indices and gallstone disease. METHODS: The study population was derived from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 and 2021-2023 datasets. To assess the association between HDL-related inflammatory indices and gallstone disease, weighted multivariable logistic regression and restricted cubic spline (RCS) analysis were utilized. Additionally, subgroup analysis was conducted to confirm the consistency of the results across different subpopulations. RESULTS: Among the 16,871 participants included in the study, 11.0% were diagnosed with gallstone disease. When compared to the lowest quartile, those in the highest quartile of lymphocyte-to-HDL cholesterol ratio (LHR), monocyte-to-HDL cholesterol ratio (MHR), neutrophil-to-HDL cholesterol ratio (NHR), and platelet-to-HDL cholesterol ratio (PHR) faced an elevated risk of gallstone disease by 58.6% (OR = 1.586, 95% CI: 1.143-2.2), 67.6% (OR = 1.676, 95% CI: 1.275-2.204), 68.7% (OR = 1.687, 95% CI: 1.244-2.287), and 42.7% (OR = 1.427, 95% CI: 1.101-1.849), respectively. The correlation between HDL-related inflammatory indices and gallstone disease was more pronounced in females, individuals without diabetes or hypertension, nonsmokers, and those who consumed alcohol. CONCLUSIONS: This research identified a positive correlation between HDL-related inflammatory indices and gallstone disease in a nationally representative sample. These indices can be derived from routine blood tests at no additional cost, making them practical and cost-effective tools for early risk stratification and potential large-scale screening.
Threshold Effect of C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index on Disease Activity in Rheumatoid Arthritis: Unveiling a Nonlinear Association.
Leng L, Tang Q, Li Y … +3 more , Zhang J, Han Y, Li X
Mediators Inflamm · 2026 · PMID 41640573 · Full text
The relationship between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and disease activity of rheumatoid arthritis (RA) has not been explored at present. This study included 1058 RA patients and used a m...
The relationship between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and disease activity of rheumatoid arthritis (RA) has not been explored at present. This study included 1058 RA patients and used a multiple linear regression model to evaluate the association between the CALLY index and 28 joint disease activity scores (DAS28) and further explored its potential nonlinear relationship using a two-stage segmented linear regression model. Multivariate adjusted analysis showed that CALLY was significantly negatively correlated with DAS28-erythrocyte sedimentation rate (ESR) ( = -0.119, 95% confidence interval [CI]: -0.145 to -0.093) and DAS28-CRP ( = -0.201, 95% CI: -0.226 to -0.177) (both < 0.001), and there was a dose-response relationship (trend < 0.001). Segmented regression analysis revealed a significant nonlinear correlation between the two, with inflection points of 0.499 and 0.555, respectively. Below the inflection point, CALLY has a significant negative impact on disease activity (DAS28-ESR: = -2.102, 95% CI: -2.498 to -1.706); DAS28-CRP: = -2.311, 95% CI: -2.591 to -2.031); after exceeding the inflection point, this negative correlation effect significantly weakens but still maintains statistical significance. The results of this study indicate a significant nonlinear relationship between the CALLY index and the DAS28 score, especially at low CALLY levels. This study suggests the potential of CALLY as a novel composite biomarker reflecting the inflammatory status and disease severity of RA.
Evaluation of Indigo Naturalis Prepared Using a Novel Method: Anti-Inflammatory Activities Against Colonic Cancer Cell Lines.
Xu X, Lin L, Ning W … +6 more , Zhou X, Ullah A, Huang X, Yang H, Wu X, Diao Y
Mediators Inflamm · 2026 · PMID 41640572 · Full text
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), and cancerous transformation of UC is closely associated with chronic inflammation of colonic tissues. Indigo naturalis (IN) prepared using a novel m...
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), and cancerous transformation of UC is closely associated with chronic inflammation of colonic tissues. Indigo naturalis (IN) prepared using a novel method (NIN) has exhibited beneficial efficacy against inflammatory and cancerous colonic cells. However, the underlying mechanism still remains to be elucidated. This study aimed to construct an inflammation model by the HT-29 colonic cancer cell line and to investigate the effect of NIN on an inflammatory cancer state and the possible mechanism. The results showed that NIN could reduce the increased expression of pro-inflammatory cytokine IL-1β in the inflammatory cancer cells and attenuate the inflammatory response; elevate the low expression of MUC2 in the inflammatory cancer state and restore the mucin secretion function; and inhibit the proliferation of HT-29 cells. Based on the activation of the aryl hydrocarbon receptor (AhR) signaling pathway, NIN increases the expression of the Wnt/β-catenin signaling pathway inhibitor Rnf43, inhibits the expression of nonphosphorylated β-catenin, and reduces the level of the pathway downstream target gene Axin2, which in turn inhibits the Wnt/β-catenin signaling pathway and inhibits the expression of Lgr5, a stem cell gene of colorectal cancer (CAC). The production of the above effects of NIN was blocked by the AhR antagonist CH223191. The in vitro studies verified that NIN alleviated UC by activing AhR signaling pathway, which in turn inhibited the Wnt/β-catenin signaling pathway. The possible mechanism of NIN on UC could be explained starting from the inflammation-cancer transformation. Furthermore, comprehensive research is expected between inflammation and cancer development.
Single-Cell Transcriptomics Reveals Biomarkers for NK Cell Dysfunction in Endometriosis-Associated Immune Dysregulation.
Li W, Zhu K, Xu B … +6 more , Nie J, Wang F, Ur Rehman Aziz A, Yu X, Wang D, Ha C
Mediators Inflamm · 2026 · PMID 41640571 · Full text
BACKGROUND: Endometriosis (EM) is associated with immune dysregulation, while dysfunction of natural killer (NK) cells is regarded as a key mechanism underlying immune escape and the persistent growth of ectopic lesions....
BACKGROUND: Endometriosis (EM) is associated with immune dysregulation, while dysfunction of natural killer (NK) cells is regarded as a key mechanism underlying immune escape and the persistent growth of ectopic lesions. METHOD: This study used single-cell RNA sequencing (scRNA-seq) on lesions from three patients with EM and on three normal endometrium samples and integrated these data with three bulk RNA-seq datasets from GEO (GSE105765, GSE7305, and GSE6364). Seurat, Monocle, limma, least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM-RFE) were used for cell clustering, trajectory inference, differential expression analysis, and feature selection. Immune-cell composition and pathway activity were evaluated with CIBERSORT and GSVA. Gene expression was validated by qPCR, and cell migration and invasiveness were assessed using wound healing and Transwell assays. RESULT: scRNA-seq resolved 11 clusters assigned to eight major cell types. By integrating pseudotime features with bulk data, 20 differentially expressed genes (DEGs) were prioritized, and machine-learning analyses identified three key genes: granulysin (GNLY), perforin 1 (PRF1), and ENTPD1. The three-gene model showed good discrimination in the training set and two external validation cohorts (AUCs 0.84, 0.67, and 0.77, respectively). GNLY and PRF1 were predominantly expressed in NK cells and CD8 T cells and correlated with activation signatures, whereas ENTPD1 was highly expressed in endometrial stromal cells and enhanced their migratory and invasive capacities. ENTPD1 may contribute to disease via adenosine signaling-mediated modulation of NK-cell function. In silico analyses also nominated candidate agents targeting this pathway, including resveratrol, ibuprofen, and danazol. CONCLUSION: This study highlights the central role of NK-cell dysfunction in EM pathogenesis and proposes GNLY, PRF1, and ENTPD1 as potential molecular diagnostic biomarkers. Notably, ENTPD1 appears to have dual functions, including immunomodulation and promotion of stromal cell migration, which promotes lesion formation. These findings provide a mechanistic rationale and actionable targets for earlier screening and targeted therapy in EM.
Differences in the Expression of Insulin-Like Growth Factor Signaling Pathway Members in Patients With Psoriasis Vulgaris and Controls.
Drahomira H, Lenka B, Zdenek F … +7 more , Jan K, Kvetoslava H, Eva C, Vit R, Ondrej F, Tereza M, Pavel B
Mediators Inflamm · 2026 · PMID 41635444 · Full text
Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) regulate cell proliferation, differentiation, metabolic processes, and immune activities. Psoriasis is a systemic inflammatory disease with metabolic d...
Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) regulate cell proliferation, differentiation, metabolic processes, and immune activities. Psoriasis is a systemic inflammatory disease with metabolic disorders as an important comorbidity in the pathogenesis of which members of the IGF family could also play a role. Therefore, we decided to evaluate the levels of members of the IGF signaling pathway in patients with psoriasis. Sixty-nine people were enrolled in our study: 34 patients with psoriasis and 35 controls. The following parameters were evaluated in serum obtained from peripheral blood: total cholesterol, triglycerides, high-density lipoprotein, fasting glucose, IGF-1, IGF-1R, IGF-2, IGF-2R, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP6, and insulin. The levels of several parameters differed between groups. The levels of fasting glucose, insulin, IGFBP3, and IGFBP6 were higher in patients with psoriasis, while the levels of IGF-1, IGF-1R, and IGBP4 were higher in controls. The results suggested that the IGF-1 signaling pathway can be involved in the pathogenesis of psoriasis and its comorbidities, especially metabolic disorders such as insulin resistance, diabetes, and metabolic syndrome. The novelty of our study is in its comprehensive assessment of the involvement of the IGF-1 signaling pathway in the pathogenesis of psoriasis and advances the understanding of the pathogenesis of psoriasis and its comorbidities.
Convergent Multistage Evidence Implicates the CCR2-Artemin Immune-Inflammation Axis in Acute Myeloid Leukemia.
Jin Y, Lu HM, Yu XH … +6 more , Su MZ, Li J, Li XM, Jin JH, Zhang LT, Wang Y
Mediators Inflamm · 2026 · PMID 41624379 · Full text
BACKGROUND: The immune system and inflammatory proteins influence hematologic malignancies, but causal links with immune cell phenotypes are unclear. METHODS: We applied a prespecified, multistage workflow: two-sample an...
BACKGROUND: The immune system and inflammatory proteins influence hematologic malignancies, but causal links with immune cell phenotypes are unclear. METHODS: We applied a prespecified, multistage workflow: two-sample and multivariable Mendelian randomization (MVMR; 731 immune traits across 12 hematologic cancers), two-step mediation Mendelian randomization (MR) of 91 circulating inflammatory proteins, MAGMA/FUMA gene and pathway enrichment, and external validation with trait-specific genetic risk scores (GRSs) in UK Biobank (UKB). We then performed perturbation assays in human monocytic leukemia cell line (THP-1) and immortalized bone marrow-derived macrophage (IBMDM) cells with artemin () mRNA readouts and examined proteomic correlations for using the Olink inflammatory panel. RESULTS: Eight immune phenotypes showed FDR-significant causal associations with malignancy, seven of which remained independent in MVMR. In acute myeloid leukemia (AML), on myeloid dendritic cells (DCs) was associated with lower risk, whereas and on transitional B cells were associated with higher risk, on IgDCD38^dim B cells was associated with chronic myeloid leukemia (CML), and HLA-DR NK cells were protective in non-Hodgkin lymphoma (NHL). Mediation MR identified three protein mediators-, , and , with mediating the -AML association. GRS analyses reproduced risk directions, most prominently the protective -AML association. In THP-1 and IBMDM models, inhibition or knockdown increased mRNA expression, functionally supporting a → regulatory relationship. Proteomic correlations positioned with immune-metabolic proteins (, , , and ). Pathway analyses highlighted membrane-proximal processes (external plasma membrane and IgG binding) and a 16p11.2 signal. CONCLUSION: This integrative analysis identified - as a mechanistically supported immune-inflammation axis contributing to AML risk, offering a potential therapeutic target and warrants direct validation in primary myeloid DCs.
Phenotypic Heterogeneity in Glaucoma: The Systemic and Vascular Landscape Behind Functional Loss.
Muñoz de Escalona Rojas JE, García Serrano JL, Navarro Martínez P
Mediators Inflamm · 2026 · PMID 41624378 · Full text
OBJECTIVE: To analyze the direct and indirect associations between structural, functional, and systemic variables in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and controls using str...
OBJECTIVE: To analyze the direct and indirect associations between structural, functional, and systemic variables in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and controls using structural equation modeling (SEM). METHODS: A cross-sectional observational study was conducted including 156 participants: 55 with POAG, 49 with NTG, and 52 age- and sex-matched controls. Clinical variables included intraocular pressure (IOP), central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR), and visual-field mean deviation (MD). Systemic variables comprised age and cardiovascular risk factors (hypertension, diabetes, and dyslipidemia). SEM was applied to assess direct and indirect effects on the diagnosis of glaucoma. RESULTS: The model showed a good overall fit ( (9) = 15.968; = 0.068; /df = 1.774; CFI = 0.972; RMSEA = 0.071) and explained 46.0% of the variance in glaucoma diagnosis ( = 0.460). The most influential predictors were VCDR ( = 0.40), age ( = 0.14), and cardiovascular risk factors ( = 0.19). A significant negative correlation was observed between CCT and MD ( = -0.29), indicating greater functional damage in eyes with thinner corneas. An inverse association between cardiovascular risk burden and IOP was also identified ( = -0.18). CONCLUSIONS: Our findings support the hypothesis of distinct glaucomatous phenotypes, including a vascular subtype with lower IOP and altered perfusion, potentially influenced by systemic comorbidities and chronic treatments. Reduced CCT was also confirmed as an independent marker of advanced functional loss. SEM helps disentangle complex mechanisms and may inform personalized therapeutic strategies, particularly in NTG.
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