Mediators Of Inflammation[JOURNAL]
Sun
200 papers
The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.
Bo X, Wang M, Liu Y … +1 more , Zhong Y
Mediators Inflamm · 2026 · PMID 41999083 · Full text
C3a is a key active factor in the complement system, capable of participating in various physiological and pathological processes by binding to its C3a receptor (C3aR). The C3a-C3aR pathway not only plays an important ro...
C3a is a key active factor in the complement system, capable of participating in various physiological and pathological processes by binding to its C3a receptor (C3aR). The C3a-C3aR pathway not only plays an important role in immune regulation but is also closely related to the occurrence and development of various inflammatory diseases, cardiovascular diseases, autoimmune diseases, and tumors. In recent years, research on the specific mechanisms of action of C3a-C3aR in different diseases has gradually deepened. This article aims to review the basic functions of the C3a-C3aR pathway, with a focus on summarizing the latest research advances in kidney diseases, cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, and tumors, and to explore its prospects as a potential therapeutic target.
The Nonlinear Relationship Between the Aggregate Index of Systemic Inflammation and Serum Neurofilament Light Chain Levels in U.S. Adults: A Cross-Sectional Study.
Wei J, Liu Y, Zhang J
Mediators Inflamm · 2026 · PMID 41984524 · Full text
BACKGROUND: Systemic inflammation is linked to chronic diseases. This study examines the relationship between the aggregate index of systemic inflammation (AISI) and serum neurofilament light chain (sNfL), a marker of ne...
BACKGROUND: Systemic inflammation is linked to chronic diseases. This study examines the relationship between the aggregate index of systemic inflammation (AISI) and serum neurofilament light chain (sNfL), a marker of neuronal damage. METHODS: Data were obtained from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Participants with complete data on AISI and sNfL were included. Multiple linear regression and subgroup analyses were used to assess the association, and the nonlinear relationship was explored through smoothed curve fitting and threshold effect analyses. RESULTS: Among 2,061 adults in NHANES 2013-2014, ln AISI was positively associated with sNfL (pg/mL) (fully adjusted β = 2.78 per 1-unit increase; 95% CI: 1.41-4.15; p < 0.0001). By quartiles of ln AISI, sNfL was higher in Q4 vs. Q1 (β = 6.22, 95% CI: 3.57-8.88; p < 0.0001), whereas Q2-Q3 were not significant after full adjustment; p for trend < 0.0001. Nonlinearity analysis identified an inflection at ln AISI = 4.34: below this value the estimate was negative and nonsignificant (β = -8.82; 95% CI: -18.10-0.46; p = 0.0627), whereas above it the association was positive and significant (β = 3.55; 95% CI: 2.05-5.04; p < 0.0001; likelihood ratio p = 0.013). Effect modification was observed by age (p for interaction = 0.0068), BMI (p for interaction = 0.0174), diabetes (p for interaction = 0.0004), hypertension (p for interaction = 0.0436), alcohol use (p for interaction = 0.0133), and stroke history (p for interaction = 0.0033). CONCLUSION: In the U.S. population, higher ln AISI values were independently associated with increased sNfL levels. A nonlinear relationship was observed between ln AISI and sNfL. This suggests that AISI may represent an important marker associated with sNfL levels beyond traditional clinical factors, and further studies are needed to better explore their association and potential underlying biological mechanisms.
FGFR2 is a Candidate Immune-Associated Marker of Diabetic Foot Ulcer That Promotes Keratinocyte Function by Activating the PI3K/Akt and MAPK Pathways.
Chen H, Sang H, Shi Y … +3 more , Pan J, Zhang C, Lei F
Mediators Inflamm · 2026 · PMID 41983566 · Full text
OBJECTIVE: Diabetic foot ulcer (DFU) is a serious complication of diabetes. This study aims to screen DFU-associated immune-related genes (IRGs) and investigate their potential functional mechanisms and clinical relevanc...
OBJECTIVE: Diabetic foot ulcer (DFU) is a serious complication of diabetes. This study aims to screen DFU-associated immune-related genes (IRGs) and investigate their potential functional mechanisms and clinical relevance. METHODS: Based on the GSE80178 dataset, the differentially expressed genes (DEGs) between DFU and diabetic foot skin (DFS) were screened out and cross-linked with IRGs to obtain differentially expressed IRGs (DE-IRGs). Functional enrichment analysis was conducted using the "clusterProfiler" R package. The protein-protein interaction (PPI) network was constructed using the STRING platform, and the core genes were identified based on topological analysis. The expression and diagnostic efficacy of core genes were verified using external datasets (GSE199939 and GSE134431). Immune cell infiltration analysis was performed using CIBERSORT algorithm. The candidate drugs were predicted through the L1000FWD database and molecular docking was carried out with Autodock Vina. The function of the core gene and its molecular mechanism were verified by constructing a high glucose (HG)-induced HaCaT cell injury model in vitro. RESULTS: A total of 108 DE-IRGs were screened out, including 48 upregulated genes and 60 downregulated genes. These genes were significantly enriched in the cytokine-cytokine receptor interaction, phosphoinositol 3-kinase (PI3K)-protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. Fibroblast growth factor receptor (FGFR) 2 was identified as the core gene, and its expression was significantly downregulated in DFU, with high diagnostic value (area under the curve [AUC] >0.95). The expression of FGFR2 was correlated with the infiltration levels of various immune cells. QL-XI-92, reversine, BRD-K67414432, LY294002, and neratinib had high binding affinity with the FGFR2 protein. HG significantly reduced the expression of FGFR2 in HaCaT cells, inhibited proliferation and migration, and promoted apoptosis and the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6; overexpression of FGFR2 reversed the above-mentioned phenomena and activated the PI3K/Akt and p38 MAPK pathways. The protective effect of FGFR2 could be reversed by LY294002 (an inhibitor of PI3K/Akt pathway) or SB202190 (a p38 MAPK inhibitor). CONCLUSION: FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.
Unveiling Epigenetic Molecular Mechanisms in Bone Fracture Risk: Insights From 731 Immune Cells, 1400 Metabolites, and Critical Genetic Pathways.
Wan X, Lu W, Xue J … +5 more , Huang J, Qian W, Hu Z, You W, Zhang Y
Mediators Inflamm · 2026 · PMID 41960642 · Full text
BACKGROUND: The aging population and advancements in medical science have heightened the focus on fractures, which affect over 150 million individuals annually, with substantial health and economic consequences. OBJECTIV...
BACKGROUND: The aging population and advancements in medical science have heightened the focus on fractures, which affect over 150 million individuals annually, with substantial health and economic consequences. OBJECTIVE: This study investigated the potential causal relationships between 731 immune cells, 1400 metabolites, and nine fracture types using Mendelian randomization (MR). METHODS: A combination of bidirectional MR, two-sample MR, and mediation MR was employed to assess potential causal links. Sensitivity analysis was performed using MR-PRESSO. Bioinformatics analyses, including functional enrichment and protein-protein interaction (PPI) network analysis, were conducted. Colocalization analysis was used to examine associations between key genes and fractures. RESULTS: Bidirectional MR identified 7 immune cell subtypes (e.g., B cells, Tregs, and monocytes) and 11 metabolite classes (e.g., lipids, amino acids) with significant MR-supported associations with fracture risk, with effects varying by skeletal site. Mediation analysis revealed that the increased wrist fracture risk associated with CD28+CD45RA-CD8br T cells was mediated by 5-methylthioadenosine (19.6%), while the reduced foot fracture risk linked to CD28-CD8dim T cells was mediated via the taurine-to-cysteine ratio (20.9%). SNP nearest gene integration highlighted enriched pathways related to immune response, cell adhesion, and metabolism. PPI network analysis pinpointed 9 hub genes, six of which (CD8A, PRKACA, IL-6, ITGB1, ITPR1, and STAT3) showed strong colocalization evidence with fractures. Moreover, DNA methylation at cg09664550 (ITGB1) showed the most significant negative impact on thoracic spine fractures (OR = 1.986), whereas cg18112163 (STAT3) conferred the strongest protective effect against foot fractures (OR = 0.602; all p < 0.05). CONCLUSIONS: The findings suggest that immune cells and metabolites may have genetically predicted effects on fracture risk, with metabolites potentially serving as key mediators. Critical pathways, hub genes, and fracture-associated SNPs were identified, along with potential epigenetic regulation via methylation sites. These preliminary insights offer novel directions for future research into the underlying mechanisms of fracture risk and intervention.
Genetic Correlations and Causal Relationships Among Allergic Diseases: A Comprehensive Mendelian Randomization Study With Multiomic Mediation Analysis.
Zhang PA, Wang JL, Fu SY … +4 more , Luo HL, Li NJ, Qin RD, Li J
Mediators Inflamm · 2026 · PMID 41954291 · Full text
BACKGROUND: Allergic diseases, including allergic asthma (AA), allergic rhinitis (AR), atopic dermatitis (AD), and allergic conjunctivitis (AC), often coexist. However, the specific inflammatory mediators driving their s...
BACKGROUND: Allergic diseases, including allergic asthma (AA), allergic rhinitis (AR), atopic dermatitis (AD), and allergic conjunctivitis (AC), often coexist. However, the specific inflammatory mediators driving their shared mechanisms remain unclear. This study explored causal relationships and identified multiomic mediators among allergic diseases using Mendelian randomization (MR). METHODS: Large-scale GWAS datasets from FinnGen and UK Biobank were analyzed. Linkage disequilibrium score regression (LDSC) and MR-robust adjusted profile scoring (MR-RAPS) assessed genetic correlations and causal links. Crucially, multivariable MR (MVMR) adjusted for classical type 2 inflammatory factors to isolate independent effects. A two-step MR framework evaluated the mediating roles of immune cells, metabolites, gut microbiota, and serum proteins. RESULTS: Six disease pairs (AA-AR, AA-AD, AR-AA, AR-AD, AD-AA, and AD-AR) showed robust causal relationships independent of type 2 inflammation markers. Mediation analyses identified key inflammatory mediators, including immune cell subsets (e.g., CD45 on granulocytes), plasma metabolites (e.g., pentose acid), gut microbiota (e.g., Bacteroides intestinalis), and notably, serum proteins such as ABHD12 and SEZ6L2. Pathway analyses highlighted cytokine-cytokine receptor interactions and lipid metabolism. CONCLUSIONS: This study maps a comprehensive causal network of allergic multimorbidity. We identified novel serum proteins and metabolic mediators beyond the classical type 2 inflammation axis, offering potential therapeutic targets for disrupting the inflammatory crosstalk between allergic diseases.
Allicin Attenuates Sepsis-Induced Acute Kidney Injury by Inhibiting Pyroptosis Through Negative Regulation of the PI3K/AKT Pathway.
Zheng Y, Li S, Zhu L … +1 more , Zhang L
Mediators Inflamm · 2026 · PMID 41953959 · Full text
Pyroptosis is a critical mechanism leading to sepsis-induced acute kidney injury (S-AKI). Allicin, an organosulfur compound extracted from garlic bulbs, protects against S-AKI through its anti-pyroptotic role, but the un...
Pyroptosis is a critical mechanism leading to sepsis-induced acute kidney injury (S-AKI). Allicin, an organosulfur compound extracted from garlic bulbs, protects against S-AKI through its anti-pyroptotic role, but the underlying pathophysiological mechanisms remain largely unknown. In in vivo and in vitro experiments, rats and HK-2 cells were induced by caecal ligation and puncture (CLP) and lipopolysaccharides (LPSs), respectively. They were then treated with allicin, insulin-like growth factor-1 (IGF-1, a PI3K/AKT agonist), or both. In this study, we found that the levels of p-PI3K, p-AKT, NF-κB, NLRP3, caspase-1, gasdermin D (GSDMD)-N, IL-1β, IL-18 and lactate dehydrogenase (LDH) were significantly increased, which was accompanied by kidney tissue and HK-2 cell pyroptosis, eventually leading to elevated serum creatinine (Scr) and blood urea nitrogen (BUN) levels, increased 7-day mortality and reduced HK-2 cell activity in CLP-induced rats and LPS-induced HK-2 cells, respectively. Moreover, we observed that allicin significantly reduced the levels of p-PI3K, p-AKT, NF-κB, NLRP3, caspase-1, GSDMD-N, IL-1β, IL-18 and LDH and inhibited pyroptosis in renal tissues and HK-2 cells, ultimately resulting in improved kidney function, 7-day survival, and enhanced HK-2 cell activity in CLP-induced rats and LPS-induced HK-2 cells. Furthermore, our results demonstrate that agonism of the PI3K/AKT pathway-by using IGF-1-could reverse the abovementioned protective role of allicin, accompanied by increased phosphorylation of PI3K and AKT in vivo and in vitro. Overall, the findings of this study demonstrate that the protective effect of allicin on S-AKI is largely dependent on the inhibition of pyroptosis through the negative regulation of the PI3K/AKT pathway.
Integrative Single-Cell and Spatial Transcriptomics Reveals the Crosstalk of CTHRC1+ CAF and MMP7+ Epithelial Axis as a Potential Therapeutic Target and Predicts Poor Clinical Outcomes in Colorectal Cancer.
Yang Y, Huang S, Zhou H … +2 more , Wang Y, Wu S
Mediators Inflamm · 2026 · PMID 41951422 · Full text
BACKGROUND: Colorectal cancer (CRC) progression is heavily influenced by the tumor microenvironment (TME), where cancer-associated fibroblasts (CAFs) are key players. However, the heterogeneity, plasticity, and functiona...
BACKGROUND: Colorectal cancer (CRC) progression is heavily influenced by the tumor microenvironment (TME), where cancer-associated fibroblasts (CAFs) are key players. However, the heterogeneity, plasticity, and functional roles of CAFs in CRC remain poorly understood. METHODS: We integrated single-cell RNA sequencing (scRNA-seq) data from four public CRC datasets and spatial transcriptomics data. Using computational approaches such as Harmony, Monocle2, and CellChat algorithms, we analyzed cellular landscapes, CAF subtype identification, developmental trajectories, transcription factor networks, and cell-cell communications to reveal CAF heterogeneity and their crosstalk with other cell subtypes in CRC. RESULTS: We identified eight distinct CAF subtypes with unique gene expression profiles and developmental plasticity. The CTHRC1+ CAF subtype was significantly associated with T cell exclusion and upregulated expression of immune checkpoint genes. We uncovered a specific communication axis between CTHRC1+ CAFs and MMP7+ malignant epithelial (Malig-Epi) cells mediated by the thrombospondin (THBS)2-SDC4 ligand-receptor signaling. High infiltration of both cell types synergistically correlates with worse prognosis and unfavorable response to immunotherapy. CONCLUSIONS: Our study delineates CAF heterogeneity in CRC and highlights the CTHRC1+ CAF subtype as a critical organizer of an immunosuppressive niche. The THBS2-SDC4 signaling pathway between CTHRC1+ CAFs and MMP7+ epithelial cells acts as a potential therapeutic target to disrupt protumorigenic crosstalk and improve clinical outcomes for CRC patients.
Pan-Immune-Inflammation Value: Related to Perforation Diameter and Pulmonary Artery Pressure in Ventricular Septal Rupture Patients.
Di X, Lin Z, Hou Q … +6 more , Chen T, Wang X, Chen C, Tang J, Liu Y, Zhao Y
Mediators Inflamm · 2026 · PMID 41948923 · Full text
OBJECTIVE: This study investigated the relationship between the pan-immune-inflammation value (PIV) and the perforation diameter in patients with ventricular septal rupture (VSR), as well as the changes in pulmonary arte...
OBJECTIVE: This study investigated the relationship between the pan-immune-inflammation value (PIV) and the perforation diameter in patients with ventricular septal rupture (VSR), as well as the changes in pulmonary artery systolic pressure (ΔPASP) after transcatheter closure. METHODS: The clinical data from 133 VSR patients who underwent transcatheter closure were analyzed. Patients were divided into high and low PIV groups based on a median cutoff value of 6. Boruta was used for exploratory variable screening; prespecified covariate sets were used for adjusted models. A generalized additive model (GAM) was used to explore the potential nonlinear relationships. Where a nonlinear association was suggested by the GAM, a piecewise linear regression model was subsequently fitted to precisely quantify the threshold effects and the differential associations of PIV/100 with ΔPASP and perforation diameter on either side of the identified inflection point. RESULTS: One hundred thirty-three patients with VSR (mean age 67 years, 50.6% female) were enrolled. Linear regression showed no statistically significant association between PIV/100 and ΔPASP. GAM suggested a possible nonlinear pattern between PIV/100 and ΔPASP (and perforation diameter). In piecewise models, an inverse association was observed above the break point, but this pattern was attenuated after multivariable adjustment and in sensitivity analyses. In discrimination analyses, adding PIV/100 to the baseline model yielded a modest numerical increase in AUC, but the incremental gain was not statistically significant. CONCLUSION: PIV may serve as an adjunct inflammatory marker in VSR patients undergoing transcatheter closure; however, the break point findings are exploratory and the incremental predictive value warrants validation in larger, independent cohorts with better adjudication of infection/systemic inflammation.
EZH2-Mediated Epigenetic Modifications Induce Pyroptosis in Dental Pulp Endothelial Cells via Activation of NLRP6 Inflammasome During Pulpitis Development.
Zhou W, Huang W, You H … +3 more , Huang Z, Zhou J, Huang Y
Mediators Inflamm · 2026 · PMID 41948911 · Full text
OBJECTIVES: Recent studies suggest that alleviating pyroptosis may be an effective strategy for treating inflammation. This research explores the changes in cellular composition and pyroptotic pathways in dental pulp tis...
OBJECTIVES: Recent studies suggest that alleviating pyroptosis may be an effective strategy for treating inflammation. This research explores the changes in cellular composition and pyroptotic pathways in dental pulp tissue during pulpitis and preliminarily validates the regulatory role of EZH2 in lipopolysaccharide (LPS)-induced pyroptosis of vascular endothelial cells (ECs) via NLRP6, aiming to provide a theoretical foundation for understanding pulpitis mechanisms. METHODS: Bioinformatics analysis of public single-cell RNA sequencing (scRNA-seq) and microarray data, together with RNA-seq of EZH2;Tie2-Cre pulp tissue, was performed to investigate the involvement of ECs and pyroptosis in pulpitis. Functional validation was conducted using an EZH2-inhibited inflammatory model and an NLRP6 knockdown model. RESULTS: Bioinformatics analysis revealed a strong association between pulpitis and EC pyroptosis. RNA-seq further demonstrated that EZH2 deficiency was associated with enhanced pyroptotic responses in ECs. In vitro, EZH2 inhibition or NLRP6 knockdown markedly attenuated LPS-induced inflammasome activation and pyroptosis in EOMA cells. This illustrates that the EZH2/NLRP6 axis plays a critical regulatory role in EC pyroptosis and suggests its potential as a therapeutic target in pulpitis. CONCLUSIONS: In summary, this study establishes ECs as key regulators in pulpitis inflammation, highlighting EZH2's role in modulating NLRP6 and the potential mechanism of pyroptosis in ECs.
The IRE1α Pathway Links Endoplasmic Reticulum Stress to Atherosclerosis-Related Inflammation and Lipid Accumulation.
Bagheri Ekta M, Elizova N, Antonov S … +2 more , Orekhov A, Sukhorukov V
Mediators Inflamm · 2026 · PMID 41948895 · Full text
Endoplasmic reticulum stress (ER stress) is closely related to the pathogenesis of atherosclerosis through various mechanisms, including inflammatory responses and foam cell formation. However, the mechanisms by which ER...
Endoplasmic reticulum stress (ER stress) is closely related to the pathogenesis of atherosclerosis through various mechanisms, including inflammatory responses and foam cell formation. However, the mechanisms by which ER stress contributes to atherosclerosis require further elucidation. In this study, we investigate the impact of the inositol-requiring enzyme 1 alpha (IRE1α) arm of the unfolded protein response (UPR) in the expression of inflammatory cytokines in monocytes and intracellular lipid accumulation in macrophages, which play a crucial role in the immune response associated with atherosclerosis. We created an IRE1α knockout (KO) THP-1 monocytic cell line using the CRISPR/Cas9 gene-editing technology and subsequently differentiated these cells into macrophages. We conducted a comparative analysis of IRE1α KO cells and control THP-1 cells, focusing on several parameters: morphological features, lipopolysaccharide (LPS)-induced proinflammatory cytokine responses, specifically interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF) α measured by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), as well as intracellular cholesterol accumulation and the expression levels of CD36 and ABCA1 genes following exposure to low-density lipoproteins (LDLs) derived from patients with atherosclerosis. Our findings demonstrate that IRE1α KO resulted in significant reduction of TNF, IL-1β, and IL-6 expression following LPS stimulation (p < 0.05). ELISA confirmed significantly reduced cytokine secretion in IRE1α KO monocytes compared to controls. Furthermore, IRE1α deficiency impaired the cellular response to atherogenic LDL, preventing lipid-induced upregulation of scavenger receptor CD36 and cholesterol efflux transporter ABCA1. Thus, IRE1α serves as a critical regulator of both inflammatory cytokine expression and lipid metabolism in THP-1 cells, highlighting its potential as a therapeutic target for inflammatory diseases and atherosclerosis. Targeting IRE1α could offer new strategies to address inflammation and lipid dysregulation in cardiovascular diseases.
Signaling Through SCFA Receptors Gpr43 and Gpr109a Drives Pro-Inflammatory M1 Macrophage Polarization in Periodontitis.
Liu K, Wang R, Kong L … +1 more , Ai L
Mediators Inflamm · 2026 · PMID 41948871 · Full text
BACKGROUND: This study investigated the link between an imbalance in microbiota-derived short-chain fatty acids (SCFAs) and dysregulated host immunity in periodontitis, focusing on the metabolic reprograming of inflammat...
BACKGROUND: This study investigated the link between an imbalance in microbiota-derived short-chain fatty acids (SCFAs) and dysregulated host immunity in periodontitis, focusing on the metabolic reprograming of inflammatory macrophages. METHODS: We conducted a systematic review and meta-analysis of SCFA levels. Bulk RNA sequencing (RNA-seq) data from human gingival tissue (n = 24) were analyzed for differential expression and pathway enrichment, with immune cell composition estimated by Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). Mouse single-cell RNA-seq (scRNA-seq) data were integrated, and myeloid cells (MCs) were subset for detailed clustering, differential analysis, and pseudotime trajectory reconstruction. RESULTS: Meta-analysis indicated a decreasing, though nonsignificant, trend in butyrate levels in periodontitis. Bulk RNA-seq identified 692 differentially expressed genes (DEGs) enriched in immune and cytokine signaling pathways. Immune deconvolution revealed an increased proportion of M1 macrophages and Tregs, alongside a decrease in M2 macrophages. Single-cell analysis confirmed the significant expansion of M1-like macrophages, which highly expressed SCFA receptors (Gpr43 and Gpr109a), inflammatory transcription factors (Nfkb1 and Hif1a), and effector molecules (Il1b). The pseudotime trajectory demonstrated a continuous M2-to-M1 polarization, marked by a decline in M2 markers and a rise in M1 markers. CONCLUSION: Periodontitis is characterized by SCFA metabolic imbalance and a shift in MCs toward a pro-inflammatory M1 state. The upregulation of SCFA receptors and the NF-κB/HIF-1 axis in M1 macrophages suggests an "SCFA receptor-metabolic sensing-inflammatory transcription" mechanism drives disease progression, providing a rationale for therapeutic strategies targeting this pathway.
The Inflammatory Nexus of Bronchopulmonary Dysplasia: From Molecular Pathways to Precision Therapeutics.
Wang F, Zhang H, Jiang O … +1 more , Mi H
Mediators Inflamm · 2026 · PMID 41948847 · Full text
Bronchopulmonary dysplasia (BPD) is a common and serious complication among preterm infants, particularly those born at extremely low gestational ages. It is primarily characterized by impaired alveolar and vascular deve...
Bronchopulmonary dysplasia (BPD) is a common and serious complication among preterm infants, particularly those born at extremely low gestational ages. It is primarily characterized by impaired alveolar and vascular development. Inflammation is increasingly recognized as a central mechanism in its pathogenesis. Both prenatal factors, such as intrauterine infection, and postnatal insults, including mechanical ventilation, oxygen toxicity, and infection, can trigger and sustain a dysregulated inflammatory response in the immature lung. This response involves the activation of inflammatory cells, such as neutrophils and macrophages, and the release of pro-inflammatory mediators, reactive oxygen species (ROS), and proteases. These factors disrupt critical developmental signaling pathways and contribute to alveolar simplification and abnormal vascular growth, which are the hallmark features of BPD. Current therapeutic strategies aim to limit these inflammatory processes and support lung development. Established interventions like caffeine and corticosteroids have demonstrated varying levels of effectiveness and safety. Emerging therapies-including anti-cytokine agents, inflammasome inhibitors, and stem cell-based approaches-offer promising avenues by specifically targeting the inflammatory cascade. Additionally, supportive strategies such as non-invasive ventilation, careful oxygen titration, and optimal nutrition play essential roles in reducing initial injury and facilitating recovery. Inflammation is a key mediator linking diverse perinatal insults to the disrupted lung development seen in BPD. A deeper understanding of the inflammatory mechanisms and timely, targeted interventions may offer improved outcomes for this vulnerable population.
Correction to "Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron-Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro".
Mediators Inflamm · 2026 · PMID 41947728 · Full text
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Investigating the Role of TNFSF12 in Thyroid Cancer Progression via Single-Cell RNA Sequencing and Integrated Multiomics Analyses.
Yu J, Li J, Gao S … +2 more , Wang L, Qiao H
Mediators Inflamm · 2026 · PMID 41930700 · Full text
BACKGROUND: Thyroid carcinoma is characterized by significant heterogeneity and immune evasion, in which myeloid cells play a pivotal role in tumor microenvironment (TME) remodeling. However, the key regulatory genes and...
BACKGROUND: Thyroid carcinoma is characterized by significant heterogeneity and immune evasion, in which myeloid cells play a pivotal role in tumor microenvironment (TME) remodeling. However, the key regulatory genes and their underlying mechanisms are not yet fully elucidated. OBJECTIVE: This study aims to identify and validate critical myeloid-derived genes involved in driving thyroid cancer progression by employing an integrated multiomics approach. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on thyroid cancer tissues, integrated with High-dimensional weighted gene co-expression network analysis (hdWGCNA) for coexpression module identification, Mendelian randomization (MR) for causal inference, and functional validation assays in thyroid carcinoma cell lines including qPCR, CCK-8, colony formation, and transwell assays. Microbial correlation analysis and molecular docking were additionally conducted to explore potential interactions. RESULTS: We identified a tumor-specific myeloid subpopulation (C5) and a disease-associated coexpression module harboring three hub genes: MERTK, MSR1, and TNFSF12. MR analysis confirmed MERTK and MSR1 as genetic risk factors for thyroid cancer progression, whereas TNFSF12 exhibited protective effects. Functional experiments demonstrated that TNFSF12 enhances proliferative, invasive, and migratory capacities in thyroid cancer cells. Furthermore, MSR1 and MERTK were found to be significantly correlated with specific intratumoral microbiota and associated with BRAF mutation and response to immunotherapy. CONCLUSION: Our study reveals a myeloid-centered regulatory network in thyroid cancer and highlights TNFSF12 as a context-dependent oncogene, offering novel insights into targeted therapy and immunotherapeutic strategies.
Trends and Prospects in Inflammation Resolution in Acute Lung Injury and Acute Respiratory Distress Syndrome: A Bibliometric Quantitative and Visualization Analysis.
Luo Z, Huang N, Luo K … +3 more , Wang C, Li J, Zou K
Mediators Inflamm · 2026 · PMID 41923487 · Full text
BACKGROUND: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are common and critical pulmonary conditions involving numerous inflammatory factors and oxidative stress responses. Inflammatory responses...
BACKGROUND: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are common and critical pulmonary conditions involving numerous inflammatory factors and oxidative stress responses. Inflammatory responses and oxidative stress are closely related to the development of ALI/ARDS and form an important theoretical basis for treatment and drug development. Although there has been extensive research on the resolution of inflammation in ALI/ARDS, no systematic bibliometric analysis has been conducted in this field. METHODS: The researchers used bibliometrics to search the Web of Science Core Collection (WOSCC) database for research literature on the resolution of inflammation in ALI/ARDS from 2005 to 2024. Visualization mapping analysis was performed using tools such as CiteSpace and VOSviewer to analyze authors, research institutions, countries, journals, cocited literature, and keywords. RESULTS: A total of 375 articles were included. The research showed an upward trend, with the highest number of publications in 2022. The United States took the leading position in this field, followed by China. JIN SW had the highest number of publications, while D'Alessio FR had the highest citation count. Harvard University had the highest intermediary centrality, the American Journal of Physiology-Lung Cellular and Molecular Physiology published the most articles, and the American Journal of Respiratory and Critical Care Medicine had the highest impact factor. Resolvin D1 (RvD1) and Resolvin E1 (RvE1) played a key role in the resolution of inflammation. Drug delivery systems (DDSs), such as black phosphorus nanosheets (BPNSs) and liposomes, could efficiently deliver these mediators to enhance therapeutic effects and reduce side effects. CONCLUSION: Over the past 20 years, interest in the resolution of inflammation in ALI/ARDS has grown. The United States has dominated research in this area. The study of RvD1 and RvE1 has become a hot topic, and the development of DDSs has provided new strategies for clinical treatment.
Electroacupuncture Ameliorates Cyclophosphamide-Induced Ovarian Impairment in Rats With Diminished Ovarian Reserve and is Associated With Th17/Treg-Related Immune Modulation.
Zhang X, Lin Z, Liu R … +3 more , Guo Z, Wang K, Ma Y
Mediators Inflamm · 2026 · PMID 41902667 · Full text
BACKGROUND: Diminished ovarian reserve (DOR) is a major challenge in reproductive medicine, especially with delayed childbearing. Current treatments show limited efficacy and side effects. Electroacupuncture (EA), a mult...
BACKGROUND: Diminished ovarian reserve (DOR) is a major challenge in reproductive medicine, especially with delayed childbearing. Current treatments show limited efficacy and side effects. Electroacupuncture (EA), a multitarget nonpharmacological therapy, may protect ovarian function and regulate immune balance. OBJECTIVES: This study investigated the protective effects of EA and its potential mechanisms in cyclophosphamide (CTX)-induced DOR in rats, with a focus on apoptosis-related changes in granulosa cells and T helper 17 (Th17)/regulatory T (Treg)-related immune modulation. METHODS: A CTX-induced DOR rat model was treated with EA at CV4 (Guanyuan) and CV6 (Qihai), with sham EA and normal groups as controls. Estrous cycle, ovarian indices, serum hormones, and cytokines were assessed. Ovarian morphology, follicle counts, apoptosis, and protein expression were evaluated by histology, TUNEL, western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Splenic Treg/Th17 cells were analyzed by flow cytometry, and RNA sequencing identified EA-regulated pathways. RESULTS: EA improved estrous cyclicity, ovarian morphology, and follicular development; improved follicle-associated marker expression; and reduced elevated FSH and LH levels in CTX-induced DOR rats. AMH and E2 showed upward trends after EA treatment, but these changes did not reach statistical significance. EA reduced TUNEL positivity, restored Ki67 expression, and favorably regulated the Bcl-2/Bax axis, while cleaved caspase-3 remained elevated and was not significantly altered. EA was also associated with normalization of Th17/Treg-related immune indices in the spleen, serum, and ovary, including reduced IL-6, IL-17A, IL-1β, TNF-α, and RORγt, and increased FOXP3, IL-10, and TGF-β1. Transcriptomic analysis revealed enrichment of immune-related pathways, consistent with the functional findings. CONCLUSION: EA ameliorated CTX-induced ovarian injury and was associated with improved follicular development, attenuation of apoptosis-related changes, and Th17/Treg-related immune modulation. These findings support a potential ovarian-protective and immunoregulatory role of EA in DOR, although further studies are required to verify endocrine efficacy and mechanistic causality.
Analysis of Autophagy-Related Gene Signature Associated With Clinical Prognosis and Immune Microenvironment in Colorectal Cancer.
Miao D, Song Y, Zhou L … +9 more , Liang G, Wang Y, He W, Huang L, Lu H, Jiang S, Jia Y, Li Z, Tong J
Mediators Inflamm · 2026 · PMID 41902657 · Full text
BACKGROUND: Autophagy has a critical involvement in the initiation and progression of various cancers, including colorectal cancer (CRC). The feasibility of using autophagy-related genes (ATGs) as prognostic tools for CR...
BACKGROUND: Autophagy has a critical involvement in the initiation and progression of various cancers, including colorectal cancer (CRC). The feasibility of using autophagy-related genes (ATGs) as prognostic tools for CRC patients is yet to be determined. METHODS: RNA sequencing data and clinical information for CRC were obtained from The Cancer Genome Atlas (TCGA) (training set) and Gene Expression Omnibus (GEO) datasets GSE39582 and GSE44076 (validation). ARGs were retrieved from the Human Autophagy Database, and differentially expressed ARGs (DAGs) were identified using the "limma" R package. Prognostic signature DAGs were established via univariate Cox and LASSO Cox regression analyses. The obtained signature was validated through expression analysis, autophagy scoring, survival prediction, and correlation with immune status. Immunohistochemistry assays and in vitro functional experiments in SW480 cells were performed to assess the biological roles of selected DAGs, particularly WIPI2. RESULTS: We constructed an 11-gene prognostic signature (CANX, NRG1, WIPI1, EIF2AK3, WDR45, PELP1, ULK1, WIPI2, DAPK1, ULK3, and MAP1LC3C), with high-risk patients showing significantly reduced overall survival compared to low-risk patients. WIPI2, highly expressed in SW480 cells, was selected for functional validation. Knockdown of WIPI2 inhibited cell proliferation, suppressed autophagy (decreased LC3B-II, increased p62), and promoted apoptosis (increased cleaved caspase-3). These findings confirm the pro-survival role of WIPI2 in CRC. The prognostic signature remained independently predictive after adjusting for clinical factors and showed a strong correlation with immune infiltration in TCGA CRC samples. CONCLUSION: The autophagy-related signature independently predicts CRC prognosis and guides immunotherapy strategies.
Associations of Inflammatory Prognosis Index With All-Cause and Cardiovascular Mortality Among Individuals With Diabetes and Prediabetes: A Retrospective Cohort Study.
Liu L, Alifu J, Mohammed AQ … +3 more , Yin G, Abdu FA, Che W
Mediators Inflamm · 2026 · PMID 41902433 · Full text
BACKGROUND: The systemic immune-inflammatory index (SII) and the systemic inflammatory response index (SIRI) have shown prognostic value in diabetes mellitus (DM). However, the impact of the inflammatory prognosis index...
BACKGROUND: The systemic immune-inflammatory index (SII) and the systemic inflammatory response index (SIRI) have shown prognostic value in diabetes mellitus (DM). However, the impact of the inflammatory prognosis index (IPI) remains unexamined. This retrospective cohort study investigates the predictive value of IPI, along with SIRI and SII, on all-cause and cardiovascular disease (CVD) mortality in individuals with DM and prediabetes mellitus (pre-DM). METHOD: We analyzed DM and pre-DM individuals from the National Health and Nutrition Examination Survey (NHANES) (1999-2018), with follow-up conducted until December 31, 2019. Cox models assessed the correlation of IPI, SIRI, and SII with mortalities, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). We also utilized restricted cubic spline (RCS) analysis, Kaplan-Meier curves, and subgroup analyses. RESULTS: The final analysis included 10,049 individuals with DM and pre-DM. Over a mean follow-up of 9 years, 2233 all-cause mortalities occurred, with 612 attributed to CVD. Fully adjusted Cox regression analysis revealed a significant correlation between continuous and higher tertiles (T3) of IPI, SIRI, and SII and increased risk of all-cause and CVD mortality across all models (all p < 0.05). Kaplan-Meier curves showed higher IPI, SIRI, and SII associated with elevated mortality risk (all log-rank p < 0.001). RCS analysis demonstrated a nonlinear correlation between IPI and all-cause and CVD mortality, as well as between SII and all-cause mortality (nonlinear p < 0.001). However, SIRI exhibited a linear association with both all-cause and CVD mortality. CONCLUSION: Elevated IPI, along with SIRI and SII, is linked to increased all-cause and CVD-related mortality in DM and pre-DM, suggesting that incorporating IPI in routine screening could help identify high-risk individuals for earlier interventions.
Orientin Mitigates High Glucose/Ox-LDL-Triggered Endothelial Cell Injury and Atherosclerosis by Regulating MARCH8-Mediated NLRP3 Inflammasome Activation.
Li Q, Gao M, Zhong N … +8 more , Zhang LR, Zhu MD, Ge WJ, Wang QZ, Chen X, Zhang L, Song FC, Lu HZ
Mediators Inflamm · 2026 · PMID 41891145 · Full text
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on...
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE mice were administered streptozotocin (STZ), fed with high-fat diet (HFD), and then treated with Orientin to test the efficacy of Orientin on ameliorating atherosclerosis through pathological and biochemical assays. Human aortic endothelial cells (HAECs) were stimulated by ox-LDL/HG followed by Orientin treatment, and the effects of Orientin on regulating HAEC viability, oxidative stress, inflammation, and endothelial-mesenchymal transition (EndMT) were assessed using cell counting kit-8 (CCK-8), fluorescein diacetate (FDA) staining, quantitative real-time PCR, immunofluorescence (IF), and western blot assays. The results showed that Orientin treatment decreased atherosclerotic plaque burden, lipid lesion, and collagen content in aortic and femoral arteries in diabetic mice. Meanwhile, Orientin alleviated hypercholesterolemia, as evidenced by decreased levels of total cholesterol, LDL-cholesterol, and triglyceride. In HAECs, Orientin treatment increased cell viability and decreased inflammation, oxidative stress, and EndMT induced by ox-LDL/HG. Furthermore, Orientin significantly inhibited reactive oxygen species (ROS)-triggered NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis, as suggested by cleavage of caspase-1 and gasdermin-D (GSDMD), generation of interleukin (IL)-18 and IL-1β, and lactate dehydrogenase (LDH) release. Mechanistically, Orientin increased E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) expression in HAECs and resulted in subsequent MARCH8-mediated ubiquitination and proteasomal degradation of the NLRP3 protein. Taken together, these data demonstrate that Orientin, which alleviates HAEC inflammation and pyroptosis through regulating the MARCH8/NLRP3 axis, might be a potential candidate for treating diabetes-accelerated atherosclerosis.
Maresin 1 Ameliorates Diabetic Kidney Disease in Mice by Promoting Macrophage M2 Polarization.
Pu Y, Ma X, Geng K … +6 more , Meng R, Li Y, Zheng C, Zhao C, Teng F, Xu Y
Mediators Inflamm · 2026 · PMID 41887186 · Full text
BACKGROUND: The progression of diabetic kidney disease (DKD) is strongly associated with a chronic inflammatory microenvironment, with macrophage polarization imbalance recognized as a pivotal driver. Maresin 1 (MaR1), a...
BACKGROUND: The progression of diabetic kidney disease (DKD) is strongly associated with a chronic inflammatory microenvironment, with macrophage polarization imbalance recognized as a pivotal driver. Maresin 1 (MaR1), a specialized proresolving lipid mediator, plays a crucial role in restoring immune homeostasis across various inflammatory conditions. However, its precise role in ameliorating kidney injury through macrophage polarization in DKD remains unclear. METHODS: The type 2 diabetes mouse model was established using a high-fat diet combined with streptozotocin induction. The therapeutic efficacy of MaR1 was assessed by evaluating metabolic parameters (blood glucose, lipid profile), renal function (urine albumin-to-creatinine ratio [ACR], serum creatinine, and blood urea nitrogen [BUN]), and renal pathology (HE staining and Masson staining). In vitro, bone marrow-derived macrophages (BMDMs) were exposed to high glucose, and the modulatory effect of MaR1 on M1/M2 polarization was assessed using RT-qPCR, immunohistochemistry, and immunofluorescence. RESULTS: MaR1 treatment significantly ameliorated metabolic abnormalities in diabetic mice (lower blood glucose and cholesterol), improved renal function (reduced ACR, serum creatinine, and BUN), and attenuated renal fibrosis (all p < 0.05). Mechanistically, MaR1 reversed macrophage polarization imbalance both in vivo and in vitro, promoting a shift from the M1 phenotype (downregulation of iNOS and TNF-α) to the M2 phenotype (upregulation of Arg-1 and IL-10). CONCLUSION: MaR1 improves metabolic disturbances and renal injury in DKD by driving macrophage polarization toward the M2 phenotype and restoring immune homeostasis. These findings highlight MaR1 as a promising candidate for targeted immunomodulatory therapies in DKD.
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