Mediators Of Inflammation[JOURNAL]
Sun
200 papers
Elevated Inflammatory Burden Index Is Association With Increased Sarcopenia: A Population-Based Study.
Xiao L, Li Y, Li X … +6 more , Luo Z, Wang C, Liu S, Huang N, Wang M, Zou K
Mediators Inflamm · 2026 · PMID 41886359 · Full text
BACKGROUND: The inflammatory burden index (IBI) is a comprehensive indicator of the inflammatory state of the body and is associated with a variety of chronic diseases. Sarcopenia is a disease characterized by a reductio...
BACKGROUND: The inflammatory burden index (IBI) is a comprehensive indicator of the inflammatory state of the body and is associated with a variety of chronic diseases. Sarcopenia is a disease characterized by a reduction in skeletal muscle mass, but the association between IBI and sarcopenia is currently unclear. METHODS: This study was based on data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 and included 4523 participants aged 20 years and older. IBI was calculated by the product of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR). Sarcopenia was defined by the extremity skeletal muscle mass index (ASM/body mass index [BMI]). The association between IBI and sarcopenia was analyzed using multivariate logistic regression models with nonlinear and subgroup analyses. RESULTS: The mean age of the participants was 39.9 years, and 52.5% were female. Higher IBI scores were associated with a higher risk of chronic disease. IBI was positively associated with sarcopenia, with the highest IBI group having a 1.94 times greater risk of sarcopenia than the lowest group (95% CI: 1.34-2.81). The natural log transformation of IBI resulted in a 42% increase in risk of sarcopenia for each unit increase (95% CI: 1.08-1.87). Nonlinear analyses showed an inflection point in the association between IBI and sarcopenia at 2.38, with a significant increase in risk before the inflection point and no longer significant after the inflection point. Subgroup analyses showed that this association was consistent across sex, age, diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD). CONCLUSION: There is a positive association between IBI and sarcopenia with nonlinear characteristics. High IBI levels may increase the risk of sarcopenia, suggesting that inflammation may play an important role in sarcopenia, providing a potential target for future interventions.
Anti-Inflammatory Effects of Stachys pilifera Extracts in LPS-Stimulated RAW264.7 Macrophages.
Salehpour Z, Fazeli M, Barati E
Mediators Inflamm · 2026 · PMID 41885707 · Full text
OBJECTIVE: Inflammation is a fundamental biological response that serves to protect the body from physical damage and harmful stimuli. However, chronic inflammation is implicated in the pathogenesis of various inflammato...
OBJECTIVE: Inflammation is a fundamental biological response that serves to protect the body from physical damage and harmful stimuli. However, chronic inflammation is implicated in the pathogenesis of various inflammatory diseases. Stachys pilifera Benth. has been traditionally used for its anti-inflammatory properties, yet its precise mechanisms of action remain to be fully elucidated. This study aims to investigate the effects of S. pilifera Benth. extract and its fractions on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells. METHODOLOGY: The anti-inflammatory potential of the methanolic extract and its ethyl acetate, butanol, and water fractions were evaluated by assessing their inhibitory effects on nitric oxide (NO) and prostaglandin E2 (PGE) production. Additionally, nuclear factor-κB (NF-κB) concentration and cyclooxygenase-2 (COX-2) gene expression were analyzed in LPS-stimulated macrophage cells. RESULTS: The methanolic extract, ethyl acetate fraction, and butanol fraction significantly reduced the production of NO and PGE, decreased NF-κB concentration, and suppressed COX-2 mRNA expression in a dose-dependent manner. The butanol fraction exhibited the most potent inhibition of NO production (IC = 37.38 ± 10.27 µg/mL), whereas the ethyl acetate fraction was the strongest suppression of PGE synthesis (IC = 86.32 ± 5.51 µg/mL). In contrast, the water fraction did not have a significant effect on these inflammatory markers. CONCLUSION: By downregulating NF-κB activity, S. pilifera Benth. effectively modulates the expression of key proinflammatory mediators, including inducible NO synthase (iNOS) and COX-2, ultimately leading to reduced NO and PGE production. These findings suggest that S. pilifera Benth. may exert its anti-inflammatory effects through inhibition of the NF-κB signaling pathway, offering potential therapeutic applications in the management of chronic inflammatory diseases.
RETRACTION: 5'-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response.
Inflammation MO
Mediators Inflamm · 2026 · PMID 41880221 · Full text
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METTL3/m6A-Dependent SERPINE1/VEGFA Axis Mediates Sublethal Heat-Induced Angiogenesis in Hepatocellular Carcinoma.
Fan Z, Gao Y, Wan J … +4 more , Zhu Y, Li M, Chen X, Yang G
Mediators Inflamm · 2026 · PMID 41873638 · Full text
Heat ablation techniques, such as microwave and radiofrequency ablation, are established interventions for hepatocellular carcinoma (HCC). However, incomplete ablation often leads to angiogenesis-driven metastasis and re...
Heat ablation techniques, such as microwave and radiofrequency ablation, are established interventions for hepatocellular carcinoma (HCC). However, incomplete ablation often leads to angiogenesis-driven metastasis and recurrence, undermining long-term treatment efficacy. The molecular mechanisms facilitating post-ablation angiogenesis remain poorly understood. In this study, we identified a marked upregulation of SERPINE1 following sublethal heat treatment, which was corroborated in both rabbit models and human HCC cell lines. Further investigation revealed that SERPINE1 promotes angiogenesis, at least in part, through vascular endothelial growth factor A (VEGFA) activation after sublethal heat exposure. We further delineated that METTL3 and IGF2BP1 regulate SERPINE1 expression via an N6-methyladenosine (m6A)-dependent pathway. The proangiogenic role of SERPINE1 was substantiated using patient-derived HCC organoids and in vivo models, where the small-molecule inhibitor PAI-039 significantly attenuated sublethal heat ablation-induced angiogenesis and tumor proliferation. Our findings illuminate the METTL3/IGF2BP1/SERPINE1/VEGFA axis as a novel therapeutic target for improving HCC heat ablation outcomes. Therapeutically, PAI-039 emerges as a potent adjunctive agent that could synergistically enhance the efficacy of thermal ablation in HCC management.
The Effects of In Utero HIV and Antiretroviral Therapy Exposure on Infant T-Cell and Monocyte Activation, Function, and Regulation of Immune-Modulatory Pathways.
Prinsloo A, Steel HC, Feucht U … +1 more , Rossouw TM
Mediators Inflamm · 2026 · PMID 41873528 · Full text
Human immunodeficiency virus (HIV) infection is characterized by chronic, systemic immune activation. It is unclear how this affects the immune system of infants born to mothers living with HIV (MLWH). The current study...
Human immunodeficiency virus (HIV) infection is characterized by chronic, systemic immune activation. It is unclear how this affects the immune system of infants born to mothers living with HIV (MLWH). The current study assessed whether maternal HIV status and in utero antiretroviral therapy (ART) exposure impact infant T-cell and monocyte activation and regulation, as well as monocyte responsiveness to stimulation at birth and early infancy. T-cell and monocyte activation and expression of immune checkpoint molecules were characterized by means of flow cytometry. Pro- and anti-inflammatory cytokine/chemokine profiles were assessed using a suspension bead array assay. Seventy-one pregnant MLWH and 77 mothers not living with HIV (MNLWH) were recruited at 22 weeks' gestation, and mother-infant pairs were followed until 6 months postpartum. MLWH had higher percentages of CD4+ and CD8+ T-cells expressing programmed cell death protein-1 (PD-1) and a higher percentage of regulatory T-cells (Tregs). HIV-exposed-but-uninfected (HEU) infants displayed disrupted CD4+ T-cell maturation with an increased number of CD8+ T-cells expressing PD-1 at the time of birth and increased T-cell exhaustion at 10 weeks of age. Higher levels of monocyte activation were observed in MLWH with increased numbers of classical (CL) monocytes expressing CCR2 and CD80. An increased percentage of CL monocytes expressing CCR2 and CD80 was noted in HEU infants at the time of birth, which persisted at 10 weeks of age. Significantly higher levels of C-reactive protein (CRP) and non-significantly higher levels of interleukin (IL)-6 and tumor necrosis factor-alpha were observed in MLWH, indicative of hyperactivated innate inflammation. HEU infants had persistently increased levels of IL-8 and transforming growth factor (TGF)-β1, and lower levels of IL-10, IFN-γ, and CRP. The latter might be secondary to cotrimoxazole use in the HEU infants while the altered cytokine levels might be indicative of altered immune programing. In summary, this cohort study showed that maternal HIV status has a transient effect on basal infant T-cell and monocyte activation, regulation, and monocyte responsiveness, which dissipates at 6 months of age, while altered cytokine levels persisted.
FOS Knockdown Alleviates Helicobacter pylori-Infected Gastritis by Suppressing Mast Cell Activation and Treg Polarization.
Ma W, Han R, Wang L
Mediators Inflamm · 2026 · PMID 41872444 · Full text
BACKGROUND: Helicobacter pylori (HP) is a major cause of gastritis, yet the epithelial mechanisms linking infection-induced stress to mast cell and Treg responses remain poorly defined. METHODS: Three datasets (GSE5081,...
BACKGROUND: Helicobacter pylori (HP) is a major cause of gastritis, yet the epithelial mechanisms linking infection-induced stress to mast cell and Treg responses remain poorly defined. METHODS: Three datasets (GSE5081, GSE27411, and GSE233973) were integrated and analyzed using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. Mast cell-related hub gene expressions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), and inflammatory cytokines were quantified using the enzyme-linked immunosorbent assay (ELISA). Histopathological changes were evaluated using hematoxylin and eosin (HE), Giemsa, and Warthin-Starry silver staining. Cell apoptosis was assessed by flow cytometry, and mast cell and Treg cell activities were analyzed by Transwell assays, histamine detection, and immunohistochemistry (IHC). RESULTS: Fos proto-oncogene (FOS), ribonucleotide reductase regulatory subunit M2 (RRM2), and RAD51 recombinase (RAD51) were identified as mast cell-related hub genes, all of which were upregulated in HP-induced gastritis mice. In vitro, HP infection or CagA stimulation increased FOS expression in gastric epithelial cells. FOS knockdown in HP-infected mice alleviated gastric mucosal injury, reduced bacterial burden, and decreased pro-inflammatory cytokine levels. FOS silencing enhanced GES-1 cell viability and suppressed apoptosis. In HP-infected GES-1 cells, FOS silencing inhibited mast cell migration, cytokine secretion, including C-C motif chemokine ligand 2 (CCL2), interleukin-33 (IL-33), and stem cell factor (SCF), as well as histamine release, accompanied by reduced Treg polarization and decreased expression of transforming growth factor-β and forkhead box P3. CONCLUSION: FOS silencing inhibited mast cell activation and Treg cell polarization in HP-induced gastritis, suggesting its promising value as an intervention point in HP-driven gastritis.
LY294002 and LiCl Mitigate Neonatal ExPEC Meningitis Through Akt/GSK3β Signaling Modulation.
Zou P, Xiao R, Sheng S … +5 more , Zhang P, Huang P, Du Y, Chen Y, Wang Y
Mediators Inflamm · 2026 · PMID 41870387 · Full text
BACKGROUND: Neonatal purulent meningitis (NPM) is a life-threatening condition associated with high mortality rates and a substantial risk of severe long-term neurological sequelae among survivors. Extraintestinal pathog...
BACKGROUND: Neonatal purulent meningitis (NPM) is a life-threatening condition associated with high mortality rates and a substantial risk of severe long-term neurological sequelae among survivors. Extraintestinal pathogenic Escherichia coli (ExPEC) is the predominant causative agent of NPM and exhibits multidrug resistance. Targeting host signaling pathways is a promising therapeutic approach. In this study, we aimed to evaluate the therapeutic potential of LY294002 (a PI3K/Akt inhibitor) and lithium chloride (LiCl) (a GSK3β inhibitor) in a neonatal mouse model of ExPEC meningitis. METHODS: Neonatal mice were infected with clinical ExPEC isolates to induce meningitis. LY294002 or LiCl was administered as an intervention. Brain bacterial load was quantified via culture, while inflammation was assessed using RT-qPCR to evaluate the expression of inflammatory cytokines; hematoxylin-eosin (HE) staining was also performed. The expression and localization of tight junction (TJ) proteins were analyzed using immunohistochemistry, and western blotting was used to quantify TJ proteins and key signaling molecules, including Akt, phosphorylated Akt (p-Akt Ser473), GSK3β, and phosphorylated GSK3β (p-GSK3β Ser9). RESULTS: ExPEC colonization in the brain tissue was confirmed via bacterial culture. Early intervention with LiCl significantly reduced bacterial load. HE staining revealed meningeal thickening in infected mice, which was alleviated by both LY294002 and LiCl treatments. Western blotting and immunohistochemistry consistently demonstrated a marked reduction in the expression of TJ proteins following ExPEC infection, and their levels were substantially restored by both the interventions. These protective effects were associated with the modulation of the Akt/GSK3β signaling pathway. CONCLUSION: LY294002 and LiCl reduced neuroinflammation and preserved the blood-brain barrier (BBB) integrity in the neonatal ExPEC meningitis model, likely via modulation of the Akt/GSK3β pathway. These results underscore the potential of this pathway as a therapeutic target and provide a basis for further preclinical investigation.
Circulating Platelet-Neutrophil Aggregates as Novel Biomarker for Coagulopathy Diagnosis and Disseminated Intravascular Coagulation Prediction in Sepsis.
Dai T, Liang S, Li B … +7 more , Zhao H, Su Y, Liu Y, Liang C, Yue X, Wang H, Wu J
Mediators Inflamm · 2026 · PMID 41869834 · Full text
BACKGROUND: Platelet-leukocyte aggregates (PLAs) drive immunothrombosis by promoting leukocyte activation and tissue factor release in sepsis. However, their utility as early predictors of sepsis-induced coagulopathy (SI...
BACKGROUND: Platelet-leukocyte aggregates (PLAs) drive immunothrombosis by promoting leukocyte activation and tissue factor release in sepsis. However, their utility as early predictors of sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) remains unestablished. This study aimed to develop and validate a PLA-based model for SIC diagnosis and DIC prediction. METHODS: A prospective prediction study was conducted with 101 sepsis patients in Beijing Jishuitan Hospital between May 2024 and May 2025. Percentage and mean fluorescence intensity (MFI) of different subtypes of PLAs were measured by flow cytometry. Receiver operating characteristic (ROC) curves and Cox regression were performed, assessing the performance of PLAs to diagnose SIC and predict DIC. RESULTS: Platelet-neutrophil aggregate MFI (PNA-MFI) demonstrated excellent diagnostic accuracy for SIC (p < 0.001, AUC = 0.789, 95% CI: 0.699-0.880, cut-off value = 2797, sensitivity = 76.2%, specificity = 78.0%, negative predictive value (NPV) = 83.9%, and positive predictive value (PPV) = 68.8%) and superior DIC prediction (p < 0.001, AUC = 0.781, 95% CI: 0.680-0.883, cut-off value = 2621, sensitivity = 83.3%, specificity = 64.9%, NPV = 92.6%, and PPV = 42.6%). Kaplan-Meier analysis showed that high PNA-MFI patients (PNA-MFI ≥ 2621) were more likely to develop DIC (log-rank p < 0.001, hazard ratio: 6.80 [high PNA-MFI/low PNA-MFI], and 95% CI:2.97-15.61). CONCLUSION: PNA-MFI is a promising biomarker for SIC diagnosis and DIC prediction. While internally validated, external validation is essential prior to clinical implementation, and further multicenter studies are warranted to definitively establish its clinical value.
Low PTGDS Expression Facilitates HNSCC by Suppressing Programmed Cell Death and Reducing B Cell-Mediated Immune Responses.
Tao D, Zhong Y, Zhu H … +1 more , Zhang Z
Mediators Inflamm · 2026 · PMID 41866775 · Full text
Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global disease burden. Evasion of programmed cell death (PCD) is a hallmark of HNSCC progression. Cancer-associated fibroblasts (CAFs) are a major c...
Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global disease burden. Evasion of programmed cell death (PCD) is a hallmark of HNSCC progression. Cancer-associated fibroblasts (CAFs) are a major cellular component of the HNSCC tumor microenvironment (TME). However, the mechanism by which CAFs contribute to PCD resistance remains poorly understood. This study included 24 single-cell sequencing samples, the Cancer Genome Atlas (TCGA) data, and spatial transcriptome data from HNSCC samples. Single-cell data were clustered using the Seurat package, and pseudotemporal trajectory analysis of CAF subsets was performed with Monocle2. The random forest algorithm was used to assess the prognostic importance of candidate genes. The ssGSEA and CIBERSORT algorithms were used to assess immune cell infiltration patterns in the TCGA samples. Gain-of-function assays, Western blotting, and immunohistochemistry were conducted to validate the biological functions of key targets. Here, we identified seven CAF subsets and clarified their potential differentiation directions. Thirty-two CAF-associated PCD regulators with prognostic significance were identified, among which, prostaglandin D2 synthase (PTGDS) and squalene epoxidase (SQLE) are the most important genes. PTGDS is significantly downregulated in HNSCC and associated with favorable prognosis. PTGDS overexpression significantly inhibited clonogenicity, proliferation, and invasion while promoting apoptosis in HNSCC cells (p < 0.05). In addition, PTGDS expression is significantly enriched in B cell-related pathways. Mechanistically, PTGDS overexpression increased chemokine (C-X-C motif) ligand 13 (CXCL13) expression and enhanced immune cell infiltration. These findings identified PTGDS as a central regulator linking CAF-mediated PCD resistance and B cell immune modulation in HNSCC, suggesting its potential as both a diagnostic biomarker and therapeutic target.
Hsa_circ_0000313/miR-1224-3p/MKNK2 Axis Modulates CD4 T Cells by Activating p38 MAPK Signaling in Myasthenia Gravis.
Li Y, Kong X, Cai H … +9 more , Tian W, Ren Y, Xu F, Peng S, Niu J, Xin G, Wang J, Zhang H, Wang L
Mediators Inflamm · 2026 · PMID 41860006 · Full text
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder in which circular RNAs (circRNAs) are increasingly implicated, with growing evidence supporting their critical role in autoimmune pathogenesis. The role of hsa...
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder in which circular RNAs (circRNAs) are increasingly implicated, with growing evidence supporting their critical role in autoimmune pathogenesis. The role of hsa_circ_0000313 in MG, including its biological functions and mechanisms, remains unknown. METHODS: Agarose gel electrophoresis, RNase R digestion, and Sanger sequencing were employed to verify the circular structure of hsa_circ_0000313, while nucleoplasmic separation experiment was used to determine its subcellular localization. Analysis of hsa_circ_0000313, miR-1224-3p, and MKNK2 expression was conducted via quantitative real-time PCR (qRT-PCR). CCK-8 assay and flow cytometry were employed to evaluate the proliferative capacity and apoptotic rate of Jurkat cells. ELISA detected inflammatory cytokine secretion. Potential interactions involving miR-1224-3p with either hsa_circ_0000313 or MKNK2 were predicted using bioinformatics tools and subsequently validated through dual-luciferase reporter assays. FISH assay was used to detect subcellular colocalization of hsa_circ_0000313 and miR-1224-3p. RESULTS: We observed that compared to healthy controls, MG patients exhibited increased expression of hsa_circ_0000313 and MKNK2, along with decreased expression of miR-1224-3p. Knockdown of hsa_circ_0000313 and MKNK2, along with overexpression of miR-1224-3p, inhibited the proliferation and secretion of inflammatory factors in Jurkat cells and promoted their apoptosis. Additionally, miR-144-3p was identified as the target miRNA of hsa_circ_0000313, and MKNK2 was identified as the target gene of miR-1244-3p. Hsa_circ_AA0000313 was confirmed to be circular and resistant to RNase R digestion. There was significant colocalization of hsa_circ_0000313 with miR-1224-3p within the cytoplasm. Inhibition of miR-1244-3p reversed the effects of hsa_circ_0000313 knockdown and MKNK2 knockdown on Jurkat cells proliferation, apoptosis, and inflammatory cytokine secretion. In LPS-stimulated Jurkat cells, hsa_circ_0000313 knockdown suppressed the p38 MAPK pathway via the miR-1224-3p/MKNK2 axis, which reduced inflammatory cytokine secretion and cell proliferation as well as promoted apoptosis. CONCLUSION: Hsa_circ_0000313 is involved in MG progression by regulating the miR-1224-3p/MKNK2 axis and can act on the p38MAPK pathway to participate in the progression of MG concomitant inflammatory infections, which may provide a promising therapeutic target in MG.
Neutrophil Percentage-to-Albumin Ratio: Unveiling a New Perspective on Mortality Risk in Intensive Care Unit Asthma Patients-A Retrospective Cohort Study.
Lin W, Chen J, Lin B
Mediators Inflamm · 2026 · PMID 41846500 · Full text
OBJECTIVES: Asthma remains a prevalent diagnosis among intensive care unit (ICU) admissions, frequently linked to worsened patient outcomes. Therefore, identifying simple and effective indicators to predict the mortality...
OBJECTIVES: Asthma remains a prevalent diagnosis among intensive care unit (ICU) admissions, frequently linked to worsened patient outcomes. Therefore, identifying simple and effective indicators to predict the mortality risk of asthma patients in the ICU is particularly important. Given the unmet need for mortality biomarkers in critical asthma, this study specifically examined neutrophil percentage-to-albumin ratio's (NPAR's) correlation with ICU and in-hospital death. MATERIALS AND METHODS: We selected 1191 eligible asthma patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) 3.0 database for analysis. This study applied a multivariate Cox regression model to explore the relationship between NPAR levels and the risk of mortality in the ICU and during hospitalization. Additionally, we used restricted cubic splines (RCSs) models to investigate the potential nonlinear dose-response relationship between NPAR levels and the risk of mortality in the ICU and during hospitalization. RESULTS: Among the 1192 enrolled asthma cases, the cohort demonstrated a mean age of 58.1 ± 18.1 years, of which 38.7% were male. Asthma patients with higher NPAR faced substantially greater mortality risks during intensive care and hospitalization (hazard ratio [HR] range 1.75-2.14, p < 0.01). The relationship between logarithmic transformation (ln) NPAR and ICU and in-hospital mortality rates is nonlinear. Threshold effect analysis showed that when the ln NPAR level exceeded 0.5, the risk of patient mortality significantly increased (HR range 1.574-1.831, p < 0.05). Additionally, subgroup analysis revealed no significant interactions. CONCLUSION: In ICU asthma patients, higher NPAR levels are associated with higher risks of ICU and in-hospital mortality, emphasizing the importance of these findings for early identification and timely intervention in reducing the mortality risk of ICU asthma patients.
Systemic Inflammation Mediates the Association Between Admission Hyperglycemia and Pulmonary Infection or Prognosis in Acute Ischemic Stroke.
Ma X, Duan J, Cheng Y … +11 more , Li W, Liang C, Yang T, Liu J, Mi Y, Du S, Xue F, Zhang G, Chang M, Shi W, Tian Y
Mediators Inflamm · 2026 · PMID 41846462 · Full text
BACKGROUND AND PERSPECTIVES: Hyperglycemia frequently occurs after the onset of acute ischemic stroke (AIS) and the distinct effects and mechanisms of long-term or transient hyperglycemia on stroke outcome are incomplete...
BACKGROUND AND PERSPECTIVES: Hyperglycemia frequently occurs after the onset of acute ischemic stroke (AIS) and the distinct effects and mechanisms of long-term or transient hyperglycemia on stroke outcome are incompletely revealed. We aimed to investigate the potential mediating role of systemic inflammation in admission glycemia status with clinical outcome. METHODS: A total of 2233 eligible AIS patients were enrolled from January 2018 to February 2024 and followed up for 12 months. Patients were stratified into three groups: normoglycemia (NG, n = 1341), persistent hyperglycemia (PHG, n = 588) and stress-induced transient hyperglycemia (SIH, n = 304). Systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) were calculated from baseline blood cell counts. The primary outcomes were in-hospital stroke-associated pneumonia (SAP) and poor functional outcome (modified Rankin Scale [mRS] >2) at 12 months. RESULTS: Among the included patients, 26.3% had PHG and 13.6% developed SIH. The rates of SAP and poor prognosis were highest in SIH group, intermediate in the PHG group and lowest in the NG group. Patients in SIH group exhibited highest systemic inflammatory levels (C-reactive protein [CRP], hsCRP, lnSII, SIRI, and neutrophil-to-lymphocyte [NLR]). After adjusting for confounders identified by LASSO regression, both tertile 3 of lnSII and SIRI were significantly associated with higher risk of SAP independent of admission glycemia status. While higher lnSII and SIRI were significantly associated with poor prognosis at 12-month only in SIH group. Mediation analysis demonstrated that lnSII partially mediated the association between glycemic status and clinical outcomes (mediation proportion: 16.7% for SAP; 10.8% for prognosis), with a similar effect observed for SIRI. The prediction model incorporating clinical variables and lnSII or SIRI yielded an AUC around 0.90 for SAP and 0.84 for 12-month prognosis. CONCLUSION: Admission hyperglycemia, particularly SIH, notably affected the incidence of SAP and poor prognosis. Systemic inflammation partially mediated the effect of hyperglycemia on clinical outcome in AIS.
Mendelian Randomization Identified SLC2A9 as a Novel cis-eQTL-Mediated Susceptibility Gene in Suppressing Renal Cancer and Its Related Metabolic Mechanisms.
Wang Y, Song Y, Ji H … +2 more , Zhu B, Xie H
Mediators Inflamm · 2026 · PMID 41837832 · Full text
OBJECTIVE: Mendelian randomization (MR) analysis has currently been widely used in combination with expression quantitative trait loci (eQTLs) or cis-eQTLs for identifying novel drug targets in various diseases. Hence in...
OBJECTIVE: Mendelian randomization (MR) analysis has currently been widely used in combination with expression quantitative trait loci (eQTLs) or cis-eQTLs for identifying novel drug targets in various diseases. Hence in this article, we first integrated MR analysis with eQTLs and cis-eQTLs to reveal the causal effects among SLC2A9 and renal cancer (RC), along with its related metabolic mechanisms. METHODS: Related genome-wide association study (GWAS) data were obtained from online datasets. Two-sample MR and summary-data-based MR study (SMR) analyses were applied to assess the causal effects among SLC2A9 eQTL or cis-eQTLs and RC, respectively. Sensitivity analysis confirmed the robustness and heterogeneity of the results. Besides, 1400 metabolites were enrolled as mediators to further reveal the related metabolic mechanisms of SLC2A9 eQTL involved in RC. RESULTS: Our results found that SLC2A9 eQTL was markedly associated with low risks of RC in the IEU OpenGWAS eQTLs dataset (discovering) (p = 0.030). The eQTLGEN and GTEx Whole Blood datasets validated the causal effects among SLC2A9 cis-eQTL and RC, reducing RC risks (both p < 0.05). The TCGA-KIRC and the CPTAC-KIRC datasets validated the mRNA and protein expression levels of SLC2A9 in RC, confirming its antitumor roles in RC (both p < 0.05). A total of five metabolites were finally identified to reveal the related metabolic mechanisms of SLC2A9 eQTL involved in RC (all p < 0.05). CONCLUSIONS: This study indicated that SLC2A9 eQTL or cis-eQTL was markedly associated with low risks of RC and played an antitumor role in RC, along with preliminary identification of five metabolic pathways for its potential mechanisms requiring further investigation.
Secretome From Human Micro-Fragmented Adipose Tissue Affects In Vitro Monocytes/Macrophages Inflammatory Activity by ICAM-1 Expression.
Coccè V, Martegani E, Paino F … +8 more , Doneda L, Alessandri G, Manfredi B, Giannì A, Ciusani E, Colombani E, Tremolada C, Pessina A
Mediators Inflamm · 2026 · PMID 41834645 · Full text
Micro-fragmented adipose tissue (MFAT) is regarded as one of the simplest and most practical biological preparations for clinical applications in tissue regenerative medicine. The clinical effectiveness of MFAT is attrib...
Micro-fragmented adipose tissue (MFAT) is regarded as one of the simplest and most practical biological preparations for clinical applications in tissue regenerative medicine. The clinical effectiveness of MFAT is attributed to its content of cells and growth factors that facilitate tissue regeneration. In this study, we investigated the biological activity of the secretome derived from cultured MFAT. Our primary focus was on its ability to influence the production of two inflammatory cytokines, RANTES (Regulated and Normal T Cell Expressed and Secreted) and MCP-1 (Monocyte Chemoattractant Protein-1), using ELISA assays, as well as its impact on the expression of Cell Adhesion Molecules (CAMs) on U-937 macrophages via flow cytometry. We also explored the potential of the MFAT secretome to affect the proliferation of both normal and cancer cells. Our results showed that the MFAT secretome inhibited the production of MCP-1 and RANTES, significantly reduced the expression of ICAM-1 (Intercellular Adhesion Molecule 1) on U-937 macrophages, and had no impact on the proliferation of normal or cancer cells. These findings suggest that the MFAT secretome is relatively safe and exhibits anti-inflammatory properties, supporting the idea that its clinical effectiveness in treating joint inflammation may, in part, be due to its paracrine effects.
ATOJIN: A Natural Products Mixture, Alleviates Atopic Dermatitis in DNCB-Induced NC/Nga Mice.
Lee SE, Cho KJ, Kim MW … +2 more , Yim HS, Ko SG
Mediators Inflamm · 2026 · PMID 41830402 · Full text
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder with increasing global prevalence. ATOJIN is a natural product composed of Phellodendron amurense Ruprecht (PAR), Schizonepeta tenuifolia (ST), So...
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder with increasing global prevalence. ATOJIN is a natural product composed of Phellodendron amurense Ruprecht (PAR), Schizonepeta tenuifolia (ST), Sophora flavescens (SF), Glycyrrhiza uralensis (GU), and Liriope platyphylla (LP), all known for their anti-inflammatory properties. This study aims to evaluate the therapeutic potential of ATOJIN in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model by assessing its effects on inflammation and immune regulation. The therapeutic efficacy of ATOJIN was evaluated through the analysis of white blood cell subtypes, serum immunoglobulin E (IgE) levels, pro-inflammatory cytokines, and histological assessments of inflammatory and mast cell infiltration, focusing on systemic immune modulation. ATOJIN effectively alleviated AD lesions and symptoms in DNCB-induced mice, demonstrating significant improvements in dermatitis scores, ear thickness, and spleen weight. It also reduced epidermal thickness and the infiltration of inflammatory and mast cells. Furthermore, ATOJIN modulated serum levels of IgE and pro-inflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, and tumor necrosis factor (TNF)-α, indicating systemic anti-inflammatory effects. These results suggest that ATOJIN mitigates AD symptoms by modulating inflammatory responses, and its efficacy, comparable to or even superior to that of the topical standard-of-care tacrolimus, highlights its potential as a promising standalone oral therapeutic agent for the systemic management of AD.
Zengwei Chengqi Decoction Reduces Inflammation in Acute Intestinal Obstruction.
Gong Y, Xuan ZH, Dong Y … +6 more , Zhang CB, Liu YC, Zhang JH, Li Q, Liu CB, Xie DM
Mediators Inflamm · 2026 · PMID 41830048 · Full text
OBJECTIVE: This study investigates the therapeutic effects of Zengwei Chengqi Decoction (ZW) on acute intestinal obstruction (AIO), focusing on its ability to alleviate inflammation and reduce associated tissue damage. N...
OBJECTIVE: This study investigates the therapeutic effects of Zengwei Chengqi Decoction (ZW) on acute intestinal obstruction (AIO), focusing on its ability to alleviate inflammation and reduce associated tissue damage. Network pharmacology and experimental animal models were used to explore the mechanisms of action. METHODS: Using network pharmacology, we identified 228 active compounds in ZW and 420 corresponding targets linked to inflammation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological pathways influenced by ZW. In vivo, an SD rat model of AIO was induced, and the therapeutic effects of ZW were assessed by histological examination of tissue damage and serum cytokine levels. RESULTS: Treatment with ZW significantly mitigated tissue damage in AIO rats. Additionally, serum levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were substantially reduced in the ZW-treated group compared to the control group (p < 0.01). CONCLUSION: ZW shows strong potential for modulating inflammation in AIO, as evidenced by reduced cytokine levels and improved tissue integrity. These findings provide valuable insights into the mechanisms underlying its therapeutic effects, positioning ZW as a promising treatment for AIO.
Luteolin Disrupts Keratinocyte-Dendritic Cell Communication in Psoriasis by Targeting Rh Family C Glycoprotein.
Zhang Q, Gao YW, Feng CC … +7 more , Yang L, Chen F, Guo S, Liu YJ, Lu QY, Ji C, Shen H
Mediators Inflamm · 2026 · PMID 41814938 · Full text
Psoriasis, a chronic inflammatory skin disease, arises from a dysregulated interaction between keratinocytes (KCs) and dendritic cells (DCs). We previously identified Rh family C glycoprotein (RHCG) as a key mediator of...
Psoriasis, a chronic inflammatory skin disease, arises from a dysregulated interaction between keratinocytes (KCs) and dendritic cells (DCs). We previously identified Rh family C glycoprotein (RHCG) as a key mediator of KC inflammation and DC activation. Here, we demonstrate that luteolin, a bioactive compound derived from the traditional Chinese formula cooling blood and detoxicating formula (CBDF), directly binds to RHCG, as confirmed by multiple computational methods and in vitro experiments. In vitro, luteolin suppressed RHCG expression in KCs, reducing CXCL14 secretion and subsequent DC activation. Spatial transcriptomics (STs) revealed that luteolin preferentially targets DC-enriched spatial domains and restores desmosomal protein expression (e.g., DSC2), which is dysregulated in psoriasis. In vivo, luteolin ameliorated psoriasis-like inflammation in imiquimod-induced mice, lowering Psoriasis Area and Severity Index (PASI) scores and normalizing pathological markers. Our findings indicate that luteolin disrupts KC-DC communication through multiple modes of action, thereby reversing tissue-level pathology and demonstrating its potential as a targeted therapy for psoriasis.
AJUBA: The Master Regulator Bridging EMT and Immune Evasion in Colorectal Cancer.
Shen W, Cui M, Liao X … +4 more , Xiong Y, Zou B, Zhang X, Shao C
Mediators Inflamm · 2026 · PMID 41814682 · Full text
BACKGROUND: Epithelial-mesenchymal transition (EMT) represents a critical process that facilitates metastatic dissemination and immune evasion in colorectal cancer (CRC); however, the molecular factors that connect EMT t...
BACKGROUND: Epithelial-mesenchymal transition (EMT) represents a critical process that facilitates metastatic dissemination and immune evasion in colorectal cancer (CRC); however, the molecular factors that connect EMT to modifications in the immune microenvironment remain poorly elucidated. In this investigation, we identify AJUBA as an essential regulator that mediates the association between EMT and immune modulation in CRC. METHODS: By integrating multi-cohort transcriptomic datasets (The Cancer Genome Atlas (TCGA)-CRC, GSE18105, GSE22598, GSE89076, and GSE110224) with single-cell RNA-seq data (GSE132465), we applied machine learning and deep learning methodologies to comprehensively identify EMT-associated genes demonstrating prognostic significance. AJUBA validation was performed at mRNA and protein levels in a cohort of 90 CRC patient samples using quantitative PCR, Western blotting, and immunohistochemical (IHC) approaches. Functional analyses involved siRNA-mediated knockdown experiments, coupled with evaluations of cell proliferation (CCK-8 assay), migration and invasion (transwell assay), clonogenic capacity (colony formation assay), and in vivo tumor growth in xenograft models. Immune infiltration was assessed via ssGSEA and CIBERSORT algorithms, and spatial transcriptomics data (GSE225857) were used to delineate AJUBA expression within tumor microdomains. RESULTS: Across multiple CRC cohorts, AJUBA exhibited marked upregulation and showed distinct enrichment in epithelial cells with activated EMT characteristics. Spatial transcriptomic profiling demonstrated AJUBA colocalization with cancer-associated fibroblasts (CAFs) within immune-excluded niches. Enhanced AJUBA expression exhibited a positive correlation with heightened infiltration of M2 macrophages and activation of VEGF/NOTCH signaling cascades. In vivo, AJUBA knockdown led to suppressed tumor growth, reduced Ki-67 proliferation indices, and diminished M2 macrophage abundance. Clinically, elevated AJUBA expression correlated with advanced nodal metastasis and served as an independent predictor of poor overall survival (OS; HR = 4.809, 95% CI: 2.385-9.695, p < 0.001). CONCLUSIONS: AJUBA functions as a key regulator that links EMT to immune modulation, promoting macrophage polarization and facilitating immune evasion in CRC. Through its coupling of EMT activation with proangiogenic signaling, AJUBA represents both a prognostic biomarker and a promising therapeutic target for alleviating immune exclusion in metastatic CRC.
Diels et Gilg Flavonoids Against Acute Lung Injury Via Block NLRP3 Inflammation.
Zhan L, Li L, Wu X … +6 more , Jiang X, Zhou J, Zhu S, Shu C, Pu J, Liang W
Mediators Inflamm · 2026 · PMID 41809141 · Full text
BACKGROUND: Diels et Gilg (Sanyeqing [SYQ]), a traditional anti-inflammatory herb, has been used to treat respiratory disorders. AIMS: To elucidate the mechanism of SYQ flavonoids in mitigating acute lung injury (ALI)....
BACKGROUND: Diels et Gilg (Sanyeqing [SYQ]), a traditional anti-inflammatory herb, has been used to treat respiratory disorders. AIMS: To elucidate the mechanism of SYQ flavonoids in mitigating acute lung injury (ALI). MATERIALS AND METHODS: An integrated approach combined network pharmacology, HPLC, lipopolysaccharide (LPS)-induced ALI mouse models, and NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-activated cellular assays (LPS + nigericin). NLRP3 knockdown (siRNA) and molecular docking were employed for mechanistic validation. RESULTS: Network pharmacology and HPLC identified procyanidin B1 and catechin as core active compounds targeting the NLRP3 inflammasome pathway. Animal experiments demonstrated that SYQ flavonoids can significantly alleviate pathological damage to lung tissue, reduce pulmonary edema, and inhibit the expression of pro-inflammatory factors, thereby exerting a protective effect against ALI. Furthermore, SYQ flavonoids exhibited protective effects against ALI by downregulating the expressions of interleukin (IL)-1β, IL-18, NLRP3, ASC, and caspase-1. Notably, when NLRP3 was knocked down using siRNA technology, it had no significant effect on the levels of IL-1β and IL-18, indicating that their therapeutic effects are mediated through the NLRP3 pathway. Finally, molecular docking confirmed that both catechin and procyanidin B1 exhibit strong binding affinities with NLRP3, providing a molecular basis for their targeted inhibition of the NLRP3 inflammasome. CONCLUSION: SYQ flavonoids alleviate ALI by specifically inhibiting the NLRP3 inflammasome, providing a mechanistic basis for its traditional use in lung inflammation.
The Mediating Factor of Immune Cell in the Causal Relationship Between Cardiovascular Disease-Related Plasma Proteins and Parkinson's Disease: A Network Mendelian Randomization Analysis.
Yao R, Chen S, Lu Y … +9 more , Li Y, Yu B, Liu Y, Zhang T, Zhu Y, Chen F, Lin Y, Wang Y, Li C
Mediators Inflamm · 2026 · PMID 41800109 · Full text
BACKGROUND: Cardiovascular diseases (CVDs) and their associated plasma proteins exhibit significant correlations with immunity and Parkinson's disease (PD). However, the specific contributions to the risk of developing P...
BACKGROUND: Cardiovascular diseases (CVDs) and their associated plasma proteins exhibit significant correlations with immunity and Parkinson's disease (PD). However, the specific contributions to the risk of developing PD remain unclear. This study aims to investigate the potential causal relationship between CVD-related plasma proteins and the risk of PD and explore the significant mediating role of immune cell phenotypes. METHODS: Using publicly available genetic data, we conducted Mendelian randomization (MR) analysis using the inverse variance weighting method to explore the causal relationship between 83 CVD-related plasma proteins and PD. Various MR analysis models were employed for sensitivity analysis. Concurrently, we utilized bioinformatics methods such as protein-protein interaction networks and pathway enrichment analysis to investigate the potential associations between CVD-related plasma proteins and PD-related genes. Finally, we employed a mediator MR design to identify the mediating effects of 731 immune cell phenotypes in the onset of PD. RESULTS: Elevated levels of Fas cell surface death receptors ( = 0.015) and nerve growth factor ( = 0.026) are associated with a reduced risk of PD, while increased levels of thrombomodulin ( = 0.028) are a risk factor for PD. Four immune phenotypes play a significant mediating role in the association between CVD-related proteins and the pathogenesis of PD. Sensitivity analysis indicates that the results are robust. CONCLUSIONS: Our study elucidates the close genetic association between CVD-related plasma proteins and PD and identifies the significant mediating role of immune cells, thereby providing valuable insights for future research and clinical applications.
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