Mediators Of Inflammation[JOURNAL]
Sun
200 papers
Association of C-Reactive Protein-Triglyceride Glucose Index With Chronic Obstructive Pulmonary Disease: Results From the NHANES and CHARLS Cohorts.
Gan J, Chen L, Zhu Y
Mediators Inflamm · 2026 · PMID 42400320 · Full text
BACKGROUND: The C-reactive protein (CRP)-triglyceride glucose index (CTI) is a new composite biomarker used to assess inflammation and insulin resistance (IR) severity. Inflammation and IR play important roles in chronic...
BACKGROUND: The C-reactive protein (CRP)-triglyceride glucose index (CTI) is a new composite biomarker used to assess inflammation and insulin resistance (IR) severity. Inflammation and IR play important roles in chronic obstructive pulmonary disease (COPD). However, the impact of CTI on COPD remains unknown. METHODS: To explore the association between CTI and the prevalence of COPD, a total of 8682 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 8986 participants from the US National Health and Nutrition Examination Survey (NHANES) were included. We used logistic multivariate regression to evaluate the association between CTI and COPD. In addition, smooth curve fitting analyzed dose-response relationships, while subgroup analyses explored effect heterogeneity. RESULTS: We found a positive correlation between CTI and the risk of COPD after adjusting for all covariates in the NHANES database (OR = 1.34, 95% confidence interval [CI]: 1.18-1.53), which is consistent with the findings obtained from Cox regression analysis in the CHARLS database (HR = 1.16, 95% CI: 1.07-1.26), with consistent dose-response trends confirmed by restricted cubic spline (RCS) analyses. Subgroup analyses confirmed consistency across most strata, with a significant interaction detected with cardiovascular disease (CVD). Sensitivity analyses further confirmed the robustness of associations. CONCLUSIONS: These findings indicate a significant association between CTI and COPD, suggesting its potential role as a biomarker for the prevention and treatment of COPD.
Moxibustion Modulates ALOX15-Mediated Lipid Peroxidation to Inhibit Ferroptosis in Synovial Inflammatory Injury of Rheumatoid Arthritis.
Wang T, Peng C, Liu Q … +6 more , Zhou Z, Gao D, Li Y, Zhang M, Hao F, Peng C
Mediators Inflamm · 2026 · PMID 42394362 · Full text
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial, cartilage, and bone damage. Emerging research evidence has linked its pathogenesis to ferroptosis, arachidonic acid (ARA)...
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial, cartilage, and bone damage. Emerging research evidence has linked its pathogenesis to ferroptosis, arachidonic acid (ARA) metabolism, and lipid peroxidation. Lipid peroxidation serves as the final executor of ferroptosis, and arachidonate lipoxygenase (ALOX)-mediated oxidative reactions enzymatically promote lipid peroxidation. Moxibustion (MOX), a traditional therapeutic modality in Chinese medicine, has demonstrated significant efficacy in our study. Specifically, MOX applied at the Zusanli (ST36) and Shenshu (BL23) acupoints effectively ameliorated paw swelling in Freund's complete adjuvant (FCA)-induced RA model rats, significantly reduced arthritis scores, and corrected ARA metabolic dysregulation. Furthermore, MOX treatment markedly decreased the expression levels of arachidonate 15-lipoxygenase (ALOX15), acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and reactive oxygen species (ROS) in the synovial tissues of RA model rats while increasing the expression of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4). Serum analyses revealed significant reductions in malondialdehyde (MDA), lipid peroxide (LPO), interleukin-12 (IL-12), and tumor necrosis factor-alpha (TNF-α) levels, alongside elevated glutathione (GSH) and superoxide dismutase (SOD) levels. The underlying mechanism involves the modulation of ALOX15-mediated lipid peroxidation to inhibit ferroptosis, thereby alleviating RA-associated inflammatory damage. These findings highlight the substantial therapeutic potential of MOX in mitigating RA-related inflammation and provide a novel theoretical basis for its clinical application in RA management.
Development and Validation of a Cytokine-Based Predictive Model for Acute GvHD and Composite Outcomes in ATG-Based Haploidentical Hematopoietic Stem Cell Transplantation.
Chen Y, Yu X, Jin Z … +3 more , Jiang C, Hu X, Xu Y
Mediators Inflamm · 2026 · PMID 42377328 · Full text
BACKGROUND: Acute graft-versus-host disease (aGvHD) stands as a critical complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Most existing predictive models, predominantly derived...
BACKGROUND: Acute graft-versus-host disease (aGvHD) stands as a critical complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Most existing predictive models, predominantly derived from HLA-matched donor cohorts, have been utilized for nonrelapse mortality (NRM) prediction; however, their utility in predicting aGvHD risk specifically in haplo-HSCT recipients receiving antithymocyte globulin (ATG)-based prophylaxis warrants further validation. METHODS: A total of 280 patients undergoing ATG-based haplo-HSCT were retrospectively analyzed across two medical centers, split into training, internal test, and external validation cohorts. We first evaluated the predictive accuracy of the previously established Mount Sinai Acute GvHD International Consortium (MAGIC) algorithm for aGvHD, steroid-refractory aGvHD (SR-aGvHD). Subsequently, plasma concentrations of candidate cytokines (ST2, REG3α, Elafin, and TNFRI), selected a priori for their links to epithelial injury and inflammatory signaling in GvHD, were assessed for their predictive and causal relationships with aGvHD using logistic regression, weighted average area under the curve (wAUC), Mendelian randomization (MR), and restricted cubic spline (RCS) analyses. A new predictive model (the HAG model) was constructed based on identified key cytokines and validated across multicenter cohorts. MR analyses utilized external genome-wide association (GWAS) datasets to validate the reliability of identified cytokines. A visual interface for the model was created using R Shiny. RESULTS: MAGIC algorithm remains effective in the ATG-based haplo-HSCT setting for predicting aGvHD, achieving AUC values of 0.693 (training), 0.658 (internal test), and 0.622 (external validation). Among candidate cytokines, a combination of ST2, REG3α, and Elafin (the HAG model) demonstrated the highest predictive accuracy. MR analysis leveraging external GWAS data supported potential causal associations of ST2 (OR = 1.280, p = 0.004), REG3α (OR = 1.300, p = 0.012), and Elafin (OR = 1.209, p = 0.039) with aGvHD risk, providing complementary biological support for their selection as candidate biomarkers. The HAG model displayed good discrimination for aGvHD (AUC = 0.636-0.701) and SR-aGvHD (AUC = 0.666-0.779). Integration of clinical factors further enhanced prediction (HAG-C model, wAUC from 0.682 to 0.701). CONCLUSION: The HAG model, incorporating ST2, REG3α, and Elafin, provides clinically meaningful prediction of aGvHD and related clinical outcomes in ATG-based haplo-HSCT recipients, and may serve as a mechanistically informed tool for risk stratification and clinical management.
Effects of Livergol and Hydroalcoholic Extracts of Barberry, Jujube, and Flixweed on Oxidative Stress and Inflammatory Gene Expression in a MASLD Animal Model.
Bahreini E, Sadri F, Babaei M … +3 more , Mohammadi Y, Hemmati Z, Rezaei T
Mediators Inflamm · 2026 · PMID 42377022 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is known as one of the most common metabolic disorders. The present study aimed to investigate the effects of livergol and hydroalcoholic extra...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is known as one of the most common metabolic disorders. The present study aimed to investigate the effects of livergol and hydroalcoholic extracts of barberry, jujube, and flixweed in an animal model of MASLD. METHODS: Forty-eight male Wistar rats were randomly assigned to six groups (n = 8): (1) Normal control, (2) MASLD, (3) Barberry (100 mg/kg), (4) Jujube (400 mg/kg), (5) Flixweed (100 mg/kg), and (6) Livergol (200 mg/kg). MASLD was induced using a high-fat diet (HFD). Animals received 70% hydroethanolic extracts from the plants investigated orally for 8 weeks. At the end of the intervention, serum and liver tissue samples were collected. RESULTS: The results showed that treatment with barberry, jujube, and livergol significantly improved body weight control and lipid profile parameters. Barberry showed the strongest lipid-lowering effect, reducing triglycerides (TG) and low-density lipoprotein (LDL)-C by ~32.0% and ~27.3%, respectively. Jujube produced the greatest reduction in malondialdehyde (MDA) levels (~25.8%), whereas barberry most effectively increased total antioxidant capacity (TAC) (~12.5%) and thiol levels (~8.7%). Barberry, jujube, and livergol also significantly downregulated proinflammatory cytokine genes (interleukin-1 beta [IL-1β], tumor necrosis factor-alpha [TNF-α], and interleukin-6 [IL-6]) and increased interleukin-10 (IL-10) expression. Additionally, histopathological indices of liver tissue improved in the treated groups. Flixweed showed only limited and mostly nonsignificant effects. CONCLUSION: Livergol and the hydroalcoholic extracts of barberry and jujube exerted significant hepatoprotective, antioxidant, and anti-inflammatory effects against MASLD-induced liver injury, with barberry demonstrating the most prominent therapeutic efficacy. These findings suggest that barberry may represent a promising candidate for future translational and clinical investigations in MASLD management.
Immune Gene INHBA is Associated With Osteoarthritic Cartilage Damage and May Mediate the Temporal Activation of the TGF-β/p38 MAPK Pathway: Integrating Multiomics Machine Learning and Experimental Validation.
Sun J, Sun Q, Chen Y … +4 more , Li X, Cui X, Zhang Y, Xie W
Mediators Inflamm · 2026 · PMID 42377012 · Full text
OBJECTIVE: This study aimed to screen and identify osteoarthritis (OA)-related core immune genes, elucidate the mechanism underlying the temporal activation of key signaling pathways mediated by these genes, and screen p...
OBJECTIVE: This study aimed to screen and identify osteoarthritis (OA)-related core immune genes, elucidate the mechanism underlying the temporal activation of key signaling pathways mediated by these genes, and screen potential therapeutic compounds, thereby providing a theoretical basis for the precision diagnosis and targeted intervention of OA. METHODS: Four sets of OA cartilage transcriptomic datasets with normal controls (NCs) were downloaded from the Gene Expression Omnibus (GEO) database. After batch correction, a training set and two independent validation sets were constructed to screen immune-related differentially expressed genes (Immune-DEGs). A total of 113 combined models were built based on 12 basic machine learning algorithms; the models were optimized via 10-fold cross-validation and evaluated in the validation sets to identify important immune genes. Subsequent functional enrichment analysis was performed to clarify the enriched signaling pathways. Core immune genes were identified by integrating Shapley additive explanations (SHAP) analysis and weighted gene coexpression network analysis (WGCNA), and single-cell pseudotime analysis was used to decipher their dynamic expression patterns during OA progression. Finally, real-time quantitative PCR (RT-qPCR) and western blot (WB) were employed to verify the expression changes of core genes and key pathway proteins in cell models and OA animal cartilage tissues with different lesion severities. Additionally, drug repurposing was conducted using the DSigDB database to screen potential therapeutic compounds, and molecular docking and molecular dynamics simulations were performed to validate the binding ability of clinically commonly used drugs to core targets. RESULTS: A total of 12 immune-DEGs significantly associated with OA were screened. Through systematic evaluation of multiple models, an exploratory OA classification model based on 10 important immune genes was constructed, showing good classification ability in the limited samples of this study. Functional enrichment analysis revealed that these important immune genes were significantly enriched in the TGF-β signaling pathway. Integration of SHAP and WGCNA analyses identified INHBA as a key hub gene associated with OA, and single-cell pseudotime analysis indicated that INHBA expression was sustainably upregulated with OA progression. In vitro and in vivo experimental validation showed that INHBA mRNA levels in human chondrocytes and INHBA mRNA levels in rat cartilage tissues continuously increased with the aggravation of OA lesions; WB results demonstrated that total TGF-β1 protein exhibited a temporal change of first increasing and then decreasing, while INHBA and downstream phosphorylated p38 MAPK protein levels continuously rose during disease progression, suggesting a temporal activation switch between the TGF-β pathway and the p38 MAPK pathway. Drug repurposing yielded 10 potential therapeutic compounds including progesterone; molecular docking indicated that diclofenac, celecoxib, glucosamine, and chondroitin sulfate could stably bind to core targets, and molecular dynamics simulations further confirmed the stable binding conformation between celecoxib and INHBA protein. CONCLUSION: This study successfully constructed an exploratory OA classification model based on 10 important immune genes, demonstrating that the core immune gene INHBA is strongly associated with OA progression and may contribute to cartilage degeneration in OA by mediating the temporal activation of the TGF-β/p38 MAPK pathway.
RETRACTION: IκB Kinase Inhibitor VII Modulates Sepsis-Induced Excessive Inflammation and Cardiac Dysfunction in 5/6 Nephrectomized Mice.
Inflammation MO
Mediators Inflamm · 2026 · PMID 42366463 · Full text
Abstract loading — click title to view on PubMed.
A Novel CAF-Related Signature for Precise Prediction of Clinical Outcomes and Immunotherapy Response for Breast Cancer Patients: Based on Multiomics Analyses and Experimental Validation.
Wang Q, Chen J, Zhang S … +6 more , Liu Y, Xu L, Tian L, Ren J, Su Z, Tang Z
Mediators Inflamm · 2026 · PMID 42359574 · Full text
OBJECTIVE: Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide. Cancer-associated fibroblasts (CAFs) is a central stromal component of the tumor microenvironment (TME), critically influence B...
OBJECTIVE: Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide. Cancer-associated fibroblasts (CAFs) is a central stromal component of the tumor microenvironment (TME), critically influence BC progression and therapeutic resistance. However, the association between CAF heterogeneity and patient prognosis or response to immunotherapy remains poorly characterized. Here, we aimed to develop a CAF-associated gene signature by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to predict clinical outcomes and immunotherapeutic response in BC. METHODS: Gene expression profiles and clinical data from BC patients were sourced from TCGA and GEO databases. scRNA-seq data preprocessed (quality control, PCA, UMAP using Seurat) identified CAF-related genes. Prognostic genes were identified via univariate Cox, lasso, and multivariate Cox regression. Single-cell Gene Set Enrichment Analysis (scGSEA) assessed the signature's link to immune infiltration and immunotherapy genes. R tools evaluated signature characteristics and real-world applications. GO enrichment analysis was used to explore signaling pathways. CAF factor expression and CD8 T-cell correlation in clinical BC samples were validated using qPCR, immunohistochemical (IHC), multiplex immunofluorescence (mIF), and Western blot. RESULTS: scRNA-seq analysis identified multiple CAF-specific marker genes that formed the core of our signature. Eight genes (ANXA5, APOD, CXCL14, GSN, IGFBP4, PPIB, TCF7L2, and TMEM98) were associated with favorable prognosis (low-risk), whereas three genes (SDC1, EMP1, and FAM114A1) conferred higher risk. A risk score model based on these 11 genes independently predicted overall survival (OS) across diverse BC pathological subtypes, demonstrating robust prognostic accuracy. Immune infiltration analysis revealed significantly reduced immune cell abundance in the high-risk group compared to the low-risk group, suggesting diminished responsiveness to immunotherapy. In tumor tissues relative to adjacent nontumor tissues, mRNA and protein levels of the high-risk genes (SDC1, EMP1, and FAM114A1) were consistently elevated (all p < 0.05). Moreover, both Western blotting and mIF showed significantly higher CAF abundance in high-risk samples (p < 0.01), concomitant with markedly lower CD8 tumor-infiltrating lymphocyte counts (p < 0.05). GO enrichment analyses indicated that CAFs promote BC evolution and progression through complex signaling networks. Key pathways included extracellular matrix (ECM) remodeling, cell adhesion, tumor associated inflammation, and oncogenic cascades such as KRAS, WNT, IL-6/STAT3, and TNFα/NF-κB highlighting CAFs as pivotal regulators and potential therapeutic targets in BC. CONCLUSION: We present a novel CAF associated gene signature that robustly predicts prognosis and immunotherapy response in BC. As an independent prognostic indicator strongly correlated with immune infiltration, this model holds promise for guiding personalized therapeutic strategies. Future validation in large, multicenter cohorts and extension to other malignancies are warranted to facilitate clinical translation of CAF targeted biomarkers.
REG3A: A Potential Fecal Biomarker for Ulcerative Colitis.
Lv X, Qi Y, Guo J … +4 more , Ba L, Wang S, Cao H, Xu X
Mediators Inflamm · 2026 · PMID 42345560 · Full text
Regenerating islet-derived protein 3-alpha (REG3A), a member of the regenerating islet-derived protein (Reg) family, belongs to the C-type lectin class of antimicrobial peptides (AMPs). It has been recognized as a critic...
Regenerating islet-derived protein 3-alpha (REG3A), a member of the regenerating islet-derived protein (Reg) family, belongs to the C-type lectin class of antimicrobial peptides (AMPs). It has been recognized as a critical component of intestinal mucosal barrier damage and repair. In a prospective cohort (82 ulcerative colitis [UC] patients, 20 controls), UC patients were stratified by clinical partial Mayo Score (pMS) and endoscopic activity. Fecal REG3A levels were measured across distinct patient cohorts, and diagnostic performance was evaluated and compared against fecal calprotectin (FC) and a combined model using receiver operating characteristic (ROC) analysis. REG3A expression was also evaluated in intestinal biopsies via immunohistochemistry. Fecal REG3A levels increased stepwise with UC clinical severity (p < 0.001), peaking in the severe activity group. A combined model of REG3A and FC outperformed either biomarker alone in differentiating disease activity, achieving the highest area under the curves (AUCs) for distinguishing remission from mild activity and mild from moderate activity. Immunohistochemistry confirmed REG3A expression in active UC colonic tissues. Our results indicate that fecal REG3A serves as a promising biomarker for assessing disease activity in UC. Its combination with FC enhances the accuracy of predicting clinical severity in UC.
Correction to "The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat".
Mediators Inflamm · 2026 · PMID 42339682 · Full text
Abstract loading — click title to view on PubMed.
Synergistic Effect of Sodium Acetate and Sodium Butyrate in Ameliorating Ethanol-Induced Hepatic Inflammation Through Modulation of the NF-κB Signaling Pathway.
Patel M, Aghara H, Chadha P … +4 more , Solanki H, Sharma D, Thiruvenkatam V, Mandal P
Mediators Inflamm · 2026 · PMID 42322178 · Full text
Chronic ethanol exposure activates inflammatory signaling pathways and inflicts hepatocellular damage, leading to alcohol-associated liver diseases (ALDs). ALD is one of the major causes of global burden, yet there are n...
Chronic ethanol exposure activates inflammatory signaling pathways and inflicts hepatocellular damage, leading to alcohol-associated liver diseases (ALDs). ALD is one of the major causes of global burden, yet there are no FDA-approved treatment options available. This study evaluates the hepatoprotective effects of short-chain fatty acids (SCFAs), mainly sodium acetate (NaA) and sodium butyrate (NaB), against ethanol-induced inflammation and oxidative stress in both in vitro (Buffalo Rat Liver-3A [BRL3A]) and in vivo (male Wistar rats) models. The treatment of NaA and NaB and their combination was given to the cell lines where maximum viability was observed at concentrations of 1.5 mM, 5 mM, and 0.1 mM + 1 mM, respectively. Additionally, reactive oxygen species (ROS) and nuclear morphology were assessed by fluorescent staining. For in vivo samples, the hepatic injury was analyzed by serum biochemical markers. Furthermore, hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were employed, which provided structural and immunological alterations in hepatic tissue. RT-qPCR profiled the expression levels of various pro-inflammatory and anti-inflammatory cytokines, as well as cytochrome P450 E1 (CYP2E1) and antioxidative stress markers. Moreover, enzyme-linked immunosorbent assay (ELISA) quantified the essential protein targets such as TNF-α, MCP-1, IL-1β, IL-6, HO-1, and Nrf2. The administration of NaA, NaB, and their combination resulted in reduced ROS levels and expression of pro-inflammatory cytokines, preserved nuclear integrity, and neutrophil infiltration. These findings were further confirmed by in silico analysis and conserved amino acid interactions, and the affinities of NaA and NaB for TNF-α and MCP-1 were observed as compared to established inhibitors or activators. This study is the first demonstration to report the synergistic effects of NaA and NaB on the feedback loop of the nuclear factor kappa B (NF-κB) signaling pathway, suggesting their potential as promising therapeutic candidates for alleviating alcohol-induced hepatic damage.
Association of Life's Crucial 9 Score With Liver Fibrosis and Mortality in U.S. Adults With MASLD: Evidence From NHANES and the Mediating Role of Systemic Inflammation.
Chen Z, Shi L, Lu J … +1 more , Su J
Mediators Inflamm · 2026 · PMID 42318783 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent. Life's Crucial 9 (LC9) combines cardiometabolic and mental health metrics linked to MASLD pathogenesis, but its asso...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent. Life's Crucial 9 (LC9) combines cardiometabolic and mental health metrics linked to MASLD pathogenesis, but its association with liver fibrosis and prognosis in MASLD remains unknown. METHODS: Using National Health and Nutrition Examination Survey (NHANES) data, we performed a prospective cohort analysis for mortality (2005-2016, n = 2524) and a cross-sectional analysis for liver fibrosis (2017-2018, n = 1277). Significant fibrosis was defined as liver stiffness measurement (LSM) ≥8.0 kPa by vibration-controlled transient elastography. Systemic inflammation was assessed using the systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV). Multivariable regression and mediation analyses were conducted. RESULTS: Higher LC9 scores were associated with lower liver stiffness (β = -0.07, 95% CI: -0.12 to -0.01). Each 1-point increase in LC9 reduced fibrosis risk by 5% (OR = 0.95), with the highest quartile showing the lowest risk (OR = 0.21). Over a median follow-up of 98 months, each 1-point LC9 increase was associated with a 3% reduction in all-cause mortality (HR = 0.97). Lower systemic inflammation partially mediated the LC9-mortality relationship (SII: 5%, PIV: 6.3%). CONCLUSION: Higher LC9 scores are associated with reduced liver fibrosis and improved survival in MASLD, with systemic inflammation partially mediating the mortality association.
Integrated Bioinformatics Methods Were Employed to Investigate Potential Molecular Links Between Obstructive Sleep Apnea and Sarcoidosis.
Li Y, Lan C, Lei H … +7 more , Lyu Z, Lin D, Shen J, Jiang H, Wang Y, Lu C, Liu Y
Mediators Inflamm · 2026 · PMID 42313509 · Full text
BACKGROUND: Previous studies have established a frequent coexistence of obstructive sleep apnea (OSA) and sarcoidosis, yet the molecular mechanisms linking these conditions are not well understood. METHODS: This study em...
BACKGROUND: Previous studies have established a frequent coexistence of obstructive sleep apnea (OSA) and sarcoidosis, yet the molecular mechanisms linking these conditions are not well understood. METHODS: This study employed integrated bioinformatics analysis and Mendelian randomization (MR) to identify potential mechanisms and infer causal relationships between OSA and sarcoidosis. Genetic instruments associated with OSA and sarcoidosis were screened, and bidirectional MR analysis was conducted to explore the causal relationship between the two conditions. Colocalization analysis was conducted to identify genes potentially associated with both OSA and sarcoidosis. Subsequently, differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed using data from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). In addition, eight machine learning algorithms were used to construct a nomogram based on the importance scores of DEGs and to identify hub genes. The results were validated using multiple methods. RESULTS: MR analysis confirmed a causal relationship between OSA and sarcoidosis (p = 0.0018 OR = 1.39 [95% CI 1.18-1.59]). We identified 35 genes associated with both OSA and sarcoidosis, among which 6 were found to be differentially expressed. KRT72, DEFA4, RNASE3, and LTF were identified as signature genes. Based on these genes, nomograms were constructed to quantitatively predict the risk of comorbid OSA and sarcoidosis. CONCLUSION: This study indicates a causal relationship between OSA and sarcoidosis. The potential mechanisms underlying this comorbidity involve immune dysregulation, inflammatory responses, and altered DNA repair and methylation. Additional contributing factors include dysregulated apoptosis, immune microenvironment remodeling, autophagy, and neural activity.
Mechanisms of Microglial NLRP3 Inflammasome Activation by Methylmalonic Acid in Methylmalonic Acidemia.
Sun S, Sun L, Su Y … +3 more , Li A, Hu L, Li Q
Mediators Inflamm · 2026 · PMID 42313492 · Full text
BACKGROUND: Microglial activation is a critical pathogenic mechanism of neurological damage in methylmalonic acidemia (MMA). The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is closely associated with...
BACKGROUND: Microglial activation is a critical pathogenic mechanism of neurological damage in methylmalonic acidemia (MMA). The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is closely associated with neuroinflammatory processes. However, the mechanism of NLRP3 inflammasome activation in microglia by methylmalonic acid (MMAcid) remains unclear. METHODS: Mouse microglia BV2 cells and hippocampal neuronal HT22 cells were stimulated with different concentrations of MMAcid. Neuronal cells were treated with conditioned medium derived from differently treated microglia. Microscopy was used to observe morphological changes of cells. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability (VB). In addition, the mRNA and protein levels were detected via qRT-PCR, ELISA, and western blot. To further validate the mechanism, we used lentivirus infection and small interfering RNA (siRNA) transfection to overexpress (OE) and knockdown (KD) extracellular signal-regulated kinase (ERK) and analyzed the inflammatory pathway. RESULTS: Direct exposure of neuronal cells to MMAcid significantly reduced cell VB, accompanied by morphological features suggestive of pyroptosis. MMAcid activated microglia, which was accompanied by increased expression of inflammatory molecules, activation of the ERK/nuclear factor-κB (NF-κB)/NLRP3 signaling pathway, and elevated secretion of interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α). Neuronal cell VB decreased when cocultured with the supernatant from MMAcid-treated microglia. Overexpression of ERK further enhanced microglial activation and potentiated MMA-induced neuronal pyroptosis-related signaling. Conversely, knocking down ERK expression in microglia reduced their activation by MMAcid and decreased cytokine secretion, but it did not completely reverse MMA-induced neuronal damage. CONCLUSION: MMAcid is associated with microglial activation, accompanied by alterations in the ERK/NF-κB/NLRP3 signaling pathway and increased release of inflammatory cytokines, which may contribute to neuronal pyroptosis-related changes.
Integrating Single-Cell Transcriptomics and Mendelian Randomization to Identify RAC1 as a Causal Metabolic Driver of Pericyte Dysfunction in Systemic Sclerosis.
Wang X, Zhang Z, Jiang E … +2 more , Zhang M, Hu G
Mediators Inflamm · 2026 · PMID 42299690 · Full text
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and progressive fibrosis. Although microvascular injury is an inciting event and pericytes are recognized as a major source o...
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and progressive fibrosis. Although microvascular injury is an inciting event and pericytes are recognized as a major source of myofibroblasts, the precise phenotypic heterogeneity of pericytes in the SSc microenvironment and the genetic mechanisms driving their pathological transition remain elusive. METHODS: This study systematically explored the cellular and genetic basis of pericyte dysfunction by integrating single-cell RNA sequencing (scRNA-seq) data from SSc patients with genome-wide association study (GWAS) data using bidirectional Mendelian randomization (MR) analysis. Pseudotime trajectory analysis was used to reconstruct developmental lineages, while cell-cell communication and metabolic pathway analyses were conducted to uncover underlying mechanisms. Multiomics validation was performed using external bulk RNA-seq datasets. RESULTS: Single-cell analysis revealed significant heterogeneity in pericyte subpopulations, specifically identifying a marked expansion of progenitor-like pericytes, which were positioned at the root of the differentiation trajectory toward fibrotic phenotypes. Bidirectional MR analysis identified RAC1 as a significant causal risk factor for SSc (OR = 2.0756, p = 0.0046). Mechanistically, RAC1-positive pericytes exhibited enhanced proinflammatory crosstalk with macrophages via the MIF-(CD74 + CD44) signaling axis. Furthermore, these activated pericytes displayed distinct metabolic reprogramming, characterized by the upregulation of riboflavin and thiamine metabolism to support their bioenergetic demands. Transcriptomic validation further confirmed the aberrant overexpression of RAC1 in SSc tissues. CONCLUSION: This study establishes a mechanistic link between RAC1-mediated activation of progenitor-like pericytes and SSc pathogenesis. RAC1 acts as a causal driver promoting pathological pericyte transition and orchestrates a proinflammatory microenvironment through metabolic reprogramming and immune recruitment, offering a novel therapeutic target for SSc.
Integrative Multiomics and Network Pharmacology Exploration of Active Components and Mechanisms of Action of Qufu Shengxin Ointment in Treating Chronic Nonhealing Wounds.
Chen H, Li Y, Chen D … +3 more , Fang Y, Gong X, Ma C
Mediators Inflamm · 2026 · PMID 42287035 · Full text
BACKGROUND: Chronic nonhealing wounds (CNHWs) are characterized by persistent inflammation and impaired autophagy, which hinder normal wound repair. Qufu Shengxin Ointment (QFSO) has shown clinical benefits in treating c...
BACKGROUND: Chronic nonhealing wounds (CNHWs) are characterized by persistent inflammation and impaired autophagy, which hinder normal wound repair. Qufu Shengxin Ointment (QFSO) has shown clinical benefits in treating chronic wounds, but its active components and molecular mechanisms remain largely unclear. This study aimed to investigate the pharmacological mechanisms of QFSO in the treatment of CNHWs. METHODS: Differentially expressed genes (DEGs) were identified from Gene Expression Omnibus (GEO) transcriptomic datasets, and weighted gene co-expression network analysis (WGCNA) was performed to screen genes associated with CNHWs. Active compounds and potential targets of QFSO were retrieved from the TCMSP database, and a compound-target network was constructed. Mendelian randomization (MR) analysis was applied to evaluate the potential causal effects of key targets on CNHW risk. Gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted to explore biological functions and immune mechanisms. Molecular docking and in vivo animal experiments were performed to validate the predicted interactions and therapeutic effects. RESULTS: About 1274 DEGs were identified between CNHW and normal wound tissues. Enrichment analyses indicated that the PI3K/Akt/mTOR pathway was significantly involved in CNHW pathogenesis. MR analysis identified AKR1B1 and VCAM1 as potential causal risk factors for CNHWs. Functional enrichment and single-cell RNA sequencing analyses revealed that these genes participate in immune-inflammatory regulation and autophagy-related processes. Molecular docking showed stable binding between key QFSO compounds and the targets AKR1B1 and VCAM1. In vivo experiments demonstrated that QFSO treatment significantly accelerated wound healing. The therapeutic effects were associated with reduced inflammation, enhanced angiogenesis, and activation of autophagy through regulation of the PI3K/Akt/mTOR pathway. CONCLUSIONS: QFSO promotes the repair of CNHWs by regulating the PI3K/Akt/mTOR pathway, enhancing autophagy, alleviating inflammation, and promoting angiogenesis. These findings identify AKR1B1 and VCAM1 as potential molecular targets for the treatment of chronic wounds.
Experimental Study of YaJieShaBa Antialcoholic Hepatic Fibrosis Through TGF-β1/Smad Signaling Pathway.
Zhang L, Bai Y, Luo S … +7 more , Liu F, Zheng L, Wan Y, Wu X, Chen Q, Xie Y, Guo P
Mediators Inflamm · 2026 · PMID 42283336 · Full text
OBJECTIVE: This study aimed to clarify the pharmacodynamic effects of YaJieShaBa (YJSB) against alcoholic hepatic fibrosis (HF) and elucidate its mechanism in regulating the transforming growth factor-β1 (TGF-β1)/Smad pa...
OBJECTIVE: This study aimed to clarify the pharmacodynamic effects of YaJieShaBa (YJSB) against alcoholic hepatic fibrosis (HF) and elucidate its mechanism in regulating the transforming growth factor-β1 (TGF-β1)/Smad pathway. METHODS: Induce the alcoholic HF model in rats using 56% ethanol (10 mL/kg). The pharmacological efficacy of YJSB in combating liver fibrosis was evaluated through comprehensive assessments of key indicators: body weight, liver mass and index, biochemical liver function parameters (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), liver fibrosis biomarkers (type Ⅲ procollagen amino-terminal propeptide [PⅢNP], type-Ⅳ collagen (COL-Ⅳ), laminin (LN), and hyaluronic acid [HA]), serum hydroxyproline (Hyp) and TGF-β1 levels, hepatocyte homogenate levels of COL-I, COL-Ⅲ, and α-smooth muscle actin (α-SMA), along with histopathological changes observed in liver tissue via hematoxylin and eosin (H&E) staining, Ag staining, and Masson staining. Pathway-focused qPCR array analysis was used to detect the expression of 72 genes related to signaling pathways such as TGF-β1, Keap1-Nrf2, and TLR4/MyD88 in liver tissue from the control group, model group, and YJSB group, identifying differentially expressed genes (DEGs) and key signaling pathways between the model group and the YJSB treatment group. Finally, based on the results of the pathway-focused qPCR array, the mechanism of action of YJSB against HF was validated using ELISA, WB, and immunofluorescence methods. Concurrently, TGF-β1 receptor inhibitors were employed in vitro experiments to determine whether YJSB could still provide additional protective effects when the TGF-β1/Smad pathway was maximally blocked. Furthermore, after confirming that YJSB could inhibit TGF-β1-induced activation, a rescue experiment was conducted by adding exogenous TGF-β1 to observe whether it could reverse the inhibitory effects of YJSB. RESULTS: YJSB administration significantly increased body mass and decreased liver index in alcoholic HF rats. Serum levels of AST, ALT, PⅢNP, COL-Ⅳ, LN, HA, Hyp, and TGF-β1 were significantly reduced, as were the levels of COL-I, Ⅲ, and α-SMA in liver homogenates. Histological analyses, including H&E, Ag, and Masson staining, revealed a significant reduction in liver damage. Pathway-focused qPCR array results showed that, compared with the blank group, 65 genes were upregulated and seven genes were downregulated in the model group, among which the relative expression levels of 40 genes were statistically significant (expression change factor ≥ 1 and p < 0.05). Compared with the model group, 68 genes were downregulated, and four genes were upregulated in the YJSB group, with 34 genes showing statistically significant relative expression levels (fold change [FC] ≥ 2 and p < 0.05). The DEGs were primarily enriched in the TGF-β1 signaling pathway. Additionally, YJSB reduced the levels of inflammatory factors IL-1β, TNF-α, IL-6, and IL-8 in liver tissue homogenates while increasing SOD, GSH-Px, and catalase (CAT) levels and decreasing MDA and ROS levels. Western blotting results showed that YJSB downregulated the expression levels of TGF-β1, Smad2, Smad3, P-Smad2, and P-Smad3 in the liver. Immunofluorescence results indicated that YJSB downregulated the expression levels of Smad4 in hepatocyte nuclei. In vitro experiments demonstrated that the mechanism of YJSB involves primarily inhibiting TGF-βR1 receptor activation, effectively downregulating P-Smad2/3 protein levels, as validated by the TGF-βR1 inhibitor LY2157299. Concurrently, in rescue experiments, the inhibitory effect of YJSB on P-Smad2/3 protein was partially reversed by exogenous TGF-β1, indicating that YJSB's antifibrotic action is highly correlated with the TGF-β1/Smad pathway. CONCLUSION: YJSB effectively inhibits the inflammatory and oxidative stress-related cascade by regulating the TGF-β1/Smad signaling pathway (TSSP), thus suppressing the progression of alcoholic HF. This demonstrates that YJSB possesses potential for combating alcoholic HF in animal models, providing experimental evidence for its subsequent research and clinical application.
Immune Infiltration-Related Genes as Potential Biomarkers and Predicted Targets for Renal Allograft Delayed Graft Function and Survival Outcome: An Integrated Machine Learning Approach and Drugs Analysis.
Zhang Y, Li Y, Qiu X … +5 more , Wu J, Bi Q, Cao P, Zhang J, Wang W
Mediators Inflamm · 2026 · PMID 42283098 · Full text
BACKGROUND: Ischemia-reperfusion injury (IRI) significantly impacts post-kidney transplantation (KTx), leading to delayed graft function (DGF) and potential graft loss. Current biomarkers and therapies for DGF and graft...
BACKGROUND: Ischemia-reperfusion injury (IRI) significantly impacts post-kidney transplantation (KTx), leading to delayed graft function (DGF) and potential graft loss. Current biomarkers and therapies for DGF and graft survival are inadequate. Immune cell infiltration after renal IRI is crucial in driving inflammation and injury. METHODS: To address this, this study utilized microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) database to identify differentially expressed immune infiltration-related genes (DE-IRGs) in IRI patients. Machine learning (ML) algorithms pinpointed hub DE-IRGs, aiding in predictive model development and classification of post-KTx IRI samples into clusters and risk groups. Regulatory networks incorporating transcription factors (TFs) and microRNAs (miRNAs) were constructed using NetworkAnalyst 3.0, and predicted compounds/commonly used immunosuppressants were explored via Enrichr and molecular docking simulations. RESULTS: Analysis revealed 47 DE-IRGs, with hub genes (adrenomedullin [ADM], Serpin Family H Member 1 [SERPINH1], Solute carrier family 2 member 3 [SLC2A3], BCL-2-associated athanogene 3 [BAG3], NFKB inhibitor alpha [NFKBIA], Kruppel-like factor 6 [KLF6], and CCAAT/enhancer-binding protein delta [CEBPD]) linked to DGF and, in part, graft survival. Predictive models showed robust performance based on internal validation, with the DGF models achieving AUCs of 0.832 and 0.975 and graft survival models showing AUCs of 0.773, 0.742, and 0.757 for 1, 2, and 3 years, respectively. Higher immune cell infiltration correlated with adverse outcomes in cluster A or high-risk groups. Key immune cells associated with DGF included activated CD8 T cells, activated dendritic cells (DCs), and effector memory CD4 T cells. Core regulatory TFs and miRNAs were identified, along with four core predicted compounds: acetaminophen, estradiol, valproic acid, and berbamine (which require further pharmacological validation), and three common immunosuppressants: cyclosporin A, mycophenolate mofetil (MMF), and tacrolimus. CONCLUSIONS: Our study identified potential hub genes most associated with immune cells during the post-KTx IRI process, shedding light on the intricate interplay between genes, immune cells, and KTx outcomes.
Myocarditis After mRNA Vaccination: A Metabolic-Innate Immune Cascade Centered on Lipid Nanoparticles.
Choi K, Choi S, Joe D … +5 more , Seo YS, Ham J, Chung H, Ramadan Y, Park YS
Mediators Inflamm · 2026 · PMID 42261850 · Full text
mRNA vaccine-associated myocarditis is a rare but clinically important adverse event whose pathogenesis remains incompletely understood. Initial hypotheses focused primarily on the spike protein antigen, with growing pre...
mRNA vaccine-associated myocarditis is a rare but clinically important adverse event whose pathogenesis remains incompletely understood. Initial hypotheses focused primarily on the spike protein antigen, with growing preclinical evidence implicating the lipid nanoparticle (LNP) delivery system as an additional and potentially important contributor to myocardial inflammation. Here, we propose a multi-hit model that integrates LNP-driven mechanisms as a central pathogenic axis, initiated by the systemic distribution and accumulation of LNPs in the heart. While the mRNA payload is cleared within days, the synthetic ionizable lipids -ALC-0315 (BNT162b2) and SM-102 (mRNA-1273) persist significantly longer than the mRNA payload itself. These two lipids differ in biodegradability and pharmacokinetic distinctions, together with differences in lipid dose and formulation, they may contribute to the divergent myocarditis rates observed between the two vaccine products. In this suggesting review, the first hit" involves the disruption of myocardial energy metabolism by these lipids, which can integrate into cellular membranes and impair mitochondrial fatty acid oxidation. This is compounded by a second hit of direct innate immune activation, preclinical studies demonstrate that LNPs engage pattern-recognition receptors (PRRs) like toll-like receptors (TLRs) and the NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines such as IL-1β and IL-18. Inflammation is then amplified via Damage-associated molecular patterns (DAMPs) released from stressed cardiomyocytes. The clinical outcome-ranging from self-limited mild myocarditis to fulminant disease with diverse histopathological patterns-is likely shaped by host susceptibility factors, including sex hormones, genetic predisposition, and prior immune priming, that modulate the intensity of this pathogenic cascade.
Crosstalk Between Inflammation and Cellular Senescence in Osteoarthritis: Modulatory Actions of Olive Oil and Its Bioactive Compounds.
Medoro A, Tardugno R, Davinelli S … +5 more , Clodoveo ML, Iorio EL, Tsolaki M, Corbo F, Scapagnini G
Mediators Inflamm · 2026 · PMID 42261702 · Full text
Osteoarthritis is a degenerative joint disorder characterized by progressive cartilage degradation, subchondral bone alterations, and persistent low-grade inflammation. Recent findings have identified a strong interplay...
Osteoarthritis is a degenerative joint disorder characterized by progressive cartilage degradation, subchondral bone alterations, and persistent low-grade inflammation. Recent findings have identified a strong interplay between inflammation and cellular senescence in osteoarthritis. Chronic inflammatory signals promote the accumulation of senescent cells, while senescent cells amplify inflammatory pathways through their senescence-associated secretory phenotype (SASP). This bidirectional loop accelerates tissue damage by perpetuating oxidative stress, matrix degradation, and the release of proinflammatory mediators that reinforce the senescence process. Likewise, the biological activities of olive oil and its bioactive compounds, including monounsaturated and polyunsaturated fatty acids (PUFA), phenolic compounds (mainly ligstroside, oleocanthal, oleuropein, and hydroxytyrosol), squalene, phytosterols, vitamins (particularly vitamin E), and carotenoids, have attracted increased attention. These compounds may synergistically exert their effects through several interrelated mechanisms that influence both inflammatory and senescence pathways. They may modulate key signaling cascades, such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Toll-like receptors (TLRs), that drive the release of proinflammatory cytokines. Moreover, by attenuating SASP, olive oil compounds can potentially attenuate the vicious cycle between inflammation and senescence, slowing cartilage degradation and preserving joint function. Here, we synthesize current findings on the molecular mechanisms and clinical implications of bioactive compounds from olive oil, emphasizing their role in modulating both inflammation and senescence during osteoarthritis.
Neutrophil Extracellular Traps in Wound Healing of Diabetes: Mechanisms, Inducers, and Therapeutic Implications.
Xue J, Wang Z, Qi W
Mediators Inflamm · 2026 · PMID 42253170 · Full text
Wound healing damage, especially diabetic foot ulcer (DFU), is a serious complication of diabetes mellitus (DM). New evidence shows that neutrophil extracellular traps (NETs) are the key factor of this pathology. This re...
Wound healing damage, especially diabetic foot ulcer (DFU), is a serious complication of diabetes mellitus (DM). New evidence shows that neutrophil extracellular traps (NETs) are the key factor of this pathology. This review summarizes the literature from 2015 to 2024 to clarify the mechanism of NETs and its harmful effects on diabetes wounds. We have provided a detailed introduction to common in vitro NETs inducers such as phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and calcium ionophore, as well as core protein markers such as citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). Importantly, evidence from animal models and human patients suggests that sustained NETs maintain inflammation, hinder angiogenesis, and delay tissue repair. Finally, we explored promising clinical therapeutic strategies that promote healing by targeting NETs, such as DNase I degradation and inhibition of specific signaling pathways, highlighting the potential of NETs inhibition strategies in improving diabetic wound care.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe