Mediators Of Inflammation[JOURNAL]
Sun
200 papers
Identification of Immune-Related Lactylation Genes in Rheumatoid Arthritis With Atherosclerosis: A Comprehensive Analysis Using Bulk and Single-Cell RNA Sequencing Data.
Hu J, Tao W, Qian X … +4 more , Liu Q, Jin Z, Kong R, Gao J
Mediators Inflamm · 2026 · PMID 42112590 · Full text
BACKGROUND: Growing evidence demonstrates that rheumatoid arthritis (RA), a chronic autoimmune disease characterized by joint inflammation and immune system dysfunction, can significantly accelerate the progression of at...
BACKGROUND: Growing evidence demonstrates that rheumatoid arthritis (RA), a chronic autoimmune disease characterized by joint inflammation and immune system dysfunction, can significantly accelerate the progression of atherosclerosis (AS). Studies have revealed that patients with RA and AS share numerous common features in terms of immune dysregulation and metabolic alterations, with abnormalities in lactate metabolism being particularly prominent. However, the role of lactate and its associated protein modification-lactylation-in the pathogenesis of RA-related AS remains unclear. The primary objective of this study is to comprehensively investigate lactylation-related genes as potential diagnostic markers for patients with concurrent RA and AS. METHODS: We identified the core genes associated with lactylation by integrating and analyzing two disease-related datasets: a RA dataset (GSE89408) and an AS dataset (GSE43292) from the GEO database. Through comprehensive analysis, we examined the functions associated with the hub genes and investigated the correlation between their expression levels and immune infiltration. Additionally, we explored the lactylation scores of different immune cells using single-cell data. RESULTS: We identified four lactylation-related hub genes (SMARCC2, CCNA2, NUP50, and GATAD2B) highly associated with concurrent RA and AS, which showed high diagnostic potential (area under the curve [AUC] > 0.88). Further analysis revealed that these four hub genes were significantly correlated with the level of immune cell infiltration. To better understand the relationship between lactylation and immune cells, we analyzed single-cell sequencing data, which demonstrated significant differences in lactylation scores across various types of immune cells. CONCLUSIONS: These findings highlight lactylation-related genes as promising diagnostic markers and provide insights into shared pathogenic mechanisms of RA and AS.
Lung Tissue Metabolome Investigation Reveals the In Vivo Effects of Zhuye Shigao Decoction in an LPS-Induced Acute Pneumonia Model in Mice.
Tang H, Sun Z, Qin W … +4 more , Cai G, Gao W, Wang Y, Gong J
Mediators Inflamm · 2026 · PMID 42112569 · Full text
Zhuye Shigao Decoction (ZSD), a classic traditional Chinese medicine (TCM) formula, has demonstrated therapeutic efficacy in clinical settings for acute pneumonia; however, its mechanism of action remains elusive. This s...
Zhuye Shigao Decoction (ZSD), a classic traditional Chinese medicine (TCM) formula, has demonstrated therapeutic efficacy in clinical settings for acute pneumonia; however, its mechanism of action remains elusive. This study aims to investigate the therapeutic effects and potential mechanisms of ZSD in lipopolysaccharide (LPS)-induced acute pneumonia in mice. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach, integrated with a gene expression omnibus (GEO) data mining technique, was employed in this investigation. The results indicated that ZSD administration significantly alleviated LPS-induced pathological changes in lung tissue. In the model group, the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were increased, whereas the levels of immunoglobulin A (IgA) and immunoglobulin M (IgM) were significantly decreased. These indicators were reversed considerably in the ZSD-high dose (ZSD-H) group. A total of 118 metabolites exhibiting significant alterations in lung tissue were identified through metabolomics analysis. Following ZSD treatment, 84 of these metabolites were negatively regulated, and the associated metabolic processes implicated multiple pathways, including sphingolipid and arachidonic acid (AA) metabolism. Differentially expressed genes (DEGs) were identified through a comprehensive analysis of GEO datasets. Integrative pathway analysis identified signaling pathways associated with ZSD treatment effects in acute pneumonia. Notably, the Janus kinase/signal transducer and activator of transcription (JAK-STAT) and Toll-like receptor (TLR) signaling pathways emerged as critical contributors to these effects. This study indicates that ZSD can exert therapeutic effects on LPS-induced acute pneumonia through a regulatory mechanism involving multiple components, targets, and pathways.
Admission Serum Ferritin Levels as a Predictor of Severe Disease in Hospitalized Pediatric Patients in Mexico.
Turrubiates-Hernandez GA, Mares-Gil JE, de la Cruz-de la Cruz C … +1 more , Tamez-Rivera O
Mediators Inflamm · 2026 · PMID 42106053 · Full text
INTRODUCTION: Biomarkers that predict the severity of a disease on admission would be a valuable tool for pediatricians. Ferritin has been proposed as a predictive biomarker for various conditions; however, multiple thre...
INTRODUCTION: Biomarkers that predict the severity of a disease on admission would be a valuable tool for pediatricians. Ferritin has been proposed as a predictive biomarker for various conditions; however, multiple thresholds have been described depending on the diagnosis. A threshold for severe pediatric disease regardless of the final diagnosis is lacking. MATERIAL AND METHODS: We performed a single-center retrospective observational study of patients admitted to the emergency department (ED) of a pediatric reference hospital in Mexico. Serum ferritin levels were requested to all admitted patients <16 years old and included in the study. Risk prediction models for various clinical outcomes were built using receiver operating characteristic (ROC) curves. RESULTS: Admission ferritin levels were significantly higher in patients who required vasopressors (p < 0.001), blood transfusion (p < 0.001), and admission to the pediatric intensive care unit (PICU; p < 0.001). Patients with admission ferritin >500 ng/mL had a longer hospital stay (p = 0.037). Admission ferritin was a predictor of all-cause mortality (area under the curve [AUC] = 0.67, 95% confidence interval [CI]: 0.54-0.80, p = 0.009; sensitivity 55%, specificity 76.3%). A cut-off point of 385 ng/mL was associated with mortality (OR 3.21, 95% CI: 1.29-7.97). CONCLUSION: We provide evidence that ferritin may be used as a predictive biomarker in the pediatric ED. In our study, ferritin levels on admission predicted all-cause mortality. Multicenter studies are required to validate our findings in a larger sample.
C1q/TNF-Related Protein 4 (C1QTNF4) Acts as an Adipokine That Ameliorates Diet-Induced Obesity by Improving Energy Metabolism and Alleviating Adipose Inflammation.
Na D, He Y, Liu X … +6 more , Huang M, Xie S, Li H, Liu J, Zhang H, Wang L
Mediators Inflamm · 2026 · PMID 42106023 · Full text
BACKGROUND: The C1q/TNF-related protein (C1QTNF) plays a crucial role in the intricate connection between obesity and inflammation, acting as a significant adipokine. This study aims to investigate the potential of C1QTN...
BACKGROUND: The C1q/TNF-related protein (C1QTNF) plays a crucial role in the intricate connection between obesity and inflammation, acting as a significant adipokine. This study aims to investigate the potential of C1QTNF4 as an antiobesity and anti-inflammatory adipokine. METHODS: Forty-eight subjects, with or without obesity and diabetes mellitus (DM), were categorized into two groups based on their health condition. Measurements of C1QTNF4, glucose, and adipokine concentrations were conducted. Seven-week-old C57BL/6J mice were segregated into four groups, with eight mice in each group of both sexes. C1QTNF4 transgenic (Tg) mice and their corresponding littermate controls were subjected to either a high-fat (HF) diet (HFD) or a standard chow diet for 14 weeks. RESULTS: C1QTNF4 and leptin levels increased, while adiponectin levels decreased in subjects with obesity and DM compared to normal individuals. C1QTNF4 Tg mice on a HFD exhibited resistance to weight gain, accompanied by an amelioration of insulin resistance (IR). Fatty liver and chronic adipose inflammation were also mitigated. In the liver and skeletal muscle of C1QTNF4 Tg mice, C1QTNF4 activated the AMP-activated protein kinase (AMPK) pathway associated with insulin sensitivity and energy expenditure. Plasma IL-6 decreased in Tg mice on a HFD, indicating that C1QTNF4 alleviates inflammation via the IL-6-JAK1/2-STAT3 pathway. CONCLUSIONS: C1QTNF4 emerges as an adipokine with a regulatory role in adipogenesis, addressing energy imbalances and reducing inflammation. This study suggests that C1QTNF4 represents a potential drug target for treating obesity, IR, and inflammation.
Integrating Inflammation and Lipid Metabolism Biomarkers for Early Risk Stratification in Acute Cerebral Infarction: A Nomogram-Based Approach.
Ding M, Dai J, Cao Z … +2 more , Wang H, Zhu X
Mediators Inflamm · 2026 · PMID 42095576 · Full text
OBJECTIVE: To assess the prognostic value of the homocysteine-to-high-density lipoprotein cholesterol (Hcy/HDL-C) ratio and the high-sensitivity C-reactive protein-to-albumin (hs-CRP/Alb) ratio as biomarkers for predicti...
OBJECTIVE: To assess the prognostic value of the homocysteine-to-high-density lipoprotein cholesterol (Hcy/HDL-C) ratio and the high-sensitivity C-reactive protein-to-albumin (hs-CRP/Alb) ratio as biomarkers for predicting functional outcomes in acute cerebral infarction (ACI) patients treated with recombinant tissue plasminogen activator (rt-PA). METHODS: A retrospective analysis was conducted on 204 ACI patients who received rt-PA. Patients were classified into two groups based on their functional outcomes at 3 months poststroke: good (modified Rankin scale [mRS] ≤ 2) and poor (mRS > 2). Logistic regression and restricted cubic spline (RCS) analyses were performed to evaluate the association between Hcy/HDL-C and hs-CRP/Alb ratios with functional outcomes. A predictive nomogram was developed incorporating these biomarkers, baseline NIHSS scores, and atrial fibrillation. The performance of this nomogram was compared to traditional risk models. RESULTS: Elevated Hcy/HDL-C and hs-CRP/Alb ratios were identified as independent predictors of poor functional outcomes in ACI patients (p < 0.05). The nomogram, incorporating these biomarkers along with NIHSS scores and atrial fibrillation, demonstrated superior predictive performance with a C-index of 0.936 and an AUC of 0.935, outperforming traditional risk models (C-index = 0.782). Subgroup analysis revealed that Hcy/HDL-C was more predictive in patients with large-artery atherosclerosis (LAA), while hs-CRP/Alb showed stronger prognostic value in patients with cardioembolic strokes. CONCLUSION: The Hcy/HDL-C and hs-CRP/Alb ratios serve as independent and valuable biomarkers for predicting poor outcomes in ACI patients post-rt-PA treatment. The nomogram incorporating these biomarkers provides superior prognostic accuracy and could be a useful tool for personalized risk assessment and management in ACI patients following thrombolytic therapy.
Salidroside and Hongjingtian Injection Inhibit the Onset and Progression of Asthma via Pyroptosis in the Ozone-Exposed Inflammation Environment.
Lu Z, Li J, Hou S … +2 more , Zhang H, Yan X
Mediators Inflamm · 2026 · PMID 42093379 · Full text
BACKGROUND: Ozone is a common air pollutant, and exposure to high concentrations of ozone can promote the onset and progression of asthma. Pyroptosis is a form of cell death associated with asthma exacerbation. METHODS:...
BACKGROUND: Ozone is a common air pollutant, and exposure to high concentrations of ozone can promote the onset and progression of asthma. Pyroptosis is a form of cell death associated with asthma exacerbation. METHODS: This study aimed to identify ozone-related pyroptosis genes through network toxicology and RNA-seq analysis and to investigate the role of pyroptosis genes in asthma using multiple asthma tissue samples and machine learning methods. Key pyroptosis genes with significant roles in asthma were identified through experiments and multiomics approaches. Using network pharmacology methods, we screened traditional Chinese medicine (TCM) components associated with key pyroptosis genes. Through molecular clustering and molecular docking, we explored the interaction between TCM components and key genes. Using animal model drug interventions, we further analyzed the therapeutic effects of TCM components targeting pyroptosis on asthma under ozone exposure. RESULTS: This study identified 16 ozone-related pyroptosis genes through network pharmacology and transcriptomics data analysis. Based on multiple asthma tissue samples and machine learning methods, the 16 pyroptosis genes were found to have diagnostic predictive roles in asthma. Through experimentation and multiomics approaches, gasdermin D (GSDMD) was identified as a key gene in exacerbating asthma under ozone exposure. Furthermore, scRNA-seq and virtual knockout revealed that GSDMD exerts a pro-inflammatory effect on the asthma microenvironment. Using network pharmacology methods, we screened for salidroside, a Chinese herbal component related to GSDMD. Through molecular clustering and molecular docking, we identified seven salidroside analogs in Hongjingtian injection (HJT). Using an animal model drug intervention, we further analyzed the intervention effects of salidroside and HJT on asthma under ozone exposure. CONCLUSIONS: Ozone promotes the onset and progression of asthma by exacerbating inflammation and pyroptosis. salidroside and its analogs can target GSDMD to inhibit asthma exacerbation in ozone-induced inflammation environments.
Ziziphus jujuba Mill. Suspension Ameliorates Scopolamine-Induced Cognitive Impairment via PTGS2-Centered Neuroinflammatory Signaling.
Liu Q, Wang Y, Wang B … +4 more , Wang J, Zhang M, Liu Y, Min X
Mediators Inflamm · 2026 · PMID 42093362 · Full text
BACKGROUND: Cognitive impairment is a common feature of neurodegenerative diseases, in which sustained neuroinflammation critically contributes to neuronal dysfunction and memory decline. As a representative condition, A...
BACKGROUND: Cognitive impairment is a common feature of neurodegenerative diseases, in which sustained neuroinflammation critically contributes to neuronal dysfunction and memory decline. As a representative condition, Alzheimer's disease (AD) provides key insights into inflammation-associated cognitive impairment. However, current anti-inflammatory interventions exhibit limited efficacy and potential adverse effects, highlighting the need for safer strategies targeting neuroinflammation-related cognitive dysfunction. OBJECTIVE: Guided by the concept of food-medicine homology, this study aimed to elucidate the molecular mechanisms by which Ziziphus jujuba alleviates cognitive impairment associated with neuroinflammation. METHODS: AD-relevant targets associated with cognitive dysfunction were obtained from Gene Expression Omnibus (GEO) and GeneCards, and active compounds of Z. jujuba were retrieved from traditional Chinese medicine systems pharmacology (TCMSP). Shared targets were prioritized using least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine (SVM) algorithms. The diagnostic value of the core target was evaluated by receiver operating characteristic (ROC) analysis and a nomogram model with calibration and decision curve analysis (DCA). Functional enrichment, localization analyses, and molecular docking were performed. Experimental validation was conducted in a scopolamine-induced cognitive impairment mouse model using the Morris water maze (MWM), histopathology, and western blotting. RESULTS: PTGS2 was identified as a key inflammatory target associated with neuroinflammation-related cognitive impairment and was enriched in the NOD-like receptor (NLR) signaling pathway. ROC and nomogram analyses indicated good diagnostic and predictive performance (area under the curve [AUC] > 0.7). PTGS2 was localized on chromosome 1 and showed relatively high expression in the cerebral cortex. Z. jujuba compounds exhibited strong binding to PTGS2 (ΔG ≤ -8.0 kcal/mol). In vivo, Z. jujuba improved cognitive performance, alleviated hippocampal injury, and downregulated PTGS2 and related inflammatory signaling pathways, including NLRP3/NF-κB/MAPK and interleukin (IL)-1β. CONCLUSION: This study demonstrates that Z. jujuba ameliorates neuroinflammation-related cognitive dysfunction primarily by suppressing PTGS2-centered inflammatory signaling. Integrating computational analyses and in vivo validation in scopolamine-induced mice, our findings support Z. jujuba as a safe multitarget intervention for inflammation-associated cognitive impairment and highlight the potential of food-medicine homology in neuroinflammatory cognitive disorders.
Single-Cell Transcriptomics Identifies BST2 as an Oncogenic Driver and Immunotherapy Biomarker in Lung Adenocarcinoma.
Zhu K, Lin M, Lin C … +8 more , Hu T, Cao Z, Huang S, Shen Y, Zeng J, He J, Shen W, Ying J
Mediators Inflamm · 2026 · PMID 42089585 · Full text
BACKGROUND: Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide. The tumor microenvironment (TME) plays a pivotal role in LUAD progression, but the specific molecular mechanisms driving ma...
BACKGROUND: Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide. The tumor microenvironment (TME) plays a pivotal role in LUAD progression, but the specific molecular mechanisms driving malignancy and immune evasion remain incompletely understood. Bone marrow stromal cell antigen 2 (BST2) has been implicated in other cancers, yet its functional role and therapeutic potential in LUAD require further elucidation. METHODS: We integrated single-cell RNA sequencing (scRNA-seq) data from primary LUAD tissues and normal lung tissues with bulk RNA-seq data from The Cancer Genome Atlas (TCGA)-LUAD and GEO cohorts. Malignant epithelial cells were identified using inferCNV analysis. Cellular trajectory and cell-cell communication analyses were systematically performed to delineate the malignant transformation process and its interactions with the TME. High-dimensional weighted gene coexpression network analysis further identified key functional modules within malignant subpopulations. The oncogenic role of BST2 was comprehensively validated through differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and in vitro cellular assays, including RT‑qPCR, MTT, colony formation, Transwell invasion, and wound healing experiments. In addition, we employed the tumor immune dysfunction and exclusion (TIDE) algorithm to evaluate its association with immunotherapy response and performed drug screening via the Clue.io platform to explore its therapeutic potential. RESULTS: scRNA-seq analysis revealed significant heterogeneity in the TME and identified two distinct subpopulations of malignant epithelial cells. Trajectory analysis uncovered a specific lineage (Lineage 4) driving the normal-to-malignant transition, while cell communication analysis highlighted interactions between malignant cells and tumor-associated macrophages (TAMs) mediated by MIF and APP signaling pathways. High-dimensional weighted gene coexpression network analysis (hdWGCNA) identified a coexpression gene module (Module 1) specifically enriched in malignant subpopulations. By intersecting with a set of immunoregulatory genes, BST2 was ultimately determined as a key candidate oncogene. BST2 was significantly upregulated in malignant epithelial cells and TAMs, and its high expression was closely associated with poor patient prognosis. GSEA demonstrated that high BST2 expression was linked to the activation of crucial oncogenic pathways, including oxidative phosphorylation, Kras signaling, and epithelial-mesenchymal transition (EMT). In vitro validation further confirmed that BST2 knockdown suppressed LUAD cell proliferation, migration, and invasion. Furthermore, elevated BST2 expression was associated with reduced efficacy of immune checkpoint blockade (ICB) therapy. CONCLUSION: Our study unveils BST2 as a critical oncogene in LUAD, promoting tumor progression and influencing the TME, particularly via TAM recruitment. BST2 expression predicts patient prognosis and immunotherapy response, positioning it as a promising biomarker and therapeutic target.
Role of Programmed Cell Death in the Pathogenesis of Kawasaki Disease: Mechanisms and Therapeutic Implications.
Ding B, Huang Z, Alifu A … +4 more , Wang K, Zhang D, Wang Y, Chen R
Mediators Inflamm · 2026 · PMID 42089438 · Full text
Programmed cell death (PCD) is a genetically regulated, orderly cell death process essential for tissue homeostasis. Contemporary PCD comprises a broad spectrum, including apoptosis, pyroptosis, ferroptosis, necroptosis,...
Programmed cell death (PCD) is a genetically regulated, orderly cell death process essential for tissue homeostasis. Contemporary PCD comprises a broad spectrum, including apoptosis, pyroptosis, ferroptosis, necroptosis, autophagy-dependent cell death, NETosis, parthanatos, and entotic cell death. Kawasaki disease (KD) is an acute pediatric systemic vasculitis and a leading cause of acquired childhood heart disease, with coronary artery lesions as the most severe complication. Mounting evidence confirms that PCD is tightly associated with KD-related vascular endothelial injury and inflammatory amplification. Among all PCD subtypes, apoptosis, pyroptosis, and ferroptosis have the most sufficient and direct evidence in KD pathogenesis, mediating vascular wall damage and inflammatory imbalance via distinct molecular pathways. This review focuses on these three well-documented PCD forms (with a brief overview of other PCD subtypes and their potential KD relevance), systematically elaborates their crosstalk with KD pathogenesis, summarizes current research progress, and proposes targeted therapeutic strategies for KD.
Novel Systemic Inflammatory Indices (SII and SIRI) as Mediators Between BMI and Hearing Loss.
Huang H, Zhou W, Du Y … +2 more , Gao Y, Fan Y
Mediators Inflamm · 2026 · PMID 42057737 · Full text
OBJECTIVE: This study aimed to examine the associations between body mass index (BMI) and hearing loss (HL), and to explore the mediating role of inflammation using data from the National Health and Nutrition Examination...
OBJECTIVE: This study aimed to examine the associations between body mass index (BMI) and hearing loss (HL), and to explore the mediating role of inflammation using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: A cohort of 5489 participants aged ≥20 years from six NHANES cycles (2005-2012 and 2015-2018) was evaluated. Linear regression analysis was used to assess the relationships between BMI and HL. Three models were developed: (1) the association between BMI and low-frequency (LF) HL and speech-frequency (SF) HL; (2) the association between BMI and inflammatory markers (systemic immune-inflammatory index [SII] and systemic inflammatory response index [SIRI]); and (3) the association between SII/SIRI and LFHL/SFHL. Mediation analyses were conducted to evaluate the role of SII and SIRI in the relationship between BMI and HL. RESULTS: Among the three groups, participants with higher BMIs exhibited higher values for SII, SIRI, LFHL, and SFHL. Positive correlations were observed between BMI and inflammation, inflammation and HL, and BMI and HL in all models. Mediation analysis revealed that SII mediated 9.87% of the effect of BMI on LFHL and 8.25% on SFHL, while SIRI mediated 17.47% and 16.59% of these effects, respectively. Although modest, these consistent mediating effects suggest inflammation contributes to, but does not wholly account for, the obesity-hearing relationship. CONCLUSION: This study indicates that systemic inflammatory markers (SII and SIRI) partially mediate the association between BMI and HL. These findings suggest that inflammation represents a potential mechanistic link in obesity-related auditory dysfunction. Future longitudinal studies are needed to validate these pathways and inform targeted prevention strategies.
Identification of Anti-Inflammatory and Analgesic Mechanisms of Naru-3 Wei Pill Using Animal Models, UHPLC-QE-MS, and Integrated Network Pharmacology.
Han Z, Kang H, Zhang A … +8 more , Qigeqin, Baolechaolu, Wulanqiqige, Wang H, Xu Y, HaSi, Anda, Xue L
Mediators Inflamm · 2026 · PMID 42052934 · Full text
BACKGROUND: Naru-3 Wei Pill is a traditional Mongolian Medicine (TMM) that has anti-inflammatory, analgesic, and antibacterial effects. The present study aimed to demonstrate the anti-inflammatory and analgesic effect of...
BACKGROUND: Naru-3 Wei Pill is a traditional Mongolian Medicine (TMM) that has anti-inflammatory, analgesic, and antibacterial effects. The present study aimed to demonstrate the anti-inflammatory and analgesic effect of Naru-3 Wei Pill, identify the core components and key targets and determine the pharmacological basis and mechanism of its blood-borne components. METHODS: The anti-inflammatory and analgesic effects of Naru-3 pills were studied using hot plate, tail flick, and acetic acid-induced writhing tests. The blood-borne components of Naru-3 Wei Pill were identified using ultrahigh-performance liquid chromatography with Q-Exactive mass spectrometry (UHPLC-QE-MS), and their targets were screened using ChEMBL, TCMIO, GeneCards, and TTD databases. Network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) network was performed. Molecular dynamics methods, PCR and western blot, were used for verification of the results. RESULTS: Multiple pain models results indicate that Naru-3 pills exert anti-inflammatory and analgesic effects by modulating the PI3K signaling pathways and reducing inflammation factors (interleukin [IL]-6). A total of 35 blood-borne components were identified, acting on 291 targets involving 172 pathways. The core targets included AKT1, SRC, mitogen-activated protein kinase 14 (MAPK14), and ESR1. Molecular docking and dynamics simulations conformed strong binding affinity of the complexes formed between Rhein and AKT1, MAPK1, and SRC, and between genistein and SRC. PCR and western blot confirm the regulation of AKT/PI3K pathway of Naru-3 pills in animal models. CONCLUSION: Naru-3 pills significantly prolonged pain thresholds and reduced pain behaviors in mice. The study identified the material basis and mechanisms of its anti-inflammatory and analgesic effects, providing a foundation for further research.
RETRACTION: Krüppel-Like Factor 5 Mediates Proinflammatory Cytokine Expression in Lipopolysaccharide-Induced Acute Lung Injury through Upregulation of Nuclear Factor-κB Phosphorylation In Vitro and In Vivo.
Of Inflammation M
Mediators Inflamm · 2026 · PMID 42050802 · Full text
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Evaluating Ribosomal Protein L19 mRNA as a Biomarker in Ulcerative Colitis: Implications for Severity Assessment.
Shi L, Jin G, Gao X … +4 more , Chen Y, Zhao Q, Lin J, Zhou G
Mediators Inflamm · 2026 · PMID 42033356 · Full text
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, characterized by immune dysregulation, genetic susceptibility, and environmental factors such as diet and psychosocial...
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, characterized by immune dysregulation, genetic susceptibility, and environmental factors such as diet and psychosocial stress. The etiology of UC is complex, involving multiple interrelated factors that drive its pathogenesis and clinical progression. METHODS: This cross-sectional study investigated the potential role of ribosomal protein L19 (RPL19) mRNA in UC. A total of 40 patients with UC and 29 healthy controls (HC) were prospectively enrolled from the Department of Gastroenterology, Affiliated Hospital of Jining Medical University, between November 2021 and November 2023. RPL19 mRNA levels in the intestinal mucosa of UC patients were quantified using quantitative PCR analysis. Subsequently, the associations of RPL19 mRNA expression with disease severity and with the levels of key inflammatory cytokines were statistically assessed. RESULTS: RPL19 mRNA expressions were significantly regulated in UC patients compared to HC. It exhibited a significant inverse correlation with the levels of both interleukin-2 (IL-2) and interleukin-4 (IL-4). Importantly, RPL19 mRNA levels also correlated with key clinical disease activity indices. CONCLUSIONS: This study demonstrates that mucosal RPL19 mRNA expression levels are significantly elevated in UC patients and correlate positively with endoscopic and histological disease severity. These findings identify RPL19 as a potential biomarker for reflecting local disease activity in UC.
The Vitamin D3 Analog Calcipotriol Attenuates Pancreatic Cancer Malignancy via Downregulating Thrombospondin 1 in Pancreatic Stellate Cells.
Wu Y, Zhang C, Ilmer M … +7 more , Weniger M, Li Q, Wang J, Miksch RC, Werner J, D'Haese JG, Renz B
Mediators Inflamm · 2026 · PMID 42033294 · Full text
Pancreatic ductal adenocarcinoma (PDAC) exhibits pronounced desmoplasia, primarily attributed to the activation of pancreatic stellate cells (PSCs) from a quiescent state (quiescent PSCs [qPSCs]) to an activated form (ac...
Pancreatic ductal adenocarcinoma (PDAC) exhibits pronounced desmoplasia, primarily attributed to the activation of pancreatic stellate cells (PSCs) from a quiescent state (quiescent PSCs [qPSCs]) to an activated form (activated PSCs [aPSCs]), which facilitates tumor progression and therapeutic resistance. This study investigates the potential of the vitamin D3 (VD) analog calcipotriol (Cal) to modulate this activation process and its impact on PDAC cell malignancy, with a particular focus on the thrombospondin 1/cluster of differentiation 47 (THBS1/CD47) signaling axis. Through analyzing VDR mRNA expression in aPSCs versus PDAC cells, we found that aPSCs are more responsive to VD signaling. Treatment with Cal significantly reduced aPSC activation, as evidenced by decreased α-SMA expression and THBS1 secretion, thereby diminishing stromal support for PDAC cell proliferation, migration, and invasion. These changes were mediated by the inhibition of the THBS1/CD47 axis, highlighting a novel mechanism by which Cal disrupts the supportive tumor microenvironment. Our findings highlight the therapeutic potential of targeting aPSCs with VD analogs in PDAC, suggesting a new direction for treatments that aim to interrupt the desmoplastic reaction and thereby inhibit PDAC progression.
Correction to "The Underlying Mechanism Involved in Gefitinib Resistance and Corresponding Experiment Validation in Lung Cancer".
Mediators Inflamm · 2026 · PMID 42033292 · Full text
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Correction to "Overexpression and Selectively Regulatory Roles of IL-23/IL-17 Axis in the Lesions of Oral Lichen Planus".
Mediators Inflamm · 2026 · PMID 42033286 · Full text
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Association Between Sleep and Cardiovascular-Kidney-Metabolic Syndrome: Mediation Analysis of Inflammatory Biomarkers.
Hu M, Xu Y, Ming J … +7 more , Zhang X, Bian X, Liang X, Wang H, Zheng L, Zhang Y, Guo Z
Mediators Inflamm · 2026 · PMID 42030030 · Full text
BACKGROUND AND AIMS: Sleep disturbances are linked to individual cardiometabolic diseases, but their association with the emerging cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of interrelated condition...
BACKGROUND AND AIMS: Sleep disturbances are linked to individual cardiometabolic diseases, but their association with the emerging cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of interrelated conditions, remains less clear. To evaluate the association of sleep factors (sleep duration, diagnosed sleep disorder, self-reported trouble sleeping) with the risk of CKM syndrome. METHODS AND RESULTS: We included 11,949 adults from the National Health and Nutrition Examination Survey (NHANES). A composite sleep score (0-3, from healthy to poor) was derived from sleep duration, diagnosed sleep disorder, and self-reported trouble sleeping. CKM syndrome was defined and staged (Stage 0-4) based on the coexistence and severity of cardiometabolic and kidney diseases. Systemic inflammation was assessed using the systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI). A poor sleep pattern was significantly associated with higher odds of CKM syndrome (fully adjusted odds ratio [OR] = 1.64, 95% confidence interval (CI): 1.37-1.95) and with more advanced CKM stages in an ordinal model, indicating a dose-response relationship. In exploratory mediation analysis, SII and SIRI appeared to partially mediate the association between self-reported trouble sleeping and CKM syndrome in initial models. However, this mediating effect was substantially attenuated and became nonsignificant for SII after comprehensive adjustment for adiposity (body mass index (BMI) and waist circumference) and lifestyle factors. CONCLUSIONS: Poor sleep patterns are robustly associated with an increased risk and severity of CKM syndrome. While systemic inflammation was correlated with both sleep disturbances and CKM, its role as an independent mediator was largely explained by shared variance with obesity and metabolic factors. These findings underscore sleep health as a potential target for multimodal risk reduction within the CKM framework, though causality needs confirmation in longitudinal studies.
Identification and Experimental Verification Reveal SLC2A3 Associated With Prognosis and Immune Infiltration in Colon Adenocarcinoma.
Zhao Z, Ju K, Lv J … +2 more , Lu Z, Luo L
Mediators Inflamm · 2026 · PMID 42029110 · Full text
Colon adenocarcinoma (COAD) exhibits marked molecular heterogeneity that limits accurate prognostic prediction and therapeutic stratification. Parthanatos, a poly (ADP-ribose) polymerase-1 (PARP1)-dependent form of regul...
Colon adenocarcinoma (COAD) exhibits marked molecular heterogeneity that limits accurate prognostic prediction and therapeutic stratification. Parthanatos, a poly (ADP-ribose) polymerase-1 (PARP1)-dependent form of regulated cell death, has been implicated in tumor biology, yet its relevance in COAD remains poorly understood. In this study, we systematically characterized parthanatos-associated genes (PAGs) using integrated transcriptomic analyses from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Distinct parthanatos-related molecular subtypes with significantly different clinical outcomes and immune landscapes were identified. A parthanatos-based prognostic scoring system was constructed using machine learning algorithms and validated in an independent cohort, demonstrating robust predictive performance and independent prognostic value. High PAG scores were associated with advanced disease stage, altered immune infiltration, increased tumor mutation burden (TMB), and differential sensitivity to chemotherapy and predicted immunotherapy response. Single-cell RNA sequencing further revealed broad cellular expression of PAG, while preliminary in vitro experiments suggested that solute carrier family 2 member 3 (SLC2A3), the most prominent risk gene in the prognostic model, may promote COAD cell proliferation and invasion, although these findings require validation in additional models. Collectively, our findings establish parthanatos as a clinically relevant regulatory axis in COAD and provide a novel framework for prognosis assessment and therapeutic targeting.
Current Progress in the Role of Ferroptosis in Skeletal Muscle Atrophy.
Chen Y, Guo Y, Zhao Z … +3 more , Yang S, Guo B, Xu J
Mediators Inflamm · 2026 · PMID 42010894 · Full text
Atrophy of skeletal muscles, caused by multiple factors, including ageing, disuse, trauma and systemic diseases, is a major pathological condition that affects physical performance and systemic health by the loss of musc...
Atrophy of skeletal muscles, caused by multiple factors, including ageing, disuse, trauma and systemic diseases, is a major pathological condition that affects physical performance and systemic health by the loss of muscle function; in effect, weakening the whole body and leading to disabling conditions such as sarcopenia, frailty and increased fall risk. First reported in 2012 by Dixon et al., ferroptosis is a newly identified, distinct type of regulated cell death characterised by unique biochemical and morphological features and differs from classic apoptosis and necrosis. One hallmark feature of ferroptosis is its iron-dependence: excessive free intracellular iron deposits catalyse rapid peroxidation of membrane lipids, and release cytotoxic lipid peroxides, which interfere with cell integrity. In recent years, significant progress has been made in elucidating the roles of ferroptosis-related pathways in skeletal muscle atrophy. Building on these advances, our review systematizes skeletal muscle atrophy into three significant categories: ageing-, disuse- and systemic disease-induced atrophy. It carefully explores the involvement of ferroptosis in each of these atrophy models. Moreover, this review identifies and discusses key ferroptosis-related molecular targets for consideration, aiming to provide insights and possible future directions for developing therapies to treat muscle-wasting disorders.
Rougan Tongluo Decoction Initiates Neuroprotection Against Cerebral Ischemia by Activating the Endogenous SLC6A8-Creatine-EARS2 Mitochondrial Pathway.
Ou C, Bai ZP, Hu GH … +3 more , Chen B, Wu DH, Long HJ
Mediators Inflamm · 2026 · PMID 41999222 · Full text
OBJECTIVE: The traditional Chinese medicine formula Rougan Tongluo Decoction (RGTL) was widely used to treat neurological injury after cerebral ischemia, though its specific underlying mechanisms remain unknown. This stu...
OBJECTIVE: The traditional Chinese medicine formula Rougan Tongluo Decoction (RGTL) was widely used to treat neurological injury after cerebral ischemia, though its specific underlying mechanisms remain unknown. This study investigates the mechanisms via which RGTL helps alleviate cerebral ischemic injury to provide theoretical support for its application in cerebral ischemia treatment. METHODS: A middle cerebral artery occlusion reperfusion (MCAO/R) rat model was established and treated with RGTL, N-acetylcysteine (NAC), creatine, or sh-EARS2. Network pharmacology and metabolomics were conducted to analyze the key efficacy-related metabolites in the hippocampal tissue. An OGD/R cell model was constructed using PC12 cells and treated with creatine, RGTL-containing serum, sh-SLC6A8, and sh-EARS2. Neuronal damage in the hippocampal tissues was assessed using HE and Nissl staining. Neuronal cell viability, mitochondrial membrane potential, and ROS levels were measured using CCK8, JC-1, and DCFH-DA assays. Mitochondrial damage was determined using transmission electron microscopy. The expression of SLC6A8/EARS2 axis and mitochondrial-related proteins (cytochrome c [Cyt c]) was examined using RT-qPCR and Western blot. RESULTS: RGTL treatment reduced TNF-α, IL-6, and ROS levels while increasing ATP and JC-1 in brain tissues of MCAO/R rats, thereby alleviating mitochondrial damage. The neuroprotective effects of RGTL were more pronounced than those of NAC. Succinic acid and creatine were identified as active drug ingredients and differential metabolites that may mediate RGTL's therapeutic effects via MMP3, GAMT, SLC6A8, and CASP3. Silencing SLC6A8 abolished the protective effects of creatine against OGD/R-induced neuronal cell apoptosis and mitochondrial damage. Creatine could bind to the EARS2 protein. Cell and animal experiments demonstrated that silencing EARS2 blocked the therapeutic effects of creatine in OGD/R and MCAO/R models, reversing its inhibition of neuronal apoptosis and mitochondrial damage. CONCLUSION: Creatine mediates the neuroprotective effects of RGTL by binding to EARS2, thus inhibiting mitochondrial damage and neuronal apoptosis to improve ischemic brain injury.
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