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Background & Aims: Patients with obstructive jaundice (OJ) are considered to be prothrombotic with increased risk of thromboembolism complications. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) and thrombosis risk in patients with OJ is unclear. In this study, we investigated NETs formation in OJ patients and the role of elevated unconjugated bilirubin (UCB) in inducing NETs, resulting in enhanced PCA and endothelial injury. Methods: NETs of OJ patients and healthy controls were measured. NETs PCA was assessed via coagulation time (CT), fibrin formation and purified coagulation complex production assays. Visualization of NETs and mitochondrial reactive oxygen species (MitoROS) were performed with a fluorescence microscope. We further used confocal microscopy to quantify the exposure of phosphatidylserine (PS), fibrin strands and FVa/Xa on Human umbilical vein endothelial cells (HUVECs). Results: Assessment of NETs components levels revealed greater NETs production in OJ patients than in healthy controls. Importantly, OJ‐NETs were responsible for enhanced PCA. UCB induced NETs formation via MitoROS accumulation and mitochondrial mobilization. HUVECs cocultured with OJ NETs lost their cell–cell junctions and consequently converted to a procoagulant phenotype. The PCA was attenuated by using DNase I alone or in combination with lactadherin. Conclusions: Our results suggest that UCB‐induced NETs play a prominent role in promoting the hypercoagulable and prothrombotic state in OJ patients. The increased MitoROS accumulation in neutrophils initiated NETosis. NETs are promising targets for indicating or improving coagulation disorders in OJ patients. [ABSTRACT FROM AUTHOR]

The study aimed to dissect the molecular mechanism of pancreatic cancer by a range of bioinformatics approaches. Three microarray datasets (GSE32676, GSE21654, and GSE14245) were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) with logarithm of fold change (|logFC|) >0.585 and p value <0.05 were identified between pancreatic cancer samples and normal controls. Transcription factors (TFs) were selected from the DEGs based on TRASFAC database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the DEGs using The Database for Annotation, Visualization and Integrated Discovery ( p value <0.05), followed by construction of protein-protein interaction (PPI) network using Search Tool for the Retrieval of Interacting Genes software. Latent pathway identification analysis was applied to analyze the DEGs-related pathways crosstalk and the pathways with high weight value were included in the pathway crosstalk network using Cytoscape. Sixty-five DEGs were screened out. CCAAT/enhancer-binding protein delta (CEBPD), FBJ osteosarcoma oncogene B (FOSB), Stratifin (SFN), Krüppel-like factor 5 (KLF5), Pentraxin 3 (PTX3), and nuclear receptor subfamily 4, group A, member 3 (NR4A3) were important TFs. Interleukin-6 (IL-6) was the hub node of the PPI network. DEGs were significantly enriched in NOD-like receptor signaling pathway which was primarily interacted with inflammation and immune related pathways (cytosolic DNA-sensing, hematopoietic cell lineage, intestinal immune network for IgA production and chemokine pathways). The study suggested CEBPD, FOSB, SFN, KLF5, PTX3, NR4A3, IL-6, and NOD-like receptor pathways were involved in pancreatic cancer. [ABSTRACT FROM AUTHOR]

The study aimed to dissect the molecular mechanism of pancreatic cancer by a range of bioinformatics approaches. Three microarray datasets (GSE32676, GSE21654, and GSE14245) were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) with logarithm of fold change (|logFC|) >0.585 and p value <0.05 were identified between pancreatic cancer samples and normal controls. Transcription factors (TFs) were selected from the DEGs based on TRASFAC database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the DEGs using The Database for Annotation, Visualization and Integrated Discovery (p value <0.05), followed by construction of protein-protein interaction (PPI) network using Search Tool for the Retrieval of Interacting Genes software. Latent pathway identification analysis was applied to analyze the DEGs-related pathways crosstalk and the pathways with high weight value were included in the pathway crosstalk network using Cytoscape. Sixty-five DEGs were screened out. CCAAT/enhancer-binding protein delta (CEBPD), FBJ osteosarcoma oncogene B (FOSB), Stratifin (SFN), Krüppel-like factor 5 (KLF5), Pentraxin 3 (PTX3), and nuclear receptor subfamily 4, group A, member 3 (NR4A3) were important TFs. Interleukin-6 (IL-6) was the hub node of the PPI network. DEGs were significantly enriched in NOD-like receptor signaling pathway which was primarily interacted with inflammation and immune related pathways (cytosolic DNA-sensing, hematopoietic cell lineage, intestinal immune network for IgA production and chemokine pathways). The study suggested CEBPD, FOSB, SFN, KLF5, PTX3, NR4A3, IL-6, and NOD-like receptor pathways were involved in pancreatic cancer.