Project description:Peritoneal macrophages are important for pathogen clearance, forming cell-pathogen aggregates held together by fibrin. This can be beneficial in limiting the spread of pathogens, however, persistent fibrin deposits can lead to abdominal adhesions which give rise to multiple comorbidities. How this process is regulated is poorly understood. Under inflammatory conditions, macrophages secrete PAI-1, a potent inhibitor of fibrinolysis. We found that macrophage fibrinolytic activity is dependent on the time of day. PAI 1 secretion by peritoneal macrophages was increased at the onset of activity (ZT13) compared to at the onset of rest (ZT1), both basally and following in vivo LPS stimulation. Furthermore, the fibrinolytic response was reduced at ZT13 compared to ZT1. We also establish a novel role for the Rev-erbα agonist SR9009 in reversing macrophage anti-fibrinolytic activity. The chrono-dependency of macrophage fibrinolytic activity was confirmed using SR9009, which potently inhibited PAI-1 and PAI-2 secretion from LPS-stimulated macrophages, boosting plasmin generation and fibrin clot lysis in the presence of both macrophages and endothelial cells. Moreover, SR9009 promoted intraperitoneal fibrinolysis in LPS-administered mice. Collectively, these data highlight a novel role for circadian regulation of macrophage fibrinolytic activity.
Project description:Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury and one of the serious life-threatening forms of respiratory failure. Alveolar procoagulation and fibrinolytic inhibition constitute the core part of the pathophysiology of ARDS, RUNX1 plays an important role in this pathogenesis. We screened for AKT3, the target gene of RUNX1, using CHIP-seq and verified its binding target by a dual luciferase assay.
Project description:There is a statistically significant difference in the expression of the PLAUR and fibrinolytic inhibitor genes (SERPINE1, A2M) in mild and moderate-to-severe cases. There is a relationship between serum D-dimer levels and the expression of the PLAUR and fibrinolytic inhibitor genes (SERPINE1, A2M).
Project description:Natto is a traditional Japanese food from soybeans fermented with Bacillus subtilis natto. Natto contains a powerful fibrinolytic enzyme called nattokinase (NK), which has thrombolytic, anti-hypertensive, anti-atherosclerotic and lipid-lowering effects. This project aims to study the effects of NK in vascular inflammation.
Project description:Fermented foods are microbial ecosystems in which bacteria and fungi convert raw ingredients into stable, nutritious, and health-promoting products. The composition and activity of these microorganisms determine the biochemical and nutritional profile of the final food. We analyzed 17 fermented foods, each in triplicate, using metaproteomics. This analysis revealed that microbial proteins contribute up to 11% of total protein and 60% of identified proteins. Detailed information on file-naming conventions (database files, MS raw files, and output files), as well as food source suppliers, fermenting microorganisms, peptide loading volumes, and LC-MS gradient lengths, is provided in the table FileAndSampleDescription_PRIDE_submission.csv.
Project description:Peptide:N-glycosidase (PNGase) enzymes produced by bacteria have the potential to influence host cellular physiology. To investigate host transcriptional responses to bacterial PNGase activity, we performed bulk RNA sequencing on whole Caenorhabditis elegans exposed to active PNGaseDJ, PNGaseF, or an inactive PNGase mutant (DJ101A). Differential gene expression and pathway enrichment analyses were used to identify biological programs affected by PNGase exposure.
