Diosmetin Inhibits NETs Formation in Neutrophils Through Regulating Nrf2 Signaling

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(6)

Published: March 1, 2025

Neutrophil extracellular traps (NETs) are important pieces of equipment for neutrophils. Excess NETs play promoting roles in cancer-associated thrombosis (CAT). Therefore, directing formation is a promising therapeutic strategy and related diseases. Diosmetin, an antioxidant flavonoid derived from dietary sources, might be involved CAT. Firstly, the tests cell-free DNA Immunofluorescence were applied to evaluate levels Luminol-based chemiluminescence DCFH-DA probe used detect reactive oxygen species (ROS) Then, network pharmacological analysis molecular docking predict potential target molecules diosmetin. The RT-qPCR was performed measure Nrf2 HO-1. A series functional assays neutrophils examine effect diosmetin on other neutrophil functions. Finally, animal model deep vein constructed assess thrombosis. Diosmetin reduced ROS mechanisms suggested that primary treatment increased HO-1 NETs-generating An inhibitor diminished negative generation. Lastly, murine results indicated via formation. exerts as anti-NETs through signaling neutrophils, showing thromboembolism pathological processes, such

Language: Английский

A mendelian randomization study on the association between 731 types of immune cells and 91 types of blood cells with venous thromboembolism

Thrombosis Journal, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 3, 2025

Venous thromboembolism (VTE) is a grave medical condition characterized by the blockage of distant blood vessels due to clots or detached vessel wall fragments, leading ischemia necrosis affected tissues. With recent introduction immunothrombosis, significance immune cells in process thrombus formation has gained prominent attention. Complex cross-talk occurs between and during infection inflammation, with actively participating clot promoting platelet recruitment thrombin activation. Nevertheless, comprehensive studies on genetic association phenotypes VTE remain scarce. This article employed Mendelian randomization (MR) investigate incidence range 731 cell types, along 91 perturbation phenotypes, utilizing single nucleotide polymorphisms as instrumental variables. Through utilization publicly available data, two-sample bi-directional MR analysis was conducted. Sensitivity analyses included Cochran's Q test, MR-Egger intercept MR-pleiotropy residual sum outlier (MR-PRESSO) leave-one-out analysis. For significant associations, replication conducted using GWAS data from deep vein thrombosis (DVT) pulmonary embolism (PE). We firstly investigated causal relationship risk. All were obtained European populations men women. The IVW revealed that CD20 naive-mature B cell, IgD- CD38dim unswitched memory may increase risk (P < 0.05). CD28- CD8dim T %T CD64 monocyte CD14 + CD16- be protective factors against DVT Then disturbed types exposure analyzed examine its occurrence VTE. Initial both environmental KCl-impacted red butyric acid-impacted accelerated 0.05), while colchicine -impacted eosinophil, reticulocyte Lipopolysaccharide (LPS) neutrophil reduced confirmed robustness reliability these positive findings. Our study presents evidence link six Additionally, we have identified two are associated DVT, three relevant PE. Not applicable.

Language: Английский

The critical role of platelets in venous thromboembolism: Pathogenesis, clinical status, and emerging therapeutic strategies

Blood Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 101302 - 101302

Published: May 1, 2025

Language: Английский