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The NE/AAT/CBG axis regulates adipose tissue glucocorticoid exposure.
Nat Commun
January 2025
University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Corticosteroid binding globulin (CBG; SERPINA6) binds >85% of circulating glucocorticoids but its influence on their metabolic actions is unproven. Targeted proteolytic cleavage of CBG by neutrophil elastase (NE; ELANE) significantly reduces CBG binding affinity, potentially increasing 'free' glucocorticoid levels at sites of inflammation. NE is inhibited by alpha-1-antitrypsin (AAT; SERPINA1).
View Article and Find Full Text PDFInhibition of Abdominal Aortic Aneurysm Progression Through the CXCL12/CXCR4 Axis via MiR206-3p Sponge.
J Cell Mol Med
January 2025
Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Notably, the C-X-C Motif Chemokine Ligand 12/C-X-C Chemokine Receptor Type 4 (CXCL12/CXCR4) signalling pathway's activation is markedly increased in a mouse model of abdominal aortic aneurysms (AAA). Nonetheless, the precise contribution of this pathway to AAA development remains to be elucidated. The AAA mouse model was induced by local incubation with elastase and oral administration of β-aminopropionitrile.
View Article and Find Full Text PDFWeakened Airway Epithelial Junctions and Enhanced Neutrophil Elastase Release Contribute to Age-Dependent Bacteremia Risk Following Pneumococcal Pneumonia.
Aging Cell
January 2025
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Streptococcus pneumoniae (Sp; pneumococcus), the most common agent of community-acquired pneumonia, can spread systemically, particularly in the elderly, highlighting the need for adjunctive therapies. The airway epithelial barrier defends against bacteremia and is dependent upon apical junctional complex (AJC) proteins such as E-cadherin. After mouse lung challenge, pneumolysin (PLY), a key Sp virulence factor, stimulates epithelial secretion of an inflammatory eicosanoid, triggering the infiltration of polymorphonuclear leukocytes (PMNs) that secrete high levels of neutrophil elastase (NE), thus promoting epithelial damage and systemic infection.
View Article and Find Full Text PDFIdentification of an exosite at the neutrophil elastase/alpha-1-antitrypsin interface.
FEBS J
January 2025
Physics, Department of Molecular and Translational Medicine, University of Brescia, Italy.
Neutrophil elastase (NE) is released by activated neutrophils during an inflammatory response and exerts proteolytic activity on elastin and other extracellular matrix components. This protease is rapidly inhibited by the plasma serine protease inhibitor alpha-1-antitrypsin (AAT), and the importance of this protective activity on lung tissue is highlighted by the development of early onset emphysema in individuals with AAT deficiency. As a serpin, AAT presents a surface-exposed reactive centre loop (RCL) whose sequence mirrors the target protease specificity.
View Article and Find Full Text PDFFeMOFs/CO loading reduces NETosis and macrophage inflammatory response in PLA based cardiovascular stent materials.
Regen Biomater
December 2024
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
Modification of polylactic acid (PLA) is a promising strategy for the next generation of bioresorbable vascular stent biomaterials. With this focus, FeMOFs nanoparticles was incorporated in PLA, and then post loading of carbon monoxide (CO) was performed by pressurization. It showed FeMOFs incorporation increased hydrophilicity of the surface and CO loading, and CO release was sustained at least for 3 days.
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