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A Model of Zymogen Factor XII: Insights into Protease Activation.
Blood Adv
January 2025
Vanderbilt University Medical Center, Nashville, Tennessee, United States.
In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.
View Article and Find Full Text PDFTalin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.
J Cell Sci
January 2025
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Talin regulates the adhesion and migration of cells in part by promoting the affinity of integrins for extracellular matrix proteins, a process that in cells such as endothelial cells and platelets requires the direct interaction of talin with both the small GTPase, Rap1-GTP, and the integrin β3 cytoplasmic tail. To study this process in more detail, we employed an optogenetic approach in living, immortalized endothelial cells to be able to regulate talin interaction with the plasma membrane. Previous studies identified talin as the Rap1-GTP effector for β3 integrin activation.
View Article and Find Full Text PDFAHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility.
Sci Rep
January 2025
Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker.
View Article and Find Full Text PDFL. Leaf Extract Dose-Dependently Modulates Oxidative Stress in the Kidney and Exerts Anti-Fibrotic and Anti-Inflammatory Properties by the Molecular Mechanisms Independent of NRF-2 Signalization Mirroring the Effects of Losartan in SHR.
Int J Mol Sci
December 2024
Department for Cardiovascular Physiology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, P.O. Box 39, 11129 Belgrade, Serbia.
Previously, we confirmed systemic antihypertensive and antioxidant properties of L. leaf extract (UE) in spontaneously hypertensive rats (SHR). Here, we aimed to evaluate whether UE can alter the NO and Nrf-2 signaling to prevent local oxidative stress and kidney damage in the model of essential hypertension.
View Article and Find Full Text PDFPlasma fibronectin is a prognostic biomarker of disability in Parkinson's disease: a prospective, multicenter cohort study.
NPJ Parkinsons Dis
January 2025
Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
In a prospective longitudinal study with 218 Parkinson's disease (PD) patients in the discovery cohort and 84 in the validation cohort, we aimed to identify novel blood biomarkers predicting disability milestones in PD. Through Least Absolute Shrinkage and Selection Operator-Cox (Lasso-Cox) regression, developed nomogram predictive model and Linear mixed-effects models, we identified low level of plasma fibronectin (pFN) as one of the best-performing risk markers in predicting disability milestones. A low level of pFN was associated with a short milestone-free survival period in PD.
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