The authors found that in human monocytes administered low density lipoprotein in doses of 50 micrograms had optimal inhibition of endogenous cholesterol synthesis which measured by [14C] acetate incorporation. There was not effect of pertussis toxin and phorbol myristate acetate on the inhibiton of endogenous cholesterol synthesis, whereas calcium channel blocker verapamil and phospholipase A2-inhibitor chloroquine decreased it. In contrast, the protein kinase C-stimulant phorbol myristate acetate alone had effects as LDL, but the protein kinase C-inhibitor H-7 had antagonist effect against LDL. Inositol phosphate generation was induced by administration of LDL in doses of 50 micrograms, which was pertussis toxin insensitive. The calcium signal was not also pertussis toxin sensitive, while occurred an intensive protein kinase C activation by administration of LDL. In signal transduction of monocytes activated by LDL may be an important role of the opening of calcium channels and activation of two enzymes, such as phospholipase A2 and protein kinase C.
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JCO Precis Oncol
January 2025
McGill University Faculty of Medicine, Montréal, QC, Canada.
Purpose: MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined.
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January 2025
Medical University of Vienna, Vienna, Austria.
In thrombosis and hemostasis, the formation of a platelet-fibrin thrombus or clot is a highly controlled process that varies, depending on the pathological context. Major signaling pathways in platelets are well established. However, studies with genetically modified mice have identified the contribution of hundreds of additional platelet-expressed proteins in arterial thrombus formation and bleeding.
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January 2025
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
The intracellular protozoan Toxoplasma gondii manipulates host cell signaling to avoid targeting by autophagosomes and lysosomal degradation. Epidermal Growth Factor Receptor (EGFR) is a mediator of this survival strategy. However, EGFR expression is limited in the brain and retina, organs affected in toxoplasmosis.
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January 2025
Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
This study presents T-1-NBAB, a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, a crucial protein in angiogenesis. T-1-NBAB's potential to interacts with and inhibit the VEGFR-2 was indicated using in silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, and bi-dimensional projection experiments. DFT experiments was utilized also to study the structural and electrostatic properties of T-1-NBAB.
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January 2025
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Aniridia Research, Saarland University, Homburg/Saar, Germany.
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