8 research outputs found
Eurón innen és túl. Válságreakciók Európa két régiójában - spanyol és magyar példán keresztül
Structure-Based beta-Secretase (BACE1) Inhibitors
Alois Alzheimer identified first abnormal deformation in the brain of diseased people with mental disorder. The disorder is clinically characterized by a progression from episodic memory problems to a slow global decline of cognitive function, ending with the final stage when patients become bedridden and death occurs on average 9 years after diagnosis. The current standard of care does not cover the approved and effective treatment of both cognitive and non-cognitive symptoms. Tremendous effort was put in investigation of the disease development. The uncovered molecular mechanism shed light on aspartic proteases, the smallest protease class with about 15 members in the human genome. Here we summarise the most important structure-based developments on one of the most popular aspartic protease target BACE1
An annotation tool for academic literature processing
In this paper, we present our annotation tool that facilitates research and annotation work by quick, yet efficient literature processing. Our tool helps users create a unique and refined collection of linked information, which can lead to more effective and faster decisions in research. The tool is currently optimized for biomedical domain, but it can adapted to other academic fields with minimal efforts
GLOBE Program Association : Kollaboratív és innovatív tudásplatform a természetes hatóanyagok K+F támogatásához
The Stilbenoid Tyrosine Kinase Inhibitor, G6, Suppresses Jak2-V617F-mediated Human Pathological Cell Growth in Vitro and in Vivo*
Using structure-based virtual screening, we previously identified a novel stilbenoid inhibitor of Jak2 tyrosine kinase named G6. Here, we hypothesized that G6 suppresses Jak2-V617F-mediated human pathological cell growth in vitro and in vivo. We found that G6 inhibited proliferation of the Jak2-V617F expressing human erythroleukemia (HEL) cell line by promoting marked cell cycle arrest and inducing apoptosis. The G6-dependent increase in apoptosis levels was concomitant with increased caspase 3/7 activity and cleavage of PARP. G6 also selectively inhibited phosphorylation of STAT5, a downstream signaling target of Jak2. Using a mouse model of Jak2-V617F-mediated hyperplasia, we found that G6 significantly decreased the percentage of blast cells in the peripheral blood, reduced splenomegaly, and corrected a pathologically low myeloid to erythroid ratio in the bone marrow by eliminating HEL cell engraftment in this tissue. In addition, drug efficacy correlated with the presence of G6 in the plasma, marrow, and spleen. Collectively, these data demonstrate that the stilbenoid compound, G6, suppresses Jak2-V617F-mediated aberrant cell growth. As such, G6 may be a potential therapeutic lead candidate against Jak2-mediated, human disease