Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of ?-amyloid (A?), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress.
Oncogenic mutations in the BRAF kinase occur in 6-8% of nonsmall cell lung cancers (NSCLCs), accounting for more than 90,000 deaths annually worldwide. The biological and clinical relevance of these BRAF mutations in NSCLC is incompletely understood. Here we demonstrate that human NSCLC cells with BRAF(V600E), but not other BRAF mutations, initially are sensitive to BRAF-inhibitor treatment. However, these BRAF(V600E) NSCLC cells rapidly acquire resistance to BRAF inhibition through at least one of two discrete molecular mechanisms: (i) loss of full-length BRAF(V600E) coupled with expression of an aberrant form of BRAF(V600E) that retains RAF pathway dependence or (ii) constitutive autocrine EGF receptor (EGFR) signaling driven by c-Jun-mediated EGFR ligand expression. BRAF(V600E) cells with EGFR-driven resistance are characterized by hyperphosphorylated protein kinase AKT, a biomarker we validated in BRAF inhibitor-resistant NSCLC clinical specimens. These data reveal the multifaceted molecular mechanisms by which NSCLCs establish and regulate BRAF oncogene dependence, provide insights into BRAF-EGFR signaling crosstalk, and uncover mechanism-based strategies to optimize clinical responses to BRAF oncogene inhibition.
A series of hesperidin derivatives were prepared and identified by IR, (1)H NMR, and MS spectra. These compounds were evaluated in vitro and in vivo based on ?-glucosidase inhibition, glucose consumption of HepG2 cells, and blood glucose level in streptozotocin-induced diabetic mice. The results revealed that all the compounds exhibited anti-hyperglycemic activities. The inhibition at 10(-3) M of compounds 3 and 7a on ?-glucosidase were 55.02% and 53.34%, respectively, as compared to 54.80% by acarbose. Treated by compound 3 and the reference drug metformin, glucose consumption of HepG2 cell were 1.78 and 2.11 mM, respectively. After the streptozotocin-induced diabetic mice were oral administrated with compound 3 at 100 mg kg(-1) d(-1) for 10 days, the blood glucose level of 3 treated mice (13.23 mM, P<0.05) showed significant difference when compared to model control (23.03 mM). Thus, compound 3 exhibited promising anti-hyperglycemic activity.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.