No abstract

Bromodomain and extraterminal domain proteins, especially bromodomain-containing protein 4 (Brd4), have recently emerged as therapeutic targets for several cancers, although the role and mechanism of Brd4 in glioblastoma multiforme (GBM) are unclear. In this study, we aimed to explore the underlying mechanisms of the anti-tumor effects of Brd4 and the bromodomain inhibitor JQ1 on glioma stem cells (GSCs). In vitro, JQ1 and small interfering RNAs targeting Brd4 (siBrd4) inhibited the proliferation and self-renewal of GSCs. In vivo, JQ1 significantly inhibited the growth of xenograft GSCs tumors. The RNA-seq analysis revealed that the PI3K-AKT pathway played an important role in GBM. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 phosphorylation was downregulated by exposure to JQ1 in GSCs, thereby reducing PI3K and AKT activity. In addition, treatment with JQ1 inhibited MMP expression, thereby inhibiting degradation of the extracellular matrix by MMP and angiogenesis in GBM tumors. Suppression of AKT phosphorylation inhibited the expression of the retinoblastoma/E2F1 complex, resulting in cell cycle arrest. In addition, treatment with siBrd4 or JQ1 induced apoptosis by activating AKT downstream target genes involved in apoptosis. In conclusion, these results suggest that Brd4 has great potential as a therapeutic target, and JQ1 has notable anti-tumor effects against GBM which may be mediated via the VEGF/PI3K/AKT signaling pathway.

8With the rapid advances in liquid crystal (LC) materials technology over recent decades, 9 many different practical devices have been developed and commercialized. LC devices have 10 found numerous applications in fields such as imaging, microscopy, spectroscopy, and optical 11 probing. Multifarious LC-based sensors have been developed to analyze label-free 12 polyelectrolytes, ions, molecules, and biological systems. The detection principle in these LC 13 sensors is based on the highly sensitive orientational response of LC molecules to minute 14 changes in surface structures. Moreover, due to their potential applications in fields such as 15 chemistry, biomedicine, and environmental science, scientists have been attracted to the 16 research and development of LCs because of their potential use in real-time sensors. This 17 review presents a brief overview of the historical background on the research progress of LCs 18 and recent trends in their use in real-time detection applications. 19 20 1. Introduction 21 Liquid crystals (LCs) are responsive to external electric and magnetic fields, and will 22 reposition themselves into collective alignment in the presence of an applied field. Today, 23 LCs are well known for their applications in display technology. Liquid crystal display (LCD) 24 technology has dominated international research efforts in display applications for quite a 25 long time, driven by consumer demand. LCD technology is so much better today that 26 continued research and development for day-to-day applications is conducted mainly in 27 industrial laboratories. 28 LCs, which assemble with polymers and aqueous solutions, have attracted much attention in recent years because of their large surface areas and unique optical properties. 1 In bulk, LC 1 molecules arrange themselves in arbitrary orientations. However, blended with various 2 surfactants, polymers, and other materials, and confined by space, LC molecules are forced to 3 assume a specific directional orientation dictated by local intermolecular forces within the 4 aqueous phase. Due to long-range orientation correlations, the energy required to perturb the 5 molecular order of LCs is very small. 2-4 The alignment of LC molecules is therefore very 6 sensitive to the type, strength, and concentration of surfactants and/or polymers existing in 7 the aqueous phase. The orientation of LCs acts as an amplifier for local perturbations caused 8 by foreign molecules adsorbed on the interface. 5 The LCs at the surface can then 9 communicate their orientations through the bulk, causing changes in orientations throughout 10