Multilayer architecture microfluidic network array for combinatorial drug testing on 3D-cultured cells.

In vitro testing of drug compounds on cell models during the drug development process represents an indispensable step in the initial screening process. Although drug testing on three-dimensional (3D) cultured cells may provide a more accurate prediction of drug efficacy, it is relatively costly and time-consuming to perform compared with conventional 2D cultures due to the thick z-axis of the 3D models. In this study, we have presented a microfluidic platform with integrated pneumatic valves for producing a thin-gel 3D cell culture-based combinatorial drug screening array (3D-µCDS array). The multilayer architecture and microfluidic layout has a smaller device footprint than a single-layer microfluidic channel arrangement, making it well suited to scaling up for high-throughput combinatorial drug screening on 3D cell model. We performed 8 × 8 combination drug screening experiments with the device using two anti-cancer drugs (doxorubicin and paclitaxel) on MDA-MB-231 and MCF-7 breast cancer cell lines for demonstration. Our results indicate that our 3D-µCDS array device allows the successful screening of multiple drug combinations while reducing the operation time and the number of sample/reagents required, making it an ideal tool for general combinatorial drug screening, as well as for applications using valuable tissues and clinical samples.

Visible light-responsive core-shell structured In2O3@CaIn2O4 photocatalyst with superior bactericidal properties and biocompatibility.

Antibacterial activity of photocatalytic substrates is primarily induced by ultraviolet light irradiation. Visible light-responsive photocatalysts were recently discovered, offering greater opportunity to use photocatalysts as disinfectants in our living environment. The development of antibacterial photocatalysts, however, has mainly focused on titanium oxide (TiO(2))-related materials with antibacterial properties not comparable with conventional chemical disinfectants. This study demonstrated that a core-shell structured In(2)O(3)@CaIn(2)O(4) substrate has superior visible light-induced bactericidal properties, as compared with several commercially available and laboratory-prepared visible light-responsive photocatalysts. The high performance is enhanced by more easily photoexcited electron transfer between the interfaces of In(2)O(3) and CaIn(2)O(4) to minimize the electron-hole recombination during photocatalysis. Additionally, when compared with TiO(2)-based photocatalysts, In(2)O(3)@CaIn(2)O(4) treatments did not induce significant cell death and tissue damage, implying a superior biocompatibility. These findings suggest that In(2)O(3)@CaIn(2)O(4) may have potential application in the development of a safer and highly bactericidal photocatalyst. FROM THE CLINICAL EDITOR: A photocatalytic susbstrate is described that functions in visible light, possesses bactericidal properties and better biocompatibility than the standard TiO(2) based methods.

Modulation of YY1 activity by SAP30.

Yin Yang 1 (YY1) is a highly conserved and multifunctional transcription factor. The diverse activities of YY1 are regulated and sometimes modified by interaction with various other proteins. By using a yeast two-hybrid screening system, SAP30 was identified as a protein that associates with YY1 and it is able to enhance YY1-mediated repression in a dose-dependent manner. SAP30 is a 30kDa nuclear protein and is a component of the human histone deacetylase complex. In this study, the interaction of SAP30 and YY1 was confirmed both by in vitro and in vivo assays. The interaction domains between YY1 and SAP30 were mapped to the C-terminal segment of YY1 (295-414) and the C-terminal 91 amino acid region of SAP30. The observation that YY1, SAP30, and HDAC1 form a complex in vivo provides evidence that YY1 also recruits HDAC1 indirectly via its binding to SAP30. These results describe a novel mechanism for YY1-mediated repression.