Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active not only conferred cytoprotection of HO-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, exhibited higher cytoprotective and neuroprotective potential and Overall, our findings showed compound could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

Microfluidic cell culture array chip for drug screening assays / 生物工程学报

We developed a novel microfluidic cell chip, which enabled drug delivery, fluid control and cell co-culture. The device consisted of an array of 6x6 cell culture chambers, a drug gradient generator and fluidic control valves. Micro-dam structures of the chambers were able to trap cells while loading and drug gradient network generated drug gradient of 6 different concentrations. Also we applied hydraulic valves to control the microfluid and simulate the microenvironment of cells. We had investigated the viability of co-culturing cells in the chip and the ability for drug screening. This microfluidic cell chip has the potential in cell-based research of high throughput drug screening.

Patterning different cells based on microfluidics and self-assembled monolayers / 生物工程学报

The ability to pattern multiple cells through precise surface engineering of cell culture substrates has promoted the development of cellular bioassays, such as differentiation, interaction and molecular signaling pathways. There are several well developed ways to pattern cells. This report describes a method for patterning multiple types of cells based on microfluidics and self-assembled monolayers. We developed two types of micro-dam structures by soft-lithography to locate cells precisely and modified the substrate by a kind of self-assembled monolayer with property of electrochemical desorption to confine cells in specific areas. Finally we could pattern an array of two different types of cells closely and precisely. Cells were confined in specific areas but still shared the same microenvironment, so they could interact through soluble molecules. The substrate was transparent and open, so we could easily apply several instruments for research. With these merits, this cell chip is appropriate for investigating the interaction between different types of cells.