Droplet microarray platforms for high-throughput drug screening.

High-throughput screening platforms are fundamental for the rapid and efficient processing of large amounts of experimental data. Parallelization and miniaturization of experiments are important for improving their cost-effectiveness. The development of miniaturized high-throughput screening platforms is essential in the fields of biotechnology, medicine, and pharmacology. Currently, most laboratories use 96- or 384-well microtiter plates for screening; however, they have disadvantages, such as high reagent and cell consumption, low throughput, and inability to avoid cross-contamination, which need to be further optimized. Droplet microarrays, as novel screening platforms, can effectively avoid these shortcomings. Here, the preparation method of the droplet microarray, method of adding compounds in parallel, and means to read the results are briefly described. Next, the latest research on droplet microarray platforms in biomedicine is presented, including their application in high-throughput culture, cell screening, high-throughput nucleic acid screening, drug development, and individualized medicine. Finally, the challenges and future trends in droplet microarray technology are summarized.

Application of Microfluidics in Drug Development from Traditional Medicine.

While there are many clinical drugs for prophylaxis and treatment, the search for those with low or no risk of side effects for the control of infectious and non-infectious diseases is a dilemma that cannot be solved by today's traditional drug development strategies. The need for new drug development strategies is becoming increasingly important, and the development of new drugs from traditional medicines is the most promising strategy. Many valuable clinical drugs have been developed based on traditional medicine, including drugs with single active ingredients similar to modern drugs and those developed from improved formulations of traditional drugs. However, the problems of traditional isolation and purification and drug screening methods should be addressed for successful drug development from traditional medicine. Advances in microfluidics have not only contributed significantly to classical drug development but have also solved many of the thorny problems of new strategies for developing new drugs from traditional drugs. In this review, we provide an overview of advanced microfluidics and its applications in drug development (drug compound synthesis, drug screening, drug delivery, and drug carrier fabrication) with a focus on its applications in conventional medicine, including the separation and purification of target components in complex samples and screening of active ingredients of conventional drugs. We hope that our review gives better insight into the potential of traditional medicine and the critical role of microfluidics in the drug development process. In addition, the emergence of new ideas and applications will bring about further advances in the field of drug development.

Hyperhomocysteinemia exaggerates adventitial inflammation and angiotensin II-induced abdominal aortic aneurysm in mice.

RATIONALE: A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role. OBJECTIVE: We determined the association and contribution of HHcy to AAA formation. METHODS AND RESULTS: We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II-infused male apolipoprotein E-deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II-induced AAA and aortic dissection in apolipoprotein E-deficient mice (vehicle versus Hcy: 50% versus 100%; P<0.05). Histology indicated HHcy markedly exaggerated aortic adventitial inflammation. Increased levels of proinflammatory interleukin-6 and monocyte chemoattractant protein-1 were preferentially colocalized within adventitial fibroblasts in HHcy plus angiotensin II mice, which suggested the importance of adventitial fibroblasts activation in Hcy-aggravated AAA. Hcy sequentially stimulated adventitial fibroblasts transformation into myofibroblasts, secretion of interleukin-6 and monocyte chemoattractant protein-1, and consequent recruitment of monocytes/macrophages to adventitial fibroblasts, which was abolished by the NADPH oxidase inhibitor diphenyliodonium. NADPH oxidase 4, but not other homologs of NADPH oxidase, was significantly upregulated by Hcy in adventitial fibroblasts, whereas NADPH oxidase 4 small interfering RNA silencing diminished Hcy-induced adventitial fibroblasts activation. Finally, folic acid supplement (0.071 µg/g per day) markedly reduced HHcy-aggravated angiotensin II-induced AAA formation in apolipoprotein E-deficient mice. CONCLUSIONS: HHcy may aggravate AAA formation at least partially via activating adventitial fibroblast NADPH oxidase 4.