A liver-immune coculture array for predicting systemic drug-induced skin sensitization.

Drug-induced skin sensitization is prevalent worldwide and can trigger life-threatening health conditions, such as Stevens Johnson Syndrome. However, existing in vitro skin models cannot adequately predict the skin sensitization effects of drugs administered into the systemic circulation because dermal inflammation and injury are preceded by conversion of parent drugs into antigenic reactive metabolites in the liver and subsequent activation of the immune system. Here, we demonstrate that recapitulation of these early tandem cellular processes in a compartmentalized liver-immune coculture array is sufficient to predict the skin sensitization potential of systemic drugs.

A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by beta-amyloid accumulation, phosphorylated tau formation, hyperactivation of glial cells, and neuronal loss. The mechanisms of AD pathogenesis, however, remain poorly understood, partially due to the lack of relevant models that can comprehensively recapitulate multistage intercellular interactions in human AD brains. Here we present a new three-dimensional (3D) human AD triculture model using neurons, astrocytes, and microglia in a 3D microfluidic platform.

3D Miniaturization of Human Organs for Drug Discovery.

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues.

New substituted isocoumarins and Dihydroisocoumarins and their cytotoxic activities.

New isocoumarins were prepared in an efficient way from 2-iodobenzoic acid derivatives and hept-1-yne in a Sonogashira reaction, followed by spontaneous cyclization. Catalytic hydrogenation gave the corresponding dihydroisocoumarins. A 4-chloroisocoumarin was prepared on an alternative pathway.

Revised structure of the alkaloid drymaritin.

In 2004, a new anti-HIV alkaloid named drymaritin was isolated from Drymaria diandra. The authors identified the alkaloid as 5-methoxycanthin-4-one on the basis of spectroscopic data. Here we describe a synthetic approach that unambiguously gave 5-methoxycanthin-4-one, but the synthetic product showed spectroscopic data significantly different from those of the Drymaria alkaloid.