Anti-DYRK1A (aa 35-47) polyclonal antibody

The widely distributed beta-carboline alkaloids exhibit promising psychopharmacological and biochemical effects. Harmine, a natural beta-carboline, can inhibit insect growth and development with unclear mechanisms. In this study, harmine (at 0-200 mg/L) showed a dose-dependent inhibitory effect on the pupal weight, length, height, pupation rate and eclosion rate of fruit flies Drosophila melanogaster, which was similar to the inhibition induced by the well-known botanical insect growth regulator azadirachtin. Moreover, the expression levels of major regulators from the developmental signaling network were down-regulated during the pupal stage except Numb, Fringe, Yorkie and Pten. The Notch, Wnt, Hedgehog and TGF-beta pathways mainly played vital roles in coping with harmine exposure in pupae stage, while the Hippo, Hedgehog and TGF-beta elements were involved in the sex differences. Notch, Hippo, Hedgehog, Dpp and Armadillo were proved to be suppressed in the developmental inhibition with fly mutants, while Numb and Punt were increased by harmine. In conclusion, harmine significantly inhibited the development of Drosophila by negatively affecting their developmental signaling network during different stages. Our results establish a preliminary understanding of the developmental signaling network subjected to botanical component-induced growth inhibition and lay the groundwork for further application.

Pancreatic beta-cell apoptosis, a hallmark of the development of type 1 diabetes (T1D), is associated with increased levels of pro-inflammatory cytokines. Thus, an agent protecting beta-cells from cytokine-induced stress should have an impact on maintaining functional beta-cell mass in T1D. Screening of a similar to 2 million-compound library identified a series of 7-azaindole derivatives as capable of protecting rat insulinoma beta-cells from death induced by pro-inflammatory cytokines. The screening hits were optimized to result in GNF3809, a compound which preserves insulin content and viability of beta-cells in both rodent and human islets under stress induced by cytokines. In vivo, orally bioavailable GNF3809 prevented elevated blood glucose level and improved oral glucose tolerance in a nonobese diabetic mouse model. This work lays the foundation for development of a new class of therapeutic interventions for T1D.