Contents
06 November 2019
Vol 11, Issue 517
Vol 11, Issue 517
Research Articles
- Reproducing human and cross-species drug toxicities using a Liver-Chip
A rat, dog, and human Liver-Chip designed using microengineered Organs-on-Chips technology recapitulates species-specific drug toxicities.
- Metal-captured inhibition of pre-mRNA processing activity by CPSF3 controls Cryptosporidium infection
Targeting parasitic endonuclease CPSF3 with an oxaborole offers a potent and selective candidate treatment against cryptosporidiosis.
- An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse
CaVβ1E boosts downstream growth differentiation factor 5 signaling to counteract muscle mass loss in denervated or aged mouse muscles.
- Identification of DHODH as a therapeutic target in small cell lung cancer
Small cell lung cancer tumors are sensitive to DHODH inhibition, highlighting a potential treatment strategy for this disease.
- Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis
Platelet-induced myeloid Socs3 expression in humans and mice contributes to unresolved atherosclerosis inflammation and sustained plaque growth.
Editors' Choice
- Antibodies go with the lymphatic flow
Lymph flow through Peyer’s patches enhances mucosal antibody production.
- Rogue tumor cells use SEMAntics to infiltrate the brain
Semaphorins promote breast cancer metastasis to brain.
- Keeping it simple: A higher-yielding process for manufacturing dendritic cells
An optimized protocol using a hollow-fiber bioreactor produces a complete dose of dendritic cell–based immunotherapies in a single batch.
About The Cover
ONLINE COVER Chipping Away at Drug Toxicity. Tissues- and organs-on-chips are microphysiological systems useful for modeling human disease and testing therapeutic compounds. This artistic rendering of a microfluidic Liver-Chip represents recent work by Jang et al. investigating drug-induced liver toxicity. Using chips containing hepatocytes, Kupffer cells, stellate cells, and sinusoidal endothelial cells from multiple species, the authors identified mechanisms of hepatoxicity of drugs and experimental compounds–some of which showed species-specific effects. The chips recapitulated liver injury induced by oxidative stress and mitochondrial dysfunction caused by a G protein–coupled receptor agonist discontinued in phase 3 trials. Results suggest the Liver-Chip could improve preclinical safety and toxicity testing to select promising candidates for drug development. [CREDIT: BRETT CLAIR AND KYUNG-JIN JANG/EMULATE, INC.]
