No abstract

Circulating tumor cell (CTC) enumeration and analysis has emerged as an important platform for cancer diagnosis and prognosis. A great challenge, however, is to efficiently capture low abundant CTCs with high purity from blood samples in a rapid and high-throughput manner for accurate and sensitive CTC detection. Herein, a new class of DNA-templated magnetic nanoparticle-quantum dot (QD)-aptamer copolymers (MQAPs) is developed for rapid magnetic isolation of CTCs from human blood with high capture efficiency and purity approaching 80%. The phenotype of CTCs is simultaneously profiled with QD photoluminescence (PL) at single cell level. These MQAPs are constructed through hybridization chain reaction to achieve amplified magnetic response, extraordinary binding selectivity for target cells over background cells, and ultra bright ensemble QD PL for single cell detection. MQAPs are free from nonspecific binding that would otherwise compromise the capture purity of target cells. As a result, facile isolation and enumeration of rare CTCs in blood samples could be achieved in 20 min with high sensitivity and accuracy.

No abstract

An emerging paradigm proposes a crucial role for lung resident mesenchymal stem cells (LR-MSCs) via a fibroblastic transdifferentiation event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Aberrant activation of Wnt/β-catenin signaling occurs in virtually all fibrotic lung diseases and is relevant to the differentiation of mesenchymal stem cells (MSCs). In vitro, by measuring the protein levels of several key components involved in Wnt/β-catenin signaling, we confirmed that this signaling pathway was activated in the myofibroblast differentiation of LR-MSCs. Targeted inhibition of Wnt/β-catenin signaling by a small molecule, ICG-001, dose-dependently impeded the proliferation and transforming growth factor-β1 (TGF-β1)-mediated fibrogenic actions of LR-MSCs. In vivo, ICG-001 exerted its lung protective effects after bleomycin treatment through blocking mesenchymal-myofibroblast transition, repressing matrix gene expression, and reducing cell apoptosis. Moreover, delayed administration of ICG-001 attenuated bleomycin-induced lung fibrosis, which may present a promising therapeutic strategy for intervention of IPF. Interestingly, these antifibrotic actions of ICG-001 are operated by a mechanism independent of any disruption of Smad activation. In conclusion, our study demonstrated that Wnt/β-catenin signaling may be an essential mechanism underlying the regulation of myofibroblast differentiation of LR-MSCs and their further participation in the development of pulmonary fibrosis.