RESUMEN
Cancer stem cells (CSCs) function as the driving force of cancer initiation and progression. Wnt/ß-catenin is the core pluripotency pathway in CSCs, while its crucial regulator has not been fully elucidated yet. Here, we evaluated the role of ZO-1, a component of the tight junction protein complex, in colorectal CSCs, and found ZO-1 downregulation in both colorectal cancer cells and spheres. Over-expression of ZO-1 can inhibit the sphere-forming capacity and CSC marker expression in spheres. Immunofluorescence staining and co-immunoprecipitation analysis further revealed the interaction between ZO-1 and ß-catenin and the repressed role of ZO-1 in ß-catenin nuclear accumulation. Using in vitro and in vivo models, we suggested the suppression effects of sulforaphane on CSCs via the ZO-1/ß-catenin axis in colorectal cancer. The findings from this study depicted for the first time that ZO-1 dampened colorectal CSCs by interacting with ß-catenin and attenuated its nuclear translocation, providing new insights into the mechanisms and applications of sulforaphane in targeting CSCs.
Asunto(s)
Neoplasias Colorrectales , Células Madre Neoplásicas , Proteína de la Zonula Occludens-1 , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Wnt , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Detecting and imaging intracellular hypochlorous acid (HClO) is of great importance owning to its prominent role in numerous pathological and physiological processes. In this contribution, a novel AIE-based fluorescent chemosensor has been developed by employing a benzothiazole derivative. The synthesized probe displayed remarkable ratiometric fluorescent response to HClO with a large emission shift (139 nm), resulting in naked-eye fluorescence changes from red to blue. Under the optimal conditions, this probe was capable of quantitatively detecting HClO within 10 s, and possessed good sensitivity and high selectivity toward HClO over other biologically relevant species. Moreover, it has been successfully utilized to image the exogenous and endogenous HClO in living cells through dual channels, and conveniently detect hypochlorous acid solution on test strips with better accuracy, demonstrating its potential for monitoring HClO in biological and environment fields.
Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Animales , Fluorescencia , Ratones , Células RAW 264.7RESUMEN
Citrus tristeza virus (CTV) is the major virus pathogen causing significant economic damage to citrus worldwide, and a single dominant gene, Ctv, provides broad spectrum resistance to CTV in Poncirus trifoliata L. Raf. Ctv was physically mapped to a 282-kb region using a P. trifoliata bacterial artificial chromosome library. This region was completely sequenced to about 8x coverage using a shotgun sequencing strategy and primer walking for gap closure. Sequence analysis predicts 22 putative genes, two mutator-like transposons and eight retrotransposons. This sequence analysis also revealed some interesting features of this region of the P. trifoliata genome: a disease resistance gene cluster with seven members and eight retrotransposons clustered in a 125-kb gene-poor region. Comparative sequence analysis suggests that six genes in the Ctv region have significant sequence similarity with their orthologs in bacterial artificial chromosome clones F7H2 and F21T11 from Arabidopsis chromosome I. However, the analysis of gene colinearity between P. trifoliata and Arabidopsis indicates that Arabidopsis genome sequence information may be of limited use for positional gene cloning in P. trifoliata and citrus. Analysis of candidate genes for Ctv is also discussed.
Asunto(s)
Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Virus de Plantas/crecimiento & desarrollo , Poncirus/genética , Secuencia de Aminoácidos , Arabidopsis/genética , Cromosomas Artificiales Bacterianos/genética , Clonación Molecular , Mapeo Contig , Elementos Transponibles de ADN/genética , ADN de Plantas/química , ADN de Plantas/genética , Genoma de Planta , Inmunidad Innata/genética , Datos de Secuencia Molecular , Familia de Multigenes , Filogenia , Enfermedades de las Plantas/virología , Poncirus/virología , Secuencias Repetitivas de Ácidos Nucleicos/genética , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , SinteníaRESUMEN
The variations of concentrations of hexachloro-cyclohexane (HCHs), dichloro diphenyl trichloroethane (DDTs) in surface sediments from the Changjiang Estuary and Zhejiang coastal area suggests that although there is a substantial decrease of these persistent trace compounds since the last two decades, they still presented in recent surface sediments. Their concentration levels in suspended matter are still quite high. In dated sedimentary cores, the DDTs and HCHs concentration peaks appeared in 1960s to 1980s, which approximately corresponded to their production and usage history.