医院临床用生物安全柜的选择和使用

生物安全柜的作用是有效降低实验室获得感染的机会,减少人与样品或样品之间交叉污染的机会,用于保护操作人员,保护实验室周围环境,保护操作样品的生物安全。本文旨在通过生物安全柜的隔离屏障原理和设计思想的阐述,引导使用人员正确合理选用生物安全柜。     

Itraconazole,a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

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Highlights? Itraconazole identified as Hh pathway inhibitor in screen of human-experienced drugs ? Itraconazole appears to act on Smoothened at distinct site from cyclopamine ? Itraconazole inhibits accumulation of Smoothened in primary cilium ? Itraconazole suppresses Hh-dependent tumor growth in vivo     

Wnt signaling in the stem cell niche

PURPOSE OF REVIEW: All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on studies that identify the Wnt signaling pathway as a mediator of HSC self-renewal and maintenance and analyzes its potential influence in context of the HSC niche. RECENT FINDINGS: The Wnt signaling pathway has emerged as a potential regulator of self-renewal for HSCs. Recent findings have demonstrated that Wnt signaling can directly promote HSC self-renewal and ability to reconstitute the hematopoietic system of lethally irradiated mice. The recent findings that osteoblasts are an important regulatory component of the HSC microenvironment, and that elements of the Wnt signaling pathway can influence osteoblast frequency, raise the possibility that Wnt signaling may influence HSC function indirectly through the niche as well. SUMMARY: In this review, the authors evaluate the experimental evidence for a direct role of Wnt signaling HSCs as well as an indirect role through its influence on the HSC niche. Defining the mechanism of action of Wnt signaling in HSC maintenance in context of the surrounding microenvironment and determining how this signal may integrate with other niche derived signals represents the next challenge HSC biology.     

aSIRTing control over cancer stem cells

Cancer stem cells lie at the root of chronic myelogenous leukemia (CML) and mediate its continued growth. Their resistance to current therapies results in an inability to eradicate the disease. In this issue of Cancer Cell, Li et al. identify SIRT1 as a new target for eliminating CML cancer stem cells.     

Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo

A key characteristic of stem cells and cancer cells is their ability to self-renew. To test if Wnt signaling can regulate the self-renewal of both stem cells and cancer cells in the hematopoietic system, we developed mice that lack beta-catenin in their hematopoietic cells. Here we show that beta-catenin-deficient mice can form HSCs, but that these cells are deficient in long-term growth and maintenance. Moreover, beta-catenin deletion causes a profound reduction in the ability of mice to develop BCR-ABL-induced chronic myelogenous leukemia (CML), while allowing progression of acute lymphocytic leukemia (ALL). These studies demonstrate that Wnt signaling is required for the self-renewal of normal and neoplastic stem cells in the hematopoietic system.     

Lymphoid precursors

Lymphopoiesis of mature and diverse populations of T, B and NK (natural killer) cells from multipotent hematopoietic stem cells is an ideal model of tissue generation and regeneration. Identification and isolation of hematolymphoid stem and progenitor cells in several laboratories over the past several years have provided populations that can be studied biologically for lineage commitment and biochemically for receptor function, signal transduction and selective gene expression. These studies may ultimately provide candidate genes involved in lineage commitment, cell death or survival, self-renewal and migratory capacities of progenitors.     

Thymic Stromal-Cell Abnormalities and Dysregulated T-Cell Development in IL-2-Deficient Mice

The role that interleukin-2 (IL-2) plays in T-cell development is not known. To address this issue, we have investigated the nature of the abnormal thymic development and autoimmune disorders that occurs in IL-2-deficient (IL-2^–/–) mice. After 4 to 5 weeks of birth, IL-2^–/– mice progressively develop a thymic disorder resulting in the disruption of thymocyte maturation. This disorder is characterized by a dramatic reduction in cellularity, the selective loss of immature CD4^-8^- (double negative; DN) and CD4⁺8⁺ (double positive; DP) thymocytes and defects in the thymic stromal-cell compartment. Immunohistochemical staining of sections of thymuses from specific pathogen-free and germ-free IL-2^–/– mice of various ages showed a progressive ,loss of cortical epithelial cells, MHC class II-expressing cells, monocytes, and macrophages. Reduced numbers of macrophages were apparent as early as week after birth. Since IL-2^–/– thymocyte progenitor populations could mature normally on transfer into a normal thymus, the thymic defect in IL-2^–/– mice appears to be due to abnormalities among thymic stromal cells. These results underscore the role of IL-2 in maintaining functional microenvironments that are necessary to support thymocyte growth, development, and selection.