Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

Objective  

We aimed to perform a preliminary study of the association between induced pluripotent stem cell (iPS)-related genes and biological behavior of human colorectal cancer (CRC) cells, and the potential for developing anti-cancer drugs targeting these genes.     

Progress in Safe Induced Pluripotent Stem Cells for Clinical Applications

诱导性多能干细胞（induced pluripotent stem cells,iPSCs）是被重新编程的、具有多能性的成体细胞。最近的研究证实,iPSCs能够达到与胚胎干细胞同样的全能性。源于成体的iPSCs对药物或毒性筛选、医疗研究以及疾病专一性治疗提供了极其有价值的细胞来源,然而,在应用于临床之前,必须克服潜在的风险,包括iPSCs诱导中病毒的整合、基因的改变。iPSCs潜在的风险涉及外源因子的转入、目标细胞的改变及诱导因子的表达和重新激活等。本文回顾iPSCs的应用前景和面临的挑战,同时对诱导安全性iPSCs的方法进行了讨论。     

Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro

Objective  

Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs). The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs), but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl₄)-induced liver inflammation model.     

Ex vivo expansions and transplantations of mouse bone marrow-derived hematopoietic stem/progenitor cells

To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34⁺/c-kit⁺ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34⁺/c-kit⁺ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34⁺/c-kit⁺ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells, CD34⁺ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34⁺/c-kit⁺ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded cells by the co-culture with MSCs may result in more rapid engraftment of neutrophils following infusion to transplant recipients. Project supported by NIH-Blood, Heart & Lung (National Institute of Health, USA, IR 01 4L70593-01) and Zhejiang Provincial Science Foundation (No. 011103397), China     

Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells

This study is aimed at investigating the potentials of ex vivo expansion and pluri-differentiation of cryopreservation of adult human bone marrow mesenchymal stem cells （hMSCs） into chondrocytes, adipocytes and neurocytes. Cryopreserved hMSCs were resuscitated and cultured for 15 passages, and then induced into chondrocytes, adipocytes and neurocytes with corresponding induction medium. The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin. The result showed that the resuscitated cells could differentiate into chondrocytes after exposure to transforming growth factor 61 （TGF-~0, insulin-like growth factor I （IGF-I） and vitamin C （Vc）, and uniformly changed morphologically from a spindle-like fibroblastic appearance to a polygonal shape in three weeks. The induced cells were heterochromatic to safranin O and expressed cartilage matrix-procollagenal （If） mRNA. The resuscitated cells cultured in induction medium consisting of dexamethasone, 3-isobutyl-l-methylxanthine, indomethacin and IGF-I showed adipogenesis, and lipid vacuoles accumulation was detectable after 21 d. The resuscitated hMSCs were also induced into neurocytes and expressed nestin and neuron specific endolase （NSE） that were special surface markers associated with neural cells at different stage. This study suggested that the resuscitated hMSCs should be still a population ofpluripotential cells and that it could be used for establishing an abundant bMSC reservoir for further experiment and treatment of various clinical discases.     

The school effectiveness movement: origins,shortcomings and future possibilities

ABSTRACT

This paper argues that the school effectiveness/school improvement movement has provided an antidote to the pessimism and fatalism of the 1970s. However, it is deficient in four important respects: (1) it places too much emphasis on the notion of progressive school management as the dynamic of change; (2) it fails to take full account of the characteristics of the education system as a whole; (3) it shows little regard for issues of social class; (4) it has little to say about issues of curriculum content and pedagogy.     

表观遗传修饰和代谢重编程对乳腺癌干细胞的调控

概乳腺癌已居我国女性恶性肿瘤死亡率首位。近来研究表明,乳腺肿瘤组织内有少量具有自我更新和分化潜能的肿瘤干细胞,这些肿瘤干细胞在乳腺癌发生、发展、转移及复发过程中起关键作用。深入研究乳腺癌干细胞的调控机制对乳腺癌的预防和治疗具有十分重要意义。本文综合近期的研究成果,概括了表观遗传修饰和代谢重编程对上皮间质转化及乳腺癌干细胞的调控机制,且系统地分析与总结了表观遗传修饰、代谢重编程、上皮间质转化和乳腺癌干细胞之间的相互关系。     

运用高通量测序研究Alport综合征多能干细胞的microRNA及其靶基因(英文)

目的:寻找来源于Alport综合征患者与正常对照者的多能干细胞差异性表达的microR NA,并对差异性表达的microR NA靶基因进行预测。创新点:本研究不同于一般的试验标本,试验标本是来源于尿肾脏管细胞诱导而成的多能干细胞。基于Alport综合征是遗传疾病,我们对一遗传家系进行了系统的分析。寻找特异性的差异性表达microR NA及其靶基因,从基因水平对Alport综合征进行研究。方法:在前期工作中,成功地从实验者与对照者的尿肾脏管细胞诱导成多能干细胞。运用高通量测序技术分析并发现实验者与对照者之间差异性表达的microR NA。对差异性表达的microR NA靶基因进行预测,并进行靶基因聚集分析,研究靶基因主要参与的生物学过程。同时进行靶基因信号传导通路的分析,研究靶基因主要参与的细胞信号传导通路。结论:在实验组与对照组之间,发现了30个具有显著差异性表达的microR NAs,包括19个上调表达与11个下调表达。差异性表达的microR NA的靶基因主要聚集在细胞膜和细胞代谢过程;靶基因主要参与嘌呤代谢通路与丝裂原活化蛋白激酶(MAPK)通路。     

转染瘦素人胎盘源间充质干细胞对经X射线辐照后人脐静脉内皮细胞的成血管潜能和周围炎症的影响

目的:放创复合伤是一种以血管损伤和促炎细胞因子缺乏为特征的难愈性创伤。瘦素(leptin)的直接应用在血管生成和炎症中起着重要作用。本研究构建了一种可持续稳定的leptin表达系统——leptin修饰的人胎盘来源间充质干细胞(HPMSCs/leptin),并探究其对经X射线辐照后的人脐静脉内皮细胞(HUVECs)的成血管潜能及周围炎症的影响和潜在机制。创新点:可持续稳定的leptin表达系统(HPMSCs/leptin)促进受X射线辐照后HUVECs的成血管潜能及外周炎症反应,有助于解决放创复合伤伤口愈合过程中血管损伤和促炎因子缺乏的问题。方法:利用慢病毒载体将leptin基因转染HPMSCs获得HPMSCs/leptin。采用X射线单次照射HUVECs,剂量为20 Gy。细胞迁移侵袭实验技术(Transwell)检测照射后HUVECs的迁移情况。在Transwell体系的基础上,建立HPMSCs与受辐照HUVECs共培养体系。CCK-8比色法测定细胞增殖。酶联免疫吸附法(ELISA)检测促炎细胞因子(粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-1α(IL-1α)、IL-6和IL-8)的分泌。实时荧光定量聚合酶链式反应(RT-qPCR)检测促血管生成因子(VEGF和bFGF)mRNA的表达。蛋白免疫印迹法(westernblot)检测核因子κB(NF-κB)和JAK/STAT信号通路的相关分子表达。结论:可持续稳定的leptin表达系统(HPMSCs/leptin)具有更好的细胞增殖、迁移和成血管潜能。HPMSCs/leptin单独培养和HPMSCs/leptin与受辐照HUVECs共培养体系中,促炎细胞因子的分泌增加与NF-κB和JAK/STAT信号通路的相互作用有关。HPMSCs/leptin可能促进X射线照射后HUVECs的成血管潜能和外周炎症反应。     

Embryonic stem cells and their genetic modification Nobel prize in Physiology or Medicine 2007

The derivation of embryonic stem cells from mice and the development of techniques that allow for targeted manipulation of its genome have allowed for the generation of mice with desired mutations. This is what led to the announcement in Stockholm in 2007 — “The Nobel Assembly at Karolinska Institute today decided to award the Nobel Prize in Physiology or Medicine for 2007 jointly to Mario R Capecchi, Martin J Evans and Oliver Smithies for their discoveries of Principles for introducing specific gene modifications in mice by the use of embryonic stem cells”. Martin J Evans was recognised for his derivation and establishment of mouse embryonic stem cells while Mario Capecchi and Oliver Smithies were honoured for techniques that allowed site-specific modification of sequences within the genome of these cells. Such cells were then used to generate animals that had their genome altered specifically and at desired locations. For this valuable body of work, all three shared the prize equally. To date, almost half of the genes in the mouse genome have been modified using their techniques. This has led to a better understanding of mammalian physiology, development and diseases. Mitradas M. Panicker is on the faculty of the National Centre for Biological Sciences, Bangalore, India. His research interests include stem cells, serotonin and its receptors and neurobiology.     

Teaching design in the first years of a traditional mechanical engineering degree: methods,issues and future perspectives

Engineering design is known as an answer to an ill-defined problem. As any answer to an ill-defined problem, it can never be completely right or absolutely wrong. The methods that universities use to teach engineering design, as a consequence of this, suffer from the same fate. However, the accumulated experience with the ‘chalk and talk’ teaching tradition has led to a reality in which the employers of fresh graduates are not happy with the engineers they are getting. Part of their complaints are related with the inability of recently graduate engineers to work in problems where the boundaries are not well defined, are interdisciplinary, require the use of effective communication and integrate non-technical issues. These skills are mostly absent from traditional engineering curricula. This paper demonstrates the implementation of engineering design perspectives enhancing some of the aforementioned skills in a traditional mechanical engineering curriculum. It emphasises in particular a design project that is tackled in a sequence of conventional courses with a focus that depends on the course objectives and disciplinary domain. This transdisciplinary design project conveys the idea (and effectively implements it concurrently) that design is multidisciplinary.     

INCLUSIVE AND SPECIAL EDUCATION: Inclusive and special education in the English educational system: historical perspectives,recent developments and future challenges

Special education in England has over the past 25 years been subject to rapid development, not least in relation to the emergence of inclusive education. Alan Hodkinson of the Faculty of Education, Community and Leisure, John Moore's University, critically examines the development of inclusion in England and the barriers that can stall the development of this important educational and societal initiative. He discusses the journey towards inclusion from educational segregation to integration and describes the current Government stance on this important subject. Alan Hodkinson suggests that many of the barriers to effective inclusion are in practice located within the loci of Government, local authorities as well as that of schools. He concludes that it is now time to develop a new vision for the education of children with special educational needs and disabilities that is supported by straightforward, co‐ordinated and well‐resourced policies. If educational policy is to achieve an inclusive consciousness, it must ensure that the views of children, their families and educational professionals are listened to, and that inclusion is by the choice of the pupils and their parents and not by compulsion.     

Review:Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,present strategies and future perspectives of therapies

INTRODUCTION OF ACUTE LUNG IN- JURY/ACUTE RESPIRATORY DISTRESS SYN- DROME (ALI/ARDS) Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure, which was defined by radiological (bilateral lung field infiltrates) and physiological (the ratio of arterial oxygen pres- sure and the inspiratory oxygen concentration, Pa O 2 /Fi O2≤300 mmHg for ALI and ≤200 mmHg for ARDS) criteria in…     

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）： the mechanism, present strategies and future perspectives of therapies

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.