Twist1、SIRT1、FGF2、TGF-β3基因在胎盘、脐带和乳牙三种间充质干细胞的表达及增殖调控作用研究

目的比较细胞增殖相关基因Twist1、SIRT1、FGF2、TGF-β3在胎盘、脐带和乳牙3种间充质干细胞中的表达差异,分析其对3种间充质干细胞的增殖调控作用。方法通过显微镜对不同传代次数的3种间充质干细胞的形态结构进行比较;经过体外传代培养,利用荧光定量PCR测定细胞增殖相关基因Twist1、SIRT1、FGF2、TGF-β3的表达水平;采用MTT法检测并比较分析3种间充质干细胞的增殖及促增殖能力。结果Twist1、TGF-β3基因在胎盘间充质干细胞中表达水平最高,FGF2基因的表达水平最低,SIRT1基因在脐带间充质干细胞中的表达水平较高。随着传代培养进行,4种基因表达水平在不同代次的间充质干细胞中的表达水平各不相同。Twist1、SIRT1、TGF-β3表达上调时3种间充质干细胞增殖能力增强,FGF2表达上调时3种间充质干细胞增殖能力减弱。结论Twist1、SIRT1、FGF2、TGF-β3在3种间充质干细胞中的表达水平存在一定差异;Twist1、SIRT1、TGF-β3对3种间充质干细胞的增殖表现为正调控作用;而FGF2基因则相反表现为负调控作用。     

间充质干细胞治疗急性胰腺炎的研究进展

间充质干细胞具有强大的免疫调节能力和促进组织修复的巨大潜能。在急性胰腺炎的发病过程能够抑制T、B淋巴细胞及多种炎症因子,并能"归巢"至损伤胰腺,促进损伤胰腺组织修复,参与了急性胰腺炎的病理生理过程。本文将对间充质干细胞在急性胰腺炎病程中的作用作一综述。     

间充质干细胞抗衰老的理论研究进展

研究抗衰老是当今社会的热点课题。干细胞是具有自我更新能力和多向分化能力的细胞,间充质干细胞包含其中。研究常用的间充质干细胞有骨髓间充质干细胞和脂肪间充质干细胞,二者均在组织修复和抗衰老方面有广泛的应用,有很好的发展前景。本文综述了近年来脂肪间充质干细胞抗衰老作用的特点、机制及应用研究进展。     

人脐带间充质干细胞移植治疗心肌肥厚模型小鼠

背景:左心室肥厚作为高血压病常见的靶器官损害,是心脑血管疾病高发病率和死亡率的独立危险因素.间充质干细胞可以促进组织修复,调节免疫反应,可作为治疗心肌肥厚的种子细胞.目的:观察人脐带间充质干细胞静脉注射治疗小鼠心肌肥厚的疗效.方法:①将C57BL/6J小鼠随机分为假手术组、人脐带间充质干细胞组、PBS组,其中人脐带间充...     

炎症环境下白细胞介素1β增强间充质干细胞的迁移及黏附能力

背景：间充质干细胞具有更新迅速、定向归巢、组织修复和免疫调节等特性,因此,有治疗炎症性疾病的潜能。在炎症情况下,白细胞介素1β高表达,外源性输入或生物体内的间充质干细胞不可避免地生存在高浓度白细胞介素1β的环境中。目的：研究在炎症环境下白细胞介素1β与间充质干细胞的相互作用及其影响间充质干细胞迁移和黏附能力的机制,为调整干细胞治疗策略提供理论基础。方法：由第一作者应用计算机在中国知网、万方、维普、PubMed、Web of Science数据库检索涉及白细胞介素1β增强间充质干细胞迁移和黏附能力的相关文献,中文数据库检索词为“白细胞介素1β,间充质干细胞,核转录因子κB,MAPK,ERK,p38,迁移,黏附”;英文数据库检索词为“IL-1β,mesenchymal stem cells,MSC,NF-κB,MAPK,ERK,p38,migration,adhesion”,最终纳入65篇进行综述分析。结果与结论：(1)在炎症环境中,白细胞介素1β可调节间充质干细胞的迁移和黏附能力,该效应可能通过白细胞介素1RI募集IRAK1,并依次激活TAK1与IKK,IKK磷酸化后,激活核转录因子κB...     

间充质干细胞在肾脏疾病治疗中的应用进展

间充质干细胞可以通过旁分泌各种细胞因子减轻炎性反应和恢复肾脏损伤，以及通过调控免疫细胞维持免疫稳态。临床前研究表明，间充质干细胞对急性肾损伤、糖尿病肾病、狼疮性肾炎及各种肾小球疾病动物模型均有明显的治疗效果。临床研究中也证明了间充质干细胞治疗人类肾病是安全、有效的。间充质干细胞疗法揭开了肾脏疾病领域新的生物治疗模式。     

间充质干细胞诱导移植耐受的研究进展及可能机制(英文)

背景:间充质干细胞能自我更新、高度增殖,具有多向分化潜能、低免疫原性及免疫调节特性。在体内和体外均能调节同种异体免疫反应,在实体器官移植中发挥着重要作用,有望成为诱导移植耐受的新途径。目的:综述间充质干细胞在实体器官移植中的应用及其免疫调节机制的最新进展。方法:应用计算机检索Pubmed 1994-01/2009-10期间相关文章,运用MeSH主题词检索,检索词为"Mesenchymal Stem Cells,Mesenchymal Stem Cell Transplantation,Organ Transplantation,Transplantation Immunology,Immunologic Graft Enhancement,Graftvs Host Disease",并限定文章语言种类为"English"。同时计算机检索万方数据库1994-01/2009-10期间相关文章,检索词为"间充质干细胞、器官移植、移植免疫"。纳入标准:文章所述内容应与间充质干细胞免疫学特性、器官移植中的应用及移植免疫进展研究相关。排除标准:重复研究或Meta分析类文章。结果与结论:共收集到200篇相关文献,86篇文献符合纳入标准。间充质干细胞具有低免疫原性及调节免疫调节特性,在诱导移植耐受和器官移植后组织修复中有着不可或缺的优势,其诱导免疫耐受的机制可能与可溶性因子、调节性T细胞、耐受性树突细胞、骨髓嵌合状态、抗炎和组织修复功能有关,并受间充质干细胞输入方式、剂量与时间的影响。     

脐带间充质干细胞修复皮肤创伤的研究进展

脐带间充质干细胞(UC-MSCs)是一种免疫原性低、易于获取和扩增的成体干细胞。UC-MSCs可以调节伤口炎性反应水平,促进血管形成、细胞增殖,抑制瘢痕形成,诱导皮肤附件形成。UC-MSCs联合其他药物作用于伤口可以促进UC-MSCs的黏附、存活、迁移和增殖等。     

Cdc42参与脐带间充质干细胞向炎性因子的趋化

背景:间充质干细胞移植后的归巢能力关系到细胞移植的疗效,研究其趋化和迁移的调控将有助于提高间充质干细胞临床应用的价值。目的:观察Cdc42在人脐带间充质干细胞定向迁移中的作用。方法:首先以组织块法分离培养人脐带间充质干细胞,与炎性因子肿瘤坏死因子α、白细胞介素1β、转化生长因子β共培养后Western检测Cdc42表达变化。化学合成Cdc42的干扰RNA,转染细胞后分别采用Transwell和Matrigel胶观察细胞迁移和黏附能力。应用Western检测Cdc42下游靶分子ERK1/2的变化。结果与结论:与炎性因子共培养后的人脐带间充质干细胞中Cdc42表达明显增加,接近无因子对照组的2倍水平。siRNA下调Cdc42的表达能够显著抑制人脐带间充质干细胞的迁移和黏附,且其下游信号分子ERK1/2的表达以及磷酸化水平均相应受到抑制。提示体外培养环境下Cdc42参与了人脐带间充质干细胞的趋化过程。     

富血小板纤维蛋白释放转化生长因子β1对骨髓间充质干细胞体外增殖的影响

背景:骨髓间充质干细胞是组织修复的理想细胞,能否提高其体外增殖的能力是促进组织修复的关键因素。目的:观察转化生长因子β1对骨髓间充质干细胞体外增殖的影响。方法:兔耳中央动脉抽血,离心制备富血小板纤维蛋白,置于新鲜的DMEM培养液中,分别于37℃下静置7,14,21,28 d,收集富血小板纤维蛋白析出液,检测析出液中转化生长因子β1质量浓度。抽取兔骨髓进行体外培养骨髓间充质干细胞,将收集的富血小板纤维蛋白析出液配制成条件培养液作用于骨髓间充质干细胞,观察其对骨髓间充质干细胞增殖的影响。结果与结论:转化生长因子β1质量浓度随着时间的递增而增高,21-28 d是质量浓度增长最快阶段,在28 d时达到高峰;同一刺激浓度下,骨髓间充质干细胞增殖在0至1 d降低,1至2 d明显升高,2至3 d为平缓期,骨髓间充质干细胞增殖速度最快的是150 ng/L组。实验证实了富血小板纤维蛋白析出液中转化生长因子β1的质量浓度随着时间的增加而增高,含有不同质量浓度转化生长因子β1的条件培养基对骨髓间充质干细胞增殖起到不同的促进作用,骨髓间充质干细胞在含有质量浓度为150 ng/L转化生长因子β1的条件培养基中培养两三天时,增殖速度为最快。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.