Twist的研究进展

Tw ist蛋白是属于碱性的螺旋-环-螺旋蛋白家族中的高度保守的转录因子,在胚胎的发生发展中发挥重要作用。Tw ist被认为是癌基因蛋白,影响肿瘤细胞的凋亡。Tw ist作为上皮-间质转变(ep ithelial-m esenchym altransition,EMT)过程中的关键调控因子,对肿瘤的侵袭和转移有重要影响。     

低氧介导信号通路调控肿瘤细胞上皮间质转化的研究进展

低氧微环境普遍存在于实体瘤中,且与实体瘤的发展和转移紧密相关。低氧诱导因子(HIF)作为响应低氧环境的主要转录因子,可促进肿瘤细胞增殖、生存、血管形成和上皮间质转化(EMT)等。EMT是上皮细胞表型向间质细胞表型转化的生物学过程,主要与其信号通路、转录因子、炎症因子及miRNAs相关,在肿瘤侵袭和转移中起着重要作用。本文总结了低氧信号通路、Wnt/β-catenin信号通路、Notch信号通路、NF-κB信号通路、Hedgehog(Hh)信号通路以及PI3K/Akt信号通路等相关信号通路对肿瘤EMT的影响。     

转录因子Slug对肝癌肿瘤干细胞特性及药物敏感性的影响

<正>肝癌在世界范围内是发病率第5和死亡率第3的癌症,其肿瘤侵袭转移和对传统化疗药物的耐受是目前治疗面临的难题。转录因子Slug主要通过调控基因的表达在肿瘤细胞中发挥功能,已有的研究主要聚焦Slug在上皮细胞的上皮-间质转化(EMT)中通过抑制E-cadherin的表达促进正常上皮细胞向肿瘤细胞恶性转化的研究,关于Slug在肿瘤干细胞和药物耐受性     

上皮间质转化及相关因子在胚胎形成和肿瘤发生发展中的作用北大核心CSCD

上皮间质转化（epithelial-mesenchymal transition,EMT）是多细胞生物胚胎形成的基础过程,主要特征为上皮细胞丧失原有特性而获得间质细胞特性. EMT不仅被广泛发现于胚胎形成过程中,而且也常在肿瘤发生发展中被观测到. 尤其是胚胎植入和肿瘤侵袭转移,这两个关系密切的生物学行为中EMT都发挥了重要作用. 同时,许多参与到EMT的蛋白分子、转录因子和生长因子等成分也正是胚胎形成和肿瘤发生发展的重要组成部分,因此EMT研究有可能成为肿瘤预防和治愈的一个突破口. 本文就EMT及相关因子在胚胎形成和肿瘤发生发展中的作用进行综述.     

转录因子TWIST及其促进肿瘤转移作用的研究进展

TWIST是胚胎发育过程中的重要转录调控因子,最近发现它在肿瘤转移的起始阶段使癌细胞发生EMT现象,即细胞从上皮极性表型向间质成纤维细胞表型的形态学上的转变,同时伴有上皮细胞分子标记的抑制和间质细胞分子标记的强烈表达,从而促进细胞的运动和迁移,使肿瘤呈现恶性表型,导致患者预后不良.目前已经证实有多种细胞信号通路和细胞内因子参与了TWIST的表达和激活,它们对TWIST功能起重要的调控作用.本文主要就目前TWIST的结构、功能及在肿瘤中的作用作一综述.     

抗氧化剂与大肠癌细胞MMP-3表达关系研究

核因子-kB(nuclear factor kappa B,NF-κB) 是一种重要的细胞转录因子,参与多种细胞增殖、凋亡和癌基因等的转录调控.细胞核因子-kB通过上调与侵袭和转移有关的多个基因蛋白表达,从而参与肿瘤的侵袭和转移.因此,通过抑制NF-κB的活化,间接下调相关下游基因蛋白表达,从而抑制肿瘤的侵袭和转移正成为一种新的抗肿瘤治疗方法.本实验旨在探讨大肠癌MMP-3蛋白表达及NF-kB抑制剂二硫氨基甲酸吡啶PDTC(pyrrolidine dithiocarbamate)对大肠癌MMP-3蛋白表达的影响,为大肠癌转移的治疗提供新的理论依据.     

microRNA与肿瘤侵袭转移

microRNA (miRNA)是一类长度为17~25 nt的单链非编码RNA,通过与靶基因mRNA互补位点的结合在转录后水平调控靶基因的表达.miRNA作为调控基因表达的重要分子在肿瘤侵袭转移中的作用越来越受到重视,阐明miRNA在肿瘤侵袭和转移中的作用机制具有重要的理论意义,同时也可以为肿瘤的诊断和治疗提供新方法.文章综述了miRNA在鼻咽癌、乳腺癌、肺癌、肝癌、结直肠癌和前列腺癌侵袭转移过程中作用机制的研究进展.     

上皮细胞间质转型与肿瘤转移

皮细胞间质转型 (epithelial-mesenchymal transitions,EMT)是具有极性的上皮细胞转换成为具有活动能力的间质细胞并获得侵袭和迁移能力的过程,它存在于人体多个生理和病理过程中。EMT的发生涉及到多个信号转导通路和复杂的分子机制,与钙连接素、生长因子、转录因子、微环境等有关。EMT与肿瘤细胞的侵袭和转移关系密切。     

波形蛋白在肝细胞癌中的研究进展

上皮-间质转化(EMT)是肝细胞癌(HCC)侵袭转移和耐药的重要机制。波形蛋白(VIM)作为EMT的标志性分子,参与调控EMT和形成间质表型肿瘤干细胞;以及VIM甲基化和外泌体直接或间接分泌VIM,促进HCC侵袭增殖、化疗耐药以及复发转移。另外,VIM结合甲胎蛋白(AFP)诊断HCC时特异性和灵敏度显著提高,其表达与HCC预后不良密切相关。     

转录因子Runx2对人乳腺癌MDA-MB-231细胞上皮-间充质转化能力的影响

目的:建立稳定敲减Runt相关转录因子2(Runx2)表达的人乳腺癌MDA-MB-231细胞系,探讨Runx2对MDA-MB-231细胞上皮-间充质转化(EMT)、转移和侵袭能力的影响。方法:利用LV-Runx2-RNAi慢病毒载体感染MDA-MB-231细胞,构建稳定低表达Runx2的MDA-MB-231细胞株,检测比较Runx2表达水平对MDA-MB-231细胞的形态及E-cadherin、N-cadherin、β-catenin和基质金属蛋白酶9(MMP-9)蛋白表达的影响。侵袭实验和软琼脂集落形成实验分析比较抑制Runx2表达对乳腺癌细胞侵袭和非锚定生长能力的效应。结果:E-cadherin蛋白表达在敲减Runx2表达的MDA-MB-231细胞中明显高于常规MDA-MB-231细胞(P0.05),而N-cadherin、β-catenin和MMP-9蛋白表达在敲减Runx2表达的MDA-MB-231细胞中明显低于常规MDA-MB-231细胞(P0.05)。敲减Runx2表达的MDA-MB-231细胞侵袭和非锚定生长能力明显低于常规MDA-MB-231细胞(P0.05)。结论:在人乳腺癌MDA-MB-231细胞中抑制Runx2表达可以通过调控EMT相关蛋白的表达进而抑制乳腺癌细胞的EMT过程,从而对细胞的侵袭和转移起负调控作用。     

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.     

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.     

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.     

'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.     

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.     

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.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.