细胞衰老：阻碍癌基因致癌的机制

细胞衰老是生物体中普遍存在的一种永久性生长抑制现象,能够防止老化的或非正常细胞的进一步生长,对抗细胞的无限增殖能力而对机体起到保护作用。近年来,体内外研究表明,癌基因诱导的细胞衰老能够抑制肿瘤的发生,但一旦衰老机制缺陷,癌基因就可能刺激细胞无限增殖而导致恶性肿瘤,引起细胞衰老的机制目前还不是很清楚,但已发现ARF-P53和P16INK4 a-RB这两条途径的活化与细胞衰老的启动和调节过程密切相关。对细胞衰老的信号传导通路及其调节因子等方面的深入研究可能为肿瘤等重大疾病的预防和治疗提供帮助。     

衰老与P16基因

p16基因被认为是肿瘤抑制基因,它的缺失与许多肿瘤有关,但近年来的研究表明p16还与细胞衰老有着紧密联系,p16的过量表达会诱导细胞发生成熟前衰老,是一个名副其实的衰老基因,这也是p16抑制肿瘤发生的机制,p16诱导衰老的分子机理是因为p16充当细胞周期素依赖性激酶抑制子,使细胞周期停滞而发生衰老,本文就近年来这一领域的进展作一综述。     

细胞衰老的遗传学分析

衰老细胞的细胞周期进程阻滞是一个主动地遗传过程，涉及正生长基因的抑制和负调节因子的上调．例如ＴＰ５３、ＣＩＰ１、Ｐ１６ＩＮＫ４等基因直接或间接地抑制细胞周期蛋白依赖激酶（ｃｙｃｌｉｎ－ｃｄｋ）活性，最终使ＲＢ蛋白发挥细胞生长阻竭功能．细胞衰老的遗传控制还涉及抗衰老基因、端粒酶及ＤＮＡ甲基化等多因素多途径的调控．细胞衰老机制的研讨有助于揭开细胞终端分化、细胞程序性死亡及肿瘤等奥秘，为治疗肿瘤、艾滋病及动脉粥样硬化等顽疾寻找新的有效途径．     

T细胞衰老与慢性肝炎病毒感染相关研究进展

机体年龄的增长和病毒感染都会引起免疫衰老,主要表现在T淋巴细胞数量、细胞亚群数量、细胞膜表面分子及功能发生变化,导致T细胞免疫功能下降和异常。T淋巴细胞衰老的主要原因是端粒长度缩短或者端粒酶功能受损而导致。而影响端粒长度和端粒酶功能的是活性氧的产生以及细胞应激通路引起的DNA损伤。当乙型肝炎病毒、丙型肝炎病毒感染机体后,机体的CD4+T淋巴细胞和CD8+T淋巴细胞功能会受到影响,表达衰老相关蛋白。我们总结了引起T细胞衰老的原因,T细胞衰老后特征和相关的信号通路,以及T细胞衰老在慢性肝炎感染免疫失调中的作用机制。     

运动训练中骨骼肌细胞凋亡的研究进展

细胞凋亡是程序化细胞死亡过程 ,是受一系列基因控制的生理性细胞死亡方式。细胞凋亡是广泛存在于组织细胞的基本生物学现象 ,是细胞应答不同有害刺激或疾病而发生的一种特殊的细胞自杀行为。通过这种细胞自杀行为 ,机体消除损伤、衰老、突变的细胞 ,以维持生理平衡。这是完全不同于坏死的一种死亡途径 ,通常对机体是有利的。细胞凋亡存在于发育、成熟和衰老过程之中 ,同时也存在于多种现代疾病中 ,细胞凋亡异常与多种肌细胞疾病的发生机制有关。探讨肌细胞凋亡的机制对预防和处理运动导致的骨骼肌损伤 ,以及某些骨骼肌疾病的运动保健与功能…     

钙感受器STIM1参与主动脉平滑肌细胞衰老的作用研究

目的:探讨钙感受器基质相互作用分子1(STIM1)参与主动脉平滑肌细胞衰老的作用研究.方法:采用过氧化氢(H2O2)诱导人主动脉平滑肌细胞建立细胞衰老模型,并用衰老相关β-半乳糖苷酶(SA-β-Gal)染色检测细胞衰老变化;利用Cre-loxP基因重组技术,制备平滑肌特异性STIM1基因敲除(sm-STIM1-KO)小...     

细胞衰老的研究进展

细胞衰老的关键特征是经长期正常生长后停止生长,并伴随着一系列功能上和形态学上的变化,但仍保持代谢功能.根据不同的诱导机制,细胞衰老分为复制衰老和应激诱导衰老两类.随着细胞衰老的深入研究,产生了多种学说,其中自由基学说、端粒学说研究得较为深入.p16INK4a/Rb,p19ARF/p53/p21Cipl是引发细胞衰老的两条重要通路,它们相互作用,但当所涉及的关键调节因子发生突变时,细胞将延缓衰老或绕过衰老程序继续增殖.     

流感病毒诱导细胞凋亡的研究进展

细胞凋亡(apoptosis)是个体发育过程中基因调控下的细胞自杀活动,是多细胞有机体为调控机体发育、维护内环境稳定,由基因编码程序的细胞主动死亡过程.细胞首先接收、识别某些特殊的生理或病理性刺激信号,然后启动细胞特有的基因或基因群,通过mRNA转录,合成一组致死效应的蛋白质,从而导致细胞解体、死亡.     

衰老与p53

P53是研究得最深入的肿瘤抑制基因,在许多人类肿瘤中都有p53基因的突变,针对p53突变基因的治疗逐渐成为肿瘤基因治疗的重要手段之一。除了作为肿瘤抑制基因外,p53还有许多重要的功能,包括细胞凋亡和细胞衰老等等,细胞凋亡的机制研究得比较清楚,但细胞衰老的分子机制不是很清楚,目前知道p53过表达会引起细胞衰老,但迁涉到的具体分子信号途径尚不清楚,本文就p53与衰老的关系的最新进展作一综述。     

流感病毒诱导细胞凋亡的研究进展

细胞凋亡（apoptosis）是个体发育过程中基因调控下的细胞自杀活动，是多细胞有机体为调控机体发育、维护内环境稳定，由基因编码程序的细胞主动死亡过程。细胞首先接收、识别某些特殊的生理或病理性刺激信号，然后启动细胞特有的基因或基因群，通过mRNA转录，合成一组致死效应的蛋白质，从而导致细胞解体、死亡。     

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.     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

État de l’art : nouveaux anticoagulants et transfusion

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.     

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.