造血干细胞自我更新的相关信号分子：作用及途径

背景：造血干细胞数目少,且在体外容易分化,这对其应用于移植存在很大的困难。 目的：文章集中阐述了Wnt、Notch、Bmi_1、Shh、HOXB4信号分子在维持造血干细胞自我更新调控中的作用及其途径。 方法：以HSC、Wnt、Notch、Bmi_1、Shh、HOXB4为检索词,检索PubMed数据库(2002-01/2008-12)。文献检索语种限制为英文。纳入与造血干细胞自我更新相关信号分子密切相关的文献。排除重复性研究和Meta分析。 结果与结论：计算机初步检索到216篇文献,对其中30篇文献进行研究。造血干细胞是具有自我更新、较强分化发育和再生能力、可以产生各种类型血细胞的始祖细胞,被广泛应用于治疗血液系统疾病,但是造血干细胞在体外容易分化,这对其应用于移植存在很大的困难。如何使造血干细胞在体外扩增和处理的同时保持造血干细胞的自我更新特性成为关键问题。近年来通过不同信号通路增强造血干细胞自我更新能力的信号分子成为研究热点。文章集中阐述了Wnt、Notch、Bmi_1、Shh、HOXB4在维持造血干细胞自我更新调控中的作用及其途径,发现上述5种信号分子均具有增强造血干细胞自我更新的功能。此外还有一些因素在维持造血干细胞自我更新的过程中起重要作用,如作为内源性因素的一系列转录因子Oct-4、Ehox、Nanog、SCL、Runx1等,探讨它们相互作用形成的调控网络如何调控造血干细胞的自我更新,将成为造血干细胞自我更新领域研究的一个重点。     

神经干细胞与运动性神经疾病

背景：神经干细胞以其所具有的多向分化潜能、自我更新、迁徙性、低免疫性等特点受到临床的广泛应用，但有关神经干细胞在运动医学领域用于防治运动性损伤等的研究成果不是很多。 目的：旨在通过分析神经干细胞的生物学特性，探讨其在临床上的应用，为神经性疾病的预防和治疗提供理论依据。 方法：应用计算机检索CNKI和PubMed数据库中1997-01/2010-10关于神经干细胞与运动性神经疾病的文章，在标题和摘要中以“神经干细胞，运动医学，失神经肌萎缩，周围神经损伤”或“Neural Stem Cell，Sports Medicine，Denervation Muscle Atrophy，Peripheral Nerve Injury”为检索词进行检索，选择文章内容与神经干细胞和运动性神经疾病相关，同一领域文献选择近期发表或发表在权威杂志上的文章，初检得到262篇文献，根据纳入标准选择31篇进行综述。 结果与结论：神经干细胞以其多向分化潜能、自我维持和更新、低免疫原性、迁徙性和来源广泛等特点为其在治疗神经退行性病变、运动性骨骼肌失神经肌萎缩和促运动性周围神经损伤的再生等提供了较为广阔的应用前景，但由于基础性研究所限，对其作用机制、诱导分化、迁移等仍有待大量的实验研究予以证实。     

诱导性多能干细胞诱导效率和方法的研究进展**◆

背景：将多能性基因导入人或动物成体细胞内,使其重编程为具有发育多潜能的干细胞,这类细胞被称为诱导性多潜能干细胞或诱导性多能干细胞。目前,有关诱导性多能干细胞的研究进展非常迅速。 目的：综述诱导性多能干细胞在转化效率及优化诱导方法等方面的研究进展。 方法：应用计算机检索Medline数据库(http://www.ncbi.nlm.nih.gov/Pubmed),检索时间范围为2006-01/2010-07,检索词为“induced pluripotent stem cells”,限定文章语言为English。共检索1 831篇文献,选用其中57篇进行综述。 结果与结论：诱导性多能干细胞的研究对生命科学产生了十分重大而深远的影响,成为干细胞领域新的研究热点,并在细胞重编程机制、诱导效率的提高、诱导方法的改进、细胞来源的扩大及向功能细胞的分化等方面取得了许多重要的进展。这些研究成果为最终的诱导性多能干细胞技术应用于临床细胞替代治疗奠定基础。     

骨髓间充质干细胞在肝衰竭中的应用

背景：近年来诸多研究已经报道了骨髓间充质干细胞在肝脏病理条件下能够分化为具部分功能的类肝细胞且可修复受损肝脏。 目的：总结和分析骨髓间充质干细胞的生物学特性及其在肝衰竭中的研究与应用。 方法：应用计算机检索CNKI和PubMed数据库中1997-01/2009-12关于“骨髓间充质干细胞在肝衰竭中的研究与应用”的文章,以“骨髓间充质干细胞,肝衰竭”或“肝干细胞,肝脏疾病” 为检索词进行检索。选择文章内容与骨髓间充质干细胞治疗肝衰竭相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到中英文共371篇文献,根据纳入标准选择31篇文章进行综述。 结果与结论：骨髓间充质干细胞是成体干细胞的一种,其具有高度自我更新能力和多向分化潜能,用于肝衰竭治疗的作用机理主要是转分化和细胞融合。随着研究不断得深入,骨髓间充质干细胞移植已逐渐开展应用至肝衰竭治疗中,但其研究有待进一步完善。     

MicroRNA在干细胞增殖与分化过程中的调控作用

背景：研究表明MicroRNA(miRNA)可通过抑制干细胞特定mRNA序列的翻译来调控干细胞的自我更新和分化。 目的：探讨miRNAs在干细胞增殖和分化过程中的作用。 方法：由第一作者检索2000/2010 PubMed数据库、Elsevier数据库及Nature数据库。英文检索词为“stem cell,embryonic stem cell(ESC), induced pluripotent stem cells(iPS cell), microRNA(miRNA)”。排除重复性研究。共保留其中的39篇进行归纳总结。 结果与结论：胚胎干细胞有特异性的miRNAs表达,miRNAs对胚胎干细胞增殖与分化起重要的调控作用;miRNAs对造血干细胞分化的多个阶段和方向有调控作用;miRNAs还参与了神经干细胞、间充质干细胞和皮肤干细胞等成体干细胞分化的调控。干细胞特异性的miRNAs可提高体细胞重编程的效率。     

胚胎干细胞向神经细胞分化的研究进展

胚胎干细胞(embryonic stem cell,ESC)是由早期胚胎内细胞团或原始生殖细胞经体外分离、抑制分化培养获得的多潜能细胞,具有发育分化的多潜能性和无限的自我更新能力,在一定条件下可定向诱导分化为某种类型细胞。ESC在体外培养扩增6个月以上仍能保持其多能性,可诱导分化为     

诱导多潜能干细胞在再生医学中的应用

背景：传统的器官或者细胞移植存在严重的供体来源不足和免疫排斥问题以及伦理学障碍。诱导多潜能干细胞有着近乎胚胎干细胞的自我更新能力和分化潜能,而且还拥有与患者一致的遗传物质,避免了免疫排斥反应,其应用前景十分广阔。 目的：综述诱导多潜能干细胞在再生医学领域应用研究的现状。 方法：应用计算机检索PubMed数据库(http://www.ncbi.nlm.nih.gov/PubMed)相关文章,检索时间为1997/2010,检索词为“induced pluripotent stem cell,diabetes,Parkinson’s disease,cardiovascular”,并限定文章语言种类为English。初检得到文献322篇,最终入选30篇文章进行综述。 结果与结论：疾病特异的诱导多潜能干细胞来源于患者本身,拥有与患者一致的遗传物质,既降低了移植后的免疫排斥,也避免了伦理学的问题。因此个体特异的诱导多潜能干细胞在再生医学领域有潜在的应用前景。     

神经干细胞分化调控机制研究进展

干细胞,顾名思义是指具有多种分化潜能和自我更新能力的细胞,受精卵是目前普遍公认的全能干细胞,而神经干细胞 (neural stem cell, NSC)由于其只能分化成各种神经细胞,因此只能算是多能干细胞.尽管目前NSC体外培养,分离已取得成功,但用于临床还不成熟,主要原因是我们对NSC自我更新和分化的具体调控机制不明,因此不能对于各种疾病的治疗做到有的放矢.本文就目前NSC定向分化调控机制的研究进展作一分析和总结.     

神经干细胞的研究进展

干细胞（stem cell，SC）是上世纪生物医学领域的重大发现，干细胞的概念是Evans在20世纪80年代提出，是指有多种分化潜能和自我更新能力的细胞。按分化潜能的大小，干细胞可分为三种类型：全能干细胞（胚胎干细胞）、单能干细胞、多能干细胞。神经干细胞即为多能干细胞，指可生成神经组织或起源于神经系统，具有自我更新能力并具有演化为不同成熟细胞潜能的细胞，90年代Roybholds等怛。从成年鼠脑纹状体中首次分离出神经干细胞（neural stem cell，NSC）。随着对神经干细胞的深入研究，突破了以往一直认为成年哺乳动物神经元不能再生的观念，而且通过基因修饰还可用于神经系统的基因治疗，表达外源性的神经递质、神经营养因子及代谢性酶，为许多难治性神经系统疾病开辟了一条全新的治疗途径。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.