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Nesprin-2 Interacts with Condensin Component SMC2. nesprin2与冷凝素组件SMC2相互作用。
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2017-01-01 Epub Date: 2017-12-27 DOI: 10.1155/2017/8607532
Xin Xing, Carmen Mroß, Linlin Hao, Martina Munck, Alexandra Herzog, Clara Mohr, C P Unnikannan, Pranav Kelkar, Angelika A Noegel, Ludwig Eichinger, Sascha Neumann

The nuclear envelope proteins, Nesprins, have been primarily studied during interphase where they function in maintaining nuclear shape, size, and positioning. We analyze here the function of Nesprin-2 in chromatin interactions in interphase and dividing cells. We characterize a region in the rod domain of Nesprin-2 that is predicted as SMC domain (aa 1436-1766). We show that this domain can interact with itself. It furthermore has the capacity to bind to SMC2 and SMC4, the core subunits of condensin. The interaction was observed during all phases of the cell cycle; it was particularly strong during S phase and persisted also during mitosis. Nesprin-2 knockdown did not affect condensin distribution; however we noticed significantly higher numbers of chromatin bridges in Nesprin-2 knockdown cells in anaphase. Thus, Nesprin-2 may have an impact on chromosomes which might be due to its interaction with condensins or to indirect mechanisms provided by its interactions at the nuclear envelope.

核膜蛋白Nesprins主要在间期被研究,在间期它们起着维持核形状、大小和定位的作用。我们分析了nesprin2在细胞间期和分裂中染色质相互作用中的作用。我们描述了nesprin2的棒状结构域中预测为SMC结构域的一个区域(aa 1436-1766)。我们证明了这个域可以与自身相互作用。此外,它还能结合凝缩蛋白的核心亚基SMC2和SMC4。在细胞周期的所有阶段都观察到这种相互作用;它在S期特别强,在有丝分裂期间也持续存在。敲低nesprin2不影响凝缩蛋白分布;然而,我们注意到,在nesprin2基因敲低的细胞后期,染色质桥的数量明显增加。因此,nesprin2可能对染色体产生影响,这可能是由于它与凝聚蛋白的相互作用,也可能是由于它在核膜上的相互作用提供的间接机制。
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引用次数: 1
Regeneration and Regrowth Potentials of Digit Tips in Amphibians and Mammals. 两栖动物和哺乳动物趾尖的再生和再生潜力。
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2017-01-01 Epub Date: 2017-04-10 DOI: 10.1155/2017/5312951
Yohan Choi, Fanwei Meng, Charles S Cox, Kevin P Lally, Johnny Huard, Yong Li

Tissue regeneration and repair have received much attention in the medical field over the years. The study of amphibians, such as newts and salamanders, has uncovered many of the processes that occur in these animals during full-limb/digit regeneration, a process that is highly limited in mammals. Understanding these processes in amphibians could shed light on how to develop and improve this process in mammals. Amputation injuries in mammals usually result in the formation of scar tissue with limited regrowth of the limb/digit; however, it has been observed that the very tips of digits (fingers and toes) can partially regrow in humans and mice under certain conditions. This review will summarize and compare the processes involved in salamander limb regeneration, mammalian wound healing, and digit regeneration in mice and humans.

近年来,组织再生与修复一直是医学界关注的热点。对蝾螈和蝾螈等两栖动物的研究揭示了这些动物在全肢/手指再生过程中发生的许多过程,这一过程在哺乳动物中非常有限。了解两栖动物的这些过程可以揭示如何在哺乳动物中发展和改进这一过程。哺乳动物的截肢损伤通常导致疤痕组织的形成,肢体/手指的再生有限;然而,据观察,在某些条件下,人类和老鼠的手指(手指和脚趾)的尖端可以部分再生。本文将对蝾螈肢体再生、哺乳动物伤口愈合以及小鼠和人类手指再生的过程进行综述和比较。
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引用次数: 11
Effect of Antioxidant Water on the Bioactivities of Cells. 抗氧化水对细胞生物活性的影响。
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2017-01-01 Epub Date: 2017-08-17 DOI: 10.1155/2017/1917239
Seong Gu Hwang, Ho-Sung Lee, Byung-Cheon Lee, GunWoong Bahng

It has been reported that water at the interface of a hydrophilic thin film forms an exclusion zone, which has a higher density than ordinary water. A similar phenomenon was observed for a hydrated hydrophilic ceramic powder, and water turns into a three-dimensional cell-like structure composed of high density water and low density water. This structured water appears to have a stimulative effect on plant growth. This report outlines our study of antioxidant properties of this structured water and its effect on cell bioactivities. Culturing media which were prepared utilizing this antioxidant structured water promoted the viability of RAW 264.7 macrophage cells by up to three times. The same tendency was observed for other cells including IEC-6, C2C12, and 3T3-L1. Also, the cytokine expression of the splenocytes taken from a mouse spleen increased in the same manner. The water also appears to suppress the viability of cancer cell, MCF-7. These results strongly suggest that the structured water helps the activities of normal cells while suppressing those of malignant cells.

有报道称,在亲水性薄膜的界面处,水形成了一个比普通水密度更高的禁区。在水合亲水性陶瓷粉中也观察到类似的现象,水变成由高密度水和低密度水组成的三维细胞状结构。这种结构水似乎对植物生长有促进作用。本报告概述了我们对这种结构水的抗氧化特性及其对细胞生物活性的影响的研究。利用该抗氧化结构水制备的培养基可使RAW 264.7巨噬细胞的活力提高3倍。在包括IEC-6、C2C12和3T3-L1在内的其他细胞中也观察到同样的趋势。此外,取自小鼠脾脏的脾细胞的细胞因子表达也以同样的方式增加。水似乎还能抑制癌细胞MCF-7的活力。这些结果强烈表明,结构水有助于正常细胞的活动,同时抑制恶性细胞的活动。
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引用次数: 8
Pulling a Ligase out of a "HAT": pCAF Mediates Ubiquitination of the Class II Transactivator. 从“HAT”中拔出连接酶:pCAF介导II类反激活子的泛素化。
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2017-01-01 Epub Date: 2017-02-12 DOI: 10.1155/2017/8093813
Julie E Morgan, Susanna F Greer

The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the "master regulator" of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region. Further, CIITA is also modified by degradative K48 polyubiquitination. However, the E3 ligase responsible for these modifications was unknown. We show CIITA ubiquitination and transactivity are enhanced with the histone acetyltransferase (HAT), p300/CBP associated factor (pCAF), and the E3 ligase region within pCAF is necessary for both. Additionally, pCAF mediated ubiquitination is independent of pCAF's HAT domain, and acetylation deficient CIITA is K48 polyubiquitinated and degraded in the presence of pCAF. Lastly, we identify the histone acetyltransferase, pCAF, as the E3 ligase responsible for CIITA's ubiquitination.

II类反激活子(CIITA)对主要组织相容性II类(MHC II)基因的转录调控至关重要。CIITA作为MHC II转录的“主调控因子”,其调控势在必行,需要多种翻译后修饰(ptm)才能发挥作用。之前我们发现了CIITA的各种泛素化事件。单泛素化对于CIITA的交易性很重要,而K63连接的泛素化与ERK1/2磷酸化参与串扰,共同介导细胞从细胞质到核区的运动。此外,CIITA还被降解的K48多泛素化修饰。然而,负责这些修饰的E3连接酶是未知的。我们发现,组蛋白乙酰转移酶(HAT)、p300/CBP相关因子(pCAF)增强了CIITA的泛素化和交易活性,而pCAF内的E3连接酶区域对两者都是必需的。此外,pCAF介导的泛素化不依赖于pCAF的HAT结构域,乙酰化缺陷的CIITA在pCAF存在下被K48多泛素化和降解。最后,我们确定了组蛋白乙酰转移酶pCAF作为E3连接酶,负责CIITA的泛素化。
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引用次数: 4
Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations 靶向炎性细胞因子的生物制剂,临床应用和局限性
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-12-19 DOI: 10.1155/2016/9259646
Peleg Rider, Y. Carmi, Idan Cohen
Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra) and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.
促炎细胞因子是许多生物过程的有效介质,在体内受到严格调节。这些细胞因子的长期不受控制的水平可以引发和衍生许多病理,包括自身免疫和癌症的发病率。因此,在过去的几十年里,通过补充抗炎重组细胞因子或通过使用阻断抗体来中和它们来调节炎症细胞因子活性的疗法已经被广泛使用。在过去的几年里,新的创新的生物制剂,阻断和调节细胞因子的活性已经出现。在这里,我们回顾了一些最新的细胞因子靶向方法,重点是抗TNF抗体或重组TNF诱饵受体,重组IL-1受体拮抗剂(IL-1Ra)和抗IL-1抗体,抗il -6受体抗体和TH17靶向抗体。我们讨论了它们作为生物药物的作用,在许多临床试验中进行了评估,并强调了它们的治疗潜力,同时强调了它们固有的局限性和临床风险。我们认为,虽然使用生物制剂全身阻断促炎细胞因子可以改善疾病的发病机制和进展,但它也可能破坏宿主对感染的防御。此外,我们概述了开发新疗法的合理需求,这些新疗法仅在炎症部位阻断炎症细胞因子,同时使其系统发挥作用。
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引用次数: 151
Localisation of Lactate Transporters in Rat and Rabbit Placentae 乳酸转运蛋白在大鼠和兔胎盘中的定位
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-10-23 DOI: 10.1155/2016/2084252
N. Moore, C. Picut, J. Charlap
The distribution of monocarboxylate transporter (MCT) isoforms 1 and 4, which mediate the plasmalemmal transport of l-lactic and pyruvic acids, has been identified in the placentae of rats and rabbits at different ages of gestation. Groups of three pregnant Sprague-Dawley rats and New Zealand White rabbits were sacrificed on gestation days (GD) 11, 14, 18, or 20 and on GD 13, 18, or 28, respectively. Placentae were removed and processed for immunohistochemical detection of MCT1 and MCT4. In the rat, staining for MCT1 was associated with lakes and blood vessels containing enucleated red blood cells (maternal vessels) while staining for MCT4 was associated with vessels containing nucleated red blood cells (embryofoetal vessels). In the rabbit, staining for MCT1 was associated with blood vessels containing nucleated red blood cells while staining for MCT4 was associated with vessels containing enucleated red blood cells. Strength of staining for MCT1 decreased during gestation in both species, but that for MCT4 was stronger than that for MCT1 and was consistent between gestation days. The results imply an opposite polarity of MCT1 and MCT4 across the trophoblast between rat and rabbit.
介导l-乳酸和丙酮酸的质浆运输的单羧酸转运体(MCT)异构体1和4在不同孕龄大鼠和家兔胎盘中的分布已被证实。分别于妊娠第11、14、18、20天和妊娠第13、18、28天处死3只妊娠的Sprague-Dawley大鼠和新西兰大白兔。取出胎盘,进行MCT1和MCT4免疫组化检测。在大鼠中,MCT1染色与湖泊和含有无核红细胞的血管(母体血管)有关,而MCT4染色与含有有核红细胞的血管(胚胎血管)有关。在家兔中,MCT1染色与含有有核红细胞的血管有关,而MCT4染色与含有无核红细胞的血管有关。MCT1的染色强度在两种物种的妊娠期间均有所下降,但MCT4的染色强度强于MCT1,并且在妊娠期间保持一致。结果表明MCT1和MCT4在大鼠和家兔之间的滋养细胞中具有相反的极性。
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引用次数: 6
Microwave-Assisted Tissue Preparation for Rapid Fixation, Decalcification, Antigen Retrieval, Cryosectioning, and Immunostaining 微波辅助组织准备快速固定,脱钙,抗原检索,冷冻切片和免疫染色
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-10-20 DOI: 10.1155/2016/7076910
K. Katoh
Microwave irradiation of tissue during fixation and subsequent histochemical staining procedures significantly reduces the time required for incubation in fixation and staining solutions. Minimizing the incubation time in fixative reduces disruption of tissue morphology, and reducing the incubation time in staining solution or antibody solution decreases nonspecific labeling. Reduction of incubation time in staining solution also decreases the level of background noise. Microwave-assisted tissue preparation is applicable for tissue fixation, decalcification of bone tissues, treatment of adipose tissues, antigen retrieval, and other special staining of tissues. Microwave-assisted tissue fixation and staining are useful tools for histological analyses. This review describes the protocols using microwave irradiation for several essential procedures in histochemical studies, and these techniques are applicable to other protocols for tissue fixation and immunostaining in the field of cell biology.
在固定和随后的组织化学染色过程中对组织进行微波照射可显著减少固定和染色溶液中孵育所需的时间。减少固定液中的孵育时间可以减少组织形态的破坏,减少染色溶液或抗体溶液中的孵育时间可以减少非特异性标记。在染色溶液中减少孵育时间也降低了背景噪声的水平。微波辅助组织制备适用于组织固定、骨组织脱钙、脂肪组织处理、抗原提取及其他组织的特殊染色。微波辅助组织固定和染色是组织分析的有用工具。本文介绍了在组织化学研究中使用微波辐照的几个基本程序的方案,这些技术适用于细胞生物学领域的组织固定和免疫染色的其他方案。
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引用次数: 18
Carbohydrate Moieties and Cytoenzymatic Characterization of Hemocytes in Whiteleg Shrimp Litopenaeus vannamei 凡纳滨对虾(Litopenaeus vannamei)血细胞碳水化合物组成及细胞酶特性研究
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-10-19 DOI: 10.1155/2016/9032181
Norma Estrada, E. Velázquez, C. Rodríguez‐Jaramillo, F. Ascencio
Hemocytes represent one of the most important defense mechanisms against foreign material in Crustacea and are also involved in a variety of other physiological responses. Fluorescent lectin-binding assays and cytochemical reactions were used to identify specificity and distribution of carbohydrate moieties and presence of several hydrolytic enzymes, in hemocytes of whiteleg shrimp Litopenaeus vannamei. Two general classes of circulating hemocytes (granular and agranular) exist in L. vannamei, which express carbohydrates residues for FITC-conjugated lectins WGA, LEA, and PNA; UEA and Con-A were not observed. Enzymatic studies indicated that acid phosphatase, nonspecific esterase, and specific esterases were present; alkaline phosphatase was not observed. The enzymes and carbohydrates are useful tools in hemocyte classification and cellular defense mechanism studies.
血细胞是甲壳类动物抵御外来物质最重要的防御机制之一,并参与多种其他生理反应。采用荧光凝集素结合试验和细胞化学反应鉴定凡纳滨对虾血细胞中碳水化合物的特异性和分布以及几种水解酶的存在。南美扁豆中存在两类循环血细胞(粒状和粒状),它们表达fitc偶联凝集素WGA、LEA和PNA的碳水化合物残基;未观察到UEA和Con-A。酶学研究表明,存在酸性磷酸酶、非特异性酯酶和特异性酯酶;未见碱性磷酸酶。酶和碳水化合物是血细胞分类和细胞防御机制研究的有用工具。
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引用次数: 9
Connexin's Connection in Breast Cancer Growth and Progression 连接蛋白在乳腺癌生长和进展中的作用
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-08-23 DOI: 10.1155/2016/9025905
Debarshi Banerjee
Gap junctions are cell-to-cell junctions that are located in the basolateral surface of two adjoining cells. A gap junction channel is composed of a family of proteins called connexins. Gap junction channels maintain intercellular communication between two cells through the exchange of ions, small metabolites, and electrical signals. Gap junction channels or connexins are widespread in terms of their expression and function in maintaining the development, differentiation, and homeostasis of vertebrate tissues. Gap junction connexins play a major role in maintaining intercellular communication among different cell types of normal mammary gland for proper development and homeostasis. Connexins have also been implicated in the pathogenesis of breast cancer. Differential expression pattern of connexins and their gap junction dependent or independent functions provide pivotal cross talk of breast tumor cells with the surrounding stromal cell in the microenvironment. Substantial research from the last 20 years has accumulated ample evidences that allow us a better understanding of the roles that connexins play in the tumorigenesis of primary breast tumor and its metastatic progression. This review will summarize the knowledge about the connexins and gap junction activities in breast cancer highlighting the differential expression and functional dynamics of connexins in the pathogenesis of the disease.
间隙连接是细胞间的连接,位于两个相邻细胞的基底外侧表面。缝隙连接通道是由一组叫做连接蛋白的蛋白质组成的。间隙连接通道通过离子、小代谢物和电信号的交换维持两个细胞之间的细胞间通讯。间隙连接通道或连接蛋白在维持脊椎动物组织的发育、分化和稳态方面的表达和功能广泛。间隙连接蛋白在维持正常乳腺不同细胞类型间的细胞间通讯以维持正常发育和稳态中起着重要作用。连接蛋白也与乳腺癌的发病机制有关。连接蛋白的差异表达模式及其依赖或独立于间隙连接的功能是微环境中乳腺肿瘤细胞与周围基质细胞的关键串扰。过去20年的大量研究已经积累了充足的证据,使我们能够更好地理解连接蛋白在原发性乳腺肿瘤发生及其转移进展中的作用。本文将对连接蛋白和间隙连接活性在乳腺癌中的作用进行综述,重点介绍连接蛋白在乳腺癌发病机制中的差异表达和功能动态。
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引用次数: 43
Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. 干细胞在再生医学和疾病治疗中的应用。
Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2016-01-01 Epub Date: 2016-07-19 DOI: 10.1155/2016/6940283
Ranjeet Singh Mahla

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

再生医学是医学科学中最新的新兴分支,涉及为严重受伤或患有慢性疾病的病人恢复组织或器官的功能。干细胞研究领域取得的巨大进步为基于细胞的疾病治疗奠定了基础,而传统药物无法治愈这些疾病。干细胞具有无限的自我更新能力和分化成其他类型细胞的潜力,是再生医学的前沿。干细胞的转分化潜能因来源而异,再生应用也随之改变。基因编辑和组织工程技术的进步,使干细胞在体内重塑成三维有机体和组织结构,实现个性化应用。本综述概述了在再生医学中,ESCs、TSPSCs、MSCs、UCSCs、BMSCs 和 iPSCs 移植和组织工程技术的最新进展。此外,本综述还讨论了干细胞在野生动物保护中的再生应用。
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引用次数: 0
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International Journal of Cell Biology
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