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Tumor necrosis factor inhibitors from poxviruses with an emphasis on tanapoxvirus-2L protein. 痘病毒的肿瘤坏死因子抑制剂,重点是痘病毒- 2l蛋白。
Pub Date : 2011-08-01 DOI: 10.2174/187221511796392033
David Jeng, Masmudur M Rahman, Grant McFadden, Karim Essani

Viruses have evolved strategies to counteract host defenses. Some tactics employ viral proteins to neutralize host immune effector proteins such as cytokines, chemokines and their receptors, which help coordinate the host responses against the virus. Tumor necrosis factor (TNF) is one of the crucial pro-inflammatory/anti-viral cytokines involved in inflammatory and autoimmune diseases. Poxvirus anti-immune proteins represent some of the most complex and efficient mechanisms of regulating TNF and its pathological effects. These proteins have considerable potential for treating TNF-related diseases. Here we discuss two major classes of poxvirus-TNF inhibitors focusing on the tanapoxvirus (TPV)-2L protein, previously called TPV-gp38. TPV-2L has been shown to interact and biologically neutralize human (h)TNF, and has been indirectly associated with the inhibition of other cytokines (hIFN-γ, hIL-2 and hIL-5). The TPV-2L protein alone has been expressed, purified and shown to bind with high affinity to hTNF, but lacked binding to the other cytokines. Further studies identified sequential binding of hβ2-microglobulin and hα2-macroglobulin to TPV-2L. The ability of a single viral protein to form multi-protein complexes suggests that TPV might also possess other novel strategies of evading the immune system. Reviewed here are patented poxvirus TNF-binding proteins and their genes to evaluate their potential therapeutic value.

病毒已经进化出对抗宿主防御的策略。一些策略利用病毒蛋白来中和宿主的免疫效应蛋白,如细胞因子、趋化因子及其受体,这些蛋白有助于协调宿主对病毒的反应。肿瘤坏死因子(TNF)是炎症和自身免疫性疾病中重要的促炎/抗病毒细胞因子之一。痘病毒抗免疫蛋白是调节肿瘤坏死因子及其病理作用的一些最复杂和有效的机制。这些蛋白在治疗tnf相关疾病方面具有相当大的潜力。在这里,我们讨论两大类痘病毒-肿瘤坏死因子抑制剂,重点是痘病毒(TPV)-2L蛋白,以前称为TPV-gp38。TPV-2L已被证明与人类(h)TNF相互作用和生物中和,并间接与抑制其他细胞因子(hIFN-γ, hIL-2和hIL-5)相关。单独的TPV-2L蛋白已被表达、纯化并显示与hTNF具有高亲和力结合,但与其他细胞因子缺乏结合。进一步的研究发现h - β2微球蛋白和h - α2巨球蛋白与TPV-2L的顺序结合。单一病毒蛋白形成多蛋白复合物的能力表明,TPV可能还具有其他逃避免疫系统的新策略。本文综述了痘病毒tnf结合蛋白及其基因的专利,以评估其潜在的治疗价值。
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引用次数: 11
Recent advances and novel applications in microbial diversity estimation based on DNA analysis methods. 基于DNA分析方法的微生物多样性估算研究进展及新应用。
Pub Date : 2011-08-01 DOI: 10.2174/187221511796392088
J A Narváez-Zapata, M A Reyes-López
This review focuses on recent patents on the exploration and quantification of microbial diversity. Only the patents based on DNA analysis are considered. In general terms, the analysis of environmental samples can be investigated by using three main approaches: microarrays based technologies, genomes/metagenomes comparison and amplification and detection of operative taxonomic units. All patents can relate to the estimation of the microbial diversity, however, many of them were initially designed to detect important medical or agronomic microorganisms. Here, we briefly review recent technological achievements for DNA analysis that offer great potentials for the identification of species.
本文综述了近年来在微生物多样性的探索和定量方面的专利。仅考虑基于DNA分析的专利。一般来说,环境样本的分析可以通过三种主要方法进行调查:基于微阵列技术,基因组/宏基因组比较和扩增以及有效分类单位的检测。所有专利都与微生物多样性的估计有关,然而,其中许多专利最初是为了检测重要的医学或农艺微生物而设计的。在此,我们简要回顾了近年来在物种鉴定方面具有巨大潜力的DNA分析技术成果。
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引用次数: 0
Recent patents on biclustering algorithms for gene expression data analysis. 基因表达数据分析的双聚类算法的最新专利。
Pub Date : 2011-08-01 DOI: 10.2174/187221511796392097
Alan Wee-Chung Liew, Ngai-Fong Law, Hong Yan

In DNA microarray experiments, discovering groups of genes that share similar transcriptional characteristics is instrumental in functional annotation, tissue classification and motif identification. However, in many situations a subset of genes only exhibits a consistent pattern over a subset of conditions. Although used extensively in gene expression data analysis, conventional clustering algorithms that consider the entire row or column in an expression matrix can therefore fail to detect useful patterns in the data. Recently, biclustering has been proposed as a powerful computational tool to detect subsets of genes that exhibit consistent pattern over subsets of conditions. In this article, we review several recent patents in bicluster analysis, and in particular, highlight a recent patent from our group about a novel geometric-based biclustering method that handles the class of bicluster patterns with linear coherent variation across the row and/or column dimension. This class of bicluster patterns is of particular importance since it subsumes all constant, additive, and multiplicative bicluster patterns normally used in gene expression data analysis.

在DNA微阵列实验中,发现具有相似转录特征的基因群有助于功能注释、组织分类和基序鉴定。然而,在许多情况下,基因的一个子集只在一个子集的条件下表现出一致的模式。尽管在基因表达数据分析中广泛使用,但考虑表达矩阵中整行或整列的传统聚类算法因此无法检测到数据中的有用模式。最近,双聚类被提出作为一种强大的计算工具来检测在条件子集中表现出一致模式的基因子集。在本文中,我们回顾了最近在双聚类分析方面的几项专利,特别强调了我们小组最近的一项专利,该专利是关于一种新的基于几何的双聚类方法,该方法处理具有跨行和/或列维线性相干变化的双聚类模式。这类双聚类模式是特别重要的,因为它包含了通常用于基因表达数据分析的所有常数、加法和乘法双聚类模式。
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引用次数: 5
DNA vaccines: a mini review. DNA疫苗:一个小回顾。
Pub Date : 2011-08-01 DOI: 10.2174/187221511796392114
Ratul Saha, Sarah Killian, Robert S Donofrio

DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Unlike traditional vaccines, DNA vaccines stimulate both arms of the immune system offering long lasting immunity. DNA vaccines not only have the potential to fight against infectious diseases such as influenza and hepatitis but they can also be used to prevent autoimmune diseases such as multiple sclerosis. In general, this article is intended as a mini-review to discuss DNA vaccination, as well as patents on different types of DNA vaccines.

DNA疫苗是疫苗接种领域的一项重大突破,与传统疫苗相比具有若干优势。与传统疫苗不同,DNA疫苗刺激免疫系统的两臂,提供持久的免疫力。DNA疫苗不仅具有对抗流感和肝炎等传染病的潜力,而且还可用于预防多发性硬化症等自身免疫性疾病。总的来说,这篇文章的目的是作为一个小型审查,讨论DNA疫苗接种,以及专利的不同类型的DNA疫苗。
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引用次数: 17
Human DNA extraction methods: patents and applications. 人类DNA提取方法:专利及应用。
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839264
Francesco M Carpi, Fabio Di Pietro, Silvia Vincenzetti, Fiorenzo Mignini, Valerio Napolioni

Since the pioneer experiments conducted by Friedrich Miescher in 1861, extraordinary advances have been achieved in the field of DNA handling. Today nucleic acids can be extracted from any type of biological material such as tissues, cells and viruses. Moreover, increasing knowledge of human genome is paving the way to an effective employment of pharmacogenomics and genetic-based predictive tests in medicine. In this context, the recovery of DNA from different sources of biological samples (e.g. archived formalin-fixed autopsy tissues, dried blood spots, frozen serum or plasma, long-term stored whole blood) is also an emerging field in genetic epidemiology studies. Thus, given the crucial role played by DNA in bio-medical research and in its related applications, here we review the main relevant issued patents and recently published advances in the field of DNA extraction and purification from human specimens.

自从1861年弗里德里希·米歇尔进行了开创性的实验以来,DNA处理领域取得了非凡的进展。今天,核酸可以从任何类型的生物材料中提取,如组织、细胞和病毒。此外,人类基因组知识的增加为药物基因组学和基于基因的医学预测测试的有效应用铺平了道路。在这种情况下,从不同来源的生物样本(例如,存档的福尔马林固定的尸检组织、干燥的血斑、冷冻的血清或血浆、长期储存的全血)中恢复DNA也是遗传流行病学研究的一个新兴领域。因此,鉴于DNA在生物医学研究及其相关应用中发挥的关键作用,我们在这里回顾了从人体标本中提取和纯化DNA领域的主要相关专利和最近发表的进展。
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引用次数: 49
Different proposed applications of bacteriorhodopsin. 细菌视紫红质的不同应用。
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839273
Seema Trivedi, Om Prakash Choudhary, Jitendra Gharu

Bacteriorhodopsin (BR) is an integral membrane protein found in "purple membrane" (the Archaea cell membrane) mainly in Halobacteria. This protein absorbs green light (wavelength 500-650 nm, with the absorption maximum at 568 nm) and converts it into an electrochemical gradient. This gradient in turn is used for ATP production. The ability of BR to convert light energy into chemical energy or sunlight into electricity has been used in different applications mainly optical appliances but also for therapeutic/medical applications and research. This review surveys some of these applications that have been patented in the last five years.

细菌视紫红质(Bacteriorhodopsin, BR)是一种完整的膜蛋白,主要存在于盐杆菌属的“紫膜”(古细菌的细胞膜)中。这种蛋白质吸收绿光(波长500-650 nm,最大吸收波长为568 nm),并将其转化为电化学梯度。这个梯度反过来又用于ATP的产生。BR将光能转化为化学能或将太阳光转化为电能的能力已用于不同的应用,主要是光学器具,但也用于治疗/医疗应用和研究。本文综述了在过去五年中获得专利的一些此类应用。
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引用次数: 17
Significance of P2X7 receptor variants to human health and disease. P2X7受体变异对人类健康和疾病的意义
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839219
Ronald Sluyter, Leanne Stokes

The human P2X7 receptor is a trimeric ligand-gated cation channel coded by the P2XR7 gene located at chromosome position 12q24. P2X7 is expressed in a wide variety of normal and disease-associated cell types. Activation of this receptor by extracellular adenosine 5'-triphosphate results in numerous downstream events including the release of pro-inflammatory mediators, cell proliferation or death, and killing of intracellular pathogens. As a result, P2X7 plays important roles in inflammation, immunity, bone homeostasis, neurological function and neoplasia. The P2XR7 gene encodes a P2X7 subunit 595 amino acids in length, however splice isoforms that can alter receptor expression and function, and modify the signaling properties downstream of receptor activation also exist. Moreover, the relative amount of P2X7 function varies between human individuals due to numerous single nucleotide polymorphisms resulting in either loss- or gain-of-function. Combinations of these polymorphisms give rise to various haplotypes that can also modify P2X7 function. Collectively, P2X7, and its splice and polymorphic variants are attracting considerable interest in relation to human health and disease, including the development and publication of a number of patents.

人类P2X7受体是一个三聚体配体门控阳离子通道,由位于染色体12q24位置的P2XR7基因编码。P2X7在多种正常和疾病相关的细胞类型中表达。细胞外腺苷5'-三磷酸激活该受体可导致许多下游事件,包括促炎介质的释放、细胞增殖或死亡以及细胞内病原体的杀死。因此,P2X7在炎症、免疫、骨稳态、神经功能和肿瘤中发挥重要作用。P2XR7基因编码一个长度为595个氨基酸的P2X7亚基,然而剪接异构体也可以改变受体的表达和功能,并改变受体激活下游的信号特性。此外,由于许多单核苷酸多态性导致功能丧失或功能获得,P2X7功能的相对量在人类个体之间有所不同。这些多态性的组合产生了各种单倍型,这些单倍型也可以改变P2X7的功能。总的来说,P2X7及其剪接和多态变体在人类健康和疾病方面引起了相当大的兴趣,包括许多专利的开发和出版。
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引用次数: 139
Recent patents in cationic lipid carriers for delivery of nucleic acids. 核酸输送用阳离子脂质载体的最新专利。
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839255
Rumiana Koynova, Boris Tenchov

Gene therapy is a medical technique intended for treatment of disorders caused by defective, missing, or overexpressing genes. Efficient delivery vectors are necessary in order to transport genetic material to the target cells. Such vectors include viral and non-viral carriers. Viral vectors transfect cells efficiently, however risks associated with their use have limited their clinical applications. Nonviral delivery systems are safer, easier to prepare, more versatile and cost effective. However, their transfection efficiency still falls behind that of the viral vectors. Considerable research into nonviral gene delivery has been conducted in the last two decades on synthetic soft materials such as cationic lipids, polymers, surfactants, and dendrimers as prospective nucleotide carriers for gene delivery. So far, cationic lipids are the most widely used constituents of nonviral gene carriers, with multiple strategies employed to improve their in vitro and in vivo transfection. Efforts in synthesizing new cationic lipids were not fully successful in closing the gap between the efficiency of the viral vectors and that of binary cationic lipid/DNA complexes. Current efforts for improving lipofection efficiency are focused on the development of multicomponent carriers including cationic lipids as key constituents. This review summarizes the recent patents on new cationic lipids as well as on multicomponent formulations enhancing their efficiency as nucleotide carriers.

基因治疗是一种用于治疗由缺陷、缺失或过度表达基因引起的疾病的医学技术。高效的传递载体是将遗传物质运送到靶细胞的必要条件。这些载体包括病毒和非病毒载体。病毒载体能有效地转染细胞,但其相关的风险限制了其临床应用。非病毒给药系统更安全、更容易制备、更通用和更具成本效益。然而,它们的转染效率仍然落后于病毒载体。在过去的二十年里,人们对非病毒基因传递进行了大量的研究,合成的软材料,如阳离子脂质、聚合物、表面活性剂和树状大分子,作为基因传递的核苷酸载体。到目前为止,阳离子脂质是非病毒基因载体中应用最广泛的成分,有多种策略可以改善它们在体外和体内的转染。合成新的阳离子脂质的努力并没有完全成功地缩小病毒载体和二元阳离子脂质/DNA复合物之间的效率差距。目前提高吸脂效率的努力主要集中在以阳离子脂质为主要成分的多组分载体的开发上。本文综述了近年来新型阳离子脂质专利以及提高其作为核苷酸载体效率的多组分制剂。
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引用次数: 34
Recent patents concerning targeted therapy of apoptosis resistance in pancreatic cancer. 胰腺癌细胞凋亡耐药靶向治疗新专利。
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839237
Kristin Werner, Felix Rückert, Hans-Detlev Saeger, Robert Grützmann, Christian Pilarsky

Pancreatic cancer is one of the most malignant forms of cancer. Due to numerous defects of the apoptosis machinery this tumor shows a high resistance towards conventional oncological therapies. On the level of the extrinsic pathway, signal transduction is flawed by over-expression of decoy receptors but also by a dysfunctional death inducing signaling complex (DISC). The mitochondrial pathway, normally stimulated by cell stress and toxic agents is impeded by over-expression of anti-apoptotic members of the Bcl 2 protein family and the so-called inhibitor of apoptosis proteins (IAPs). To overcome the dysfunction of the apoptosis pathway, new therapeutics focus on molecular targets within the apoptosis pathway. Recently, many new treatment modalities have been reported like recombinant ligands of the cell death receptors or inhibitors of anti-apoptotic Bcl-2 members. Furthermore, various substances for the direct activation of the caspase cascade were patented and the over-expression of IAPs could be treated by binding inhibitors or using RNA interference techniques. The present review aims at giving an overview on these new treatment modalities.

胰腺癌是最恶性的癌症之一。由于细胞凋亡机制的许多缺陷,这种肿瘤对常规肿瘤治疗表现出很高的耐药性。在外在通路的水平上,信号转导由于诱饵受体的过度表达以及功能失调的死亡诱导信号复合体(DISC)而存在缺陷。线粒体途径通常受到细胞应激和有毒物质的刺激,但被Bcl 2蛋白家族抗凋亡成员和所谓的凋亡抑制蛋白(IAPs)的过度表达所阻碍。为了克服细胞凋亡途径的功能障碍,新的治疗方法关注细胞凋亡途径中的分子靶点。最近,许多新的治疗方式被报道,如细胞死亡受体的重组配体或抗凋亡Bcl-2成员的抑制剂。此外,用于直接激活caspase级联的各种物质已获得专利,IAPs的过表达可以通过结合抑制剂或RNA干扰技术进行处理。本综述旨在对这些新的治疗方式进行综述。
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引用次数: 7
The diagnostic and therapeutic importance of human growth hormone isoforms. 人类生长激素异构体的诊断和治疗意义。
Pub Date : 2011-04-01 DOI: 10.2174/187221511794839228
Marina María de Jesús Romero-Prado, Noa Beatriz Martín-Cófreces

The study of human growth hormone isoforms has conduced to the elaboration of patents related to very important items: codifying and regulatory sequences, production of the protein at large-scale, modifications to prolong half-life as monomer, dimer and fusion protein for treatments directed to growth-associated diseases. The designs to identification and quantification of hGH are besides the formers establishing very important basis of patented sources that can be used for a specific and opportune diagnosis and treatment of biological abnormalities or undesirable effects when these growth hormones are involved.

对人类生长激素同种异构体的研究有助于制定与非常重要的项目有关的专利:编码和调节序列,大规模生产蛋白质,修改以延长作为单体、二聚体和融合蛋白的半衰期,用于治疗与生长有关的疾病。对生长激素的鉴定和定量的设计,除了上述的设计之外,还为专利来源建立了非常重要的基础,这些专利来源可用于在涉及这些生长激素时对生物异常或不良影响进行特异性和及时的诊断和治疗。
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引用次数: 1
期刊
Recent patents on DNA & gene sequences
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