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Role of GPCRs towards Cell: An explanation of G-Protein Coupled Receptor Structure gpcr在细胞中的作用:对g蛋白偶联受体结构的解释
Pub Date : 2017-03-27 DOI: 10.15406/JSRT.2017.02.00065
A. Sahdev, Nidhi Sharma, V. Raj
The molecular framework means the plasma membrane which is made up of phospholipid bilayer consist of Gprotein coupled receptor. The name GPCR refers to a common mode of receptor signalling via GTPbinding protein on the inside of the cells. Because their polypeptide chain passes seven times through the plasma membrane, GPCRs are also called as SEVENTRANSMEMBRANE (7TM) receptor. 7TM receptors mediate the physiological signals from the outside of the cells. Then these signal can be a change in the concentration of protein, lipid, neurotransmitters, ions, hormones, odourants, tastants, etc., or an influx to the eye. GPCRs transform these signals to the inside of the cells and elicit a series of reactions involving other nucleotide, protein and metal ions, which eventually deliver a message and appropriate cellular and physiological response1,2 (Figure 1). Receptor is a molecule on or in a cell with which a drug, hormones, neurotransmitters etc. can initially interacts. GProtein coupled receptors are heptahelical, serpentine receptor and are multifunctional receptor having a lots of clinical implications.3
分子框架是指由磷脂双分子层组成的质膜,由g蛋白偶联受体组成。GPCR的名称是指通过细胞内部的GTPbinding蛋白传递受体信号的一种常见模式。由于其多肽链穿过质膜7次,因此也被称为7 -跨膜受体(7TM)。7TM受体介导来自细胞外部的生理信号。然后,这些信号可能是蛋白质、脂质、神经递质、离子、激素、气味剂、味觉剂等浓度的变化,或者流入眼睛。GPCRs将这些信号转化到细胞内部,引发一系列涉及其他核苷酸、蛋白质和金属离子的反应,最终传递信息和适当的细胞和生理反应1,2(图1)。受体是细胞上或细胞内的一种分子,药物、激素、神经递质等最初可以与之相互作用。g蛋白偶联受体是七螺旋、蛇形受体,是一种多功能受体,具有广泛的临床应用价值
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引用次数: 0
Fabrication of tissue-engineered vascular grafts using low sustained intraluminal pressure to sod human adipose-derived stromal vascular fraction cells onto ePTFE 利用低持续腔内压力将人脂肪来源的间质血管部分细胞转移到ePTFE上制备组织工程血管移植物
Pub Date : 2017-03-23 DOI: 10.15406/JSRT.2017.02.00064
H. J. Paek, Stuart K. Williams, A. Yang, Courtney Kim, Shannon Iwami, Todd Case, S. Berman, Eugene Bol, P. Kosnik
Every year millions of Americans are affected by cardiovascular and peripheral arterial diseases. When a patient’s own blood vessels are not suitable for surgical intervention, alternative graft sources are necessary. In this study, the lumens of expanded polytetrafluoroethylene (ePTFE) conduits were coated with freshly isolated adipose-derived stromal vascular fraction (SVF) cells or cultured adipose-derived stromal cells (ASCs) by a single-stage method called “pressure sodding,” using low sustained intraluminal pressure. ePTFE vascular conduits were sodded in as short as 5 minutes. The luminal surface coverage of grafts immediately following pressure sodding and subsequent exposure to physiological luminal flow was evaluated by nuclear staining of the attached cells to the conduit. Cell behavior associated with the sodding process and subsequent shear stress via luminal flow was examined through tissue factor quantification. After exposure to luminal flow at a rate approximating physiological shear in human coronary arteries, the sodded cells remained on the ePTFE conduits. When cultured SVF cells (ASCs, attached stromal cells) were used, average normalized tissue factor levels increased with the application of a luminal flow following the cell sodding process. However, when freshly isolated SVF cells were used, the average normalized tissue factor did not significantly change even after luminal flow. When these cell-coated vascular grafts were implanted into the carotid arteries of dogs, they remained patent for at least 140 days. This novel method of pressure sodding is critical to rapid fabrication of tissue-engineered vascular grafts which can facilitate a successful point-of-care treatment for a number of vascular diseases.
每年有数百万美国人受到心血管和外周动脉疾病的影响。当患者自身的血管不适合手术干预时,就需要替代的移植物来源。在本研究中,利用持续低腔内压力,用新分离的脂肪源性基质血管组分(SVF)细胞或培养的脂肪源性基质细胞(ASCs)包裹膨化聚四氟乙烯(ePTFE)导管的管腔。ePTFE血管导管在短短5分钟内被铺设。通过对导管上附着细胞的核染色来评估压力灌注和随后暴露于生理管腔流后移植物的管腔表面覆盖率。通过组织因子量化,研究了细胞行为与灌注过程和随后的腔流剪切应力的关系。在以近似人类冠状动脉的生理剪切速率暴露于腔内血流后,被灌注的细胞仍留在ePTFE导管上。当使用培养的SVF细胞(ASCs,附着的基质细胞)时,平均标准化组织因子水平随着细胞灌注过程后管腔流的应用而增加。然而,当使用新鲜分离的SVF细胞时,即使经过管腔流动,平均归一化组织因子也没有显着变化。当这些细胞包裹的血管移植物被植入狗的颈动脉时,它们至少保持140天的专利。这种新颖的压力灌注方法对于快速制造组织工程血管移植物至关重要,它可以促进许多血管疾病的成功护理点治疗。
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引用次数: 0
The effect of mesoporous silica particles on stem cell differentiation 介孔二氧化硅颗粒对干细胞分化的影响
Pub Date : 2017-03-21 DOI: 10.15406/jsrt.2017.02.00063
Patrik Ivert, Alex, er Otterbeck, M. Panchenko, Jan Hoeber, S. Vasylovska, Chunfang Zhou, A. Garcia‐Bennett, E. Kozlova
Mesoporous silica particles (MSPs) are characterized by ordered porosity, sharp pore size distributions, high internal surface areas, and large pore volumes.1,2 Control over these structural parameters makes them an ideal candidate for drug encapsulation, perfectly suited to uptake and carry large amounts of drugs that then get released with constant concentration.3–5 The release of the actives can be diffusion controlled or may be triggered by a change in media temperature or pH.6 Creation of simultaneous release profiles is possible by using different pore structures (e. g., 2D hexagonal and 3D cubic) that enable a continuous discharge of a fine tuned mixture of active drugs over a given period of time.
介孔二氧化硅颗粒(MSPs)具有孔隙有序、孔径分布尖锐、内表面积大、孔体积大等特点。1,2对这些结构参数的控制使它们成为药物包封的理想候选物,非常适合于吸收和携带大量药物,然后以恒定的浓度释放。3-5活性物质的释放可以由扩散控制,也可以由介质温度或ph值的变化触发。6通过使用不同的孔结构(例如,二维六边形和三维立方),可以在给定的时间内连续释放精细调节的活性药物混合物。
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引用次数: 3
Evidence of C1q tumor necrosis factor gene family in the sea star asterias rubens 海星肿瘤坏死因子C1q基因家族的证据
Pub Date : 2017-03-21 DOI: 10.15406/jsrt.2017.02.00062
M. Leclerc
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引用次数: 0
The promise of mesenchymal stem cells for intervertebral disc repair 间充质干细胞用于椎间盘修复的前景
Pub Date : 2017-02-28 DOI: 10.15406/JSRT.2017.02.00061
J. Melrose
Disc degeneration (DD) is a major musculoskeletal condition affecting 80% of the general global population [1]. The associated low back pain (LBP) has major socioeconomic impact reviewed in [2]. In the past 25 years a number of promising biological therapies have been investigated for the treatment of degenerative Disc Disease (DDD) and these have identified many potential molecular targets for biologic intervention [3-5]. These include agents which induce cellular proliferation, matrix production, regulate matrix metallo protease (MMP) and tissue inhibitor of metallo protease (TIMP) production, inflammation, vascular ingrowth and cell viability [6]. The cell density in the IVD is low [7] and disc cells are exposed to a hostile environment of low oxygen tension, high lactic acid levels, low nutrition and a high hydrostatic pressure leading to cell death and a diminution in cell numbers over time due to cellular senescence [8,9], apoptosis [10,11] and autophagy [12,13]. The resultant decline in cell number with DD places severe demands on any therapeutic measures to alleviate this condition.
椎间盘退变(DD)是影响全球80%人口的主要肌肉骨骼疾病[1]。相关的腰痛(LBP)在[2]中有重要的社会经济影响。在过去的25年里,人们研究了许多有前景的生物疗法来治疗退行性椎间盘病(DDD),并确定了许多潜在的生物干预分子靶点[3-5]。这些药物包括诱导细胞增殖、基质生成、调节基质金属蛋白酶(MMP)和金属蛋白酶组织抑制剂(TIMP)生成、炎症、血管长入和细胞活力[6]。IVD中的细胞密度很低[7],椎间盘细胞暴露在低氧张力、高乳酸水平、低营养和高静水压力的恶劣环境中,导致细胞死亡,细胞数量随着时间的推移而减少,原因是细胞衰老[8,9]、细胞凋亡[10,11]和自噬[12,13]。由此导致的DD细胞数量下降对任何治疗措施都提出了严峻的要求,以减轻这种情况。
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引用次数: 2
Out with the old, in with the new… strategies based on stem cells to design new models of alzheimer’s disease 以干细胞为基础设计阿尔茨海默病的新模型
Pub Date : 2017-02-24 DOI: 10.15406/JSRT.2017.02.00060
A. Revilla
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引用次数: 0
Evidence of complement c1q tumor necrosis factorrelated protein 4 in the sea star asterias rubens: a new sea star cytokine 一种新的海星细胞因子:补体c1q肿瘤坏死因子相关蛋白4的证据
Pub Date : 2017-02-23 DOI: 10.15406/JSRT.2017.02.00058
M. Leclerc
In the present paper, we show a survey of the A. rubens sea star genome for genes associated with NF-kappa-B proteins implied in the immune response: the Complement C1q tumor necrosis factor-related protein 4 (a cytokine) which modulates the NF-kappa-B action in mammals, is described in sea star model.
在本文中,我们展示了对a . rubens海星基因组中与NF-kappa-B蛋白相关的基因的调查,暗示免疫反应:补体C1q肿瘤坏死因子相关蛋白4(一种细胞因子)在哺乳动物中调节NF-kappa-B的作用,在海星模型中被描述。
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引用次数: 1
Evidence of complement decay-accelerating factor transmembrane isoform gene of complement factor b of complement factor h genes in the sea star asterias rubens: three vertebrate regulators of complement pathways in an invertebrate 补体衰变加速因子、补体因子b和补体因子h基因跨膜异构体基因在海星中的证据:一种无脊椎动物补体通路的三种调节因子
Pub Date : 2017-02-23 DOI: 10.15406/JSRT.2017.02.00059
M. Leclerc
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引用次数: 0
Inflammatory bowel diseases: current therapeutic approaches and potential of using stem cells 炎症性肠病:目前的治疗方法和使用干细胞的潜力
Pub Date : 2017-02-20 DOI: 10.15406/jsrt.2017.02.00057
Tripurari Mishra, Aditi Sarswat, Kirtishri Mishra, An, S. Srivastava
Inflammatory bowel diseases (IBDs) are chronic and progressively deteriorating in nature without many promising curative treatments. Chronic inflammation of not well defined origins is considered to be the root cause of the problem which affects intestinal mucosa with or without transmural involvement. IBDs are divided in two main categories: Crohn's disease (CD) and ulcerative colitis (UC). While there is no long lasting cure for IBDs, current therapies can only reduce the causative inflammatory process with the hope to induce long-term remission. Treatment modalities for the IBDs are still evolving. The increased understanding of the underlying immunopathology has helped identify new targeted treatment options like immunosuppressive antibodies directed against signaling molecules. Use of stem cells, which are capable of modulating the immune system, can offer a long lasting relief to the patients suffering from the disease. The goal for stem cell-based therapy is to achieve long lasting cure, if not a permanent one. To achieve this, it would be desirable to obtain cell types, whether genetically modified or naturally occurring, having a high migratory ability in addition to homing ability into the afflicted parts of intestine. These cells should also have high in vivosurvival potential, and then be able to regulate the immune reaction without provoking any response from the host’s immune system and repair the injured tissue. Hematopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) therapies are being investigated as a treatment for IBDs. MSC therapy is well tolerated and has minimal established side-effects compared to HSC therapy, which involves ablative chemotherapy. Several clinical studies using MSCs have been initiated and some early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, which can be resolved only by scientifically unveiling the mechanisms of therapeutic action of stem cells. In this review, we summarize current therapies for IBDs and recent advances in the field of stem cell therapy, which offer promise to become the next generation treatment of choice.
炎症性肠病(IBDs)是一种慢性且逐渐恶化的疾病,没有很多有希望的治疗方法。起源不明的慢性炎症被认为是影响肠粘膜的问题的根本原因,无论有无跨壁受累。ibd主要分为两大类:克罗恩病(CD)和溃疡性结肠炎(UC)。虽然没有长期治愈IBDs的方法,但目前的治疗方法只能减少炎症过程,并希望诱导长期缓解。ibd的治疗方式仍在不断发展。对潜在免疫病理的进一步了解有助于确定新的靶向治疗方案,如针对信号分子的免疫抑制抗体。使用能够调节免疫系统的干细胞,可以为患有这种疾病的患者提供持久的缓解。干细胞疗法的目标是实现长期的治愈,如果不是永久的。为了实现这一目标,人们希望获得的细胞类型,无论是转基因的还是自然产生的,除了能够归巢到受影响的肠道部位外,还具有高迁移能力。这些细胞还应该具有较高的活体存活潜力,然后能够在不引起宿主免疫系统任何反应的情况下调节免疫反应并修复受损组织。造血干细胞(HSC)和间充质基质细胞(MSC)疗法正在被研究作为IBDs的治疗方法。与涉及消融化疗的HSC治疗相比,MSC治疗耐受性良好,副作用最小。一些使用间充质干细胞的临床研究已经开始,一些早期的结果表明了一些固有的问题。在每一项研究中,优化MSC治疗似乎是最紧迫的问题,只有科学地揭示干细胞治疗作用的机制才能解决这一问题。在这篇综述中,我们总结了目前ibd的治疗方法和干细胞治疗领域的最新进展,这些研究有望成为下一代治疗的选择。
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引用次数: 3
Haploidentical stem cell transplantation: a mini review 单倍体干细胞移植:一个小回顾
Pub Date : 2017-02-06 DOI: 10.15406/JSRT.2017.2.00056
A. Mathur, H. Malhotra
Hematopoietic stem cell transplantation is arguably one of the most significant therapeutic measures initiated in the recent era, however this therapeutic entity from the outset was significantly limited by HLA matched donor availability. The advent of haploidentical stem cell transplantation with recently improving outcomes and reduced graft failure rates has provided the much needed boom to this aspect of modern day therapeutics by expanding the donor pool and reducing the wait time for a stem cell transplant which is prognostically important especially in aggressive leukemia’s and lymphomas.
造血干细胞移植可以说是近年来最重要的治疗手段之一,然而这种治疗手段从一开始就受到HLA匹配供体的严重限制。单倍体干细胞移植的出现,最近改善了结果,降低了移植失败率,扩大了供体池,减少了干细胞移植的等待时间,这对预后非常重要,特别是对侵袭性白血病和淋巴瘤。
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引用次数: 0
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Journal of stem cell research & therapeutics
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