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The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment 细胞器应激在糖尿病和肥胖症中的作用:对治疗的启示
Pub Date : 2015-11-03 DOI: 10.1155/2015/972891
Yi-Cheng Chang, S. Hee, M. Hsieh, Y. Jeng, L. Chuang
The type 2 diabetes pandemic in recent decades is a huge global health threat. This pandemic is primarily attributed to the surplus of nutrients and the increased prevalence of obesity worldwide. In contrast, calorie restriction and weight reduction can drastically prevent type 2 diabetes, indicating a central role of nutrient excess in the development of diabetes. Recently, the molecular links between excessive nutrients, organelle stress, and development of metabolic disease have been extensively studied. Specifically, excessive nutrients trigger endoplasmic reticulum stress and increase the production of mitochondrial reactive oxygen species, leading to activation of stress signaling pathway, inflammatory response, lipogenesis, and pancreatic beta-cell death. Autophagy is required for clearance of hepatic lipid clearance, alleviation of pancreatic beta-cell stress, and white adipocyte differentiation. ROS scavengers, chemical chaperones, and autophagy activators have demonstrated promising effects for the treatment of insulin resistance and diabetes in preclinical models. Further results from clinical trials are eagerly awaited.
近几十年来,2型糖尿病的流行是一个巨大的全球健康威胁。这种流行病的主要原因是营养过剩和全世界肥胖流行率的增加。相比之下,限制热量摄入和减轻体重可以大大预防2型糖尿病,这表明营养过剩在糖尿病的发展中起着核心作用。近年来,营养过剩、细胞器应激和代谢性疾病发展之间的分子联系得到了广泛的研究。具体来说,过多的营养会触发内质网应激,增加线粒体活性氧的产生,导致应激信号通路激活、炎症反应、脂肪生成和胰腺β细胞死亡。自噬是清除肝脏脂质、减轻胰腺β细胞应激和白色脂肪细胞分化所必需的。在临床前模型中,活性氧清除剂、化学伴侣和自噬激活剂在治疗胰岛素抵抗和糖尿病方面已显示出良好的效果。人们热切期待临床试验的进一步结果。
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引用次数: 20
The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients E2F1和SV40在埃及弥漫性大b细胞淋巴瘤患者预后中的作用及关系
Pub Date : 2015-10-27 DOI: 10.1155/2015/919834
R. Samaka, H. Aiad, M. Kandil, N. Asaad, Nanes S. Holah
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (p<0.001 for all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, and p<0.001). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.
弥漫性大b细胞淋巴瘤(DLBCL)是世界上最常见的淋巴瘤类型。淋巴瘤的发病机制尚不清楚。SV40通过大t抗原(L-TAG)诱导恶性转化,并通过结合p53和pRb并使其失活来促进转化。L-TAG可以结合pRb,促进E2F1转录因子的激活,从而诱导进入S期所需基因的表达,导致细胞转化。本免疫组化研究旨在评估SV40 L-TAG和E2F1在埃及弥漫性大b细胞淋巴瘤(DLBCL)患者预后中的作用和关系。本研究回顾性分析了105例组织标本,其中20例为卵泡增生,85例为DLBCL。3/85(4%)的DLBCL患者检测到SV40 L-TAG。高Ki-67标记指数(Ki-67 LI)和凋亡计数与高E2F1表达相关(p<0.001)。E2F1与SV40无显著相关性。E2F1表达是影响DLBCL患者总生存的首要独立预后因素(HR = 5.79, 95% CI = 2.3 ~ 14.6, p<0.001)。E2F1的上调与肿瘤发生、预后和治疗反应预测有关,但似乎与SV40无关。
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引用次数: 11
Genetic Polymorphism and Expression of CXCR4 in Breast Cancer 乳腺癌中CXCR4基因多态性及表达
Pub Date : 2015-10-20 DOI: 10.1155/2015/289510
Marina Okuyama Kishima, Karen Brajão de Oliveira, C. B. Ariza, C. D. de Oliveira, R. Losi Guembarovski, Bruna Karina Banin Hirata, F. C. de Almeida, G. A. F. Vitiello, K. P. Trugilo, A. L. Guembarovski, Walter Jorge Sobrinho, C. Z. Campos, M. Watanabe
CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis.
CXCR4基因多态性及其表达水平与癌症的发展和预后相关。本研究旨在探讨CXCR4 rs2228014多态性对乳腺癌样本中CXCR4 rs2228014 mRNA和蛋白表达的影响。观察发现,患者的CXCR4 mRNA相对表达量比正常乳腺高5.7倍,但与患者的临床病理特征(核分级、淋巴结状态、ER状态、PR状态、p53染色、Ki67指数、HER-2状态)无关。此外,CXCR4 mRNA的相对表达量也不受T等位基因存在或不存在的影响(p = 0.301)。在免疫组化分析中,不同基因型CXCR4细胞质蛋白染色无差异(p = 0.757);而在浸润性乳腺癌中,细胞质中CXCR4染色较高(p < 0.01)。总之,本研究结果表明rs2228014基因变异不会改变CXCR4 mRNA或蛋白的表达。然而,与正常组织相比,该受体在肿瘤中的RNA和蛋白质水平表达更多,这表明其在乳腺癌发生的一般情况下具有良好的适用性。
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引用次数: 13
An Efficient Protocol for Deriving Liver Stem Cells from Neonatal Mice: Validating Its Differentiation Potential 从新生小鼠中提取肝干细胞的有效方法:验证其分化潜力
Pub Date : 2015-10-18 DOI: 10.1155/2015/219206
S. Dhanasekaran, Devilakshmi Sithambaram, K. Govarthanan, B. Biswal, R. Verma
The success of liver regeneration depends on the availability of suitable cell types and their potential to differentiate into functional hepatocytes. To identify the stem cells which have the ability to differentiate into hepatocytes, we used neonatal liver as source. However, the current protocol for isolating stem cells from liver involves enzymes like collagenase, hyaluronidase exposed for longer duration which limits the success. This results in the keen interest to develop an easy single step enzyme digestion protocol for isolating stem cells from liver for tissue engineering approaches. Thus, the unlimited availability of cell type favors setting up the functional recovery of the damaged liver, ensuring ahead success towards treating liver diseases. We attempted to isolate liver stem derived cells (LDSCs) from mouse neonatal liver using single step minimal exposure to enzyme followed by in vitro culturing. The cells isolated were characterized for stem cell markers and subjected to lineage differentiation. Further, LDSCs were induced to hepatocyte differentiation and validated with hepatocyte markers. Finally, we developed a reproducible, efficient protocol for isolation of LDSCs with functional hepatocytes differentiation potential, which further can be used as in vitro model system for assessing drug toxicity assays in various preclinical trials.
肝再生的成功取决于合适的细胞类型的可用性及其分化为功能性肝细胞的潜力。为了鉴定具有向肝细胞分化能力的干细胞,我们以新生儿肝脏为来源。然而,目前从肝脏中分离干细胞的方法涉及到胶原酶、透明质酸酶等酶,暴露时间较长,这限制了成功。这导致了对开发一种简单的单步酶消化方案的强烈兴趣,用于从肝脏中分离干细胞用于组织工程方法。因此,细胞类型的无限可用性有利于建立受损肝脏的功能恢复,确保未来成功治疗肝脏疾病。我们试图从小鼠新生肝脏中分离肝干细胞(LDSCs),采用单步最小暴露于酶,然后进行体外培养。分离的细胞被鉴定为干细胞标记,并进行谱系分化。进一步,LDSCs被诱导为肝细胞分化,并用肝细胞标记物进行验证。最后,我们开发了一种可重复的、高效的方案,用于分离具有功能性肝细胞分化潜力的LDSCs,该方案进一步可用于各种临床前试验中评估药物毒性的体外模型系统。
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引用次数: 1
Analysis of Color Consistency in Retinal Fundus Photography: Application of Color Management and Development of an Eye Model Standard 视网膜眼底摄影中色彩一致性分析:色彩管理的应用及眼模型标准的制定
Pub Date : 2014-12-30 DOI: 10.1155/2014/398462
Christye Sisson, Susan P. Farnand, M. Fairchild, Bill Fischer
Color variation in retinal fundus photography represents a significant gap in the standardization of color for fundus cameras. Fundus cameras are used in the context of ophthalmology as a method of documenting a patient’s retina to monitor pathology over time.This form of ophthalmic imaging is also used in clinical trial research and, increasingly, teleophthalmology, as a stand in for an in-person examination. Given the increased reliance on these images as representations of the appearance of a patient’s eye, it becomes important to identify inconsistencies between devices and provide the most accurate rendering of the retina possible. This research aims to identify these inconsistencies and reconcile them by proposing an eye color model standard. The authors could not identify other attempts to reconcile retinal color at capture, only after the fact image adjustment [1, 2] or application of current color management practices (Figure 1) [3].
视网膜眼底摄影中的颜色变化代表了眼底相机颜色标准化的重大差距。眼底相机在眼科的背景下使用,作为一种记录患者视网膜的方法,以监测病理随着时间的推移。这种形式的眼科成像也用于临床试验研究,并越来越多地用于远距眼科,作为面对面检查的代表。鉴于越来越依赖这些图像作为患者眼睛外观的表示,识别设备之间的不一致并提供尽可能准确的视网膜渲染变得非常重要。本研究旨在通过提出眼睛颜色模型标准来识别这些不一致并加以调和。作者无法识别其他在捕获时调和视网膜颜色的尝试,只有在事实图像调整后[1,2]或应用当前的颜色管理实践(图1)[3]。
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引用次数: 8
Using a Novel Whole Slide Imaging Software Platform for an International Multicenter Validation Study to Assess the Histological Growth Pattern of Liver Metastases 在一项国际多中心验证研究中,使用一种新颖的全切片成像软件平台来评估肝转移的组织学生长模式
Pub Date : 2014-12-30 DOI: 10.1155/2014/812391
Yves Sucaet, W. Waelput, P. Vermeulen, G. G. Van den Eynden
The histological growth pattern (HGP) of solid tumor metastases to liver is an easy-to-assess and integrative histopathological parameter of tumor-stromal interactions [1]. With preliminary data suggesting that theHGPof colorectal cancer liver metastases has prognostic value [2], we hypothesize that it also might predict response to therapy [1, 3]. To enhance pathological assessments, we organized an internationalmulticenter validation study within the LiverMetastasis Research Consortium.
实体瘤转移到肝脏的组织学生长模式(HGP)是肿瘤-间质相互作用的一个易于评估且综合的组织病理学参数[1]。初步数据表明,结直肠癌肝转移灶的hgpv具有预后价值[2],我们假设它也可以预测治疗反应[1,3]。为了加强病理评估,我们在肝转移研究联盟组织了一项国际多中心验证研究。
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引用次数: 0
Staining Correction in Digital Pathology with Dye Amount Look-Up Table 染色量查表在数字病理染色校正中的应用
Pub Date : 2014-12-30 DOI: 10.1155/2014/964708
P. Bautista, Y. Yagi
Automated image analysis of histology images is affected by the staining variations in histology slides. In general, training images are used to optimize the parameters of an image analysis system. Color, being one of the dominant features of stained tissue samples, is being commonly utilized as feature to segment or classify the different stained tissue components. However, the colors impressed on the tissue components vary with the staining condition of the sample. Hence, when the staining conditions of the slides for the training and test images differ, the accuracy of the analysis results would likely degrade. In this work we present a method to correct the staining condition of the histology images by constructing a look-up table (LUT) of the stained pixels' dye amounts. The present method allows the user to not only correct the staining condition of a given histology image with respect to the staining condition of the reference slide, but to also recreate his/her preferred staining condition for the given image. The results of our experiments with hematoxylin and eosin (H&E) stained tissue images showed the effectiveness of the present method.
组织学图像的自动图像分析受组织学切片染色变化的影响。一般来说,训练图像是用来优化图像分析系统的参数。颜色作为染色组织样本的主要特征之一,被广泛用作对不同染色组织成分进行分割或分类的特征。然而,印在组织成分上的颜色随样品的染色条件而变化。因此,当训练图像和测试图像的载玻片染色条件不同时,分析结果的准确性可能会降低。在这项工作中,我们提出了一种方法,通过构建一个查找表(LUT)的染色像素的染料量来纠正组织学图像的染色条件。本方法允许用户不仅校正相对于参考载玻片的染色条件的给定组织学图像的染色条件,而且还重建他/她对给定图像的首选染色条件。苏木精和伊红(H&E)染色组织图像的实验结果表明了该方法的有效性。
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引用次数: 0
Development of a Prototype for Hepatocellular Carcinoma Classification Based on Morphological Features Automatically Measured in Whole Slide Images 基于全幻灯片图像中形态学特征自动测量的肝细胞癌分类原型的开发
Pub Date : 2014-12-30 DOI: 10.1155/2014/817192
Yoshiko Yamashita, T. Kiyuna, M. Sakamoto, A. Hashiguchi, M. Ishikawa, Y. Murakami, Masahiro Yamaguchi
The advent of new digital imaging technologies including high-throughput slide scanners is making a very compelling case as part of the clinical workflow. Tools developed for morphometric image analysis are accelerating the transition of pathology into a more quantitative science. The system for detection of regions suspected to be cancerous in gastric and colorectal tissue is already available. There is a real need for not only cancer detection but also quantification of histological features, because quantitative morphological characteristics can include important diagnostic and prognostic information. If an association between quantitative features and clinical findings is indicated, quantification of morphological features would be extremely useful to select the best treatment. Image measurement technology also has the potential for investigative pathology. We have developed a prototype system for both quantification of morphological features and automated identification of hepatocellular carcinoma (HCC) within whole slide images (WSI) of liver biopsy based on image recognition and measurement techniques. Our system displays quantified cell and tissue features as histogram, bar graph, and heat map on the screen. Displaying all features in such a unified visualization makes it easy to interpret quantitative feature. In this paper, we present a prototype designed specifically for morphological feature visualization in an easy-to-understand manner.
包括高通量切片扫描仪在内的新型数字成像技术的出现正在成为临床工作流程的一部分,这是一个非常引人注目的案例。用于形态测量图像分析的工具正在加速病理学向定量科学的转变。用于检测胃和结直肠组织中疑似癌变区域的系统已经可用。不仅需要癌症检测,还需要组织学特征的量化,因为定量形态学特征可以包括重要的诊断和预后信息。如果定量特征与临床表现之间存在关联,则形态学特征的定量将对选择最佳治疗非常有用。图像测量技术也有潜在的调查病理学。基于图像识别和测量技术,我们开发了一个原型系统,用于肝脏活检的全切片图像(WSI)中形态学特征的定量和肝细胞癌(HCC)的自动识别。我们的系统在屏幕上显示定量的细胞和组织特征,如直方图,条形图和热图。在这样一个统一的可视化中显示所有的特征,可以很容易地解释定量特征。在本文中,我们以易于理解的方式提出了一个专门用于形态学特征可视化的原型。
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引用次数: 7
Point-of-Use QA in Digital Pathology Slides 数字病理切片的使用点质量保证
Pub Date : 2014-12-30 DOI: 10.1155/2014/590813
D. Brettle, D. Treanor, C. Revie, M. Shires
In digital histopathology traditionally prepared and stained slides are scanned in a dedicated scanner to produce extremely high resolution images.The resultant image fidelity is affected bymany variables including the staining processes, scanner design/setup, and ultimately the image display. Little or no routine quality control is applied at any of these stages and as a result widely varying images can be produced for the same sample.
在数字组织病理学中,传统上制备和染色的载玻片在专用扫描仪中扫描以产生极高分辨率的图像。由此产生的图像保真度受到许多变量的影响,包括染色过程、扫描仪设计/设置以及最终的图像显示。在这些阶段中很少或没有应用常规质量控制,因此对同一样品可以产生差异很大的图像。
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引用次数: 0
Color Management in Digital Pathology 数字病理学中的色彩管理
Pub Date : 2014-12-30 DOI: 10.1155/2014/652757
W. Revie, M. Shires, P. Jackson, D. Brettle, R. Cochrane, D. Treanor
In digital microscopes and whole slide imaging systems, images of slides are captured, transmitted, and reproduced on a computer display. In order to allow pathologists to interpret these images accurately and efficiently, it is important that colors from the slides are displayed in a consistent and reliable fashion. The final color of the image presented to the viewing pathologist depends on several steps through the imaging pathway, including sample illumination, magnification, image capture, compression, storage, and reproduction on the computer display. There are many possible system designs and, within a single system, different setup options which can affect the final image leading to significant variation in image appearances. This paper summarizes recent work by members of the International Color Consortium Medical Imaging Working Group to develop test materials and methods for the assessment of color calibration of digital microscope systems. This work includes sharing of ideas on device calibration and image processing and display. The paper further discusses the challenges encountered in the development of a suitable color target that includes a set of patches with spectra similar to those encountered when viewing pathology slides with stained tissue samples.
在数字显微镜和整个载玻片成像系统中,载玻片的图像被捕获、传输并在计算机显示器上再现。为了使病理学家能够准确有效地解释这些图像,重要的是,幻灯片上的颜色以一致和可靠的方式显示。呈现给观察病理学家的图像的最终颜色取决于通过成像途径的几个步骤,包括样品照明、放大、图像捕获、压缩、存储和在计算机显示器上复制。有许多可能的系统设计,在单个系统中,不同的设置选项可能会影响最终图像,导致图像外观的显着变化。本文总结了国际色彩联盟医学成像工作组成员最近在开发数字显微镜系统色彩校准评估的测试材料和方法方面的工作。这项工作包括分享关于设备校准和图像处理和显示的想法。本文进一步讨论了在开发合适的颜色目标时遇到的挑战,该目标包括一组具有类似于观察带有染色组织样本的病理切片时遇到的光谱的斑块。
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引用次数: 14
期刊
Analytical Cellular Pathology (Amsterdam)
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