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Kinematic and Dynamic Characteristics of Pulsating Flow in 180�Tube 180°管内脉动流动的运动学与动力学特性
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2019.07854
T. Hung, Ruei-Hung Kuo, C. Chiang
: Kinematic and dynamic characteristics of pulsating flow in a model of human aortic arch are obtained by a computational analysis. Three-dimensional flow processes are summarized by pressure distributions on the symmetric plane together with velocity and pressure contours on a few cross sections for systolic acceleration and deceleration. Without considering the effects of aortic tapering and the carotid arteries, the development of tubular boundary layer with centrifugal forces and pulsation are also analyzed for flow separation and backflow during systolic deceleration.
从瞬态管状边界层的运动学和动力学特性出发,对人主动脉弓内的脉动流进行了研究。结果只能通过快速加速和减速收缩流的三维流体动力学(CFD)分析得到。流动基于规定的进口速度VO(t),可以表示为瞬时雷诺数Re(t) = ρ dvo /μ,其中D为管径,ρ为血液密度,μ为动态粘度。计算压力场需要一个下游端段的参考压力。压力是基于冯永昌教授的《生物力学:循环》一书中的脉搏。采用Hirt等人提出的Navier-Stokes方程的任意Lagrangian-Eulerian (ALE)公式的有限体积法[2]。
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引用次数: 0
Hierarchical Rigid Registration of Femur Surface Model Based on AnatomicalFeatures 基于解剖特征的股骨表面模型分层刚性配准
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2020.08933
Xiaozhong Chen
Existing model registration of individual bones does not have a high certainly of success due to the lack of anatomic semantic. In light of the surface anatomy and functional structure of bones, we hypothesized individual femur models would be aligned through feature points both in geometrical level and in anatomic level, and proposed a hierarchical approach for the rigid registration (HRR) of point cloud models of femur with high resolution. Firstly, a coarse registration between two simplified point cloud models was implemented based on the extraction of geometric feature points (GFPs); and then, according to the anatomic feature points (AFPs) in two level namely shape features and structure features, the fine weight-based registration was performed to achieve anatomical alignment; finally, the origin source model was automatically transformed by applying the obtained coarse matrix and fine one in sequence. Experimental results show that the hierarchical registration method can rapidly and accurately register point clouds of individual femurs, and achieves the medical semantic alignment, and provides a basic tool for the understanding and comparison of femur anatomy and structure.
由于缺乏解剖学语义,现有的个体骨模型配准成功率不高。根据骨骼的表面解剖和功能结构,我们假设单个股骨模型在几何水平和解剖水平上通过特征点对齐,并提出了一种高分辨率股骨点云模型刚性配准(HRR)的分层方法。首先,在提取几何特征点(gfp)的基础上实现两种简化点云模型之间的粗配准;然后,根据形状特征和结构特征两个层次的解剖特征点(AFPs)进行精细权重配准,实现解剖对准;最后,将得到的粗矩阵和细矩阵依次进行源源模型的自动变换。实验结果表明,层次配准方法能够快速准确地配准单个股骨的点云,实现医学语义对齐,为了解和比较股骨解剖结构提供了基本工具。
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引用次数: 3
Application of Dual Modality Contrast Agent Combined with Multi-Scale Representation in Ultrasound-Magnetic Resonance Imaging Registration Scheme 双模态造影剂结合多尺度表示在超声磁共振成像配准方案中的应用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2020.010805
M. Hou, Wei-yu Kevin Chiang, Weiqiang Hong, Mao-Yun Yang, W. Yu
To achieve the image registration/fusion and perfect the quality of the integration, with dual modality contrast agent (DMCA), a novel multi-scale representation registration method between ultrasound imaging (US) and magnetic resonance imaging (MRI) is presented in the paper, and how DMCA influence on registration accuracy is chiefly discussed. Owing to US’s intense speckle noise, it is a tremendous challenge to register US with any other modality images. How to improve the algorithms for US processing has become the bottleneck, and in the short term it is difficult to have a breakthrough. In that case, DMCA is employed in both US and MRI to enhance the region of interest. Then, because multi-scale representation is a strategy that attempts to diminish or eliminate several possible local minima and lead to convex optimization problems to be solved quickly and more efficiently, a multi-scale representation Gaussian pyramid based affine registration (MRGP-AR) scheme is constructed to complete the US-MRI registration process. In view of the above-mentioned method, the comparison tests indicate that US-MRI registration/fusion may be a remarkable method for gaining high-quality registration image. The experiments also show that it is feasible that novel nano-materials combined with excellent algorithm are used to solve some hard tasks in medical image processing field.
为了实现图像的配准/融合,提高图像的融合质量,采用双模态造影剂(DMCA),提出了一种超声成像(US)与磁共振成像(MRI)之间的多尺度表示配准方法,并重点讨论了DMCA对配准精度的影响。由于US具有强烈的散斑噪声,因此将US与其他模态图像进行配准是一个巨大的挑战。如何改进美国处理的算法成为瓶颈,短期内很难有突破。在这种情况下,DMCA在US和MRI中都被用于增强感兴趣的区域。然后,由于多尺度表示是一种试图减少或消除几个可能的局部最小值并使凸优化问题更快、更有效地解决的策略,因此构建了基于多尺度表示高斯金字塔的仿射配准(MRGP-AR)方案来完成US-MRI配准过程。对比试验表明,US-MRI配准/融合可能是获得高质量配准图像的一种显著方法。实验还表明,利用新型纳米材料结合优秀的算法解决医学图像处理领域的一些难题是可行的。
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引用次数: 0
Genetically Encoded FRET Biosensor Detects the Enzymatic Activity ofProstate-Specific Antigen 基因编码FRET生物传感器检测前列腺特异性抗原的酶活性
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2020.09595
Hui Yao, Liqun Wang, Jia Guo, Weimin Liu, Jingjing Li, Yingxiao Wang, Linhong Deng, Mingxing Ouyang
: Prostate cancer is the most common cancer among men beyond 50 years old, and ranked the second in mortality. The level of Prostate-speci fi c antigen (PSA) in serum has been a routine biomarker for clinical assessment of the cancer development, which is detected mostly by antibody-based immunoassays. The proteolytic activity of PSA also has important functions. Here a genetically encoded biosensor based on fl uorescence resonance energy transfer (FRET) tech-nology was developed to measure PSA activity. In vitro assay showed that the biosensor containing a substrate peptide ‘ RLSSYYSGAG ’ had 400% FRET change in response to 1 µg/ml PSA within 90 min, and could detect PSA activity at 25 ng/ml. PSA didn ’ t show enzymatic activity toward the biosensor in serum solution, likely re fl ecting the existence of other inhibitory factors besides Zn 2+ . By expressing the biosensor on cell plasma membrane, the FRET responses were signi fi cant, but couldn ’ t distinguish well the cultured prostate cancer cells from non-prostate cancer cells under microscopy imaging, indicating insuf fi cient speci- fi city to PSA. The biosensor with the previously known ‘ HSSKLQ ’ substrate showed little response to PSA in solution. In summary, we developed a genetically encoded FRET biosensor to detect PSA activity, which may serve as a useful tool for relevant applications, such as screening PSA activation substrates or inhi-bitors; the puri fi ed biosensor protein can also be an alternative choice for measur-ing PSA activity besides currently commercialized Mu-HSSKLQ-AMC substrate from chemical synthesis.
前列腺癌是50岁以上男性中最常见的癌症,死亡率排名第二。血清中前列腺特异性抗原(PSA)水平已成为临床评估癌症发展的常规生物标志物,主要通过基于抗体的免疫分析检测。PSA的蛋白水解活性也具有重要的功能。本文开发了一种基于荧光共振能量转移(FRET)技术的基因编码生物传感器来测量PSA活性。体外实验表明,含有底物肽“RLSSYYSGAG”的生物传感器在1 μ g/ml PSA作用下90 min内FRET变化400%,并能检测25 ng/ml的PSA活性。血清溶液中PSA对生物传感器没有表现出酶促活性,可能反映了除zn2 +外还有其他抑制因子的存在。通过在细胞质膜上表达生物传感器,FRET反应明显,但在显微镜成像下不能很好地区分培养的前列腺癌细胞和非前列腺癌细胞,表明对PSA的特异性不足。该生物传感器具有先前已知的“HSSKLQ”底物,对溶液中的PSA反应很小。总之,我们开发了一种基因编码的FRET生物传感器来检测PSA活性,这可能是一个有用的工具,用于相关应用,如筛选PSA激活底物或抑制剂;除了目前商业化的化学合成Mu-HSSKLQ-AMC底物外,纯化的生物传感器蛋白也可以作为测量PSA活性的另一种选择。
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引用次数: 3
Multifrequency Microwave Imaging for Brain Stroke Detection 多频微波成像用于脑卒中检测
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2019.07101
Lulu Wang
: Early diagnosis of stroke with timely treatment could reduce adult permanent disability significantly [1]. Conventional medical imaging tools such as X-ray, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have been widely used for diagnosis of brain disease. However, each of these methods has some limitations. X-ray imaging produces harmful radiation to the human body and challenging to identify early-stage abnormal tissue due to the relatively small dielectric proprieties contrast between the healthy tissue and abnormal tissue at X-ray frequencies [2]. PET provides useful information about soft tissues, but it is expensive and produces poor resolution. CT and MRI are unsuitable for continuously monitoring strokes due to produce harmful radiations (CT), expensive (MRI), time-consuming and not easy to develop a portable system [3,4]. Therefore, develop a new screening method is urgently needed to improve the effectiveness of disease detection. Microwave imaging is a relatively new non-invasive and cost-effective method for imaging of breast and brain tissues, which has continuously attracted many researchers’ interests the past two The authors previously developed a holographic microwave imaging (HMI) method for dielectric object detection with a particular focus on brain stroke This paper investigates the feasibility of multifrequency HMI for brain stroke detection. A numerical system was developed to demonstrate the proposed theory. Various experiments were carried out to evaluate the performance of the proposed method. Results of experiments carried out using multifrequency HMI have been compared with the results obtained by using single frequency HMI. Results showed that multifrequency HMI could detect strokes and provide more accurate results of size and location than the single frequency HMI algorithm.
早期诊断并及时治疗可显著减少成人永久性残疾[0]。传统的医学成像工具,如x射线、超声、计算机断层扫描(CT)、磁共振成像(MRI)和正电子发射断层扫描(PET)等,已广泛用于脑部疾病的诊断。然而,每种方法都有一些局限性。x射线成像对人体产生有害辐射,由于健康组织和异常组织在x射线频率[2]下介电特性对比相对较小,因此对早期异常组织的识别具有挑战性。PET提供了有关软组织的有用信息,但价格昂贵且分辨率较差。CT和MRI由于产生有害辐射(CT)、昂贵(MRI)、耗时和不易开发便携式系统而不适合连续监测脑卒中[3,4]。因此,迫切需要开发一种新的筛查方法来提高疾病检测的有效性。微波成像是一种相对较新的、无创的、低成本的乳腺和脑组织成像方法,在过去的两年中不断引起许多研究者的兴趣。作者先前开发了一种用于介质目标检测的全息微波成像(HMI)方法,特别是针对脑卒中,本文探讨了多频HMI用于脑卒中检测的可行性。开发了一个数值系统来证明所提出的理论。进行了各种实验来评估所提出方法的性能。用多频人机界面与单频人机界面的实验结果进行了比较。结果表明,与单频HMI算法相比,多频HMI算法可以检测笔画,并提供更准确的笔画大小和位置结果。
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引用次数: 1
A C-GAN denoising algorithm in Projection Domain for Micro-CT 微ct投影域C-GAN去噪算法
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2019.07386
Lujie Chen, Liang Zheng, Maosen Lian, Shouhua Luo
Micro-CT provides a high-resolution 3D imaging of micro-architecture in a non-invasive way, which becomes a significant tool in biomedical research and preclinical applications. Due to the limited power of micro-focus X-ray tube, photon starving occurs and noise is inevitable for the projection images, resulting in the degradation of spatial resolution, contrast and image details. In this paper, we propose a C-GAN (Conditional Generative Adversarial Nets) denoising algorithm in projection domain for Micro-CT imaging. The noise statistic property is utilized directly and a novel variance loss is developed to suppress the blurry effects during denoising procedure. Conditional Generative Adversarial Networks (C-GAN) is employed as a framework to implement the denoising task. To guarantee the pixelwised accuracy, fully convolutional network is served as the generator structure. During the alternative training of the generator and the discriminator, the network is able to learn noise distribution automatically. Moreover, residual learning and skip connection architecture are applied for faster network training and further feature fusion. To evaluate the denoising performance, mouse lung, milkvetch root and bamboo stick are imaged by micro-CT in the experiments. Compared with BM3D, CNN-MSE and CNN-VGG, the proposed method can suppress noise effectively and recover image details without introducing any artifacts or blurry effect. The result proves that our method is feasible, efficient and practical.
Micro-CT以无创的方式提供了微结构的高分辨率3D成像,成为生物医学研究和临床前应用的重要工具。由于微聚焦x射线管的功率有限,投影图像不可避免地会产生光子饥饿和噪声,从而导致空间分辨率、对比度和图像细节的下降。本文提出了一种基于C-GAN(条件生成对抗网络)的投影域微ct图像去噪算法。直接利用噪声统计特性,提出了一种新的方差损失方法来抑制去噪过程中的模糊效应。采用条件生成对抗网络(C-GAN)作为框架实现去噪任务。为了保证图像的像素化精度,我们采用了全卷积网络作为生成器结构。在产生器和鉴别器交替训练的过程中,网络能够自动学习噪声分布。此外,残差学习和跳跃连接架构的应用加快了网络训练速度,进一步实现了特征融合。实验采用微ct对小鼠肺、黄芪根和竹竿进行图像处理,评价其去噪效果。与BM3D、CNN-MSE和CNN-VGG相比,该方法能够有效抑制噪声,恢复图像细节,不引入伪影和模糊效果。结果证明了该方法的可行性、有效性和实用性。
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引用次数: 7
The Effect of Continued Training with Crocin on Apoptosis Markers in Liver Tissue of High Fat Diet Induced Diabetic Rats 持续用藏红花素训练对高脂饮食诱导的糖尿病大鼠肝组织凋亡标志物的影响
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-01-01 DOI: 10.32604/mcb.2020.011532
Zahra Alimanesh, Zeynab Alimanesh, F. Davari, S. - Shadmehri, M. Ahmadi, S. Hosseini, S. Dolati, Alemeh Hariri Far
: Diabetes mellitus (DM) disease can affect process of apoptosis by increasing oxidative stress, nevertheless exercise and crocin can improve apoptosis; therefore present study aimed to investigate the effect of continued training with crocin on apoptosis markers in liver tissue of diabetic rats. In this experimental study 32 diabetic rats based on fasting glucose divided into four groups of eight rats including: 1) sham, 2) training, 3) crocin, and 4) training with crocin also for investigate the effect of DM induction on apoptosis markers, eight healthy rats assigned in healthy control group. During eight weeks groups 2 and 4 ran 60 minutes on treadmill with intensity of 50 – 55% maximum speed for three sessions per week and groups 3 and 4 received 25 mg/kg/day crocin peritoneally. Shapiro ’ post-hot statistical analysis of data (P ≤ 0.05) . DM induction signi fi cantly increased Bcl-2 as well as decreased Bax and P52 (P ≤ 0.05) nevertheless training and training with crocin signi fi cantly decreased Bcl-2 and increased Bax and P53 (P ≤ 0.05) ; crocin signi fi cantly decreased Bcl-2 and increased P53 (P ≤ 0.05) and training with crocin had higher effect on increase of Bax and P53 compare to training (P ≤ 0.05) also increase of Bax compare to crocin. Although training and crocin alone can improve apoptotic markers in diabetic rats, nevertheless training simultaneously with crocin have better effects than training alone.
糖尿病(DM)可通过增加氧化应激影响细胞凋亡过程,而运动和藏红花素可促进细胞凋亡;因此,本研究旨在探讨藏红花素持续训练对糖尿病大鼠肝组织凋亡标志物的影响。本实验以32只空腹血糖为基础,将糖尿病大鼠分为4组,每组8只,分别为:1)假手术组,2)训练组,3)藏红花素组,4)藏红花素训练组,研究DM诱导对细胞凋亡标志物的影响,8只健康大鼠作为健康对照组。在8周内,第2组和第4组在跑步机上以最大速度50 - 55%的强度跑步60分钟,每周3次,第3组和第4组腹腔注射25 mg/kg/天的藏红花素。夏皮罗热后数据统计分析(P≤0.05)。DM诱导显著升高Bcl-2,降低Bax和P52 (P≤0.05),而训练和藏红花素联合训练显著降低Bcl-2,升高Bax和P53 (P≤0.05);藏红花素能显著降低Bcl-2,升高P53 (P≤0.05),且训练对Bax和P53的升高作用高于训练(P≤0.05),Bax的升高作用高于藏红花素(P≤0.05)。虽然单独训练和藏红花素可以改善糖尿病大鼠的凋亡标志物,但同时训练和藏红花素比单独训练效果更好。
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引用次数: 4
Impact of Plaque Erosion on Stress/Strain and Flow Shear Stress Calculation: An OCT-Based FSI Modeling Study 斑块侵蚀对应力/应变和流动剪切应力计算的影响:基于oct的FSI模型研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-11-15 DOI: 10.32604/mcb.2019.07522
Liang Wang, H. Jia, Luping He, R. Lv, Xiaoya Guo, Chun Yang, D. Giddens, H. Samady, A. Maehara, G. Mintz, D. Tang
Plaque erosion, one of the primary causes for coronary thrombosis, is responsible for about one third of the patients with acute coronary syndrome (ACS) [1]. Histological studies characterized the eroded plaque as a plaque with following morphological features: 1) plaque intima having direct contact with intraluminal thrombus due to the absence of endothelium or endothelial injury; 2) without rupture in the fibrous cap; 3) abundance of proteoglycans and smooth muscle cells on the luminal surface under the thrombus [2]. These characteristics has been applied in in vivo diagnosis of plaque erosion using  optical coherence tomography (OCT) image technology and specific treatment strategy has also been developed for plaque erosion related ACS [3]. However, The pathogenesis mechanisms that cause plaque erosion are not fully understood [2]. It is postulated that plaque erosion has close association with biomechanical conditions in the coronary vessel [2]. In this work, a patient-specific OCT-based modeling approach was develop 3D fluid-structure interaction (FSI) models to investigate the biomechanical conditions in eroded plaque and investigate the impact of erosion-induced inflammation on plaque stress/strain conditions. Patient-specific OCT data of eroded coronary plaque were acquired from one male patient (age: 64) with frequency-domain OCT C7XR system and the Dragon Fly catheter (Lightlab Imaging/St. Jude Medical). Erosion sites were identified as the luminal surface having direct contact with intraluminal thrombus on the OCT images. Biplane X-ray angiographic data (Allura Xper FD10 System, Philips, Bothel, WA)  were also acquired with the information of the location of the coronary artery stenosis and vessel curvature. OCT images were segmented manually with external elastic membrane (EEM) contour assumed to have positive remodeling ratio 1.1 for this plaque. The trailing edge of the lipid-rich necrotic core (lipid) was also assumed since it cannot be seen on the OCT images.  Co-registration of OCT and angiographic data were performed to reconstruct the 3D coronary geometry. Our FSI modeling procedures with pre-shrink–stretch process and anisotropic material properties were previously developed. Blood flow was assumed to be laminar, Newtonian and incompressible, with arbitrary Lagrangian–Eulerian formulation of the Navier–Stokes equations used as the governing equations. The governing equations of the structure models included equations of motion, the nonlinear Cauchy–Green strain–displacement relation and Mooney–Rivlin material properties. To reflect tissue weakening caused by erosion-induced inflammation, the material stiffness of plaque intima at the erosion site was adjust to one tenth of un-eroded fibrous plaque tissue [2]. Three FSI models were constructed to investigate the impacts of erosion-induced inflammation and lipid component on plaque stress/strain conditions: M1, without erosion (this means plaque intima at the erosion sites were
这表明侵蚀和脂质成分的影响对与斑块评估密切相关的应力/应变计算有影响。
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引用次数: 0
Epigenetic Modulations Induction Using DSCR1 Ectopic Expression in Breast Cancer Cells 乳腺癌细胞中DSCR1异位表达的表观遗传调控诱导
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-04-03 DOI: 10.32604/MCB.2019.04366
Z. N. Boroujeni, Atefeh Shirkavand, A. Aleyasin
Today, prognosis, diagnosis and treatment of cancers are progressing with non-invasive methods, including investigation and modification of the DNA methylation profile in cancer cells. One of the effective factors in regulating gene expression in mammals is DNA methylation. Methylation alterations of genes by external factors can change the expression of genes and inhibit the cancer. In the present study, we investigated the effect of down syndrome critical region 1 gene (DSCR1) ectopic expression on the methylation status of the BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM and CXCR4 genes in breast cancer cell lines. The effect of DSCR1 ectopic expression on cell viability in MCF7, MDA-MB-468, MDA-MB-231 and MCF10A cell lines was evaluated using MTT assay after the cells treated by lentivirus vectors harboring DSCR1 for 72 hrs. Methylation status of BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM and CXCR4 genes in breast cancer cell lines was assessed by Restriction Enzyme PCR (REP) method. Also, methylation changes of these genes in breast cancer cell lines after treatment by lentivirus vectors harboring DSCR1 for 7 days were analyzed by REP method. To confirm the effect of DSCR1 on methylation of genes, Real-time PCR was performed. The MTT assay results indicated that DSCR1 ectopic expression reduced cell viability in all three human breast cancer cell lines. Our results showed that DSCR1 ectopic expression after 6 days reversed the hypomethylation status of the BCL-XL, ITGA6, TCF3, VIM and CXCR4 genes and hypermethylation of RASSF1A and DOK7 genes. The expression levels of BCL-XL, ITGA6, TCF3, VIM and CXCR4 mRNA significantly reduced (P<0.05) and the expression levels of RASSF1A and DOK7 mRNA significantly increased (P<0.05).   Our findings reveal for the first time the impact of DSCR1 ectopic expression on the methylation status of breast cancer cells and identify a novel agent for epigenetic therapy.
今天,癌症的预后、诊断和治疗正在通过非侵入性方法取得进展,包括研究和修改癌细胞中的DNA甲基化谱。DNA甲基化是调控哺乳动物基因表达的有效因素之一。外部因素对基因的甲基化改变可以改变基因的表达,从而抑制肿瘤的发生。在本研究中,我们研究了唐氏综合征关键区1基因(DSCR1)异位表达对乳腺癌细胞系BCL-XL、ITGA6、TCF3、RASSF1A、DOK7、VIM和CXCR4基因甲基化状态的影响。在MCF7、MDA-MB-468、MDA-MB-231和MCF10A细胞系中,采用MTT法检测DSCR1异位表达对细胞活力的影响。采用限制性内切酶PCR (REP)方法检测乳腺癌细胞系BCL-XL、ITGA6、TCF3、RASSF1A、DOK7、VIM和CXCR4基因的甲基化状态。用REP方法分析了DSCR1慢病毒载体作用7天后乳腺癌细胞株中这些基因的甲基化变化。为了证实DSCR1对基因甲基化的影响,我们进行了Real-time PCR。MTT分析结果表明,DSCR1异位表达降低了所有三种人乳腺癌细胞系的细胞活力。我们的研究结果显示,DSCR1异位表达6天后逆转了BCL-XL、ITGA6、TCF3、VIM和CXCR4基因的低甲基化状态以及RASSF1A和DOK7基因的高甲基化状态。BCL-XL、ITGA6、TCF3、VIM、CXCR4 mRNA表达量显著降低(P<0.05), RASSF1A、DOK7 mRNA表达量显著升高(P<0.05)。我们的研究结果首次揭示了DSCR1异位表达对乳腺癌细胞甲基化状态的影响,并确定了一种新的表观遗传治疗药物。
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引用次数: 0
Mitochondrial Remodeling in Endothelial Cells under Cyclic Stretch is Independent of Drp1 Activation 内皮细胞在循环拉伸下的线粒体重塑与Drp1激活无关
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-04-03 DOI: 10.32604/MCB.2019.05199
M. Baba, Ayano Shinmura, S. Tada, T. Amo, A. Tsukamoto
Mitochondria in endothelial cells remodel morphologically when supraphysiological cyclic stretch is exerted on the cells. During remodeling, mitochondria become shorter, but how they do so remains elusive. Drp1 is a regulator of mitochondrial morphologies. It shortens mitochondria by shifting the balance from mitochondrial fusion to fission. In this study, we hypothesized that Drp1 activation is involved in mitochondrial remodeling under supraphysiological cyclic stretch. To verify the involvement of Drp1, its activation was first quantified with Western blotting, but Drp1 was not significantly activated in endothelial cells under supraphysiological cyclic stretch. Next, Drp1 activation was inhibited with Mdivi-1, but this did not inhibit mitochondrial remodeling. Intracellular Ca2+ increase activates Drp1 through calcineurin. First, we inhibited the intracellular Ca2+ increase with Gd3+ and thapsigargin, but this did not inhibit mitochondrial remodeling. Next, we inhibited calcineurin with cyclosporin A, but this also did not inhibit mitochondrial remodeling. These results indicate that mitochondrial remodeling under supraphysiological cyclic stretch is independent of Drp1 activation. In endothelial cells under supraphysiological cyclic stretch, reactive oxygen species (ROS) are generated. Mitochondrial morphologies are remodeled by ROS generation. When ROS was eliminated with N-acetyl-L-cysteine, mitochondrial remodeling was inhibited. Furthermore, when the polymerization of the actin cytoskeleton was inhibited with cytochalasin D, mitochondrial remodeling was also inhibited. These results suggest that ROS and actin cytoskeleton are rather involved in mitochondrial remodeling. In conclusion, the present results suggest that mitochondrial remodeling in endothelial cells under supraphysiological cyclic stretch is induced by ROS in association with actin cytoskeleton rather than through Drp1 activation.
当超生理周期拉伸作用于内皮细胞时,线粒体会发生形态重塑。在重塑过程中,线粒体变得更短,但它们是如何做到的仍然是一个谜。Drp1是线粒体形态的调节因子。它通过改变线粒体融合到裂变的平衡来缩短线粒体。在本研究中,我们假设Drp1的激活参与了超生理循环拉伸下的线粒体重塑。为了验证Drp1的参与,首先用Western blotting对其激活进行了量化,但在生理上循环拉伸的内皮细胞中,Drp1没有明显激活。接下来,Mdivi-1抑制了Drp1的激活,但这并没有抑制线粒体重塑。细胞内Ca2+增加通过钙调磷酸酶激活Drp1。首先,我们用Gd3+和thapsigargin抑制细胞内Ca2+的增加,但这并没有抑制线粒体重塑。接下来,我们用环孢素A抑制钙调磷酸酶,但这也没有抑制线粒体重塑。这些结果表明,超生理循环拉伸下的线粒体重塑与Drp1的激活无关。在超生理循环拉伸下,内皮细胞产生活性氧(ROS)。线粒体形态被ROS的产生重塑。当用n -乙酰- l-半胱氨酸消除ROS时,线粒体重塑受到抑制。此外,当细胞松弛素D抑制肌动蛋白骨架的聚合时,线粒体重塑也受到抑制。这些结果表明活性氧和肌动蛋白细胞骨架在线粒体重塑中起着重要的作用。综上所述,目前的研究结果表明,内皮细胞在超生理循环拉伸下的线粒体重塑是由与肌动蛋白细胞骨架相关的ROS诱导的,而不是通过Drp1激活。
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引用次数: 1
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Molecular & Cellular Biomechanics
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