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Prediction of low birth weight using Random Forest: A comparison with Logistic Regression 使用随机森林预测低出生体重:与逻辑回归的比较
Pub Date : 2017-07-03 DOI: 10.22037/JPS.V8I3.15412
Parisa Ahmadi, H. Alavi-Majd, S. Khodakarim, Leili Tapak, N. Kariman, Payam Amini, Forough Pazhuheian
Low birth weight (neonate weighing less than 2500 g) is associated with several maternal and fetal factors, all interrelated with each other [ 1 ]. This study is aimed to survey maternal risk factors associated with low birth weight neonates using data mining (Random Forest) to account for interactions between them. We also intended to compare Random Forest with traditional Logistic regression. The dataset used in the present study consisted of 600 volunteer pregnant women.  This cross-sectional study was carried out in Milad hospital, Tehran, during 2005-2009. Ten potential risk factors that are commonly associated with low birth weight were selected by using Random Forest technique. Several criteria such as the area under ROC curve were considered in comparing Random Forest with Logistic Regression.According to both criteria, four top rank variables identified by Random Forest were pregnancy age, body mass index during the third three months of pregnancy, mother’s age and body mass index during the first three months of pregnancy, respectively. In addition, in terms of different criteria the Random Forest technique outperformed the Logistic regression (area under ROC curve: 93% ; Total Accuracy:95% ; Kappa Coefficient: 66%).The results of the present study showed that using Random Forest improved the prediction of low birth weight compared with Logistic Regression. This is because of the fact that the former accounts for all interactions between covariates. Therefore, this approach is a promising classifier for predicting low birth weight .
低出生体重(新生儿体重低于2500 g)与多种母胎因素有关,且相互关联[1]。本研究旨在利用数据挖掘(随机森林)来调查与低出生体重新生儿相关的孕产妇危险因素,以解释它们之间的相互作用。我们还打算将随机森林与传统逻辑回归进行比较。本研究使用的数据集包括600名自愿怀孕的妇女。这项横断面研究于2005-2009年在德黑兰Milad医院进行。采用随机森林技术选择10个与低出生体重相关的潜在危险因素。在比较随机森林和逻辑回归时,考虑了几个标准,如ROC曲线下面积。根据这两个标准,随机森林确定的四个最重要的变量分别是怀孕年龄、怀孕第三个月的体重指数、母亲年龄和怀孕前三个月的体重指数。此外,就不同的标准而言,随机森林技术优于Logistic回归(ROC曲线下面积:93%;总准确率:95%;Kappa系数:66%)。本研究结果表明,与Logistic回归相比,使用随机森林可以改善低出生体重的预测。这是因为前者解释了协变量之间的所有相互作用。因此,该方法是预测低出生体重的一种很有前途的分类器。
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引用次数: 13
Assessment of the safety of chicken egg yolk antibody (IgY) consumption by lipid peroxidation marker in mice 用脂质过氧化标记评价小鼠食用鸡蛋黄抗体(IgY)的安全性
Pub Date : 2017-07-03 DOI: 10.22037/JPS.V8I3.17032
F. Kazerouni, Hoda Zeynalian, F. Ebrahimi, A. Rahimipour, Mostafa Bakhshi, Roghaieh Samadi
Production of antibodies in chickens (IgY) has significantly attracted attention of scientists. Numerous publications have reported use of IgY in diagnosis, therapy and prophylaxis. Production of antigen-specific antibodies in chicken can help treat and prevent infectious diseases. The aim of this study was to assess the safety  of IgY( anti  E. coli O157:H7)  on the antioxidant system in mice .Therefore in  this study, three different  doses of IgY against E. coli O157:H7 (0.9375, 1.875 and  3.75 g / kg)  were administrated through oral route to 18 mice (treated groups) and PBS to the control group  and 14 days after administration, blood samples were collected from the mice. Serum malondialdehyde (MDA) level and catalase, glutathione peroxidase and superoxide dismutase activity were measured using commercial kits. Oral administration of IgY against E. coli O157:H7 in  doses  of 0.9375, 1.875 and 3.75 g / kg  caused no  deaths and showed no toxic effects on mice. In this study, after 14 days of  IgY administration there were no significant changes in the activity of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) and  MDA  serum level   compared to the control group. Our findings revealed that oral administration of IgY against E. coli O157:H7 does not show any toxic effects and does not   disturb the antioxidant system in mice . These findings could be indicative of safety of oral administration  of  IgY in mice.
鸡体内产生的抗体(IgY)引起了科学家们的极大关注。许多出版物报道了IgY在诊断、治疗和预防中的应用。鸡体内产生抗原特异性抗体有助于治疗和预防传染病。为了研究抗O157:H7大肠杆菌IgY对小鼠抗氧化系统的安全性,本研究采用三种不同剂量的抗O157:H7大肠杆菌IgY(0.9375、1.875和3.75 g / kg)分别口服给药组(18只)和对照组(PBS),给药后14 d采集小鼠血液。测定血清丙二醛(MDA)水平及过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶活性。口服剂量分别为0.9375、1.875和3.75 g / kg的IgY抗大肠杆菌O157:H7,未造成小鼠死亡,对小鼠无毒性作用。在本研究中,IgY给药14天后,抗氧化酶(过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶)活性和血清丙二醛水平与对照组相比无显著变化。我们的研究结果表明,口服IgY抗大肠杆菌O157:H7没有任何毒性作用,也不会干扰小鼠的抗氧化系统。这些发现可能表明口服IgY小鼠的安全性。
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引用次数: 0
Calculation of exposure rate constant for 60Co, 22Na and 111In Sources with FLUKA Monte Carlo Code 用FLUKA蒙特卡罗程序计算60Co, 22Na和111In源的曝光率常数
Pub Date : 2017-06-25 DOI: 10.22037/JPS.V8I3.12143
Daryoush Khoramian, V. Saba
Exposure rate constant (G) relates activity of a point source to exposure rate at certain distance. It’s an important parameter in radiation protection, medical uses and radiological assessments. In this study, exposure rate constant for three radionuclides include 60 Co, 22 Na and 111 In were calculated with FLUKA Monte Carlo method. Each source was simulated and exposure rate at different distances of 20, 30, 40, 60, 80, 100, 120, 150, 200 and 300cm from the sources were measured. For dose measurements,   a farmer ionization chamber was simulated with active volume of 0.6cm 3 , inner electrode of aluminium with diameter of1mm and wall of pure graphite with thickness of 0.75mm. Calculated exposure rate constants for 60 Co, 22 Na and 111 In at 20 to 300cm from the source ranged from 33.45 to 0.16 mR/(mCi.h), 29.12 to 0.10 mR/(mCi.h) and 8.73 to 0.03 mR/(mCi.h) respectively which show a decreasing trend. Comparison of our results with other studies show that there are good agreement for 60 Co and 22 Na; the present values for exposure rate constant for 111 In was higher than previous reports.
暴露率常数(G)是点源的活度与一定距离上的暴露率的关系。它是辐射防护、医疗用途和放射评估的重要参数。本研究用FLUKA蒙特卡罗方法计算了60 Co、22 Na和111 In三种放射性核素的暴露率常数。模拟每个源,并测量距离源20、30、40、60、80、100、120、150、200和300cm不同距离的暴露率。剂量测量模拟农民电离室,其有效体积为0.6cm 3,内电极为直径为1mm的铝,壁为厚度为0.75mm的纯石墨。60 Co、22 Na和111 In在距离源20 ~ 300cm处的暴露率常数分别为33.45 ~ 0.16 mR/(mCi.h)、29.12 ~ 0.10 mR/(mCi.h)和8.73 ~ 0.03 mR/(mCi.h),并呈下降趋势。我们的结果与其他研究结果的比较表明,60 Co和22 Na有很好的一致性;111 - In的暴露率常数的现值高于以前的报告。
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引用次数: 0
The probability of influence of the abscopal effect on reduction of similar far away 4T1 cell line tumors by irradiation of main tumor 主肿瘤辐照对相似远处4T1细胞系肿瘤的体外效应影响的概率
Pub Date : 2017-06-25 DOI: 10.22037/JPS.V8I3.12674
H. Zarei, H. Mozdarani, A. Mahmoudzadeh, Mohsen Bakhshandeh, N. Nayeri
The most important problem with radiotherapy is the limitation of whole body irradiation of a metastatic patient. There are evidence showing that similar effect will occur in non-irradiated tumors similar to the irradiated ones. This effect is called abscopal effect. In the present study, the abscopal effect on local induced mice breast cancers has been investigated. One million of 4T1 mice breast cancer cell line was injected to balb/c mice subcutaneously while being under anesthesia. After the growth of tumors till becoming palpable, one of two induced tumors were exposed to total 28 Gy, with gamma rays emitted from a cobalt -60 tele-therapy machine in 14 fractions with 2 Gy daily doses. Tumor volumes were measured, using the caliper. The data was analyzed by the use of non-parametrical and ANOVA tests. Similar growth in non-irradiated control tumors was seen. After 10 or 11 fractions of one- side irradiation and total dose of 20 to 22 Gy, however, non-irradiated tumors, similar to irradiated ones, showed similar effect, reduction of size and volume different from control groups (P<0.05).The reduction of non-irradiated tumors relative to irradiation of another tumor in the same mouse is the emblem of occurrence of the abscopal effect. The mechanism of the abscopal effect is unknown but it could be related to the release of cytokines from irradiated tumors with their receptors existing on the surface of non-irradiated tumors. By induction of this effect, the remission probability of small metastases after local irradiation could be possible.
放射治疗最重要的问题是对转移病人全身照射的限制。有证据表明,在未辐照的肿瘤中也会出现类似的效果。这种效应被称为抽象效应。在本研究中,研究了其对局部诱导小鼠乳腺癌的体外作用。将100万株4T1小鼠乳腺癌细胞系麻醉下皮下注射到balb/c小鼠体内。在肿瘤生长到可触及的程度后,将两个诱导肿瘤中的一个暴露在总剂量为28 Gy的环境中,由钴-60远程治疗机以每天2 Gy的剂量分14次发射伽马射线。用卡尺测量肿瘤体积。数据分析采用非参数和方差分析检验。在未辐照的对照肿瘤中也观察到类似的生长。经10次或11次单侧照射,总剂量为20 ~ 22 Gy时,未照射组与照射组效果相似,肿瘤体积缩小与对照组差异有统计学意义(P<0.05)。在同一只小鼠中,未照射的肿瘤相对于另一个肿瘤的照射减少,是发生抽离效应的标志。体外效应的机制尚不清楚,但可能与辐照肿瘤释放细胞因子及其受体存在于非辐照肿瘤表面有关。通过诱导这种效应,局部照射后小转移的缓解概率可能成为可能。
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引用次数: 0
In vitro assay of alkaline phosphatase enzyme activity in liver and fasciola hepatica parasite 肝脏和肝片形吸虫碱性磷酸酶活性的体外测定
Pub Date : 2017-06-19 DOI: 10.22037/JPS.V8I3.11560
S. Aghaei, A. Farahnak, T. Golmohamadi, M. Eshraghian, Mohammad-bagher Molaei-Rad
The present work was designed to determine alkaline phosphatase (ALP) activity level in Fasciola hepatica parasite and Fasciola infected livers to evaluate the effects of liver infection on enzyme activity and to compare enzyme activity in liver and parasite. The sheep livers were collected and adult Fasciola hepatica parasites were isolated and washed with PBS buffer. Collected healthy and infected livers and parasite were homogenized and extract solutions were centrifuged and stored at -20°C. ALP enzymes activity was measured in the extract solution of samples. Proteins of the samples were measured and protein bands were detected through using Bradford and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) methods respectively. Independent two samples t-test was performed to determine significant difference between different groups. The mean values of the assayed ALP specific activities of infected and healthy livers and Fasciola hepatica parasite were estimated 0.163,0.133,0.048 U/mg protein/ml correspondingly. Gel electrophoresis (SDS-PAGE) of Fasciola hepatica and liver extract solution samples displayed different protein bands, including ALP enzyme. Statistical analysis did not show significant difference between enzyme’s activity in infected and healthy livers (P>0.05). However, the liver demonstrated more than ALP activity level to parasite (P<0.05). The findings show that ALP enzymes activity in Fasciola hepatica infected livers could not be concerned as a specific pathological biomarker in fascioliasis, but meanwhile this enzyme displays interest activity in parasite.
本研究旨在测定肝片形吸虫和肝片形吸虫感染肝脏中碱性磷酸酶(ALP)的活性水平,以评价肝脏感染对酶活性的影响,并比较肝片形吸虫和肝片形吸虫肝脏中酶活性的差异。收集羊肝脏,分离成体肝片吸虫,PBS缓冲液清洗。收集健康和感染肝脏及寄生虫均质,提取液离心,-20℃保存。测定样品提取液中ALP酶活性。分别采用Bradford法和十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)法对样品进行蛋白质测定和蛋白条带检测。采用独立两样本t检验,确定各组间存在显著性差异。感染和健康肝脏及肝片吸虫ALP特异性活性的平均值分别为0.163、0.133和0.048 U/mg蛋白/ml。肝片吸虫和肝提取液样品的凝胶电泳(SDS-PAGE)显示出不同的蛋白条带,包括ALP酶。经统计学分析,感染肝脏与健康肝脏酶活性差异无统计学意义(P>0.05)。肝脏对寄生虫的ALP活性高于肝脏(P<0.05)。结果表明,肝片形吸虫感染肝脏中ALP酶活性不能作为片形吸虫病的特异性病理生物标志物,但该酶在寄生虫中表现出感兴趣的活性。
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引用次数: 0
Synergistic effects of serotonin and D-lys3- GHRP-6 on food intakes in food deprived male rats 血清素和D-lys3- GHRP-6对缺食雄性大鼠食物摄取量的协同作用
Pub Date : 2017-06-14 DOI: 10.22037/JPS.V8I3.15784
F. Mahmoudi
Serotonin exerts an inhibitory effect on food intakes. D-Lys3 -GHRP-6 is a ghrelin receptor antagonist which inhibits fasting or ghrelin- induced food intake. In the present study, the effects of serotonin on food intakes were investigated in D-Lys 3 - GHRP-6- treated food-deprived male rats. Twenty food-deprived male rats in four groups (5 in each) received third cerebral ventricular injection of saline, 10µg serotonin, 20nmol D-Lys 3 -GHRP-6 or combination of D-Lys 3 -GHRP-6 and serotonin respectively.  Mean of one hour food intakes were measured. Data was analyzed by one-way analysis of variance (ANOVA) with post hoc Tukey’s test.  In all cases, P<0.05 was considered to be statistically significant. Serotonin, D-Lys 3 - GHRP-6 or combination of serotonin/D-Lys 3 - GHRP-6 decreased the mean food intakes significantly when compared to saline. A significant decrease was observed on mean food intakes between combination of D-Lys 3 -GHRP-6 and serotonin group and serotonin or D-Lys 3 - GHRP-6 groups. A significant decrease was not observed on food intakes between serotonin and D-Lys 3 - GHRP-6 groups. Serotonin and D-Lys 3 -GHRP-6 may exert synergistic inhibitory effects on food intake in rats. Decrease of the ghrelin pathway activity may have a role in mediating the inhibitory effects of serotonin on food intakes.
血清素对食物摄入有抑制作用。D-Lys3 - ghrp -6是一种胃饥饿素受体拮抗剂,可抑制空腹或胃饥饿素诱导的食物摄入。在本研究中,研究了血清素对d- lys3 - GHRP-6处理的食物剥夺雄性大鼠食物摄入量的影响。四组20只缺食雄性大鼠(每组5只)分别给予第三脑室注射生理盐水、10µg血清素、20nmol D-Lys 3 -GHRP-6或D-Lys 3 -GHRP-6与血清素的组合。测量了一小时的平均食物摄入量。数据分析采用单因素方差分析(ANOVA)和事后Tukey检验。在所有情况下,P<0.05被认为具有统计学意义。与生理盐水相比,血清素、D-Lys 3 - GHRP-6或血清素/D-Lys 3 - GHRP-6的组合显著降低了平均食物摄入量。D-Lys 3 -GHRP-6与5 -羟色胺组和5 -羟色胺或D-Lys 3 -GHRP-6组的平均食物摄入量显著降低。在5 -羟色胺组和d -赖氨酸3 - GHRP-6组之间,食物摄入量没有明显减少。5 -羟色胺和d -赖氨酸3 -GHRP-6可能对大鼠进食有协同抑制作用。ghrelin通路活性的降低可能在调节血清素对食物摄入的抑制作用中起作用。
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引用次数: 0
Evaluation of CXCR4, VLA4, and VLA5 expression in peripheral mobilized hematopoietic stem cells in presence of Sotalol Sotalol对外周血造血干细胞CXCR4、VLA4和VLA5表达的影响
Pub Date : 2017-06-13 DOI: 10.22037/JPS.V8I3.15233
Fatemeh Taghavirad, M. Hamidpour, M. Soleimani, Abass Hjifathali
Hematopoietic stem cells (HSC), are considered as an important source for HSCT transplantation. There are several regulators for stem cells migration and homing, among which the nervous system is an important one. This study is going to investigate the   role of nervous system in homing of hematopoietic stem cells. In an experimental study, mononuclear cells were isolated from peripheral blood and treated by a beta adrenergic receptors blocker (Sotalol). After treating the cells with different concentrations 0.5- 500 (mM/ml) for 1- 24 hours, RNA was extracted and the expression of VLA4, VLA5 and CXCR4 genes were determinated through RT-PCR method.The results of this study demonstrated high expression in genes associated with homing of the cells after being treated with drug for 1 hour: CXCR4 gene expression increases in 10 and 50 mM/ml, VLA4 gene expression in 50mM/ml and VLA5 gene expression in 10 mM/ml concentration of Sotalol.Using beta adrenergic receptors blockers in appropriate time and dose of drug can affect the expression of genes which involved in HSCs homing and will lead to high success rate of transplantation of these cells.
造血干细胞(HSC)被认为是造血干细胞移植的重要来源。干细胞迁移和归巢有多种调控机制,其中神经系统是一个重要的调控机制。本研究将探讨神经系统在造血干细胞归巢中的作用。在一项实验研究中,从外周血中分离出单个核细胞,并用β肾上腺素能受体阻滞剂(索他洛尔)处理。不同浓度0.5 ~ 500 (mM/ml)处理细胞1 ~ 24小时后,提取RNA, RT-PCR法检测VLA4、VLA5和CXCR4基因的表达。本研究结果显示,在药物作用1小时后,细胞归巢相关基因高表达:CXCR4基因表达在浓度为10和50mM/ml时升高,VLA4基因表达在浓度为50mM/ml时升高,VLA5基因表达在浓度为10 mM/ml时升高。在适当的时间和剂量下使用β -肾上腺素受体阻滞剂可以影响造血干细胞归巢相关基因的表达,从而提高造血干细胞移植成功率。
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引用次数: 1
National Health Information Network: Lessons Learned From the USA and the UK 国家卫生信息网络:美国和英国的经验教训
Pub Date : 2017-03-13 DOI: 10.22037/JPS.V8I2.15209
H. Moghaddasi, R. Rabiei, F. Asadi, A. Mohammadpour
National Health Information Network (NHIN) is a network in which all health care organizations, government agencies and other health-related organizations are connected to each other to exchange information about health. Due to the necessity of a framework for NHIN development, in this paper, according to the literature review, a definition for NHIN framework was provided, and then the NHIN related projects were reviewed in the United States of America (USA) and the United Kingdom (UK), NHIN and National Programme for Information Technology in the NHS (NPfIT), respectively. The Review of NHIN framework in the countries studied show some similarities and differences in each dimension that are discussed in this framework. NHIN guiding principles in the NHS NPfIT were not regarded or were considered incomplete, compared to the US. NHIN architecture in the US is decentralized while it is centralized in the UK. Based on the review of NHIN framework, these two countries represent important points that can be used in many other countries. However, it can be said that the development of NHIN does not only mean the implementation of national system or systems, or the binding of local health information systems, but It also needs to build on a framework in which many of the issues related to the formation of NHIN would be considered; including the cooperation between government, private sector and stakeholders with regard to local, national and international needs.
国家卫生信息网(NHIN)是所有卫生保健组织、政府机构和其他与卫生有关的组织相互连接以交换卫生信息的网络。鉴于全民健康保险发展需要一个框架,本文在文献综述的基础上,对全民健康保险框架进行了定义,并分别对美国(USA)和英国(UK)的全民健康保险相关项目、全民健康保险和国家信息技术计划(NPfIT)进行了回顾。对所研究国家NHIN框架的审查表明,在该框架中讨论的每个方面都有一些相似之处和差异。与美国相比,NHS NPfIT中的NHIN指导原则不被视为或被认为是不完整的。美国的NHIN架构是去中心化的,而英国是中心化的。基于对NHIN框架的审查,这两个国家代表了许多其他国家可以借鉴的要点。然而,可以说,国家卫生信息系统的发展不仅意味着国家系统或系统的实施,或地方卫生信息系统的约束,而且还需要建立一个框架,其中将考虑与国家卫生信息系统形成有关的许多问题;包括政府、私营部门和利益相关者就地方、国家和国际需求进行合作。
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引用次数: 1
Ligand screening approach to find potential inhibitors of GP1 from Ebola Virus 寻找埃博拉病毒GP1潜在抑制剂的配体筛选方法
Pub Date : 2017-03-13 DOI: 10.22037/JPS.V8I2.13549
G. Rigi, R. Armand, Ebrahim Torktaz
Ebola is one of the members of filoviruses family. It causes severe hemorrhagic with the human mortality rate of 50-90%. In the initial steps of infection, it enters the host cell by Glyco protein1 (GP1). GP1 is a big subunit with the molecular weight of 130 kDa. Its N-terminal domain is responsible for attaching the host cell. In the present study, a database containing 100.000 drug like chemicals which was obtained from Zinc has been screened. The top successive hits were then analyzed regarding Lipinski rules, oral toxicity value and recorded biological properties. Finally, 3 new ligands were introduced as new theoretical inhibitors of Ebola virus entry. Hit #1 (Heptacyclo[18.7.0.02,10.03,8.011,19.012,17.021,26] heptacosa1(20),2(10),3,5,7,11(19),12,14,16,21,23,25-didecaene-9,18,27-trione) indicated the binding affinity of -10.7 kcal/mol with previous biological reports indicating no toxicity on human cell line. Hit#3 (1,1',3,3'-tetraethyl-5'-(4-nitrophenyl)spiro[1,3-diazinane-5,6'-5H-furo[2,3-d]pyrimidine]-2,2',4,4',6 pentone) with the binding affinity of -9.7 kcal/mol theoretically passed pharmacological filters and the toxicity class of 4 theoretically revealed that this hit also can be a potential anti GP1 agent. Moreover, hit#4(10-(Hydroxymethyl)-7,18-dimethoxy-6,17-dimethyl-21-methyl-11.21     diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),6,15(20),17-tetraene-5,8,12,16,19-pentone) also indicated the binding affinity of -9.7 kcal/mol and was matched with Lipinski rules and the toxicity class 4, suggesting that it can be safe in low dose usage. Based on the pharmacological properties, hit #1, 3 and 4 are presented as the new hypothetical drugs against GP1. Moreover, hit#1 has previously been recorded as nontoxic activity on human cell line and makes it an appropriate candidate for further in vitro and in vivo studies.
埃博拉病毒是丝状病毒家族的一员。它引起严重的出血,人类死亡率为50-90%。在感染的最初阶段,它通过Glyco蛋白1 (GP1)进入宿主细胞。GP1是一个大亚基,分子量为130 kDa。它的n端结构域负责附着宿主细胞。在本研究中,筛选了一个包含100,000种从锌中获得的药物样化学物质的数据库。然后根据利平斯基规则、口服毒性值和记录的生物学特性对连续命中的前几名进行分析。最后,介绍了3种新的配体作为埃博拉病毒进入的新的理论抑制剂。Hit #1 (Heptacyclo[18.7.0.02,10.03,8.011,19.012,17.021,26] heptacosa1(20),2(10),3,5,7,11(19),12,14,16,21,23,25-didecaene-9,18,27-trione)与先前的生物学报道显示-10.7 kcal/mol的结合亲和力,对人细胞系无毒性。Hit#3(1,1',3,3'-四乙基-5'-(4-硝基苯基)螺[1,3-二嗪-5,6'- 5h -呋喃[2,3-d]嘧啶]-2,2',4,4',6戊酮)的结合亲和力为-9.7 kcal/mol,理论上通过了药理学过滤,理论上毒性等级为4,表明该Hit也可能是一种潜在的抗GP1药物。此外,hit#4(10-(羟甲基)-7,18-二甲氧基-6,17-二甲基-21-甲基-11.21二氮五环[11.7.1.02,11.04,9.015,20]henicosa4(9),6,15(20),17-四烯-5,8,12,16,19-戊酮)也显示出-9.7 kcal/mol的结合亲和力,符合Lipinski规则,毒性等级为4级,提示低剂量使用是安全的。根据GP1的药理特性,hit #1、hit # 3和hit # 4作为新的假设药物被提出。此外,hit#1先前已被记录为对人类细胞系的无毒活性,使其成为进一步体外和体内研究的合适候选者。
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引用次数: 0
Loss of Human Tyrosinase DOPA Oxidase Activity in Artificial M374 Arg and M 374 Lys Mutants 人工M374 Arg和M374 Lys突变体中酪氨酸酶多巴氧化酶活性的丧失
Pub Date : 2017-03-13 DOI: 10.22037/JPS.V8I2.15240
Roudabeh Behzadi Andouhjerdi, M. Sadeghizadeh
Tyrosinase (Ec: 1.14.18.1) is a copper - containing enzyme which is distributed in all domains of life such as prokaryote, eukaryote, mammals, invertebrates and plants. Tyrosinase catalyzes the oxidation of monophenols to diphenols and diphenols to o-quinones . The tyrosinase crystallographic data shows two histidine -rich regions named CuA and CuB. A loop containing residues M374, S375 and V377 connects the CuA and CuB Centers. This loop is essential for stability of the enzyme. In this study, site directed mutagenesis was used for the replacement of M374 by Arginine and Lysine.in synthesized cDNA cloned in pET 28b (+) . These mutations don't affect the orientation of the Histidin 367(H367) side chain, resulting in loss of activity.
酪氨酸酶(Ec: 1.14.18.1)是一种含铜酶,广泛存在于原核生物、真核生物、哺乳动物、无脊椎动物和植物等生命的各个领域。酪氨酸酶催化单酚氧化为二酚和二酚氧化为邻醌。酪氨酸酶结晶学数据显示了两个组氨酸丰富的区域,称为CuA和CuB。含有残基M374, S375和V377的环路连接CuA和CuB中心。这个环对酶的稳定性至关重要。本研究采用定点诱变技术,用精氨酸和赖氨酸替代M374。克隆于pET 28b(+)的合成cDNA。这些突变不影响组氨酸367(H367)侧链的方向,导致活性丧失。
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引用次数: 0
期刊
Journal of paramedical sciences
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