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The 3’-untranslated region contributes to the pregnane X receptor(PXR) expression downregulation by PXR ligands and up-regulation by glucocorticoids

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Acta Pharmaceutica Sinica B 2020年第1期10卷 136-152页

作者： Tomas Smutny Jan Dusek Lucie Hyrsova Jana Nekvindova alzbeta Horvatova Stanislav Micuda Sabine Gerbal-Chaloin Petr Pavek Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec KraloveCharles UniversityHradec Kralove CZ-50005Czech Republic Institute of Clinical Biochemistry and Diagnostics University Hospital Hradec KraloveHradec Kralove CZ-50005Czech Republic Department of Pharmacology Faculty of Medicine in Hradec KraloveCharles UniversityHradec Kralove CZ-50003Czech Republic IRMB INSERMUniversity MontpellierMontpellierFrance

Pregnane X receptor(PXR)is the major regulator of xenobiotic *** itself is controlled by various signaling molecules including ***,negative feed-back regulation has been proposed at the transcriptional *** examined the involvement of the 3’-untranslated region(3’-UTR)of NR1I2 mRNA and microRNAs in PXR-and glucocorticoid receptor(GR)-mediated regulation of NR1I2 gene *** ligands were found to significantly downregulate NR1I2 mRNA expression in a set of 14 human hepatocyte ***,PXR was downregulated by PCN in the C57/BL6 mice *** mechanistic studies with the full-length 3’-UTR cloned into luciferase reporter or expression vectors,we showed that the 3’-UTR reduces PXR *** the miRNAs tested,miR-18a-5p inhibited both NR 112 expression and CYP3A4 gene ***,we observed significant upregulation of miR-18a-5p expression 6 h after treatment with the PXR ligand rifampicin,which indicates a putative mechanism underlying NR1I2 negative feed-back regulation in hepatic ***,glucocorticoids upregulated NR1I2 expression not only through the promoter region but also via 3’-UTR regulation,which likely involves downregulation of *** conclude that miR-18a-5p is involved in the down-regulation of NR1I2expression by its ligands and in the upregulation of NR1I2 mRNA expression by glucocorticoids in hepatic cells.

关键词： Gene expression MicroRNA Glucocorticoid Regulation Pregnane X receptor Cytochrome P4503A4

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Perceptual complexity of soil-landscape maps: a user evaluation of color organization in legend designs using eye tracking

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International Journal of Digital Earth 2017年第6期10卷 560-581页

作者： Arzu Coltekin alzbeta brychto.a Amy L.Griffin Anthony C.Robinson Mark Imhof Chris Pettit Department of Geography University of ZurichZürichSwitzerland School of Physical Environmentaland Mathematical SciencesUNSWCanberraAustralia GeoVISTA Center Department of GeographyThe Pennsylvania State UniversityState CollegePAUSA Department of Economic Development JobsTransport and ResourceState Government of VictoriaAgriculture Victoria City Futures Research Centre University of New South WalesSydneyAustralia

We compared the ability of two legend designs on a soil-landscape map to efficiently and effectively support map reading tasks with the goal of better understanding how the design choices affect user *** such knowledge is essential to design effective interfaces for digital earth *** of the two legends contained an alphabetical ordering of categories,while the other used a perceptual grouping based on the Munsell color *** tested the two legends for 4 tasks with 20 experts(in geography-related domains).We analyzed traditional usability metrics and participants’eye movements to identify the possible reasons behind their success and failure in the experimental ***,an overwhelming majority of the participants failed to arrive at the correct responses for two of the four tasks,irrespective of the legend ***,participants’prior knowledge of soils and map interpretation abilities led to interesting performance differences between the two legend *** discuss how participant background might have played a role in performance and why some tasks were particularly hard to solve despite participants’relatively high levels of experience in map *** on our observations,we caution soil cartographers to be aware of the perceptual complexity of soil-landscape maps.

关键词： Soil-landscape maps legend design visual complexity color empirical study eye tracking

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Endoscopic radiofrequency ablation for malignant biliary obstruction

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1383-1396页

作者： Jana Jarosova Peter Macinga alzbeta Hujova Jan Kral Ondrej Urban Julius Spicak Tomas Hucl Department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePraha 14021Czech Republic Department of Internal Medicine II–Gastroenterology and Geriatrics University Hospital OlomoucFaculty of Medicine and DentristryPalacky University OlomoucOlomouc 77900Czech Republic

Cholangiocarcinoma and pancreatic cancer are the most common causes of malignant biliary *** majority of patients are diagnosed at a late stage when surgical resection is rarely *** these cases,palliative chemotherapy and radiotherapy provide only limited benefit and are associated with poor *** ablation(RFA)is a procedure for locoregional control of tumours,whereby a high-frequency alternating current turned into thermal energy causes coagulative necrosis of the tissue surrounding the *** subsequent release of debris and tumour antigens by necrotic cells can stimulate local and systemic *** development of endoluminal RFA catheters has led to the emergence of endoscopically delivered RFA,a treatment mainly used for malignant biliary strictures to prolong survival and/or stent *** indications include recanalisation of occluded biliary stents and treatment of intraductal ampullary adenoma or benign biliary *** article presents a comprehensive review of endobiliary RFA,mainly focusing on its use in patients with malignant biliary *** available data suggest that biliary RFA may be a promising modality,having positive impacts on survival and stent patency and boasting a reasonable safety ***,further studies with better characterised and stratified patient populations are needed before the method becomes accepted within routine clinical practice.

关键词： Radiofrequency Ablation Biliary Stenosis Cholangiocarcinoma Pancreatic cancer

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The Social Enrichment and Training of Large Cats and Cheetahs

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Journal of Life Sciences 2014年第3期8卷 266-268页

作者： Ivana Gardianova alzbeta Kocourkova Faculty of Agrobiology Food andNatural Resources Czech University of Life Sciences Prague Suchdol 16521 Czech Republic

Environmental enrichment increases the expression of behavior and welfare. The aim of the study was to analyze situation of the social enrichment （training） of big cats and cheetahs in Czech and Slovak zoos based on the evaluation questionnaire. It was found out that social enrichment, as part of the environmental enrichment, was used in 50% of animal, 16 animal get training only. A lot of animal had positive reactions on enrichment.

关键词： Big cats environmental enrichment social enrichment questionary.

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Principles of Indirect Tax Harmonization in the EU

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Economics World 2017年第6期5卷 608-617页

作者： Jaroslav Korecko alzbeta Suhanyiova Ladislav Suhanyi University of Presov Presov Slovakia

Since the beginning of 60s of the 20th century the European Community has been voicing its concerns about the need for tax harmonization. First attitudes towards tax harmonization were very ambitious. The aim was not only to reach structural harmonization in the Member States, but also harmonization of tax base and tax rates. The article explores the nature and conditions of the harmonization process while addressing its legislative modifications. The article analyses and compares the most important indirect taxes （value added tax, excise duties） in the Member States of the EU. Despite decades of efforts to harmonize taxes countries continuously apply national taxes. Heads of the Union argue that this approach can lead to disintegration in the future.

关键词： harmonization competition VAT (value added tax) excise duty

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Investigation of NAD(P)H Fluorescence Decay in Living Cardiomyocytes with Spectrally-resolved Fluorescence Lifetime Spectroscopy

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Chinese Journal of Biomedical Engineering(English Edition) 2009年第3期18卷 107-128页

作者： CHENG Ying ANEBA Swida CHORVAT Jr. Dusan BASSIEN-Capsa Valerie ZANG Wei-jin CHORVATOVA alzbeta Department of Cardiovascular Surgery Beijing University Shenzhen Hospital Shenzhen 518036 China Research Centre CHU Sainte-Justine Montreal 113 T 1 C5 Canada Department of Biophotonics International Laser Centre Bratislava 81219 Slovakia School of Medicine Xi ＇ an Jiaotong University Xi ＇ an 710061 China Department of Pediatrics University of Montreal Montreal H3 T 1 C5 Canada

Objective：To study the mitochondrial redox state in experimental animals to sensitively detect early signs of mitochondrial function in pathophysiologieal conditions, such as isehemia. Methods： Fluorescence of nieotinamide adenine dinucleotide （phosphate） , or NAD（P）H, the principal electron donor in mitochondrial respiration responsible for vital ATP supply of cardiomyocytes, is studied for non-invasive fluorescent probing of the mitochondrial function. Examination of NAD （P）H fluorescence in living cardiomyocytes following excitation by UV-pulsed laser diode and detection by spectrally-resolved time-correlated single photon counting （TCSPC） , is based on the simultaneous measurement of the fluorescence spectra and lifetime. Results ： The dynamic characteristics of NAD （P） H fluorescence decay in living rat cardiomyocytes show that at least a 3-exponential decay model, with 0.4 - 0.7 ns, 1.2 - 1.9 ns and 8.0 - 13.0 ns lifetimes, is necessary to describe cardiomyocyte autofluorescenee （AF）. Decay-associated spectra （DSA） revealed the presence of 4 spectrally-distinct populations of NADH molecules in eardiomyocytes with spectral maximum at 470 nm for short-lifetime pool for the first time, and emission peaks at 450 nm, 470 nm and 490 nm for intermediate and long-lifetime pools. Increased mitochondrial NADH content ratio by ketone bodies enhanced the AF intensity, without the significant change in fluorescent lifetimes. Rotenone, the inhibitor of Complex I of the mitochondrial respiratory chain, increased AF and shortened the average fluorescence lifetime. Dinitrophenol （DNP）, an uncoupling agent of the mitochondrial oxidative phosphorylation, lowered AF,broadened the spectral shoulder at 520 nm and increased the average lifetime. These effects, comparable to the changes in the concentration and in the rate of dehydrogenation of NADH in vitro, were also examined under ischemia-mimetic conditions. Conclusion： Our findings anticipate a contribution of both conformationa

关键词： NAD (P) H autofluorescence (AF) fluorescence lifetime mitochondria living cardiomyocyte

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活体心肌细胞NAD(P)H荧光的光谱分辨的荧光寿命光谱研究

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透析与人工器官 2012年第4期23卷 20-37页

作者：程颖 ANEBA Swida Swida CHORVAT Jr.Dusan Jr.Dusan BASSIEN-Capasa Valerie Valerie 臧伟进 CHORVATOVA alzbeta alzbeta 北京大学深圳医院深圳518036 蒙特利尔大学医学中心圣-贾斯廷医院研究中心加拿大H3T1C5 斯洛伐克国际激光中心斯洛伐克西安交通大学医学院西安710061 蒙特利尔大学儿科学部加拿大H3T1C5

目的研究实验动物心肌线粒体氧化还原状态,监测缺血时线粒体功能改变的早期信号.方法线粒体呼吸链主要电子供应者烟酰胺腺嘌呤(磷酸)二核苷酸,或NAD(P)H荧光为无创荧光标记,用光谱分辨的时间相关单光子计数(TCSPC)检测紫外光(UV)激发... 详细信息

目的研究实验动物心肌线粒体氧化还原状态,监测缺血时线粒体功能改变的早期信号.方法线粒体呼吸链主要电子供应者烟酰胺腺嘌呤(磷酸)二核苷酸,或NAD(P)H荧光为无创荧光标记,用光谱分辨的时间相关单光子计数(TCSPC)检测紫外光(UV)激发的心肌自发荧光(AF)光谱和荧光寿命.结果需用至少3个荧光寿命池0.4～0.7 ns,1.2～1.9 ns和8.0～13.0 ns描述心肌AF.相关衰减光谱(DAS)显示4个NAD(P)H荧光固有光谱,分别为峰值470 nm的短荧光寿命池,及450 nm,470 nm和490 nm的中间和长荧光寿命池.酮体增加线粒体NADH产量,提高AF强度,但不改变荧光寿命.线粒体呼吸阻断剂Rotenone,显著增加AF强度和缩短平均荧光寿命.氧化磷酸化解偶联剂Dinitrophenol (DNP),显著降低AF强度,在520 nm处增宽荧光光谱并显著延长平均荧光寿命.这些结果和NADH荧光动力学离体实验(in vitro)及模拟缺血状态实验有可比性.结论研究可解释NADH构象改变,以及从NADH到异戎酸脱氢酶(LipDH)结合的黄素蛋白间能量转移的荧光动力学变化.光谱分辨的荧光寿命显微技术提供了在细胞水平上研究心肌能量代谢或线粒体功能障碍的新工具.

关键词： NAD(P)H 自发荧光光谱分辨的荧光寿命线粒体存活心肌细胞

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