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Antiviral therapy in cytomegalovirus-positive ulcerative colitis:A systematic review and meta-analysis

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World Journal of Gastroenterology 2014年第10期20卷 2695-2703页

作者： uri kopylov Noa Eliakim-Raz Andrew Szilagy Ernest Seidman Shomron Ben-Horin Lior Katz Department of Gastroenterology Sheba Medical Center Tel Hashomer Ramat Gan 5262 Israel Division of Gastroenterology McGill University Health Center Montreal Quebec H3G 1A4Canada Sackler School of Medicine Tel-Aviv University Ramat-Aviv Tel-Aviv 69978Israel Department of Medicine E Beilinson Hospital Rabin Medical Center Petach Tikva 49100 Israel Division of Gastroenterology Jewish General Hospital McGill University Montreal Quebec H3T 1E2Canada

AIM: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients.

关键词： Ulcerative colitis Cytomegalovirus Colectomy Antiviral treatment Gancyclovir Foscarnet

Significance of low level infliximab in the absence of anti-infliximab antibodies

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World Journal of Gastroenterology 2015年第6期21卷 1907-1914页

作者： Bella Ungar Adi Anafy Henit Yanai Yulia Ron Miri Yavzori Orit Picard Ella Fudim Ronen Loebstein uri kopylov Yehuda Chowers Iris Dotan Rami Eliakim Shomron Ben-Horin Department of Gastroenterology Sheba Medical Center Tel Hashomer and Sack-ler School of Medicine Tel-Aviv University IBD Center Department of Gastroenterology Tel-Aviv Sourasky Medical Center and Sackler School of Medicine Tel-Aviv University Institute of Clinical Pharmacology Sheba Medical Center Tel Hashomer and Sackler School of Medicine Tel-Aviv University Rambam Health Care Campus and Bruce Rappaport School of Medicine Technion Institute of Technology

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN ***:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was *** with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ***:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P<0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+*** with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P<0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level ***:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.

关键词： Inflammatory bowel disease Biological therapy Infl

Cytomegalovirus positive ulcerative colitis:A single center experience and literature review

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World Journal of Gastrointestinal Pathophysiology 2013年第1期4卷 18-23页

作者： uri kopylov Gila Sasson Bella Geyshis Michal Tepperberg Oikawa Iris Barshack Rami Eliakim Shomron Ben-Horin Department of Gastroenterology Sheba Medical CenterRamat Gan 52621Israel Internal Medicine D Sheba Medical CenterRamat Gan 52621Israel Central Virology Laboratory Public Health LaboratoriesIsrael Ministry of HealthRamat Gan 52621Israel Department of Pathology Sheba Medical CenterRamat Gan 52621Israel

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral ***:This was a retrospective case-controlled *** database of UC patients in our institution was scanned for documented presence of CMV on colonic ***,clinical data,endoscopy findings and pathology reports were extracted from the patients' charts and electronic *** available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also *** primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the ***:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were *** treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue *** patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment *** the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient ***:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral ***-CMV-positive patients with mild disease may recover without antiviral therapy.

关键词： Ulcerative colitis Cytomegalovirus Gancyclovir Cyclosporine Immunohistochemistry

Polyhydroxybutyrate/Hydroxyapatite Highly Porous Scaffold for Small Bone Defects Replacement in the Nonload-bearing Parts

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Journal of Bionic Engineering 2017年第4期14卷 648-658页

作者： Fedor Senatov Natalia Anisimova Mikhail Kiselevskiy Aleksey kopylov Viktor Tcherdyntsev Aleksey Maksimkin National University of Science and Technology MISIS Leninskiy pr. 4 Moscow 119049 Russian Federation N.N. Blokhin Russian Cancer Research Center Kashirskoye sh. 23 Moscow 115478 Russian Federation

In the present work, Polyhydroxybutyrate （PHB）/Hydroxyapatite （HA） porous composites （10%, 20%, 30 %, 40%, 50% weight HA） were obtained by sintering. PHB/20% HA optimally combines satisfactory mechanical properties with a high content of the bioactive component （HA）. Porous PHB/20% HA scaffolds have shown high mechanical properties （compressive strength of 106 MPa and Young＇s modulus of 901 MPa）. A high volume fraction of interconnected pores （〉 50 vol.%） was achieved with pore size of 50 grn - 500 gm. Biocompatibility of porous pure PHB and PHB/20%HA, as its osseointegration were assessed in vitro and after implantation in laboratory animals. PHB/20% HA （-5% ＋ 0.9%） and pure PHB ~3% ~ 1.4%） samples after 24 hours of incubation with human leucocytes showed no significant level of cytotoxicity when p = 0.648 （p-value）. In vitro massive adhesion of mouse Multipotent Mesenchymal Stromal Cells （MMSC） to the surface of both porous samples was shown. PHB/20% HA induced more intensive MMSC proliferation compared to pure PHB, which are 31% ＋ 6.1% and 20% ＋ 5.7 % respectively when p = 0.039. We observed the resorption （implant surface area was reduced by 49 %） and integration of the porous PHB/20% HA samples into surrounding tissues after 30 days of implantation. The signs of osteoclasts accumulation, neo-angigenesis and new bone formation were observed, which make PHB/20% HA promising for bone tissue engineering.

关键词： polyhydroxybutyrate hydroxyapatite scaffold porous structure implant bone regeneration

Highly transparent ytterbium doped yttrium lanthanum oxide ceramics

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Journal of Rare Earths 2014年第3期32卷 254-258页

作者： M.Ivanov Yu.kopylov V.Kravchenko 李江 A.Medvedev 潘裕柏 Institute of Electrophysics UrB of RAS 106Amundsena 620016 Ekaterinburg Russia Institute of Radioengineering and Electronics named after V.A. Kotelnikov RAS Vvedensky Sq. 1 Fryazino Moscow region 141120 Russia Shanghai Institute of Ceramics Chinese Academy of Science Ural Federal University 19 Mira 620002 Ekaterinburg Russia

To prepare ytterbium doped lanthania yttria nanopowder a method of laser evaporation of mixed oxides was used. After calcinations of the powder at 1200 ℃ a pure single-phase solid solution yb3＋：（LaxY1-x）2O3 was formed in the nanoparticles. Influence of lanthanum oxide as an isovalent additive on the yttria structure was investigated. The lanthanium ions were proved to be a good aid to sinter yttria ceramics doped with Yb3＋ at moderate temperatures about 1650 ℃. The ceramics with relative density higher than 99.99% and grain size about 40 μm were fabricated. Full transmittance of 1.8 mm thick Yb0.11 La0.23Y1.66O3 ceramics reached 82.5% at 800 nm. This material could be a good gain medium for ytterbium high power pulse lasers.

关键词： RE-doped ceramics nanopowders ytterbium oxide transparency

Critical Assessment of the Current WADA Approach for the Detection of 4-Chlorodehydromethyltestosteron

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Journal of Analytical Sciences, Methods and Instrumentation 2016年第4期6卷 65-82页

作者： Arthur T. kopylov Institute of Biomedical Chemistry Moscow Russia

This paper is focused on application of method for detection of novel metabolites of 4-chlorodehydromethyltestosterone (known as oral turinabol, OT), which were postulated as long-term metabolites. The method started to be applied without rigorous validation, verification and excretion assay assisted as evidences for existence of the declared detectable compounds as true metabolites derived after OT biotransformation. This method has been started to use almost in its original form which arose in 2012 year for the very first time and never been revised and re-confirmed in peer-reviewed journals. Usually WADA encourages accredited laboratories to publish their results of methods development, validation and specific excretion studies in peer-reviewed journals. However, an incorrect method with neglected validation design and implicit data contradictions is currently widely applied. The author of this presented paper was athletes’ representative on repeated occasion and has been provided with several full documentation packages of OT novel metabolites analysis. Thus, the author makes its own conclusion based on its own evidences of that currently employed method and data analysis is exactly the same declared in a wrong way as emerged from the original paper.

关键词： Anti-Doping Mass Spectrometry Substance Identification Data Analysis 4-Chlorodehydromethyltestosterone Turinabol

G-Quadruplex(G4) Motifs in the Maize(Zea mays L.) Genome Are Enriched at Specific Locations in Thousands of Genes Coupled to Energy Status,Hypoxia,Low Sugar,and Nutrient Deprivation

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Journal of Genetics and Genomics 2014年第12期41卷 627-647页

作者： Carson M.Andorf Mykhailo kopylov Drena Dobbs Karen E.Koch M.Elizabeth Stroupe Carolyn J.Lawrence Hank W.Bass USDA-ARS Corn Insects and Crop Genetics Research Unit Iowa State University Department of Computer Science Iowa State University Institute of Molecular Biophysics Florida State University Department of Genetics Development and Cell BiologyIowa State University Plant Molecular and Cellular Biology Program Horticultural Sciences DepartmentGenetics InstituteUniversity of Florida Department of Biological Science Florida State University Department of Agronomy Iowa State University

The G-quadruplex （G4） elements comprise a class of nucleic acid structures formed by stacking of guanine base quartets in a quadruple helix. This （34 DNA can form within or across single-stranded DNA molecules and is mutually exclusive with duplex B-form DNA. The reversibility and structural diversity of G4s make them highly versatile genetic structures, as demonstrated by their roles in various functions including telomere metabolism, genome maintenance, immunoglobulin gene diversification, transcription, and translation. Sequence motifs capable of forming G4 DNA are typically located in telomere repeat DNA and other non-telomeric genomic loci. To investigate their potential roles in a large-genome model plant species, we computationaily identified 149,988 non-telomeric G4 motifs in maize （Zea mays L., B73 AGPv2）, 29% of which were in non-repetitive genomic regions. G4 motif hotspots exhibited non-random enrichment in genes at two locations on the antisense strand, one in the 5~ UTR and the other at the 5~ end of the first intron. Several genic G4 motifs were shown to adopt sequence-specific and potassium-dependent G4 DNA structures in vitro. The G4 motifs were prevalent in key regulatory genes associated with hypoxia （group VII ERFs）, oxidative stress （D J-1/GATasel）, and energy status （AMPK/ SnRK） pathways. They also showed statistical enrichment for genes in metabolic pathways that function in glycolysis, sugar degradation, inositol metabolism, and base excision repair. Collectively, the maize G4 motifs may represent conditional regulatory elements that can aid in energy status gene responses. Such a network of elements could provide a mechanistic basis for linking energy status signals to gene regulation in maize, a model genetic system and major world crop species for feed, food, and fuel.

关键词： Maize G-quadruplex G4 Hypoxia Sucrose synthase

Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3

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Acta Pharmaceutica Sinica B 2019年第4期9卷 724-733页

作者： Dan Xiao Yue Zhang Rui Wang Yujie Fu Tong Zhou Hongtao Diao Zhixia Wang Yuan Lin Zhange Li Lin Wen Xujuan Kang Philipp kopylov Dmitri Shchekochikhin Yong Zhang Baofeng Yang Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)Harbin Medical UniversityHarbin 150081China Department of Pharmacy The First Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Department of Preventive and Emergency Cardiology Sechenov First Moscow State Medical UniversityMoscow 119991Russian Federation Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbin 150086China Department of Pharmacology and Therapeutics Melbourne School of Biomedical SciencesFaculty of MedicineDentistry and Health SciencesThe University of MelbourneMelbourne 3010Australia

Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction(TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II(AngII). Emodin upregulated expression of metastasis associated protein 3(MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis;in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis via upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.

关键词： Emodin Cardiac fibrosis MTA3 Angiotensin Ⅱ Cardiac fibroblast Mouse

Pharmacodynamics of frigid zone plant Taxus cuspidata *** *** skin melanin deposition,oxidation,inflammation and allergy

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Frigid Zone Medicine 2023年第1期3卷 42-52页

作者： Yang Shi Ling Liu Heyang Sun Chen Chen Jing Feng Yongchao Chen Yuan Lin Philipp kopylov Qi Wang Yong Zhang Department of Pharmacology(the State-Province Key Laboratories of Biomedicine Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Department of Medicinal chemistry and natural medicinal chemistry College of PharmacyHarbin Medical UniversityHarbin 150081China Research Unit of Noninfectious Chronic Diseases in Frigid Zone Chinese Academy of Medical Sciences2019RU070Harbin 150081China Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbin 150086China Department of Preventive and Emergency Cardiology Sechenov First Moscow State Medical UniversityMoscow 119991Russia

Background:Taxus cuspidata *** *** a precious species of frigid zone plant belonging to the Taxaceae family,which possesses anticancer,anti-inflammatory,hypoglycemic,and antibacterial pharmacological *** taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities,whether Taxus cuspidata *** *** skin-protective actions against injuries remained *** study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition,oxidation,inflammation,and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin ***:Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis *** capacity was evaluated by measuring superoxide dismutase(SOD)concentration and glutathione(GSH)content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay *** quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4(GPX4).Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in *** a mouse model of skin allergy induced by 4-aminopyridine(4-AP),allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay(ELISA)*** proinflammatory factors tumor necrosis factor(TNF)-αand interleukin(IL)-1βwere measured by *** and eosin(HE)staining was conducted to assess the degree of skin ***:All three Taxus extracts including Taxus chinensis essential oil,Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals,of which Taxus chinensis essential oil produced the greatest *** contrast,the three Taxus extracts elev

关键词： Taxus cuspidata S.et Z. skin melanin deposition oxidation inflammation allergy