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Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

World Journal of Gastroenterology 2010年第8期16卷 966-972页

作者： Sebastian Mueller Gunda Millonig lucie Sarovska Stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel Thomas Longerich Peter Schirmacher Helmut Karl Seitz Department of Medicine and Center for Alcohol Research Salem Medical Center University of Heidelberg Institute of Medical Biometry and Informatics University of Heidelberg Institute of Clinical Pharmacology University of Bern Department of Pa-thology University of Heidelberg

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of ***:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

关键词： Alcoholic liver disease Alcoholic steatohep-atitis Liver cirrhosis Bilirubin Tissue elasticity imaging FibroScan

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Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated and cholestatic rats

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World Journal of Gastroenterology 2017年第43期23卷 7678-7692页

作者： Eva Dolezelova Alena Prasnicka Jolana Cermanova Alejandro Carazo lucie Hyrsova Milos Hroch Jaroslav Mokry Michaela Adamcova Alena Mrkvicova Petr Pavek Stanislav Micuda Department of Biological and Medical Sciences Charles UniversityFaculty of Pharmacy in Hradec Kralove Department of Pharmacology Charles UniversityFaculty of Medicine in Hradec Kralove Department of Pharmacology and Toxicology Charles UniversityFaculty of Pharmacy in Hradec Kralove Department of Medical Biochemistry Charles UniversityFaculty of Medicine in Hradec Kralove Department of Histology and Embryology Charles UniversityFaculty of Medicine in Hradec Kralove Department of Physiology Charles UniversityFaculty of Medicine in Hradec Kralove

AIM To investigate the effect of resveratrol on biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats. METHODS Resveratrol(RSV) or saline were administered to rats by daily oral gavage for 28 d after sham operation or reversible bile duct obstruction(BDO). Bile was collected 24 h after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate azithromycin. Bile acids,glutathione and azithromycin were measured in bile to quantify their level of biliary secretion. Liver expression of enzymes and transporters relevant for bile production and biliary secretion of major bile constituents and drugs were analyzed at the m RNA and protein levels using q RT-PCR and Western blot analysis,respectively. The TR-FRET PXR Competitive Binding Assay kit was used to determine the agonism of RSV at the pregnane X receptor. RESULTS RSV increased bile flow in sham-operated rats due to increased biliary secretion of bile acids(BA) and glutathione. This effect was accompanied by the induction of the hepatic rate-limiting transporters for bile acids and glutathione,Bsep and Mrp2,respectively. RSV also induced Cyp7 a1,an enzyme that is crucial for bile acid synthesis; Mrp4,a transporter important for BA secretion from hepatocytes to blood; and Mdr1,the major apical transporter for xenobiotics. The findings were supported by increased biliary secretion of azithromycin. The TR-FRET PXR competitive binding assay confirmed RSV as a weak agonist of the human nuclear receptor PXR,which is a transcriptional regulator of Mdr1/Mrp2. RSV demonstrated significant hepatoprotective properties against BDO-induced cirrhosis. RSV also reduced bile flow in BDO rats without any corresponding change in the levels of the transporters and enzymes involved in RSV-mediated hepatoprotection. CONCLUSION Resveratrol administration for 28 d has a distinct effect on bile flow and biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats.

关键词： Resveratrol Bile production Bile acids Pregnane X receptor Azithromycin

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Characterisation and seasonal variations of particles in the atmosphere of rural, urban and industrial areas：Organic compounds

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Journal of Environmental Sciences 2016年第6期28卷 45-56页

作者： Fabrice Cazier Paul Genevray Dorothée Dewaele Habiba Nouali Anthony Verdin Frédéric Ledoux Adam Hachimi lucie Courcot Sylvain Billet Saad Bouhsina Pirouz Shirali Guillaume Garcon Dominique Courcot Common Center of Measurements (CCM) Univ. Littoral Cote d'Opale F-59140 Dunkirk France Unit of Environmental Chemistry and Interactions with Life UCEIV-EA4492 Univ. Littoral Cote d'Opale F-59140 Dunkirk France MicroPolluants Technologie SA 4 Rue de Bort Les Orgues F-57070 Saint Julien Les Metz France Oceanology and Geosciences Laboratory LOG UMR 8187 Univ. Littoral C6te d'Opale F-62230 Wimereux France Impact of Chemical Environment on Human Health Univ. Lille CHU Lille Institut Pasteur de Lille EA4483-IMPECS 59000 LILLE France

Atmospheric aerosol samples（PM2.5–0.3, i.e., atmospheric particles ranging from 0.3 to2.5 μm） were collected during two periods： spring–summer 2008 and autumn–winter 2008–2009, using high volume samplers equipped with cascade impactors. Two sites located in the Northern France were compared in this study： a highly industrialised city（Dunkirk） and a rural site（Rubrouck）. Physicochemical analysis of particulate matter（PM） was undertaken to propose parameters that could be used to distinguish the various sources and to exhibit seasonal variations but also to provide knowledge of chemical element composition for the interpretation of future toxicological studies. The study showed that PM2.5–0.3concentration in the atmosphere of the rural area remains stable along the year and was significantly lower than in the urban or industrial ones, for which concentrations increase during *** concentrations of polycyclic aromatic hydrocarbons（PAHs）, dioxins, furans and dioxin like polychlorinated biphenyls（DL-PCBs）, generated by industrial activities, traffic and municipal wastes incineration were detected in the samples. Specific criteria like Carbon Preference Index（CPI） and Combustion PAHs/Total PAHs ratio（CPAHs/TPAHs） were used to identify the possible sources of atmospheric pollution. They revealed that paraffins are mainly emitted by biogenic sources in spring–summer whereas as in the case of PAHs, they have numerous anthropogenic emission sources in autumn-winter（mainly from traffic and domestic heating）.

关键词： Environmental monitoring Airborne particles PAHs Paraffins Dioxins

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Environmental Impact of Lefa Gold Mining on Its Local Population, Republic of Guinea

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Natural Resources 2019年第8期10卷 305-323页

作者： Benjamin Kolie Jun Yao Geoffrey Sunahara lucie Duonamou Department of Mine Institute of Mine and Geology of Boke Conakry Guinea School of Water Resources and Environment Department of Environment Engineering China University of Geosciences (Beijing) Beijing China School of Nature Conservation Beijing Forestry University Beijing China

Republic of Guinea’s environmental situation is characterized by the continued degradation of natural resources. Lefa gold mine is one of the Guinean Republic’s gold companies which support the socioeconomic improvement. It operates in the northeastern part of the country and extracts the ore gold by open pit method by using cyanide. The exploitation of the Lefa Gold Mine impacts?the natural resources and the surrounding population. This paper considers the impact of Lefa Gold Mine activities on the environment and its local population including ecological disturbance, destruction of fauna and flora, land and landscape degradation. The study was carried out in April to July 2013 in two villages, Fayalala Carrefour, and Lèro Karta. Questionnaires were illustrated for data collection, and the proposed sampling size number (1204 respondents) consisted of the two villages and the surrounding villages was?founded on the proximity to the mine sites and their degree of suffering?after a direct impact of mining activities. 961 (79.82% of respondents) adhered?to the research to provide information about the situation. The principal objective of this paper was to provide new information on the problems existing in the achievement of mining policies that will help to mitigate the environmental impacts of gold mining activities on the local population. From the respondents, the results showed that the Lefa gold mine’s activities contaminated the farmland (31.21%), allowed the extinction of many animals and plant species (28.19%), which caused the change of the landscape of the study area. However, the most important situation was the life of the surrounding population. Therefore, the study has proposed a serial of recommendation to help Lefa gold mine reduce the impact of their activities on the environment and local population.

关键词： Gold Mining Environmental Impact Socioeconomic Impact Cyanide

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In vitro comparison of human plasma-based and self-assembled tissue-engineered skin substitutes:two different manufacturing processes for the treatment of deep and difficult to heal injuries

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Burns & Trauma 2023年第1期11卷 800-813页

作者： Álvaro Sierra-Sánchez Brice Magne Etienne Savard Christian Martel Karel Ferland Martin A.Barbier Anabelle Demers Danielle Larouche Salvador Arias-Santiago lucie Germain LOEX Tissue Engineering Laboratory and Department of Surgery Faculty of MedicineUniversitéLaval140118e rueQuébec(Québec)G1J 1Z4Canada CHU de Québec-UniversitéLaval Research Center Division of Regenerative Medicine140118e rueQuébec(Québec)G1J 1Z4Canada Unidad de Producción Celular e Ingeniería Tisular(UPCIT) Virgen de las Nieves University Hospitalibs.GRANADAAndalusian Network for the design and translation of Advanced TherapiesAv.de las Fuerzas ArmadasNº24ªPlanta Ed.de Gobierno18014GranadaSpain Department of Dermatology Virgen de las Nieves University HospitalAv.MadridNº11-1518012GranadaSpain Department of Dermatology Faculty of MedicineUniversity of GranadaAv.de la InvestigaciónNº1118016GranadaSpain

Background:The aim of this in vitro study was to compare side-by-side two models of human bilayered tissue-engineered skin substitutes(hbTESSs)designed for the treatment of severely burned *** are the scaffold-free self-assembled skin substitute(SASS)and the human plasma-based skin substitute(HPSS).Methods:Fibroblasts and keratinocytes from three humans were extracted from skin biopsies(N=3)and cells from the same donor were used to produce both hbTESS *** SASS manu-facture,keratinocytes were seeded over three self-assembled dermal sheets comprising fibroblasts and the extracellular matrix they produced(n=12),while for HPSS production,keratinocytes were cultured over hydrogels composed of fibroblasts embedded in either plasma as unique biomaterial(Fibrin),plasma combined with hyaluronic acid(Fibrin-HA)or plasma combined with collagen(Fibrin-Col)(n/biomaterial=9).The production time was 46-55 days for SASSs and 32-39 days for *** were characterized by histology,mechanical testing,PrestoBlue™-assay,immunofluorescence(Ki67,Keratin(K)10,K15,K19,Loricrin,type IV collagen)and Western blot(type I and IV collagens).Results:The SASSs were more resistant to tensile forces(p-value<0.01)but less elastic(p-value<0.001)compared to HPSSs.A higher number of proliferative Ki67+cells were found in SASSs although their metabolic activity was *** epidermal differentiation,no significant difference was observed in the expression of K10,K15,K19 and ***,the production of type I and type IV collagens and the adhesive strength of the dermal-epidermal junction was higher in ***:This study demonstrates,for the first time,that both hbTESS models present similar in vitro biological ***,mechanical properties differ and future in vivo experiments will aim to compare their wound healing potential.

关键词： Biomaterial Burn Fibrin Human plasma Self-assembly Skin substitute Tissue engineering

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Binding of naturally occurring hydroxycinnamic acids to bovine serum albumin

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Natural Science 2010年第6期2卷 563-570页

作者： lucie Trnkova Iva Bousova Vladimir Kubicek Jaroslav Drsata Charles University in Prague Faculty of Pharmacy Hradec Králové Czech Republic Charles University in Prague Faculty of Pharmacy Hradec Králové Czech Republic University of Hradec Králové Faculty of Education Hradec Králové Czech Republic

Hydroxycinnamic acids (HCAs) possess numer- ous biological effects including antioxidant, antiallergic, antimicrobial, and immunomodulatory activities and due to these properties are widely used in folk medicine. Nevertheless, they can interact with protein molecules and cause some structural and functional changes. The possib- ility of HCAs binding to bovine serum albumin (BSA) under physiological conditions was inve- stigated by the UV-VIS absorption spectroscopy and fluorescence quenching method. Apart from rosmarinic acid, all tested HCAs quenched tryptophan fluorescence of BSA in the studied range of concentrations (0-20 μM) mainly by static quenching mechanism (formation of non- fluorescent HCA-BSA complexes). The binding constants, number of binding sites and free energy changes were determined. The binding affinities of HCAs were ranked in the order: chlorogenic acid > sinapic acid ≥ caffeic acid > ferulic acid > o-coumaric acid > p-coumaric acid ≥ m-coumaric acid, which was confirmed by spectral overlaps of BSA emission spectrum with absorption spectrum of HCA. All free energy changes possessed negative sign indicating the spontaneity of HCA-BSA interaction.

关键词： Bovine Serum Albumin Hydroxycinnamic Acid Fluorescence Quenching Protein-Ligand Binding

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乙烷氧化脱氢用Ni/Al_2O_3催化剂中活性镍物种前驱体(英文)

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催化学报 2013年第10期34卷 1905-1913页

作者： lucie Smoláková árka Botková Libor apek Peter Priecel Agnieszka Soltysek Martin Kout Lenka Matějová Department of Physical Chemistry Faculty of Chemical TechnologyUniversity of Pardubice Nanotechnology Centre V B-Technical University of Ostrava

Ni/Al2O3 catalysts for oxidative dehydrogenation(ODH) of ethane were prepared by impregnation of Al2O3 with nickel acetate or nickel nitrate,and by mechanical mixing of NiO and *** Ni-based catalysts were characterized by N2 adsorption-desorption,X-ray diffraction,diffuse reflectance UV-visible diffuse reflectance spectroscopy,and temperature-programmed reduction of *** results showed that formation of crystalline NiO particles with a size of < 8 nm and/or non-stoichiometric NiO species in the Ni/Al2O3 catalysts led to more active species in ODH of ethane under the investigated reaction *** contrast,tetrahedral Ni species present in the catalysts led to higher selectivity for *** of large crystalline NiO particles(22-32 nm) over Ni/Al2O3 catalysts decreased the selectivity for ethene.

关键词： Alumina Ethane Oxidative dehydrogenation Nickel species

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钾促进的Co-Mn-Al混合氧化物催化剂上模拟废气中N_2O的分解减排(英文)

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催化学报 2011年第5期32卷 816-820页

作者： lucie OBALOV Květue JIRTOV Kateina KARSKOV Frantiek KOVANDA Faculty of Metallurgy and Materials Engineering VB-Technical University of Ostrava Institute of Chemical Process Fundamentals of the ASCR v.v.i. Institute of Chemical Technology

Intrinsic data of N2O catalytic decomposition over a K-promoted Co-Mn-Al mixed oxide prepared by the thermal treatment of a layered double hydroxide was used for the design of a pilot reactor for the abatement of N2O emissions from the off-gases in HNO3 production.A pseudo-homogeneous one-dimensional model of an ideal plug flow reactor under an isothermal regime(450°C)was used for reactor design.A catalyst particle diameter of 3 mm is a compromise size because increasing the size of the catalyst particle leads to a decrease in the reaction rate because of an internal diffusion limitation,and particles with a smaller diameter cause a large pressure drop.A catalyst bed of 11.5 m 3 was estimated for the target N2O conversion of 90%upon the treatment of 30000 m 3 /h of exhaust gas(0.1 mol%N2O,0.005 mol% NO,0.9 mol%H2O,5 mol%O2)at 450°C and 130 kPa.

关键词： nitrous oxide catalytic decomposition nitric acid production emission abatement

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TREM-1 multimerization is essential for its activation on monocytes and neutrophils

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Cellular & Molecular Immunology 2019年第5期16卷 460-472页

作者： Kevin Carrasco Amir Boufenzer lucie Jolly Helene Le Cordier Guanbo Wang Albert JR Heck Adelheid Cerwenka Emilie Vinolo Alexis Nazabal Alexandre Kriznik Pierre Launay Sebastien Gibot Marc Derive INOTREM Vandœuvre-les-NancyFrance UMR-S 1116 Defaillance cardiovasculaire aigue et chroniqueVandœuvre-les-NancyFrance UMR7365 Ingénierie Moléculaire et Physiopathologie Articulaire(IMoPA)CNRS-Universitéde LorraineVandœuvre-les-NancyFrance Biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences and Netherlands Proteomics CenterUtrecht UniversityUtrechtThe Netherlands Innate Immunity German Cancer Research Center(DKFZ)HeidelbergGermany CovalX ZurichSwitzerland Service Commun de Biophysique Interactions Moléculaires(SCBIM) FR3209Biopole de l’Universitede LorraineVandœuvre-les-NancyFrance Inatherys Evry CedexFrance

The triggering receptor expressed on myeloid cells-1(TREM-1)is a receptor expressed on innate immune *** promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptors(TLRs),TREM-1 has been characterized as a major player in the pathophysiology of acute and chronic inflammatory diseases,such as septic shock,myocardial infarction,atherosclerosis,and inflammatory bowel ***,the molecular events leading to the activation of TREM-1 in innate immune cells remain ***,we show that TREM-1 is activated by multimerization and that the levels of intracellular Ca 2+release,reactive oxygen species,and cytokine production correlate with the degree of TREM-1 ***-1 activation on primary human monocytes by LPS required a two-step process consisting of upregulation followed by clustering of TREM-1 at the cell surface,in contrast to primary human neutrophils,where LPS induced a rapid cell membrane reorganization of TREM-1,which confirmed that TREM-1 is regulated differently in primary human neutrophils and *** addition,we show that the ectodomain of TREM-1 is able to homooligomerize in a concentration-dependent manner,which suggests that the clustering of TREM-1 on the membrane promotes its *** further show that the adapter protein DAP12 stabilizes TREM-1 surface expression and ***-1 multimerization at the cell surface is also mediated by its endogenous ligand,a conclusion supported by the ability of the TREM-1 inhibitor LR12 to limit TREM-1 *** results provide evidence for ligand-induced,receptor-mediated dimerization of ***,our findings uncover the mechanisms necessary for TREM-1 activation in monocytes and neutrophils.

关键词： TREM-1 multimerization activation monocytes neutrophils

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Tryptophan:A gut microbiota-derived metabolites regulating inflammation

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2017年第1期8卷 7-9页

作者： lucie Etienne-Mesmin Benoit Chassaing Andrew T Gewirtz Center for Inflammation Immunityand InfectionInstitute for Biomedical SciencesGeorgia State UniversityAtlantaGA 30303United States

Inflammatory bowel diseases(IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions over the world. The etiology of IBD is still not well defined, but evidence suggest that it results from per-turbation of the homeostasis between the intestinal microbiota and the mucosal immune system, with the involvement of both genetic and environmental factors. Genome wide association studies, which involve large-scale genome-wide screening of potential polymorphism, have identified several mutations associated with IBD. Among them, Card9, a gene encoding an adapter molecule involved in innate immune response to fungi(via type C-lectin sensing) through the activation of IL-22 signaling pathway, has been identified as one IBD susceptible genes. Dietary compounds, which represent a source of energy and metabolites for gut bacteria, are also appreciated to be important actors in the etiology of IBD, for example by altering gut microbiota composition and by regulating the generation of short chain fatty acids. A noteworthy study published in the June 2016 issue of Nature Medicine by Lamas and colleagues investigates the interaction between Card9 and the gut microbiota in the generation of the microbiota-derived tryptophan metabolite. This study highlights the role of tryptophan in dampening intestinal inflammation in susceptible hosts.

关键词： Intestinal inflammation Tryptophan Microbiota

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