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| 1 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC 'responders'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 2 | An integrated approach for increasing breeding efficiency in apple and peach in Europe显示文摘Despite the availability of whole genome sequences of apple and peach,there has been a considerable gap between genomics and breeding.To bridge the gap,the European Union funded the FruitBreedomics project(March 2011 to August 2015)involving 28 research institutes and private companies.Three complementary approaches were pursued:(i)tool and software development,(ii)deciphering genetic control of main horticultural traits taking into account allelic diversity and(iii)developing plant materials,tools and methodologies for breeders.Decisive breakthroughs were made including the making available of ready-to-go DNA diagnostic tests for Marker Assisted Breeding,development of new,dense SNP arrays in apple and peach,new phenotypic methods for some complex traits,software for gene/QTL discovery on breeding germplasm via Pedigree Based Analysis(PBA).This resulted in the discovery of highly predictive molecular markers for traits of horticultural interest via PBA and via Genome Wide Association Studies(GWAS)on several European genebank collections.FruitBreedomics also developed pre-breeding plant materials in which multiple sources of resistance were pyramided and software that can support breeders in their selection activities.Through FruitBreedomics,significant progresses were made in the field of apple and peach breeding,genetics,genomics and bioinformatics of which advantage will be made by breeders,germplasm curators and scientists.A major part of the data collected during the project has been stored in the FruitBreedomics database and has been made available to the public.This review covers the scientific discoveries made in this major endeavour,and perspective in the apple and peach breeding and genomics in Europe and beyond. | Francois Laurens Maria JoséAranzana Pere Arus Daniele Bassi Marco Bink Joan Bonany Andrea Caprera Luca Corelli-Grappadelli Evelyne Costes Charles-Eric Durel Jehan-Baptiste Mauroux Hélène Muranty Nelson Nazzicari Thierry Pascal Andrea Patocchi Andreas Peil Bénédicte Quilot-Turion Laura Rossini Alessandra Stella Michela Troggio Riccardo Velasco Eric van de Weg | 2018 | Horticulture Research2018，5，1： | 10 |
| 3 | Optimizing stem cells for cardiac repair:Current status and new frontiers in regenerative cardiology显示文摘Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel 'pharmacooptimizer' as well as genetic modifications. | Shant Der Sarkissian Thierry Lévesque Nicolas Noiseux | 2017 | World Journal of Stem Cells2017，9，1： | 6 |
| 4 | Levels of insecticide resistance to deltamethrin,malathion,and temephos,and associated mechanisms in Aedes aegypti mosquitoes from the Guadeloupe and Saint Martin islands(French West Indies)显示文摘Background:In the Guadeloupe and Saint Martin islands,Aedes aegypti mosquitoes are the only recognized vectors of dengue,chikungunya,and Zika viruses.For around 40 years,malathion was used as a mosquito adulticide and temephos as a larvicide.Since the European Union banned the use of these two insecticide molecules in the first decade of the 21st century,deltamethrin and Bacillus thuringiensis var.israelensis are the remaining adulticide and larvicide,respectively,used in Guadeloupe.In order to improve the management of vector control activities in Guadeloupe and Saint Martin,we investigated Ae.aegypti resistance to and mechanisms associated with deltamethrin,malathion,and temephos.Methods:Ae.aegypti mosquitoes were collected from six different localities of Guadeloupe and Saint Martin.Larvae were used for malathion and temephos bioassays,and adult mosquitoes for deltamethrin bioassays,following World Health Organization recommendations.Knockdown resistance(Kdr)genotyping for V1016I and F1534C mutations,and expression levels of eight enzymes involved in detoxification mechanisms were examined in comparison with the susceptible reference Bora Bora strain.Results:Resistance ratios(RR50)calculated for Ae.aegypti larvae showed high resistance levels to temephos(from 8.9 to 33.1-fold)and low resistance levels to malathion(from 1.7 to 4.4-fold).Adult females displayed moderate resistance levels to deltamethrin regarding the time necessary to affect 50%of individuals,varying from 8.0 to 28.1-fold.Molecular investigations on adult mosquitoes showed high resistant allele frequencies for V1016I and F1534C(from 85 to 96%and from 90 to 98%,respectively),as well as an overexpression of the glutathione S-transferase gene,GSTe2,the carboxylesterase CCEae3a,and the cytochrome genes 014614,CYP6BB2,CYP6M11,and CYP9J23.Conclusions:Ae.aegypti populations from Guadeloupe and Saint Martin exhibit multiple resistance to organophosphates(temephos and malathion),and pyrethroids(deltamethrin).The mechanisms associated with these resistance patterns show strong frequencies of F1534C and V1016I Kdr mutations,and an over-expression of CCEae3a,GSTe2,and four cytochrome P450 genes(014614,CYP9J23,CYP6M11,CYP6BB2).These results will form the baseline for a deeper understanding of the insecticide resistance levels and associated mechanisms of Ae.aegypti populations and will be used to improve vector control strategies in Guadeloupe and Saint Martin. | Daniella Goindin Christelle Delannay Andric Gelasse Cedric Ramdini Thierry Gaude Frederic Faucon Jean-Philippe David Joël Gustave Anubis Vega-Rua Florence Fouque | 2017 | Infectious Diseases of Poverty2017，6，1： | 3 |
| 5 | Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890<!-- Doctopic: VH -->显示文摘 | Christophe Hézode Hélène Fontaine Céline Dorival Dominique Larrey Fabien Zoulim Valérie Canva Victor de Ledinghen Thierry Poynard Didier Samuel Marc Bourlière Jean-Pierre Zarski Jean-Jacques Raabe Laurent Alric Patrick Marcellin Ghassan Riachi Pierre-Henr | 2013 | Journal of Hepatology2013，，： | 2 |
| 6 | Soluble CD40 ligand in prediction of acute severe pancreatitis显示文摘瞄准:在胰腺炎严厉估计可溶的 CD40L (sCD40L ) 的早可预测性。方法:在 2000 年 2 月和 2003 年 2 月之间,有尖锐胰腺炎的 279 个连续病人有希望地在我们的学习被注册。在这份报告, 40 个病人与温和并且有严重胰腺炎的 40 个病人随机被学习。sCD40L 集中被测量在承认以后的 48 个小时。结果:sCD40L 层次显著地更高在在严重胰腺炎的承认以后的 48 个小时比在温和胰腺炎。用 1000 的截止,检测疾病的一堂严重功课的 sCD40L 的 pg/L,敏感和特性为 CRP 与 72% 和 81% 相比分别地是 78% 和 62% 。发现那 CRP 的逻辑回归分析统计上是唯一的能检测疾病的一堂严重功课的重要标记。结论:这些调查结果显示 CRP 仍然是一个珍贵标记而 sCD40L 层次应该在进一步的研究被估计,决定尖锐胰腺炎的严厉和预后。 | Jean Louis Frossard Philippe Morel Brenda Kwak Catherine Pastor Thierry Berney Léo Buhler Alain Von Laufen Sandrine Demulder Francois Mach | 2006 | World Journal of Gastroenterology2006，12，10： | 2 |
| 7 | The tail suspension test: A new method for screening antidepressants in mice 显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology1985，85，3： | 1 |
| 8 | A new SURE approach to im- age denoising: interscale othonormal wavelet thresholding 显示文摘 | Flofian L Thierry B Michael U | 2007 | IEEE Transactions on hnage Processing2007，16，3： | 1 |
| 9 | The tail suspension test:a newmethod for screening antidepressants in mice显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology(Berl)1985，85，3： | 1 |
| 10 | The tail suspension test:a new method for screening antidepressants in mice显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology(Berl)1985，85，3： | 1 |
| 11 | The tail suspension test:a new method for screening antidepressants in Mice显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology1985，85，3： | 1 |
| 12 | The tail suspension test: a new method for screening antidepressants in mice显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology1985，85，3： | 1 |
| 13 | Analysis of cell wall neutral sugar composition, β-galactosidase activity and related cDNA clone throughout the development of Vitis vinifera grape berries 显示文摘 | Bamavon L Thierry D Nancy T | 2000 | Plant Physiol Biochem2000，38，4： | 1 |
| 14 | Liver Stiffness Measurement in Children Using FibroScan: Feasibility Study and Comparison With Fibrotest, Aspartate Transaminase to Platelets Ratio Index, and Liver Biopsy显示文摘 | Victor de Lédinghen Brigitte Le Bail Laurent Rebouissoux Céline Fournier Juliette Foucher Véronique Miette Laurent Castéra Laurent Sandrin Wassil Merrouche Frédéric Lavrand Thierry Lamireau | 2007 | Journal of Pediatric Gastroenterology and Nutrition2007，，4： | 1 |
| 15 | The tail suspension test:a new method for screening antidepressants in mice显示文摘 | STERU L CHERMAT R THIERRY B | 1985 | Psychopharmacology (Berl)1985，85，3： | 1 |
| 16 | Use and abuse of flexible intramedullary nailing in children and adolescents显示文摘 | PIERRE L THIERRY H PIERRE J | 2006 | Pediatr Orthop2006，26，6： | 1 |
| 17 | The tail suspension test : a new method for screening antidepressants in mice 显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology (Serl)1985，85，3： | 1 |
| 18 | The suspension test:a new method for screening antidepressants in mice显示文摘 | Steru L Chermat R Thierry B | 1985 | Psychopharmacology1985，85，3： | 1 |
| 19 | The tail suspension test: a new method for screening antidepressants in mice 显示文摘 | Stem L Chermat R Thierry B | 1985 | Psychoparmacology1985，85，3： | 1 |
| 20 | Evidence of diversity and recombination in Arsenophonus symbionts of the Bemisia tabaci spe- cies complex显示文摘 | Mouton L Thierry M Henri H | 2012 | Microbiology2012，12，1： | 1 |
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