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Rim-differentiation vs. mixture of constitutional isomers: A binding study between pillar[5]arene-based glycoclusters and lectins from pathogenic bacteria

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中国化学快报：英文版 2023年第2期34卷 214-218页

作者： Zhiping Liu fanny Demontrond Anne Imberty Andrew C.-h.Sue Sébastien Vidal hongxia Zhao Tianjin Key Lab for Modern Drug Delivery and high-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Institut de Chimie et Biochimie Moléculaires et Supramoléculaires Laboratoire de Chimie Organique 2-GlycochimieUMR 5246CNRSUniversitéClaude Bernard Lyon 1Universitéde LyonVilleurbanne 69622France CNRS Univ.Grenoble AlpesCERMAVGrenoble 38000France College of Chemistry and Chemical Engineering Xiamen UniversityXiamen 361005China CNRS Institut de Chimie des Substances NaturellesUniversitéParis-SaclayUPR 2301Gif-sur-Yvette 91198France

Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strategy. In this study, a series of constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto a penta-propargyl rim-differentiated pillar[5]arene(RD-P[5])scaffold through Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as Lec A and Lec B from Pseudomonas aeruginosa and concanavalin A(Con A), were evaluated subsequently by isothermal titration calorimetric studies. Most of these isomerfree RD-P[5] pentavalent glycoclusters, except the fucosylated ones, display good affinities to ***, the dissociation constants observed are similar to those displayed by an analogous pentavalent glycocluster consisting of four P[5] constitutional isomers, in which the RD-P[5] component merely accounts for 7% in the mixture. Our results revealed that high constitutional purity is not essential for achieving effective multivalent interactions between P[5]-based glycoclusters and lectins, presumably as a result of the conformationally labile nature of the P[5] scaffold. This information provides valuable design principles for low-cost and facile syntheses of glycosylated P[5]s for biomedical applications.

关键词： Glycocluster Lectin Pillararene Multivalency Constitutional purity

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Partial Beclin 1 silencing aggravates doxorubicin-and Fasinduced apoptosis in hepG2 cells

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World Journal of Gastroenterology 2006年第18期12卷 2895-2900页

作者： fanny Daniel Agnès Legrand Dominique Pessayre Nathalie Vadrot Véronique Descatoire Dominique Bernuau Institut National de la Santé et de la Recherche Médicale INSERMU773Centre de Recherche Bichat Beaujon CRB3BP 416F-75018ParisFrance Université paris 7 Denis Diderot site BichatBP 416F-75018ParisFrance

AIM： To investigate the role of Beclin 1 on the susceptibility of hepG2 cells to undergo apoptosis after anti-Fas antibody or doxorubicin treatment. METhODS： Beclin 1 silencing was achieved using RNA interference. DNA ploidy, the percentage of apoptotic cells and the mitochondrial membrane potential were assessed by flow cytometry. Levels of Beclin 1, BCI-XL and cytochrome c, and the cleavage of poly （ADP-ribose） polymerase （PARP） were assayed by using Western blots. RESULTS： Beclin 1 expression decreased by 75% 72 h after Beclin 1 siRNA transfection. Partial Beclin 1 silencing significantly increased the percentage of subG1 cells 24 and 40 h after treatment with doxorubicin or anti-Fas antibody, respectively, and this potentiation was abrogated by treatment with a pan-caspase inhibitor. Partial Beclin 1 silencing also increased PARP cleavage, mitochondrial membrane depolarization and cytosolic cytochrome c. The pro-apoptotic consequences of partial Beclin 1 silencing were not associated with a decline in Bcl-XL expression.CONCLUSION： Partial Beclin 1 silencing aggravates mitochondrial permeabilization and apoptosis in hepG2 cells treated with an anti-Fas antibody or with doxorubicin.

关键词： Beclin 1 Apoptosis hepG2 cells Anti-Fas antibody Doxorubicin

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c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

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World Journal of Gastroenterology 2008年第41期14卷 6339-6346页

作者： Meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence Michel Alain Mauviel Dominique Bernuau fanny Daniel Institut National de laSanté et de la Recherche Médicale U697 Hpital Saint-Louis Institut National de la Santé et de la RechercheMédicale U591 Faculté de Médecine Necker Institut National de la Santé et de la RechercheMédicale U773 Centre de Recherche Bichat Beaujon CRB3and Université Paris 7 Denis Diderot site Bichat

AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （Ihh） proliferation. METhODS： Ihhs stably transfected with c-Fos （Ihh- Fos） or an empty vector （Ihh-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3h-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3h]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to Ihh-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in Ihh- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate

关键词： c-Fos Cyclin DI GSK-3 Cell growth, Cell cycle hepatoma Epidermal growth factor

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Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors

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Journal of Geriatric Cardiology 2019年第11期16卷 806-811页

作者： Marjorie Bernier Sarah-Line Lancrerot fanny Rocher Elise K Van-Obberghen Pierre Olivier Thibaud Lavrut Nadège Parassol-Girard Milou-Daniel Drici Department of Pharmacology and Toxicology PharmacoVigilance CenterUniversity of Nice Côte d'Azur Medical CenterHôpital de Cimiez4 Avenue Reine VictoriaBP 117906003NiceFrance Emergency Department Short Stay Unit University of Nice Côte d'Azur Medical CenterHôpital Pasteur 230Voie Romaine 06001NiceFrance

Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug ***,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised *** aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very *** Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective *** were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).Conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.

关键词： Dabigatran Drug interaction hemorrhage P-gp inhibitors,The elderly

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Synthesis, Resolution and Absolute Configuration of 2,3-Dihydro-2-Tert-Butyl-3-N-Benzylquinazolin-4-One: A Possible Chiral Auxiliary for Synthesis of β-Amino Cyclohexancarboxylic Acid

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International Journal of Organic Chemistry 2014年第1期4卷 48-54页

作者： fanny A. Cabrera-Rivera Jaime Escalante Centro de Investigaciones Químicas Universidad Autónoma del Estado de Morelos Cuernavaca Mexico

3-Benzyl-2-(tert-butyl)-2,3-dihydroquinazolin-4(1h)-one rac-11 was resolved via the preparation of diastereomers with N-phthalyl-L-alanine chloride and its absolute configuration was determined by X-ray crystallographic analysis. This heterocycle has potential as a substrate chiral in asymmetric induction due to the steric effects of its tert-butyl group.

关键词： Chiral Auxiliary 2-Tert-Butyl-Quinazolin-4-One

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The functional complex network approach to foster forest resilience to global changes

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Forest Ecosystems 2019年第3期6卷 194-209页

作者： Christian Messier Jürgen Bauhus Frederik Doyon fanny Maure Rita Sousa-Silva Philippe Nolet Marco Mina Núria Aquilué Marie-Josée Fortin Klaus Puettmann Département des sciences naturelles and Institut des sciences de la forêt tempérée (ISFORT) Université du Québec en Outaouais(UQO)58 rue PrincipaleRiponQC J0V 1V0 Canada Centre d’étude de la forêt Université du Québec à Montréal (UQAM)Case postale 8888succursale Centre-VilleMontréalQC H3C 3P8Canada Chair of Silviculture Institute of Forest SciencesUniversity of FreiburgTennenbacherstr.479106 FreiburgGermany Swiss Federal Institute for Forest Snow and Landscape Research WSLBirmensdorfSwitzerland Department of Ecology and Evolution University of TorontoTorontoON M5S 3B2Canada Department of Ecosystems and Society Oregon State UniversityCorvallisOR 97331USA

human impacts on Earth's ecosystems have greatly intensified in the last decades. This is reflected in unexpected disturbance events, as well as new and increasing socio-economic demands, all of which are affecting the resilience of forest ecosystems worldwide and the provision of important ecosystem services. This Anthropocene era is forcing us to reconsider past and current forest management and silvicultural practices, and search for new ones that are more flexible and better at dealing with the increasing uncertainty brought about by these accelerating and cumulative global changes. here, we briefly review the focus and limitations of past and current forest management and silvicultural practices mainly as developed in Europe and North America. We then discuss some recent promising concepts, such as managing forests as complex adaptive systems, and approaches based on resilience, functional diversity, assisted migration and multi-species plantations, to propose a novel approach to integrate the functionality of species-traits into a functional complex network approach as a flexible and multi-scale way to manage forests for the Anthropocene. This approach takes into consideration the high level of uncertainty associated with future environmental and societal changes. It relies on the quantification and dynamic monitoring of functional diversity and complex network indices to manage forests as a functional complex network. Using this novel approach, the most efficient forest management and silvicultural practices can be determined, as well as where, at what scale, and at what intensity landscape-scale resistance, resilience and adaptive capacity of forests to global changes can be improved.

关键词： forest management North America Ecosystem services

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Immunodetection of Tau microtubule-associated protein in human sperm and testis

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Asian Journal of Andrology 2014年第6期16卷 927-928页

作者： Juiien Sigala fanny Jumeau Marie-raure Caillet-Boudin Nicolas Sergeant Caroline Ballot jean-Marc Rigot Franqois Marcelli Meryem Tardivel Luc Buee Valerie Mitchell EA 4308 Gametogenese et Qualite du Gamete Institut de Biologie de la Reproduction-Spermiolegie-gECOS H(Spital Jeanne de Flandre Centre Hospitalier Regional Universitaire de Lille Lille France INSERM U837 Alzheimer et Tauopathies Place de Verdun Lille France Departement d'Andrologie Hopital Calmette Lille France BICeL Universite Lille Nord de France-Centre hospitalier Regional Universitaire de Lille-IFR114 Lille France

Dear Editor, The cytosolic protein Tau is naturally present in human neurons, where it has a pivotal role in controlling microtubule stability. hyperphosphorylation of Tau （observed during neurodegenerative diseases, such as Alzheimer＇s disease） impairs the protein＇s ability to bind microtubules. This results in microtubule disassembly and the formation of Tau aggregates, Tau protein is also widely expressed in peripheral tissues. In the male reproductive system, screening for Tau has focused solely on the rodent and bovine testis. In the present study, we used immunofluorescence and immunoenzymatic techniques （with a Tau-specific antibody） to investigate the presence of Tau protein in human ejaculated sperm and testicular tissue.

关键词： MANChETTE

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Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in helicobacter pylori

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Gastroenterology Report 2019年第1期7卷 42-49,I0002页

作者： Eng-Guan Chua Aleksandra W.Debowski KMary Webberley fanny Peters Binit Lamichhane Mun-Fai Loke Jamuna Vadivelu Chin-Yen Tay Barry J.Marshall Michael J.Wise The Marshall Centre for Infectious Diseases Research and Training University of Western AustraliaPerthWestern AustraliaAustralia School of Biomedical Sciences Faculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical Microbiology University of MalayaKuala LumpurWilayah PersekutuanMalaysia Shenzhen Dapeng New District Kuichong People hospital ShenzhenGuangdongChina UM Marshall Centre University of MalayaKuala LumpurWilayah PersekutuanMalaysia School of Computer Science and Software Engineering University of Western AustraliaPerthWestern AustraliaAustralia

Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate helicobacter pylori ***,the global emergence of metronidazole resistance in hp poses a major challenge to health *** of RdxA is known to be a major mechanism of conferring metronidazole resistance in ***,metronidazole resistance can also arise in *** strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this ***:We performed whole-genome sequencing on 121 *** clinical strains,among which 73 were ***-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was *** sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in ***:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant *** of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole *** sites included R16h/C in RdxA,D85N in the inner-membrane protein RclC(hP0565),V265I in a biotin carboxylase protein(hP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(hP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in *** that merit further investigation.

关键词： helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment

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Effect of Ambient Temperature and humidity Conditions on the Efficacy of Organic Treatments against Varroa destructor in Different Climatic Zones of Chile

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Journal of Agricultural Science and Technology(A) 2013年第6期3卷 I0003-I0003,475-483页

作者： Aldea Patricia Rodriguez Rafael Olivares Alejandra Farffin Macarena Riveros Daniel Nfifiez fanny Trivelli Luz Center for Apicultural Entrepreneurship of Universidad Mayor CEAP1MA YOR-Camino La Pirc~mide Huechuraba Santiago 5 750Chile

Varroasis is a disease caused by the mite Varroa destructor, which affects honeybees worldwide. It is estimated that it entered Chile in 1992, and it must be controlled through different types of treatments such as thymol, formic and oxalic acid in different formulations and presentations. This kind of organic products has shown a variable acaricidal capacity, since different factors affect their efficacy such as ambient temperature and humidity, product presentation and location inside the hive, etc.. In Chile, beekeeping takes place in four different climatic zones, in which ambient temperature and humidity as well as the duration of the apicultural season are different. Therefore, the aim of this study was to determine how ambient temperature and humidity influence the efficacy of the organic treatments used in the beekeeping season. Different apiaries were installed in those climatic zones in three seasons between the years 2009 and 2012. All beehives received the same management in each apiary and it was evaluated the same organic treatments in different formulations and presentations. All the beehives were positive to Varroa, which was obtained using samples of adult bees and the soapy water test before and after each treatment. A thermo-hygrometer was installed in each apiary in order to monitor the ambient temperature （T°） and humidity （h°） conditions, which were registered daily for a period of 30 days since the beginning. It was obtained that the treatments＇ efficacy increases as the minimum T° and average T° rose, whereas on the contrary, the efficacy decreases when maximum h° was higher.

关键词： Varroa organics treatments effectiveness acaricidal effects.

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Cadmium-induced oxidative damage and antioxidant defense mechanisms in Glycine max L.

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Journal of Coastal Life Medicine 2014年第10期 791-798页

作者： Emiliano Felici Alicia Molina Cesar Almeida Martin Fernández Baldo fanny Zirulnik María Roxana Gomez Area Analytical Chemistry INQUISAL-CONICETFaculty of ChemistryBiochemistry and PharmacyNational University of San LuisChacabuco 917San LuisD5700HHWArgentina Area Biological Chemistry Faculty of ChemistryBiochemistry and PharmacyNational University of San LuisChacabuco 917San LuisD5700HHWArgentina

Objective:To analyze the effect of Cadmium(Cd)on the metabolism of reduced glutathione(GSh)in roots and leaves of Glycine max ***:A capillary electrophoresis methodology was optimized to determinate simultaneously GSh and reduced and oxidized GSh in a precise and accurate *** functional role of the genes involved in GSh cellular metabolism(γ-glutamylcysteine synthetase),GSh synthetase and glutathione reductase(GR)was ***,the activities of antioxidant enzymes as GR and superoxide dismutases were ***:The studies ofγ-glutamylcysteine synthetase and GSh synthetase gene expression showed an increase and GR showed a decrease in Cd-treated *** and superoxide dismutases activities increased at 24 h and 6 h respectively in roots under Cd *** content was higher and showed a significant increase in roots and leaves at 6 h and 24 h of ***:The results of the present study showed a better understanding in signaling pathway by alterations in antioxidant mechanisms by Cd in soybean seedlings.

关键词： Soybean Cadmium toxicity Oxidative stress Antioxidant defense Glutathione Capillary electrophoresis

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