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Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

World Journal of Hepatology 2016年第21期8卷 902-914页

作者： sylvie Lagaye sonia Brun Jesintha Gaston Hong shen Ruzena stranska Claire Camus Clarisse Dubray Géraldine Rousseau Pierre-Philippe Massault Jerome Courcambeck Firas Bassisi Philippe Halfon stanislas Pol institut Pasteur INSERM institut Cochin INSERM U1016CNRS UMR8104Universite Paris Descartes(UMR S1016) Genoscience Pharma KU Leuven Rega Institute Laboratoire Alphabio APHP Groupe Hospitalier La Pitie Salpe-triereService de Chirurgie digestive et Hepato bilio pancreatique APHP Groupe Hospitalier CochinService de Chirurgie digestiveHepato-biliaire et Endocrinienne Universite Paris descartes APHP Groupe Hospitalier CochinUnite d’Hepatologie institut Pasteur Departement de Recherche TranslationnelleINSERM

AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODs: non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with Gns-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. REsULTs: The antiviral efficacy of a new antiviral drug, Gns-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, Gns-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).COnCLUsIOn: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative Gns-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.

关键词： Host antiviral therapy Hepatitis C virus Tissue culture Autophagy Quinoline derivative

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Microscopic Features, Antioxidant and Antibacterial Capacities of Plants of the Congolese Cosmetopoeia, Raw Materials of Cosmeceuticals

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Journal of Biosciences and Medicines 2020年第9期8卷 149-166页

作者： Isaac Kaba Elaka Paulin Mutwale Kapepula nadège Kabamba ngombe Jonathan Mukanya Mpoyi Dorcas Mukundi Lukusa Messie Muipata Muabilwa Carmel Kandhe Gabha’Bey Cyprien Mbundu Lukukula Boniface nlandu Lukebakio Monique Kandolo Okuna Didi Mana Kialengila Paul Tshilumbu Kantola Centre d’Etudes des substances naturelles d’Origine Végétale (CEsnOV) Faculty of Pharmaceutical Sciences University of Kinshasa Kinshasa Democratic Republic of Congo Laboratory of Experimental and Pharmaceutical Microbiology Faculty of Pharmaceutical Sciences University of Kinshasa Kinshasa Democratic Republic of Congo institut national d’Etudes et de recherches en Agronomie (InERA) University of Kinshasa Kinshasa Democratic Republic of Congo Bolimo sARL Kinshasa Democratic Republic of Congo Laboratory of Drug Analysis Faculty of Pharmaceutical Sciences University of Kinshasa Kinshasa Democratic Republic of Congo

Cosmeceuticals are the fastest growing products in the cosmetics field and represent a hybrid between cosmetics and drugs. The main benefits reported for cosmeceutical herbal extracts, used in skin care, include antioxidant and antimicrobial activities and the tyrosinase inhibiting effect. The aim of this study was to evaluate the antioxidant and antibacterial activities of extracts from Chromolaena odorata, Mitracarpus villosus, senna alata, Tetradenia riparia, Cannabis sativa and Pterocarpus soyauxii used traditionally in the management of skin and skin annexes pathologies;additionally to determine their microscopical characteristics and their chromatographic fingerprints. Microscopic analyses showed the specific botanical microscopic characters for each plant that constitute the database useful for the identification and authentication of these botanicals. To the best of our knowledge, our work is the first to describe the microscopic histological characters of studied plants except for Cannabis sativa. The results of the TLC chromatographic analysis revealed the richness in phenolic compounds, terpenes in all extracts and Pterocarpus soyauxii contained coumarins. All extracts displayed high ABTs and DPPH radical-scavenging activities connected with their ICsub>50sub> values at the concentration range of 1 - 125 μg/mL with Cannabis sativa and Pterocarpus soyauxii as the most active. All plant extracts exhibited antibacterial activity on Escherichia coli, Pseudomonas aeruginosa and staphylococcus aureus to varying degrees. Cannabis sativa exhibited strong effect on staphylococcus aureus and Escherichia coli. Chromolaena odorata and Tetradenia riparia showed a marked effect on Escherichia coli. Although certain crude extracts from studied botanicals have been shown to be inactive, fractionation studies are needed to determine the active f

关键词： Cannabis sativa Chromolaena odorata Cosmeceuticals Cosmetopoeia Mitracarpus villosus Pterocarpus soyauxii senna alata Tetradenia riparia Yelena

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In Vitro Picloram-lnduced somatic Embryogenesis from Leaflets of Cherry （Prunus incisa Thunb,）

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Journal of Life sciences 2011年第11期5卷 913-920页

作者： Ben Mahmoud Kaouther Elloumi nadhra Chakroun Ahlem Ahmed Jemmali Philippe Druart institut national Agronomique de Tunisie Cite El Mahrajene Tunis 1082 Tunisie departement Biotechnologie et Physiologie Vegetale Institut National de la Recherche Agronomique de Tunisie Rue Hedi KarrayAriana 2080 Tunisie Unite ＂Genie Biologique ＂ Departement Sciences du Vivant Centre Wallon de Recherches Agronomiques Chaussee de Charleroi234 Gembloux 5030 Belgique

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neural stem cells isolated from amyloid precursor proteinmutated mice for drug discovery

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World Journal of stem Cells 2013年第4期5卷 229-237页

作者： Vito Antonio Baldassarro Mercedez Fernández Giulia Lizzo Michela Paradisi Luciana Giardino Laura Calzà Giulia Lizzo Health science and Technologies Interdepartmental Center for Industrial Research(HsT-ICIR) department of Veterinary Medicine and University of Bologna Health science and Technolo-gies Interdepartmental Centre for Industrial Research(HsT-ICIR)and IRET Foundation institut de recherches servier 125 Chemin de Ronde

AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new ***: neural stem cells(nsCs) were isolated from the subventricular zone of Wild type(Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro(DIVs) in mitogen withdrawal conditions,spontaneous differentiation was studied using specific neural markers(MAP2 and TuJ-1 for neurons, GFAP forastroglial cells and CnPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEn PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using sTRInG web ***: As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated nsCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 *** gene expression neurogenesis pathway revealed11 altered genes in Tg2576 nsCs compared to ***: Tg2576 nsCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells.

关键词： neural stem cells Alzheimer’s disease neuron maturation Drug discovery

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***2f1/2 are required for the specification of cone photoreceptors in the developing retina

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Annals of Eye science 2018年第1期 446-446页

作者： Awais Javed Pierre Mattar Michel Cayouette Cellular neurobiology Research Unit Institut de Recherches Cliniques de Montreal(IRCM)MontrealQCCanada Molecular Biology Program Universitéde MontréalMontrealQCCanada department of Medicine Universitéde MontréalMontrealQCCanada Division of Experimental Medicine Department of Anatomy and Cell BiologyMcGill UniversityMontrealQCCanada

Background:Rods and cones are critical for light *** there has been considerable work done in elucidating the molecular mechanisms involved in rod development,not much is known about how the cone cell fate decision is made by the multipotent retinal progenitor cells during *** of the promoter regions of nrl and trβ2,rod and cone differentiation factors respectively,revealed DnA binding motifs of two POU-domain containing transcription factors,Pou2f1 and *** experiments showed that Pou2f1/2 are expressed during the peak of cone genesis in the embryonic ***,we hypothesize that Pou2f1/2 specify cone cell fate in the developing ***:We used immunofluorescence and in situ hybridization to establish the spatiotemporal expression of Pou2f1/2 during *** performed in vivo electroporation in post-natal mice to misexpress Pou2f1/2 and used antibodies specific to proteins expressed in cones such as Rxrγand s-opsin to count *** ex vivo electroporation of embryonic retinal explants,we knocked out Pou2f1 and Pou2f2 using CRIsPR/Cas9 gRnAs at the peak of cone production ***,we transfected post-natal retinal explants with a combination of regulatory elements of nrl or thrb with control backbone vector,Pou2f1 or Pou2f2 using ***:We found that Pou2f1/2 are expressed in retinal progenitor cells in the developing retina and subsequently in the differentiated ***2f1/2 misexpression outside the cone genesis window led to an increase in cones at the expense of ***2f1/2 indel knockouts generated by CRIsPR/Cas9 gRnAs led to a decrease in cones and a converse increase in ***,we found that Pou2f1/2 activate the cis-regulatory module(CRM)of the thrb gene and repress the activity of the CRM of ***:These results uncover novel players that establish the complex gene regulatory network for cone photoreceptor fate specification in the retinal proge

关键词： Cones rods cell biology molecular biology retinogenesis

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AnTIRACIsME,MYTHOLOGIE ET CRITIQUE de LA 《MYTHOLOGIE BLAnCHE》——éléments pour une histoire de la pensée critique contemporaine,en Occident et en Chine

人文新视野

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人文新视野 2021年第2期 51-67页

作者： YE shuxian QI Zhaoyuan Université Jiaotong de shanghai l'Académie des sciences sociales de Chine 3. Centre d'études Francophones Université des études Internationales de Xi'an

L’institut de la Mythologie de l’UniversitéJiaotong de shanghai a tenu un grand forum 《Mythologie et antiracisme》;le 14 novembre 2020. Ce forum a,de plus,donnélieuàune conférence de presse sur la publication de deux ouvrages:la traduction en chinois d’Athènes noire de Martin Bernal;et Crise de la modernitéet recherches des origines culturelles de nous-même,YE shuxian;.

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recherches sUR LA REPRODUCTIOn ET LA CROIssAnCE de L'OsTREA CUCULLATA BORn

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海洋与湖沼 1957年 139-140页

作者： TCHAnG si ET,Lou TZE-KOnG institut Je Biologic Marine Acadania stnica institut Je Biologic Marine Acadania stnica

En Chine l'huitre est un important mollusque cultivé, et consommé en toutes facons: fraiche, séchée, conserve, ou huile d'hu(?)tre. En outre, les coquilles des hu(?)tres fournissent des matériaux pour l'industrie de la production de chaux. Les hu(?)tres formérent jadis sur nos c(?)tes d'innombrables bancs naturels. Puis, cesbanes ont commencé à restreindre à cause de l'exploitation intense. Alors on a

关键词： Plus recherches sUR LA REPRODUCTIOn ET LA CROIssAnCE de L’OsTREA CUCULLATA BORn exp

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*** Endocytic Adaptor Protein numb Functions in Müller Glia to Maintain Retinal Polarity and Photoreceptor survival through the Polarity determinant Crumbs

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Annals of Eye science 2019年第1期 221-221页

作者： Maude Vinette Marie-Claude Bélanger Christine Jolicoeur Mina Gabraie Pierre Lachapelle Michel Cayouette Cellular neurobiology Research Unit Institut de recherches cliniques de Montréal(IRCM)MontrealQCCanada Integrated Program in neuroscience McGill UniversityMontrealQCCanada Division of Experimental Medicine McGill UniversityMontrealQCCanada department of Ophthalmology Research Institute of the McGill University Health CentreMontrealQCCanada department of neurology and neurosurgery McGill UniversityMontrealQCCanada department of Medicine Universitéde MontréalMontrealQCCanada

Background:The loss of cell polarity plays a key part in retinal dystrophies such as retinitis pigmentosa(RP)and Leber congenital amaurosis(LCA),resulting in photoreceptor(PR)degeneration and vision *** not knowing the direct genotype-to-phenotype correlation,many disease-causing mutations in the polarity determinant Crumbs(Crb1),have been ***,the loss of Crb1 in mice was shown to cause PR death,due to the loss of adhesions between PR and Müller cells at the apical surface of the ***,although the role of Crb1 in neuron polarity and survival is well established,little is known about how its intracellular trafficking is *** future treatments for retinal degenerative diseases in mind,the goal of this project is to understand the mechanism by which Crb1 is regulated and how it maintains retinal *** work in our laboratory showed that numb,an endocytic adaptor protein,is an important regulator of protein trafficking in retinal *** therefore hypothesized that numb might function as regulator of Crb1 in Müller ***:To study numb function in Müller cells,we generated a conditional knockout(cKO)mouse line to inactivate numb specifically in Müller cells by crossing a Glast-CreERT2 mouse line with a numb-floxed *** 30 days,mice were administered tamoxifen to trigger inactivation of numb and retinas were then collected at time points varying from 2 weeks to 17 months for ***,we studied the retinal morphology and outer limiting membrane integrity by histology and *** electron microscopy(EM),adhesions between Müller glia and photoreceptors were analysed and retinal function was assayed in live mice by electroretinography(ERG).To detect protein expression levels,protein extracts were prepared from cKO and control retinas for *** test for the presence of a biochemical interaction,Hek-293 cells were transfected with numb and Crb1 vectors,and protein ext

关键词： degeneration retinal polarity Crumbs-related dystrophies(Crb1-related dystrophies)

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Level structure in 69As

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IMP & HIRFL Annual Report 2004年 74-74页

作者： I. stefanescu,J. Eberth,G. Gersch,T. steinhardt,O. Thelen,n. Warr,D. Weisshaar,B. G. Carlsson,I. Ragnarsson,G. de Angelis,T. Martinez,A. Jungclaus,R. schwengner,K. P. Lieb,E. A. stefanova,D. Curien institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany Horia-Hulubei national institute for Physics and nuclear Engineering P. O. Box MG-6 Bucharest Romania institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany institut für Kernphysik Universitt zu Kln Zülpicher strasse 77 D-50937 Kln Germany department of Mathematical Physics Lund institute of Technology P. O. Box 118 H-22100 Lund sweden department of Mathematical Physics Lund institute of Technology P. O. Box 118 H-22100 Lund sweden Istituto nazionale di Fisica nucleare Laboratori nazionali di Legnaro via Romea 4 I-35020 Legnaro Italy Istituto nazionale di Fisica nucleare Laboratori nazionali di Legnaro via Romea 4 I-35020 Legnaro Italy departamento de Fisica Teórica Universidad Autonoma de Madrid E-28049 Madrid spain institut für Kern- und Hadronenphysik Forschungszentrum Rossendorf D-01314 Dresden Germany Ⅱ Physikalisches institut Universitt Gttingen D-37073 Gttingen Germany Ⅱ Physikalisches institut Universitt Gttingen D-37073 Gttingen Germany institute for nuclear Research and nuclear Energy BAs 1784 sofia Bulgaria institut de recherches subatomiques CnRs-In2P3 F-67037 strasbourg France

High-spin states in 69As were populated via the 40Ca(32s, 3p)69As reaction at 95 MeV beam energy. The 32s beam was provided by the VIVITROn accelerator of the Ires strasbourg. A target of 1 mg/cm2 With 15 mg/cm2 gold backing was used. Measurements of γ-γand γ-γ-γcoincidences were performed with the EUROBALL array

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