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4. A holistic approach of conservation agriculture that unites engineering, research, on-farm demonstration and extension in Cambodia

Author

Boulakia, Stephane, Kong, R., Husson, O., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., and Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase

Subjects
Training and extension (date), Demonstrations, Design, Farm/Enterprise Scale, Conservation agriculture, Diagnostic, Assessment
Abstract

This poster describes the Diagnostic, Design, Assessment, Training and Extension (DATE) approach to gaining a holistic understanding of an agricultural system. LTRA-12 (Conservation agriculture for food security in Cambodia and the Philippines)

Published
2014

5. Enhancing ecological processes under diversified direct seeding mulch-based cropping systems in Cambodia

Author

Boulakia, Stephane, Kong, R., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., and Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase

Subjects
Direct seeding, Farm/Enterprise Scale, Conservation agriculture, Conservation tillage, Mulch-based
Abstract

minimum soil disturbance, permanent soil cover, diversify crop rotation LTRA-12 (Conservation agriculture for food security in Cambodia and the Philippines)

Published
2014

6. Striga asiatica : a driving-force for dissemination of conservation agriculture systems based on Stylosanthes guianensis in Madagascar

Author

Michellon, R., Husson, O., Moussa, N., Randrianjafizanaka, M. T., Naudin, K., Letourmy, P., Andrianaivo, A. P., Rakotondramanana, R., Raveloarijaona, N., Enjalric, F., Penot, E., Séguy, L., Systèmes de Cultures Annuelles (UPR 102 SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), ONG TAFA (Tany sy Fampandrosoana), ONG TAFA, BP 266, 110, Antsirabe, Madagascar, Systèmes de culture et rizicultures durables (URP SCRID), Institut de Recherche pour le Développement (IRD)-Université d'Antananarivo-Africa Rice Center (AfricaRice)-FOFIFA-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Consultative Group on International Agricultural Research [CGIAR], GSDM, GSDM Madagascar, FAFIALA, CVS, Tsivatrinikamo, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Ranoarisoa, Mahafaka Karen, Systèmes de Cultures Annuelles (UPR SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université d'Antananarivo-Centre National de Recherche Appliquée au Développement Rural (FOFIFA)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Africa Rice Center [Côte d'Ivoire] (AfricaRice), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
[SDE] Environmental Sciences, F08 - Systèmes et modes de culture, Striga asiatica, Oryza sativa, Stylosanthes guianensis, Zea mays, Culture sous couvert végétal, [SDE]Environmental Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

7. Gestion agronomique de la résistance du riz à la pyriculariose : le projet GARP

Author

Jean-Loup Notteghem, Elsa Ballini, Bouzinac, S., Breseghello, F., Cobucci, T., Chabanne, A., Dusserre, J., Michellon, R., Jean-Benoit Morel, Louis-Marie Raboin, Ramanantsoanirina, A., Séguy, L., Sester, M., Taillebois, J., Didier Tharreau, Michel Vales, Biologie et Génétique des Interactions Plantes-Agents Pathogènes, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure Agronomique de Montpellier (ENSA M)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Biologie et Génétique des Interactions Plante-Parasite (UMR BGPI), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Empresa Brasileira de Pesquisa Agropecuária (Embrapa), Ministério da Agricultura, Pecuária e Abastecimento [Brasil] (MAPA), Governo do Brasil-Governo do Brasil, CNPAF, Brazilian Agricultural Research Corporation (Embrapa), and Centre National de Recherche Appliquée au Développement Rural (FOFIFA)

Subjects
résistance aux maladies, expression génique, MAGNAPORTHE ORYZAE, RESISTANCE PARTIELLE, [SDV]Life Sciences [q-bio], PYRICULARIOSE DU RIZ, nutrition azotée, FERTILISATION AZOTEE, fertilisation, métabolisme azoté, épidémiologie végétale, pathologie végétale, pratique culturale
Abstract

National audience; Les conséquences des pratiques agricoles, et notamment de la fertilisation azotée, influentelles sur l'expression de la résistance des plantes ? C'est à cette question que le projet GARP tentera de répondre. Les expérimentateurs ont observé que les pratiques agronomiques sont des facteurs importants de modulation du niveau des épidémies de pyriculariose du riz causée par Magnaporthe oryzae. Il est notamment connu que la fertilisation azotée favorise les épidémies, alors que des systèmes « agroécologiques » qui incluent le semis direct sur couverture végétale, permettent d'atteindre des rendements élevés en limitant le niveau des épidémies. L'hypothèse qui est privilégiée est que le contrôle des épidémies résulterait de différences de la dynamique du métabolisme de l'azote. Les systèmes agroécologiques réguleraient les apports d’azote et permettraient une expression satisfaisante de la résistance partielle, alors que dans des systèmes conventionnels les apports d'azote massifs induiraient une répression des voies métaboliques impliquées dans la résistance. Des expérimentations préliminaires menées en serre avec des apports azotés différents indiquent que la voie du métabolisme de l'azote serait antagoniste de celle des mécanismes de défense. Mesurer les épidémies dans des systèmes de culture différents, évaluer l'impact de ces épidémies sur les rendements, sont une composante du projet GARP. L'analyse de la dynamique du métabolisme de l'azote sera menée par des dosages chimiques de différentes formes d'azote aux stades phénologiques clés du développement du riz. Au laboratoire, dans des conditions de fertilisation azotée différentielles, on reprendra les études de l'expression de gènes indicateurs clés des voies métaboliques des mécanismes de défense et du métabolisme de l'azote. Ces études d'expression de gènes régulateurs de ces voies métaboliques seront également conduites sur des échantillons prélevés en plein champ. Les bases génétiques de la sensibilisation par l'azote seront également déterminées par des approches de cartographie QTL et de génétique inverse). Le projet GARP permettra d’approfondir les connaissances sur les interactions entre mécanismes de résistance/sensibilité à la pyriculariose et métabolisme de l’azote, et d’en tirer les conséquences pour élaborer des méthodes agronomiques de gestion de l'expression de la résistance partielle.

Published
2010

9. La mise en place de systèmes de culture en semis direct

Author

Husson, O., Charpentier, H., Naudin, K., Razanamparany, C., Moussa, N., Michellon, R., Razafintsalama, H., Rakotoarinivo, C., Rakotondramanana, R., Enjalric, F., Séguy, L., and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA] Life Sciences [q-bio]/Agricultural sciences
Published
2009

10. Fiches techniques plantes de couvertures : légumineuses pérennes. Stylosanthes guianensis

Author

Husson, O., Charpentier, H., Razanamparany, C., Moussa, N., Michellon, R., Naudin, K., Razafintsalama, H., Rakotoarinivo, C., Rakotondramanana, R., Séguy, L., and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA] Life Sciences [q-bio]/Agricultural sciences, F01 - Culture des plantes, Plante de couverture, F08 - Systèmes et modes de culture, Stylosanthes guianensis
Published
2008

11. Dispositifs pour l'évalutation des impacts des systèmes de culture sur les dégâts des insectes terricoles sur le riz pluvial à Madagascar

Author

Ratnadass, A., Rafamatanantsoa, E., Rajaonera, T.E., Ramahandry, F., Ramarofidy, M., Randriamanantsoa, R., Séguy, L., Fonctionnement agroécologique et performances des systèmes de cultures horticoles (UPR HORTSYS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centre National de Recherche Appliquée au Développement Rural (FOFIFA), and Ranoarisoa, Mahafaka Karen

Subjects
[SDE] Environmental Sciences, Semis direct, Lutte anti-insecte, F08 - Systèmes et modes de culture, Oryza sativa, H10 - Ravageurs des plantes, Lutte biologique, Culture sous couvert végétal, Heteronychus, [SDE]Environmental Sciences, Riz pluvial, Système de culture
Published
2008

12. Conduite des systèmes de culture sur couverts végétaux et affouragement des vaches laitières : guide pour les Hautes Terres de Madagascar

Author

Rasamizafimanantsoa, A. H., Rakotonirainy, H. J., Randrianaivoarivony, J.-M., Rahetlah, B. V., Razafimpamoa, H. L., Razanamparany, C., Moussa, N., Michellon, R., Rakotondramanana, R., Husson, O., Lecomte, P., Naudin, K., Tillard, E., Randrianasolo, J., Séguy, L., Thomas, P., and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA] Life Sciences [q-bio]/Agricultural sciences
Published
2008

13. Méthodologie d'évaluation des impacts des systèmes de culture sur les dégâts des insectes terricoles sur le riz pluvial à Madagascar [Poster] = A methodology for assessing the impacts of cropping systems on soil insect pest damage to upland rice in Madagascar

Author

Ratnadass, A., Rafamatanantsoa, E., Rajaonera, T.E., Ramahandry, F., Ramarofidy, M., Randriamanantsoa, R., Séguy, L., Systèmes de Cultures Annuelles (UPR SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Systèmes de culture et rizicultures durables (URP SCRID), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université d'Antananarivo-Centre National de Recherche Appliquée au Développement Rural (FOFIFA)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Africa Rice Center [Côte d'Ivoire] (AfricaRice), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences
Published
2007

14. Le coton SCV à Madagascar, 10 ans de sites TAFA [Poster]

Author

Naudin, K., Razafintsalama, H., Séguy, L., Systèmes de Cultures Annuelles (UPR SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), ONG TAFA (Tany sy Fampandrosoana), ONG TAFA, and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences
Published
2007

15. Impact of a direct seeding, mulch-based, conservation agriculture (DMC) rainfed rice-based system on soil pest and striga infestation and damage in Madagascar = Impact des systèmes de semis direct sur couverture végétale permanente à base de riz pluvial sur l'infestation et les dégâts des pestes et du Striga à Madagascar

Author

Ratnadass, A., Andrianaivo, A. P., Michellon, R., Moussa, N., Randriamanantsoa, R., Séguy, L., Ranoarisoa, Mahafaka Karen, Systèmes de Cultures Annuelles (UPR SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Systèmes de culture et rizicultures durables (URP SCRID), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université d'Antananarivo-Centre National de Recherche Appliquée au Développement Rural (FOFIFA)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Africa Rice Center [Côte d'Ivoire] (AfricaRice), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), ONG TAFA (Tany sy Fampandrosoana), and ONG TAFA, BP 266, 110, Antsirabe, Madagascar

Subjects
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences
Published
2006

16. Effects of soil and plant management on crop pests and diseases

Author

Ratnadass, A., Michellon, R., Randriamanantsoa, R., Séguy, L., Systèmes de Cultures Annuelles (UPR SCA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Systèmes de culture et rizicultures durables (URP SCRID), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université d'Antananarivo-Centre National de Recherche Appliquée au Développement Rural (FOFIFA)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Africa Rice Center [Côte d'Ivoire] (AfricaRice), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), and Ranoarisoa, Mahafaka Karen

Subjects
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Mulch, Rotation culturale, F08 - Systèmes et modes de culture, Travail du sol, P36 - Erosion, conservation et récupération des sols, Maladie des plantes, H20 - Maladies des plantes, F07 - Façons culturales, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences, Gestion du sol, Pratique culturale, Disponibilité d'élément nutritif, Système de culture, Amélioration des sols
Published
2006

18. Recommendation of hybrid corn on mollisols of western upland areas in Cambodia

Author

Kong, R., Sar, V., Soueng, K., Thy, B., Boulakia, Stephane, Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Kong, R., Sar, V., Soueng, K., Thy, B., Boulakia, Stephane, Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

Hybrid of corn are widely grown since early 2000s by smallholders in the western areas of Cambodia. A large number of hybrids are available on the market.

Published
2014

19. Potentials and challenges of Conservation Agriculture in the western upland areas of Cambodia. A case study in RattanakMundol, Battambang Province

Author

Kong, R., Boulakia, Stephane, Sar, V., Soeurng, K., Thy, B., Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Kong, R., Boulakia, Stephane, Sar, V., Soeurng, K., Thy, B., Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

This poster presents efforts to introduce direct seeding mulch-based cropping systems (DMC) to smallholder subsistence farmers in Rattanak Mundol, Cambodia. It compares corn yields under DMC and conventional practices and identifies potentials and challenges for adoption and scaling up.

Published
2014

20. Recommendation of hybrid corn on mollisols of western upland areas in Cambodia

Author

Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Kong, R., Sar, V., Soueng, K., Thy, B., Boulakia, Stephane, Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Kong, R., Sar, V., Soueng, K., Thy, B., Boulakia, Stephane, Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

Hybrid of corn are widely grown since early 2000s by smallholders in the western areas of Cambodia. A large number of hybrids are available on the market.

Published
2014

21. A holistic approach of conservation agriculture that unites engineering, research, on-farm demonstration and extension in Cambodia

Author

Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Boulakia, Stephane, Kong, R., Husson, O., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Boulakia, Stephane, Kong, R., Husson, O., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

This poster describes the Diagnostic, Design, Assessment, Training and Extension (DATE) approach to gaining a holistic understanding of an agricultural system.

Published
2014

22. Enhancing ecological processes under diversified direct seeding mulch-based cropping systems in Cambodia

Author

Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Boulakia, Stephane, Kong, R., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Boulakia, Stephane, Kong, R., Leng, V., Sar, V., Soeurng, K., Thy, B., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

minimum soil disturbance, permanent soil cover, diversify crop rotation

Published
2014

23. Potentials and challenges of Conservation Agriculture in the western upland areas of Cambodia. A case study in RattanakMundol, Battambang Province

Author

Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Kong, R., Boulakia, Stephane, Sar, V., Soeurng, K., Thy, B., Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., Séguy, L., Sustainable Agriculture and Natural Resource Management (SANREM) Knowledgebase, Kong, R., Boulakia, Stephane, Sar, V., Soeurng, K., Thy, B., Leng, V., Huot, L., Nhem, S., Pheav, S., Reyes, Manuel R., Tivet, F., and Séguy, L.

Abstract

This poster presents efforts to introduce direct seeding mulch-based cropping systems (DMC) to smallholder subsistence farmers in Rattanak Mundol, Cambodia. It compares corn yields under DMC and conventional practices and identifies potentials and challenges for adoption and scaling up.

Published
2014

27. Bioinspired Bottlebrush Polymers Effectively Alleviate Frictional Damage Both In Vitro and In Vivo.

Author

Pham DA, Wang CS, Séguy L, Zhang H, Benbabaali S, Faivre J, Sim S, Xie G, Olszewski M, Rabanel JM, Moldovan F, Matyjaszewski K, and Banquy X

Subjects
Animals, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Mice, Humans, Lubrication, Surface Properties, Lubricants chemistry, Biomimetic Materials chemistry, Biomimetic Materials pharmacology, Friction, Hyaluronic Acid chemistry, Polymers chemistry, Polymers pharmacology
Abstract

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.g., cartilage, eye, and contact lens), forming a robust, biocompatible layer for surface lubrication and protection. The tribological performance and biocompatibility are further enhanced in the presence of hyaluronic acid (HA) both in vitro and in vivo. The exceptional lubrication performance and favorable interaction with HA position the synthesized triblock polymer as a promising candidate for innovative treatments addressing deficiencies in bio-lubricant systems., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Published
2024
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28. In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration.

Author

Séguy L, Daressy F, Lahlil S, Corvaisier S, Dumontet V, Litaudon M, Apel C, Roussi F, Wiels J, Robert A, Groo AC, and Malzert-Fréon A

Subjects
Animals, Mice, Administration, Oral, Emulsions, Myeloid Cell Leukemia Sequence 1 Protein, Particle Size, Nanostructures, Antineoplastic Agents pharmacology, Lymphoproliferative Disorders
Abstract

MCL-1, an anti-apoptotic member of the BCL-2 protein family, is overexpressed in many types of cancer and contributes to chemotherapy resistance. The drimane derivative NA1-115-7 is a natural compound isolated from Zygogynum pancheri that can be considered as a very promising lead for treating MCL-1-dependent hematological malignancies. As this drug suffers from low stability in acidic conditions and poor aqueous solubility, we evaluated the potential oral use of NA1-115-7 by encapsulating it in lipid nanoemulsions (NA-NEs) prepared by spontaneous emulsification. NA-NEs showed a particle size of 41.9 ± 2.2 nm, PDI of 0.131 ± 0.016, zeta potential of -5.8 ± 3.4 mV, encapsulation efficiency of approximately 100 % at a concentration of 24 mM. The stability of NA-1-115-7 was sixfold higher than that of the unencapsulated drug in simulated gastric fluid. NA-NEs significantly restored apoptosis and halved the effective doses of NA1-115-7 on BL2, a Burkitt lymphoma cell line, without toxicity in normal cells. Such a drug-delivery system appears to be particularly interesting for the oral administration of NA1-115-7, as it improves its solubility and stability, as well as efficacy, by reducing the therapeutic dose, making it possible to further consider in-vivo studies of this promising drug in BL2 xenografted mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2023
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29. NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.

Author

Daressy F, Séguy L, Favre L, Corvaisier S, Apel C, Groo AC, Litaudon M, Dumontet V, Malzert-Fréon A, Desrat S, Roussi F, Robert A, and Wiels J

Subjects
Apoptosis, Bridged Bicyclo Compounds, Heterocyclic, Cell Line, Tumor, Humans, Leukocytes, Mononuclear metabolism, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Myocytes, Cardiac metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Sulfonamides, Winteraceae metabolism, bcl-2 Homologous Antagonist-Killer Protein metabolism, bcl-X Protein metabolism, Antineoplastic Agents pharmacology, Hematologic Neoplasms drug therapy
Abstract

The overexpression of antiapoptotic members (BCL-2, BCL-xL, MCL-1, etc.) of the BCL-2 family contributes to tumor development and resistance to chemotherapy or radiotherapy. Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax). However, acquired resistance to venetoclax or chemotherapy drugs due to an upregulation of MCL-1 has been observed, rendering MCL-1 an attractive new target for treatment. Six MCL-1 inhibitors (S64315, AZD-5991, AMG-176, AMG-397, ABBV-467 and PRT1419) have been evaluated in clinical trials since 2016, but some were affected by safety issues and none are currently used clinically. There is, therefore, still a need for alternative molecules. We previously described two drimane derivatives as the first covalent BH3 mimetics targeting MCL-1. Here, we described the characterization and biological efficacy of one of these compounds (NA1-115-7), isolated from Zygogynum pancheri, a plant belonging to the Winteraceae family. NA1-115-7 specifically induced the apoptosis of MCL-1-dependent tumor cells, with two hours of treatment sufficient to trigger cell death. The treatment of lymphoma cells with NA1-115-7 stabilized MCL-1, disrupted its interactions with BAK, and rapidly induced apoptosis through a BAK- and BAX-mediated process. Importantly, a similar treatment with NA1-115-7 was not toxic to erythrocytes, peripheral blood mononuclear cells, platelets, or cardiomyocytes. These results highlight the potential of natural products for use as specific BH3 mimetics non-toxic to normal cells, and they suggest that NA1-115-7 may be a promising tool for use in cancer treatment., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Published
2022
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30. How nano-engineered delivery systems can help marketed and repurposed drugs in Alzheimer's disease treatment?

Author

Séguy L, Groo AC, and Malzert-Fréon A

Subjects
Biological Availability, Drug Delivery Systems methods, Drug Repositioning, Humans, Pharmaceutical Preparations, Alzheimer Disease drug therapy
Abstract

Given the continual increase in the number of patients and the lack of curative treatment, the development of new therapies to treat Alzheimer's disease (AD) is becoming ever more urgent. In this review, we summarize the most promising preclinical studies in, and the significant benefits offered by, nanocarriers to realize the full potential of marketed drugs and identify repurposed drugs. No clinical trials have yet been conducted on nanocarriers for drug repurposing in AD. However, recent preclinical results suggest that nanocarriers could overcome the bioavailability and/or selectivity issues of repurposed drugs, improving their therapeutic efficacy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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31. Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer's Disease Treatment.

Author

Séguy L, Guyon L, Maurel M, Verdié P, Davis A, Corvaisier S, Lisowski V, Dallemagne P, Groo AC, and Malzert-Fréon A

Abstract

Background and Purpose: The activation of 5-HT 4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer's disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood-brain barrier shuttle peptide., Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C 18 /HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties., Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

Published
2021
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32. Design of Non-Haemolytic Nanoemulsions for Intravenous Administration of Hydrophobic APIs.

Author

Séguy L, Groo AC, Goux D, Hennequin D, and Malzert-Fréon A

Abstract

Among advanced formulation strategies, nanoemulsions are considered useful drug-delivery systems allowing to improve the solubility and the bioavailability of lipophilic drugs. To select safe excipients for nanoemulsion formulation and to discard any haemolytic potential, an in vitro miniaturized test was performed on human whole blood. From haemolysis results obtained on eighteen of the most commonly used excipients, a medium chain triglyceride, a surfactant, and a solubilizer were selected for formulation assays. Based on a design of experiments and a ternary diagram, the feasibility of nanoemulsions was determined. The composition was defined to produce monodisperse nanodroplets with a diameter of either 50 or 120 nm, and their physicochemical properties were optimized to be suitable for intravenous administration. These nanoemulsions, stable over 21 days in storage conditions, were shown to be able to encapsulate with high encapsulation efficiency and high drug loading, up to 16% ( w / w ), two water practically insoluble drug models: ibuprofen and fenofibrate. Both drugs may be released according to a modulable profile in sink conditions. Such nanoemulsions appear as a very promising and attractive strategy for the efficient early preclinical development of hydrophobic drugs.

Published
2020
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