Scientific Publications

Muzamil Shah , Sabir Nawaz , Hasnain Jan , Noor Uddin , Ashaq Ali , Sumaira Anjum, Nathalie Giglioli-Guivarc'h f, Christophe Hano, Bilal Haider Abbasi
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The purpose of current study was green synthesis of silver nanoparticles (AgNPs) from seeds and wild Silybum plants in comparison with their respective extracts followed by characterization and biological potency. The biologically synthesized AgNPs were subjected to characterization using techniques like XRD, FTIR, TEM, HPLC and SPE. Highly crystalline and stable NPs were obtained using Silybum wild plant (NP1) and seeds (NP3) with size range between 18.12 and 13.20 nm respectively. The synthesized NPs and their respective extracts revealed a vast range of biological applications showing antibacterial, antioxidant, anti-inflammatory, cytotoxic and antiaging potencies. The highest antioxidant activity (478.23 ± 1.9 μM, 176.91 ± 1.3 μM, 83.5 ± 1.6% μgAAE/ mg, 156.32 ± 0.6 μgAAE/mg) for ABTS, FRAP, FRSA, TRP respectively was shown by seed extract (NP4) followed by highest value of (117.35 ± 0.9 μgAAE/mg) for TAC by wild extract (NP2). The highest antifungal activity (3 mm ± 0.76) against Candida albicans was shown by NP3 while antibacterial activity of (6 mm against Klebsiella pneumonia) was shown by NP3 and NP4. The highest anti-inflammatory activity (38.56 ± 1.29 against COX1) was shown by NP2. Similarly, the high value of (48.89 ± 1.34 against Pentosidine-Like AGEs) was shown by NP4. Also, the high anti-diabetic activity (38.74 ± 1.09 against α-amylase) was shown by NP4. The extracts and the synthesized NPs have shown activity against hepato-cellular carcinoma (HepG2) human cells. The HPLC analysis revealed that the highest value of silymarin component (silybin B 2289 mg/g DW) was found for NP4. Silydianin is responsible for capping. Among the green synthesized AgNPs and the extracts used, the effect of NP4 was most promising for further use.

Sullivan Renouard , Cyrielle Corbin, Samantha Drouet , Barbara Medvedec, Joël Doussot, Cyril Colas , Benoît Maunit , Avninder Bhambra , Eric Gontier, Nathalie Jullian, François Mesnard , Michèle Boitel-C
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Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.

Bilal Haider Abbasi, Adnan Zahir, Waqar Ahmad , Muhammad Nadeem , Nathalie Giglioli-Guivarc’h , Christophe Hano (3)
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Zinc oxide nanoparticles (NPs) have emerged as a novel elicitor for enhanced biosynthesis of secondary metabolites in in vitro plant cell cultures. The current study was aimed to explore elicitation abilities of ZnO-NPs for enhanced accumulation of lignans and neolignans in cell cultures of Linum usitatissimum. We optimized concentration of zinc oxide NPs before carrying out a full-fledged experiment. Subsequently, an optimum dose of 100 mg/l was introduced into the culture medium on day 0, days 0 and 15, and finally days 0 and 25. We observed that repeated elicitation stimulated various parameters and physiological responses in Linum usitatissimum cell cultures than one-time elicitation. Repeated elicitation of cell cultures on day 0 and 15 resulted in highest fresh weight (412.16 g/l) and lignans production (secoisolariciresinol diglucoside 284.12 mg/l: lariciresinol diglucoside 86.97 mg/l). Contrarily, repeated elicitation on day 0 and 25 resulted in highest DW (13.53 g/l), total phenolic production (537.44 mg/l), total flavonoid production (123.83 mg/l) and neolignans production (dehydrodiconiferyl alcohol glucoside 493.28 mg/l: guaiacylglycerol-β-coniferyl alcohol ether glucoside 307.69 mg/l). Enhancement in plant growth and secondary metabolites accumulation was several fold higher than controls. Furthermore, a linear relationship existed between total phenolic and flavonoid contents which in turn was correlated with higher antioxidant activities.

Samantha Drouet, Bilal Haider Abbasi, Annie Falguieres , Waqar Ahmad , S. Sumaira , Clothilde Ferroud , Joël Doussot, Jean Raymond Vanier, Christophe Hano
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Fruits of Silybum marianum (L.) Gaernt are the main source of taxifolin derived flavonolignans. Together, these molecules constitute a mixture called silymarin with many useful applications for cosmetic and pharmaceutic industries. Here, a validated method for the separation of the silymarin constituents has been developed to ensure precision and accuracy in their quantification. Each compound was separated with a high reproducibility. Precision and repeatability of the quantification method were validated according to the AOAC recommendations. The method was then applied to study the natural variability of wild accessions of S. marianum. Analysis of the variation in the fruits composition of these 12 accessions from Pakistan evidenced a huge natural diversity. Correlation analysis suggested a synergistic action of the different flavonolignans to reach the maximal antioxidant activity, as determined by cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) assays. Principal component analysis (PCA) separated the 12 accessions into three distinct groups that were differing from their silymarin contents, whereas hierarchical clustering analysis (HCA) evidenced strong variations in their silymarin composition, leading to the identification of new silybin-rich chemotypes. These results proved that the present method allows for an efficient separation and quantification of the main flavonolignans with potent antioxidant activities.

AlbaHafiza Rida Riaz
Syed Salman Hashmi
Tariq Khan
Christophe Hano
Nathalie Giglioli-Guivarc’h
Bilal Haider Abbasi
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Melatonin as plant growth regulator induces differential effects on metabolites that are responsible for reduction, capping and stabilization of zinc oxide nanoparticles. Phytochemical analysis of callus cultures was performed and results were compared with callus cultures supplemented with other plant growth regulators (α-napthalene acetic acid, 2,4-dichlorophenoxy acetic acid and thidiazuron). Highest total phenolic and flavonoid content [42.23 mg of gallic acid equivalent (GAE) g−1 DW and 36.4 mg of (quercetin equivalent) g−1 DW, respectively] were recorded at melatonin (1.0 µM) + NAA (13.5 µM). ZnONPs were synthesized from NAA (13.5 µM) and melatonin (1.0 µM) + NAA (13.5 µM)-induced calli extracts separately and characterized via X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). FTIR analysis confirmed the presence of phenolics and flavonoids that were mainly found responsible for reduction and capping of ZnONPs. SEM analysis showed triangular shaped ZnONPs synthesized from melatonin + NAA callus extract and these NPs were more dispersed as compared to the spherical-agglomerates of ZnONPs synthesized from NAA-mediated callus extract. Melatonin + NAA callus extract-mediated ZnONPs (having smaller size) were more potent against multiple drug resistant bacterial strains, e.g. Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa by producing zone of inhibitions 17 ± 0.76 mm,10 ± 0.57 mm and 13 ± 0.54 mm, respectively.

Waqar Ahmad
Muhammad Nadeem
Adnan Zahir
Laurine Garros
Samantha Drouet
Sullivan Renouard
Joel Doussot
Nathalie Giglioli-Guivarc’h
Christophe Hano
Bilal Haider Abbasi
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Linum usitatissimum is a source of pharmacologically active lignans and neolignans. An effective protocol has been established for the enhanced biosynthesis of lignans and neolignans in cell cultures of Linum usitatissimum by using chitosan addition. Gene expression analysis of monolignols (PAL, CCR and CAD), lignans (DIR, PLR and UGT) and neolignans (PCBER) biosynthetic genes by RT-qPCR as well as monolignol biosynthetic PAL, CCR and CAD enzyme activities evidenced a stimulation following chitosan treatment. Validated reverse phase high-performance liquid chromatography coupled to diode array detection was used to quantify secoisolariciresinol diglucoside (SDG) and lariciresinol diglucoside (LDG), dehydrodiconiferyl alcohol glucoside (DCG) and guaiacylglycerol-β-coniferyl alcohol ether glucoside (GGCG) showed that chitosan treated cell cultures had better accumulation of these metabolites. Maximum enhancements of 7.3-fold (28 mg/g DW) occurred for LDG, 3.5-fold (58.85 mg/g DW) in DCG and while the least enhancement of 2-fold (18.42 mg/g DW) for SDG was observed in 10 mg/l chitosan treated cell cultures than to controls. Furthermore, same concentration of chitosan also resulted in 1.3-fold increase in antioxidant activity. Compared to the lignans and neolignans accumulations observed in wild type and RNAi-PLR transgenic flaxseeds, chitosan-treated cell cultures appeared to be a very effective production system for these compounds.

Saridakis Emmanuel
Vishwakarma Rishi
Lai-Kee-Him Josephine
Martin Kevin
Simon Isabelle
Cohen-Gonsaud Martin
Coste Franck
Bron Patrick
Margeat Emmanuel
Boudvillain Marc
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The bacterial Rho factor is a ring-shaped motor triggering genome-wide transcription termination and R-loop dissociation. Rho is essential in many species, including in Mycobacterium tuberculosis where rho gene inactivation leads to rapid death. Yet, the M. tuberculosis Rho [MtbRho] factor displays poor NTPase and helicase activities, and resistance to the natural Rho inhibitor bicyclomycin [BCM] that remain unexplained. To address these issues, we solved the cryo-EM structure of MtbRho at 3.3 Å resolution. The MtbRho hexamer is poised into a pre-catalytic, open-ring state wherein specific contacts stabilize ATP in intersubunit ATPase pockets, thereby explaining the cofactor preference of MtbRho. We reveal a leucine-to-methionine substitution that creates a steric bulk in BCM binding cavities near the positions of ATP γ-phosphates, and confers resistance to BCM at the expense of motor efficiency. Our work contributes to explain the unusual features of MtbRho and provides a framework for future antibiotic development.

Łukaszyk Ewa Anna
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This paper aims to reflect on the perspectives of a critical return to certain aspects of the Postelian heritage, while in the recent decades the figure of this heterodox Renaissance thinker has been downgraded from fascinating to merely secondary. Indeed, his equation between intercultural communication and universal concordia remains generally valid to the present day, even for those who do not share his Adamitic and cabbalistic conceptions of language. On the other hand, his concept of congregator mundi appears as a valuable starting point for the discussion on the role and prerogatives of the intellectual as a mediator between human societies and the transcendent sphere. One may compare it with the recent thought of Giorgio Agamben, re-collocating the intellectual and the cultural critic in the line of the monotheistic prophets.

Moesgaard Jens-Christian
Sarah Guillaume
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Les résultats que nous présentons ici ont été obtenus dans le cadre d’un projet de recherche actuellement en cours, portant sur la monnaie ducale normande au Xe siècle. Ce projet a été rendu possible grâce à une bourse de recherche accordée par Le Studium, qui a pour mission de faire venir des chercheurs étrangers (in casu JCM) dans la Région Centre-Val de Loire pendant un an pour mener un projet de recherche en collaboration avec des chercheurs de la région (in casu Marc et GS de l’IRAMAT-CEB, CNRS/Université d’Orléans, UMR 5060). Prenant comme point de départ l’étude incontournable de Françoise Dumas portant sur les 8584 monnaies conservées du trésor de Fécamp, enfoui vers 980/9853 , notre projet aboutira à une monographie sur la monnaie normande du Xe siècle. Il nous a cependant semblé que l’aspect que nous présentons ici a une valeur exemplaire qui justifie sa publication en avant-première. Un de nos objectifs est l’étude de la composition élémentaire des pièces, spécialité de l’IRAMAT-CEB. Nous avons pour l’heure analysé 134 monnaies normandes par LA-ICP-MS (spectrométrie de masse couplée à un plasma inductif avec prélèvement par ablation laser), une méthode d’analyse quasi-non destructive qui permet de doser les constituants majeurs des alliages monétaires (dans ce cas l’argent et le cuivre) ainsi qu’un grand nombre d’éléments mineurs et traces.

Traversino Di Cristo Massimiliano
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Among the most debated questions of today's historiography, comparison is increasingly relevant. This is mainly due to the impact it has on fields of study as different as anthropology, law, religion, history, etc., and the extremely variegated articulation to which it gives rise between them. In my paper, I will concentrate on the ambit of normative history and consider the case of Alberico Gentili (†1608). With respect to Gentili, comparison helps us trace the role of theology and religious ideas in early-modern legal debates on prince and sovereignty. Special attention will be given to the distinction between God’s absolute and ordered power (potentia Dei absoluta and ordinata) and to Gentili’s image of Luther.