Scientific publications

Grape Cane Extracts as Multifunctional Rejuvenating Cosmetic Ingredient: Evaluation of Sirtuin Activity, Tyrosinase Inhibition and Bioavailability Potential


Magdalena Anna Malinowska, Kévin Billet, Samantha Drouet, Thibaut Munsch, Marianne Unlubayir, Duangjai Tungmunnithum, Nathalie Giglioli-Guivarc’h, Christophe Hano, Arnaud Lanoue

DOI https://doi.org/10.3390/molecules25092203
Scientific Field Life & Health Sciences
Fellow Dr Magdalena Malinowska
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Grape canes are waste biomass of viticulture containing bioactive polyphenols valuable in cosmetics. Whereas several studies reported the cosmetic activities of E-resveratrol, only few described the potential of E-ε-viniferin, the second major constituent of grape cane extracts (GCE), and none of them investigated GCE as a natural blend of polyphenols for cosmetic applications. In this study, we considered the potential of GCE from polyphenol-rich grape varieties as multifunctional cosmetic ingredients. HPLC analysis was performed to quantify major polyphenols in GCE i.e., catechin, epicatechin, E-resveratrol, E-piceatannol, ampelopsin A, E-ε-viniferin, hopeaphenol, isohopeaphenol, E-miyabenol C and E-vitisin B from selected cultivars. Skin whitening potential through tyrosinase inhibition assay and the activation capacity of cell longevity protein (SIRT1) of GCE were compared to pure E-resveratrol and E-ε-viniferin. Drug-likeness of GCE polyphenols were calculated, allowing the prediction of skin permeability and bioavailability. Finally, the present data enabled the consideration of GCE from polyphenol-rich varieties as multifunctional cosmetic ingredients in accordance with green chemistry practices.


Thermal restraint of a bacterial exopolysaccharide of shallow vent origin


Maria Teresa Caccamo, Vincenzo Zammuto, Concetta Gugliandolo, Claire Madeleine-Perdrillat, Antonio Spano, Salvatore Magazu

DOI 10.1016/j.ijbiomac.2018.03.160
Scientific Field Life & Health Sciences
Fellow Prof. Salvatore Magazù
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To dynamically characterize the thermal properties of the fructose-rich exopolysaccharide (EPS1-T14), produced by the marine thermophilic Bacillus licheniformis T14, the Attenuated Total Reflectance Fourier Transform Infra-Red spectroscopy was coupled to variable temperature ranging from ambient to 80 °C.

The spectra were analyzed by the following innovative mathematical tools: i) non-ideal spectral deviation, ii) OH-stretching band frequency center shift, iii) spectral distance, and iv) wavelet cross-correlation analysis.

The thermal restraint analysis revealed that the whole EPS1-T14 system possessed high stability until 80 °C, and suggested that fucose was mainly involved in the EPS1-T14 thermal stability, whereas glucose was responsible for its molecular flexibility.

Our results provide novel insights into the thermal stability properties of the whole EPS1-T14 and into the role of its main monosaccharidic units. As a new biopolymer, the thermostable EPS1-T14 could be used in traditional biotechnology fields and in new biomedical areas, as nanocarriers, requiring high temperature processes.


Access to Unprotected β-Fluoroalkyl β-Amino Acids and Their α-Hydroxy Derivatives


Volodymyr Sukach, Serhii Melnykov, Sylvain Bertho, Iryna Diachenko, Pascal Retailleau, Mykhailo Vovk, Isabelle Gillaizeau

DOI https://doi.org/10.1021/acs.orglett.9b00622
Scientific Field Life & Health Sciences
Fellow Dr Volodymyr Sukach
Link to the publication

Unprotected β-(het)aryl-β-fluoroalkyl β-amino acids and their α-hydroxy derivatives can be readily obtained using a decarboxylative Mannich-type reaction without protection/deprotection steps. This protocol utilizes lithium hexamethyldisilazide and (het)arylfluoroalkyl ketones to generate NH-ketimine intermediates. The mild reaction conditions allow the preparation of original fluorinated β-amino acids as useful building blocks in a practical and scalable manner.


GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors


Samantha Sperduti, Silvia Limoncella, Clara Lazzaretti, Elia Paradiso, Laura Riccetti, Sara Turchi, Ilaria Ferrigno, Jessika Bertacchini, Carla Palumbo, Francesco Potì, Salvatore Longobardi, Robert P. Millar, Manuela Simoni, Claire L. Newton, Livio Casarini

DOI 10.3390/ijms20225548
Scientific Field Life & Health Sciences
Fellow Prof. Manuela Simoni
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Commercial gonadotropin-releasing hormone (GnRH) antagonists differ by 1–2 amino acids and are used to inhibit gonadotropin production during assisted reproduction technologies (ART). In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro. GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist. We evaluated intracellular calcium (Ca2+) and cAMP increases, cAMP-responsive element binding-protein (CREB) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation, β-catenin activation and mouse luteinizing-hormone β-encoding gene (Lhb) transcription by bioluminescence resonance energy transfer (BRET), Western blotting, immunostaining and real-time PCR as appropriate. The kinetics of GnRH-induced Ca2+ rapid increase revealed dose-response accumulation with potency (EC50) of 23 nM in transfected HEK293 cells, transfected SH-SY5Y and LβT2 cells. Cetrorelix inhibited the 3 × EC50 GnRH-activated calcium signaling at concentrations of 1 nM–1 µM, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM–1 µM range in both transfected HEK293 and SH-SY5Y cells in vitro. In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation. All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH. Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 µM GnRH-induced β-catenin activation, Lhb gene expression increase occurring upon LβT2 cell treatment by 1 µM GnRH was similarly inhibited by all antagonists. To conclude, this study has demonstrated Cetrorelix-, Ganirelix- and Teverelix-specific biased effects at the intracellular level, not affecting the efficacy of antagonists in inhibiting Lhb gene transcription.


Follicle-Stimulating Hormone: Fertility and Beyond


Manuela Simoni, Ilpo Huhtaniemi, Daniele Santi, Livio Casarini

DOI https://doi.org/10.3389/fendo.2019.00610
Scientific Field Life & Health Sciences
Fellow Prof. Manuela Simoni
Link to the publication

Editorial on the Research Topic.

Propagating life to the next generation is a hormone-dependent process relying on the individualwish to generate own progeny and resulting in maintenance of species. This Research Topicis dedicated to Follicle–Stimulating Hormone (FSH) and itsreceptor (FSHR) and their rolein reproduction. FSH is a typical example of a drug which entered clinical use in the “pre-evidence-basedmedicine era,” just for its efficacy in stimulating gonadal function and fertility in hypogonadotropichypogonadism. More recently, FSH entered clinical use in controlled ovarian stimulation in orderto obtain multiple follicular growth for assisted reproduction. Given the progressive increase incouple infertility, the demand for assisted reproduction grows steadily and the FSH market isflourishing. Yet, very little was known about the FSH mode of action until a few years ago,and the therapeutic use of FSH is still far from being evidence-based. But great progress in ourunderstanding of FSH action was made in the last two decades and, since not many scientistsaround the world are active in the gonadotropin/FSH research “niche,” we thought it was time tocall them to report to tell us their view on the state-of-the-art. The result is this “Research Topic.”


Glycosylation Pattern and in vitro Bioactivity of Reference Follitropin alfa and Biosimilars


Laura Riccetti, Samantha Sperduti , Clara Lazzaretti , Danièle Klett , Francesco de Pascali , Elia Paradiso, Silvia Limoncella, Francesco Potì, Simonetta Tagliavini, Tommaso Trenti, Eugenio Galano, Angelo Palmese, Abhijeet Satwekar, Jessica Daolio, Alessia Nicoli, Maria Teresa Villani, Lorenzo Aguzzoli, Eric Reiter , Manuela Simoni , Livio Casarini

DOI https://doi.org/10.3389/fendo.2019.00503
Scientific Field Life & Health Sciences
Fellow Prof. Manuela Simoni
Link to the publication

Recombinant follicle-stimulating hormone (FSH) (follitropin alfa) and biosimilar preparations are available for clinical use. They have specific FSH activity and a unique glycosylation profile dependent on source cells. The aim of the study is to compare the originator (reference) follitropin alfa (Gonal-f®)- with biosimilar preparations (Bemfola® and Ovaleap®)-induced cellular responses in vitro. Gonadotropin N-glycosylation profiles were analyzed by ELISA lectin assay, revealing preparation specific-patterns of glycan species (Kruskal-Wallis test; p < 0.05, n = 6) and by glycotope mapping. Increasing concentrations of Gonal-f® or biosimilar (1 × 10−3-1 × 103 ng/ml) were used for treating human primary granulosa lutein cells (hGLC) and FSH receptor (FSHR)-transfected HEK293 cells in vitro. Intracellular cAMP production, Ca2+ increase and β-arrestin 2 recruitment were evaluated by BRET, CREB, and ERK1/2 phosphorylation by Western blotting. 12-h gene expression, and 8- and 24-h progesterone and estradiol synthesis were measured by real-time PCR and immunoassay, respectively. We found preparation-specific glycosylation patterns by lectin assay (Kruskal-Wallis test; p < 0.001; n = 6), and similar cAMP production and β-arrestin 2 recruitment in FSHR-transfected HEK293 cells (cAMP EC50 range = 12 ± 0.9–24 ± 1.7 ng/ml; β-arrestin 2 EC50 range = 140 ± 14.1–313 ± 18.7 ng/ml; Kruskal-Wallis test; p ≥ 0.05; n = 4). Kinetics analysis revealed that intracellular Ca2+ increased upon cell treatment by 4 μg/ml Gonal-f®, while equal concentrations of biosimilars failed to induced a response (Kruskal-Wallis test; p < 0.05; n = 3). All preparations induced both 8 and 24 h-progesterone and estradiol synthesis in hGLC, while no different EC50s were demonstrated (Kruskal-Wallis test; p > 0.05; n = 5). Apart from preparation-specific intracellular Ca2+ increases achieved at supra-physiological hormone doses, all compounds induced similar intracellular responses and steroidogenesis, reflecting similar bioactivity, and overall structural homogeneity.


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The chemical synthesis of C 60 fullerene in the laboratory is still a challenge. In order to achieve this goal, we propose a synthetic route based on the dimerization between two pentacyclopentacorannulene (C 30 H 10) fragments employing the Diels-Alder cycloaddition reaction. Density functional calculations indicate that a step wise non-concerted dimerization mechanism of C 30 H 10 is favored over a one stage dimerization.


Ultrasonic identification technique in recycling of lithium ion batteries


Michiel Postema, Satyajit Phadke, Anthony Novell, Rustem Uzbekov, Cuthbert Nyamupangedengu, Meriem Anouti, Ayache Bouakaz

DOI 10.1109/AFRICON46755.2019.9133954
Scientific Field Materials and Energy sciences
Fellow Prof. Michiel Postema
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The recycling of lithium ion batteries has been mentioned as one of the near-future waste management necessities. In order for recycling to be economically viable, straightforward and cost effective techniques need to be developed to separate the individual materials in a composite electrode. Ultrasonic separation might be such a technique, provided that lithium ion battery microparticles respond predictably to a sound field. Lithium ion battery cathodes contain hydrophobic carbon. Owing to the incompressibility of a solid, the thin gaseous layer surrounding these hydrophobic particles must oscillate asymmetrically, when subjected to ultrasound. Consequently, the harmonic content of the ultrasound signal radiated from hydrophobic microparticles must be higher than that from hydrophilic microparticles with the same size. The question of whether the harmonic signal response generated by physical hydrophobic microparticles present in lithium ion battery cathodes is higher than the harmonic response of other component materials in the cathode is the focus of this paper. The scattering response of cathode materials subjected to 1-MHz ultrasound was measured and compared. The cathode materials C65, PVDF, and NMC respond differently to 1-MHz ultrasound. The superharmonic response of C65 has been attributed to asymmetric oscillations owing to its hydrophobicity. In addition, C65 hydrophobic microparticles might be suitable candidates for harmonic imaging.


Prévention de l’AVC ischémique / Stroke prevention


Kevin Janot, Guillaume Charbonnier, Fakhreddine Boustia, Igor Lima Maldonado, Richard Bibi, Julien Pucheux, Denis Herbreteau

DOI https://doi.org/10.1016/j.lpm.2019.05.001
Scientific Field Life & Health Sciences
Fellow Prof. Igor Lima Maldonado
Link to the publication

L’accident vasculaire cérébral (AVC) est la première cause de handicap acquis de l’adulte, la deuxième cause de démence et la troisième cause de mortalité en France. Parmi les AVC, 89 % sont ischémiques. Le vieillissement de la population laisse présager une augmentation du nombre de patients victimes d’AVC dans les années à venir.

La prévention des infarctus cérébraux est un enjeu important de la prise en charge des AVC compte tenu du risque élevé de récidive. Après un premier infarctus cérébral, le risque de récidive est estimé à 10 % la première année et entre 20 et 30 % à 5 ans. La survenue d’un AVC est favorisée par des facteurs de risque cardiovasculaire connus et accessibles à la prévention. Le contrôle des facteurs de risque comme l’hypertension artérielle (HTA), le diabète, la dyslipidémie et le tabac est indispensable en cas d’AVC d’origine athéromateuse ou de suspicion de pathologie athéroscléreuse sous-jacente. Lorsque la cause d’un infarctus cérébral ou d’un accident ischémique transitoire (AIT) est connue, le traitement spécifique de l’étiologie est un élément indispensable à la prévention secondaire.


Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay


Javad Alizadeh, Shahla Shojaei, Simone da Silva Rosa, Adel Rezaei Moghadam, Amir Zeki, Mohammad Hashemi, Marek Los, Joseph Gordon, Saeid Ghavami

DOI 10.3791/57646
Scientific Field Life & Health Sciences
Fellow Prof. Marek Los
Link to the publication

The Rho GTPase family belongs to the Ras superfamily and includes approximately 20 members in humans. Rho GTPases are important in the regulation of diverse cellular functions, including cytoskeletal dynamics, cell motility, cell polarity, axonal guidance, vesicular trafficking, and cell cycle control. Changes in Rho GTPase signaling play an essential regulatory role in many pathological conditions, such as cancer, central nervous system diseases, and immune system-dependent diseases. The posttranslational modification of Rho GTPases (i.e., prenylation by mevalonate pathway intermediates) and GTP binding are key factors which affect the activation of this protein. In this paper, two essential and simple methods are provided to detect a broad range of Rho GTPase prenylation and GTP binding activities. Details of the technical procedures that have been used are explained step by step in this manuscript.