Towards the Clinical Use of Phytoplankton Carotenoid Pigments to Cure Cancer

International audienceBeyond their major ecolophysiological functions, phytoplankton pigments exert biological and pharmacological activities in human cells that allow considering their clinical use to cure various pathologies. Although much of our knowledge relating to their cell pharmacology and bioactivity has come from in vitro studies in cell culture models, recent in vivo studies have validated the potential of phytoplankton carotenoid pigments to limit inflammation and metabolic disorders, retinal diseases, degenerative diseases, tumor progression, and hepatotoxicity. Aside from these promising results, additional studies are now required to precise their pharmacokinetics, pharmacological targets, and clinical efficacy in humans. The availability of highly purified pigments at rational costs will be a milestone to set up clinical trials and develop new therapies using microalgae pigments. This short paper focuses on the great potential of phytoplankton carotenoid pigments to prevent and cure cancers. Marine and freshwater microalgae have evolved a wide range of pigments that belong to the chlorophylls, carotenoids and phycobiliproteins families. Extensive research has proved that microalgae pigments exert significant biological and pharmacological activities in human cells. Beyond their well-known antioxidant activity, used as a commercial argument to sell algae-based cosmetics and nutraceutics, it is now clearly established that microalgae pigments have a great potential as health nutrients to prevent cancer, as biotechnological probes for cancer diagnosis and as anticancer drugs to trigger cancer cells apoptosis, prevent tumor angiogenesis, reduce the risk of metastasis, sensitize cancer cells to chemotherapy, destroy cancer cells by tumor phototherapy and filter UV to limit cancer cells initiation. Numerous studies aiming to identify antiproliferative molecules from microalgae extracts led to the isolation of carotenoids and to the demonstration of their high antiproliferative, cytostatic, cytotoxic, and/or pro-apoptotic activity in cancer cell cultures [1,2]. As an example, our research team performed the bioguided isolation of pigments from Duniella tertiolecta and found that violaxanthin was the most antiproliferative molecule contained in Dt dichloromethane extract [3]. We also recently reported the strong antiproliferative activity of zeaxanthin and β-cryptoxanthin in human invasive melanoma cells, after their bioguided isolation from Cyanophora paradoxa ethanolic extracts [4]

Sédimentologie, paléontologie et paléoenvironnements côtiers de la région de Porrentruy (Sud-Rhénan, Paléogène, Jura, Suisse): implications géodynamiques

Abstract.: Located in the distal part of the Swiss Molasse Basin and in the southern extension of the Rhine Graben, the conglomeratic deposits belonging to the Gompholithes & Conglomérats stratigraphic group have been the object of detailed sedimentological and paleontological studies. The great number of outcrops that came into sight during the building works of the Transjurane highway in the vicinity of Porrentruy (Swiss Jura) lead to a better understanding of Rupelian paleoenvironments (Early Oligocene). The sedimentological and paleontological studies reveal the existence of coastal environments with Mesozoic limestone cliffs notched by canyons with torrential rivers. Those rivers eroding the Mesozoic series create pebbles deposits forming marine deltas prograding towards North. In protected areas, some lacustrine environments can develop. These conglomeratic deposits are strongly bound to the Rupelian tectonic activity. The rhenish distension and the activity of the transform faults located between the Rhine Graben and the Bresse basin divide the Mesozoic blocks in horst and graben structures, thus allowing the erosion of sediments in higher regions (horst) and their transport in lower zones (graben). The discovery of rare pebbles made of endogene and effusive rocks in those conglomeratic deposits shows a transport coming from the Vosges massifs towards south to the Porrentruy region, probably with the support of a littoral drift. Although the surrection of the Vosges and Schwarzwald massifs (and the beginning of their erosion) is normally attributed to the base of the Miocene, the presence of those pebbles attests the existence of faults putting the basement of the Vosges massif to erosion since the base of Rupelia

Tracking selenium in the Chalk aquifer of northern France: Sr isotope constraints

International audienceGroundwater at the southern and eastern edges of France's Paris Basin has a selenium content that at times exceeds the European Framework Directive's drinking-water limit value of 10 µg/L. To better understand the dynamics of the Chalk groundwater being tapped to supply the city of Lille and the Se origins, we used a combination of geochemical and isotopic tools. Strontium isotopes, coupled with Ca/Sr, Mg/Sr and Se/Sr ratios, were used to identify the main groundwater bodies and their mixings, with the Mg/Sr ratio constraining a ternary system. Groundwater in the agricultural aquifer-recharge zone represents a first end-member and displays the youngest water ages of the catchment along with the highest strontium isotopic signature (0.7084) and low Se contents. Anaerobic groundwater constitutes a second major end-member affected by water-rock interactions over a long residence time, with the lowest strontium isotopic signature (0.7079) and the lowest Se content, its low SF6 content confirming the contribution of old water. Se-rich groundwater containing up to 30 µg/L of Se represents a third major end-member, with an intermediate Sr isotopic ratio, and is mainly constrained by the clayey Se-rich formation overlying the Chalk aquifer. The spatial and temporal Se variability in the groundwater is clearly linked to the presence of this formation identified as Tertiary and also to the hydrological conditions; saturation of the Se-rich clays by oxygenated groundwater enhances Se mobility and also Sr adsorption onto the clays. This multi-tool study including Sr isotopes successfully identified the Se origins in the aquifer and has led to a better understanding of the regional mixing and processes affecting the Chalk groundwater

A Bibliometric Analysis of Microalgae Research in the World, Europe, and the European Atlantic Area

A bibliographic database of scientific papers published by authors affiliated worldwide, especially focused in Europe and in the European Atlantic Area, and containing the keywords “microalga(e)” or “phytoplankton” was built. A corpus of 79,020 publications was obtained and analyzed using the Orbit Intellixir software to highlight the evolution of the research domain. Publication rates from 1960 to 2019, organization of the research, collaboration networks between countries and organizations, emerging and fading research concepts, major studied species, and associated concepts, as well as journals publishing microalgae research were considered. As a result, of the 79,020 papers published worldwide, 26,137 included authors from Europe (33% of world production) and 6989 from the European Atlantic Area (AA) (27% of European production, 9% of world production). The main worldwide scientific research topics found in this study were phytoplankton, community, bloom, diatoms, distribution, ecosystem, coastal, chlorophyll, zooplankton, photosynthesis, and primary production. At the European scale, the most studied topics were related to the environment, food, chemicals, pigments, protein, feed, and drugs. The highest scientific trends and market opportunities analysis identified bioplastics and biostimulants as top emerging concepts at the European level and agricultural, animal feed, and blue biotechnology at the European AA level

Synthesis of C,N'-linked bis-heterocycles using a deprotometalation-iodination-N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells

International audienceBenzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium-zinc combination prepared from ZnCl2*TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine, 1 equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3 equiv). Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81, 82, 67 and 42% yields, respectively. These yields are higher (10% more) than those obtained using ZnCl2*TMEDA (0.5 equiv) and LiTMP (1.5 equiv), except in the case of benzoxazole (10% less). The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2 equiv) and Cs2CO3 (2 equiv), and using acetonitrile as solvent (no other ligand) to provide after 24 h reflux the expected N-arylated azoles in yields ranging from 33 to 81%. Using benzotriazole also led to N-arylation products, but in lower 34, 39, 36 and 6% yields, respectively. A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. Most of the C,N'-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72 h treatment at 10-5 M

Paleogeography of the Upper Rhine Graben (URG) and the Swiss Molasse Basin (SMB) from Eocene to Pliocene

Twenty paleogeographic maps are presented for Middle Eocene (Lutetian) to Late Pliocene times according to the stratigraphical data given in the companion paper by Berger et al. this volume. Following a first lacustrine-continental sedimentation during the Middle Eocene, two and locally three Rupelian transgressive events were identified with the first corresponding with the Early Rupelian Middle Pechelbronn beds and the second and third with the Late Rupelian ≪ Serie Grise ≫ (Fischschiefer and equivalents). During the Early Rupelian (Middle Pechelbronn beds), a connection between North Sea and URG is clearly demonstrated, but a general connection between North Sea, URG and Paratethys, via the Alpine sea, is proposed, but not proved, during the late Rupelian. Whereas in the southern URG, a major hiatus spans Early Aquitanian to Pliocene times, Early and Middle Miocene marine, brackish and freshwater facies occur in the northern URG and in the Molasse Basin (OMM, OSM); however, no marine connections between these basins could be demonstrated during this time. After the deposition of the molasse series, a very complex drainage pattern developed during the Late Miocene and Pliocene, with a clear connection to the Bresse Graben during the Piacenzian (Sundgau gravels). During the Late Miocene, Pliocene and Quaternary sedimentation persisted in the northern URG with hardly any interruptions. The present drainage pattern of the Rhine river (from Alpine area to the lower Rhine Embayment) was not established before the Early Pleistocen

Implementation of agronomical and geochemical modules into a 3D groundwater code for assessing nitrate storage and transport through unconfined Chalk aquifer

International audienceChalk aquifer is the main water resource for domestic water supply in many parts in northern France. In same basin, groundwater is frequently affected by quality problems concerning nitrates. Often close to or above the drinking water standards, nitrate concentration in groundwater is mainly due to historical agriculture practices, combined with leakage and aquifer recharge through the vadose zone. The complexity of processes occurring into such an environment leads to take into account a lot of knowledge on agronomy, geochemistry and hydrogeology in order to understand, model and predict the spatiotemporal evolution of nitrate content and provide a decision support tool for the water producers and stakeholders. To succeed in this challenge, conceptual and numerical models representing accurately the Chalk aquifer specificity need to be developed. A multidisciplinary approach is developed to simulate storage and transport from the ground surface until groundwater. This involves a new agronomic module " NITRATE " (NItrogen TRansfer for Arable soil to groundwaTEr), a soil-crop model allowing to calculate nitrogen mass balance in arable soil, and the " PHREEQC " numerical code for geochemical calculations, both coupled with the 3D transient groundwater numerical code " MARTHE ". Otherwise, new development achieved on MARTHE code allows the use of dual porosity and permeability calculations needed in the fissured Chalk aquifer context. This method concerning the integration of existing multidisciplinary tools is a real challenge to reduce the number of parameters by selecting the relevant equations and simplifying the equations without altering the signal. The robustness and the validity of these numerical developments are tested step by step with several simulations constrained by climate forcing, land use and nitrogen inputs over several decades. In the first time, simulations are performed in a 1D vertical unsaturated soil column for representing experimental nitrates vertical soil profiles (0-30m depth experimental measurements in Somme region). In the second time, this approach is used to simulate with a 3D model a drinking water catchment area in order to compared nitrate contents time series calculated and measured in the domestic water pumping well since 1995 (field in northern France – Avre Basin region). This numerical tool will help the decision-making in all activities in relation with water uses

Synthesis of azafluorenones and related compounds using deprotocupration-aroylation followed by intramolecular direct arylation

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.International audienceThe efficiency of the deprotocupration-aroylation of 2-chloropyridine using lithiocuprates prepared from CuX (X=Cl, Br) and LiTMP (TMP=2,2,6,6-tetramethylpiperidido, 2 equiv) was investigated. CuCl was identified as a more suitable copper source than CuBr for this purpose. Different diaryl ketones bearing a halogen at the 2 position of one of the aryl groups were synthesized in this way from azines and thiophenes. These were then involved in palladium-catalyzed ring closure: substrates underwent expected CH-activation-type arylation to afford fluorenone-type compounds, and were also subjected to cyclization reactions leading to xanthones, notably in the presence of oxygen-containing substituents or reagents

Degradation of the luminance and impedance evolution analysis of an OLED under thermal and electrical stress

Organic light emitting diodes are one of the most innovative light sources. They do not require semiconductor fabrication techniques like the LED family, they are simple to construct and are used in many original applications. The inconvenient of this product is that it does not have a long lasting useful life with more then 10000 hours. Therefore, this paper will present a parametric method to design an aging model of the OLED based on luminance decay and electrical impedance evolution. Accelerated tests using thermal factor and currentdensity will be applied to large warm white OLED panels. A log-normal model for the luminance decay will be merged withdesign of experiments method to include the stress factors as well as impedance characteristics resulting in an effective degradation model that can estimate the lifetime of the OLED