Brice Martin Couillaud  Dr. Philippe Espeau  Dr. Nathalie Mignet  Dr. Yohann Corvis 《ChemMedChem》2019,14(1):8-23

The solid-form screening of active principal ingredients is a challenge for pharmaceutical drug development, as more than 80 % of marketed drugs are formulated in the solid form. A broad and comprehensive study of the various solid forms of drugs is needed to enhance their translation into the clinic. Therefore, the most suitable solid form must be taken into consideration regarding ex vivo and in vivo stability, targeting, solubility, dissolution rate, and bioavailability. In this review, techniques of solid-form screening are covered, including differences in solid forms such as polymorphs, solvates, salts, co-crystals, and amorphous particles. Moreover, solid drug size reduction is also discussed, with insight into the emergence of drug nanocrystal formulations. An overview of the smallest nanocrystals reported in the literature and on the market is also provided, along with their applications and routes of administration.  相似文献   

    

Cline Lafarge  Nathalie Cayot 《Food Science & Nutrition》2019,7(3):918-929

Some green extraction methods were selected and tested for the extraction of volatile compounds from different samples of the microalga Chlorella vulgaris: ultrasound‐assisted liquid–liquid extraction using environment‐friendly solvents (LLE) and solid‐phase microextraction (SPME). The obtained profiles of volatile chemical compounds were different. Only one molecule was found in common to both extractions. Using the SPME method, the main chemical classes of identified volatile compounds were sulfuric compounds, aldehydes, and alcohols. Using the LLE method, the volatile profile was more balanced with alkanes, fatty acids, terpenes, alcohols, and aldehydes. Multivariate data analyses permitted discrimination among samples. Additionally, the relationship between the physicochemical properties of identified volatile compounds and the methods of extraction was studied. The results showed that the LLE extraction allowed the extraction of volatile compounds having a high boiling point (>160°C) and a high log P (>3). The SPME method was more effective to extract volatile compounds with a low boiling point (<160°C) and a low log P (<3). It is thus necessary to combine several extraction methods to obtain a complete view of the volatile profile for microalgae samples.  相似文献   

    

Mariona Rabionet  Pauline Bernard  Melanie Pichery  Christian Marsching  Aline Bayerle  Shaalee Dworski  Mustafa A. Kamani  Chandramohan Chitraju  Nina L. Gluchowski  Katlyn R. Gabriel  Abolfazl Asadi  Philipp Ebel  Menno Hoekstra  Sabrina Dumas  James M. Ntambi  Anders Jacobsson  Klaus Willecke  Jeffrey A. Medin  Nathalie Jonca  Roger Sandhoff 《Lipids》2022,57(3):183-195

1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1-OAC levels indicating they are one source of epidermal 1-OACs. In search of potential enzymes responsible for 1-OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl-CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). Overall levels of 1-OACs did not decrease in any mouse model. In Cers3 and Dgat2-deficient epidermis they even increased in correlation with deficient skin barrier function. Dagt2 deficiency reshapes 1-OAC synthesis with an increase in 1-OACs with N-linked non-hydroxylated fatty acids and a 60% decrease compared to control in levels of 1-OACs with N-linked hydroxylated palmitate. As none of the single enzyme deficiencies we examined resulted in a lack of 1-OACs, we conclude that either there is functional redundancy in forming 1-OAC and more than one enzyme is involved, and/or an unknown acyltransferase of the epidermis performs the final step of 1-OAC synthesis, the implications of which are discussed.  相似文献   

    

Luis Benet  Luca Ferranti  Nathalie Revol 《Concurrency and Computation》2024,36(1):e7856

As developers of libraries implementing interval arithmetic, we faced the same difficulties when it comes to testing our libraries. What must be tested? How can we devise relevant test cases for unit testing? How can we ensure a high (and possibly 100%) test coverage? Before considering these questions, we briefly recall the main features of interval arithmetic and of the IEEE 1788-2015 standard for interval arithmetic. After listing the different aspects that, in our opinion, must be tested, we contribute a first step towards offering a test suite for an interval arithmetic library. First we define a format that enables the exchange of test cases, so that they can be read and tried easily. Then we offer a first set of test cases, for a selected set of mathematical functions. Next, we examine how the Julia interval arithmetic library, IntervalArithmetic.jl, actually performs to these tests. As this is an ongoing work, we list extra tests that we deem important to perform.  相似文献   

    

Claire Plissonneau  Adeline Sivignon  Benoit Chassaing  Frederic Capel  Vincent Martin  Monique Etienne  Ivan Wawrzyniak  Pierre Chausse  Frederic Dutheil  Guillaume Mairesse  Guillaume Chesneau  Nathalie Boisseau  Nicolas Barnich 《International journal of molecular sciences》2022,23(11)

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn’s disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.  相似文献   

    

Louise Fliedel  Khair Alhareth  Johanne Seguin  Marwa El-Khashab  Audrey Chissey  Nathalie Mignet  Thierry Fournier  Karine Andrieux 《International journal of molecular sciences》2022,23(11)

Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design.  相似文献   

    

Julie Bigarreau  Nathalie Rouach  Anselme L. Perrier  Franck Mouthon  Mathieu Charvriat 《International journal of molecular sciences》2022,23(3)

Generation of relevant and robust models for neurological disorders is of main importance for both target identification and drug discovery. The non-cell autonomous effects of glial cells on neurons have been described in a broad range of neurodegenerative and neurodevelopmental disorders, pointing to neuroglial interactions as novel alternative targets for therapeutics development. Interestingly, the recent breakthrough discovery of human induced pluripotent stem cells (hiPSCs) has opened a new road for studying neurological and neurodevelopmental disorders “in a dish”. Here, we provide an overview of the generation and modeling of both neuronal and glial cells from human iPSCs and a brief synthesis of recent work investigating neuroglial interactions using hiPSCs in a pathophysiological context.  相似文献   

    

Kim Doyon-Lalibert  Matheus Aranguren  Michelle Byrns  Josiane Chagnon-Choquet  Matteo Paniconi  Jean-Pierre Routy  Ccile Tremblay  Marie-Claude Quintal  Nathalie Brassard  Daniel E. Kaufmann  Johanne Poudrier  Michel Roger 《International journal of molecular sciences》2022,23(23)

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Lou Legouez  Brnice Le Dieu-Lugon  Shrine Feillet  Gaëtan Riou  Melissa Yeddou  Thibault Plouchart  Nathalie Dourmap  Marie-Anne Le Ray  Stphane Marret  Bruno J. Gonzalez  Carine Cleren 《International journal of molecular sciences》2022,23(24)

Cerebral palsy (CP) is defined as permanent disorders of movement and posture. Prematurity and hypoxia–ischemia (HI) are risk factors of CP, and boys display a greater vulnerability to develop CP. Magnesium sulfate (MgSO₄) is administered to mothers at risk of preterm delivery as a neuroprotective agent. However, its effectiveness is only partial at long term. To prolong MgSO₄ effects, it was combined with 4-phenylbutyrate (4-PBA). A mouse model of neonatal HI, generating lesions similar to those reported in preterms, was realized. At short term, at the behavioral and cellular levels, and in both sexes, the MgSO₄/4-PBA association did not alter the total prevention induced by MgSO₄ alone. At long term, the association extended the MgSO₄ preventive effects on HI-induced motor and cognitive deficits. This might be sustained by the promotion of oligodendrocyte precursor differentiation after HI at short term, which led to improvement of white matter integrity at long term. Interestingly, at long term, at a behavioral level, sex-dependent responses to HI were observed. This might partly be explained by early sex-dependent pathological processes that occur after HI. Indeed, at short term, apoptosis through mitochondrial pathways seemed to be activated in females but not in males, and only the MgSO₄/4-PBA association seemed to counter this apoptotic process.  相似文献   

    

Nathalie Jedrecy  Vishal Jagtap  Christian Hebert  Loïc Becerra  David Hrabovsky  Antoine Barbier  Xavier Portier 《Advanced Electronic Materials》2021,7(1):2000723

Resistive switching in oxide-based structures is intensively studied for the development of ultra-fast non-volatile memories with low consumption and neuromorphic electronic devices. Here, evidence of interface-controlled, reversible, bi-polar resistance switch in prototype multiferroic BaTiO₃/La_0.75Sr_0.25MnO₃ (BTO/LSMO) system is given. The analysis of current–voltage hysteresis curves of a thick Au/BTO/LSMO structure reveals the existence of a 2.55 nm-thick barrier layer at the bottom BTO/LSMO interface, leading to a tunnel electroresistance of ≈1700%. In the native state where BTO polarization points downward, high resolution electron microscopy and electron energy loss spectroscopy show Ba/(La,Sr) and Ti/Mn cationic intermixing, together with a valency reduction of Mn cations and an oxygen deficiency at the interface. This results in a high resistance state, due to partial loss of the metallicity and of the double exchange magnetic interaction in the oxygen-deficient LSMO. The switch to the low resistance state, achieved by upward electric field, is explained in terms of re-oxydation of Mn cations at the interface (decrease of the Mn3+/Mn4+ ratio), with oxygen vacancies migration from LSMO to BTO. This work emphasizes the crucial role of ionic exchanges and of redox processes at interfaces, both on ferroelectric bound charge screening and on resistive switching.  相似文献