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Purpose This paper aims to study the dimensions and subdimensions of humanitarian supply chain resilience through the case of an non-governmental organization (NGO) logistics organization facing the international COVID-19 pandemic. Design/methodology/approach The methodology of this empirical research paper is based on a qualitative study using semistructured interviews with key actors of the Médecins Sans Frontières Logistique (MSF Log), NGO during the COVID-19 crisis in 2020 and 2021. Findings The data analysis highlighted four main dimensions of humanitarian supply chain resilience: organizational capacity, collaboration, flexibility and humanitarian culture. The transversal importance of the information system and that of the humanitarian culture were also pointed out. Furthermore, the authors have identified the subdimensions of each dimension; these subdimensions further elaborate the main dimension and provide a more detailed understanding of the concept. These dimensions require both proactive and reactive actions to be effective. Finally, based on these empirical results, a conceptual model of humanitarian supply chain resilience is proposed. Research limitations/implications Additionally, further research can be done to explore the impact of digital technologies on the humanitarian supply chain resilience and how these technologies can be used to improve the resilience of humanitarian supply chains. Additionally, future research can also be conducted to explore how to measure the resilience of humanitarian supply chains and how to develop methods to improve the resilience of these supply chains. Practical implications The dimensions and subdimensions of resilience that have been highlighted may provide a guide for managers to target their actions, both responsively and proactively, to act on resilience over time when facing a crisis such as an international pandemic. Originality/value The value of this research is linked to the findings that result not only from literature about resilience but are also founded on an empirical and qualitative study of an NGO logistics organization facing an international crisis. The research provides an in-depth understanding of the practical application of supply chain resilience in a humanitarian context and the specific challenges and opportunities that arose during the COVID-19 pandemic for MSF Log. It also highlights the importance of information systems and humanitarian culture in maintaining the supply chain resilience. The findings of this research can be used as a guide for other humanitarian organizations to improve their supply chain resilience in times of crisis.

Bryophyllum pinnatum (Lam) Pers. (Crassulaceae) is widely used in folk medicine as leaf juice, aqueous, or hydro-ethanolic extracts. It is also listed as a medicinal plant in several countries such as France and Brazil. The main reported constituents are flavone glycosides, especially those with the rare 3-O-α-l-arabinopyranosyl-(1 → 2)-α-l-rhamnopyranoside moiety. Despite several phytochemical screenings indicating the presence of cyanide derivatives or alkaloids, there are no reports of nitrogenous metabolite characterization from this plant species. Nevertheless, the occurrence and the type of such compounds are of particular interest, as they may account for some of the numerous biological activities and ethnomedicinal uses described for B. pinnatum and could be regarded as chemical/taxonomic markers. Consequently, a hydro-ethanolic extract of B. pinnatum was investigated by using UHPLC-HRMS/MS and the nitrile glucoside sarmentosin was detected for the first time within the genus Bryophyllum/Kalanchoe. Considering the wide use of B. pinnatum and its closely related species for health purposes, the target metabolite was isolated by a combination of centrifugal partition chromatography in elution/extrusion mode and MPLC in order to confirm its structure. A linear, selective, precise, fast, and reliable 1H NMR quantitation method was then developed and validated and may become a tool for easy quality assessment of the plant species. The amount of sarmentosin was determined as 2.07% of the examined sample. Sarmentosin was also detected in Kalanchoe laciniata, confirming the occurrence of this compound within the genus.

International audience; This paper presents a validation of a new protocol for the characterization of drying shrinkage of cement paste. The method consists of using environmental scanning electronic microscope (ESEM) or climatic chamber (CC) assisted by digital image correlation (DIC) to study the drying shrinkage of cement-based materials. The final motivation is to study the influence of the drying rate on cement-based materials’ delayed strain at the microscopic scale. Hence, the impact of specimen shape, size, and the imposed relative humidity history on the drying shrinkage is studied. Results show that for a given material, the amplitude of drying shrinkage is independent of the rate of drying and the specimen shape. Advantage was taken of the two techniques proposed in this paper to perform drying length change measurement both in ESEM and CC.

The alkaloid tazopsine 1 was introduced in the late 2000s as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with the potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, precluding its direct repurposing against the disease. The targeted N-alkylation of nor-DXM 15 produced a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2′-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against P. falciparum liver and blood stages, with respectively 760 ± 130 nM and 2.1 ± 0.4 μM IC50 values, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5- to 8-fold increase in activity relative to DXM 3 against P. falciparum stages I–II and V gametocytes, with 18.5 μM and 13.2 μM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan cycle activity, paving the way for further therapeutic development (e.g., investigation of its prophylactic activity in vivo).

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-products. The major challenge in this approach lies in the application of fundamental discoveries in light-harvesting systems for the improvement of plant or algal photosynthesis. Here, we underline some of the latest fundamental discoveries on the molecular mechanisms and regulation of light harvesting that can potentially be exploited for the optimization of photosynthesis.

The alkaloid tazopsine

International audience; The effect of temperature on water vapour desorption isotherms can be described simply using the Clausius-Clapeyron equation and the isosteric energy of adsorption, the latter conventionally estimated using two (or more) isotherms obtained at different temperatures. This approach has some disadvantages, however, and this article puts forward a simple alternative methodology for characterising this isosteric energy experimentally. Our method is based on monitoring the relative humidity of a cementitious material heated under sealed conditions. The evolution of the relative humidity as a function of temperature makes it possible to directly evaluate the isosteric energy. In practice, the tests are performed using a cell of the type that is used for self-desiccation studies.

In this study, the objective was to verify whether or not the classical Richard-Fick model was able to take into account the size effect on drying. First, mass loss experiments are made on ordinary cement paste cylinders of 3.6 × 18 cm geometry that enable us to calibrate the model parameters. Second, the quality of identification and drying model was checked by predicting mass loss evolution of small prism of 1 × 5 × 10 mm size dried at different steps of relative humidity. The results demonstrate that the present drying model is able to predict the drying of specimen for different sizes and levels of humidity at ambient temperature. And finally, drying shrinkage experiments for different rates of drying are performed on cement paste cylinders of 3.6 × 18 cm; then, the prediction of drying shrinkage evolution was made using a simple model where the drying shrinkage is supposed to be linear with respect to the relative humidity. The result appears to be satisfactory. Since the spatio-temporal evolution of water content is needed as input to shrinkage prediction, the latter result confirms that the identification of drying model parameters is trustworthy.

"Chiniy-tref" (CT) is a traditional preparation used in folk medicine in Martinique Island (French West Indies) that is nowadays mainly taken orally to prevent or act against any "manifestation of evil". CT is easily prepared at home by macerating larvae of the endemic swallowtail Battus polydamas (ssp.) cebriones (Dalman, 1823), sometimes accompanied by a leaf of its host-plant Aristolochia trilobata L., in commercial rum. We have previously reported the detection of nephrotoxic and carcinogenic aristolochic acids (AAs) I and II in CT, leading the Regional Health Agency (ARS) of Martinique to issue an alert regarding the potential risks associated with its consumption in 2015. In order to complete the toxicity risk assessment for oral consumption of CT, a full qualitative analysis of AAs and their analogues (AAAs) was performed, as well as a quantitative determination of the major AAs, namely AAs I and II. The phytochemical profiling of AAAs present in CT, that also corresponds to that of B. polydamas cebriones larvae feeding on A. trilobata, has been established for the first time by ultra-high performance liquid chromatography/electrospray ionization quadrupole time of-flight tandem mass spectrometry. AAs I and II were quantified in a small panel of tinctures by using a validated UHPLC/UV method, allowing us to estimate the probable daily intakes of these toxins by CT consumers. The results proved the existence of a real risk of renal toxicity and carcinogenicity associated with the chronic oral consumption of CT in Martinique, and more generally of similar "snake bottles" throughout the Caribbean.

Ethnopharmacological relevance Previous ethnobotanical surveys from the north Andean part of Chile, where different ethnic groups are co-existing, with the preeminence of Aymara and Atacama traditions, revealed an extensive domestic use of the local flora. In these communities, traditional medicinal uses are mainly related to the treatment of respiratory, gastro-intestinal and urinary disorders, pain and inflammation, which is closely linked to epidemiological observations. Aim of the study As these symptoms may be related to infectious diseases, a bioguided evaluation of antibacterial and antifungal activity was conducted on eighteen species selected with the Taira community, in Ollague. Materials and methods Screening was performed using a large panel of pathogenic germs involved in the main community acquired infectious diseases, represented by Gram positive and Gram negative bacteria of clinical interest and by human pathogenic fungi, using a bioguided approach. Results and conclusions Gram positive strains of clinical interest were highly sensitive to Aloysia deserticola (Verbenaceae) and Krameria lappacea (Krameriaceae) extracts. The bioguided approach led us to identify the isolated neolignan from K. lappacea conocarpan (1), and triterpenoids form A. deserticola (oleanolic acid (6) and ursolic acid (10)), as the main bioactive compounds.

Made available in DSpace on 2019-10-04T12:37:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01. Added 1 bitstream(s) on 2019-10-09T18:34:07Z : No. of bitstreams: 1 S0102-695X2019000200191.pdf: 1411392 bytes, checksum: 5a8ec7aa769f17312d1bd6c4d5ed4f32 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) EU Finatec Natural products have been the most valuable source of chemical compounds in the discovery of novel medicines. Secondary metabolites from terrestrial and marine organisms have found considerable use in the treatment of numerous diseases and have been considered lead molecules both in their natural form and as templates for medicinal chemistry. Brazil has an exceptionally rich biodiversity, and a valuable source of secondary metabolites that can be useful for the development of bioproducts. Ipomoea species, Convolvulaceae, are mostly found in tropical and sub-tropical regions, including South America and many are used for nutritional and medicinal purposes. Ipomoea procumbens Mart. & Choisy is endemic from South America, and this is the first study reported on the chemical composition and biological activities of this species. The present work reports the tentatively identification of natural products present in the extracts using a high performance liquid chromatography-high resolution mass spectrometry method. Additionally, the antioxidant and antifungal biological activities of the leaves, roots and steams extracts and fractions of this species were evaluated. While for the antioxidant activity the hydromethanol fractions (leaves, stem and roots) were more active, the methanol fractions of leaves and stem provided better results for the antifungal assay. (C) 2018 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Farmacognosia. Univ Paris 05, Lab Pharmacognosy, UMR CNRS Ctr Natl Rech Sci, Fac Pharm, Paris, France Univ Estadual Paulista, Inst Quim, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, Dept Quim Organ, Araraquara, SP, Brazil Univ Estadual Londrina, Dept Quim, Londrina, PR, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Lab Micol Clin, Araraquara, SP, Brazil Secretaria Meio Ambiente Estado Sao Paulo, Inst Bot, Sao Paulo, SP, Brazil Univ Estadual Paulista, Inst Quim, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, Dept Quim Organ, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Anal Clin, Lab Micol Clin, Araraquara, SP, Brazil FAPESP: 2010/52327-5 FAPESP: 2013/07600-3 EU: 269301 FAPESP: 2010/17329-7 Finatec: 120/2017

Two aromatic species from the Atacama people traditional medicine, Aloysia deserticola (Phil.) Lu-Irving & O’Leary and Artemisia copa Phil. var. copa, from Antofagasta area (North of Chile)...

Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in traditional medicine all over tropical areas, especially in Brazil, to relieve inflammation-associated symptoms. Flavonol glycosides with unusual sugar moiety are among the major metabolites. Nevertheless, there are not enough quality control studies that can contribute to authentication of B. pinnatum and determination of their markers. As it is also used as medicinal plant in several countries, it is necessary to provide data related to safety, efficacy and quality. In this context, this work aims to isolate the major flavonoids from B. pinnatum hydroethanolic extract, to validate a method to quantify the content of chemical markers and to evaluate their xanthine oxidase inhibition and antioxidant activity. The extract was submitted to centrifugal partition chromatography (CPC). The solvents system CyHex-EtOAc-EtOH-H2O, 0.5:9:3:5.5, v/v/v/v was selected by shake-flask method. Four flavonoids (quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (1), kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (2), quercetin 3-O-α-L-rhamnopyranoside (3) and kaempferol 3-O-α-L-rhamnopyranoside (4)) were isolated in a single and fast CPC run and their structures were confirmed by NMR analysis. An UPLC-DAD quantification method was established for the first time with validation of required parameters, according to RDC 166/2017. The calibration curves were linear with correlation coefficient ranging from 0.9996 to 0.9997 while the values of LOD (0.0077–1.984 ng.mL−1), LOQ (0.0263–6.012 ng.mL−1), recovery (≥ 80.7 %) and inter-day (%RSD ≤ 3.581) and intra-day precision (%RSD ≤ 2.628) were satisfactory. Quantitative analysis of these compounds showed that the proportion of 1, 2 and 3 were 2.43, 0.25 and 0.33 % (24.3 mg.g−1, 0.25 mg.g−1 and 0.33 mg.g−1 of extract), respectively. Moreover, in vitro xanthine oxidase (XO), DPPH and ABTS inhibition were evaluated for the extract and the major flavonoids. Compounds 2 (168 μM) and 3 (124 μM) moderately inhibited XO, while compounds 1 and 3 displayed average radical scavenging activity. In conclusion, our results suggest the flavonoid 1 as a specific marker which may be used for quality control of B. pinnatum hydroethanolic leaves extract.

EDF operates a fleet of 56 nuclear reactors. For 24 of these reactors, the concrete containment building is a double wall structure. The inner wall is prestressed and has no metallic liner. Every ten years, the leak-tightness of the inner wall is verified by performing a pressure test. The leakage rate has to remain below a given threshold. As time passes, the leakage rate is getting closer to this threshold, so important coating programs are underway to keep the leakage rate within the regulatory limits. Therefore, it is important for EDF to be able to forecast the evolution of leakage, which depends on the concrete saturation and the level of prestress. The prestress decrease is related to creep and shrinkage of concrete and tendons relaxation (this last factor is considered negligible at ambient temperature). To tackle this issue, EDF has launched an important research program around the VERCORS mock-up, which is a containment building at scale 1/3 and has used this research program to improve its ability to predict the evolution of leak-tightness with time. In this paper, the different tools of the digital twin are presented, as well as an example of the use of the models originally developed on the VERCORS mock-up to help the choice of coating strategy for the third pressure test of an industrial containment building.

Cryptophycin-1 is a cyanotoxin produced by filamentous cyanobacteria. It has been evaluated as an anticancer agent with great potential. However, its synthesis provides insufficient yield for industrial use. An alternative solution for metabolite efficient production is to stress cyanobacteria by modifying the environmental conditions of the culture (Nostoc sp. ATCC 53789). Here, we examined the effects of light photoperiod, wavelength, and intensity. In light photoperiod, photoperiods 24:0 and 16:8 (light:dark) were tested while in wavelength, orange-red light was compared with blue. Medium, high, and very high light intensity experiments were performed to test the effect of light stress. For a 10-day period, growth was measured, metabolite concentration was calculated through HPLC, and the related curves were drawn. The differentiation of light wavelength had a major effect on the culture, as orange-red filter contributed to noticeable increase in both growth and doubled the cyanotoxin concentration in comparison to blue light. Remarkably, constant light provides higher cryptophycin yield, but slightly lower growth rate. Lastly, the microorganism prefers medium light intensities for both growth and metabolite expression. The combination of these optimal conditions would contribute to the further exploitation of cryptophycin.

Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.

Cette relecture du phénomène du e-paiement qu’est le portefeuille électronique MoMo s’intéresse à l’adoption large et rapide d’une application au Congo Brazzaville. Cette application fut développée initialement au Kenya, elle est aujourd’hui présente massivement en Afrique. Elle offre plusieurs services originaux et intuitifs et a été rapidement adoptée par les utilisateurs au Congo. Nous proposons d’analyser les déterminants de cette adoption, en nous appuyant sur le corpus théorique lié à l’adoption des technologies de l'information (Davis, 1989 ; Venkatesh, 2000 ; Gallivan, 2001 ; Venkatesh et Bala, 2008) et sur les spécificités socio-économiques du Congo Brazzaville. Cet article s'appuie sur une recherche empirique avec une phase d’analyse exploratoire et de compréhension de l’environnement des primo adoptants qui se concentre ici sur l’inversion de la logique de l’adoption des TI.

A series of 10 natural and semisynthetic flavonoids (1 to 10) were obtained from Gardenia oudiepe (Rubiaceae), an endemic plant from New Caledonia. Most of them were polymethoxylated flavones (PMFs) of rare occurrence. After a cell viability screening test, PMFs 2 and 3 showed significant cytotoxic activity against A2058 human melanoma cells (IC50 = 3.92 and 8.18 μM, respectively) and were selected for in-depth pharmacological assays. Both compounds inhibited cell migration and induced apoptosis and cell cycle arrest after 72h of treatment. Immunofluorescence assays indicated that these outcomes were possibly related to the induction of cytoskeleton disruption associated to actin and tubulin depolymerization. These data were confirmed by molecular docking studies, which showed a good interaction between PMFs 2 and 3 and tubulin, particularly at the colchicine binding site. As A2058 are considered as chemoresistant to conventional chemotherapy, compounds 2 and 3 (½IC50) were associated to clinically-used antimelanoma drugs (vemurafenib and dacarbazine) and combined therapies efficacy was assessed by the MTT assay. PMFs 2 restored the sensitivity of A2058 cells to dacarbazine treatment (IC50 = 49.38 μM vs. >100 μM). Taken together, these data suggest that PMFs from G. oudiepe could be potential leaders for the design of new antimelanoma drugs.

Pseudomonas aeruginosa is capable to deploy a collection of virulence factors that are not only essential for host infection and persistence, but also to escape from the host immune system and to become more resistant to drug therapies. Thus, developing anti-virulence agents that may directly counteract with specific virulence factors or disturb higher regulatory pathways controlling the production of virulence armories are urgently needed. In this regard, this study reports that Pistacia lentiscus L. fruit cyclohexane extract (PLFE1) thwarts P. aeruginosa virulence by targeting mainly the pyocyanin pigment production by interfering with 4-hydroxy-2-alkylquinolines molecules production. Importantly, the anti-virulence activity of PLFE1 appears to be associated with membrane homeostasis alteration through the modulation of SigX, an extracytoplasmic function sigma factor involved in cell wall stress response. A thorough chemical analysis of PLFE1 allowed us to identify the ginkgolic acid (C17:1) and hydroginkgolic acid (C15:0) as the main bioactive membrane-interactive compounds responsible for the observed increased membrane stiffness and anti-virulence activity against P. aeruginosa. This study delivers a promising perspective for the potential future use of PLFE1 or ginkgolic acid molecules as an adjuvant therapy to fight against P. aeruginosa infections.

Three novel tracers designed as fluorescent surrogates of artemisinin-derived antimalarial drugs (i.e., dihydroartemisinin, artemether, arteether, and artemisone) were synthesized from dihydroartemisinin. One of these tracers, corresponding to a dihydroartemisinin/artemether/arteether mimic, showed a combination of excellent physicochemical and biological properties such as hydrolytic stability, high inhibitory potency against blood-stage parasites, similar ring-stage survival assay values than the clinical antimalarials, high cytopermeability and specific labeling of live P. falciparum cells, alkylation of heme, as well as specific covalent labeling of drug-sensitive and drug-resistant P. falciparum proteomes at physiological concentrations, consistent with a multitarget action of the drugs. Our study demonstrates that probes containing the complete structural core of clinical artemisinin derivatives can be stable in biochemical and cellular settings, and recapitulate the complex mechanisms of these frontline, yet threatened, antimalarial drugs.

International audience; A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives meth-oxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of he-mozoin formation is totally or partially responsible for its antiparasitic effect.

Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.

Demand for active, natural, safe and biomimetic (similar to human molecules) plantderived cosmetic ingredients is always greater because consumers are increasingly suspicious of the potential toxicity of current ingredients. In this context, interest has increased for polar lipids like ceramides, sphingolipids or glycolipids that share structural properties with the skin lipids. In the same manner, processes to obtain such lipids should be driven by the principles of green chemistry and sustainable development. The identified needs are biodegradability, biocompatibility, efficiency, quality and profitability. In this research for new and novel natural or ‘green’ compounds, the development of bioactive lipids thanks to ecofriendly processes has obviously intensified, especially for cosmetic and agro-food industries. This paper reviews extraction methods for polar lipids (glycolipids and phospholipids), especially ecoprocesses (supercritical fluid extraction, microwaves, sonication, enzyme extraction…), and promising chromatographic methods like countercurrent chromatography, supercritical fluid chromatography or high performance chromatography coupled to mass spectrometry Interests of polar lipids for cosmetic industries are exemplified to show their broad applications mostly relying on their amphiphilic properties allowing them to play functional roles (liposome or micelle structures for example) or physiological roles (skin barrier function or anti-ageing effect).