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Jamaaoui A.,CNRS Heterogeneous Materials Study Group | Pop O.,CNRS Heterogeneous Materials Study Group | Dubois F.,CNRS Heterogeneous Materials Study Group | Costa G.,CNRS Chemistry of Natural Substances Laboratory
Theoretical and Applied Fracture Mechanics | Year: 2017

The objective of this study is to estimate the influence of mixed mode on the global fracture energy. The experimental tests were carried out using three Douglas genotypes. In order to evaluate the fracture parameters the Wedge Splitting Tests were performed. The fracture parameters were estimated from the optical measurements coupled with numerical and analytical approaches. Firstly, the fracture energy was estimated from the work of fracture calculated from the splitting force - Crack Opening Displacement curve. In this case, the Crack Opening Displacement was measured by means of Mark Tracking method. Secondly, the fracture parameters and, consequently the fracture energy was evaluated using an integrated mixed mode approach. In this second case, the experimental measurements were performed by Digital Image Correlation. The fracture energy corresponding to opening and shear modes was calculated by using an adjustment procedure coupled with Stress Intensity Factor calculation and the phase angle. This second approach allowing the calculation of fracture energy without the influence of experimental noises. The results show that the proposed integrated mixed mode approach allows evaluate the part of each mode in the fracture process. © 2017 Elsevier Ltd.


Ghezali L.,CNRS Chemistry of Natural Substances Laboratory | Leger D.Y.,CNRS Chemistry of Natural Substances Laboratory | Limami Y.,CNRS Chemistry of Natural Substances Laboratory | Cook-Moreau J.,University of Limoges | And 2 more authors.
Experimental Cell Research | Year: 2013

Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both celllines. © 2013 Elsevier Inc.


Di Meo F.,CNRS Chemistry of Natural Substances Laboratory | Sancho Garcia J.C.,University of Alicante | Dangles O.,University of Avignon | Trouillas P.,CNRS Chemistry of Natural Substances Laboratory | Trouillas P.,University of Mons
Journal of Chemical Theory and Computation | Year: 2012

Anthocyanidins are a class of π-conjugated systems responsible for red, blue, and purple colors of plants. They exhibit the capacity of aggregation in the presence of other natural compounds including flavonols. Such complexations induce color modulation in plants, which is known as copigmentation. It is largely driven by π-interactions existing between pigments and copigments. In this work, the energies of copigmentation-complexation and self-association are systematically evaluated for an anthocyanidin/flavonol couple prototype (3-O-methylcyanidin/quercetin). To describe noncovalent interactions, DFT-D appears mandatory to reach a large accuracy. Due to the chemical complexity of this phenomenon, we also aim at assessing the relevance of both B3P86-D2 and ωB97X-D functionals. The benchmarking has shown that B3P86-D2 possesses enough accuracy when dealing with π-π interactions with respect to both spin component scaled Møller-Plesset second-order perturbation theory post Hartree-Fock method and experimental data. UV-vis absorption properties are then evaluated with time-dependent DFT for the different complexes. The use of range-separated hybrid functionals, such as ωB97X-D, helped to correctly disentangle and interpret the origin of the UV-vis experimental shifts attributed to the subtle copigmentation phenomenon. © 2012 American Chemical Society.


Saad N.,CNRS Chemistry of Natural Substances Laboratory | Delattre C.,GREENTECH Biotechnologies | Urdaci M.,French National Center for Scientific Research | Schmitter J.M.,University of Bordeaux 1 | And 2 more authors.
LWT - Food Science and Technology | Year: 2013

Probiotics and prebiotics play an important role in human nutrition. In recent years there has been a significant increase in research on the characterization and verification potential health benefits associated with the use of probiotic and prebiotic. The main effects attributed to selected probiotics/prebiotic products have been proved by clinical trials, while others have been acquired on the basis of in vitro tests which require in vivo transposition in order to be validated. The main clinical reports in the literature for the application of probiotic have been done for the treatment of infectious diseases including viral, bacterial or antibiotic associated diarrhoea, relief of chronic bowel inflammatory diseases, immuno-modulation, lowering of serum cholesterol, decreased risk of colon cancer, improve lactose digestion, reduce allergies, and effect on intestinal microbiota. Although the large investigation for the health benefits, information on probiotic species, a specific strain-therapeutic application, and sufficient dosages, is not sufficiently studied to allow practical and rational consumption. Moreover, prebiotic oligosaccharides although provided curative and nutritional values, they are poorly understood in regard to their origin, the processes employed to generate them, their fermentation profiles, and dosages required for health effects. The present review summarizes guidelines reported on the literature in regard to clinician or therapeutic trials of probiotic and prebiotic. © 2012 Elsevier Ltd.


Millot M.,CNRS Chemistry of Natural Substances Laboratory | Dieu A.,CNRS Chemistry of Natural Substances Laboratory | Tomasi S.,CNRS Chemistry Institute of Rennes
Natural Product Reports | Year: 2016

Covering: up to 2016. When looking for dibenzofuran in the biochemical databases, most papers and reviews deal with pollutants and polychlorinated dibenzofurans like dioxins. But dibenzofurans are also biosynthetized by a wide diversity of organisms in nature. Even if dibenzofurans from natural sources represent a small class of secondary metabolites, compared to flavonoids, xanthones or terpenoids, they are often endowed with interesting biological properties which have been recently described. This review provides an update on papers describing dibenzofurans from lichens, ascomycetes and cultured mycobionts. Other sources, such as basidiomycetes, myxomycetes or plants produce sporadically interesting dibenzofurans in terms of structures and activities. © 2016 The Royal Society of Chemistry.


Bourven I.,CNRS Research Group on Water, Soil and Environment | Costa G.,CNRS Chemistry of Natural Substances Laboratory | Guibaud G.,CNRS Research Group on Water, Soil and Environment
Bioresource Technology | Year: 2012

Exopolymeric substances (EPS) were extracted by EDTA from activated and anaerobic granular sludge. Due to the presence of EDTA in EPS extract, interferences were pointed out for the characterization of EPS by means of the colorimetric methods and fluorescence spectroscopy. Other methods have been investigated to characterize the EPS protein fraction. Size exclusion chromatography (SEC), performed at a fluorescence excitation-emission matrix of 221/360. nm (tryptophan protein-like substances) for detection, was suitable and allowed obtaining a fingerprint of the protein-like substance fractions and determining apparent molecular weight (MW). Polyacrylamide gel electrophoresis (PAGE) was performed under either native or denaturing conditions. Various staining applications after EPS migration are effective in obtaining a protein (silver staining) or glycoprotein (PAS staining) fingerprint or MW distribution. SEC and PAGE are both appropriate techniques for the qualitative characterization of protein fractions from EPS extracted by EDTA and moreover differentiate EPS according to sludge origin and type. © 2011 Elsevier Ltd.


Limami Y.,CNRS Chemistry of Natural Substances Laboratory | Pinon A.,CNRS Chemistry of Natural Substances Laboratory | Riaz A.,FC College | Simon A.,CNRS Chemistry of Natural Substances Laboratory
Cellular and Molecular Biology | Year: 2015

Targeting cancer cells is one of the challenges of current treatment strategies. TRAIL represents a promising therapeutic approach and over the past decades there was an increased interest in targeting TRAIL signaling to treat cancer. Indeed, TRAIL can specifically target cancer cells and exhibits very low cytotoxicity towards normal cells. However, rapidly accumulating experimental evidence has started to shed light on multiple factors which induce resistance against TRAIL in cancer cells. This resistance consists of various mechanisms including downregulation of death receptors and caspase-8 and overexpression of decoy receptors as well as antiapoptotic factors such as members of Bcl-2 family. Even if several studies focused on elucidating those resistance mechanisms, there still remain gray areas that need to be fully elucidated. Thus, therapeutic approaches could consist of targeting both resistance signaling pathways and TRAIL signaling to enhance TRAIL therapy efficiency. © 2015.


Bertrand J.,CNRS Chemistry of Natural Substances Laboratory | Liagre B.,CNRS Chemistry of Natural Substances Laboratory | Ghezali L.,CNRS Chemistry of Natural Substances Laboratory | Beneytout J.-L.,CNRS Chemistry of Natural Substances Laboratory | Leger D.Y.,CNRS Chemistry of Natural Substances Laboratory
Apoptosis | Year: 2013

Cyclooxygenase-2 (COX-2) has been found to be highly expressed in many types of cancers and to contribute to tumorigenesis via the inhibition of apoptosis, increased angiogenesis and invasiveness. In hematological malignancies, COX-2 expression was found to correlate with poor patient prognosis. However, the exact role of COX-2 expression in these malignancies, and particularly in erythroleukemias, remains unclear. The aim of this work was to describe and understand the relationships between COX-2 expression and apoptosis rate in erythroleukemia cells after apoptosis induction by several anticancer agents. We used three different erythroleukemia cell lines in which COX-2 expression was modulated by transfection with either COX-2 siRNA or COX-2 cDNA. These cellular models were then treated with apoptosis inducers and apoptosis onset and intensity was followed. Cell signalling was evaluated in unstimulated transfected cells or after apoptosis induction. We found that COX-2 inhibition rendered erythroleukemia cells more sensitive to apoptosis induction and that in cells overexpressing COX-2 apoptosis induction was reduced. We demonstrated that COX-2 inhibition decreased the pro-survival Akt signalling and activated the negative regulator of Akt signalling, phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Conversely, in COX-2 overexpressing cells, Akt signalling was activated and PTEN was inhibited. In these last cells, inhibition of casein kinase 2 or Akt signalling restored sensitivity to apoptotic agents. Our findings highlighted that COX-2 can positively regulate Akt signalling mostly through PTEN inhibition, partly via casein kinase 2 activation, and enhances survival of erythroleukemia cells exposed to anticancer agents. © 2013 Springer Science+Business Media New York.


Ghezali L.,CNRS Chemistry of Natural Substances Laboratory | Liagre B.,CNRS Chemistry of Natural Substances Laboratory | Limami Y.,CNRS Chemistry of Natural Substances Laboratory | Beneytout J.-L.,CNRS Chemistry of Natural Substances Laboratory | Leger D.Y.,CNRS Chemistry of Natural Substances Laboratory
PLoS ONE | Year: 2014

Differentiation therapy is a means to treat cancer and is induced by different agents with low toxicity and more specificity than traditional ones. Diosgenin, a plant steroid, is able to induce megakaryocytic differentiation or apoptosis in human HEL erythroleukemia cells in a dose-dependent manner. However, the exact mechanism by which diosgenin induces megakaryocytic differentiation has not been elucidated. In this study, we studied the involvement of Sonic Hedgehog in megakaryocytic differentiation induced by diosgenin in HEL cells. First, we showed that different elements of the Hedgehog pathway are expressed in our model by qRT-PCR. Then, we focused our interest on key elements in the Sonic Hedgehog pathway: Smoothened receptor, GLI transcription factor and the ligand Sonic Hedgehog. We showed that Smoothened and Sonic Hedgehog were overexpressed in disogenin-treated cells and that GLI transcription factors were activated. Then, we showed that SMO inhibition using siSMO or the GLI antagonist GANT-61, blocked megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, we demonstrated that Sonic Hedgehog pathway inhibition led to inhibition of ERK1/2 activation, a major physiological pathway involved in megakaryocytic differentiation. In conclusion, our study reports, for the first time, a crucial role for the Sonic Hedgehog pathway in diosgenin-induced megakaryocytic differentiation in HEL cells. © 2014 Ghezali et al.


Drogat N.,CNRS Chemistry of Natural Substances Laboratory | Granet R.,CNRS Chemistry of Natural Substances Laboratory | Le Morvan C.,CNRS Chemistry of Natural Substances Laboratory | Begaud-Grimaud G.,CNRS Chemistry of Natural Substances Laboratory | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

This Letter reports the synthesis and characterization of a new series of water-stable and soluble photosensitizers (PS-CNCs) composed of cellulose nanocrystals (CNCs) bearing polyaminated chlorin p6. With a view to improve cancer cell targeting, these photosensitizers were assayed for their antitumor activity against HaCat cell line. IC50 values fell within the nanomolar-range, making these photosensitizers promising for further in vitro and in vivo investigations. © 2012 Elsevier Ltd. All rights reserved.

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