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101.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector
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Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
102.
Zein‐based ultrathin fibers containing ceramic nanofillers obtained by electrospinning. II. Mechanical properties,gas barrier,and sustained release capacity of biocide thymol in multilayer polylactide films
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The combination of electrospinning technology and nanomaterials such as nanoclays can synergistically lead to novel materials with enhanced properties and functionalities for their usage in passive and active packaging applications. Part I of this work was focused on the development of ultrathin zein fibers containing nanoclays, which were oriented along the fiber axis and increased the thermal properties. Part II presents the use of the hybrid fibers as passive and active components in multilayer packaging structures. The hybrid fibers are incorporated in poly(lactic acid) films via a two‐step process: Electrospinning and compression molding. The composites thus produced presented improved mechanical and barrier properties than the unfilled material. The natural biocide extract thymol is then incorporated in the coating, and its sustained release properties are shown. The antimicrobial capacity of the hybrid fibers was also determined against foodborne bacteria. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40768. 相似文献
103.
Jean-Luc Caillaud Stphane Deguillaume Michel Vincent Jean-Claude Giannotta Jean-Michel Widmaier 《Polymer International》1996,40(1):1-7
The addition of metallic fillers is recognized to impart improvement of acoustic properties to polyurethane-based materials used for marine applications. The system under consideration was obtained by the reaction of a triisocyanateterminated prepolymer with 1,4-butanediol, in the presence of various concentrations of lead powder. With increasing lead content, gelation time is reduced and an Einstein-type law does not apply. The kinetics of the reaction were determined by Fourier transform infrared spectroscopy. Deviation from the classic second order is observed for the filled systems, and the higher the lead content, the more important the deviation is, showing undoubtedly the catalytic effect of the metallic powder. 相似文献
104.
An improved colorimetric method, based on the well-known reaction between amylose and iodine, is described. Native starch is dissolved in ureadimethylsulfoxide and the resulting solution defatted with ethanol. An aliquot of the lipid-free solution is then reacted with iodine and the absorbance of the blue-coloured amylose-iodine complex measured, thus determining the iodine-binding capacity of starch (Blue Value). A collaborative study was conducted, according to official guidelines, to determine the method's repeatability and reproducibility: 8 participants were each sent 8 starch samples from different botanic origin for duplicate analysis. Statistical evaluation of the results gave good precision results, with an average repeatability relative standard deviation of 2.1% and an average reproducibility relative standard deviation of 5.6%. The method is, therefore, suitable to determine precisely the amylose content of native starch. 相似文献
105.
Estimation of freezing storage time and quality changes in hake (Merluccius merluccius, L.) by low field NMR 总被引:4,自引:0,他引:4
The potential of low field NMR (LF NMR) as a fast monitoring technique to estimate the quality of hake (Merluccius merluccius) frozen stored at -10°C for up to 6months was evaluated. LF NMR clearly detected three populations of water: water strongly bound to macromolecules (T(2b)), trapped water (T(21)) and free water (T(22)). As storage time increased, and concomitant with an increase in the T(22) and a decrease in the T(21) water populations, the water holding capacity (WHC) and apparent viscosity values decreased and the shear strength increased, reflecting the characteristic loss of juiciness and tougher texture developed by hake during frozen storage. Two mathematical models were constructed: a simple regression using the biexponential analysis of the relaxation times (T(21), T(22)) and amplitudes (A(21), A(22)) and a partial least square regression (PLS) of CONTIN analysis. Both models seemed suitable to estimate the quality of the product. 相似文献
106.
Manuela Caniça José Luis Capelo‐Martinez Francisco Brito Gilberto Igrejas Patrícia Poeta 《Journal of the science of food and agriculture》2013,93(3):517-526
BACKGROUND: There has been concern about the increase of antimicrobial resistant bacteria and protection of animal and public health, along with food safety. In the present study, we evaluate the incidence of antimicrobial resistance among 192 strains of Escherichia coli isolated from faecal samples of healthy food‐producing animals at slaughter in Portugal. RESULTS: Ninety‐seven % of the pig isolates, 74% from sheep and 55% from cattle were resistant to one or more antimicrobial agents, with the resistances to ampicillin, streptomycin, tetracycline and trimethoprim–sulfamethoxazole the most common phenotype detected. Genes encoding resistance to antimicrobial agents were detected in most of the resistant isolates. Ninety‐three % of the resistant isolates were included in the A or B1 phylogenetic groups, and the virulence gene fimA (alone or in association with papC or aer genes) was detected in 137 of the resistant isolates. Five isolates from pigs belonging to phylogroup B2 and D were resistant to five different antimicrobial agents. CONCLUSION: Our data shows a high percentage of antibiotic resistance in E. coli isolates from food animals, and raises important questions in the potential impact of antibiotic use in animals and the possible transmission of resistant bacteria to humans through the food chain. © 2012 Society of Chemical Industry 相似文献
107.
Casein glycomacropeptide (CMP) found in cheese whey is a C-terminal hydrophilic glycopeptide released from κ-casein by the action of chymosin during cheese making. In a previous work a self-assembly model for CMP at room temperature was proposed, involving a first step of hydrophobic assembly followed by a second step of electrostatic interactions which occurs below pH 4.5. The objective of the present work was to study, by dynamic light scattering (DLS), the effect of heating (35–85 °C) on the pH-driven CMP self-assembly and its impact on the dynamics of CMP gelation. The concentration of CMP was 3% w/w for DLS and 12% w/w for rheological measurements. The solutions at pH 4.5 and 6.5 did not show any change in the particle size distributions upon heating. In contrast the solutions at pH lower than 4.5 that showed electrostatic self-assembly at room temperature were affected by heating. The mean diameter of assembled CMP increased by decreasing pH. For all solutions with pH lower than 4.5, the particle size did not change on cooling, suggesting that the assembled CMP forms formed during heating were stable. The gel point determined as G′–G″ crossover, occurred in all systems at 70 °C, but at different times. The rate of self-assembly determined by DLS as well as the rate of gelation increased with increasing temperature and decreasing pH from 4 to 2. Increasing temperature and decreasing pH, the first step of CMP self-assembly by hydrophobic interactions is speed out. All the self-assembled structures and the gels formed at different temperatures were pH-reversible but did not revert to the initial size (monomer) but to associated forms that correspond mainly to CMP dimers. 相似文献
108.
Davide Slaghenaufi Stéphanie Marchand-Marion Tristan Richard Pierre Waffo-Teguo Jonathan Bisson Jean-Pierre Monti Jean-Michel Merillon Gilles de Revel 《Food chemistry》2013
Flavours extracted from oak wood during barrel ageing contribute to the organoleptic character of wines and spirits. The aim of this work was to identify the glycosidic precursors of the key volatile compounds responsible for oak wood aroma. Oak extract is a very complex matrix and, furthermore, precursors are present in very small quantities. Preparative centrifugal partition chromatography (CPC) is a promising solution for purifying the oak extract. The solvent system was selected on the basis of the partition coefficient of glycosidase enzyme activity (Kca). Thanks to the efficacy of CPC separation, three glucoside gallates were subsequently isolated by HPLC chromatography. Vanillin-(6′-O-galloyl)-O-β-d-glucopyranoside, 3,4,5-trimethoxyphenyl-(6′-O-galloyl)-O-β-d-glucopyranoside, and (6R,9R)-3-oxo-α-ionol-9-O-(6′-O-galloyl)-β-glucopyranoside (macarangioside E) were isolated and identified. This was the first time that vanillin-(6′-O-galloyl)-O-β-d-glucopyranoside was identified and the first time that macarangioside E was isolated from oak wood. Heating macarangioside E resulted in the formation of megastigmatrienone, which has an aroma reminiscent of tobacco. 相似文献
109.
Blanc F Bernard H Alessandri S Bublin M Paty E Leung SA Patient KA Wal JM 《Molecular nutrition & food research》2008,52(Z2):S166-S175
Highly purified allergens namely cow's milk alpha-lactalbumin (ALA). (Bos d 4), beta-lactoglobulin (BLG) (Bos d 5) and casein (Bos d 8) and goat's milk casein were prepared from the raw milk from a single animal with a known genetic background. Consequently the natural isoforms are limited, constant and characterized. Purification included selective precipitations and chromatographical steps. Characterization of structure and allergenic activity assessment of milk allergens were carried out using physicochemical and immunochemical methods. Taken together data demonstrated the absence of impurities and of contamination by other milk allergens in each preparation. NMR and circular dichroism analyses confirmed the native conformation and proper folding of ALA and BLG and the expected absence of folding of bovine and caprine casein. Enzyme immuno assays confirmed the native conformation of BLG and the purity and immunoreactivity of all the proteins. The allergenic activity, e. g. the IgE binding capacity, of purified proteins was identical as that of those proteins when present in milk. The purified proteins also demonstrated the ability to provoke the degranulation of humanized rat basophilic leukaemia cells. All the data thus confirm the purity, identity, structural conformation and functionality of the prepared milk allergens. 相似文献
110.
Juliana C. Santos Alexandre Funck Isabelle J. L. Silva-Fernandes Silvia H. B. Rabenhorst Carlos A. R. Martinez Marcelo L. Ribeiro 《International journal of molecular sciences》2014,15(10):17333-17343
It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis. 相似文献