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Sample records for acid-amino acid conjugates

  1. Fatty acid-amino acid conjugates diversification in lepidopteran caterpillars.

    Science.gov (United States)

    Yoshinaga, Naoko; Alborn, Hans T; Nakanishi, Tomoaki; Suckling, David M; Nishida, Ritsuo; Tumlinson, James H; Mori, Naoki

    2010-03-01

    Fatty acid amino acid conjugates (FACs) have been found in noctuid as well as sphingid caterpillar oral secretions; in particular, volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] and its biochemical precursor, N-linolenoyl-L-glutamine, are known elicitors of induced volatile emissions in corn plants. These induced volatiles, in turn, attract natural enemies of the caterpillars. In a previous study, we showed that N-linolenoyl-L-glutamine in larval Spodoptera litura plays an important role in nitrogen assimilation which might be an explanation for caterpillars synthesizing FACs despite an increased risk of attracting natural enemies. However, the presence of FACs in lepidopteran species outside these families of agricultural interest is not well known. We conducted FAC screening of 29 lepidopteran species, and found them in 19 of these species. Thus, FACs are commonly synthesized through a broad range of lepidopteran caterpillars. Since all FAC-containing species had N-linolenoyl-L-glutamine and/or N-linoleoyl-L-glutamine in common, and the evolutionarily earliest species among them had only these two FACs, these glutamine conjugates might be the evolutionarily older FACs. Furthermore, some species had glutamic acid conjugates, and some had hydroxylated FACs. Comparing the diversity of FACs with lepidopteran phylogeny indicates that glutamic acid conjugates can be synthesized by relatively primitive species, while hydroxylation of fatty acids is limited mostly to larger and more developed macrolepidopteran species.

  2. Physiological function and ecological aspects of fatty acid-amino acid conjugates in insects.

    Science.gov (United States)

    Yoshinaga, Naoko

    2016-07-01

    In tritrophic interactions, plants recognize herbivore-produced elicitors and release a blend of volatile compounds (VOCs), which work as chemical cues for parasitoids or predators to locate their hosts. From detection of elicitors to VOC emissions, plants utilize sophisticated systems that resemble the plant-microbe interaction system. Fatty acid-amino acid conjugates (FACs), a class of insect elicitors, resemble compounds synthesized by microbes in nature. Recent evidence suggests that the recognition of insect elicitors by an ancestral microbe-associated defense system may be the origin of tritrophic interactions mediated by FACs. Here we discuss our findings in light of how plants have customized this defense to be effective against insect herbivores, and how some insects have successfully adapted to these defenses.

  3. Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Joppolo Di Ventimiglia, Samuele

    2003-01-01

    Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them...

  4. Unique roles of acidic amino acids in phase transformation of calcium phosphates.

    Science.gov (United States)

    Chu, Xiaobin; Jiang, Wenge; Zhang, Zhisen; Yan, Yang; Pan, Haihua; Xu, Xurong; Tang, Ruikang

    2011-02-10

    Although phase transformation is suggested as a key step in biomineralization, the chemical scenario about how organic molecules mediate inorganic phase transformations is still unclear. The inhibitory effect of amino acids on hydroxyapatite (HAP, the main inorganic component of biological hard tissues such as bone and enamel) formation was concluded by the previous biomimetic modeling based upon direct solution crystallization. Here we demonstrate that acidic amino acids, Asp and Glu, could promote HAP crystallization from its precursor crystal, brushite (DCPD). However, such a promotion effect could not be observed when the nonacidic amino acids were applied in the transformation-based HAP formation. We found that the specific modification of acidic amino acid on crystal-solution interfaces played a key role in the phase transition. The distinct properties between DCPD and HAP in the solution resulted in an interfacial energy barrier to suppress the spontaneous formation of HAP phase on DCPD phase. Different from the other amino acids, the carboxylate-rich amino acids, Asp and Glu, could modify the interfacial characteristics of these two calcium phosphate crystals to make them similar to each other. The experiments confirmed that the involvement of Asp or Glu reduced the interfacial energy barrier between DCPD and HAP, leading to a trigger effect on the phase transformation. An in-depth understanding about the unique roles of acidic amino acids may contribute to understanding phase transformation controls druing biomineralization.

  5. Profile of Fatty Acids, Amino Acids, Carotenoid Total, and α-Tocopherol from Flying Fish Eggs

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    Aulia Azka

    2015-12-01

    Full Text Available Flying fish are found in waters of eastern Indonesia, which until now is still limited information about nutritional content. The purpose of this research was determine the composition of fatty acids, amino acids, total carotenoids, α-tocopherol flying fish eggs (Hyrundicthys sp.. The composition of fatty acid was measured by gas chromatography (GC, while amino acids, total carotenoids, α-tocopherol was measured by High performanced Liquid Chromatography (HPLC. Egg contained 22 fatty acids such as saturated fatty acid 29.71%, monounsaturated fatty acid 7.86%, and polysaturated fatty acid 13.64%. The result showed that eggs flying fish contained 17 amino acids, such as essential amino acid 14.96% and non-essential amino acids 20.27%. Eggs contained a total carotenoid of 245.37 ppm. α-tocopherol content of flying fish eggs by 1.06 ppm.

  6. Chiral acidic amino acids induce chiral hierarchical structure in calcium carbonate

    Science.gov (United States)

    Jiang, Wenge; Pacella, Michael S.; Athanasiadou, Dimitra; Nelea, Valentin; Vali, Hojatollah; Hazen, Robert M.; Gray, Jeffrey J.; McKee, Marc D.

    2017-04-01

    Chirality is ubiquitous in biology, including in biomineralization, where it is found in many hardened structures of invertebrate marine and terrestrial organisms (for example, spiralling gastropod shells). Here we show that chiral, hierarchically organized architectures for calcium carbonate (vaterite) can be controlled simply by adding chiral acidic amino acids (Asp and Glu). Chiral, vaterite toroidal suprastructure having a `right-handed' (counterclockwise) spiralling morphology is induced by L-enantiomers of Asp and Glu, whereas `left-handed' (clockwise) morphology is induced by D-enantiomers, and sequentially switching between amino-acid enantiomers causes a switch in chirality. Nanoparticle tilting after binding of chiral amino acids is proposed as a chiral growth mechanism, where a `mother' subunit nanoparticle spawns a slightly tilted, consequential `daughter' nanoparticle, which by amplification over various length scales creates oriented mineral platelets and chiral vaterite suprastructures. These findings suggest a molecular mechanism for how biomineralization-related enantiomers might exert hierarchical control to form extended chiral suprastructures.

  7. Synthesis and Characterization of Fatty Acid/Amino Acid Self-Assemblies

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    Joanna Gajowy

    2014-10-01

    Full Text Available In this paper, we discuss the synthesis and self-assembling behavior of new copolymers derived from fatty acid/amino acid components, namely dimers of linoleic acid (DLA and tyrosine derived diphenols containing alkyl ester pendent chains, designated as “R” (DTR. Specific pendent chains were ethyl (E and hexyl (H. These poly(aliphatic/aromatic-ester-amides were further reacted with poly(ethylene glycol (PEG and poly(ethylene glycol methyl ether of different molecular masses, thus resulting in ABA type (hydrophilic-hydrophobic-hydrophilic triblock copolymers. We used Fourier transform infrared (FTIR and nuclear magnetic resonance (NMR spectroscopies to evaluate the chemical structure of the final materials. The molecular masses were estimated by gel permeation chromatography (GPC measurements. The self-organization of these new polymeric systems into micellar/nanospheric structures in aqueous environment was evaluated using ultraviolet/visible (UV-VIS spectroscopy, dynamic light scattering (DLS and transmission electron microscopy (TEM. The polymers were found to spontaneously self-assemble into nanoparticles with sizes in the range 196–239 nm and critical micelle concentration (CMC of 0.125–0.250 mg/mL. The results are quite promising and these materials are capable of self-organizing into well-defined micelles/nanospheres encapsulating bioactive molecules, e.g., vitamins or antibacterial peptides for antibacterial coatings on medical devices.

  8. Effects of organic acids, amino acids and ethanol on the radio-degradation of patulin in an aqueous model system

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Hyejeong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Department of Food Science and Technology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lim, Sangyong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Jo, Cheorun [Department of Animal Science and Biotechnology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Chung, Jinwoo [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of); Kim, Soohyun [Glycomics Team, Korea Basic Science Institute, Daejeon 305-333 (Korea, Republic of); Kwon, Joong-Ho [Department of Food Science and Technology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Kim, Dongho [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Chonbuk, Jeongeup 580-185 (Korea, Republic of)], E-mail: fungikim@kaeri.re.kr

    2008-06-15

    The effects of organic acids, amino acids, and ethanol on the radio-degradation of patulin by gamma irradiation in an aqueous model system were investigated. The patulin, dissolved in distilled water at a concentration of 50 ppm, was practically degraded by the gamma irradiation at the dose of 1.0 kGy, while 33% of the patulin remained in apple juice. In the aqueous model system, the radio-degradation of patulin was partially inhibited by the addition of organic acids, amino acids, and ethanol. The proportions of remaining patulin after irradiation with the dose of 1.0 kGy in the 1% solution of malic acid, citric acid, lactic acid, acetic acid, ascorbic acid, and ethanol were 31.4%, 2.3%, 31.2%, 6.1%, 50.8%, and 12.5%, respectively. During 30 days of storage, the remaining patulin was reduced gradually in the solution of ascorbic acid and malic acid compared to being stable in other samples. The amino acids, serine, threonine, and histidine, inhibited the radio-degradation of patulin. In conclusion, it was suggested that 1 kGy of gamma irradiation (recommended radiation doses for radicidation and/or quarantine in fruits) is effective for the reduction of patulin, but the nutritional elements should be considered because the radio-degradation effects are environment dependent.

  9. Kinetics of oxidation of acidic amino acids by sodium N-bromobenzenesulphonamide in acid medium: A mechanistic approach

    Indian Academy of Sciences (India)

    Puttaswamy; Nirmala Vaz

    2001-08-01

    Kinetics of oxidation of acidic amino acids (glutamic acid (Glu) and aspartic acid (Asp)) by sodium N-bromobenzenesulphonamide (bromamine-B or BAB) has been carried out in aqueous HClO4 medium at 30°C. The rate shows firstorder dependence each on [BAB]o and [amino acid]o and inverse first-order on [H+]. At [H+] > 0 60 mol dm-3, the rate levelled off indicating zero-order dependence on [H+] and, under these conditions, the rate has fractional order dependence on [amino acid]. Succinic and malonic acids have been identified as the products. Variation of ionic strength and addition of the reaction product benzenesulphonamide or halide ions had no significant effect on the reaction rate. There is positive effect of dielectric constant of the solvent. Proton inventory studies in H2O-D2O mixtures showed the involvement of a single exchangeable proton of the OH- ion in the transition state. Kinetic investigations have revealed that the order of reactivity is Asp > Glu. The rate laws proposed and derived in agreement with experimental results are discussed.

  10. The acidic amino acids of tulip: isolation of γ-ethylideneglutamic acid

    Science.gov (United States)

    Fowden, L.

    1966-01-01

    1. γ-Ethylideneglutamic acid has been isolated from fruit capsules of tulip plants. 2. The assigned structure was indicated by examining the products formed after oxidation and catalytic hydrogenation and was confirmed by nuclear-magnetic-resonance spectroscopy and by synthesis of γ-ethylglutamic acid. 3. The ability of γ-ethylideneglutamic acid to participate in transamination and decarboxylation reactions was examined. PMID:5938664

  11. In situ synthesis carbonated hydroxyapatite layers on enamel slices with acidic amino acids by a novel two-step method

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiaoguang [Department of Pediatric Dentistry, The Hospital of Stomatology, Jilin University, Changchun 130021 (China); Zhao, Xu [College of Chemistry, Jilin University, Changchun 130021 (China); Li, Yi, E-mail: lyi99@jlu.edu.cn [Department of Pediatric Dentistry, The Hospital of Stomatology, Jilin University, Changchun 130021 (China); Yang, Tao [Department of Stomatology, Children' s Hospital of Changchun, 130051 (China); Yan, Xiujuan; Wang, Ke [Department of Pediatric Dentistry, The Hospital of Stomatology, Jilin University, Changchun 130021 (China)

    2015-09-01

    In situ fabrication of carbonated hydroxyapatite (CHA) remineralization layer on an enamel slice was completed in a novel, biomimetic two-step method. First, a CaCO{sub 3} layer was synthesized on the surface of demineralized enamel using an acidic amino acid (aspartic acid or glutamate acid) as a soft template. Second, at the same concentration of the acidic amino acid, rod-like carbonated hydroxyapatite was produced with the CaCO{sub 3} layer as a sacrificial template and a reactant. The morphology, crystallinity and other physicochemical properties of the crystals were characterized using field emission scanning electron microscopy (FESEM), Fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and energy-dispersive X-ray analysis (EDAX), respectively. Acidic amino acid could promote the uniform deposition of hydroxyapatite with rod-like crystals via absorption of phosphate and carbonate ions from the reaction solution. Moreover, compared with hydroxyapatite crystals coated on the enamel when synthesized by a one-step method, the CaCO{sub 3} coating that was synthesized in the first step acted as an active bridge layer and sacrificial template. It played a vital role in orienting the artificial coating layer through the template effect. The results show that the rod-like carbonated hydroxyapatite crystals grow into bundles, which are similar in size and appearance to prisms in human enamel, when using the two-step method with either aspartic acid or acidic glutamate (20.00 mmol/L). - Graphical abstract: FESEM images of enamel slices etched for 60 s and repaired by the two-step method with Glu concentration of 20.00 mmol/L. (A) The boundary (dotted line) of the repaired areas (b) and unrepaired areas (a). (Some selected areas of etched enamel slices were coated with a nail polish before the reaction, which was removed by acetone after the reaction); (B) high magnification image of Ga, (C) high magnification image of Gb. In situ fabrication of

  12. Development of an assay to simultaneously measure orotic acid, amino acids, and acylcarnitines in dried blood spots.

    Science.gov (United States)

    Held, Patrice K; Haynes, Christopher A; De Jesús, Víctor R; Baker, Mei W

    2014-09-25

    Orotic aciduria in the presence of hyperammonemia is a key indicator for a defect in the urea cycle, specifically ornithine transcarbamylase (OTC) deficiency. Current newborn screening (NBS) protocols can detect several defects of the urea cycle, but screening for OTC deficiency remains a challenge due to the lack of a suitable assay. The purpose of this study was to develop a high-throughput assay to measure orotic acid in dried blood spot (DBS) specimens as an indicator for urea cycle dysfunction, which can be readily incorporated into routine NBS. Orotic acid was extracted from DBS punches and analyzed using flow-injection analysis tandem mass spectrometry (FIA-MS/MS) with negative-mode ionization, requiring amino acids, acylcarnitines, and orotic acid. We describe 2 assays which can quantify orotic acid in DBS: a stand-alone method and a combined method for analysis of orotic acid, amino acids, and acylcarnitines. Both methods demonstrated orotic acid recovery of 75-85% at multiple levels of enrichment. Precision was also comparable to traditional FIA-MS/MS methods. Analysis of residual presumptively normal NBS specimens demonstrated a 5:1 signal to noise ratio and the average concentration of orotic acid was approximately 1.2 μmol/l. The concentration of amino acids and acylcarnitines as measured by the combined method showed no significant differences when compared to the conventional newborn screening assay. In addition, retrospective analysis of confirmed patients and presumptively normal newborn screening specimens suggests potential for the methods to identify patients with OTC deficiency, as well as other urea cycle defects. The assays described here quantify orotic acid in DBS using a simple extraction and FIA-MS/MS analysis procedures that can be implemented into current NBS protocols. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Complexation and molecular modeling studies of europium(III)-gallic acid-amino acid complexes.

    Science.gov (United States)

    Taha, Mohamed; Khan, Imran; Coutinho, João A P

    2016-04-01

    With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan was studied by glass electrode potentiometry in aqueous solution containing 0.1M NaNO3 at (298.2 ± 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complex species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV-visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions.

  14. Kinetics and mechanism of the oxidation of some neutral and acidic -amino acids by tetrabutylammonium tribromide

    Indian Academy of Sciences (India)

    Raghvendra Shukla; Pradeep K Sharma; Kalyan K Banerji

    2004-03-01

    The oxidation of eleven amino acids by tetrabutylammonium tribromide (TBATB) in aqueous acetic acid results in the formation of the corresponding carbonyl compounds and ammonia. The reaction is first order with respect to TBATB. Michaelis-Menten type kinetics is observed with some of the amino acids while others exhibit second-order dependence. It failed to induce polymerization of acrylonitrile. The effect of solvent composition indicate that the rate of reaction increases with increase in the polarity of the medium. Addition of tetrabutylammonium chloride has no effect on the rate of oxidation. Addition of bromide ion causes decrease in the oxidation rate but only to a limiting value. The reaction is susceptible to both polar and steric effects of the substituents. A suitable mechanism has been proposed.

  15. FATTY ACIDS, AMINO ACIDS, MINERAL CONTENTS, AND PROXIMATE COMPOSITION OF SOME BROWN SEAWEEDS(1).

    Science.gov (United States)

    Tabarsa, Mehdi; Rezaei, Masoud; Ramezanpour, Zohreh; Robert Waaland, J; Rabiei, Reza

    2012-04-01

    This study was conducted to create a nutritional database on brown seaweeds and to popularize their consumption and utilization in Iran. The fatty acid contents, amino acids profiles, and certain mineral elements composition of some brown seaweeds, Padina pavonica (L.) Thivy, Dictyota dichotoma (Huds.) J. V. Lamour., and Colpomenia sinuosa (Mert. ex Roth) Derbés et Solier were determined. Total lipid content ranged from 1.46 ± 0.38 to 2.94 ± 0.94 g · 100 g(-1) dry weight (dwt), and the most abundant fatty acids were C16:0, C18:1, C20:4 ω6, and C20:5 ω3. The unsaturated fatty acids predominated in all species and had balanced sources of ω3 and ω6 acids. Highest total polyunsaturated fatty acid (PUFA) levels occurred in C. sinuosa. The protein content of D. dichotoma was 17.73 ± 0.29 g · 100 g(-1) dwt, significantly higher than the other seaweeds examined. Among amino acids essential to human nutrition, methionine (Met; in D. dichotoma and P. pavonica) and lysine (Lys; in C. sinuosa) were present in high concentrations. The crude fiber content varied by 9.5 ± 11.6 g · 100 g(-1) dwt in all species. Chemical analysis indicated that ash content was between 27.02 ± 0.6 and 39.28 ± 0.7 g · 100 g(-1) dwt, and that these seaweeds contained higher amounts of both macrominerals (7,308-9,160 mg · 100 g(-1) dwt; Na, K, Ca) and trace elements (263-1,594 mg · 100 g(-1) dwt; Fe, Ni, Mn, Cu, Co) than have been reported for edible land plants. C. sinuosa had the highest amount of Ca, Fe, and a considerable content of Na was measured in P. pavonica.

  16. Quantitative determination of carboxylic acids, amino acids, carbohydrates, ethanol and hydroxymethylfurfural in honey by (1)H NMR.

    Science.gov (United States)

    del Campo, Gloria; Zuriarrain, Juan; Zuriarrain, Andoni; Berregi, Iñaki

    2016-04-01

    A method using (1)H NMR spectroscopy has been developed to quantify simultaneously thirteen analytes in honeys without previous separation or pre-concentration steps. The method has been successfully applied to determine carboxylic acids (acetic, formic, lactic, malic and succinic acids), amino acids (alanine, phenylalanine, proline and tyrosine), carbohydrates (α- and β-glucose and fructose), ethanol and hydroxymethylfurfural in eucalyptus, heather, lavender, orange blossom, thyme and rosemary honeys. Quantification was performed by using the area of the signal of each analyte in the honey spectra, together with external standards. The regression analysis of the signal area against concentration plots, used for the calibration of each analyte, indicates a good linearity over the concentration ranges found in honeys, with correlation coefficients higher than 0.985 for the thirteen quantified analytes. The recovery studies give values over the 93.7-105.4% range with relative standard deviations lower than 7.4%. Good precision, with relative standard deviations over the range of 0.78-5.21% is obtained.

  17. Role of lysine and acidic amino acid residues on the insecticidal activity of Jackbean urease.

    Science.gov (United States)

    Real-Guerra, Rafael; Carlini, Célia Regina; Stanisçuaski, Fernanda

    2013-09-01

    Canavalia ensiformis has three isoforms of urease: Jackbean urease (JBU), Jackbean urease II and canatoxin. These isoforms present several biological activities, independent from the enzymatic property, such as entomotoxicity and antifungal properties. The entomotoxic activity is a property of the whole protein, as well as of a 10 kDa peptide released by insect digestive enzymes. Here we have used chemical modification to observe the influence of lysines and acidic residues on JBU enzymatic and insecticidal activities. Chemical modification of lysine residues was performed with dimethylamine-borane complex and formaldehyde, and acidic residues were modified by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and ethylenediamine. Derivatized ureases, called JBU-Lys (lysine-modified) and JBU-Ac (acidic residues-modified), were assayed for their biochemical and insecticidal properties. Neither modification altered significantly the kinetic parameters analyzed, indicating that no residue critical for the enzyme activity was affected and that the modifications did not incur in any significant structural alteration. On the other hand, both modifications reduced the toxic activity of the native protein fed to Dysdercus peruvianus. The changes observed in the entomotoxic property of the derivatized proteins reflect alterations in different steps of JBU's toxicity towards insects. JBU-Ac is not susceptible to hydrolysis by insect digestive enzymes, hence impairing the release of toxic peptide(s), while JBU-Lys is processed as the native protein. On the other hand, the antidiuretic effect of JBU on Rhodnius prolixus is altered in JBU-Lys, but not in JBU-Ac. Altogether, these data emphasize the role of lysine and acidic residues on the insecticidal properties of ureases.

  18. Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Yue Jing

    2015-04-01

    Full Text Available Fifteen semi-synthetic derivatives of asiatic acid (AA have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3, while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4–10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11–17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.

  19. Radiolytic Modification of Sulfur Containing Acidic Amino Residues in Model Peptides: Fundamental Studies for Protein Footprinting

    Energy Technology Data Exchange (ETDEWEB)

    Xu,G.; Chance, M.

    2005-01-01

    Protein footprinting based on hydroxyl radical-mediated modification and quantitative mass spectroscopic analysis is a proven technique for examining protein structure, protein-ligand interactions, and structural allostery upon protein complex formation. The reactive and solvent-accessible amino acid side chains function as structural probes; however, correct structural analysis depends on the identification and quantification of all the relevant oxidative modifications within the protein sequence. Sulfur-containing amino acids are oxidized readily and the mechanisms of oxidation are particularly complex, although they have been extensively investigated by EPR and other spectroscopic methods. Here we have undertaken a detailed mass spectrometry study (using electrospray ionization mass spectrometry and tandem mass spectrometry) of model peptides containing cysteine (Cys-SH), cystine (disulfide bonded Cys), and methionine after oxidation using {gamma}-rays or synchrotron X-rays and have compared these results to those expected from oxidation mechanisms proposed in the literature. Radiolysis of cysteine leads to cysteine sulfonic acid (+48 Da mass shift) and cystine as the major products; other minor products including cysteine sulfinic acid (+32 Da mass shift) and serine (-16 Da mass shift) are observed. Radiolysis of cystine results in the oxidative opening of the disulfide bond and generation of cysteine sulfonic acid and sulfinic acid; however, the rate of oxidation is significantly less than that for cysteine. Radiolysis of methionine gives rise primarily to methionine sulfoxide (+16 Da mass shift); this can be further oxidized to methionine sulfone (+32 Da mass shift) or another product with a -32 Da mass shift likely due to aldehyde formation at the {gamma}-carbon. Due to the high reactivity of sulfur-containing amino acids, the extent of oxidation is easily influenced by secondary oxidation events or the presence of redox reagents used in standard proteolytic

  20. Characterization of Fatty Acid, Amino Acid and Volatile Compound Compositions and Bioactive Components of Seven Coffee (Coffea robusta Cultivars Grown in Hainan Province, China

    Directory of Open Access Journals (Sweden)

    Wenjiang Dong

    2015-09-01

    Full Text Available Compositions of fatty acid, amino acids, and volatile compound were investigated in green coffee beans of seven cultivars of Coffea robusta grown in Hainan Province, China. The chlorogenic acids, trigonelline, caffeine, total lipid, and total protein contents as well as color parameters were measured. Chemometric techniques, principal component analysis (PCA, hierarchical cluster analysis (HCA, and analysis of one-way variance (ANOVA were performed on the complete data set to reveal chemical differences among all cultivars and identify markers characteristic of a particular botanical origin of the coffee. The major fatty acids of coffee were linoleic acid, palmitic acid, oleic acid, and arachic acid. Leucine (0.84 g/100 g DW, lysine (0.63 g/100 g DW, and arginine (0.61 g/100 g DW were the predominant essential amino acids (EAAs in the coffee samples. Seventy-nine volatile compounds were identified and semi-quantified by HS-SPME/GC-MS. PCA of the complete data matrix demonstrated that there were significant differences among all cultivars, HCA supported the results of PCA and achieved a satisfactory classification performance.

  1. Characterization of Fatty Acid, Amino Acid and Volatile Compound Compositions and Bioactive Components of Seven Coffee (Coffea robusta) Cultivars Grown in Hainan Province, China.

    Science.gov (United States)

    Dong, Wenjiang; Tan, Lehe; Zhao, Jianping; Hu, Rongsuo; Lu, Minquan

    2015-09-14

    Compositions of fatty acid, amino acids, and volatile compound were investigated in green coffee beans of seven cultivars of Coffea robusta grown in Hainan Province, China. The chlorogenic acids, trigonelline, caffeine, total lipid, and total protein contents as well as color parameters were measured. Chemometric techniques, principal component analysis (PCA), hierarchical cluster analysis (HCA), and analysis of one-way variance (ANOVA) were performed on the complete data set to reveal chemical differences among all cultivars and identify markers characteristic of a particular botanical origin of the coffee. The major fatty acids of coffee were linoleic acid, palmitic acid, oleic acid, and arachic acid. Leucine (0.84 g/100 g DW), lysine (0.63 g/100 g DW), and arginine (0.61 g/100 g DW) were the predominant essential amino acids (EAAs) in the coffee samples. Seventy-nine volatile compounds were identified and semi-quantified by HS-SPME/GC-MS. PCA of the complete data matrix demonstrated that there were significant differences among all cultivars, HCA supported the results of PCA and achieved a satisfactory classification performance.

  2. Synthesis and structure-activity studies on acidic amino acids and related diacids as NMDA receptor ligands

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1994-01-01

    , of (S)-glutamic acid (1) receptors. A number of amino acids and diacids structurally related to AMAA were synthesized and tested electrophysiologically and in receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA agonist approximately equipotent with AMAA in the [3H......]CPP-binding assay (IC50 = 7 +/- 3 microM) and electropharmacologically in the rat cortical wedge model (EC50 = 8 +/- 2 microM). In contrast to this, the tertbutyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a, c were studied...... by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very...

  3. Involvement of arginine 878 together with Ca2+ in mouse aminopeptidase A substrate specificity for N-terminal acidic amino-acid residues

    Science.gov (United States)

    Couvineau, Pierre; de Almeida, Hugo; Maigret, Bernard; Llorens-Cortes, Catherine

    2017-01-01

    Aminopeptidase A (APA) is a membrane-bound zinc metalloprotease cleaving, in the brain, the N-terminal aspartyl residue of angiotensin II to generate angiotensin III, which exerts a tonic stimulatory effect on the control of blood pressure in hypertensive animals. Using a refined APA structure derived from the human APA crystal structure, we docked the specific and selective APA inhibitor, EC33 in the presence of Ca2+. We report the presence in the S1 subsite of Arg-887 (Arg-878 in mouse APA), the guanidinium moiety of which established an interaction with the electronegative sulfonate group of EC33. Mutagenic replacement of Arg-878 with an alanine or a lysine residue decreased the affinity of the recombinant enzymes for the acidic substrate, α-L-glutamyl-β-naphthylamide, with a slight decrease in substrate hydrolysis velocity either with or without Ca2+. In the absence of Ca2+, the mutations modified the substrate specificity of APA for the acidic substrate, the mutated enzymes hydrolyzing more efficiently basic and neutral substrates, although the addition of Ca2+ partially restored the acidic substrate specificity. The analysis of the 3D models of the Arg-878 mutated APAs revealed a change in the volume of the S1 subsite, which may impair the binding and/or the optimal positioning of the substrate in the active site as well as its hydrolysis. These findings demonstrate the key role of Arg-878 together with Ca2 + in APA substrate specificity for N-terminal acidic amino acid residues by ensuring the optimal positioning of acidic substrates during catalysis. PMID:28877217

  4. Organic biomarkers in deep-sea regions affected by bottom trawling: pigments, fatty acids, amino acids and carbohydrates in surface sediments from the La Fonera (Palamós) Canyon, NW Mediterranean Sea

    OpenAIRE

    E. Sañé; Martín, J.; Puig, P.; Palanques, A.

    2013-01-01

    Deep-sea ecosystems are in general adapted to a limited variability of physical conditions, resulting in high vulnerability and slow recovery rates from anthropogenic perturbations such as bottom trawling. Commercial trawling is the most recurrent and pervasive of human impacts on the deep-sea floor, but studies on its consequences on the biogeochemistry of deep-sea sediments are still scarce. Pigments, fatty acids, amino acids and carbohydrates were analysed in sediments fr...

  5. Organic biomarkers in deep-sea regions affected by bottom trawling: pigments, fatty acids, amino acids and carbohydrates in surface sediments from the La Fonera (Palamós) Canyon, NW Mediterranean Sea

    OpenAIRE

    E. Sañé; Martín, J.; Puig, P.; Palanques, A.

    2012-01-01

    Deep-sea ecosystems are in general adapted to a limited variability of physical conditions, resulting in high vulnerability and slow recovery rates from anthropogenic perturbations such as bottom trawling. Commercial trawling is the most recurrent and pervasive of human impacts on the deep-sea floor, but studies on its consequences on the biogeochemistry of deep-sea sediments are still scarce. Pigments, fatty acids, amino acids and carbohydrates were analyzed in sediments from the flanks of t...

  6. Structure Effect of Diacid/Triacid on Self-Assembly of Binary Organogels Based on Glutamic Acid Amino Derivative

    Directory of Open Access Journals (Sweden)

    Jinming Dai

    2013-01-01

    Full Text Available The gelation behaviors of binary organogels composed of N-(4-aminobenzoyl-L-glutamic acid diethyl ester with sebacic acid and citric acid in various organic solvents were designed and investigated. Their gelation behaviors in 20 solvents were tested as new binary organic gelators. It showed that the molecular structures and organic solvents have played a crucial role in the gelation behavior of all gelator mixtures. More carboxyl groups in molecular skeletons in the present mixture gelators are unfavorable for the gelation of organic solvents. The mixture containing sebacic acid can form 5 kinds of organogels, while another mixture containing citric acid can only form 3 kinds of organogels in different solvents. Morphological studies revealed that the gelator molecules self-assemble into different aggregates from wrinkle and belt to fiber with change of solvents. Spectral studies indicated that there existed different H-bond formations and hydrophobic forces, depending on solvents and molecular structures. The as-prepared nanomaterials have wide perspectives in nanoscience and functional textile materials with special microstructures.

  7. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  8. Ionic interaction of positive amino acid residues of fungal hydrophobin RolA with acidic amino acid residues of cutinase CutL1.

    Science.gov (United States)

    Takahashi, Toru; Tanaka, Takumi; Tsushima, Yusei; Muragaki, Kimihide; Uehara, Kenji; Takeuchi, Shunsuke; Maeda, Hiroshi; Yamagata, Youhei; Nakayama, Mayumi; Yoshimi, Akira; Abe, Keietsu

    2015-04-01

    Hydrophobins are amphipathic proteins secreted by filamentous fungi. When the industrial fungus Aspergillus oryzae is grown in a liquid medium containing the polyester polybutylene succinate co-adipate (PBSA), it produces RolA, a hydrophobin, and CutL1, a PBSA-degrading cutinase. Secreted RolA attaches to the surface of the PBSA particles and recruits CutL1, which then condenses on the particles and stimulates the hydrolysis of PBSA. Here, we identified amino acid residues that are required for the RolA-CutL1 interaction by using site-directed mutagenesis. We quantitatively analyzed kinetic profiles of the interactions between RolA variants and CutL1 variants by using a quartz crystal microbalance (QCM). The QCM analyses revealed that Asp142, Asp171 and Glu31, located on the hydrophilic molecular surface of CutL1, and His32 and Lys34, located in the N-terminus of RolA, play crucial roles in the RolA-CutL1 interaction via ionic interactions. RolA immobilized on a QCM electrode strongly interacted with CutL1 (K(D)  = 6.5 nM); however, RolA with CutL1 variants, or RolA variants with CutL1, showed markedly larger KD values, particularly in the interaction between the double variant RolA-H32S/K34S and the triple variant CutL1-E31S/D142S/D171S (K(D)  = 78.0 nM). We discuss a molecular prototype model of hydrophobin-based enzyme recruitment at the solid-water interface.

  9. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  10. Glutamic Acid - Amino Acid, Neurotransmitter, and Drug - Is Responsible for Protein Synthesis Rhythm in Hepatocyte Populations in vitro and in vivo.

    Science.gov (United States)

    Brodsky, V Y; Malchenko, L A; Konchenko, D S; Zvezdina, N D; Dubovaya, T K

    2016-08-01

    Primary cultures of rat hepatocytes were studied in serum-free media. Ultradian protein synthesis rhythm was used as a marker of cell synchronization in the population. Addition of glutamic acid (0.2 mg/ml) to the medium of nonsynchronous sparse cultures resulted in detection of a common protein synthesis rhythm, hence in synchronization of the cells. The antagonist of glutamic acid metabotropic receptors MCPG (0.01 mg/ml) added together with glutamic acid abolished the synchronization effect; in sparse cultures, no rhythm was detected. Feeding rats with glutamic acid (30 mg with food) resulted in protein synthesis rhythm in sparse cultures obtained from the rats. After feeding without glutamic acid, linear kinetics of protein synthesis was revealed. Thus, glutamic acid, a component of blood as a non-neural transmitter, can synchronize the activity of hepatocytes and can form common rhythm of protein synthesis in vitro and in vivo. This effect is realized via receptors. Mechanisms of cell-cell communication are discussed on analyzing effects of non-neural functions of neurotransmitters. Glutamic acid is used clinically in humans. Hence, a previously unknown function of this drug is revealed.

  11. Health benefits of conjugated linoleic acid (CLA).

    Science.gov (United States)

    Koba, Kazunori; Yanagita, Teruyoshi

    2014-01-01

    Conjugated linoleic acid (CLA) is a group of positional and geometric (cis or trans) isomers of linoleic acid with a conjugated double bond. The most representative CLA isomers are 9c,11t-18:2 and 10t,12c-18:2. CLA has been shown to exert various potent physiological functions such as anticarcinogenic, antiobese, antidiabetic and antihypertensive properties. This means CLA can be effective to prevent lifestyle diseases or metabolic syndromes. Also, reports suggest that physiological effects of CLA are different between the isomers, for example the 10t,12c isomer is anticarcinogenic, antiobese and antidiabetic, whereas the 9c,11t isomer is mainly anticarcinogenic. We describe here the physiological properties of CLA including the possible mechanism and the possibility to benefit human health.

  12. Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Pinto, Andrea; Conti, Paola; Grazioso, Giovanni;

    2011-01-01

    The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have been...

  13. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  14. Varying Response of the Concentration and Yield of Soybean Seed Mineral Elements, Carbohydrates, Organic Acids, Amino Acids, Protein, and Oil to Phosphorus Starvation and CO2 Enrichment.

    Science.gov (United States)

    Singh, Shardendu K; Barnaby, Jinyoung Y; Reddy, Vangimalla R; Sicher, Richard C

    2016-01-01

    A detailed investigation of the concentration (e.g., mg g(-1) seed) and total yield (e.g., g plant(-1)) of seed mineral elements and metabolic profile under phosphorus (P) starvation at ambient (aCO2) and elevated carbon dioxide (eCO2) in soybean is limited. Soybean plants were grown in a controlled environment at either sufficient (0.50 mM P, control) or deficient (0.10 and 0.01 mM, P-stress) levels of P under aCO2 and eCO2 (400 and 800 μmol mol(-1), respectively). Both the concentration and yield of 36 out of 38 seed components responded to P treatment and on average 25 and 11 components increased and decreased, respectively, in response to P starvation. Concentrations of carbohydrates (e.g., glucose, sugar alcohols), organic acids (e.g., succinate, glycerate) and amino acids increased while oil, and several minerals declined under P deficiency. However, the yield of the majority of seed components declined except several amino acids (e.g., phenylalanine, serine) under P deficiency. The concentration-based relationship between seed protein and oil was negative (r(2) = 0.96), whereas yield-based relationship was positive (r(2) = 0.99) across treatments. The CO2 treatment also altered the concentration of 28 out of 38 seed components, of which 23 showed decreasing (e.g., sucrose, glucose, citrate, aconitate, several minerals, and amino acids) while C, iron, Mn, glycerate, and oil showed increasing trends at eCO2. Despite a decreased concentration, yields of the majority of seed components were increased in response to eCO2, which was attributable to the increased seed production especially near sufficient P nutrition. The P × CO2 interactions for the concentration of amino acids and the yield of several components were due to the lack of their response to eCO2 under control or the severe P starvation, respectively. Thus, P deficiency primarily reduced the concentration of oil and mineral elements but enhanced a majority of other components. However, seed

  15. Varying Response of the Concentration and Yield of Soybean Seed Mineral Elements, Carbohydrates, Organic Acids, Amino Acids, Protein, and Oil to Phosphorus Starvation and CO2 Enrichment

    Science.gov (United States)

    Singh, Shardendu K.; Barnaby, Jinyoung Y.; Reddy, Vangimalla R.; Sicher, Richard C.

    2016-01-01

    A detailed investigation of the concentration (e.g., mg g-1 seed) and total yield (e.g., g plant-1) of seed mineral elements and metabolic profile under phosphorus (P) starvation at ambient (aCO2) and elevated carbon dioxide (eCO2) in soybean is limited. Soybean plants were grown in a controlled environment at either sufficient (0.50 mM P, control) or deficient (0.10 and 0.01 mM, P-stress) levels of P under aCO2 and eCO2 (400 and 800 μmol mol-1, respectively). Both the concentration and yield of 36 out of 38 seed components responded to P treatment and on average 25 and 11 components increased and decreased, respectively, in response to P starvation. Concentrations of carbohydrates (e.g., glucose, sugar alcohols), organic acids (e.g., succinate, glycerate) and amino acids increased while oil, and several minerals declined under P deficiency. However, the yield of the majority of seed components declined except several amino acids (e.g., phenylalanine, serine) under P deficiency. The concentration-based relationship between seed protein and oil was negative (r2 = 0.96), whereas yield-based relationship was positive (r2 = 0.99) across treatments. The CO2 treatment also altered the concentration of 28 out of 38 seed components, of which 23 showed decreasing (e.g., sucrose, glucose, citrate, aconitate, several minerals, and amino acids) while C, iron, Mn, glycerate, and oil showed increasing trends at eCO2. Despite a decreased concentration, yields of the majority of seed components were increased in response to eCO2, which was attributable to the increased seed production especially near sufficient P nutrition. The P × CO2 interactions for the concentration of amino acids and the yield of several components were due to the lack of their response to eCO2 under control or the severe P starvation, respectively. Thus, P deficiency primarily reduced the concentration of oil and mineral elements but enhanced a majority of other components. However, seed components yield

  16. Acceleration of curing period of pastrami manufactured from buffalo meat: II-Fatty acids, amino acids, nutritional value and sensory evaluation

    Directory of Open Access Journals (Sweden)

    Ibrahim, Hayam M.A.

    2001-04-01

    Full Text Available Upon accelerating the curing period of pastrami (dry cured meat prepared from buffalo lean round muscles using heat treatment (~71ºC internally, the results indicated that: the peroxide and thiobarbituric acid (TBA values increased with increasing the aging period. Percentage of the released free fatty acids was 1.21 after heat treatment and increased gradually to reach 1.47 after hanging in air at room temperature for drying and complete curing up to 6 days. The major saturated and unsaturated fatty acids in all of the pastrami samples were palmitic (16:0, oleic (18:1 and linoleic (18:2 fatty acids. The main three identified polyunsaturated fatty acids (linoleic, linolenic and arachidonic were of high percentages in the accelerated cured samples than in the control one. The ratio of the unsaturated: saturated fatty acids was similar in either the heat treated (1.28:1 and the control (1.27: 1 pastrami samples. Similar findings were found for the ratio of total essential amino acids (EAAS: total amino acids (AAS. The Essential Amino Acids Index (EAAI that possesses higher percentage for the heat treated sample than that for the control one proved the higher biological acceptance of the heat accelerated cured pastrami sample. The predicted protein efficiency ratio (PER of all the investigated samples reached more than 2.42 of casein. Sensory evaluation of the pastrami sample processed to an internal temperature of ~71ºC proved by the panelists to be of attractive color, more tasty, of good characteristic odor and more tender than the control samples which were prepared and cured for 3 weeks without using heat treatment.En relación a la aceleración del período de cura del pastrami (carne curada en seco preparada a partir de carne magra de búfalo usando un tratamiento térmico (~71ºC internamente, los resultados indicaron que los valores de peróxido y ácido tiobarbitúrico (TBA aumentaron con el envejecimiento. El porcentaje de

  17. Organic biomarkers in deep-sea regions affected by bottom trawling: pigments, fatty acids, amino acids and carbohydrates in surface sediments from the La Fonera (Palamós Canyon, NW Mediterranean Sea

    Directory of Open Access Journals (Sweden)

    E. Sañé

    2012-12-01

    Full Text Available Deep-sea ecosystems are in general adapted to a limited variability of physical conditions, resulting in high vulnerability and slow recovery rates from anthropogenic perturbations such as bottom trawling. Commercial trawling is the most recurrent and pervasive of human impacts on the deep-sea floor, but studies on its consequences on the biogeochemistry of deep-sea sediments are still scarce. Pigments, fatty acids, amino acids and carbohydrates were analyzed in sediments from the flanks of the La Fonera (Palamós submarine canyon (NW Mediterranean Sea, where a commercial bottom trawling fishery has been active for more than 70 yr. More specifically, we investigated how trawling-induced sediment reworking affects the quality of sedimentary organic matter which reaches the seafloor and accumulates in the sediment column, which is fundamental for the development of benthic communities. Sediment samples were collected during two oceanographic cruises in spring and autumn 2011. The sampled sites included trawl fishing grounds as well as pristine (control areas. We report that bottom trawling in the flanks of the La Fonera Canyon has caused an alteration of the quality of the organic matter accumulated in the upper 5 cm of the seafloor. The use of a wide pool of biochemical tracers characterized by different reactivity to degradation allowed us to discriminate the long-term effects of trawled-induced sediment reworking from the natural variability caused by the seasonal cycle of production and sinking of biogenic particles. Differences between untrawled and trawled areas were evidenced by labile amino acids, while differences between spring and autumn samples were detected only by the more labile indicators chlorophyll a and mono-unsaturated fatty acids. These results suggest that changes in the biochemical composition of the sedimentary organic matter caused by bottom trawling can be more relevant than those associated with natural

  18. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  19. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    FENG ZeWang; ZHAO XinQi; BI Hua

    2008-01-01

    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in dichloromethane at room temperature.

  20. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in di-chloromethane at room temperature.

  1. Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates.

    Science.gov (United States)

    Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P

    2014-05-25

    Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.

  2. Conjugated Linoleic Acid (CLA-An Overview

    Directory of Open Access Journals (Sweden)

    D J Crumb

    2011-09-01

    Full Text Available Summary: Conjugated linoleic acid (CLA is a group of octadecadienoic acids that are naturally present in the highest concentrations in foods originating in ruminant animals, and dairy products such as milk. Especially large numbers of CLA polymers have been detected in beef, lamb and milk fat. Results from many in vitro and animal studies, though conflicting, have suggested that CLA supplementation may have beneficial effect on obesity, weight management, cancer, diabetes and atherosclerosis. This article provides a brief overview on the functionality, safety and toxicity of CLA as described in literature. .   Industrial Relevance: CLA is a functional food and dietary supplement ingredient with potential benefits against a number of metabolic chronic diseases. However, the mechanism of action and its toxicological effects are not very well understood. These factors may play an important role in the effectiveness as CLA as a viable functional dietary bioactive compound.

  3. Conjugated Linoleic Acid and Importance to Health

    Directory of Open Access Journals (Sweden)

    Canan Asal Ulus

    2017-01-01

    Full Text Available The development in science  technology and the researches made in the health field showed that nutrition increases the effectiveness of medical treatment as well as maintaining the human health and singularly effective in the treatment of certain diseases. In recent years, the importance of nutritional elements called ‘Functional foods’ has increased. Functional foods provide physiological benefits and can reduce the risk of chronic diseases beyond their nutritional benefits. One of these functional compounds is conjugated linoleic acid (CLA isomers which have significant effects on human health and previously have been demonstrated in the researches carried out on people and animals. CLA’s attracted more attention after detection of its body fat accumulation reducing, antidiabetic, immune system enhancing, arteriosclerosis reducing, bone mineralization increasing effects.

  4. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  5. Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates.

    Science.gov (United States)

    Piotrowska, Alicja; Bajguz, Andrzej

    2011-12-01

    Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.

  6. Diversity of (dihydro) hydroxycinnamic acid conjugates in Colombian potato tubers

    NARCIS (Netherlands)

    Narvaez Cuenca, C.E.; Vincken, J.P.; Zheng, Chaoya; Gruppen, H.

    2013-01-01

    In potato tuber, caffeic acid (the predominant hydroxycinnamic acid (HCA)), its conjugates (HCAcs; i.e. chlorogenic acid (ChA), crypto-ChA, and neo-ChA), and anthocyanin-linked HCAs have been extensively described in the literature. In contrast, only little information is available on the occurrence

  7. BSA-boronic acid conjugate as lectin mimetics.

    Science.gov (United States)

    Narla, Satya Nandana; Pinnamaneni, Poornima; Nie, Huan; Li, Yu; Sun, Xue-Long

    2014-01-10

    We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin mimetics are expected to provide an important tool for glycomics and biosensor research and applications.

  8. Preparation of Conjugated Linoleic Acid and Identification of Its Isomers

    Institute of Scientific and Technical Information of China (English)

    郭诤; 张根旺; 孙彦

    2003-01-01

    Conjugated linoleic acid(CLA)is a kind of fatty acid with physiological activities and potential appli-cation prospect ,A synthesis method of conjugated linoleic acid and a purification technology were studied .CLA was prepared and purified by urea-complexation and conjugation using safflower oil as raw material,The purity of CLA and total recovery of the product was more than 95% and 48%,respectively,The main isomers produced in alkali-catalyzed conjugation were identified by gas chromatography (GC)linked to mass spectrometry(MS) and Fourier transform infrared spectroscopy(FTIR),The total amount of the two main isomers (9cis,11trans-and 10trans,12cis-CLA) determined by GC was more than 90% of the product.

  9. Conjugated linoleic acid isomers and cancer.

    Science.gov (United States)

    Kelley, Nirvair S; Hubbard, Neil E; Erickson, Kent L

    2007-12-01

    We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer. We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis. The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway. The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.

  10. New phenstatin-fatty acid conjugates: synthesis and evaluation.

    Science.gov (United States)

    Chen, Jinhui; Brown, David P; Wang, Yi-Jun; Chen, Zhe-Sheng

    2013-09-15

    New phenstatin-fatty acid conjugates have been synthesized and tested against the KB-3-1, H460, MCF-7 and HEK293 cell lines, with an increase in anti-proliferative activity being observed at the micro-molar level paralleling an increase in un-saturation in the fatty acid component.

  11. Synthesis of novel fullerene α-amino acid conjugates

    Institute of Scientific and Technical Information of China (English)

    Jing Zhang; Yan Xia Wang; Feng Kang; Ying Ya Shao; Zong Jie Li; Xin Lin Yang

    2008-01-01

    Aspartie acid and glutamic acid with protected α-amino and α-carboxyl groups had been used to react with the activated hydroxyl group of N-substituted 3,4-fuUero pyrrolidine.The products were deprotected,affording two monofullerene α-amino acids,monofullerene aspartic acid(mFas)and monofullerene glutamic acid(mFgu).Then a bifullerene glutamic acid conjugate (bFguC)was synthesized by reaction of mFgu containing protected amino group with N-subsfimted 3,4-fullero pyrrolidine.

  12. Morroniside cinnamic acid conjugate as an anti-inflammatory agent.

    Science.gov (United States)

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru

    2010-08-15

    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

  13. The Preparation and Characterization of Conjugated Linolenic Acid

    Institute of Scientific and Technical Information of China (English)

    Cao Ying; Yang Lin; Chen Zhen-Yu

    2004-01-01

    Conjugated Linolenic Acid (CLN) has recently been shown to have a more strong cytotoxic effect on various human tumor cell lines than CLA. In CLN, all the three double bonds are conjugated, whereas they are methylene-interrupted in LN. Some seed oil, such as tung oil and pomegranate seed oil, principally consist of CLN, accounting for 76.5% and 75.5%, respectively.CLN can be characterized using the combination of gas chromatography (GC), highperformance liquid chromatography (HPLC) and UV /VIS spectrophotomea-ic analysis. GC can separate the CLN from other fatty acids and HPLC can separate the individual CLN isomers.The conjugated triene formation has a maximum absorbency at 268 nm and the conjugated diene formation has an absorbency at 235 nm in UV spectrum.CLN was prepared from linseed oil by isomerization reaction in our present study. By treating at was isomerized and the product was purified by recrystallizing in the methanol. The GC and UV /VIS spectrophotometric analysis were used to characterize the obtained products. It was found that the a-LN in the linseed oil was converted to the corresponding conjugated diene acids and CLN. The GC analysis also showed that there formed about 20% CLN when reacting for 10h with 40% KOH/ethylene glycol.

  14. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    Science.gov (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M

    2013-06-03

    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  15. Incorporation of conjugated linoleic acid (CLA and α-linolenic acid (LNA in pacu fillets

    Directory of Open Access Journals (Sweden)

    Deoclécio José Barilli

    2014-03-01

    Full Text Available The objective of this study was to evaluate the incorporation of conjugated linoleic acid and α-linolenic acid in fillets of pacu fish raised in net cages and fed diets enriched with these acids. The fish were fed for 49 days, and at the end of this period the fatty acid content in the fillets was determined by gas chromatography. Concentrations of α-linolenic acid, eicosapentaenoic acid, and the total omega-3 (n-3 fatty acid in the fillets increased, improving the n-6/n-3 ratio. In addition, the incorporation of conjugated linoleic acid in the fish fillets proved well established. This study showed that the use of diets enriched with conjugated linoleic acid and α-linolenic acid results in the incorporation of these acids in the of pacu fish fillets, improving their nutritional quality.

  16. Palladium-catalyzed enantioselective conjugate addition of arylboronic acids

    NARCIS (Netherlands)

    Gini, F; Hessen, B; Minnaard, AJ

    2005-01-01

    The first asymmetric palladium-catalyzed conjugate addition of arylboronic acids to alpha,beta-unsaturated aldehydes, ketones, and esters is described. For cyclic substrates, excellent chemo-, regio-, and enantioselectivities are achieved when a Pd(O2CCF3)(2)/DuPHOS catalyst is applied.

  17. Catalytic production of conjugated fatty acids and oils.

    Science.gov (United States)

    Philippaerts, An; Goossens, Steven; Jacobs, Pierre A; Sels, Bert F

    2011-06-20

    The reactive double bonds in conjugated vegetable oils are of high interest in industry. Traditionally, conjugated vegetable oils are added to paints, varnishes, and inks to improve their drying properties, while recently there is an increased interest in their use in the production of bioplastics. Besides the industrial applications, also food manufactures are interested in conjugated vegetable oils due to their various positive health effects. While the isomer type is less important for their industrial purposes, the beneficial health effects are mainly associated with the c9,t11, t10,c12 and t9,t11 CLA isomers. The production of CLA-enriched oils as additives in functional foods thus requires a high CLA isomer selectivity. Currently, CLAs are produced by conjugation of oils high in linoleic acid, for example soybean and safflower oil, using homogeneous bases. Although high CLA productivities and very high isomer selectivities are obtained, this process faces many ecological drawbacks. Moreover, CLA-enriched oils can not be produced directly with the homogeneous bases. Literature reports describe many catalytic processes to conjugate linoleic acid, linoleic acid methyl ester, and vegetable oils rich in linoleic acid: biocatalysts, for example enzymes and cells; metal catalysts, for example homogeneous metal complexes and heterogeneous catalysts; and photocatalysts. This Review discusses state-of-the-art catalytic processes in comparison with some new catalytic production routes. For each category of catalytic process, the CLA productivities and the CLA isomer selectivity are compared. Heterogeneous catalysis seems the most attractive approach for CLA production due to its easy recovery process, provided that the competing hydrogenation reaction is limited and the CLA production rate competes with the current homogeneous base catalysis. The most important criteria to obtain high CLA productivity and isomer selectivity are (1) absence of a hydrogen donor, (2

  18. Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid.

    Science.gov (United States)

    Vu, Chi B; Bemis, Jean E; Benson, Ericka; Bista, Pradeep; Carney, David; Fahrner, Richard; Lee, Diana; Liu, Feng; Lonkar, Pallavi; Milne, Jill C; Nichols, Andrew J; Picarella, Dominic; Shoelson, Adam; Smith, Jesse; Ting, Amal; Wensley, Allison; Yeager, Maisy; Zimmer, Michael; Jirousek, Michael R

    2016-02-11

    This report describes the synthesis and preliminary biological characterization of novel fatty acid niacin conjugates and fatty acid salicylate conjugates. These molecular entities were created by covalently linking two bioactive molecules, either niacin or salicylic acid, to an omega-3 fatty acid. This methodology allows the simultaneous intracellular delivery of two bioactives in order to elicit a pharmacological response that could not be replicated by administering the bioactives individually or in combination. The fatty acid niacin conjugate 5 has been shown to be an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. On the other hand, the fatty acid salicylate conjugate 11 has been shown to have a unique anti-inflammatory profile based on its ability to modulate the NF-κB pathway through the intracellular release of the two bioactives.

  19. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    Science.gov (United States)

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  20. Metabolic Interactions between Vitamin A and Conjugated Linoleic Acid

    Directory of Open Access Journals (Sweden)

    Gianfranca Carta

    2014-03-01

    Full Text Available Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4. However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  1. Metabolic interactions between vitamin A and conjugated linoleic acid.

    Science.gov (United States)

    Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Ortiz, Berenice; Giordano, Elena; Belury, Martha A; Quadro, Loredana; Banni, Sebastiano

    2014-03-24

    Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  2. Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

    Science.gov (United States)

    Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung

    2014-01-01

    Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

  3. Analysis of Peptides and Conjugates by Amino Acid Analysis

    DEFF Research Database (Denmark)

    Højrup, Peter

    2015-01-01

    Amino acid analysis is a highly accurate method for characterization of the composition of synthetic peptides. Together with mass spectrometry, it gives a reliable control of peptide quality and quantity before conjugation and immunization.Peptides are hydrolyzed, preferably in gas phase, with 6 M...... HCl at 110 °C for 20-24 h and the resulting amino acids analyzed by ion-exchange chromatography with post-column ninhydrin derivatization. Depending on the hydrolysis conditions, tryptophan is destroyed, and cysteine also, unless derivatized, and the amides, glutamine and asparagine, are deamidated...... to glutamic acid and aspartic acid, respectively. Three different ways of calculating results are suggested, and taking the above limitations into account, a quantitation better than 5 % can usually be obtained....

  4. Incorporation of conjugated linoleic acid and vaccenic acid into lipids from rat tissues and plasma

    DEFF Research Database (Denmark)

    Lund, Pia; Sejrsen, Kristen; Straarup, Ellen Marie

    2006-01-01

    The objective of this study was to determine the incorporation of conjugated linoleic acid (CLA) into triacylglycerols (TAG) and phospholipids (PL) of tissues and plasma, and to interpret the role of dietary-derived vaccenic acid (VA) in increasing the tissue content of CLA (c9,t11) and the influ...

  5. Development and application of nanoparticles synthesized with folic acid-conjugated soy protein

    Science.gov (United States)

    In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-conjug...

  6. Antitumor Agents 255. Novel Glycyrrhetinic Acid-Dehydrozingerone Conjugates as Cytotoxic Agents

    OpenAIRE

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F.; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L.; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-01-01

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anticancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap...

  7. Dynamical Approach to Multiequilibria Problems for Mixtures of Acids and Their Conjugated Bases

    Science.gov (United States)

    Glaser, Rainer E.; Delarosa, Marco A.; Salau, Ahmed Olasunkanmi; Chicone, Carmen

    2014-01-01

    Mathematical methods are described for the determination of steady-state concentrations of all species in multiequilibria systems consisting of several acids and their conjugated bases in aqueous solutions. The main example consists of a mixture of a diprotic acid H[subscript 2]A, a monoprotic acid HB, and their conjugate bases. The reaction…

  8. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Science.gov (United States)

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification....

  9. Conjugated Linoleic Acids Reduce Body Fat in Healthy Postmenopausal Women

    DEFF Research Database (Denmark)

    Raff, M.; Tholstrup, T.; Toubro, S.

    2009-01-01

    Isomers of conjugated linoleic acids (CLA) reduce fat mass FM) and increase insulin sensitivity in some, but not all, murine studies. In humans, this effect is still debatable. In this study, we compared the effect of 2 CLA supplements on total and regional FM assessed by dual energy X-ray absorp......Isomers of conjugated linoleic acids (CLA) reduce fat mass FM) and increase insulin sensitivity in some, but not all, murine studies. In humans, this effect is still debatable. In this study, we compared the effect of 2 CLA supplements on total and regional FM assessed by dual energy X......-ray absorptiometry, changes in serum insulin and glucose concentrations, and adipose tissue (AT) gene expression in humans. In a double-blind, parallel, 16-wk intervention, we randomized 81 healthy postmenopausal women to 1) 5.5 g/d of 40/40% of cis9, trans11-CLA (c9, t11-CLA) and trans10, cis12-CLA (t10, c12-CLA......) (CLA-mix); 2) cis9, trans11-CLA (c9, t11-CLA); or 3) control (olive oil). We assessed all variables before and after the intervention. The CLA-mix group had less total FM (4%) and lower-body FM (7%) than the control (P = 0.02 and

  10. Conjugated linoleic acid isomers: differences in metabolism and biological effects.

    Science.gov (United States)

    Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, Maria Puy

    2009-01-01

    The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis-9,trans-11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans-10,cis-12 isomer is more efficiently oxidized than the cis-9,trans-11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis-9,trans-11 and trans-10,cis-12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis-9,trans-11 isomer is mainly responsible for the anticarcinogenic effect, the trans-10,cis-12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently.

  11. Implication of conjugated linoleic acid (CLA) in human health.

    Science.gov (United States)

    Dilzer, Allison; Park, Yeonhwa

    2012-01-01

    Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its variety of biologically beneficial effects. CLA reduces body fat, cardiovascular diseases and cancer, and modulates immune and inflammatory responses as well as improves bone mass. It has been suggested that the overall effects of CLA are the results of interactions between two major isomers, cis-9,trans-11 and trans-10,cis-12. This review will primarily focus on current CLA publications involving humans, which are also summarized in the tables. Along with a number of beneficial effects of CLA, there are safety considerations for CLA supplementation in humans, which include effects on liver functions, milk fat depression, glucose metabolism, and oxidative stresses.

  12. Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism.

    Science.gov (United States)

    Kim, Yoo; Kim, Jonggun; Whang, Kwang-Youn; Park, Yeonhwa

    2016-02-01

    Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.

  13. Dietary conjugated linoleic acids decrease leptin in porcine adipose tissue.

    Science.gov (United States)

    Di Giancamillo, Alessia; Rossi, Raffaella; Vitari, Francesca; Pastorelli, Grazia; Corino, Carlo; Domeneghini, Cinzia

    2009-10-01

    We investigated the effects of dietary conjugated linoleic acids (CLA) on white adipose tissue (WAT) in heavy pigs. Twelve pigs were assigned to 1 of 2 groups supplemented with either 0 or 0.75% of a CLA preparation (isomeric mixture) and were slaughtered at 159 +/- 2.3 kg live weight. Their subcutaneous WAT was analyzed by both chemical and microanatomical methods. The WAT of CLA-fed pigs tended to have a higher protein content (P = 0.064) and smaller adipocytes (P = 0.053) than that of control (CTR) pigs. The number of proliferating preadipocytes tended to be greater (P = 0.076) in pigs fed CLA, whereas the number of apoptotic adipocytes was greater (P leptin (Ob) expression was lower (P = 0.048) in adipocytes from treated pigs and Western blot quantification of Ob revealed lower levels (P tissue.

  14. Antitumor Agents 255. Novel Glycyrrhetinic Acid-Dehydrozingerone Conjugates as Cytotoxic Agents

    Science.gov (United States)

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F.; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L.; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-01-01

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anticancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED50 values of 0.6, 0.8, and 0.9 μM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anticancer drug discovery and development. PMID:17591444

  15. Dietary conjugated linoleic acid supplementation of laying hens: effects on egg fatty acid composition and quality

    Directory of Open Access Journals (Sweden)

    A. Franchini

    2011-03-01

    Full Text Available Conjugated linoleic acid (CLA is a common term for a group of positional and geometric isomers of linoleic acid; the most commonly found in natural products is cis-9, trans-11-octadecanoic acid. Naturally occurring CLA is produced as an intermediate product of microbial metabolism of linoleic acid in the rumen. For this reason the CLA concentration is higher in ruminant products, such as milk, cheese and meat compared to products derived from monogastrics, particularly chicken meat and egg yolk. Recent investigations suggest that CLA have anticarcinogenic properties, antiatherosclerotic and antioxidant activity (Ip et al., 1995; Nicolosi et al., 1997; Du et al., 2001...

  16. Production of carrier-peptide conjugates using chemically reactive unnatural amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Young, Travis; Schultz, Peter G.

    2015-08-18

    Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

  17. Production of carrier-peptide conjugates using chemically reactive unnatural amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Young, Travis; Schultz, Peter G

    2014-01-28

    Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

  18. Production of carrier-peptide conjugates using chemically reactive unnatural amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Young, Travis; Schultz, Peter G

    2013-12-17

    Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

  19. Kinetic Optimization of Folic Acid Polymer Conjugates for Drug Targeting

    Directory of Open Access Journals (Sweden)

    Jacob M. Ngoy

    2011-01-01

    Full Text Available Problem statement: Folic Acid (FA is an essential, bioavailable water soluble B-complex vitamin that helps in the replication of normal cells. It is obtained from natural sources and it deficiency can leads to oncogenic cells development. Within this frame work in mind, we designed and synthesized a new bioconjugate carrier that can enhance the effectiveness of FA. Approach: The polymeric carrier: Polysucscinimide (PSI was synthesized via the polycondensation of aspartic acid by attaching 3-(N,N-Dimethylamino Propylamine (DMP and 1,3-P-propylenediamine (PDA for solubility behavior and reactivity for FA site anchoring. Also the use of an ester 2-(1H-benzotrial-1- yl-1,1,3,3-tetramethylurium Hexafluorophosphate (HBTU as coupling agent to FA. The bioreversible binding of the water-soluble and biocompatible macromolecular were attested through kinetic studies. The kinetic reactions were investigated through the nuclear resonance (H1NMR spectra analysis. Results and Conclusion: The H1NMR optimization reaction times were found within the range of 120-130 min (80-85% as optimum coupling. The yield of the FA occurred within the same time range but with maximum incorporation between 90-100%. The growth of FA incorporation in terms of reaction time resulted to an increase inherent viscosity relative to the decrease of water solubility of the conjugate obtained.

  20. Nonlinear Optical Properties of Au-Nanoparticles Conjugated with Lipoic Acid in Water

    Science.gov (United States)

    Trejo-Durán, M.; Cornejo-Monroy, D.; Alvarado-Méndez, E.; Olivares-Vargas, A.; Castano, V. M.

    2014-08-01

    Gold nanoparticles were chemically conjugated with lipoic acid to control their optical properties. Z-scan and other optical techniques were used to characterize the non-linear behavior of the resulting nanostructured materials. The results show that the nonlinearity is of thermal origin, which can be controlled by the use of lipoic acid as well as other organic molecules conjugated onto metal nanoparticles. In particular, the presence of lipoic acid increases n_2 and dn/dT.

  1. Isolation of novel indole-3-acetic acid conjugates by immunoaffinity extraction.

    Science.gov (United States)

    Pencík, Ales; Rolcík, Jakub; Novák, Ondrej; Magnus, Volker; Barták, Petr; Buchtík, Roman; Salopek-Sondi, Branka; Strnad, Miroslav

    2009-12-15

    An analytical protocol for the isolation and quantification of indole-3-acetic acid (IAA) and its amino acid conjugates was developed. IAA is an important phytohormone and formation of its conjugates plays a crucial role in regulating IAA levels in plants. The developed protocol combines a highly specific immunoaffinity extraction with a sensitive and selective LC-MS/MS analysis. By using internal standards for each of the studied compounds, IAA and seven amino acid conjugates were analyzed in quantities of fresh plant material as low as 30 mg. In seeds of Helleborus niger, physiological levels of these compounds were found to range from 7.5 nmol g(-1) fresh weight (IAA) to 0.44 pmol g(-1) fresh weight (conjugate with Ala). To our knowledge, the identification of IAA conjugates with Gly, Phe and Val from higher plants is reported here for the first time.

  2. Synthesis and structural elucidation of glutathione and N-aceyl-cysteine conjugates of 5-aminosalicylic acid

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.

    1993-01-01

    The ability of 5-aminosalicylic acid (5-ASA) to be oxidized to a quinone monoimine compound capable of conjugating with nucleophilic compounds such as N-acetyl-cysteine (NAC) and glutathione (GSH) has been investigated in vitro. Three isomeric conjugates of 5-ASA and NAC as well as three isomeric...

  3. Chemical characteristics, fatty acid composition and conjugated linoleic acid (CLA) content of traditional Greek yogurts.

    Science.gov (United States)

    Serafeimidou, Amalia; Zlatanos, Spiros; Laskaridis, Kostas; Sagredos, Angelos

    2012-10-15

    Many studies with conjugated linoleic acid (CLA) indicate that it has a protective effect against mammary cancer. Because dairy products are the most important dietary sources of CLA, we have investigated the CLA concentrations and additionally the fatty acid profiles and chemical composition of several commercial, traditional, Greek yogurts from different geographical origin. The fat content of yogurts was in the order of goatCLA/100 g fat. Low-fat milk yogurts showed lower values of c-9, t-11 CLA content on lipid basis compared to full-fat yogurts. Samples from mountain areas showed average c-9, t-11 CLA content higher than those from prairie districts. The highest amounts of saturated fatty acids (SFA) were found in low-fat yogurts, of monounsaturated fatty acids (MUFA) in sheep milk yogurts and of polyunsaturated fatty acid (PUFA) in low-fat cow milk yogurts.

  4. Simultaneous Determination of Neutral Sugar, Uronic Acid, Amino Sugar and Sialic Acid of Polysaccharides by Gas Chromatography%气相色谱法同时测定多糖中的中性糖、糖醛酸、氨基糖和唾液酸

    Institute of Scientific and Technical Information of China (English)

    李波; 芦菲; 田素玉

    2011-01-01

    Neutral sugar, uronic acid, amino sugar and sialic acid were effectively determined simultaneously by gas chromatography after methanolysis and trimethylsilylation. Three standard monosaccharide mixtures (including Ara, Rha, Fuc, Xyl, Man, Gal, Gle, GlcA, GalA, GalNAc, GlcNAc, Neu5Ac) and two polysaccharide samples (okara polysaccharide DFP, Coprinus comatus polysaccharide F32) were methanolysis by 1 mol/L HC1/methanol at 85 ℃ for 18 -24 h, neutralized with Ag2CO3 and re-N-acetylated by adding acetic anhydride for 24 h in the dark. After removing the silver salts, the dried residue was trimethylsilylated by adding silylation reagent (pyridine/hexamethyldisilazane/chlorotrimethylsilane = 5: 1:1 ) for 30 min at room temperature. Then the final products were analyzed by gas chromatography. This method needs fewer amount of sample, and has higher sensitivity and resolution. It can simultaneous detect kinds of monosaccharides. It will have a great potential for application.%采用甲醇解和硅烷衍生化,用气相色谱法同时测定样品中的中性糖、糖醛酸、N-乙酰氨基糖和唾液酸,取得了很好的效果。3种标准单糖混合物(包含阿拉伯糖、鼠李糖、岩藻糖、木糖、甘露糖、半乳糖、葡萄糖、葡萄糖醛酸、半乳糖醛酸、N-乙酰半乳糖、N-乙酰葡萄糖、5-乙酰唾液酸)和2种多糖样品(豆腐渣多糖DFP、鸡腿菇多糖F32)用1mol/L盐酸甲醇在85℃反应18~24h,碳酸银中和,加入乙酸酐室温暗处反应24h,使氨基糖重新引入N-乙酰基,除银盐,干燥,加入硅烷化试剂[y(吡啶):y(六甲基二硅氨烷):V(三甲基氯硅烷)=5:1:1),室温放置30min,最后用气相色谱进行分析。

  5. Synthesis and characterization of polyamidoamine conjugates of neridronic acid

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2015-10-01

    Full Text Available of water and it was performed at room temperature thereby making the reaction environmentally friendly and economically viable. These conjugates are potential prodrugs and they were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier...

  6. Comparison of linoleic and conjugated linoleic acids in enzymatic acidolysis of tristearin

    DEFF Research Database (Denmark)

    Yang, Tiankui; Xu, Xuebing; Li, L.T.

    2001-01-01

    tristearin (SSS) and linoleic (L) or conjugated linoleic (cL) acids (1:6, mol/mol). The other was between tristearin and the mixture of linoleic and conjugated linoleic acids (1:3:3, mol/mol/mol). Acyl incorporation and migration together with triacylglycerol composition of the products were monitored...... with gas chromatography, pancreatic lipase hydrolysis, and high performance liquid chromatography. Both acyl incorporation and migration of linoleic acid were faster than those of conjugated linoleic acid. At 5 h reaction, there were 13.0% LLL, 46.5% LSL, 27.7% LSS, and 5.6% SSS in the product for a system...... between tristearin and linoleic acid; whereas there were 2.4% cLcLcL, 10.4% cLScL, 50.9% cLSS, and 36.2% SSS in the product for a system between tristearin and conjugated linoleic acid. The results suggest that linoleic acid was more reactive than conjugated linoleic acid in the enzymatic acidolysis...

  7. Conjugated linolenic acids (CLnA, super CLA – natural sources and biological activity

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2014-11-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a wide range of biological activity. Among them conjugated fatty acids are of great interest. Conjugated linoleic acids (CLA, which exert a multidirectional health-benefiting influence, and conjugated linolenic acids (CLnA, super CLA are examples of this group of fatty acids. CLnA are a group of positional and geometric isomers of octadecatrienoic acid (C18:3, which possess double bonds at positions 9, 11, 13 or 8, 10, 12 of their chain. Some vegetable oils are rich sources of CLnA, e.g. bitter melon oil (from Momordica charantia seeds and pomegranate oil (from Punica granatum seeds. The aim of this paper was to present information concerning natural sources and health-promoting activities of conjugated linolenic acids.The presented data reveal that conjugated linolenic acids may be very useful in prevention and treatment of many diseases, especially diabetes, arteriosclerosis , obesity and cancers (mammary, prostate and colon cancer. Among many potential mechanisms of their action, the fact that some CLnA are converted by oxidoreductases into CLA is very important. It seems to be very reasonable to conduct research concerning the possibility of CLnA use in prevention of many diseases.

  8. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability.

    Science.gov (United States)

    Manju, S; Sreenivasan, K

    2011-07-01

    Polymer-drug conjugates have gained much attention largely to circumvent lower drug solubility and to enhance drug stability. Curcumin is widely known for its medicinal properties including its anticancer efficacy. One of the serious drawbacks of curcumin is its poor water solubility which leads to reduced bioavailability. With a view to address these issues, we synthesized hyaluronic acid-curcumin (HA-Cur) conjugate. The drug conjugate was characterized using FT-IR, NMR, Dynamic light scattering and TEM techniques. The conjugates, interestingly found to assembles as micelles in aqueous phase. The formation of micelles seems to improve the stability of the drug in physiological pH. We also assessed cytotoxicity of the conjugate using L929 fibroblast cells and quantified by MTT assay. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Targeted gene correction using psoralen, chlorambucil and camptothecin conjugates of triplex forming peptide nucleic acid (PNA)

    DEFF Research Database (Denmark)

    Birkedal, Henrik; Nielsen, Peter E

    2011-01-01

    Gene correction activation effects of a small series of triplex forming peptide nucleic acid (PNA) covalently conjugated to the DNA interacting ligands psoralen, chlorambucil and camptothecin targeted proximal to a stop codon mutation in an EGFP reporter gene were studied. A 15-mer homopyrimidine...... PNA conjugated to the topoisomerase I inhibitor camptothecin was found to increase the frequency of repair domain mediated gene correctional events of the EGFP reporter in an in vitro HeLa cell nuclear extract assay, whereas PNA psoralen or chlorambucil conjugates both of which form covalent and also....... Consistent with the extract experiments, treatment with adduct forming PNA conjugates (psoralen and chlorambucil) resulted in a decrease in background correction frequencies in transiently transfected cells, whereas unmodified PNA or the PNA-camptothecin conjugate had little or no effect. These results...

  10. Fatty acid profiles in tissues of mice fed conjugated linoleic acid

    DEFF Research Database (Denmark)

    Gøttsche, Jesper; Straarup, Ellen Marie

    2006-01-01

    The incorporation of vaccenic acid (VA, 0.5 and 1.2%), conjugated linoleic acid (CLA, mixture of primarily c9,t11- and t10,c12-CLA, 1.2%), linoleic acid (LA, 1.2%) and oleic acid (OA, 1.2%) into different tissues of mice was examined. The effects on the fatty acid composition of triacylglycerols...... (TAG) and phospholipids (PL) in kidney, spleen, liver and adipose tissue were investigated. VA and CLA (c9,t11- and t10,c12-CLA) were primarily found in TAG, especially in kidney and adipose tissue, respectively. Conversion of VA to c9,t11-CLA was indicated by our results, as both fatty acids were...... incorporated into all the analyzed tissues when a diet containing VA but not c9,t11-CLA was fed. Most of the observed effects on the fatty acid profiles were seen in the CLA group, whereas only minor effects were observed in the VA groups compared with the CA group. Thus, CLA increased n-3 polyunsaturated...

  11. Synthesis and photophysicochemical studies of a water soluble conjugate between folic acid and zinc tetraaminophthalocyanine

    Energy Technology Data Exchange (ETDEWEB)

    Khoza, Phindile; Antunes, Edith [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa); Chen, Ji-Yao [State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai 200433 (China); Nyokong, Tebello, E-mail: t.nyokong@ru.ac.za [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa)

    2013-02-15

    This work reports on the synthesis of zinc tetraaminophthalocyanine (ZnTAPc) functionalized with folic acid (FA), forming ZnTAPcFA. The conjugate between FA and ZnTAPc was soluble in water whereas ZnTAPc alone is not. The structure of ZnTAPcFA conjugate was elucidated by {sup 1}H NMR, MALDI-TOF mass and FTIR spectra. Photophysical and photochemical studies of ZnTAPcFA were conducted in DMSO. The increase in fluorescence quantum yield of the conjugate was accompanied by a decrease in the triplet and singlet oxygen quantum yields. The changes in triplet quantum and singlet oxygen quantum yields were marginal when ZnTAPc was simply mixed with FA without a chemical bond. - Highlights: Black-Right-Pointing-Pointer A conjugate between folic acid and a zinc tetraaminophthalocyanine was formed. Black-Right-Pointing-Pointer The conjugate is water soluble even though the phthalocyanine alone is not. Black-Right-Pointing-Pointer The fluorescence quantum yield of the conjugate was enhanced compared to the phthalocyanine alone. Black-Right-Pointing-Pointer Triplet quantum yields decreased for the conjugate.

  12. The Immunomodulatory Activity of Jacaric Acid, a Conjugated Linolenic Acid Isomer, on Murine Peritoneal Macrophages.

    Directory of Open Access Journals (Sweden)

    Wai Nam Liu

    Full Text Available This study aims at demonstrating the immunomodulatory property of jacaric acid, a conjugated linolenic acid (CLNA isomer that is present in jacaranda seed oil, on murine peritoneal macrophages. Our results showed that jacaric acid exhibited no significant cytotoxicity on the thioglycollate-elicited murine peritoneal macrophages as revealed by the neutral red uptake assay, but markedly increased their cytostatic activity on the T-cell lymphoma MBL-2 cells as measured by the fluorometric CyQuant® NF Cell Proliferation Assay Kit. Flow cytometric analysis indicated that jacaric acid could enhance the endocytic activity of macrophages and elevated their intracellular production of superoxide anion. Moreover, jacaric acid-treated macrophages showed an increase in the production of nitric oxide which was accompanied by an increase in the expression level of inducible nitric oxide synthase protein. In addition, the secretion of several pro-inflammatory cytokines, including interferon-γ, interleukin-1β and tumor necrosis factor-α, was up-regulated. Collectively, our results indicated that the naturally-occurring CLNA isomer, jacaric acid, could exhibit immunomodulating activity on the murine peritoneal macrophages in vitro, suggesting that this CLNA isomer may act as an immunopotentiator which can be exploited for the treatment of some immunological disorders with minimal toxicity and fewer side effects.

  13. Lewis acid adducts of narrow band gap conjugated polymers.

    Science.gov (United States)

    Welch, Gregory C; Bazan, Guillermo C

    2011-03-30

    We report on the interaction of Lewis acids with narrow band gap conjugated copolymers containing donor and acceptor units. Examination of the widely used poly[(4,4-bis(2-ethylhexyl)cyclopenta-[2,1-b:3,4-b']dithiophene)-2,6-(diyl-alt-benzo[2,1,3]thiadiazole)-4,7-diyl] (1) shows weaker binding with B(C(6)F(5))(3) when compared with a small molecule that contains a cyclopenta-[2,1-b:3,4-b']dithiophene (CDT) unit flanked by two benzo[2,1,3]thiadiazole (BT) fragments. Studies on model compounds representative of 1, together with a comparison between B(C(6)F(5))(3) and BBr(3), indicate that the propensity for Lewis acid coordination is decreased because of steric encumbrance surrounding the BT nitrogen sites. These observations led to the design of chromophores that incorporate an acceptor unit with a more basic nitrogen site, namely pyridal[2,1,3]thiadiazole (PT). That this strategy leads to a stronger B-N interaction was demonstrated through the examination of the reaction of B(C(6)F(5))(3) with two small molecules bis(4,4-bis(hexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-4,7-pyridal[2,1,3]thiadiazole (8) and bis{2-thienyl-(4,4-bis(hexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)}-4,7-pyridal[2,1,3]thiadiazole (9) and two polymer systems (poly[(4,4-bis(2-ethylhexyl)cyclopenta-[2,1-b:3,4-b']dithiophene)-2,6-diyl-alt-([1,2,5]thiadiazolo[3,4-c]pyridine)-4,7-diyl] (10) and poly[(4,4-bis(2-ethylhexyl)cyclopenta-[2,1-b:3,4-b']dithiophene)-2,6-diyl-alt-(4',7'-bis(2-thienyl)-[1,2,5]thiadiazolo[3,4-c]pyridine)-5,5-diyl] (11). From a materials perspective, it is worth pointing out that through the binding of B(C(6)F(5))(3), new NIR-absorbing polymers can be generated with band gaps from 1.31 to 0.89 eV. A combination of studies involving ultraviolet photoemission spectroscopy and density functional theory shows that the narrowing of the band gap upon borane coordination to the pyridal nitrogen on PT is a result of lowering the energies of both the highest occupied molecular

  14. Preparation and Characterization of Self-Assembled Nanoparticles of Hyaluronic Acid-Deoxycholic Acid Conjugates

    Directory of Open Access Journals (Sweden)

    Xuemeng Dong

    2010-01-01

    Full Text Available Novel amphiphilic biopolymers were synthesized using hyaluronic acid (HA as a hydrophilic segment and deoxycholic acid (DOCA as a hydrophobic segment by a 1-ethyl-3-(3-dimethylaminopropyl carbodiimide mediated coupling reaction. The structural characteristics of the HA-DOCA conjugates were investigated using H1 NMR. Self-assembled nanoparticles were prepared based on HA-DOCA conjugates, and its characteristics were investigated using dynamic laser light scattering, transmission electron microscopy (TEM, and fluorescence spectroscopy. The mean diameter was about 293.5 nm with unimodal size distribution in distilled water. The TEM images revealed that the shape of HA-DOCA self-aggregates was spherical. The critical aggregation concentration (CAC was in the range of 0.025–0.056 mg/mL. The partition equilibrium constant (Kv of pyrene in self-aggregates solution was from 1.45×104 to 3.64×104. The aggregation number of DOCA groups per hydrophobic microdomain, estimated by the fluorescence quenching method using cetylpyridinium chloride, increased with increasing degree of substitution.

  15. Comparison of linoleic and conjugated linoleic acids in enzymatic acidolysis of tristearin

    DEFF Research Database (Denmark)

    Yang, Tiankui; Xu, Xuebing; Li, L.T.

    2001-01-01

    The acyl incorporation and migration of linoleic and conjugated linoleic acids in enzymatic acidolysis were compared in a solvent-free system. Two systems were used in the Lipozyme RM IM-catalyzed acidolysis at 60C temperature and 5% by weight enzyme load (based on substrates). One included...... with gas chromatography, pancreatic lipase hydrolysis, and high performance liquid chromatography. Both acyl incorporation and migration of linoleic acid were faster than those of conjugated linoleic acid. At 5 h reaction, there were 13.0% LLL, 46.5% LSL, 27.7% LSS, and 5.6% SSS in the product for a system...

  16. Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents.

    Science.gov (United States)

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-09-15

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anti-cancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED(50) values of 0.6, 0.8, and 0.9 microM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development.

  17. GSTP1-1 stereospecifically catalyzes glutathione conjugation of ethacrynic acid

    NARCIS (Netherlands)

    Iersel, M.L.P.S. van; Lipzig, M.M.H. van; Rietjens, I.M.C.M.; Vervoort, J.; Bladeren, P.J. van

    1998-01-01

    Using 1H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one

  18. GSTP1-1 stereospecifically catalyzes glutathione conjugation of ethacrynic acid

    NARCIS (Netherlands)

    Iersel, M.L.P.S. van; Lipzig, M.M.H. van; Rietjens, I.M.C.M.; Vervoort, J.; Bladeren, P.J. van

    1998-01-01

    Using 1H NMR two diastereoisomers of the ethacrynic acid glutathione conjugate (EASG) as well as ethacrynic acid (EA) could be distinguished and quantified individually. Chemically prepared EASG consists of equal amounts of both diastereoisomers. GSTP1-1 stereospecifically catalyzes formation of one

  19. A rapid biosensor-based method for quantification of free and glucose-conjugated salicylic acid

    Science.gov (United States)

    Salicylic acid (SA) is an important signalling molecule in plant defenses against biotrophic pathogens. It is also involved in several other processes such as heat production, flowering, and germination. SA exists in the plant as free SA and as an inert glucose conjugate (salicylic acid 2-O-ß-D-...

  20. The effects of conjugated linoleic acid (CLA) and canola oil on the ...

    African Journals Online (AJOL)

    huis

    Keywords: Conjugated linoleic acid, unsaturated fatty acids, egg yolk and albumen pH, .... were housed in individual cages with a light regimen of 16 h light : 8 h darkness. .... Nutritional studies showed that CLA isomers were readily incorporated into ... This data suggested that the t-10, c-12 CLA isomer might have a higher.

  1. Conjugated Linoleic Acid Is a Preferential Substrate for Fatty Acid Nitration*

    Science.gov (United States)

    Bonacci, Gustavo; Baker, Paul R. S.; Salvatore, Sonia R.; Shores, Darla; Khoo, Nicholas K. H.; Koenitzer, Jeffrey R.; Vitturi, Dario A.; Woodcock, Steven R.; Golin-Bisello, Franca; Cole, Marsha P.; Watkins, Simon; St. Croix, Claudette; Batthyany, Carlos I.; Freeman, Bruce A.; Schopfer, Francisco J.

    2012-01-01

    The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the primary endogenous substrate for fatty acid nitration in vitro and in vivo, yielding up to 105 greater extent of nitration products as compared with bis-allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification. Nitroalkene derivatives of CLA and their metabolites are detected in the plasma of healthy humans and are increased in tissues undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite supplementation in rodents elevates NO2-CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic epithelium. These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms. PMID:23144452

  2. Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

    Science.gov (United States)

    Sidova, Veronika; Zoufaly, Pavel; Pokorny, Jan; Dzubak, Petr; Hajduch, Marian; Popa, Igor

    2017-01-01

    In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 μM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 μM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development. PMID:28158265

  3. Study on synthesis and distribution in vivo of 5-Fu-cholic acid conjugate

    Institute of Scientific and Technical Information of China (English)

    Jie Li; Li Hai; Wei Jia Liu; Xiao Chun Wu; Yong Wu

    2009-01-01

    A series of hepatic targeting drugs,5-Fu-cholic acid conjugate T1-T5,were synthesized.5-Fu and cholic acid was selected as starting material,after N-hydroxymethylation,condensation,hydrogenolysis to obtain carboxylated 5-Fu 5a--e.Carboxylated 5-Fu 5a--e were eondensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e,7a-e were deproteeted to get T1-T5.

  4. Dextran and 5-aminosalicylic acid (5-ASA) conjugates: synthesis, characterisation and enzymic hydrolysis.

    Science.gov (United States)

    Ahmad, Shavej; Tester, Richard F; Corbett, Alistair; Karkalas, John

    2006-11-27

    Mesalamine (5-aminosalicylic acid) is the drug of choice for the treatment of Crohn's disease. A scheme for the synthesis of 5-aminosalicylic acid (5-ASA) conjugates of dextrans was developed with a focus on Crohn's disease applications. Dextrans were oxidised using sodium periodate (NaIO(4)), where the aldehyde groups formed were coupled with the alpha-amino (-NH(2)) group of 5-ASA. The resulting imine bonds were unstable in water and were consequently reduced to secondary amine groups. The effects of different aspects of the conjugation reaction were studied. These included the following: the molecular weight of the dextrans, the molar proportion of NaIO(4) to the dextrans (for periodate oxidation), the pH of the conjugation solutions, the ratio 5-ASA to oxidised polysaccharide and the relationship between the degree of conjugation and the amount of enzyme hydrolysis. Conjugates incubated in HCl were stable in 0.5 and 1.0M HCl, but they underwent degradation in 2.0 and 4.0M HCl. Dextrans (MW 20,000) with various degrees of oxidation (12%, 26%, 46%, 65%, 90% and 93%) were also prepared. Each oxidised dextran sample was conjugated with 5-ASA, and the product was quantified by high-performance liquid chromatography (HPLC). Dextrans with a maximum degree of oxidation (93%) unsurprisingly gave maximum conjugation of 5-ASA (49.1mg per 100mg of product) but were resistant to dextranase hydrolysis. Less oxidised dextrans (12%) conjugated proportionally less 5-ASA (15.1mg per 100mg of product) but were successfully hydrolysed by dextranase, suggesting their potential applications for the treatment of Crohn's disease in the distal ileum and proximal colon.

  5. Conjugated linoleic acid as a potential protective factor in prevention of breast cancer 

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2013-01-01

    Full Text Available Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid occurs in the largest quantities, constituting over 90�0of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  6. The In vitro Effects of Nano-encapsulated Conjugated Linoleic Acid on Stability of Conjugated Linoleic Acid and Fermentation Profiles in the Rumen

    OpenAIRE

    Heo, Wan; Kim, Eun Tae; Cho, Sung Do; Kim, Jun Ho; Kwon, Seong Min; Jeong, Ha Yeon; Ki, Kwang Seok; Yoon, Ho Baek; Ahn, Young Dae; Lee, Sung Sill; Kim, Young Jun

    2016-01-01

    This study was aimed to evaluate the stability of conjugated linoleic acids (CLAs) by nano-encapsulation against in vitro ruminal biohydrogenation by microbial enzymatic conversion. CLAs (free fatty acid form of CLA [CLA-FFA], nano-encapsulated CLA-FFA, triglyceride form of CLA [CLA-TG], and nano-encapsulated CLA-TG) were used in the in vitro fermentation experiments. When Butyrivibrio fibrisolvens (B. fibrisolvens) was incubated with CLA-FFAs, the concentrations of cis-9, trans-11 CLA and va...

  7. 21 CFR 573.637 - Methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10, cis-12-octadecadienoic...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methyl esters of conjugated linoleic acid (cis-9... § 573.637 Methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10, cis-12-octadecadienoic acids). The food additive, methyl esters of conjugated linoleic acid (cis-9, trans-11 and trans-10...

  8. Identification and quantification of (dihydro) hydroxycinnamic acids and their conjugates in potato by UHPLC–DAD–ESI-MSn

    NARCIS (Netherlands)

    Narvaez Cuenca, C.E.; Vincken, J.P.; Gruppen, H.

    2012-01-01

    Hydroxycinnamic acid conjugates (HCAcs) and dihydrohydroxycinamic acid conjugates (DHCAcs) were identified and quantified in potato tuber extracts by UHPLC–DAD–ESI-MSn. The HCAcs and DHCAcs identification took place by screening for product ions and neutral losses in combination with UV spectra. Thi

  9. Quantitative Structure-property Relationship Studies on Amino Acid Conjugates of Jasmonic Acid as Defense Signaling Molecules

    Institute of Scientific and Technical Information of China (English)

    Zu-Guang Li; Ke-Xian Chen; Hai-Ying Xie; Jian-Rong Gao

    2009-01-01

    Jasmonates and related compounds, including amino acid conjugates of jasmonic acid, have regulatory functions in the signaling pathway for plant developmental processes and responses to the complex equilibrium of biotic and abiotic stress.But the molecular details of the signaling mechanism are still poorly understood. Statistically significant quantitative structure-property relationship models (r2 > 0.990) constructed by genetic function approximation and molecular field analysis were generated for the purpose of deriving structural requirements for lipophilicity of amino acid conjugates of jasmonic acid. The best models derived in the present study provide some valuable academic information in terms of the 213D-descriptors influencing the lipophilicity, which may contribute to further understanding the mechanism of exogenous application of jasmonates in their signaling pathway and designing novel analogs ofjasmonic acid as ecological pesticides.

  10. Novel molecular anti-colorectalcancer conjugate:chlorambucil-adipic acid dihydrizide-glutamine.

    Science.gov (United States)

    Tabasi, Maryam Akhavan; Amanlou, Massoud; Siadat, Seyed Davar; Nourmohammadi, Zahra; Omoomi, Farnoor Davachi; Ebrahimi, Seyed Esmaeil Sadat; Aghasadeghi, Mohammad Reza; Rahimi, Pooneh; Pourhosseini, Sahar; Mehravi, Bita; Ardestani, Mehdi Shafiee

    2013-11-01

    Cancer is one of the most fatal diseases in the world and it has been years that finding new drugs and chemotherapeutic techniques with lowest side effects become one of the most important challenging matters needs really hard efforts. Chlorambucil (CBL), an ancient direct-acting alkylating anticancer agent, is commonly used for initial treatment of some kinds of cancers but the use of CBL is often limited because of the unpleasant side effects due to its lack of specificity for targeting cancer cells. In this research we tried to increase the specificity of CBL by producing a novel conjugate by using glutamine amino acid (Glut). Based on previous studies, poly amines and nitrogen compounds noticeably are used by cancer cells increasingly; therefore we decided to increase the efficiency and specificity of CBL by designing and producing a novel anti cancer conjugate using glutamine amino acid as an uptake enhancer, CBL, and Adipic acid Dihydrazide (ADH) as a spacer and linker. The biological tests were carried out on HT29 colorectal cancer cell line to evaluate its anticancer properties. Biological tests like MTT assay, finding IC50, evaluating the induced mechanism of the death of our novel CBL-Glutamine conjugate on HT29 cells, testing abnormal toxicity of this conjugate on mice in comparison with CBL drug were careid out. We found that not only CBL-Glutamine conjugate preserved its anti cancer property with regard to CBL drug, but also it represent lower abnormal toxicity in mice. Apoptosis was detected as its mechanism of the death. Our present study provides a promising strategy for targeting cancer cells using amino acids nano-conjugate drugs. The future perspectives have also been highlighted in continuing similar and relative researches.

  11. Enhancing charge storage of conjugated polymer electrodes with phenolic acids

    Science.gov (United States)

    Wagner, Michal; Rębiś, Tomasz; Inganäs, Olle

    2016-01-01

    We here present studies of electrochemical doping of poly(1-aminoanthraquinone) (PAAQ) films with three structurally different phenolic acids. The examined phenolic acids (sinapic, ferulic and syringic acid) were selected due to their resemblance to redox active groups, which can be found in lignin. The outstanding electrochemical stability of PAAQ films synthesized for this work enabled extensive cycling of phenolic acid-doped PAAQ films. Potentiodynamic and charge-discharge studies revealed that phenolic acid-doped PAAQ films exhibited enhanced capacitance in comparison to undoped PAAQ films, together with appearance of redox activity characteristics specific for each dopant. Electrochemical kinetic studies performed on microelectrodes affirmed the fast electron transfer for hydroquinone-to-quinone reactions with these phenolic compounds. These results imply the potential application of phenolic acids in cheap and degradable energy storage devices.

  12. Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review.

    Science.gov (United States)

    Heinze, Verónica M; Actis, Adriana B

    2012-02-01

    The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000-2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.

  13. Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate

    NARCIS (Netherlands)

    Rudolph, G; Kloeters-Plachky, P; Sauer, P; Stiehl, A

    Background Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. Methods We studied

  14. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    DEFF Research Database (Denmark)

    León, John Jairo Castillo; Rindzevicius, Tomas; Wu, Kaiyu

    2014-01-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The sur...

  15. Lead detoxification activities of a class of novel DMSA--amino acid conjugates.

    Science.gov (United States)

    Xu, Yanxia; Wang, Yuji; Wang, Ling; Zhao, Ming; Zhang, Xiaoyi; Hu, Xiaomin; Hou, Baoguang; Peng, Li; Zheng, Meiqing; Wu, Jianhui; Peng, Shiqi

    2011-06-20

    The coupling of the 1-carboxyl of DMSA with l-amino acids led to a class of novel 1-(carbonyl-l-amino-acid)-2,3-dimercaptosuccinic acids (DMSA--amino acid conjugates, DMSA-Gly, -Ser, -Val, -Leu, -Ile, -Asn, -Asp, -Gln, -Glu, -Met, -Phe, and -Trp). In the in vivo evaluation of Pb-loaded mice, 0.4 mmol/kg of the conjugates effectively decreased the Pb levels of the femur, brain, kidney, liver, and blood, greatly enhanced urination, and increased the Pb levels of both urine and feces, while causing no redistributions of Pb to the other organs, especially to the brain. With respect to lowering the bone and brain Pb, DMSA-Ile, -Asn, -Gln, and -Met were more effective than DMSA. This benefit was attributed to their high transmembrane ability. In contrast to Pb, the essential metals such as Fe, Cu, Zn, and Ca of the treated mice were not affected by the administration of the conjugates. Silico molecular modeling predicted that the conjugates had little hepatotoxicity, except possibly for DMSA-Phe.

  16. Synthesis and cytotoxic activities of a series of novel N-methylbisindolylmaleimide amino acid ester conjugates

    Institute of Scientific and Technical Information of China (English)

    Ke Wang; Zheng Yan; Nan Wang; Zhan Zhu Liu

    2012-01-01

    A series of novel N-methylbisindolylmaleimides and natural amino acid conjugates were synthesized and evaluated for their inhibitory activity against six tumor cell lines.Most of the compounds exhibited moderate in vitro cytotoxic activities in the range of 10-100 μmol/L.

  17. Highly enantioselective rhodium-catalyzed conjugate addition of arylboronic acids to enones at room temperature

    NARCIS (Netherlands)

    Martina, SLX; Minnaard, AJ; Hessen, B; Feringa, BL; Martina, Sébastien L.X.; Feringa, Bernard

    2005-01-01

    The rhodium-phosphoramidite-catalyzed asymmetric conjugate addition of arylboronic acids to enones proceeds at room temperature using [Rh(OH)(cod)](2) or [RhCl(cod)](2)/KOH as stable and readily available catalyst precursors. (c) 2005 Published by Elsevier Ltd.

  18. Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids Using Monodentate Phosphoramidite Ligands

    NARCIS (Netherlands)

    -G Boiteau, J.; Imbos, R.; J. Minnaard, A.; Feringa, B.L.

    2003-01-01

    Monodentate phosphoramidites have been used for the first time as chiral ligands in the Rh-catalyzed enantioselective conjugate addition of arylboronic acids to enones, unsaturated esters, lactones, and nitro alkenes. High reaction rates and ee’s up to 89% have been obtained.

  19. Conjugated linoleic acid (CLA: effect modulation of body composition and lipid profile

    Directory of Open Access Journals (Sweden)

    A. Baddini Feitoza

    Full Text Available Conjugated linoleic acid (CLA refers to a family of polyunsaturated fatty acids, being represented by a group of isomers of linoleic acid called conjugated for having a double bound after a simple bound. Among its isomers, trans-10,cis-12 and cis-9, cis-12 CLA stand out. These isomers can lead to different effects on the body: anticarcinogenic, antidiabetogenic, antiatherogenesis and positive body composition alteration. The objective of this review is to describe their mechanisms of action, effects on body composition, on plasmatic lipoproteins and supplementation. Studies about CLA supplementation show its capacity of reducing fat percentage, body mass and of promoting an improvement in lipid metabolism. One of the adverse effects attributed to one of the isomers is insulin resistance by body fat redistribution. Limitations in the scientific models used in CLA researches make impossible to draw conclusions about the action of this fatty acid on human metabolism.

  20. Optimization of conjugated linoleic acid triglycerides via enzymatic esterification in no-solvent system

    Institute of Scientific and Technical Information of China (English)

    YI Dan; SUN Xiuqin; LI Guangyou; LIU Fayi; LIN Xuezheng; SHEN Jihong

    2009-01-01

    We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60°C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.

  1. Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Browne, Elisse C; Parakh, Sonam; Duncan, Luke F; Langford, Steven J; Atkin, Julie D; Abbott, Belinda M

    2016-04-01

    Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.

  2. Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers.

    Science.gov (United States)

    Panda, Siva S; Detistov, Oleksandr S; Girgis, Adel S; Mohapatra, Prabhu P; Samir, Ahmed; Katritzky, Alan R

    2016-05-01

    Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6 μM and 149.3 μM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67 μM and 92.9 μM, respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Selective binding of glutathione conjugates of fatty acid derivatives by plant glutathione transferases.

    Science.gov (United States)

    Dixon, David P; Edwards, Robert

    2009-08-07

    Proteomic studies with Arabidopsis thaliana have revealed that the plant-specific Tau (U) class glutathione transferases (GSTs) are selectively retained by S-hexylglutathione affinity supports. Overexpression of members of the Arabidopsis GST superfamily in Escherichia coli showed that 25 of the complement of 28 GSTUs caused the aberrant accumulation of acylated glutathione thioesters in vivo, a perturbation that was not observed with other GST classes. Each GSTU caused a specific group of fatty acyl derivatives to accumulate, which varied in chain length (C(6) to C(18)), additional oxygen content (0 or 1), and desaturation (0 or 1). Thioesters bound tightly to recombinant GSTs (K(d) approximately 1 microm), explaining their accumulation. Transient expression of GSTUs in Nicotiana benthamiana followed by recovery by Strep-tag affinity chromatography allowed the respective plant ligands to be extracted and characterized. Again, each GST showed a distinct profile of recovered metabolites, notably glutathionylated oxophytodienoic acid and related oxygenated fatty acids. Similarly, the expression of the major Tau protein GSTU19 in the endogenous host Arabidopsis led to the selective binding of the glutathionylated oxophytodienoic acid-glutathione conjugate, with the enzyme able to catalyze the conjugation reaction. Additional ligands identified in planta included other fatty acid derivatives including divinyl ethers and glutathionylated chlorogenic acid. The strong and specific retention of various oxygenated fatty acids by each GSTU and the conservation in binding observed in the different hosts suggest that these proteins have selective roles in binding and conjugating these unstable metabolites in vivo.

  4. Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells.

    Science.gov (United States)

    Masur, F; Benesch, F; Pfannkuche, H; Fuhrmann, H; Gäbel, G

    2016-04-01

    Conjugated linoleic acids (CLA), particularly cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12), are used as feed additives to adapt to constantly increasing demands on the performance of lactating cows. Under these feeding conditions, the rumen wall, and the rumen epithelial cells (REC) in particular, are directly exposed to high amounts of CLA. This study determined the effect of CLA on the fatty acid (FA) metabolism of REC and expression of genes known to be modulated by FA. Cultured REC were incubated with c9t11, t10c12, and the structurally similar FA linoleic acid (LA), oleic acid (OA), and trans-vaccenic acid (TVA) for 48 h at a concentration of 100 µM. Cellular FA levels were determined by gas chromatography. Messenger RNA expression levels of stearoyl-CoA desaturase (SCD) and monocarboxylate transporter (MCT) 1 and 4 were quantified by reverse transcription-quantitative PCR. Fatty acid evaluation revealed significant effects of CLA, LA, OA, and TVA on the amount of FA metabolites of β-oxidation and elongation and of metabolites related to desaturation by SCD. The observed changes in FA content point (among others) to the ability of REC to synthesize c9t11 from TVA endogenously. The mRNA expression levels of SCD identified a decrease after CLA, LA, OA, or TVA treatment. In line with the changes in mRNA expression, we found reduced amounts of C16:1n-7 cis-9 and C18:1n-9 cis-9, the main products of SCD. The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) α antagonist suggested that activation of PPARα is involved in the changes of MCT1, MCT4, and SCD mRNA expression induced by c9t11. Participation of PPARγ in the changes of MCT1 and SCD mRNA expression was shown by the application of the respective antagonist. The study demonstrates that exposure to CLA affects both FA metabolism and regulatory pathways within REC.

  5. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    OpenAIRE

    Vaughan Roger A; Garcia-Smith Randi; Bisoffi Marco; Conn Carole A; Trujillo Kristina A

    2012-01-01

    Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA) or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determine...

  6. Folic acid-CdTe quantum dot conjugates and their applications for cancer cell targeting

    Energy Technology Data Exchange (ETDEWEB)

    Suriamoorthy, Preethi; Zhang, Xing; Hao, Guiyang; Joly, Alan G.; Singh, S.; Hossu, Marius; Sun, Xiankai; Chen, Wei

    2010-12-01

    In this study, we report the preparation,luminescence, and targeting properties of folic acid- CdTe quantum dot conjugates. Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide chemistry. The in-fluence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy transfer between them was observed. To investigate the efficiency of folic acid-CdTe nanoconjugates for tumor targeting, pure CdTe quantum dots and folic acid-coated CdTe quantum dots were incubated with human naso- pharyngeal epidermal carcinoma cell line with positive expressing folic acid receptors (KB cells) and lung cancer cells without expression of folic acid receptors (A549 cells). For the cancer cells with positive folate receptors (KB cells), the uptake for CdTe quantum dots is very low, but for folic acid-CdTe nanoconjugates, the uptake is very high. For the lung cancer cells without folate receptors (A549 cells), the uptake for folic acid- CdTe nanoconjugates is also very low. The results indicate that folic acid is an effective targeting molecule for tumor cells with overexpressed folate receptors.

  7. Endogenous Bioactive Jasmonate Is Composed of a Set of (+)-7-iso-JA-Amino Acid Conjugates.

    Science.gov (United States)

    Yan, Jianbin; Li, Suhua; Gu, Min; Yao, Ruifeng; Li, Yuwen; Chen, Juan; Yang, Mai; Tong, Jianhua; Xiao, Langtao; Nan, Fajun; Xie, Daoxin

    2016-12-01

    Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently derepress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. So far, (+)-7-iso-JA-l-Ile has been the only identified endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met, and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules. Furthermore, our studies uncover the general characteristics for all the bioactive JA molecules, and provide a new strategy to synthetically generate novel active JA molecules.

  8. Correlating Physicochemical Properties of Boronic Acid-Chitosan Conjugates to Glucose Adsorption Sensitivity

    Directory of Open Access Journals (Sweden)

    Nashiru Billa

    2012-12-01

    Full Text Available Phenyl boronic acid (PBA, which is known to interact with glucose, was covalently bonded to chitosan by direct reductive N-alkylation of chitosan with 4-formylphenylboronic acid (4-FPBA. Evidence of PBA bonding on chitosan was assessed by FTIR, ToF-SIMS, SEM, DSC and glucose adsorption sensitivity measurements. FTIR spectra showed strong signals at 1560 and 630 cm−1 indicating the formation of p-substituted benzene. Similarly, ToF-SIMS analyses on the conjugates registered fragments of boron ion (B− at 11.0 m/z whose intensity increased in proportion to 4-FPBA loading. The degree to which PBA was bonded to chitosan was related to the 4-FPBA load used in the reaction (termed F1 through to F6 with increasing 4-FPBA load. Glucose adsorption sensitivity to PBA-bonded chitosan was directly related to the amount of PBA functionality within the conjugates and the physical nature of the matrices (porous or crystalline. Topographic analysis by SEM revealed that PBA-chitosan conjugates F1, F2 and F3 have porous matrices and their sensitivity to glucose adsorption was directly proportional to the degree of PBA substitution onto chitosan. Conversely, conjugates F4, F5 and F6 appeared crystalline under SEM and glucose adsorption sensitivity decreased in proportion to amount of PBA bonded to chitosan. The crystalline nature of the conjugates was confirmed by DSC, where the exothermic event related to the melting of the bonded PBA moiety, occurred at 338 °C. Thus, decreased sensitivity to glucose adsorption by the conjugates can be ascribed to the crystallinity imparted by increased content of the bonded PBA moiety, providing an optimal loading of PBA in terms of maximizing response to glucose.

  9. Unusual doping of donor-acceptor-type conjugated polymers using lewis acids.

    Science.gov (United States)

    Poverenov, Elena; Zamoshchik, Natalia; Patra, Asit; Ridelman, Yonatan; Bendikov, Michael

    2014-04-02

    Conjugated polymers that can undergo unusual nonoxidative doping were designed. A series of polymers based on donor-acceptor-donor (DAD) moieties 2,1,3-benzoselenadiazole, 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazolebenzo[2,1,5]oxodiazole, and 2-hexylbenzotriazole as acceptor fragments and 3,4-ethylenedioxyselenophene (EDOS) and 3,4-ethylenedioxythiophene (EDOT) as donor fragments was prepared. When the studied polymers were reacted with Lewis acids and bases, notable optical switching and conductivity changes were observed, evidencing the exceptional case of efficient nonoxidative doping/dedoping. Remarkably, in previously reported works, coordination of Lewis acids causes band gap shift but not doping of the conductive polymer, while in the present study, coordination of Lewis acid to highly donating EDOT and EDOS moieties led to polymer doping. The polymers show remarkable stability after numerous switching cycles from neutral to doped states and vice versa and can be switched both electrochemically and chemically. The reactivity of the prepared polymers with Lewis acids and bases of different strengths was studied. Calculation studies of the Lewis acid coordination mode, its effect on polymer energies and band gap, support the unusual doping. The reported doping approach opens up the possibility to control the conjugation, color change, and switching of states of conjugated polymers without oxidation.

  10. Effect of dietary conjugated linoleic acid (CLA) on carcass quality ...

    African Journals Online (AJOL)

    mdenli

    linoleic acid (CLA) on carcass characteristics, serum lipid variables and histopathological ... were not detected in any breast tissues collected from the broiler carcasses. ... There are four different aflatoxins produced by these fungi, AFB1, B2, G1 and ..... Experimental studies on aflatoxin B1 and M1 deposition and clearance.

  11. New conjugated hydroxydienoic fatty acids and acetotriacylglycerols from Securidaca longipedunculata seed oil.

    Science.gov (United States)

    Smith, C R; Madrigal, R V; Plattner, R D

    1979-02-26

    Like other members of the plant family Polygalaceae, Securidaca longipedunculata Fres., is a source of fatty acids and triacylglycerols with unusual structures. Its seed oil contains at least seven chromatographically distinct groups of triacylglycerols divided into two series: One series represents monoacetotriacylglycerols, and the other 'normal' triacylglycerols having only long-chain fatty acids. Each series has groups containing zero, one or two conjugated hydroxydienoic acids. In addition, there is a small amount of triacylglycerol incorporating three hydroxy acids. In addition to coriolic (13-hydroxyoctadeca-cis-9,trans-11-dienoic) acid (27%), two of its previously unknown homologs are present: 11-hydroxyhexadeca-cis-7,trans-9-dienoic acid (15%) and 9-hydroxytetradeca-cis-5,trans-7-dienoic acid (2%).

  12. Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes.

    Science.gov (United States)

    Slovak, J E; Mealey, K; Court, M H

    2017-04-01

    Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15-17% that of dog and human liver microsomes. However, CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was threefold for total conjugation and for phenol glucosidation, sixfold for phenol glucuronidation, and 11-fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species.

  13. Metabolism of Exogenous Indoleacetic Acid to Its Amide Conjugates in Cucumis sativus L. 12

    Science.gov (United States)

    Purves, William K.; Hollenberg, Stanley M.

    1982-01-01

    Incubation of hypocotyl segments of light-grown Cucumis sativus L. in 0.1 millimolar 3-indoleacetic acid for 16 hours led to the formation of indoleacetylaspartate and indoleacetylglutamate. There was no evidence for the formation of other conjugates of 3-indoleacetic acid with individual amino acids during the period from 4 to 48 hours of incubation. Indoleacetylglutamate reached its maximum concentration after about 4 hours of incubation and indoleacetylaspartate after about 8 hours. These levels remained unchanged for at least 40 hours. Indoleacetylaspartate caused small increases in cucumber hypocotyl segment growth at high concentrations, 1 millimolar being more effective than 0.1 millimolar. PMID:16662461

  14. Effects of mycophenolic acid-glucosamine conjugates on the base of kidney targeted drug delivery.

    Science.gov (United States)

    Wang, Xiaohong; Lin, Yan; Zeng, Yingchun; Sun, Xun; Gong, Tao; Zhang, Zhirong

    2013-11-01

    Mycophenolic acid has played an important role in treating immunosuppression and autoimmune diseases. Nevertheless, the agent needs a high dosage in treatment, following some side effects. To tackle this problem, in this study, mycophenolic acid-glucosamine conjugate (MGC), modified by 2-glucosamine, was synthesized to achieve kidney targeting and improved drug efficacy with a lower dosage. (1)H NMR, (13)C NMR and HRMS spectroscopy were used to verify the conjugate whose stability was good in vitro. The transport of MGC by human proximal renal tubular epithelial HK-2 cells was temperature-, time-, concentration-dependent and saturable, suggesting the involvement of carrier-mediated uptake. In addition, the cellular uptake of MGC dropped substantially with the inhibition of megalin receptor. The specific tissue distribution indicated the commendable renal-targeting capability of MGC. The concentration of MGC was improved in the kidney except for other tissues, about 6.76 times higher than that of MPA. Further, the bioavailability of MGC in plasma decreased as compared with mycophenolic acid. Moreover, therapeutic effect of MGC was enhanced significantly compared with MPA in the acute kidney injury model. All the findings suggested the potential of mycophenolic acid-glucosamine conjugate in kidney targeted drug delivery.

  15. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism

    OpenAIRE

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation al...

  16. Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

    Science.gov (United States)

    2012-01-01

    level of hair follicle cell apoptosis within 24 hours of the initial burn injury.27 Intravenous injection of semapimod, a selective inhibitor of...effect of such treat- ment was unclear. Singer and coworkers have also demonstrated 30% reduction in depth of hair follicle necrosis after systemic...whether topical application of antibodies targeting tumor necrosis factor-a (TNF-a) or interleukin-6 (IL-6) conjugated to hyaluronic acid (HA) could

  17. Lewis acid activation of pyridines for nucleophilic aromatic substitution and conjugate addition.

    Science.gov (United States)

    Abou-Shehada, Sarah; Teasdale, Matthew C; Bull, Steven D; Wade, Charles E; Williams, Jonathan M J

    2015-03-01

    A clean, mild and sustainable method for the functionalization of pyridines and their analogues is reported. A zinc-based Lewis acid is used to activate pyridine and its analogues towards nucleophilic aromatic substitution, conjugate addition, and cyclization reactions by binding to the nitrogen on the pyridine ring and activating the pyridine ring core towards further functionalization. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  19. THE IMPACT OF CONJUGATED LINOLEIC ACID ADDITION ON PH VALUE OF LONGISSIMUS DORSI MUSCLE

    Directory of Open Access Journals (Sweden)

    Przemysław WASILEWSKI

    2009-08-01

    Full Text Available The subject of research was 60 crossbred gilts, divided into 6 groups, fed the fodder with addition of conjugated linoleic acid (CLA or sunflower oil (SFO in amount: 0.5; 1.0; and 2.0 %, respectively. Animals were slaughtered with the body weight ca. 95 kg. The aim of research was to determine pH value of loin meat tissue (Longissimus dorsi of right half-carcass in 45 minutes, 2, 3, 4, 5, 6 hours and 24 hours after slaughter. Results were statistically elaborated using one-way variance analysis. Longissimus dorsi muscle pH values measured 45 minutes after slaughter in case of all groups of pigs were in range from 6.34 up to 6.47, what shows good meat quality. The lowest pH1 (measured 45 minutes after slaughter had meat of fatteners where addition of 2 % sunflower oil was given into fodder and the highest value of this trait was in group of individuals where also was given sunflower oil in 1 % amount. Statistical significant differences in pH value measured in different time after slaughter i.e. after 45 minutes, 2, 3, 4, 6 and 24 hours between tested groups of pigs were not stated. The exception is the result of pH measurement 5 hours after slaughter. Statistical significant differences were between group of pigs getting 0.5 % addition of conjugated linoleic acid characterized by the highest pH value of meat and group of animals fed the fodder with 1 % addition of conjugated linoleic acid (P≤0.01. On the basis of the results obtained in presented paper may be stated that feeding pigs with addition of conjugated linoleic acid in amounts 0.5; 1.0 and 2.0 % did not impact negatively on meat quality defined by pH value.

  20. Detection of biologically active isomers of conjugated linoleic acid in kaymak

    OpenAIRE

    Ökten, Sevtap; Gönç, Siddik; Tokusoglu, Özlem; Sibel Akalin, A.

    2005-01-01

    Numerous physiological effects are attributed to conjugated linoleic acids (CLA). Biologically active isomers of CLA ( cis -9, trans -11 (C18:2) and trans- 10, cis- 12 (C18:2)) have been reported to have anticarcinogenic, antioxidative and antiatherosclerotic properties. Relatively rich sources of CLA include milk fat-containing foods such as kaymak. Kaymak is a kind of concentrated cream which is traditionally manufactured from buffalo or cow's milk mainly in Turkey . The objective of this s...

  1. Novel liver-specific cholic acid-cytarabine conjugates with potent antitumor activities: Synthesis and biological characterization

    Institute of Scientific and Technical Information of China (English)

    Dan-qi CHEN; Xin WANG; Lin CHEN; Jin-xue HE; Ze-hong MIAO; Jing-kang SHEN

    2011-01-01

    Aim: Cytarabine is an efficient anticancer agent for acute myelogenous leukemia, but with short plasma half-life and rapid deamination to its inactive metabolite. The aim of this study was to design and synthesize novel cholic acid-cytarabine conjugates to improve its pharmacokinetic parameters.Methods: The in vitro stability of novel cholic acid-cytarabine conjugates was investigated in simulated gastric and intestinal fluid, mouse blood and liver homogenate using HPLC. The portacaval samples of the conjugates were examined in male Sprague-Dawley rats using LC/MS, and in vivo distribution was examined in male Kunming mice using LC/MS. Antitumor activities were tested in HL60 cells using MTT assay.Results: Cholic acid-cytarabine compounds with four different linkers were designed and synthesized. All the four cholic acid-cytarabine conjugates could release cytarabine when incubated with the simulated gastric and intestinal fluid, mouse blood and liver homoge-nate. The conjugates 6,/2, and 16 were present in the portacaval samples, whereas the conjugate 7 was not detected. The conju-gates 6 and 16 showed high specificity in targeting the liver (liver target index 34.9 and 16.3, respectively) and good absorption in vivo, as compared with cytarabine. In cytarabine-sensitive HL60 cells, the conjugates 6, 12, and 16 retained potent antitumor activities.Conclusion: Three novel cholic acid-cytarabine conjugates with good liver-targeting properties and absorption were obtained. Further optimization of the conjugates is needed in the future.

  2. Bioavailability of Echinacea Constituents: Caco-2 Monolayers and Pharmacokinetics of the Alkylamides and Caffeic Acid Conjugates

    Directory of Open Access Journals (Sweden)

    R. Lehmann

    2005-10-01

    Full Text Available Many studies have been done over the years to assess the effectiveness of Echinacea as an immunomodulator. We have assessed the potential bioavailability of alkyl- amides and caffeic acid conjugates using Caco-2 monolayers and compared it to their actual bioavailability in a Phase I clinical trial. The caffeic acid conjugates permeated poorly through the Caco-2 monolayers. Alkylamides were found to diffuse rapidly through Caco-2 monolayers. Differences in diffusion rates for each alkylamide correlated to structural variations, with saturation and N-terminal methylation contributing to decreases in diffusion rates. Alkylamide diffusion is not affected by the presence of other constituents and the results for a synthetic alkylamide were in line with those for alkylamides found in an ethanolic Echinacea preparation. We examined plasma from healthy volunteers for 12 hours after ingestion of Echinacea tablets manufactured from an ethanolic liquid extract. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkylamides were detected in plasma 20 minutes after tablet ingestion and for each alkylamide, pharmacokinetic profiles were devised. The data are consistent with the dosing regimen of one tablet three times daily and supports their usage as the primary markers for quality Echinacea preparations.

  3. Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid

    Directory of Open Access Journals (Sweden)

    Buddhadev Layek

    2015-12-01

    Full Text Available Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA.

  4. Design of Ru-zeolites for hydrogen-free production of conjugated linoleic acids.

    Science.gov (United States)

    Philippaerts, An; Goossens, Steven; Vermandel, Walter; Tromp, Moniek; Turner, Stuart; Geboers, Jan; Van Tendeloo, Gustaaf; Jacobs, Pierre A; Sels, Bert F

    2011-06-20

    While conjugated vegetable oils are currently used as additives in the drying agents of oils and paints, they are also attractive molecules for making bio-plastics. Moreover, conjugated oils will soon be accepted as nutritional additives for "functional food" products. While current manufacture of conjugated vegetable oils or conjugated linoleic acids (CLAs) uses a homogeneous base as isomerisation catalyst, a heterogeneous alternative is not available today. This contribution presents the direct production of CLAs over Ru supported on different zeolites, varying in topology (ZSM-5, BETA, Y), Si/Al ratio and countercation (H(+), Na(+), Cs(+)). Ru/Cs-USY, with a Si/Al ratio of 40, was identified as the most active and selective catalyst for isomerisation of methyl linoleate (cis-9,cis-12 (C18:2)) to CLA at 165 °C. Interestingly, no hydrogen pre-treatment of the catalyst or addition of hydrogen donors is required to achieve industrially relevant isomerisation productivities, namely, 0.7 g of CLA per litre of solvent per minute. Moreover, the biologically most active CLA isomers, namely, cis-9,trans-11, trans-10,cis-12 and trans-9,trans-11, were the main products, especially at low catalyst concentrations. Ex situ physicochemical characterisation with CO chemisorption, extended X-ray absorption fine structure measurements, transmission electron microscopy analysis, and temperature-programmed oxidation reveals the presence of highly dispersed RuO(2) species in Ru/Cs-USY(40).

  5. Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Edelman, Ravit; Assaraf, Yehuda G; Levitzky, Inna; Shahar, Tal; Livney, Yoav D

    2017-02-15

    Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44. We demonstrate that Maillard reaction-based covalent conjugates of BSA-HA self-assemble into NPs, which efficiently entrap hydrophobic cytotoxic drugs including paclitaxel and imidazoacridinones. Furthermore, BSA-HA conjugates stabilized paclitaxel and prevented its aggregation and crystallization. The diameter of the NPs was < 15 nm, thus enabling CD44 receptor-mediated endocytosis. These NPs were selectively internalized by ovarian cancer cells overexpressing CD44, but not by cognate cells lacking this HA receptor. Moreover, free HA abolished the endocytosis of drug-loaded BSA-HA conjugates. Consistently, drug-loaded NPs were markedly more cytotoxic to cancer cells overexpressing CD44 than to cells lacking CD44, due to selective internalization, which could be competitively inhibited by excess free HA. Finally, a CD44-targeted antibody which blocks receptor activity, abolished internalization of drug-loaded NPs. In conclusion, a novel cytotoxic drug-loaded nanomedicine platform has been developed, which is based on natural biocompatible biopolymers, capabale of targeting cancer cells with functional surface expression of CD44.

  6. Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain

    DEFF Research Database (Denmark)

    Koppelhus, Uffe; Shiraishi, Takehiko; Zachar, Vladimir;

    2008-01-01

    Conjugation to cationic cell penetrating peptides (such as Tat, Penetratin, or oligo arginines) efficiently improves the cellular uptake of large hydrophilic molecules such as oligonucleotides and peptide nucleic acids, but the cellular uptake is predominantly via an unproductive endosomal pathwa...

  7. Protein and energy metabolism of young male Wistar rats fed conjugated linoleic acid as structured triacylglycerol

    DEFF Research Database (Denmark)

    Jørgensen, H.; Hansen, C. H.; Mu, Huiling

    2010-01-01

    Twelve 4-week-old male Wistar rats weighing 100 g were fed diets semi-ad libitum for 22 d containing either 1.5% conjugated linoleic acid (CLA-diet) or high oleic sunflower oil (Control-diet). The CLA was structured triacylglycerol with predominantly cis-9, trans-11 and trans-10, cis-12 fatty aci...... isomers in the inner position and oleic acid in the other positions of the glycerol molecule. The rats were kept individually in metabolic cages. From days 8-16 energy, nitrogen (N) and carbon...

  8. Sulfated Steroid–Amino Acid Conjugates from the Irish Marine Sponge Polymastia boletiformis

    Directory of Open Access Journals (Sweden)

    Vangelis Smyrniotopoulos

    2015-03-01

    Full Text Available Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2. Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

  9. Synthesis of glycerides containing n-3 fatty acids and conjugated linoleic acid by solvent-free acidolysis of fish oil.

    Science.gov (United States)

    Garcia, H S; Arcos, J A; Ward, D J; Hill, C G

    2000-12-05

    Menhaden oil, a rich source of n-3 fatty acids, was interesterified with conjugated linoleic acid (CLA) in a reaction medium composed solely of substrates and either free or immobilized commercial lipase preparations. Of five lipases tested, an immobilized preparation from Mucor miehei provided the fastest rate of incorporation of CLA into fish oil acylglycerols; however, and as observed with most of the lipases utilized, a significant proportion of the n-3 fatty acid residues were liberated in the process. A soluble lipase from Candida rugosa converted free CLA to acylglycerol residues while leaving the n-3 fatty acid residues virtually untouched. Even though the reaction rate was slower for this enzyme than for the other four lipase preparations, the specificity of the free C. rugosa lipase gives it the greatest potential for commercial use in preparing fish oils enriched in CLA residues but still retaining their original n-3 fatty acid residues.

  10. Synthesis and DNA Cleavage Studies of 2,6-Dimethoxyhydroquinone- 3-Mercaptoacetic Acid Conjugates

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In an effort to investigate the use of short peptide chains as carriers of new anti-tumor agents, we synthesized four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys(DMQ-MA)-Phe -Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Ile-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Val-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-Ome. The cytotoxic agent conjugated to the N-terminal and the ξ-amino group of Lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3- mercaptoacetic acid (DMQ-MA). The tripeptides were synthesized by coupling protected amino acid residues according to Pfp/DCC methods (Pfp: pentafluorophenol, DCC:N,N'-dicyclohexyl- carbodiimide) in solution. Agarose gel electrophoresis showed that these compounds can cleave supercoiled DNA into open-circular form in drug concentration as low as 4-50 μM without H2O2 and UV irradiation. Further studies on their cytotoxicity for these conjugates are ongoing.

  11. Disulfide bond reduction-triggered molecular hydrogels of folic acid-Taxol conjugates.

    Science.gov (United States)

    Yang, Chengbiao; Li, Dongxia; Fengzhao, Qianqi; Wang, Lianyong; Wang, Ling; Yang, Zhimou

    2013-09-25

    Molecular hydrogels of therapeutic agents are a novel kind of self-delivery system that can sustain release of drugs or pro-drugs. We have previously developed a molecular hydrogelator of folic acid (FA)-Taxol conjugate triggered by phosphatase. In this paper, we report a novel molecular hydrogelator system of FA-Taxol conjugates with improved synthetic strategy. The hydrogels are formed by the reduction of disulfide bond by glutathione (GSH). These hydrogels could sustain release of Taxol through ester bond hydrolysis. Compared with intravenous (i.v.) injection of clinically used Taxol® with four times the dosage, our hydrogel could inhibit tumor growth more efficiently by a single dose of intra-tumor (i.t.) administration. These observations suggested the big potential of this novel gelation system of Taxol for cancer therapy.

  12. Self-assembled Nanoparticles based on Folic Acid Modiifed Carboxymethyl Chitosan Conjugated with Targeting Antibody

    Institute of Scientific and Technical Information of China (English)

    HU Zhengyu; ZHENG Hua; LI Dan; XIONG Xiong; TAN Mingyuan; HUANG Dan; GUO Xing; ZHANG Xueqiong; YAN Han

    2016-01-01

    Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia (AML). Moreover, methotrexate (MTX) was chosen as model drug and encapsulate within folic acid modified carboxymethyl chitosan (FA-CMCS) nanoparticles through self-assembling. The chemical structure, morphology, release and targeting of nanoparticles were characterized by routine detection. It is demonstrated that the mean diameter is about 150 nm, the release rate increases with the decreasing of pH, the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5:2, and nanoparticles can effectively bind onto HL60 cells in vitro. The experimental results indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potential pH-sensitive drug delivery system with leukemic targeting properties.

  13. DNA detection using water-soluble conjugated polymers and peptide nucleic acid probes

    Science.gov (United States)

    Gaylord, Brent S.; Heeger, Alan J.; Bazan, Guillermo C.

    2002-08-01

    The light-harvesting properties of cationic conjugated polymers are used to sensitize the emission of a dye on a specific peptide nucleic acid (PNA) sequence for the purpose of homogeneous, "real-time" DNA detection. Signal transduction is controlled by hybridization of the neutral PNA probe and the negative DNA target. Electrostatic interactions bring the hybrid complex and cationic polymer within distances required for Förster energy transfer. Conjugated polymer excitation provides fluorescein emission >25 times higher than that obtained by exciting the dye, allowing detection of target DNA at concentrations of 10 pM with a standard fluorometer. A simple and highly sensitive assay with optical amplification that uses the improved hybridization behavior of PNA/DNA complexes is thus demonstrated.

  14. Dietary conjugated linoleic acid reciprocally modifies ketogenesis and lipid secretion by the rat liver.

    Science.gov (United States)

    Sakono, M; Miyanaga, F; Kawahara, S; Yamauchi, K; Fukuda, N; Watanabe, K; Iwata, T; Sugano, M

    1999-09-01

    The effects of dietary conjugated linoleic acid (CLA) and linoleic acid (LA) on ketone body production and lipid secretion were compared in isolated perfused rat liver. After feeding the 1% CLA diet for 2 wk, the concentration of post-perfused liver cholesterol was significantly reduced by CLA feeding, whereas that of triacylglycerol remained unchanged. Livers from CLA-fed rats produced significantly more ketone bodies; and the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to be consistently higher in the liver perfusate. Conversely, cumulative secretions of triacylglycerol and cholesterol were consistently lower in the livers of rats fed CLA, and the reduction in the latter was statistically significant. Thus dietary CLA appeared to exert its hypolipidemic effect at least in part through an enhanced beta-oxidation of fatty acids at the expense of esterification of fatty acid in the liver.

  15. Two new conjugated ketonic fatty acids from the stem bark of Juglans mandshurica.

    Science.gov (United States)

    Yao, Da-Lei; Zhang, Chang-Hao; Li, Ren; Luo, Jie; Jin, Mei; Piao, Jin-Hua; Zheng, Ming-Shan; Cui, Jiong-Mo; Son, Jong Keun; Li, Gao

    2015-04-01

    The present study was designed to isolate and characterize novel chemical constituents of the stem bark of Juglans mandshurica Maxim. (Juglandaceae). The chemical constituents were isolated and purified by various chromatographic techniques. The structures of the compounds were elucidated on the basis of spectral data (1D and 2D NMR, HR-ESI-MS, CD, UV, and IR) and by the comparisons of spectroscopic data with the reported values in the literatures. Two long chain polyunsaturated fatty acids (1 and 2) were obtained and identified as (S)-(8E,10E)-12-hydroxy-7-oxo-8,10-octadecadienoic acid (1) and (S)-(8E, 10E)-12-hydroxy-7-oxo-8,10-octadecadienoic acid methyl ester (2). To the best of our knowledge, this is the first report on the isolation and structural elucidation of the two new conjugated ketonic fatty acids from this genus.

  16. Determination of conjugated bile acids in human bile and duodenal fluid by reverse-phase high-performance liquid chromatography.

    Science.gov (United States)

    Bloch, C A; Watkins, J B

    1978-05-01

    A simple mehtod using reverse-phase liquid chromatography is presented for resolution and quantitation of the major conjugated bile acids of man, including the glycine and taurine conjugates of the dihydroxy bile acids, chenodeoxycholic and deoxycholic acid. Using modern, high-performance chromatographic equipment, analysis time is less than 30 minutes. The quantitative range of the method, with detection by refractive index, is 0.05 to 0.1 mumol of bile acid and the limit of detection for an injection sample is 0.01 mumol. This provides a sensitivity sufficient for analysis of dilute duodenal and gallbladder bile with minimal sample preparation.

  17. Predicting cellulose solvating capabilities of acid-base conjugate ionic liquids.

    Science.gov (United States)

    Parviainen, Arno; King, Alistair W T; Mutikainen, Ilpo; Hummel, Michael; Selg, Christoph; Hauru, Lauri K J; Sixta, Herbert; Kilpeläinen, Ilkka

    2013-11-01

    Different acid-base conjugates were made by combining a range of bases and superbases with acetic and propionic acid. Only the combinations that contained superbases were capable of dissolving cellulose. Proton affinities were calculated for the bases. A range, within which cellulose dissolution occurred, when combined with acetic or propionic acid, was defined for further use. This was above a proton affinity value of about 240 kcal mol(-1) at the MP2/6-311+G(d,p)//MP2/ 6-311+G(d,p) ab initio level. Understanding dissolution allowed us to determine that cation acidity contributed considerably to the ability of ionic liquids to dissolve cellulose and not just the basicity of the anion. By XRD analyses of suitable crystals, hydrogen bonding interactions between anion and cation were found to be the dominant interactions in the crystalline state. From determination of viscosities of these conjugates over a temperature range, certain structures were found to have as low a viscosity as 1-ethyl-3-methylimidazolium acetate, which was reflected in their high rate of cellulose dissolution but not necessarily the quantitative solubility of cellulose in those ionic liquids. 1,5-Diazabicyclo[4.3.0]non-5-enium propionate, which is one of the best structures for cellulose dissolution, was then distilled using laboratory equipment to demonstrate its recyclability.

  18. A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

    Science.gov (United States)

    Zhong, Ting; Yao, Xin; Zhang, Shuang; Guo, Yang; Duan, Xiao-Chuan; Ren, Wei; Dan Huang; Yin, Yi-Fan; Zhang, Xuan

    2016-11-01

    The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX:DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in the in vitro experiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.

  19. Pyridine salvage and nicotinic acid conjugate synthesis in leaves of mangrove species.

    Science.gov (United States)

    Ashihara, Hiroshi; Yin, Yuling; Deng, Wei-Wei; Watanabe, Shin

    2010-01-01

    The metabolic fate of [carbonyl-14C]nicotinamide was surveyed in leaf disks of seven mangrove species, Bruguiera gymnorrhiza, Rhizophora stylosa, Kandeliaobovata, Sonneratia alba, Pemphis acidula, Lumnitzera racemosa and Avicennia marina, with and without 250 mM NaCl. Uptake of [14C]nicotinamide by leaf disks was stimulated by 250 mM NaCl in K. candel, R. stylosa, A. marina and L. racemosa. [Carbonyl-14C]nicotinamide was converted to nicotinic acid and was utilised for the synthesis of nucleotides and nicotinic acid conjugates. Formation of nicotinic acid by the deaminase reaction was rapid; there was little accumulation of nicotinamide in the disks 3h after administration. Radioactivity from [carbonyl-14C]nicotinamide was incorporated into pyridine nucleotides (mainly NAD and NADP) in all mangrove leaves, and the rates varied from 2% (in L. racemosa) to 15% (S. alba) of the total radioactivity taken up. NaCl generally reduced nicotinic acid salvage for NAD and NADP. In all mangrove leaf disks, the most heavily labelled compounds (up to 70% of total radioactivity) were trigonelline (N-methylnicotinic acid) and/or nicotinic acid N-glucoside. Trigonelline was formed in all mangrove plants, but N-glucoside synthesis was found only in leaves of A. marina and K. obovata. In A. marina, incorporation of radioactivity into N-glucoside (51%) was much greater than incorporation into trigonelline (2%). In general, NaCl stimulates the synthesis of these pyridine conjugates. The rate of decarboxylation of nicotinic acid in roots of A. marina seedlings was much greater than for the corresponding reaction observed in leaves.

  20. Development of materials consisting of conjugated polymer doped with folic acid

    Directory of Open Access Journals (Sweden)

    Vicente Kupfer

    2012-06-01

    Full Text Available The development of new materials made from the combination between conjugated polymers and new dopants is the objective of various researches groups around the world. This work presented the synthesis and characterization of Polyaniline (PAni doped with folic acid. The material was synthesized through oxidative polymerization of the previously prepared emulsion of aniline in different concentrations with adding of the folic acid. The materials were characterized by spectroscopic techniques (infrared and UV-Vis, thermogravimetric analysis and electrochemical impedance spectroscopy. The infrared results suggested the effective formation of the materials and the results of the UV-Vis corroborate with this hypothesis. The thermogravimetric curves showed an intermediate behavior of the resulting materials coming from the starting materials (folic acid and PANi. By measuring the conductivity could be affirmed that the material behaved as semiconductors.

  1. Human breast milk enrichment in conjugated linoleic acid after consumption of a conjugated linoleic acid-rich food product: a pilot study.

    Science.gov (United States)

    Moutsioulis, Athena A; Rule, Daniel C; Murrieta, Charles M; Bauman, Dale E; Lock, Adam L; Barbano, David M; Carey, Gale B

    2008-07-01

    Human breast milk is a complex mixture of organic and inorganic compounds. Some compounds, such as conjugated linoleic acid (CLA), come partly from the mother's diet and are produced by the mother's body and secreted into the milk. Although several studies have examined the effect of chronic CLA supplementation on breast milk CLA appearance, little is known about the transfer of food CLA to breast milk over the short term. The objective of this study was to conduct a preliminary analysis of the kinetics of CLA appearance in breast milk over the short term. Seven women expressed breast milk at 4- to 6-hour intervals for 2 days after eating either CLA-enriched (1912 mg CLA) or control (231 mg CLA) cookies. Milk samples were freeze-dried, fatty acid methyl esters were prepared using methanolic-potassium hydroxide (KOH), and CLA isomers were quantified by gas chromatography. Analysis revealed the following: (1) CLA enrichment of total fatty acids in the breast milk for 48 hours post ingestion of the CLA-enriched cookies was 2.9-fold above control; (2) total breast milk CLA content for 48 hours post CLA-enriched cookies ingestion was 46% greater than post CLA-moderate cookies ingestion; (3) after ingestion of the CLA-enriched cookies, breast milk CLA enrichment plateaued between 8 to 28 hours. This preliminary study suggests that breast milk fatty acids are enriched in CLA compared to control within 28 hours after the ingestion of a CLA-rich food product and invites further research on the extent and timing with which breast milk composition reflects dietary CLA content.

  2. The In vitro Effects of Nano-encapsulated Conjugated Linoleic Acid on Stability of Conjugated Linoleic Acid and Fermentation Profiles in the Rumen.

    Science.gov (United States)

    Heo, Wan; Kim, Eun Tae; Cho, Sung Do; Kim, Jun Ho; Kwon, Seong Min; Jeong, Ha Yeon; Ki, Kwang Seok; Yoon, Ho Baek; Ahn, Young Dae; Lee, Sung Sill; Kim, Young Jun

    2016-03-01

    This study was aimed to evaluate the stability of conjugated linoleic acids (CLAs) by nano-encapsulation against in vitro ruminal biohydrogenation by microbial enzymatic conversion. CLAs (free fatty acid form of CLA [CLA-FFA], nano-encapsulated CLA-FFA, triglyceride form of CLA [CLA-TG], and nano-encapsulated CLA-TG) were used in the in vitro fermentation experiments. When Butyrivibrio fibrisolvens (B. fibrisolvens) was incubated with CLA-FFAs, the concentrations of cis-9, trans-11 CLA and vaccenic acid (VA) slightly was decreased and increased by nano-encapsulation, respectively. When B. fibrisolvens was incubated with CLA-TG, the concentrations of cis-9, trans-11 CLA and VA decreased, but these were increased when B. fibrisolvens was incubated with nano-encapsulated CLA-TG. The nano-encapsulation was more effective against the in vitro biohydrogenation activity of B.fibrisolvens incubated with CLA-FFA than with CLA-TG. In the in vitro ruminal incubation test, the total gas production and concentration of total volatile fatty acids incubated with nano-encapsulated CLA-FFA and CLA-TG were increased significantly after 24 h incubation (pNano-encapsulated CLA-FFA might, thus, improve the ruminal fermentation characteristics without adverse effects on the incubation process. In addition, nano-encapsulated CLA-FFA increased the population of Fibrobacter succinogenes and decreased the population of B. fibrisolvens population. These results indicate that nano-encapsulation could be applied to enhance CLA levels in ruminants by increasing the stability of CLA without causing adverse effects on ruminal fermentation.

  3. Potent Antibacterial Antisense Peptide-Peptide Nucleic Acid Conjugates Against Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Ghosal, Anubrata; Nielsen, Peter E

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections in hospital settings, especially with immune compromised patients, and the increasing prevalence of multidrug resistant strains urges search for new drugs with novel mechanisms of action. In this study we introduce...... essential bacterial gene involved in fatty acid synthesis) of P. aeruginosa (PA01) and characterized these compounds according to their antimicrobial activity and mode of action. Four antisense PNA oligomers conjugated to the H-(R-Ahx-R)(4)-Ahx-ßala or the H-(R-Ahx)(6)-ßala peptide exhibited complete growth...

  4. Production of phosphatidylcholine containing conjugated linoleic acid mediated by phospholipase A2

    OpenAIRE

    Yamamoto, Yukihiro; Hosokawa, Masashi; Miyashita, Kazuo

    2006-01-01

    Esterification of lysophosphatidylcholine (LPC) with conjugated linoleic acid (CLA) was carried out using porcine pancreatic phospholipase A2 (PLA2). PLA2 only slightly synthesized phosphatidylcholine containing CLA (CLA-PC) at 2.6% by the addition of water. Addition of formamide in place of water markedly increased the yield of CLA-PC. In addition, synthesis of CLA-PC by PLA2 was affected by the amount of substrate CLA and PLA2 in the reaction system. Under optimal reaction conditions using ...

  5. Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.

    Science.gov (United States)

    Lee, Hye-In; Kim, Young-Jin

    2016-06-01

    Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.

  6. The Conjugates of Phenolic Acids in Lichens of the Order Lecanorales

    Directory of Open Access Journals (Sweden)

    T. N. NIKOLAEVA

    2014-06-01

    Full Text Available Lichens are symbiotic associations of a fungus (usually an ascomycete and a photobiont, which may be an alga and/or a cyanobacterium. Lichens dominate on about 6–8% of land surface, mainly in the habitats with severe climatic conditions. Lichenized fungi are among the pioneer vegetation on bare rock or soil. Mat-forming species contribute substantially to the soil cover in tundras and high mountain elevations. Lichens are rich in water-soluble compounds which can be leached-out the lichen thalli with atmospheric depositions. We have recently described the occurrence of water-soluble phenolics in lichens (Zagoskina et al 2013. These compounds can play important role in the ecosystem functioning and primary soil formation (weathering, humification. The aim of this work was to study qualitative composition of water-soluble phenolics in the lichen species widespread in the soil cover of tundra zone. The air-dried thalli of Alectoria ochroleuca, Cetraria islandica, C.nigricans, C.nivalis, Cladonia arbuscula and C.stellaris were homogenized to powder and used for the study. Lichens were collected in Khibiny mountains, Kola Peninsula in August 2013. Phenolic compounds were extracted by distilled water (1h, 30C and analyzed by TLC before and after the acid hydrolysis. It was found that all the lichens under the study contained the conjugates of phenol carboxylic acids. We have identified that non-phenolic part in some of these conjugates was represented by sugars and amino acids. The TLC of the hydrolizates of water extracts revealed occurrence of p-oxybenzoic acid in all of the species studied. The lichens Cetraria islandica, С.nigricans and Cladonia stellaris contained also vanillic acid. These phenolic acids are widespread in plant kingdom and are known as products of lignin decomposition in higher plants. The physiological role of water-soluble phenolics in lichens as well as their environmental role are need to be understood in future studies.

  7. The roasting process does not influence the extent of conjugation of coffee chlorogenic and phenolic acids.

    Science.gov (United States)

    Sanchez-Bridge, Belén; Renouf, Mathieu; Sauser, Julien; Beaumont, Maurice; Actis-Goretta, Lucas

    2016-05-01

    Understanding the bioavailability and metabolism of coffee compounds will contribute to identify the unknown biological mechanism(s) linked to their beneficial effects. The influence of the roasting process on the metabolism of coffee chlorogenic acids in humans was evaluated. In a randomized, double-blind, crossover study, 12 healthy volunteers consumed four instant coffees namely, high roasted coffee (HRC), low roasted coffee (LRC), unroasted coffee (URC), and in vitro hydrolyzed unroasted coffee (HURC). The sum of areas under the curve (AUC) ranged from 8.65-17.6 to 30.9-126 µM/h (P coffee drinks. Despite different absorption rates, the extent of conjugation was comparable between HRC, LRC, and URC coffees but different for HURC. The most abundant circulating metabolites during the first 5 H were dihydroferulic acid (DHFA), caffeic acid-3'-O-sulfate (CA3S) and isoferulic-3'-O-glucuronide (iFA3G). DHFA and 5-4-dihydro-m-coumaric acid (mDHCoA) were the main metabolites in the period of 5-24 H. The phenolic compounds after consumption of HURC were most rapidly absorbed (Tmax 1 H) compared with the other coffees (Tmax between 9 and 11 H). Using coffees with different degrees of roasting we highlighted that in spite of different absorption rates the extent of conjugation of phenolic acids was comparable. In addition, by using a hydrolyzed unroasted coffee we demonstrated an increased absorption of phenolic acids in the small intestine. © 2016 BioFactors, 42(3):259-267, 2016.

  8. Lipid oxidation stability of omega-3- and conjugated linoleic acid-enriched sous vide chicken meat.

    Science.gov (United States)

    Narciso-Gaytán, C; Shin, D; Sams, A R; Keeton, J T; Miller, R K; Smith, S B; Sánchez-Plata, M X

    2011-02-01

    Lipid oxidation is known to occur rather rapidly in cooked chicken meat containing relatively high amounts of polyunsaturated fatty acids. To assess the lipid oxidation stability of sous vide chicken meat enriched with n-3 and conjugated linoleic acid (CLA) fatty acids, 624 Cobb × Ross broilers were raised during a 6-wk feeding period. The birds were fed diets containing CLA (50% cis-9, trans-11 and 50% trans-10, cis-12 isomers), flaxseed oil (FSO), or menhaden fish oil (MFO), each supplemented with 42 or 200 mg/kg of vitamin E (dl-α-tocopheryl acetate). Breast or thigh meat was vacuum-packed, cooked (74°C), cooled in ice water, and stored at 4.4°C for 0, 5, 10, 15, and 30 d. The lipid oxidation development of the meat was estimated by quantification of malonaldehyde (MDA) values, using the 2-thiobarbituric acid reactive substances analysis. Fatty acid, nonheme iron, moisture, and fat analyses were performed as well. Results showed that dietary CLA induced deposition of cis-9, trans-11 and trans-10, cis-12 CLA isomers, increased the proportion of saturated fatty acids, and decreased the proportions of monounsaturated and polyunsaturated fatty acids. Flaxseed oil induced higher deposition of C18:1, C18:2, C18:3, and C20:4 fatty acids, whereas MFO induced higher deposition of n-3 fatty acids, eicosapentaenoic acid (C20:5), and docosahexaenoic acid (C22:6; P 0.05) lipid oxidation development. In conclusion, dietary CLA, FSO, and MFO influenced the fatty acid composition of chicken muscle and the lipid oxidation stability of meat over the storage time. Supranutritional supplementation of vitamin E enhanced the lipid oxidation stability of sous vide chicken meat.

  9. Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

    Directory of Open Access Journals (Sweden)

    Tatyana V. Abramova

    2013-12-01

    Full Text Available Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP method were obtained by the phosphotriester block liquid phase synthesis. The phosphotriester approach to the oligonucleotide synthesis was shown to be a versatile and economic strategy for preparing the required amount of high quality samples of nucleotide–amino acid conjugates.

  10. Shortcut access to peptidosteroid conjugates: building blocks for solid-phase bile acid scaffold decoration by convergent ligation.

    Science.gov (United States)

    Verzele, Dieter; Figaroli, Sara; Madder, Annemieke

    2011-12-07

    We present three versatile solid-supported scaffold building blocks based on the (deoxy)cholic acid framework and decorated with handles for further derivatization by modern ligation techniques such as click chemistry, Staudinger ligation or native chemical ligation. Straightforward procedures are presented for the synthesis and analysis of the steroid constructs. These building blocks offer a new, facile and shorter access route to bile acid-peptide conjugates on solid-phase with emphasis on heterodipodal conjugates with defined spatial arrangements. As such, we provide versatile new synthons to the toolbox for bile acid decoration.

  11. Shortcut Access to Peptidosteroid Conjugates: Building Blocks for Solid-Phase Bile Acid Scaffold Decoration by Convergent Ligation

    Directory of Open Access Journals (Sweden)

    Sara Figaroli

    2011-12-01

    Full Text Available We present three versatile solid-supported scaffold building blocks based on the (deoxycholic acid framework and decorated with handles for further derivatization by modern ligation techniques such as click chemistry, Staudinger ligation or native chemical ligation. Straightforward procedures are presented for the synthesis and analysis of the steroid constructs. These building blocks offer a new, facile and shorter access route to bile acid-peptide conjugates on solid-phase with emphasis on heterodipodal conjugates with defined spatial arrangements. As such, we provide versatile new synthons to the toolbox for bile acid decoration.

  12. Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands

    NARCIS (Netherlands)

    Rist, L.; Mueller, A.; Barthel, C.; Snijders, B.; Jansen, M.; Simões-Wüst, A.P.; Huber, M.; Kummeling, I.; Mandach, U. von; Steinhart, H.; Thijs, C.

    2007-01-01

    The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding m

  13. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    Science.gov (United States)

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  14. Conjugated fatty acid synthesis: residues 111 and 115 influence product partitioning of Momordica charantia conjugase.

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-05-11

    Conjugated linolenic acids (CLNs), 18:3 Δ(9,11,13), lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ(9,12,15)). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ(9cis,11trans,13cis)) or α-eleostearic acid (18:3 Δ(9cis,11trans,13trans)). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation.

  15. Investigating the chemical changes of chlorogenic acids during coffee brewing: conjugate addition of water to the olefinic moiety of chlorogenic acids and their quinides.

    Science.gov (United States)

    Matei, Marius Febi; Jaiswal, Rakesh; Kuhnert, Nikolai

    2012-12-12

    Coffee is one of the most popular and consumed beverages in the world and is associated with a series of benefits for human health. In this study we focus on the reactivity of chlorogenic acids, the most abundant secondary metabolites in coffee, during the coffee brewing process. We report on the hydroxylation of the chlorogenic acid cinnamoyl substituent by conjugate addition of water to form 3-hydroxydihydrocaffeic acid derivatives using a series of model compounds including monocaffeoyl and dicaffeoylquinic acids and quinic acid lactones. The regiochemistry of conjugate addition was established based on targeted tandem MS experiments. Following conjugate addition of water a reversible water elimination yielding cis-cinnamoyl derivatives accompanied by acyl migration products was observed in model systems. We also report the formation of all of these derivatives during the coffee brewing process.

  16. Determination of hepatic uridine 5'-diphosphoglucuronic acid concentration by conjugation with diethylstilbestrol.

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1982-03-01

    A sensitive and reliable assay for uridine 5'-diphosphoglucuronic acid (UDPGA) was developed that involved conjugation of diethylstilbestrol (DES) in vitro. This conjugation reaction is solely dependent upon UDPGA concentration. The assay uses 0.13 M Tris-HCl, pH 7.4, 6.7 mM MgCl2, 0.05% Brig 58, 0.25 mg guinea pig liver microsomal protein, 0.13 mM 3H-DES (0.2 microCi/ml), and 200 microliters of boiled 10% liver homogenate in a total volume of 0.5 ml. After a 60-min incubation at 37 degrees C, unconjugated DES is extracted into 5 ml of chloroform and the residual metabolized 3H-DES in the aqueous phase is determined by liquid scintillation spectrometry. After addition of beta-glucuronidase to the aqueous phase, about 90% of the radioactivity could be extracted into chloroform, demonstrating the DES-glucuronic acid is the primary metabolite. Thus, this method easily permits quantitation of UDPGA in rat liver in the 1-10 nmol range.

  17. Folic Acid-Chitosan Conjugated Nanoparticles for Improving Tumor-Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huijuan Song

    2013-01-01

    Full Text Available Objective. To prepare folic acid-chitosan conjugated nanoparticles (FA-CS NPs and evaluate their targeting specificity on tumor cells. Methods. Chitosan (CS NPs were prepared by ionic cross linking method, and folic acid (FA was conjugated with CS NPs by electrostatic interaction. The properties of NPs were investigated, and doxorubicin hydrochloride (Dox as a model drug was encapsulated for investigating drug release pattern in vitro. The cytotoxicity and cellular uptake of FA-CS NPs were also investigated. Results. The results reveal that the obtained FA-CS NPs were monodisperse nanoparticles with suitable average size and positive surface charge. Dox was easily loaded into FA-CS NPs, and the release pattern showed a long and biphasic drug release. Noticeable phagocytosis effect was observed in the presence of rhodamine B-labeled FA-CSNPs when incubating with the folate receptor-positive SMMC-7221 cells. Conclusion. Compared with the unmodified CS NPs, FA-CS NPs showed much higher cell uptaking ability due to the known folate-receptor mediated endocytosis. FA-CS NPs provide a potential way to enhance the using efficiency of antitumor drug by folate receptor mediated targeting delivery.

  18. Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Monika Kovačević

    2014-08-01

    Full Text Available Our previous studies showed that alteration of dipeptides Y-Fca-Ala-OMe (III into Y-Ala-Fca-OMe (IV (Y = Ac, Boc; Fca = 1'-aminoferrocene-1-carboxylic acid significantly influenced their conformational space. The novel bioconjugates Y-Fca-Pro-OMe (1, Y = Ac; 2, Y = Boc and Y-Pro-Fca-OMe (3, Y = Boc; 4, Y = Ac have been prepared in order to investigate the influence of proline, a well-known turn-inducer, on the conformational properties of small organometallic peptides with an exchanged constituent amino acid sequences. For this purpose, peptides 1–4 were subjected to detailed spectroscopic analysis (IR, NMR, CD spectroscopy in solution. The conformation of peptide 3 in the solid state was determined. Furthermore, the ability of the prepared conjugates to inhibit the growth of estrogen receptor-responsive MCF-7 mammary carcinoma cells and HeLa cervical carcinoma cells was tested.

  19. Research advance of conjugated linoleic acids%共轭亚油酸研究进展

    Institute of Scientific and Technical Information of China (English)

    谷利伟; 赵金兰

    2001-01-01

    Conjugated linoletic acids were naturally occured isomers of linoleic acid, which were new functional lipids possessing many physiological benefits including anticarcinogenesis, antioxidant, inhibition of body fat accumulation, growth and immune stimulation. Their physiological effects, resource and preparation were reviewed.%共轭亚油酸是天然存在于食品中的亚油酸异构体,具有抗癌、抗氧化、降低血清胆固醇、抑制脂肪积累、促进生长、刺激免疫等作用,是一种新的保键功能脂质。本文对其生理功能、来源等研究情况进行论述。

  20. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Na-Young Park

    2010-01-01

    Full Text Available Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA, a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage. We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

  1. Conjugated linoleic acid (CLA) formation in edible oils by photoisomerization: a review.

    Science.gov (United States)

    Gangidi, Rahul Reddy; Lokesh, Belur Ramaswamy

    2014-05-01

    Conjugated linoleic acid (CLA) that is commonly found in dairy and ruminant fats, is geometrical and positional isomer of linoleic acid (LA). Edible oils are not good sources of CLA. Attempts have been made to generate CLA in edible oils through photoisomerization procedures. CLA isomers have several proven health benefits. This article reviews procedures for producing CLA containing edible oils by photoisomerization approach and applications of photoisomerized oils for food uses. The article reviews (1) the photoisomerized production of CLA containing oils on lab scale, with customized equipment, at pilot plant scale; (2) the effects of iodine content, photoisomerization time, refining, interference from minor components of oils, efficacy of different edible oils containing LA, interference from antioxidants; (3) the chemical kinetics, oxidative stability; and (4) photoisomerized oils for frying oils and as drying oils.The review also briefly covers methods of measurement of CLA.

  2. Effect of conjugated linoleic acid on fungal delta6-desaturase activity in a transformed yeast system.

    Science.gov (United States)

    Chuang, L T; Thurmond, J M; Liu, J W; Kirchner, S J; Mukerji, P; Bray, T M; Huang, Y S

    2001-02-01

    Conjugated linoleic acid (CLA; 18:2), a group of positional and geometric isomers of linoleic acid (LA; 18:2n-6), has been shown to modulate immune function through its effect on eicosanoid synthesis. This effect has been attributed to a reduced production of n-6 polyunsaturated fatty acid (PUFA), the precursor of eicosanoids. Since delta6-desaturase is the rate-limiting enzyme of the n-6 PUFA production, it is our hypothesis that CLA, which has similar chemical structure to LA, interacts directly with delta6-desaturase. A unique and simple model, i.e., baker's yeast (Saccharomyces cerevisiae) transformed with fungal delta6-desaturase gene, previously established, was used to investigate the direct effect of CLA on delta6-desaturase. This model allows LA to be converted to y-linolenic acid (GLA; 18:3n-6) but not GLA to its metabolite(s). No metabolites of CLA were found in the lipids of the yeast transformed with delta6-desaturase. The inability to convert CLA to conjugated GLA was not due to the failure of yeast cells to take up the CLA isomers. CLA mixture and individual isomers significantly inhibited the activity of delta6-desaturase of the transformed yeast in vivo. Even though its uptake by the yeast was low, CLA c9,t11 isomer was found to be the most potent inhibitor of the four isomers tested, owing to its high inhibitory effect on delta6-desaturase. Since CLA did not cause significant changes in the level of delta6-desaturase mRNA, the inhibition of GLA production could not be attributed to suppression of delta6-desaturase gene expression at the transcriptional level.

  3. Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

    DEFF Research Database (Denmark)

    Obsen, Thomas; Faergeman, Nils J; Chung, Soonkyu;

    2012-01-01

    Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid......]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10......,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within...

  4. CONJUGATED LINOLEIC ACIDS (CLA) DECREASE THE BREAST CANCER RISK IN DMBA-TREATED RATS.

    Science.gov (United States)

    Białek, Agnieszka; Tokarz, Andrzej; Zagrodzki, Paweł

    2016-01-01

    The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids.

  5. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  6. In vitro investigation of self-assembled nanoparticles based on hyaluronic acid-deoxycholic acid conjugates for controlled release doxorubicin: effect of degree of substitution of deoxycholic acid.

    Science.gov (United States)

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang

    2015-03-31

    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin-mediated cancer therapy.

  7. Influence of dietary conjugated linoleic acid (CLA and L-Lysine on heavy pigs performances and meat quality

    Directory of Open Access Journals (Sweden)

    C. Corino

    2010-01-01

    Full Text Available Conjugated linoleic acid (CLA refers to a group of positional and geometric fatty acid isomers derived from linoleic acid. Dietary CLA supplementation has been shown to increase feed efficiency and may reduce body fat content in swine as recently reviewed by Corino et al., (2005. There was only one research conducted in heavy pig in which the authors did not observed any significant effect of dietary CLA on growth performances and lean tissue (Corino et al., 2003.

  8. Production of conjugated linoleic and conjugated α-linolenic acid in a reconstituted skim milk-based medium by bifidobacterial strains isolated from human breast milk.

    Science.gov (United States)

    Villar-Tajadura, María Antonia; Rodríguez-Alcalá, Luis Miguel; Martín, Virginia; Gómez de Segura, Aránzazu; Rodríguez, Juan Miguel; Requena, Teresa; Fontecha, Javier

    2014-01-01

    Eight bifidobacterial strains isolated from human breast milk have been tested for their abilities to convert linoleic acid (LA) and α-linolenic acid (LNA) to conjugated linoleic acid (CLA) and conjugated α-linolenic acid (CLNA), respectively. These bioactive lipids display important properties that may contribute to the maintenance and improvement human health. Three selected Bifidobacterium breve strains produced CLA from LA and CLNA from LNA in MRS (160-170 and 210-230 μg mL(-1), resp.) and, also, in reconstituted skim milk (75-95 and 210-244 μg mL(-1), resp.). These bifidobacterial strains were also able to simultaneously produce both CLA (90-105 μg mL(-1)) and CLNA (290-320 μg mL(-1)) in reconstituted skim milk. Globally, our findings suggest that these bifidobacterial strains are potential candidates for the design of new fermented dairy products naturally containing very high concentrations of these bioactive lipids. To our knowledge, this is the first study describing CLNA production and coproduction of CLA and CLNA by Bifidobacterium breve strains isolated from human milk in reconstituted skim milk.

  9. Production of Conjugated Linoleic and Conjugated α-Linolenic Acid in a Reconstituted Skim Milk-Based Medium by Bifidobacterial Strains Isolated from Human Breast Milk

    Directory of Open Access Journals (Sweden)

    María Antonia Villar-Tajadura

    2014-01-01

    Full Text Available Eight bifidobacterial strains isolated from human breast milk have been tested for their abilities to convert linoleic acid (LA and α-linolenic acid (LNA to conjugated linoleic acid (CLA and conjugated α-linolenic acid (CLNA, respectively. These bioactive lipids display important properties that may contribute to the maintenance and improvement human health. Three selected Bifidobacterium breve strains produced CLA from LA and CLNA from LNA in MRS (160–170 and 210–230 μg mL−1, resp. and, also, in reconstituted skim milk (75–95 and 210–244 μg mL−1, resp.. These bifidobacterial strains were also able to simultaneously produce both CLA (90–105 μg mL−1 and CLNA (290–320 μg mL−1 in reconstituted skim milk. Globally, our findings suggest that these bifidobacterial strains are potential candidates for the design of new fermented dairy products naturally containing very high concentrations of these bioactive lipids. To our knowledge, this is the first study describing CLNA production and coproduction of CLA and CLNA by Bifidobacterium breve strains isolated from human milk in reconstituted skim milk.

  10. Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

    Science.gov (United States)

    Yang, Susan Q; DeGuire, Jason R; Lavery, Paula; Mak, Ivy L; Weiler, Hope A; Santosa, Sylvia

    2016-05-01

    We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs.

  11. Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue.

    Science.gov (United States)

    Adkins, Yuriko; Belda, Benjamin J; Pedersen, Theresa L; Fedor, Dawn M; Mackey, Bruce E; Newman, John W; Kelley, Darshan S

    2017-05-01

    Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F1α (P < 0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-, DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA-derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and PGF1α, PGF2α, and F2-isoprostanes. DHA counteracted CLA-induced effects in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins, respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased anti-inflammatory oxylipins and diminished concentration of CLA-induced pro-inflammatory oxylipins in AT.

  12. Comparison between conjugated linoleic acid and essential fatty acids in preventing oxidative stress in bovine mammary epithelial cells.

    Science.gov (United States)

    Basiricò, L; Morera, P; Dipasquale, D; Tröscher, A; Bernabucci, U

    2017-03-01

    Some in vitro and in vivo studies have demonstrated protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation. However, only a few and conflicting studies have been conducted showing the antioxidant potential of essential fatty acids. The objectives of the study were to compare the effects of CLA to other essential fatty acids on the thiol redox status of bovine mammary epithelia cells (BME-UV1) and their protective role against oxidative damage on the mammary gland by an in vitro study. The BME-UV1 cells were treated with complete medium containing 50 μM of cis-9,trans-11 CLA, trans-10,cis-12 CLA, α-linolenic acid, γ-linolenic acid, and linoleic acid. To assess the cellular antioxidant response, glutathione, NADPH, and γ-glutamyl-cysteine ligase activity were measured 48 h after addition of fatty acids (FA). Intracellular reactive oxygen species and malondialdehyde production were also assessed in cells supplemented with FA. Reactive oxygen species production after 3 h of H2O2 exposure was assessed to evaluate and to compare the potential protection of different FA against H2O2-induced oxidative stress. All FA treatments induced an intracellular GSH increase, matched by high concentrations of NADPH and an increase of γ-glutamyl-cysteine ligase activity. Cells supplemented with FA showed a reduction in intracellular malondialdehyde levels. In particular, CLA isomers and linoleic acid supplementation showed a better antioxidant cellular response against oxidative damage induced by H2O2 compared with other FA. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  13. Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres.

    Science.gov (United States)

    Shen, Zheyu; Li, Yan; Kohama, Kazuhiro; Oneill, Brian; Bi, Jingxiu

    2011-01-01

    Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX-AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2h were incubated for 70h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRα) and AoSMC cells (without FRα) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug

  14. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    Science.gov (United States)

    Castillo, John J.; Rindzevicius, Tomas; Wu, Kaiyu; Schmidt, Michael S.; Janik, Katarzyna A.; Boisen, Anja; Svendsen, Winnie; Rozlosnik, Noemi; Castillo-León, Jaime

    2014-07-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.

  15. Novel PH Sensitive Nanocarrier Agents Based on Citric Acid Dendrimers Containing Conjugated β-Cyclodextrins

    Directory of Open Access Journals (Sweden)

    Hassan Namazi

    2011-06-01

    Full Text Available Introduction: In this work, the use of β-cyclodextrine (β-CD-modified dendrimers as a nanocapsule with a biocompatible shell have studied. β-CD-modified dendrimers have designed and synthesized to enhance the loading capacity of the final dendrimers with encapsulation properties. Methods: To achieve β-CD-modified dendrimers, first citric acid dendrimers were synthesized and then the end functional groups of dendrimers were grafted to β-CD through ester linkages. The molecular structures of resulted dendrimers were verified using common spectroscopic methods such as 1H NMR, FT-IR and the diameters of obtained nanocarriers were evaluated with using dynamic light scattering (DLS experiments. The isolated dendrimers were utilized as the drug delivery agents and the encapsulation and the controlled release of guest drug molecule Naltrexone (NLX was investigated in different pH’s using UV spectroscopy method. Results: It was established that the loading capacity of dendrimers depend on several factors such as their generation and the structure and number of conjugated modifier end groups. Conclusion: Increasing in the number of branches and the size of interior voids and number of conjugated β-CDs cause to enhance the loading capacity.

  16. Tritium labeled amino acid conjugates of prostaglandins and thromboxanes as labeled ligands in prostanoid radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Sautebin, L.; Kindahl, H.; Kumlin, M.; Granstroem, E.

    1985-09-01

    Conjugates of prostaglandins and thromboxanes with tritium labeled amino acids were prepared and employed as labeled ligands in prostaglandin and thromboxane radioimmunoassays. Assays for PGF2 alpha, 15-keto-13, 14-dihydro-PGF2 alpha, TXB2 and 15-keto-13,14-dihydro-TXB2 were evaluated in comparative studies using either these heterologous ligands or the corresponding homologous tritiated eicosanoid as tracers. Binding properties for the respective antibodies were found to be similar using either tracer. Three biological studies were also conducted, viz. study of the release of TXB2 during collagen induced platelet aggregation, of 15-keto-13,14-dihydro-TXB2 during guinea pig pulmonary anaphylaxis, and of PGF2 alpha during bovine luteolysis. The analyses gave comparable results using either the heterologous or the homologous assay. Thus, this type of labeled prostanoid conjugates may serve as a convenient alternative to homologous tracers in radioimmunoassay. Heterologous tracers may even in certain cases provide the only simple solution to the problem of preparing a labeled ligand of high specific activity.

  17. Metabolism of c9,t11-conjugated linoleic acid (CLA) in humans.

    Science.gov (United States)

    Mele, Maria Cristina; Cannelli, Giorgio; Carta, Gianfranca; Cordeddu, Lina; Melis, Maria Paola; Murru, Elisabetta; Stanton, Catherine; Banni, Sebastiano

    2013-08-01

    The c9,t11 isomer of conjugated linoleic acid (CLA) is the most abundant CLA form present in the human diet, and is particularly prevalent in milk and dairy products, and is known to exert several health benefits in experimental animal models. A possible mechanism of action of c9,t11CLA relies on its metabolism via desaturases and elongases and partial beta oxidation in peroxisomes. In this study, we aimed to establish plasma incorporation of c9,t11CLA and its downstream metabolites in healthy volunteers after daily dietary intakes of 0.8g, 1.6g or 3.2g of c9,t11CLA in capsule form for two months. Following supplementation, the plasma concentrations of c9,t11CLA and its metabolites conjugated dienes (CD) 18:3 and the beta oxidation product CD 16:2 were incorporated in a linear fashion, while on the other hand CD 20:3 reached a plateau following intakes of 1.6g/d of dietary intake, and was not further increased following higher CLA intakes. We may conclude that supplementation of c9,t11 CLA levels result in linear responses of CLA and its main metabolites in plasma. In addition, only the highest concentration of CLA intake tested (3.2g/d) yielded plasma concentrations of CLA and metabolites close to the range found sufficient to exert nutritional effects in experimental animal models.

  18. Photosensitizer-Conjugated Hyaluronic Acid-Shielded Polydopamine Nanoparticles for Targeted Photomediated Tumor Therapy.

    Science.gov (United States)

    Han, Jieun; Park, Wooram; Park, Sin-Jung; Na, Kun

    2016-03-01

    Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS-biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy. This novel photomedicine consisted of a PD-NP core and a PS-conjugated hyaluronic acid (PS-HA) shell. The PD-NP and the PS-HA play roles as a quencher for PSs and a cancer targeting moiety, respectively. The synthesized PS-HA-shielded PD-NPs (PHPD-NPs) had a relatively narrow size distribution (approximately 130 nm) with uniform spherical shapes. In response to cancer-specific intracellular enzymes (e.g., hyaluronidase), the PHPD-NPs exhibited an excellent singlet oxygen generation capacity for PDT. Furthermore, an efficient photothermal conversion ability for photothermal therapy (PTT) was also shown in the PHPD-NPs system. These properties provide superior therapeutic efficacy against cancer cells. In mice tumor model, the photoactive restorative effects of the PHPD-NPs were much higher in cancer microenvironments compared to that in the normal tissue. As a result, the PHPD-NPs showed a significant antitumor activity in in vivo mice tumor model. The nanoparticle photomedicine design is a novel strategy for effective tumor therapy.

  19. Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes.

    Science.gov (United States)

    Cox, Bryan D; Muccio, Donald D; Hamilton, Tracy P

    2013-05-01

    Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all-trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers (6-7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers (6-7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers (6-7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations.

  20. Conjugated linoleic acids as functional food: an insight into their health benefits

    Science.gov (United States)

    Benjamin, Sailas; Spener, Friedrich

    2009-01-01

    This review evaluates the health benefits of the functional food, conjugated linoleic acids (CLA) - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, hundreds of reports - principally based on in vitro, microbial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studies highlight that CLA, apart form the classical nuclear transcription factors-mediated mechanism of action, appear to exhibit a number of inter-dependent molecular signalling pathways accounting for their reported health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti-atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic effects. On the other hand, negative effects of CLA have been reported such as fatty liver and spleen, induction of colon carcinogenesis and hyperproinsulinaemia. As far as human consumption is concerned, a definite conclusion for CLA safety has not been reached yet. Parameters such as administration of the type of CLA isomer and/or their combination with other polyunsaturated fatty acids, mode of administration (eg., as free fatty acid or its triglyceride form, liquid or solid), daily dose and duration of consumption, gender, age, or ethnic and geographical backgrounds remain to be determined. Yet, it appears from trials so far conducted that CLA are functional food having prevailing beneficial health effects for humans. PMID:19761624

  1. Conjugated linoleic acids as functional food: an insight into their health benefits

    Directory of Open Access Journals (Sweden)

    Benjamin Sailas

    2009-09-01

    Full Text Available Abstract This review evaluates the health benefits of the functional food, conjugated linoleic acids (CLA - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, hundreds of reports - principally based on in vitro, microbial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studies highlight that CLA, apart form the classical nuclear transcription factors-mediated mechanism of action, appear to exhibit a number of inter-dependent molecular signalling pathways accounting for their reported health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti-atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic effects. On the other hand, negative effects of CLA have been reported such as fatty liver and spleen, induction of colon carcinogenesis and hyperproinsulinaemia. As far as human consumption is concerned, a definite conclusion for CLA safety has not been reached yet. Parameters such as administration of the type of CLA isomer and/or their combination with other polyunsaturated fatty acids, mode of administration (eg., as free fatty acid or its triglyceride form, liquid or solid, daily dose and duration of consumption, gender, age, or ethnic and geographical backgrounds remain to be determined. Yet, it appears from trials so far conducted that CLA are functional food having prevailing beneficial health effects for humans.

  2. Physico-chemical modifications of conjugated linoleic acid for ruminal protection and oxidative stability

    Directory of Open Access Journals (Sweden)

    Choi Yun-Jaie

    2008-06-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA, 18:2n-6]. Although ruminant milk and meat products represent the largest natural source of CLA and therefore, their concentration in ruminant lipids are of interest to human health, chemical or physical modifications of CLA should be needed as a means to enhance oxidative stability, to improve post-ruminal bioavailability, and to increase the clinical application. In fact, CLA are rapidly decomposed to form furan fatty acids when its are oxidized in air, and the effectiveness of dietary supplements of CLA may be related to the extent that their metabolisms by rumen bacteria are avoided. For these reasons, many scientists have examined the effect of manufacturing and protection on the stability of CLA in ruminants and food products. In this review, physico-chemical modifications of CLA for ruminal protection such as calcium salt (Ca, formaldehyde protection (FP, lipid encapsulation (LE, and amide linkage (AL, and for oxidative stability such as green tea catechin (GTC, cyclodextrin (CD, arginine (Arg, amylase, and PEGylation are proposed.

  3. Physico-chemical modifications of conjugated linoleic acid for ruminal protection and oxidative stability.

    Science.gov (United States)

    Moon, Hyun-Seuk; Lee, Hong-Gu; Chung, Chung-Soo; Choi, Yun-Jaie; Cho, Chong-Su

    2008-06-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6]. Although ruminant milk and meat products represent the largest natural source of CLA and therefore, their concentration in ruminant lipids are of interest to human health, chemical or physical modifications of CLA should be needed as a means to enhance oxidative stability, to improve post-ruminal bioavailability, and to increase the clinical application. In fact, CLA are rapidly decomposed to form furan fatty acids when its are oxidized in air, and the effectiveness of dietary supplements of CLA may be related to the extent that their metabolisms by rumen bacteria are avoided. For these reasons, many scientists have examined the effect of manufacturing and protection on the stability of CLA in ruminants and food products. In this review, physico-chemical modifications of CLA for ruminal protection such as calcium salt (Ca), formaldehyde protection (FP), lipid encapsulation (LE), and amide linkage (AL), and for oxidative stability such as green tea catechin (GTC), cyclodextrin (CD), arginine (Arg), amylase, and PEGylation are proposed.

  4. Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

    Directory of Open Access Journals (Sweden)

    Dan Yuan

    2014-10-01

    Full Text Available This article reports the synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS to build the peptide segment (Phe-Arg-Gly-Asp or naphthAla-Phe-Arg-Gly-Asp with fully protected groups, and later, an amidation reaction in liquid phase connects these three parts together. The overall yield of these multiple step synthesis is about 34%. Besides exhibiting excellent solubility, these conjugates of saccharide–amino acids–nucleobase (SAN, like the previously reported conjugates of nucleobase–amino acids–saccharide (NAS and nucleobase–saccharide–amino acids (NSA, are mammalian cell compatible.

  5. Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil hyperactivation and protects from experimental colon inflammation in rats.

    Directory of Open Access Journals (Sweden)

    Tarek Boussetta

    Full Text Available BACKGROUND: Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO. The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE: These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.

  6. Anionic magnetite nanoparticle conjugated with pyrrolidinyl peptide nucleic acid for DNA base discrimination

    Science.gov (United States)

    Khadsai, Sudarat; Rutnakornpituk, Boonjira; Vilaivan, Tirayut; Nakkuntod, Maliwan; Rutnakornpituk, Metha

    2016-09-01

    Magnetite nanoparticles (MNPs) were surface modified with anionic poly( N-acryloyl glycine) (PNAG) and streptavidin for specific interaction with biotin-conjugated pyrrolidinyl peptide nucleic acid (PNA). Hydrodynamic size ( D h) of PNAG-grafted MNPs varied from 334 to 496 nm depending on the loading ratio of the MNP to NAG in the reaction. UV-visible and fluorescence spectrophotometries were used to confirm the successful immobilization of streptavidin and PNA on the MNPs. About 291 pmol of the PNA/mg MNP was immobilized on the particle surface. The PNA-functionalized MNPs were effectively used as solid supports to differentiate between fully complementary and non-complementary/single-base mismatch DNA using the PNA probe. These novel anionic MNPs can be efficiently applicable for use as a magnetically guidable support for DNA base discrimination.

  7. Preliminary observations on the effects of milk fortification with conjugated linoleic acid in yogurt preparation

    Science.gov (United States)

    Salamon, R. V.; Albert, I.; András, C. D.; Csapó, J.; Ibănescu, C.

    2015-04-01

    The fortification and enrichment of food with health benefic natural or natural identical substances creating new functional foods became an important issue for food researchers and processors. However, often occurs that the obtained products (despite of their health benefic activity) cannot be marketed due to strange or accustomed taste and/or texture. The aim of the research was to elucidate the effect of conjugated linoleic acid (CLA) enrichment of raw milk on the rheological properties of the obtained yogurt. The results show that the values of the complex viscosity at 50 rad.s-1 (correlated with the thickness and sliminess of the food gel structures) of the CLA-enriched yogurt was the lowest among the studied samples, meaning the enriched yogurt is more creamy than the commercial products. These observations gave us the hope that, in this case, the texture of enriched product will not present any drawback related to consumer quality judgment.

  8. Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene.

    Science.gov (United States)

    Hernández, V; Máñez, S; Recio, M C; Giner, R M; Ríos, J L

    2005-10-01

    Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic acid. The most salient findings were that in vitro dehydrocostic acid inhibits leukotriene B(4) production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesquiterpenoid was effective on some models of acute edema induced by PLA(2) and 12-O-tetradecanoylphorbol 13-acetate (TPA) Comparison of these data with that known for ilicic acid firmly suggests that the presence of a semiplanar ring A is essential for an improved inhibitory activity on inflammatory mediators.

  9. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    Science.gov (United States)

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P muscle and liver (SREBP1, both P muscle and reduced (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  10. Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells.

    Science.gov (United States)

    O'Shea, M; Devery, R; Lawless, F; Murphy, J; Stanton, C

    The relationship between growth and the antioxidant enzyme defence system in human MCF-7 (breast) cancer cells treated with bovine milk fat enriched with conjugated linoleic acid (CLA) was studied. Milk enriched in CLA was obtained from cows on pasture supplemented with full fat rapeseeds and full fat soyabeans (1). Cell number decreased up to 90% (p milk fat yielding CLA concentrations between 16.9 and 22.6 ppm. Growth suppression and prooxidant effects of milk fat CLA were independent of the variable composition of the milk fat samples, suggesting that CLA was the active ingredient in milk fat responsible for the cytotoxic effect. Mixtures containing isomers of CLA (c9, t11-, t10, c12-, c11, t13- and minor amounts of other isomers) and linoleic acid (LA) at similar concentrations to the milk fat samples were as effective at inhibiting growth and stimulating peroxidation of MCF-7 cells as the milk fatty acids. Incubation of the cells with the c9, t11 CLA isomer (20 ppm) or the mixture of CLA isomers (20 ppm) for 8 days resulted in a 60% decrease (p milk fat than the c9, t11 synthetic CLA isomer. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities were induced in MCF-7 cells exposed to milk fat (containing 16.9-22.6 ppm CLA) over 8 days. The data indicate that milk fat triglyceride-bound CLA, consisting primarily of the c9, t11 isomer, was cytotoxic towards MCF-7 cells.

  11. Production of conjugated linoleic acids by Lactobacillusplantarum strains isolated from naturally fermented Chinese pickles

    Institute of Scientific and Technical Information of China (English)

    Pei LIU; Sheng-rong SHEN; Hui RUAN; Qian ZHOU; Liu-liu MA; Guo-qing HE

    2011-01-01

    Naturally fermented pickles harbour many lactic acid bacteria (LAB).Forty-three LAB strains with conjugated linoleic acid (CLA)-producing ability were isolated from three naturally fermented pickle brines.Of these isolates,Ip15 identified as Lactobacillus plantarum by API 50 CHL system and full-length 16S rDNA sequence analysis exhibited the highest CLA-producing ability (26.1% conversion) at 48 h in de Man Rogosa Sharpe (MRS) broth in the presence of 100 μg/ml of linoleic acid (LA).Compared to other strains,L.plantarum strain Ip15 showed the highest tolerance upon increased levels of LA in the medium,I.e.,up to 600 pg/ml.This strain converted about 25% of LA into CLA isomers [predominantly cis-9,trans-11 CLA (9-CLA) and trans-10,cis-12 CLA (10-CLA)],of which 75% was 9-CLA.Interestingly,though the conversion rate of LA into CLA by Ip15 remained stable between 100 to 600 μg/ml LA levels in the medium,it dropped sharply at 1000 μg/ml.Taken together,the Ip15 strain displayed relatively high LA tolerance with higher conversion rate,which implies that this strain is a valuable candidate for enhancing the CLA content in food-sources like pickles.

  12. Non-covalent conjugates of single-walled carbon nanotubes and folic acid for interaction with cells overexpressing folate receptors

    DEFF Research Database (Denmark)

    Castillo, John J.; Rindzevicius, Tomas; Novoa, Leidy V.

    2013-01-01

    We here present amethod to form a noncovalent conjugate of single-walled carbon nanotubes and folic acid aimed to interact with cells over-expressing folate receptors. The bonding was obtained without covalent chemical functionalization using a simple, rapid “one pot” synthesis method. The zeta p...

  13. Folic acid conjugated self-assembled layered double hydroxide nanoparticles for high-efficacy-targeted drug delivery.

    Science.gov (United States)

    Yan, Li; Chen, Wei; Zhu, Xiaoyue; Huang, Longbiao; Wang, Zhigang; Zhu, Guangyu; Roy, V A L; Yu, K N; Chen, Xianfeng

    2013-12-04

    Enhanced selectivity and efficacy is important for advanced drug delivery. Herein, a novel type of folic acid conjugated self-assembled layered double hydroxide nanoparticles is reported. These nanoparticles have a drug loading capacity of 27 wt% and are able to enter cell nuclei and dramatically improve the efficacy of MTX.

  14. Accurate pKa Calculation of the Conjugate Acids of Alkanolamines, Alkaloids and Nucleotide Bases by Quantum Chemical Methods

    NARCIS (Netherlands)

    Gangarapu, S.; Marcelis, A.T.M.; Zuilhof, H.

    2013-01-01

    The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum

  15. Synthesis, Characterization, and Saccharide Binding Studies of Bile Acid − Porphyrin Conjugates

    Directory of Open Access Journals (Sweden)

    Vladimír Král

    2007-01-01

    Full Text Available Synthesis and characterization of bile acid-porphyrin conjugates (BAPs are reported. Binding of saccharides with BAPs in aqueous methanol was studied by monitoring changes in the visible absorption spectral of the porphyrin-moieties. Although these studies clearly showed absorbance changes, suggesting quite high if non-selective binding, the mass spectral studies do not unambiguously support these results.

  16. The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine.

    Science.gov (United States)

    Hu, Sherry Shu-Jung; Bradshaw, Heather B; Benton, Valery M; Chen, Jay Shih-Chieh; Huang, Susan M; Minassi, Alberto; Bisogno, Tiziana; Masuda, Kim; Tan, Bo; Roskoski, Robert; Cravatt, Benjamin F; Di Marzo, Vincenzo; Walker, J Michael

    2009-10-01

    N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine and the other is via metabolism of a putative N-arachidonoyl tyrosine (NA-tyrosine). In the present study we investigated these biosynthetic mechanisms and report that NADA synthesis requires TH in dopaminergic terminals; however, NA-tyrosine, which we identify here as an endogenous lipid, is not an intermediate. We show that NADA biosynthesis primarily occurs through an enzyme-mediated conjugation of arachidonic acid with dopamine. While this conjugation likely involves a complex of enzymes, our data suggest a direct involvement of fatty acid amide hydrolase in NADA biosynthesis either as a rate-limiting enzyme that liberates arachidonic acid from AEA, or as a conjugation enzyme, or both.

  17. Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

    Directory of Open Access Journals (Sweden)

    Ortensia I. Parisi

    2017-08-01

    Full Text Available Background: Melanins are high molecular weight pigments responsible for the mammalian skin and hair colour and play a key role in skin protection from UV radiation; however, their overproduction and excessive accumulation lead to pigmentation problems including melasma, freckles, uneven colouring, and age spots. Therefore, the modulation of melanin synthesis represents a critical issue in medicine and cosmetology. In the present study, an innovative polymeric antioxidant to be used as skin whitening agent is developed by the conjugation of dextran with rosmarinic acid. Methods: Dextran-rosmarinic acid conjugates (DEX-RA were synthesized in a one-pot method starting from Origanum vulgare aqueous leaf extract and dextran. The total polyphenol content and the antioxidant activity were assessed by Folin-Ciocalteau assay and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH and bleaching tests, respectively. The efficacy of DEX-RA was evaluated by inhibition of tyrosinase activity, in vitro diffusion and stability studies and in vivo studies. The biocompatibility of the conjugates was investigated by 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazoliumbromide (MTT and EPISKIN™ model. Results: Efficacy and safety studies confirmed the antioxidant and tyrosinase inhibitory activities and the biocompatibility of the synthesized conjugates. Conclusion: The polymeric conjugates, comparing to the free antioxidant, show a long-lasting efficacy combined to an enhanced stability resulting in an improved performance of the cosmetic formulations prepared using this innovative whitening agent as a bioactive ingredient.

  18. Synthesis and antiulcer activity evaluation of conjugates of amino acids with N-aroyl- N, N'-dicyclohexyl urea

    Directory of Open Access Journals (Sweden)

    Subudhi Bharat

    2011-12-01

    Full Text Available Abstract Amino acids are safe molecules with variable efficacy against ulceration. Considering the good antioxidant potential of N-aroyl- N, N'-dicyclohexyl urea and antiulcer activities of amino acids, a series of amino acid conjugates of N-aroyl- N, N'-dicyclohexyl urea was synthesized and the effect against ulceration in albino rats induced by pyloric ligation was screened. All these compounds were found to be safe and active. Reduction of ulcer index was significant for all compounds. Conjugates of methionine and histidine exhibited enhanced antiulcer activity comparable to omeprazole in terms of inhibition of release of gastric juice, hydrochloric acid and neutralization activity. The promising efficacy and safety of these compounds is interesting for further investigation.

  19. Methoxinine - an alternative stable amino acid substitute for oxidation-sensitive methionine in radiolabelled peptide conjugates.

    Science.gov (United States)

    Grob, Nathalie M; Behe, Martin; von Guggenberg, Elisabeth; Schibli, Roger; Mindt, Thomas L

    2017-01-01

    Radiolabelled peptides with high specificity and affinity towards receptors that are overexpressed by tumour cells are used in nuclear medicine for the diagnosis (imaging) and therapy of cancer. In some cases, the sequences of peptides under investigations contain methionine (Met), an amino acid prone to oxidation during radiolabelling procedures. The formation of oxidative side products can affect the purity of the final radiopharmaceutical product and/or impair its specificity and affinity towards the corresponding receptor. The replacement of Met with oxidation resistant amino acid analogues, for example, norleucine (Nle), can provide a solution. While this approach has been applied successfully to different radiolabelled peptides, a Met → Nle switch only preserves the length of the amino acid side chain important for hydrophobic interactions but not its hydrogen-bonding properties. We report here the use of methoxinine (Mox), a non-canonical amino acid that resembles more closely the electronic properties of Met in comparison to Nle. Specifically, we replaced Met(15) by Mox(15) and Nle(15) in the binding sequence of a radiometal-labelled human gastrin derivative [d-Glu(10) ]HG(10-17), named MG11 (d-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ). A comparison of the physicochemical properties of (177) Lu-DOTA[X(15) ]MG11 (X = Met, Nle, Mox) in vitro (cell internalization/externalization properties, receptor affinity (IC50 ), blood plasma stability and logD) showed that Mox indeed represents a suitable, oxidation-stable amino acid substitute of Met in radiolabelled peptide conjugates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  20. Toxicity of Carboxylic Acid-Containing Drugs: The Role of Acyl Migration and CoA Conjugation Investigated.

    Science.gov (United States)

    Lassila, Toni; Hokkanen, Juho; Aatsinki, Sanna-Mari; Mattila, Sampo; Turpeinen, Miia; Tolonen, Ari

    2015-12-21

    Many carboxylic acid-containing drugs are associated with idiosyncratic drug toxicity (IDT), which may be caused by reactive acyl glucuronide metabolites. The rate of acyl migration has been earlier suggested as a predictor of acyl glucuronide reactivity. Additionally, acyl Coenzyme A (CoA) conjugates are known to be reactive. Here, 13 drugs with a carboxylic acid moiety were incubated with human liver microsomes to produce acyl glucuronide conjugates for the determination of acyl glucuronide half-lives by acyl migration and with HepaRG cells to monitor the formation of acyl CoA conjugates, their further conjugate metabolites, and trans-acylation products with glutathione. Additionally, in vitro cytotoxicity and mitochondrial toxicity experiments were performed with HepaRG cells to compare the predictability of toxicity. Clearly, longer acyl glucuronide half-lives were observed for safe drugs compared to drugs that can cause IDT. Correlation between half-lives and toxicity classification increased when "relative half-lives," taking into account the formation of isomeric AG-forms due to acyl migration and eliminating the effect of hydrolysis, were used instead of plain disappearance of the initial 1-O-β-AG-form. Correlation was improved further when a daily dose of the drug was taken into account. CoA and related conjugates were detected primarily for the drugs that have the capability to cause IDT, although some exceptions to this were observed. Cytotoxicity and mitochondrial toxicity did not correlate to drug safety. On the basis of the results, the short relative half-life of the acyl glucuronide (high acyl migration rate), high daily dose and detection of acyl CoA conjugates, or further metabolites derived from acyl CoA together seem to indicate that carboxylic acid-containing drugs have a higher probability to cause drug-induced liver injury (DILI).

  1. ELECTRIC CONDUCTIVITY OF LONGISSIMUS DORSI MUSCLE OF PIGS FED THE FODDER WITH ADDITION OF CONJUGATED LINOLEIC ACID

    Directory of Open Access Journals (Sweden)

    Przemysław WASILEWSKI

    2009-06-01

    Full Text Available The aim of research was to investigate the impact of feeding pigs the fodder with addition of different level of conjugated linoleic acid on results of electric conductivity of Longissimus dorsi muscle. Electric conductivity (LF, Ger. Leitfähigkeitmessung is the method of meat quality estimation. This technique uses high relationships between electric conductivity and the other parameters of meat quality. In breeding and production of pigs the aim is to obtain fatteners of low fat and high meat content simultaneously keeping good meat tissue quality. One of the ways of their quality improvement is using fodder supplements as i.e. conjugated linoleic acid (CLA. Results of many research proved that conjugated linoleic acid impacts also in a favourable way on humans health because reduces cholesterol level, prevents from heart attacks and some cancers, stimulates immune system and has antiinfl ammatory properties. Statistical analysis covered the results of 60 crossbred gilts, divided into 6 groups, fed the fodder with addition of conjugated linoleic acid (CLA or sunfl ower oil (SFO in amounts: 0.5; 1.0; and 2.0 %, respectively. Fattening period of animals lasted for 8 weeks with ad-libitum feeding. In 1, 3, 6 hour, 24 hours, 3 and 7 days after slaughter electric conductivity of muscle tissue was measured – muscle Longissimus dorsi. Electric conductivity measured in different time after slaughter was not statistically diversed between tested groups of animals. The results concerned electric conductivity of muscle Longissimus dorsi of pigs fed the fodder with addition of conjugated linoleic acid should be stated as satisfactory and proved normal meat. Therefore, feeding pigs the fodder with CLA addition in amount of 0.5; 1.0 and 2.0 % did not impacts negatively on meat quality.

  2. The effect of conjugated linoleic acid on the fatty acid composition of ...

    African Journals Online (AJOL)

    rahim aydin

    models. CLA was first isolated from grilled ground beef (Ha et al., 1987) and found to be a ... in the fatty acid composition of the aorta, liver and plasma of rabbits (Lee, 1996). ... CLA was stored under an argon atmosphere at -20 °C until used.

  3. Effect of Conjugated Linoleic Acid Feeding on the Growth Performance and Meat Fatty Acid Profiles in Broiler: Meta-analysis

    Directory of Open Access Journals (Sweden)

    Sangbuem Cho

    2013-07-01

    Full Text Available The effect of conjugated linoleic acid (CLA feeding on growth performance and fatty acid profiles in thigh meat of broiler chicken was investigated using meta-analysis with a total of 9 studies. Overall effects were calculated by standardized mean differences between treatment (CLA fed and control using Hedges’s adjusted g from fixed and random effect models. Meta-regression was conducted to evaluate the effect of CLA levels. Subgroups in the same study were designated according to used levels of CLA, CP levels or substituted oils in diets. The effects on final body weight, weight gain, feed intake and feed conversion ratio were investigated as growth parameters. Total saturated and unsaturated fatty acid concentrations and C16:0, C18:0, C18:2 and C18:3 concentrations in thigh meat of broiler chicken were used as fatty acid profile parameters. The overall effect of CLA feeding on final weight was negative and it was only significant in fixed effect model (p<0.01. Significantly lower weight gain, feed intake and higher feed conversion ratio compared to control were found (p<0.05. CLA feeding on the overall increased total saturated fatty acid concentration in broilers compared to the control diet (p<0.01. Total unsaturated fatty acid concentration was significantly decreased by CLA feeding (p<0.01. As for individual fatty acid profiles, C16:0, C18:0 and C18:3 were increased and C18:2 was significantly decreased by CLA feeding (p<0.01. In conclusion, CLA was proved not to be beneficial for improving growth performance, whereas it might be supposed that CLA is effective modulating n-6/n-3 fatty acids ratio in thigh meat. However, the economical compensation of the loss from suppressed growth performance and increased saturated fatty acids with the benefit from enhanced n-6/n-3 ratio should be investigated in further studies in order to propose an appropriate use of dietary CLA in the broiler industry.

  4. Conjugated linoleic acid increases in milk from cows fed condensed corn distillers solubles and fish oil.

    Science.gov (United States)

    Bharathan, M; Schingoethe, D J; Hippen, A R; Kalscheur, K F; Gibson, M L; Karges, K

    2008-07-01

    Twelve lactating Holstein cows were randomly assigned to 1 of 4 experimental diets in a replicated 4 x 4 Latin square design with 4-wk periods to ascertain the lactational response to feeding fish oil (FO), condensed corn distillers solubles (CDS) as a source of extra linoleic acid, or both. Diets contained either no FO or 0.5% FO and either no CDS or 10% CDS in a 2 x 2 factorial arrangement of treatments. Diets were fed as total mixed rations for ad libitum consumption. The forage to concentrate ratio was 55:45 on a dry matter basis for all diets and the diets contained 16.2% crude protein. The ether extract concentrations were 2.86, 3.22, 4.77, and 5.02% for control, FO, CDS, and FOCDS diets, respectively. Inclusion of FO or CDS or both had no effect on dry matter intake, feed efficiency, body weight, and body condition scores compared with diets without FO and CDS, respectively. Yields of milk (33.3 kg/d), energy-corrected milk, protein, lactose, and milk urea N were similar for all diets. Feeding FO and CDS decreased milk fat percentages (3.85, 3.39, 3.33, and 3.12%) and yields compared with diets without FO and CDS. Proportions of trans-11 C18:1 (vaccenic acid), cis-9 trans-11 conjugated linoleic acid (CLA; 0.52, 0.90, 1.11, and 1.52 g/100 g of fatty acids), and trans-10 cis-12 CLA (0.07, 0.14, 0.13, and 0.16 g/100 g of fatty acids) in milk fat were increased by FO and CDS. No interactions were observed between FO and CDS on cis-9 trans-11 CLA although vaccenic acid tended to be higher with the interaction. The addition of CDS to diets increased trans-10 C18:1. Greater ratios of vaccenic acid to cis-9 trans-11 CLA in plasma than in milk fat indicate tissue synthesis of cis-9 trans-11 CLA in the mammary gland from vaccenic acid in cows fed FO or CDS. Feeding fish oil at 0.5% of diet dry matter with a C18:2 n-6 rich source such as CDS increased the milk CLA content but decreased milk fat percentages.

  5. Azide-alkyne cycloaddition for universal post-synthetic modifications of nucleic acids and effective synthesis of bioactive nucleic acid conjugates.

    Science.gov (United States)

    Su, Yu-Chih; Lo, Yu-Lun; Hwang, Chi-Ching; Wang, Li-Fang; Wu, Min Hui; Wang, Eng-Chi; Wang, Yun-Ming; Wang, Tzu-Pin

    2014-09-14

    The regioselective post-synthetic modifications of nucleic acids are essential to studies of these molecules for science and applications. Here we report a facile universal approach by harnessing versatile phosphoramidation reactions to regioselectively incorporate alkynyl/azido groups into post-synthetic nucleic acids primed with phosphate at the 5' termini. With and without the presence of copper, the modified nucleic acids were subjected to azide-alkyne cycloaddition to afford various nucleic acid conjugates including a peptide-oligonucleotide conjugate (POC) with high yield. The POC was inoculated with human A549 cells and demonstrated excellent cell-penetrating ability despite cell deformation caused by a small amount of residual copper chelated to the POC. The combination of phosphoramidation and azide-alkyne cycloaddition reactions thus provides a universal regioselective strategy to post-synthetically modify nucleic acids. This study also explicated the toxicity of residual copper in synthesized bioconjugates destined for biological systems.

  6. Folic acid-modified methotrexate-conjugated PEGylated poly(ɛ-caprolactone) nanoparticles for targeted delivery

    Science.gov (United States)

    Issarachot, Ousanee; Suksiriworapong, Jiraphong; Takano, Mikihisa; Yumoto, Ryoko; Junyaprasert, Varaporn Buraphacheep

    2014-02-01

    Functionalized nanoparticles of polymer-drug conjugates of PEGylated poly(ɛ-caprolactone) (PEGylated P(CL)) with methotrexate (MTX) and folic acid (FOL) were developed and investigated for their targeting efficiency. FOL- and MTX-conjugated PEGylated P(CL) copolymers were employed to prepare P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs. By varying the amount of MTX, the different characteristics of nanoparticles were obtained. The results showed that an increase in particle size and more negative surface charge of P(MTXCLCL)2-PEG NPs were related to an increased amount of MTX along the polymer backbone. After being decorated with FOL, the particle size increased by nearly twofolds while the zeta potential decreased. All nanoparticles were spherical as observed under SEM micrographs. The release profiles showed pH-dependent and sustained release over 20 days. Higher extent of MTX was released in pH 4.5 medium as compared to the drug release in pH 7.4 medium. All nanoparticles showed greater toxicity to MCF-7 cells than A549 cells. In addition, FOL-P(MTXCLCL)2-PEG NPs exhibited the highest toxicity to MCF-7 cells as compared to all P(MTXCLCL)2-PEG NPs and free MTX. Furthermore, FOL-P(MTXCLCL)2-PEG NPs were internalized into MCF-7 cells higher than P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs incubated with free FOL. The results indicated that FOL-P(MTXCLCL)2-PEG NPs efficiently entered into MCF-7 cells via folate receptor-mediated endocytosis together with adsorptive endocytosis.

  7. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

    Science.gov (United States)

    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (∼141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  8. Chemical, physical, and sensory properties of dairy products enriched with conjugated linoleic acid.

    Science.gov (United States)

    Jones, E L; Shingfield, K J; Kohen, C; Jones, A K; Lupoli, B; Grandison, A S; Beever, D E; Williams, C M; Calder, P C; Yaqoob, P

    2005-08-01

    Recent studies have illustrated the effects of cis-9,trans-11 conjugated linoleic acid (CLA) on human health. Ruminant-derived meat, milk and dairy products are the predominant sources of cis-9,trans-11 CLA in the human diet. This study evaluated the processing properties, texture, storage characteristics, and organoleptic properties of UHT milk, Caerphilly cheese, and butter produced from a milk enriched to a level of cis-9,trans-11 CLA that has been shown to have biological effects in humans. Forty-nine early-lactation Holstein-British Friesian cows were fed total mixed rations containing 0 (control) or 45 g/kg (on dry matter basis) of a mixture (1:2 wt/wt) of fish oil and sunflower oil during two consecutive 7-d periods to produce a control and CLA-enhanced milk, respectively. Milk produced from cows fed the control and fish and sunflower oil diets contained 0.54 and 4.68 g of total CLA/100 g of fatty acids, respectively. Enrichment of CLA in raw milk from the fish and sunflower oil diet was also accompanied by substantial increases in trans C18:1 levels, lowered C18:0, cis-C18:1, and total saturated fatty acid concentrations, and small increases in n-3 polyunsaturated fatty acid content. The CLA-enriched milk was used for the manufacture of UHT milk, butter, and cheese. Both the CLA-enhanced butter and cheese were less firm than control products. Although the sensory profiles of the CLA-enriched milk, butter, and cheese differed from those of the control products with respect to some attributes, the overall impression and flavor did not differ. In conclusion, it is feasible to produce CLA-enriched dairy products with acceptable storage and sensory characteristics.

  9. Influence of conjugated linoleic acid (CLA on intramuscular fatty acid composition in rabbit

    Directory of Open Access Journals (Sweden)

    C. Corino

    2010-01-01

    Full Text Available The impact of feeding CLA has been thoroughly investigated in pigs, and Thiel- Cooper et al. (2001, Ostrowska et al. (2003, Lo Fiego et al. (2004, found that CLA modifies lipid fatty acid profile, negatively affecting some nutritional lipid indexes. So far,much less attention has been paid to rabbits. Recently, Corino et al. (2003 have shown that supplementing rabbit diets with CLA has limited effect on the chemical composition of meat and at a high slaughter weight reduces intramuscular fat content. The present research has been carried out to evaluate the effect of dietary CLA supplementation on cis-9, trans-11 and trans-10,cis-12- C18:2 isomers content, and on fatty acid composition of rabbit intramuscular lipids.

  10. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

    Science.gov (United States)

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.

  11. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  12. Hyaluronic Acid Conjugated Magnetic Prussian Blue@Quantum Dot Nanoparticles for Cancer Theranostics

    Science.gov (United States)

    Yang, Yongbo; Jing, Lijia; Li, Xiaoda; Lin, Li; Yue, Xiuli; Dai, Zhifei

    2017-01-01

    A multifunctional nanotheranostic agent was developed by conjugating both hyaluronic acid and bovine serum albumin coated CuInS2-ZnS quantum dots onto the surface of magnetic Prussian blue nanoparticles. The obtained nanoagent could serve as an efficient contrast agent to simultaneously enhance near infrared (NIR) fluorescence and magnetic resonance (MR) imaging greatly. The coexistence of magnetic core and CD44 ligand hyaluronic acid was found to largely improve the specific uptake of the nanoagent by CD44 overexpressed HeLa cells upon applying an external magnetic field. Both NIR fluorescence and MR imaging in vivo proved high accumulation of the nanoagent at tumor site due to its excellent CD44 receptor/magnetic dual targeting capability. After intravenous injection of the nanoagent and treatment of external magnetic field, the tumor in nude mice was efficiently ablated upon NIR laser irradiation and the tumor growth inhibition was more than 89.95%. Such nanotheranostic agent is of crucial importance for accurately identifying the size and location of the tumor before therapy, monitoring the photothermal treatment procedure in real-time during therapy, assessing the effectiveness after therapy. PMID:28255343

  13. Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid.

    Science.gov (United States)

    Heo, Wan; Kim, Jun Ho; Pan, Jeong Hoon; Kim, Young Jun

    2016-02-17

    In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA.

  14. Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidities, photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and their conjugate bases.

    Science.gov (United States)

    Tian, Zhixin; Wang, Xue-Bin; Wang, Lai-Sheng; Kass, Steven R

    2009-01-28

    Deprotonation of tyrosine in the gas phase was found to occur preferentially at the phenolic site, and the conjugate base consists of a 70:30 mixture of phenoxide and carboxylate anions at equilibrium. This result was established by developing a chemical probe for differentiating these two isomers, and the presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5 kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55 +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D exchange behavior of deprotonated tyrosine was examined using three different alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three deuterium atoms was observed. Two pathways are proposed to account for these results, and all of the experimental findings are supplemented with B3LYP/aug-cc-pVDZ and G3B3 calculations. In addition, it was found that electrospray ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial source produces a deprotonated [M-H]- anion with the gas-phase equilibrium composition rather than the structure of the ion that exists in aqueous media. Electrospray ionization from acetonitrile, however, leads largely to the liquid-phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was found to behave in a similar manner. Thus, the electrospray conditions that are employed for the analysis of a compound can alter the isomeric composition of the resulting anion.

  15. Effect of pH on conjugated linoleic acid (CLA) formation of linolenic acid biohydrogenation by ruminal microorganisms.

    Science.gov (United States)

    Lee, Yongjae

    2013-08-01

    Conventional beliefs surrounding the linolenic acid (LNA; cis-9 cis-12 cis-15 C18:3) biohydrogenation (BH) pathway propose that it converts to stearic acid (SA) without the formation of conjugated linoleic acid (CLA) as intermediate isomers. However, an advanced study (Lee and Jenkins, 2011) verified that LNA BH yields multiple CLAs. This study utilized the stable isotope tracer to investigate the BH intermediates of (13)C-LNA with different pH conditions (5.5 and 6.5). The (13)C enrichment was calculated as a (13)C/(12)C ratio of labeled minus unlabeled. After 24 h, eight CLA isomers were significantly enriched on both pH treatment, this result verifies that these CLAs originated from (13)C-LNA BH which supports the results of Lee and Jenkins (2011). The enrichment of cis-cis double bond CLAs (cis-9 cis-11 and cis-10 cis-12 CLA) were significantly higher at low pH conditions. Furthermore, the concentration of cis-10 cis-12 CLA at low pH was four times higher than at high pH conditions after a 3 h incubation. These differences support the LNA BH pathways partial switch under different pH conditions, with a strong influence on the cis-cis CLA at low pH. Several mono-, di-, and tri-enoic fatty acid isomers were enriched during 24 h of incubation, but the enrichment was decreased or restricted at low pH treatment. Based on these results, it is proposed that low pH conditions may cause a changed or limited capacity of the isomerization and reduction steps in BH.

  16. Intake of conjugated linoleic acid, fat and other fatty acids in relation to postmenopausal breast cancer : the Netherlands cohort study on diet and cancer

    NARCIS (Netherlands)

    Voorrips, L.E.; Brants, H.A.M.; Kardinaal, A.F.M.; Hiddink, G.J.; Brandt, P.A. van den

    2002-01-01

    Background: Conjugated linoleic acid (CLA), which is present in milk products and meat from ruminants, appears to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. To date, few epidemiologic data are available in humans. Objective: This study evaluated the rela

  17. 99mTc-DTPA-amino acids conjugate as specific SPECT pharmaceuticals for tumor imaging.

    Science.gov (United States)

    Sinha, Deepa; Shukla, Gauri; Tiwari, Anjani K; Chaturvedi, Shubhra; Chuttani, Krishna; Chandra, Harish; Mishra, Anil K

    2009-08-01

    (99m)Tc-Diethylene triamine pentaacetic acid-bis (amide) conjugates have been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compounds were synthesized by the condensation reaction of DTPA bis(anhydride) with different l-amino acids (methyl tryptophan, and 5-hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. (99m)Tc-labeled compounds were found stable for about 24 h under physiological conditions with more than 95% radiolabeling yield. Blood kinetic studies of all these complexes showed a bi-exponential pattern as well as quick wash out from the blood circulation. The biological t(1/2)(F) and t(1/2)(S) were found to be 20 +/- 0.001 min for DTPA-(Me-Trp)(2) and 18 +/- 0.001 min for DTPA-(5HT)(2) and t(1/2) (slow) 5 h 45 min +/- 0.001, 5 h 30 +/- 0.001 min for DTPA-(Me-Trp)(2), and DTPA-(5HT)(2), respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in right thigh. Radioconjugate derived from l-5-hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived from l-methyl tryptophan shows relatively less accumulation at the tumor site. Tumor-to-muscles ratios were 5.07 +/- 0.001, and 4.2 +/- 0.001 at 1 and 4 h for (99m)Tc-DTPA-(Me trp)(2) and 4.97 +/- 0.001 and 5.8 +/- 0.001 at 1 and 4 h after postinjection for (99m)Tc-DTPA-(5HT)(2), respectively. The preliminary results with these amino acid based ligands are encouraging to carrying out further in vivo experiments for targeted tumor imaging.

  18. Effects of different vegetable oils on rumen fermentation and conjugated linoleic acid concentration in vitro

    Science.gov (United States)

    Roy, Amitava; Mandal, Guru Prasad; Patra, Amlan Kumar

    2017-01-01

    Aim: The objective of this study was to investigate the effect of different vegetable oils on rumen fermentation and concentrations of beneficial cis-9 trans-11 C18:2 conjugated linoleic acid (CLA) and trans-11 C18:1 fatty acid (FA) in the rumen fluid in an in vitro condition. Materials and Methods: Six vegetable oils including sunflower, soybean, sesame, rice bran, groundnut, and mustard oils were used at three dose levels (0%, 3% and 4% of substrate dry matter [DM] basis) in three replicates for each treatment in a completely randomized design using 6 × 3 factorial arrangement. Rumen fluid for microbial culture was collected from four goats fed on a diet of concentrate mixture and berseem hay at a ratio of 60:40 on DM basis. The in vitro fermentation was performed in 100 ml conical flakes containing 50 ml of culture media and 0.5 g of substrates containing 0%, 3% and 4% vegetable oils. Results: Oils supplementation did not affect (p>0.05) in vitro DM digestibility, and concentrations of total volatile FAs and ammonia-N. Sunflower oil and soybean oil decreased (p0.05) on protozoal numbers. Both trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations were increased (p0.05) increase the trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations as compared to the control. The concentrations of stearic, oleic, linoleic, and linolenic acids were not altered (p>0.05) due to the addition of any vegetable oils. Conclusion: Supplementation of sunflower and soybean oils enhanced beneficial trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations in rumen fluid, while sesame, rice bran, groundnut, and mustard oils were ineffective in this study. PMID:28246442

  19. Effects of different vegetable oils on rumen fermentation and conjugated linoleic acid concentration in vitro

    Directory of Open Access Journals (Sweden)

    Amitava Roy

    2017-01-01

    Full Text Available Aim: The objective of this study was to investigate the effect of different vegetable oils on rumen fermentation and concentrations of beneficial cis-9 trans-11 C18:2 conjugated linoleic acid (CLA and trans-11 C18:1 fatty acid (FA in the rumen fluid in an in vitro condition. Materials and Methods: Six vegetable oils including sunflower, soybean, sesame, rice bran, groundnut, and mustard oils were used at three dose levels (0%, 3% and 4% of substrate dry matter [DM] basis in three replicates for each treatment in a completely randomized design using 6 × 3 factorial arrangement. Rumen fluid for microbial culture was collected from four goats fed on a diet of concentrate mixture and berseem hay at a ratio of 60:40 on DM basis. The in vitro fermentation was performed in 100 ml conical flakes containing 50 ml of culture media and 0.5 g of substrates containing 0%, 3% and 4% vegetable oils. Results: Oils supplementation did not affect (p>0.05 in vitro DM digestibility, and concentrations of total volatile FAs and ammonia-N. Sunflower oil and soybean oil decreased (p0.05 on protozoal numbers. Both trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations were increased (p0.05 increase the trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations as compared to the control. The concentrations of stearic, oleic, linoleic, and linolenic acids were not altered (p>0.05 due to the addition of any vegetable oils. Conclusion: Supplementation of sunflower and soybean oils enhanced beneficial trans-11 C18:1 FA and cis-9, trans-11 CLA concentrations in rumen fluid, while sesame, rice bran, groundnut, and mustard oils were ineffective in this study.

  20. Isomer-specific effects of conjugated linoleic acid on HDL functionality associated with reverse cholesterol transport.

    Science.gov (United States)

    Nicod, Nathalie; Parker, Robert S; Giordano, Elena; Maestro, Virginia; Davalos, Alberto; Visioli, Francesco

    2015-02-01

    High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-β-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-β-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-β-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.

  1. Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain

    Science.gov (United States)

    Nikan, Mehran; Osborn, Maire F; Coles, Andrew H; Godinho, Bruno MDC; Hall, Lauren M; Haraszti, Reka A; Hassler, Matthew R; Echeverria, Dimas; Aronin, Neil; Khvorova, Anastasia

    2016-01-01

    The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6–60 μg). Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression in both the ipsilateral striatum (up to 73%) and cortex (up to 51%) after 1 week. Moreover, following a bilateral intrastriatal injection (60 μg), we achieve up to 80% silencing of a secondary target, Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose. Thus, DHA conjugation is a novel strategy for improving siRNA activity in mouse brain, with potential to act as a new therapeutic platform for the treatment of neurodegenerative disorders. PMID:27504598

  2. Fabrication and Protein Conjugation of Aligned Polypyrrole-Poly(L-lactic acid) Fibers Film with the Conductivity and Stability.

    Science.gov (United States)

    Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Yang, Anneng; Han, Wei

    2016-03-01

    The conducting composite scaffold, including fiber-cores of aligned poly(L-lactic acid) (PLLA) and shell-layer of polypyrrole (PPy), was fabricated, and then bovine serum albumin (BSA) was conjugated on the PPy shell-layer. Aligned PLLA fibers (about 300 nm diameter) were obtained by electrospinning and rotating drum collection, and then coated by PPy nanoparticles (NPs, about 50 nm diameter) via chemical oxidation. The surface resistivity of PPy-PLLA fibers film were 0.971, 0.874 kΩ. cm at the fiber's vertical and parallel directions, respectively. The results of PPy-PLLA fibers film immersed in phosphate buffer saline for 8 d indicated that the fibers morphology and the film conductivity were not significantly changed, and the fluorescent images showed that FITC-labeled BSA (FITC-BSA) were successfully conjugated in the fibers film with carbodiimide chemistry, and the largest amount of FITC-BSA conjugated in the fibers film from 100 μg/mL proteins solution was 31.31 μg/cm2 due to lots of poly(glutamic acid) in surface-nanogrooves of the fibers surface. Under electrical stimulation of 100 mV, the fibers film was accompanied the release of all conjugated FITC-BSA with the detachment of some PPy NPs. These results suggested that PPy-PLLA fibers film would be potentially applied in the construction of degradable tissue engineering scaffold with protein factors, especially neurotrophic factors for nerve tissue repair.

  3. Dietary Supplementation with Conjugated Linoleic Acid Plus n-3 Polyunsaturated Fatty Acid Increases Food IntakeBrown Adipose Tissue in Rats

    OpenAIRE

    Morris, Amanda C.; Williams, Lynda M.; Wahle, Klaus W.; Jung-Heun Ha; Shabina Bashir; Mitchell, Sharon E.; Alan A. Sneddon; D. Vernon Rayner

    2009-01-01

    The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3) was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose tissue and uncoupling protein-1 expression were increased. Plasma adiponectin, triglyceride and cholesterol levels were reduced while leptin, ghrelin and liver weight and lipid content were unchanged. Hypothalamic gene expression ...

  4. System Development from Organic Solvents to Ionic Liquids for Synthesiz-ing Ascorbyl Esters with Conjugated Linoleic Acids

    DEFF Research Database (Denmark)

    Yang, Zhiyong; Schultz, Lise; Guo, Zheng;

    2012-01-01

    The aim of this paper is to screen suitable reaction systems for the modification of antioxidants through enzy-matic synthesis. Enzymatic esterification of ascorbic acid with conjugated linoleic acid (CLA) was investigated as a mod-el. Four organic solvents and five different enzymes were evaluated....... Results show that only Novozym® 435 turned out to be a useful enzymatic preparation for the production of ascorbyl-CLA ester. The optimum reaction conditions in the or-ganic solvent system were 4 h at 55°C and at a molar ratio of 5 (CLA/ascorbic acid). The esterification reaction was trans...

  5. Self-assembled ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates for targeted gene delivery.

    Science.gov (United States)

    Liang, Kun; Bae, Ki Hyun; Lee, Fan; Xu, Keming; Chung, Joo Eun; Gao, Shu Jun; Kurisawa, Motoichi

    2016-03-28

    Nanosized polyelectrolyte complexes are attractive delivery vehicles for the transfer of therapeutic genes to diseased cells. Here we report the application of self-assembled ternary complexes constructed with plasmid DNA, branched polyethylenimine and hyaluronic acid-green tea catechin conjugates for targeted gene delivery. These conjugates not only stabilize plasmid DNA/polyethylenimine complexes via the strong DNA-binding affinity of green tea catechin, but also facilitate their transport into CD44-overexpressing cells via receptor-mediated endocytosis. The hydrodynamic size, surface charge and physical stability of the complexes are characterized. We demonstrate that the stabilized ternary complexes display enhanced resistance to nuclease attack and polyanion-induced dissociation. Moreover, the ternary complexes can efficiently transfect the difficult-to-transfect HCT-116 colon cancer cell line even in serum-supplemented media due to their enhanced stability and CD44-targeting ability. Confocal microscopic analysis demonstrates that the stabilized ternary complexes are able to promote the nuclear transport of plasmid DNA more effectively than binary complexes and hyaluronic acid-coated ternary complexes. The present study suggests that the ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates can be widely utilized for CD44-targeted delivery of nucleic acid-based therapeutics.

  6. Conjugated linoleic acid protects against gliadin-induced depletion of intestinal defenses.

    Science.gov (United States)

    Bergamo, Paolo; Gogliettino, Marta; Palmieri, Gianna; Cocca, Ennio; Maurano, Francesco; Stefanile, Rosita; Balestrieri, Marco; Mazzarella, Giuseppe; David, Chella; Rossi, Mauro

    2011-09-01

    The involvement of oxidative stress in gluten-induced toxicity has been evidenced in vitro and in clinical studies but has never been examined in vivo. We recently demonstrated the protective activity of conjugated linoleic acid (CLA), which functions by the activation of nuclear factor erythroid 2-related factor2 (Nrf2), a key transcription factor for the synthesis of antioxidant and detoxifying enzymes (phase 2). Here, we evaluate the involvement of nuclear factor erythroid 2-related factor2 in gliadin-mediated toxicity in human Caco-2 intestinal cells and in gliadin-sensitive human leukocyte antigen-DQ8 transgenic mice (DQ8) and the protective activity of CLA. Gliadin effects in differentiated Caco-2 cells and in DQ8 mice, fed with a gliadin-containing diet with or without CLA supplementation, were evaluated by combining enzymatic, immunochemical, immunohistochemical, and quantitative real-time PCR (qRT-PCR) assays. Gliadin toxicity was accompanied by downregulation of phase 2 and elevates proteasome-acylpeptide hydrolase activities in vitro and in vivo. Notably, gliadin was unable to generate severe oxidative stress extent or pathological consequences in DQ8 mice intestine comparable to those found in celiac patients and the alterations produced were hampered by CLA. The beneficial effects of CLA against the depletion of crucial intestinal cytoprotective defenses indicates a novel nutritional approach for the treatment of intestinal disease associated with altered redox homeostasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Enrichment of milk with conjugated linoleic acid by supplementing diets with fish and sunflower oil.

    Science.gov (United States)

    Abo El-Nor, S A H; Khattab, Mostafa S A

    2012-07-15

    There is an increase interesting in enrichment of milk with Conjugated Linoleic Acid (CLA) due to its anti-oxidative and anti-carcinogenic properties. The objective of this study was to investigate the effect of supplementing diets fed to lactating goats with sunflower, fish oil and its blend. Eight lactating Nubian goats were fed a base diet (T1), diet supplemented with 2% sunflower oil (on dry matter (DM) basis) (T2), diet supplemented with 2% fish oil (T3) and diet supplemented with 2% sunflower and fish oil (T4) for 84 day. Milk composition milk fat, protein (%) decreased in T2, T3 and T4 compared with control (T1) while there was no significant differences between treatments in milk lactose content. CLA content in milk fat was higher in response to fish oil or sunflower and fish oil blend compared with control (T1). The results indicated that supplementing diets fed to lactating goats with sunflower, fish oil increased CLA contents in the milk 2-4 times than control.

  8. Conjugated Linoleic Acid: Potential Health Benefits as a Functional Food Ingredient.

    Science.gov (United States)

    Kim, Jun Ho; Kim, Yoo; Kim, Young Jun; Park, Yeonhwa

    2016-01-01

    Conjugated linoleic acid (CLA) has drawn significant attention since the 1980s for its various biological activities. CLA consists mainly of two isomers, cis-9,trans-11 and trans-10,cis-12, and the mixture of these two (CLA mix or 50:50) has been approved for food as GRAS (generally recognized as safe) in the United States since 2008. Along with its original discovery as an anticancer component, CLA has been shown to prevent the development of atherosclerosis, reduce body fat while improving lean body mass, and modulate immune and/or inflammatory responses. This review summarizes the clinical trials involving CLA since 2012; additional uses of CLA for age-associated health issues are discussed; and CLA's potential health concerns, including glucose homeostasis, oxidative stress, hepatic steatosis, and milk-fat depression, are examined. With ongoing applications to food products, CLA consumption is expected to rise and close monitoring of not only its efficacy but also its known and unknown consequences are required to ensure proper applications of CLA.

  9. Preparation and characterization of aqueous dispersions of high amylose starch and conjugated linoleic acid complex.

    Science.gov (United States)

    Seo, Tae-Rang; Kim, Hee-Young; Lim, Seung-Taik

    2016-11-15

    Crystalline starch-CLA complexes were prepared by blending an alcoholic solution of conjugated linoleic acid (CLA) in an aqueous high-amylose maize starch dispersion. Recovery yield of CLA in the precipitates obtained by centrifuging the dispersion was dependent on reaction conditions such as temperature, time and pH. The CLA recovery reached a maximum when the reaction was performed at 90°C for 6h at neutral pH, with 67.7% of the initial CLA being co-precipitated with starch. The precipitates contained amylose-CLA complex exhibiting a V6I-type crystalline structure under X-ray diffraction analysis and a type II polymorph under DSC analysis. Ultrasonic treatment for the re-dispersed starch-CLA complex in water resulted in the reduction of hydrodynamic diameter of the complex particles to 201.5nm. The dispersion exhibited a zeta potential of -27.0mV and remained stable in an ambient storage without forming precipitates for more than 4weeks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Formation of redispersible polyelectrolyte complex nanoparticles from gallic acid-chitosan conjugate and gum arabic.

    Science.gov (United States)

    Hu, Qiaobin; Wang, Taoran; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

    2016-11-01

    Polyelectrolyte complex (PEC) nanoparticles between chitosan (CS) and biomacromolecules offer better physicochemical properties as delivery vehicles for nutrients than other CS-based nanoparticles. Our major objective was to fabricate PEC nanoparticles between water soluble gallic acid-chitosan conjugate (GA-CS) and gum arabic. The optimal fabrication method, physicochemical characteristics and stability were investigated. Furthermore, we also evaluated the effects of nano spray drying technology on the morphology and redispersibility of nanoparticle powders using Buchi B-90 Nano Spray Dryer. Results showed that the mass ratio between GA-CS and gum arabic and the preparation pH had significant contributions in determining the particle size and count rate of the nanoparticles, with the ratio of 3:1 and pH 5.0 being the optimal conditions that resulted in 112.2nm and 122.9kcps. The polyethylene glycol (PEG) played a vital role in forming the well-separated spray dried nanoparticles. The most homogeneous nanoparticles with the smoothest surface were obtained when the mass ratio of GA-CS and PEG was 1:0.5. In addition, the GA-CS/gum arabic spray dried nanoparticles exhibited excellent water-redispersibiliy compared to native CS/gum arabic nanoparticles. Our results demonstrated GA-CS/gum arabic nanoparticles were successfully fabricated with promising physicochemical properties and great potential for their applications in food and pharmaceutical industries. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Mathematical Modelling to Predict Oxidative Behaviour of Conjugated Linoleic Acid in the Food Processing Industry

    Directory of Open Access Journals (Sweden)

    Aitziber Ojanguren

    2013-06-01

    Full Text Available Industrial processes that apply high temperatures in the presence of oxygen may compromise the stability of conjugated linoleic acid (CLA bioactive isomers. Statistical techniques are used in this study to model and predict, on a laboratory scale, the oxidative behaviour of oil with high CLA content, controlling the limiting factors of food processing. This modelling aims to estimate the impact of an industrial frying process (140 °C, 7 L/h air on the oxidation of CLA oil for use as frying oil instead of sunflower oil. A factorial design was constructed within a temperature (80–200 °C and air flow (7–20 L/h range. Oil stability index (Rancimat method was used as a measure of oxidation. Three-level full factorial design was used to obtain a quadratic model for CLA oil, enabling the oxidative behaviour to be predicted under predetermined process conditions (temperature and air flow. It is deduced that temperatures applied in food processes affect the oxidation of CLA to a greater extent than air flow. As a result, it is estimated that the oxidative stability of CLA oil is less resistant to industrial frying than sunflower oil. In conclusion, thanks to the mathematical model, a good choice of the appropriate industrial food process can be selected to avoid the oxidation of the bioactive isomers of CLA, ensuring its functionality in novel applications.

  12. The effect of conjugated linoleic acid supplementation on the nutritional status of COPD patients.

    Science.gov (United States)

    Ghobadi, Hassan; Matin, Somaieh; Nemati, Ali; Naghizadeh-Baghi, Abbas

    2016-01-01

    COPD patients are susceptible to anorexia, reduction of caloric intake, weight loss, and malnutrition. One of the possible mechanisms is the increase of inflammatory markers such as interleukin 1β (IL1β), is highly correlated with anorexia. Considering the anti-inflammatory role of conjugated linoleic acid (CLA), this study aimed to investigate the effect of CLA supplementation on the nutritional status of COPD patients. In a double-blind clinical trial, 93 COPD patients who volunteered to participate in the study and who filled out a written consent form, were randomly assigned to control or supplementation groups. The patients in the supplementation group received 3.2 g of CLA on a daily basis for 6 weeks, while those in the control group received placebo on a daily basis for 6 weeks. For IL1β assessment, the patients' anthropometric indices and appetite score were checked and their blood samples were collected both before and after the treatment. Moreover, in order to investigate the changes in the caloric intake trend during the study, their dietary intake levels were assessed using 24-hour dietary recall, 3 days a week at the onset, in the 4th week, and at the end of the study. Eventually, 90 patients completed the study. The results demonstrated a significant increase in appetite score (P=0.001), average caloric intake (P=0.01), and macronutrient intake (Pnutritional status of patients suffering from COPD through adjusting the serum level of IL1β.

  13. The effects of conjugated linoleic acids on breast cancer: A systematic review

    Directory of Open Access Journals (Sweden)

    Arman Arab

    2016-01-01

    Full Text Available Recently prevention strategies for breast cancer are focused on lifestyle modification such as diet. Some dietary factors such as Conjugated linoleic acid (CLA can lower the risk of breast cancer, metastasis and some factors concerning this malignancy. Many studies have been established in this field, but their results are inconsistent. Therefore, we evaluated this association based on systematic review among published scientific literature. We performed an electronic search using PubMed, Cochrane, Scopus, Google Scholar and Persian database (Iran Medex, magiran to identify relevant studies. We summarized the findings of 8 papers in this review. Although, three cohort studies were not overall identified a protective effect of CLA dietary intake or CLA content in breast tissue on breast cancer incidence, metastasis and death, one of them showed an inverse association after adjusting for age. Also, among case-control studies a weak inverse association between breast cancer risk and CLA dietary intake and serum levels among post-menopausal women was reported. Besides, a clinical trial showed that some indicator of breast tumor decreased after CLA administration among women with breast adenocarcinoma. Lacking published evidence suggested inconsistent results. So, further well-designed studies are required, particularly in considering the main breast cancer risk factors.

  14. Soy lipophilic protein nanoparticles as a novel delivery vehicle for conjugated linoleic acid.

    Science.gov (United States)

    Gao, Zhi-Ming; Zhu, Le-Ping; Yang, Xiao-Quan; He, Xiu-Ting; Wang, Jin-Mei; Guo, Jian; Qi, Jun-Ru; Wang, Li-Juan; Yin, Shou-Wei

    2014-06-01

    Soy lipophilic protein nanoparticles (LPP), which present a novel delivery vehicle for conjugated linoleic acid (CLA), were fabricated by ultrasonication of the soy lipophilic protein (LP), which exhibits unique characteristics including a high loading capacity, oxidation protection and a sustained releasing profile in vitro for CLA. The CLA-loaded LPP exhibited a mean diameter of 170 ± 0.63 nm and a loading capacity of 26.3 ± 0.40% (w/w). A coating of sodium caseinate (SC) on the surface improved the colloidal stability of the CLA-loaded LPP. This encapsulation conferred protection against the oxidation of CLA, by which the head space-oxygen consumption and hydrogen peroxide value were obviously decreased in comparison with the SC-encapsulated CLA and CLA alone. The delivery system enables a sustained releasing profile of CLA in a simulated gastrointestinal tract (GIT). These findings illustrate that the LPP could act as an effective delivery device for CLA, which could provide oxidation stability and a sustained release property.

  15. Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

    Science.gov (United States)

    Hayward, Stephen L.; Wilson, Christina L.; Kidambi, Srivatsan

    2016-01-01

    Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study the uptake pathway in key cells in the brain including primary astrocytes, microglia, and human GBM cells. We observed that the HALNPs specifically target GBM cells over other brain cells due to higher expression of CD44 in tumor cells. Furthermore, CD44 driven HALNP uptake into GBM cells resulted in lysosomal evasion and increased efficacy of Doxorubicin, a model anti-neoplastic agent, while the astrocytes and microglia cells exhibited extensive HALNP-lysosome co-localization and decreased antineoplastic potency. In summary, novel CD44 targeted lipid based nanocarriers appear to be proficient in mediating site-specific delivery of drugs via CD44 receptors in GBM cells, with an improved therapeutic margin and safety. PMID:27120809

  16. Curcumin-cysteine and curcumin-tryptophan conjugate as fluorescence turn on sensors for picric Acid in aqueous media.

    Science.gov (United States)

    Gogoi, Bedanta; Sen Sarma, Neelotpal

    2015-06-03

    Rapid detection of picric acid in real sample is of outmost importance from the perspective of health, safety, and environment. In this study, a very simple and cost-effective detection of picric acid is accomplished by developing a couple of biobased conjugates curcumin-cysteine (CC) and curcumin-tryptophan (CT), which undergo efficient fluorescence turn on toward picric acid in aqueous media. Both the probes experience about 26.5-fold fluorescence enhancements at 70 nM concentration of the analyte. Here, the fluorescence turn on process is governed by the aggregation induced emission, which is induced from the electrostatic interaction between the conjugates with picric acid. The detection limit of CC and CT are about 13.51 and 13.54 nM of picric acid, respectively. Importantly, both the probes exhibit high selectivity and low interference of other analogues toward the detection of picric acid. In addition, the probes are highly photostable, show low response time and are practically applicable for sensing picric acid in real environmental samples, which is the ultimate goal of this work.

  17. Conjugated linoleic acid of dairy foods is affected by cows’ feeding system and processing of milk

    Directory of Open Access Journals (Sweden)

    Juan Pablo Avilez Ruiz

    2016-04-01

    Full Text Available ABSTRACT The distribution of conjugated linoleic acid (CLA in dairy products commercially available in Chile is poorly understood. This study aimed to assess the content of CLA in dairy cow products from Chile and the effect of processing fresh milk into dairy products. Samples of raw milk were categorized into two groups based on the animal feeding system utilized by the dairy farm: 1 grazing based systems (Los Lagos region; and 2 housing systems using total mixed ration (TMR diets (Los Angeles region. Simultaneously, commercial samples of condensed milk, powdered milk, butter and Gouda cheese were analyzed. Furthermore, samples of raw milk and processed products (powdered and sweetened condensed milk were also analyzed. Dairy farms based on grazing systems had higher levels of CLA in raw milk than TMR farms. In addition, average values of CLA were 1.72 g 100 g−1 of total fatty acids, in spring milk in the Los Lagos region, and 0.42 g 100 g−1 in summer milk, in the Los Angeles region. Similarly, the CLA content of dairy products was higher than that of raw milk. Milk processing affected the transferring of CLA from fresh milk into the final products. Sweetened condensed milk presented lower CLA values than raw and powdered milk. In conclusion, this study indicates the importance of the production systems to the CLA content as well as the effects of milk processing into dairy products. To sum up, more research is needed to elucidate the exact effect of the processing conditions of dairy products on the CLA content.

  18. Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body weight in lactating sows.

    Science.gov (United States)

    Lee, Sung-Hoon; Joo, Young-Kuk; Lee, Jin-Woo; Ha, Young-Joo; Yeo, Joon-Mo; Kim, Wan-Young

    2014-01-01

    This study was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) on the performance of lactating sows and piglets as well as the immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows with an average body weight (BW) of 232.0 ± 6.38 kg were randomly selected and assigned to two dietary treatments (n = 9 for each treatment), control (no CLA addition) and 1% CLA supplementation. For the control diet, CLA was replaced with soybean oil. Experimental diets were fed to sows during a 28-day lactation period. Litter size for each sow was standardized to nine piglets by cross-fostering within 24 hours after birth. Sow milk and blood samples were taken from sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was significantly (p sows fed control diet compared to sows fed CLA diet. Piglet weights at weaning and weight gain during suckling were significantly (p sows fed CLA compared to sows fed control diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly (p sows fed CLA than in sows fed soybean oil. IgG concentrations of the groups supplemented with CLA increased by 49% in sow serum (p Sows fed CLA showed an increase of 10% in milk yield compared with sows fed soybean oil (p sows fed CLA than in sows fed soybean oil. Solid-not-fat yield was significantly (p sows supplemented with CLA than in sows fed control diet and also protein-to-fat ratio in milk was significantly (p sows fed CLA compared with the control group. The results show that CLA supplementation to sows increased milk yield without losing BW during lactation, whereas soybean oil supplementation resulted in severe BW loss.

  19. An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

    Directory of Open Access Journals (Sweden)

    Albert W. M. Lee

    2011-01-01

    Full Text Available Two mesitylene based neutral receptors 1 and 2 bearing two thiourea binding sites were constructed as fluorescent probes for sensing dicarboxylates. Their binding affinities toward dicarboxylates, aspartate and glutamate have been investigated in acetonitrile solution by fluorescence titration experiments. Both fluorescent sensors exhibited some ability to discriminate the antipodal forms of aspartate and glutamate.

  20. Milk phospholipids: Organic milk and milk rich in conjugated linoleic acid compared with conventional milk.

    Science.gov (United States)

    Ferreiro, T; Gayoso, L; Rodríguez-Otero, J L

    2015-01-01

    The objective of this study was to compare the phospholipid content of conventional milk with that of organic milk and milk rich in conjugated linoleic acid (CLA). The membrane enclosing the fat globules of milk is composed, in part, of phospholipids, which have properties of interest for the development of so-called functional foods and technologically novel ingredients. They include phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), and the sphingophospholipid sphingomyelin (SM). Milk from organically managed cows contains higher levels of vitamins, antioxidants, and unsaturated fatty acids than conventionally produced milk, but we know of no study with analogous comparisons of major phospholipid contents. In addition, the use of polyunsaturated-lipid-rich feed supplement (extruded linseed) has been reported to increase the phospholipid content of milk. Because supplementation with linseed and increased unsaturated fatty acid content are the main dietary modifications used for production of CLA-rich milk, we investigated whether these modifications would lead to this milk having higher phospholipid content. We used HPLC with evaporative light scattering detection to determine PE, PI, PC, PS, and SM contents in 16 samples of organic milk and 8 samples of CLA-rich milk, in each case together with matching reference samples of conventionally produced milk taken on the same days and in the same geographical areas as the organic and CLA-rich samples. Compared with conventional milk and milk fat, organic milk and milk fat had significantly higher levels of all the phospholipids studied. This is attributable to the differences between the 2 systems of milk production, among which the most influential are probably differences in diet and physical exercise. The CLA-rich milk fat had significantly higher levels of PI, PS, and PC than conventional milk fat, which is also attributed to dietary differences: rations for

  1. Rh(I)-Catalyzed Coupling of Conjugated Enynones with Arylboronic Acids: Synthesis of Furyl-Containing Triarylmethanes.

    Science.gov (United States)

    Xia, Ying; Chen, Li; Qu, Peiyuan; Ji, Guojing; Feng, Sheng; Xiao, Qing; Zhang, Yan; Wang, Jianbo

    2016-11-04

    Conjugated enynones can be used as carbene precursors to couple with arylboronic acids in the presence of Rh(I) catalyst. This reaction shows good functional compatibility, and a range of furyl-containing triarylmethanes can be smoothly synthesized from easily available starting materials under mild reaction conditions. Mechanistically, the formation of Rh(I) (2-furyl)carbene species and the subsequent carbene migratory insertion are proposed as the key steps in this reaction.

  2. Synthesis, and Investigation of the Reactive Oxygen Species of a Novel Cyclicpeptide-2,6-dimethoxyhydroquinone-3- mercaptoacetic Acid Conjugate

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, we report the synthesis of a potential anti-cancer agent: Cyclo[Val Lys(DMQ-MA)-Gaba]. The cytotoxic agent conjugated to the N-terminal and the ξ-amino group of lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). By employing the rhodamine B degradation method and ESR spectra, we testify the reactive oxygen species---hydroxyl radicals produced by the drug.

  3. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40

    DEFF Research Database (Denmark)

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole

    2011-01-01

    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravatio...... in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes....

  4. Self-quenched covalent fluorescent dye-nucleic acid conjugates as polymeric substrates for enzymatic nuclease assays.

    Science.gov (United States)

    Trubetskoy, Vladimir S; Hagstrom, James E; Budker, Vladimir G

    2002-01-01

    A fluorescent method is described for assessing nuclease activity. The technique is based on the preparation of quenched fluorophore-nucleic acid covalent conjugates and their subsequent dequenching due to degradation by nucleases. The resulting fluorescence increase can be measured by a spectrofluorometer and exhibits subpicogram per milliliter sensitivity level for RNase A and low picogram per milliliter level for DNase I. The method is adaptable for quantitative nuclease inhibitor testing.

  5. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria.

    Science.gov (United States)

    Sanabria-Ríos, David J; Rivera-Torres, Yaritza; Rosario, Joshua; Gutierrez, Ricardo; Torres-García, Yeireliz; Montano, Nashbly; Ortíz-Soto, Gabriela; Ríos-Olivares, Eddy; Rodríguez, José W; Carballeira, Néstor M

    2015-11-15

    The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 μg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 μg/mL (IC50=100.2±13.9 μg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains.

  6. Surface functionalization of titanium substrates with chitosan-lauric acid conjugate to enhance osteoblasts functions and inhibit bacteria adhesion.

    Science.gov (United States)

    Zhao, Lu; Hu, Yan; Xu, Dawei; Cai, Kaiyong

    2014-07-01

    Orthopedic implants failures are generally related to poor osseointegration and/or bacterial infection in clinical application. Surface functionalization of an implant is one promising alternative for enhancing osseointegration and/or reducing bacterial infection, thus ensuring the long term survival of the implant. In this study, titanium (Ti) substrates were surface functionalized with a polydopamine (PDOP) film as an intermediate layer for post-immobilization of chitosan-lauric acid (Chi-LA) conjugate. Chi-LA conjugate was synthesized and characterized by Fourier transform infrared spectroscopy (FTIR) and hydrogen proton nuclear magnetic resonance (NMR) spectrometer, respectively. Lauric acid (LA), a natural saturated fatty acid, was used mainly due to its good antibacterial property. Scanning electron microscopy (SEM) and water contact angle measurements were employed to detect the morphology changes and surface wettability of Ti substrates. The results suggested that Chi-LA conjugate was successfully immobilized onto the surfaces of Ti substrates. In vitro tests confirmed that the cell adhesion, cell viability, intracellular alkaline phosphatase activity and mineralization capacity of osteoblasts were remarkably improved when cultured onto Chi-LA surface functionalized Ti substrates. Antibacterial assay against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) showed that the Chi-LA modified Ti substrates efficiently inhibited the adhesion and growth of bacteria. Overall, this study developed a promising approach to fabricate functional Ti-based orthopedic implants, which could enhance the biological functions of osteoblasts and concurrently reduce bacteria adhesion.

  7. Physicochemical characterization of amphiphilic nanoparticles based on the novel starch-deoxycholic acid conjugates and self-aggregates.

    Science.gov (United States)

    Yang, Jinlong; Gao, Chunmei; Lü, Shaoyu; Zhang, Xinjie; Yu, Chuanming; Liu, Mingzhu

    2014-02-15

    Novel amphiphilic polymers (starch-deoxycholic acid, St-DCA) were firstly synthesized on the basis of starch (St) as a hydrophilic segment and deoxycholic acid (DCA) as a hydrophobic segment. Hydrophobically modified starch contained 5.4-8.9 deoxycholic acid groups per 100 anhydroglucose units of starch. Self-aggregates of St-DCA conjugates were formed in the PBS media. Physicochemical characterizations of St-DCA conjugates were investigated. The mean sizes of self-aggregates decreased with the degree of substitution (DS) and pH increasing. Zeta potential indicated that nanoparticles were covered with negatively charged starch shells from -5.4 to -23 mV. TEM images demonstrated that nanoparticles were of spherical shape. The critical aggregation concentrations (cac) were dependent on the DS and pH in the range of 0.0185-0.0441 mg/mL. Thus, the study suggested that self-aggregated nanoparticles of St-DCA conjugates could have good pH-responsive and potential application in pharmaceutical and biomedical fields as the delivery of anti-tumor drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Carcass traits and meat quality of pigs fed on fodder supplemented with sunflower oil or conjugated linoleic acid

    Directory of Open Access Journals (Sweden)

    Pavel NEVRKLA

    2016-09-01

    Full Text Available The aim of the study was to compare meat and fat content and meat quality of pigs fed diet supplemented with sunflower oil (SFO or conjugated linoleic acid (CLA and animals not receiving the supplement SFO or CLA (control group. The experiment consisted of 116 pigs, divided into three groups: two experimental (n = 40 where animals were fed feed supplemented with 2% sunflower oil (SFO or conjugated linoleic acid (CLA and control (n = 36. Fattening pigs were kept and fed in standardized conditions. The animals were slaughtered at a body weight of 120 kg. Meat quality traits (pH, drip loss, backfat fat content, colour, MLLT muscle dry matter content, fat in the dry matter, IMF in MLLT were determined. Summarizing obtained results it should be concluded that 2% sunflower oil or conjugated linoleic acid did not affect the meat quality. The experimental animals were characterized by high meat content (58.26% - SFO addition; 57.63% - CLA addition; 57.99% C group and low fat content (from 14.35 mm in SFO group up to 14.70 mm in CLA group.

  9. Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

    Science.gov (United States)

    Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

    2017-02-01

    Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

    Science.gov (United States)

    Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

    2016-01-01

    Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

  11. Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria

    Directory of Open Access Journals (Sweden)

    Ji-Hoon Kim

    2017-06-01

    Full Text Available The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin. In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control. Chitosan-caffeic acid conjugate (CCA showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL. Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris.

  12. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation

    Science.gov (United States)

    Parwe, Sharad P; Chaudhari, Priti N; Mohite, Kavita K; Selukar, Balaji S; Nande, Smita S; Garnaik, Baijayantimala

    2014-01-01

    Ciprofloxacin was conjugated with polylactide (PLA) via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide) (two-, three-, four-, six-arm, star-shaped) homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000) and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm) having pore size (62–102 nm) using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. PMID:24741303

  13. The effect of conjugated linoleic acid supplements on oxidative and antioxidative status of dairy cows.

    Science.gov (United States)

    Hanschke, N; Kankofer, M; Ruda, L; Höltershinken, M; Meyer, U; Frank, J; Dänicke, S; Rehage, J

    2016-10-01

    Dairy cows develop frequently negative energy balance around parturition and in early lactation, resulting in excessive mobilization of body fat and subsequently in increased risk of ketosis and other diseases. Dietary conjugated linoleic acid (CLA) supplements are used in dairy cows mainly for their depressing effect on milk fat content, but are also proposed to have antioxidative properties. As negative energy balance is associated with oxidative stress, which is also assumed to contribute to disease development, the present study was conducted to examine effects of CLA on oxidative and antioxidative status of lactating dairy cows. German Holstein cows (primiparous n=13, multiparous n=32) were divided into 3 dietary treatment groups receiving 100g/d of control fat supplement, containing 87% stearic acid (CON; n=14), 50g/d of control fat supplement and 50g/d of CLA supplement (CLA 50; n=15), or 100g/d of CLA supplement (CLA 100; n=16). The CLA supplement was lipid-encapsulated and contained 12% of trans-10,cis-12 CLA and cis-9,trans-11 CLA each. Supplementation took place between d1 and 182 postpartum; d 182 until 252 postpartum served as a depletion period. Blood was sampled at d -21, 1, 21, 70, 105, 140, 182, 224, and 252 relative to calving. The antioxidative status was determined using the ferric-reducing ability of plasma, α-tocopherol, α-tocopherol-to-cholesterol mass ratio, and retinol. For determination of oxidative status concentrations of hydroperoxides, thiobarbituric acid-reactive substances (TBARS), N'-formylkynurenine, and bityrosine were measured. Mixed models of fixed and random effects with repeated measures were used to evaluate period 1 (d -21 to 140) and 2 (d182-252) separately. Cows showed increased oxidative stress and lipid peroxidation during the periparturient period in terms of increased serum concentrations of hydroperoxides and TBARS, which decreased throughout lactation. During period 1, the supplemented cows had lower TBARS

  14. Conjugating an anticancer drug onto thiolated hyaluronic acid by acid liable hydrazone linkage for its gelation and dual stimuli-response release.

    Science.gov (United States)

    Fu, Chaoping; Li, Hailiang; Li, Nannan; Miao, Xiangwan; Xie, Minqiang; Du, Wenjun; Zhang, Li-Ming

    2015-09-05

    A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by (1)H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.

  15. Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress.

    Science.gov (United States)

    Bergamo, Paolo; Maurano, Francesco; Rossi, Mauro

    2007-07-01

    Conjugated linoleic acid (CLA) exhibits anticancer and anti-inflammatory properties. Its ability to increase total GSH (GSH+GSSG) amount and gamma-glutamylcysteine ligase (gammaGCL) protein expression was recently associated with the inhibition of typical pathological signs in MRL/MpJ-Fas(lpr) mice (MRL/lpr). In the present study the ability of CLA to modulate oxidative stress and phase 2 enzyme activity in the same animal model was investigated. Disease severity was associated with age-dependent production of anti-double-stranded DNA antibodies (anti-dsDNA IgGs) and with enhanced extent of oxidative stress markers: reduced total GSH, increased protein 3-nitrotyrosines (3-NT), and protein-bound carbonyl (PC) amounts. To examine the effect of CLA on antioxidant status, CLA or olive oil (as control) was administered to pregnant MRL/lpr mice. Significantly higher total GSH and Trolox equivalent antioxidant capacity (TEAC) levels were measured in serum of CLA-treated dams (and their pups), as compared with controls. Finally, the antioxidant and chemopreventive properties of CLA were investigated in old MRL/lpr mice. Sera of CLA-treated mice contained higher concentrations of total GSH which were negatively correlated with the levels of oxidative stress markers. Moreover, increased GSH, gammaGCL, glutathione S-transferase (GSTs), and NAD(P)H:quinone oxidoreductase (NQO1) activities were measured in liver and spleen of CLA-treated animals. In conclusion our data indicate that the activation of detoxifying enzymes may be one of the mechanisms whereby dietary CLA down-regulates oxidative stress in MRL/lpr mice.

  16. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.

    Science.gov (United States)

    Steck, Susan E; Chalecki, Allison M; Miller, Paul; Conway, Jason; Austin, Gregory L; Hardin, James W; Albright, Craig D; Thuillier, Philippe

    2007-05-01

    Conjugated linoleic acid (CLA) alters body composition in animal models, but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans. In the present study, we performed a randomized, double-blind, placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise healthy obese humans. Forty-eight participants (13 males and 35 females) were randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA for 12 wk. Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect calorimetry. Clinical laboratory values and adverse-event reporting were used to monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P < 0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol and sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells occurred in the 6.4 g/d CLA group, although all values remained within normal limits. The intervention was well tolerated and no severe adverse events were reported, although mild gastrointestinal adverse events were reported in all treatment groups. In conclusion, whereas CLA may increase lean body mass in obese humans, it may also increase markers of inflammation in the short term.

  17. Effects of dietary conjugated linoleic acids on cellular immune response of piglets after cyclosporin A injection.

    Science.gov (United States)

    Liu, Y X; Zhu, K Y; Liu, Y L; Jiang, D F

    2016-10-01

    The present study investigated the effects of dietary conjugated linoleic acid (CLA) on the cellular immune response of piglets after cyclosporin A (CsA) treatment. The experimental study had a 2×2 factorial design, and the main factors consisted of diets (0% or 2% CLA) and immunosuppression treatments (CsA or saline injection). CsA injection significantly increased feed : gain (F : G) of piglets (P<0.05); however, dietary CLA significantly decreased F : G of piglets (P<0.05). Dietary CLA partly ameliorated the deterioration of the feed conversion rate caused by CsA treatment (P<0.01). CsA treatment significantly decreased the percentages of CD4+ and CD8+ T lymphocytes in the thymus (P<0.01). Dietary CLA increased the percentages of CD4+ CD8+ double-positive and CD8+ single-positive T lymphocytes in the thymus (P<0.05), and had the trend to inhibit the decrease of CD4+ T lymphocytes in the thymus after CsA injection (P=0.07). CsA treatment significantly depleted the peripheral blood CD3+, CD4+ and CD8+ T lymphocytes (P<0.01). Dietary CLA significantly increased the number of peripheral blood CD8+ T lymphocytes and interleukin-2 (IL-2) production (P<0.05), and inhibited the decreases of peripheral blood CD3+, CD4+ and CD8+ T lymphocytes counts (P<0.01) as well as IL-2 production (P<0.05) after CsA treatment. Dietary CLA partly rescued the decrease of lymphocyte proliferation after CsA injection (P<0.05). In summary, dietary CLA effectively ameliorated CsA-induced cellular immunosuppression in piglets.

  18. Transport of methylmercury—cysteine conjugate by system L—tpye amino acid transporters and its transportermediated toxicity

    Institute of Scientific and Technical Information of China (English)

    KanaY; KimDK

    2002-01-01

    Methylmercury(MeHg) is widely known for its potent neurotoxicity and the causal substance of Minamata disease.Since the conjugates of MeHg with thiol compounds are easily formed in vivo,the metabolism and transport of glutathione,cysteine and their derivatives are important determinants of tissue distribution and elimination of MeHg.It has been proposed that the amino acid transport system L,which transports large neutral amino acids,is one of the major routes for MeHg mobilization.We have identified two isoforms of system L amino acid transporters:L-type amino acid transkporter-1(LAT1) and LAT2 and found that they transport MeHg as a cysteine-conjugate (MeHg-Cys).We have further found that a classical system L inhibitor BCH[2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid] rescued T24 human bladder carcinoma cells expressing LAT1 form the toxicity of MeHg-Cysl.We concluded that the cytotoxicity of MeHg is mediated by system L transporters.The fact that BCH reduced the toxicity of MeHg-Cys suggests that the high-affinity inhibitors of system L transporters could be a new rationable to avoid MeHg-toxicity.

  19. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid polymer for nanofiber fabrication and antibacterial evaluation

    Directory of Open Access Journals (Sweden)

    Parwe SP

    2014-03-01

    Full Text Available Sharad P Parwe, Priti N Chaudhari, Kavita K Mohite, Balaji S Selukar, Smita S Nande, Baijayantimala Garnaik Polymer Science and Engineering Division, National Chemical Laboratory, Pune, India Abstract: Ciprofloxacin was conjugated with polylactide (PLA via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl piperazin-1-yl-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide (two-, three-, four-, six-arm, star-shaped homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000 and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm having pore size (62–102 nm using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. Keywords: zinc prolinate, ciprofloxacin conjugated polylactides, CP-PLA, electrospinning, nonwoven nanofibers, drug release, antibacterial activity, MDR

  20. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    Science.gov (United States)

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

    2017-01-01

    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

  1. Amino Acid Chirality and Ferrocene Conformation Guided Self-Assembly and Gelation of Ferrocene-Peptide Conjugates.

    Science.gov (United States)

    Adhikari, Bimalendu; Singh, Charanpreet; Shah, Afzal; Lough, Alan J; Kraatz, Heinz-Bernhard

    2015-08-03

    The self-assembly and gelation behavior of a series of mono- and disubstituted ferrocene (Fc)-peptide conjugates as a function of ferrocene conformation and amino acid chirality are described. The results reveal that ferrocene-peptide conjugates self-assemble into organogels by controlling the conformation of the central ferrocene core, through inter- versus intramolecular hydrogen bonding in the attached peptide chain(s). The chirality controlled assembling studies showed that two monosubstituted Fc conjugates FcCO-LFLFLA-OMe and FcCO-LFLFDA-OMe form gels with nanofibrillar network structures, whereas the other two diastereomers FcCO-DFLFLA-OMe and FcCO-LFDFLA-OMe exclusively produced straight nanorods and non-interconnected small fibers, respectively. This suggests the potential tuning of gelation behavior and nanoscale morphology by altering the chirality of constituted amino acids. The current study confirms the profound effect of diastereomerism and no influence of enantiomers on gelation. Correspondingly, the diastereomeric and enantiomeric Fc[CO-FFA-OMe]2 were constructed for the study of chirality-organized structures.

  2. Versatile preparation of intracellular-acidity-sensitive oxime-linked polysaccharide-doxorubicin conjugate for malignancy therapeutic.

    Science.gov (United States)

    Xu, Weiguo; Ding, Jianxun; Xiao, Chunsheng; Li, Lingyu; Zhuang, Xiuli; Chen, Xuesi

    2015-06-01

    Recently, chemotherapy has been one of the most important therapeutic approaches for malignant tumors. The tumor tissular or intracellular microenvironment-sensitive polymer-doxorubicin (DOX) conjugates demonstrate great potential for improved antitumor efficacy and reduced side effects. In this work, the acid-sensitive dextran-DOX conjugate (noted as Dex-O-DOX) was synthesized through the versatile efficient oximation reaction between the terminal aldehyde group of polysaccharide and the amino group in DOX in the buffer solution of sodium acetate/acetic acid. The insensitive one, i.e., Dex-b-DOX, was prepared similarly as Dex-O-DOX with a supplemented reduction reaction. The DOX release from Dex-O-DOX was pH-dependent and accelerated by the decreased pH. The efficient intracellular DOX release from Dex-O-DOX toward the human hepatoma HepG2 cells was further confirmed. Furthermore, Dex-O-DOX exhibited a closer antiproliferative activity to free DOX·HCl as the extension of time. More importantly, compared with Dex-b-DOX, Dex-O-DOX exhibited higher antitumor activity and lower toxicity, which were further confirmed by the systemic histological and immunohistochemical analyses. Hence, the facilely prepared smart polysaccharide-DOX conjugates, i.e., Dex-O-DOX, exhibited great potential in the clinical chemotherapy of malignancy.

  3. Ligand-Directed Acid-Sensitive Amidophosphate 5‑Trifluoromethyl-2′-Deoxyuridine Conjugate as a Potential Theranostic Agent

    NARCIS (Netherlands)

    Godovikova, T.S.; Kaptein, R.; Silnikov, V.N.; et al., [No Value

    2013-01-01

    Herein, we report a novel strategy to engineer an acid-sensitive anticancer theranostic agent using a vector− drug ensemble. The ensemble was synthesized by directly conjugating the linoleic acid (LA)-modified branched polyethyleneimine with a chemotherapeutic drug trifluorothymidine. Linoleic acid

  4. The effect of conjugated linoneic acid, a natural trans fat from milk and meat, on human blood pressure: results from a randomized crossover feeding study

    NARCIS (Netherlands)

    Engberink, M.F.; Geleijnse, J.M.; Wanders, A.J.; Brouwer, I.A.

    2012-01-01

    Cis-9, trans-11 conjugated linoleic acid (CLA) is a natural trans fatty acid that is largely restricted to ruminant fats and consumed in foods and supplements. Its role in blood pressure (BP) regulation is still unclear. We examined the effect of cis-9, trans-11 CLA on BP compared with oleic acid. A

  5. The effect of conjugated linoneic acid, a natural trans fat from milk and meat, on human blood pressure: results from a randomized crossover feeding study

    NARCIS (Netherlands)

    Engberink, M.F.; Geleijnse, J.M.; Wanders, A.J.; Brouwer, I.A.

    2012-01-01

    Cis-9, trans-11 conjugated linoleic acid (CLA) is a natural trans fatty acid that is largely restricted to ruminant fats and consumed in foods and supplements. Its role in blood pressure (BP) regulation is still unclear. We examined the effect of cis-9, trans-11 CLA on BP compared with oleic acid. A

  6. Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate.

    Science.gov (United States)

    Junyaprasert, Varaporn Buraphacheep; Dhanahiranpruk, Sirithip; Suksiriworapong, Jiraphong; Sripha, Kittisak; Moongkarndi, Primchanien

    2015-12-01

    Folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FOL) decorated methotrexate (MTX)-conjugated nanoparticles were developed for targeted delivery of MTX to folate receptor-expressed tumor cells. The synthesis of TPGS-FOL followed 3-step process. Firstly, the terminal hydroxyl group of TPGS was converted to sulfonyl chloride using mesyl chloride in comparison with nosyl and tosyl chlorides. The highest conversion efficiency and yield were obtained by mesyl chloride due to the formation of higher reactive intermediate in a presence of triethylamine. Secondly, the substitution of sulfonyl group by sodium azide produced considerably high yield with conversion efficiency of over 90%. Lastly, the coupling reaction of azido-substituted TPGS and propargyl folamide by click reaction resulted in 96% conjugation efficiency without polymer degradation. To fabricate the folate receptor-targeted nanoparticles, 10 and 20%mol MTX-conjugated PEGylated poly(ϵ-caprolactone) nanoparticles were decorated with TPGS-FOL. The size and size distribution of MTX-conjugated nanoparticles relatively increased with %MTX. The MTX release from the nanoparticles was accelerated in acidic medium with an increase of %MTX but retarded in physiological pH medium. The decoration of TPGS-FOL onto the nanoparticles slightly enlarged the size and size distribution of the nanoparticles; however, it did not affect the surface charge. The cytotoxicity and cellular uptake of MCF-7 cells demonstrated that 10% MTX-conjugated nanoparticles and FOL-decorated nanoparticles possessed higher toxicity and uptake efficiency than 20% MTX-conjugated nanoparticles and undecorated nanoparticles, respectively. The results indicated that FOL-10% MTX-conjugated nanoparticles exhibited potential targeted delivery of MTX to folate receptor-expressed cancer cells.

  7. Expression of adipose microRNAs is sensitive to dietary conjugated linoleic acid treatment in mice.

    Directory of Open Access Journals (Sweden)

    Pilar Parra

    Full Text Available BACKGROUND: Investigation of microRNAs (miRNAs in obesity, their genetic targets and influence by dietary modulators is of great interest because it may potentially identify novel pathways involved in this complex metabolic disorder and influence future therapeutic approaches. This study aimed to determine whether miRNAs expression may be influenced by conjugated linoleic acid (CLA, currently used to induce fat loss. METHODOLOGY/PRINCIPAL FINDINGS: We determined retroperitoneal adipose tissue (rWAT expression of five miRNAs related to adipocyte differentiation (miRNA-143 and lipid metabolism (miRNA-103 and -107 and altered in obesity (miRNA-221 and -222, using the TaqMan®MicroRNA Assay (Applied-Biosystems. In the first experiment, mice were fed with a standard fat diet and orally treated with sunflower oil (control group and 3 or 10 mg CLA/day for 37 days. In the second experiment, mice were fed with a high fat diet for 65 days. For the first 30 days, mice received the same doses of CLA described above and, from that time onwards, animals received a double dose. Results showed that expression of selected miRNAs was modified in response to CLA treatment and metabolic status. Interestingly, a strong correlation was observed between miR-103 and -107 expression, as well as miR-221 and -222 in both experiments. Moreover, changes in miRNAs expression correlated with several adipocyte gene expressions: miR-103 and -107 correlated with genes involved in fatty acid metabolism whereas miR-221 and miR-222 correlated with the expression of adipocytokines. Regarding the minor changes observed in miR-143 expression, no differences in expression of adipogenic markers were observed. CONCLUSIONS/SIGNIFICANCE: Although elucidating the functional implications of miRNAs is beyond the scope of this study, these findings provide the first evidence that miRNAs expression may be influenced by dietary manipulation, reflecting or even contributing to the new metabolic

  8. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    Directory of Open Access Journals (Sweden)

    Liu Suling

    2008-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA, a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. Methods The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. Results The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2 stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA

  9. Strong and long-lasting antinociceptive and anti-inflammatory conjugate of naturally occurring oleanolic acid and aspirin

    Directory of Open Access Journals (Sweden)

    Barbara Bednarczyk-Cwynar

    2016-07-01

    Full Text Available The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7 and aspirin in dioxane. Analgesic effect of OAO-ASA (8 for the range of doses 0.3 – 300.0 mg/kg (p.o. was performed in mice using a hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8 did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c. the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c. did not affect the antinociceptive effect of OAO-ASA (8, therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o. in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8 was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8 is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8 on TNF-α level

  10. Fabrication of uniform DNA-conjugated hydrogel microparticles via replica molding for facile nucleic acid hybridization assays.

    Science.gov (United States)

    Lewis, Christina L; Choi, Chang-Hyung; Lin, Yan; Lee, Chang-Soo; Yi, Hyunmin

    2010-07-01

    We identify and investigate several critical parameters in the fabrication of single-stranded DNA conjugated poly(ethylene glycol) (PEG) microparticles based on replica molding (RM) for highly uniform and robust nucleic acid hybridization assays. The effects of PEG-diacrylate, probe DNA, and photoinitiator concentrations on the overall fluorescence and target DNA penetration depth upon hybridization are examined. Fluorescence and confocal microscopy results illustrate high conjugation capacity of the probe and target DNA, femtomole sensitivity, and sequence specificity. Combined, these findings demonstrate a significant step toward simple, robust, and scalable procedures to manufacture highly uniform and high-capacity hybridization assay particles in a well-controlled manner by exploiting many advantages that the batch processing-based RM technique offers. We envision that the results presented here may be readily applied to rapid and high-throughput hybridization assays for a wide variety of applications in bioprocess monitoring, food safety, and biological threat detection.

  11. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  12. Aliphatic acid-conjugated antimicrobial peptides--potential agents with anti-tumor, multidrug resistance-reversing activity and enhanced stability.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Wang, Xuekun; Huang, Wenlong; Qian, Hai

    2015-07-28

    Compared with traditional therapeutics, antimicrobial peptides as novel anti-tumor agents have prominent advantages of higher specificity and circumvention of multi-drug resistance. In a previous study, we found that B1, an antimicrobial peptide derived from Cathelicidin-BF15, presented specific anti-tumor activity against several tumor cells. Since aliphatic chain-conjugated peptides have shown ameliorative activity and stability, we conjugated aliphatic acids with different lengths to the amino terminal of B1. All the conjugated peptides exhibited improved anti-tumor activity over B1. Further investigations revealed that the peptides were capable of disrupting the cell membrane, stimulating cytochrome c release into the cytosol, which results in apoptosis. The peptides also acted against multidrug resistant cells and had multidrug resistance-reversing effects. Additionally, conjugation of aliphatic acid enhanced the peptide stability in plasma. In summary, aliphatic acid-modified peptides might be promising anti-tumor agents in the future.

  13. Inflammatory markers in patients with metabolic syndrome after the intake of fatty acids n-3 and conjugated linoleic acid (CLA

    Directory of Open Access Journals (Sweden)

    Campos Mondragón, M.G; Oliart Ros, R. M. ; Angulo Guerrero, J. O.

    2013-03-01

    Full Text Available ABSTRACTIntroduction: The metabolic syndrome (MS increa -ses the odds of dying for cardiovascular disease, theworld’s leading cause of death. It has been shown thatpolyunsaturated fatty acids have a protective role in cardiovascular disease and its comorbidities.Objective: To assess the effect of three kinds ofpolyunsaturated fatty acids on the chronic inflammation in MS.Methods: The study group was 45 adults with MSdiagnose according to IDF criteria. Each group of treatment was assigned cuasi-randomly to 15 subjects during six weeks: a 1.8 g/d n-3 (1.08 g eicosapentoaenoicacid EPA + 0.72 g docosahexaenoic acid DHA, b 2.0g/d conjugated linoleic acid (CLA, 50:50, cis9:trans11,trans10:cis12, c 40 g/d walnut Juglans regia. The results at the beginning and the end of the essay werecompared in each group, using the t-Student test and p <0.01 as statistical signification value.Results:In the patients supplemented with n-3 fattyacids, significantly decreased the level of IL-6 (from9.81 ±1.28 to 8.47 ±0.81 pg/ml, p=0.002, leptin(from 25.94 ±5.06 ng/ml to 20.53 ±3.96 ng/ml,p=0.003 and homocysteine (from 18.80 ±1.95 to16.72 ±1.99 µmol/l, p=0.007, in erythrocytes decreased the percentage α-linolenic content (from 1.90±0.77 to 1.26 ±0.17 %, p=0.004 and the n6/n3 rate(from 4.48 ±1.06 to 3.11 a ±0.60, p=0.000, while increased the percentage of EPA (from 1.13 ±0.45 to1.58 ±0.42 %, p=0.009 and DHA (from 2.61 ±0.36 to4.64 ±0.91 %, p=0.000. In the group that consumedwalnut declined the levels of TNF-α (from 8.75 ±2.06pg/ml to 6.68 ±0.97 pg/ml, p=0.002 and IL-6 (from10.61 ±1.45 to 8.72 ±0.79 pg/ml, p=0.000, in erythrocytes increased the α-linolenic content (from 1.86±0.65 to 2.62 ±0.72 %, p=0.005. In the group thatconsumed CLA decreased the level of homocysteine(from 18.01 ±2.65 to 15.34 ±2.26 µmol/l, p=0.006.Conclusions: The groups that consumed n-3 fattyacids in supplements (EPA/DHA and in walnut, becameevident the modification in

  14. Influence of diet enriched with conjugated linoleic acids on their distribution in tissues of rats with DMBA induced tumors

    Directory of Open Access Journals (Sweden)

    Kazimierska Weronika

    2010-11-01

    Full Text Available Abstract Backround Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid with proven beneficial influence on health. They show e.g. anticarcinogenic, antiobesity, and antiatherogenic effect. Milk, dairy products and meat of poligastric animals are their most valuable dietary sources, with cis-9, trans-11 CLA (RA - rumenic acid being the predominant isomer. Dietary supplements with CLA became very popular, mainly among the overweight and bodybuilders. The aim of this study was to examine the influence of the food supplements with conjugated linoleic acid on carcinogenesis in female Sprague-Dawley rats and evaluation of CLA and other fatty acids distribution in their bodies. Animals were divided into four groups depending on the diet supplementation (oil or Bio-C.L.A. (Pharma Nord Denmark given intragastrically and presence or absence of carcinogenic agent (7,12-dimethylbenz[a]antharcene. Animals were decapitated at 21st week of experiment and serum and microsomes were extracted. Results and conclusions The mammary tumours (adenocarcinoma occurred in groups treated with DMBA. Diet enriched with CLA decreased the cancer morbidity (67% in Bio-C.L.A. compared to 88% in oil and delayed the cancer induction (p = 0.0018. There were no differences in body and organs weight. The supplement used in the study was a mixture of several fatty acids with the greatest proportion of CLA isomers: trans-10, cis-12 (33% and cis-9, trans-11 (31%. Both of them were present in tissues but the content of rumenic acid was greater. Dietary supplementation had also significant impact on other fatty acids content, both in serum and in microsomes.

  15. [Evaluation of the possibilities to increase the content of conjugated linoleic acid (CLA) in meat and meat product].

    Science.gov (United States)

    Piotrowska, Anna; Swiader, Katarzyna; Waszkiewicz-Robak, Bozena; Swiderski, Franciszek

    2012-01-01

    The paper characterizes pro-health properties of conjugated linoleic acid (CLA) and assesses the possibility of increasing their content in pork and pork meat products. Studies conducted on animals indicate antitumor, antiatherosclerotic and antiinflammatory effect ofCLA, also find impact on reducing body fat and increasing muscle growth. However, the number of observations concerning human populations is insufficient to fully evaluate the relationship between CLA intake and reducing the risk of lifestyle diseases. Therefore, it is necessary to conduct further research. Literature data indicate that the use in pigs feed suplementation with CLA preparations, can increase the content of these compounds in the meat and also show, that isomer cis-9, trans-11 is accumulated at significantly higher level. However, these changes were accompanied by increased the share of saturated fatty acids at the expense of monounsaturated which is unfavorable for human health. A better way to increase the CLA content in pork meat appears to be the addition of CLA preparation during the production process, because it does not affect the level of saturated fats. Pork and pork meat products enriched in CLA are characterized by low susceptibility to oxidation, which may result from the coupling of double bonds, antioxidantive properties of conjugated linoleic acid and the increased content of saturated fatty acids. The issue of beneficial effects on human health of pork and pork products with a higher content of CLA, requires further studies conducted on humans. Only then these products can be classified as a functional foods.

  16. [Bioconversion of conjugated linoleic acid by resting cells of Lactobacillus plantarum ZS2058 in potassium phosphate buffer system].

    Science.gov (United States)

    Niu, Xiao-yan; Chen, Wei; Tian, Feng-wei; Zhao, Jian-xin; Zhang, Hao

    2007-04-01

    Lactobacillus plantarum ZS2058, which was screened from the Chinese traditional fermented vegetable, has the capacity to convert the linoleic acid (LA) into conjugated linoleic acid (CLA). Some specific isomers of CLA with potentially beneficial physiological and anticarcinogenic effects, were efficiently produced from free linoleic acid by washed cells of Lactobacillus plantarum ZS2058 under aerobic conditions. The produced CLA isomers are identified as the mixture of cis-9, trans-ll-octadecadienoic acid (CLA1) trans-10, cis-12-octadecadienoic acid (CLA2), 96.4% of which is CLA1. The washed cells of Lactobacillus plantarum ZS2058 producing high levels of c9, t11-CLA were obtained by cultivated in MRS media containing 0.5 mg/mL linoleic acid, indicating that the enzyme system for CLA production is induced by linoleic acid. After a 24-hour bioconversion at 37 degrees C with shaking (120 r/min), 312.4 microg/mL c9, t11-CLA is produced. And after a 36-hour bioconversion, the content of c9, t11-CLA decreases while hydroxy-octadecaenoic acid increases. In addition, the c9, t11-CLA isomer can be transformed to hydroxy- octadecaenoic acid when the mixed CLA (c9, t11-CLA and t10, c12-CLA) were used as the substrate, which suggests that c9, t11-CLA is one of the intermediates of the bioconversion products from free LA by washed cells of Lactobacillus plantarum ZS2058.

  17. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women

    DEFF Research Database (Denmark)

    Tholstrup, Tine; Raff, Marianne; Straarup, Ellen Marie

    2008-01-01

    . The plasma cytokines interleukin-6 and tumor necrosis factor-a were not affected by the treatments, nor were any of the other variables measured. In conclusion, oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease, whereas the c9, t11 CLA......A mixture of trans-10, cis-12 (t10,c12) and cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA mixture) reduced atherosclerosis in animals, thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest. We gave 75 healthy postmenopausal...

  18. Chemometric analysis of the interactions among different parameters describing health conditions, breast cancer risk and fatty acids profile in serum of rats supplemented with conjugated linoleic acids.

    Science.gov (United States)

    Białek, Agnieszka; Zagrodzki, Paweł; Tokarz, Andrzej

    2016-03-01

    We investigated how different doses of conjugated linoleic acids applied for various periods of time influence breast cancer risk and fatty acids profile in serum of rats treated or not with 7,12-dimethylbenz[a]anthracene (DMBA). We also search for interactions among parameters describing health conditions and cancer risk. Animals were divided into 18 groups with different diet modifications (vegetable oil, 1.0%, 2.0% additions of CLA) and different periods of supplementation. In groups treated with DMBA mammary adenocarcinomas appeared. Due to the complexity of experiment apart from statistical analysis a chemometric tool-Partial Least Square method was applied. Analysis of pairs of correlated parameters allowed to identify some regularities concerning the relationships between fatty acid profiles and clinical features of animals. Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration. These two factors underlined the differences in fatty acids profiles among clusters of animals.

  19. Starter cultures and cattle feed manipulation enhance conjugated linoleic acid concentrations in Cheddar cheese.

    Science.gov (United States)

    Mohan, M S; Anand, S; Kalscheur, K F; Hassan, A N; Hippen, A R

    2013-04-01

    Conjugated linoleic acid (CLA) is a fatty acid (FA) that provides several health benefits to humans. The feeding of fish oil-supplemented diets to dairy cows has been extensively studied as a means to improve the CLA content in milk. Several studies have also been conducted on the ability of many microorganisms to produce CLA by utilizing substrates containing linoleic acid. In the present study, the dietary manipulated milk was used in combination with the CLA-producing culture to manufacture Cheddar cheese. The two diets fed to cattle were control and treatment diets to obtain control and treatment milk, respectively. The treatment diet containing fish oil (0.75% of dry matter) was fed to 32 dairy cows grouped in a pen for 18 d to increase the total CLA content in milk. Treatment milk had a CLA content of 1.60 g/100g of FA compared with 0.58 g/100g of FA in control milk obtained by feeding the control diet. A 2 × 2 factorial design with 3 replicates was used to test the combined effect of the CLA-producing starter culture of Lactococcus lactis (CI4b) versus a commercial CLA nonproducing cheese starter as the control culture, and type of milk (control vs. treatment milk) on CLA content in Cheddar cheese. Chemical composition (moisture, salt, fat, and protein) was not affected by the type of culture used. However, the age of the cheese affected the sensory properties and microbiological counts in the different treatments. Ripening with the CI4b culture was found to be effective in further enhancing the CLA content. The CI4b cheeses made from control milk and treatment milk contained 1.09 and 2.41 (±0.18) g of total CLA/100g of FA after 1 mo of ripening, which increased to 1.44 and 2.61 (±0.18) g of total CLA/100g of FA after 6 mo of ripening, respectively. The use of treatment milk resulted in an increase in the CLA isomers (trans-7,cis-9+cis-9,trans-11, trans-9,cis-11+cis-10,trans-12, trans-10,cis-12, cis-9,cis-11, trans-11,cis-13, cis-11,cis-13, trans-11,trans

  20. Detection of biologically active isomers of conjugated linoleic acid in kaymak

    Directory of Open Access Journals (Sweden)

    Ökten, Sevtap

    2005-12-01

    Full Text Available Numerous physiological effects are attributed to conjugated linoleic acids (CLA. Biologically active isomers of CLA ( cis -9, trans -11 (C18:2 and trans- 10, cis- 12 (C18:2 have been reported to have anticarcinogenic, antioxidative and antiatherosclerotic properties. Relatively rich sources of CLA include milk fat-containing foods such as kaymak. Kaymak is a kind of concentrated cream which is traditionally manufactured from buffalo or cow's milk mainly in Turkey . The objective of this study was to determine CLA concentrations during kaymak production. Kaymak was manufactured from cow's milk which was enriched with unfermented cream. Biologically active isomers of CLA in raw milk, cream and kaymak were analyzed using gas chromatography. The method was quick, repeatable and sensitive for the CLA determination of samples. Significant differences were found among the concentrations of both isomer and total CLA during the production process (pNumerosos efectos fisiológicos se atribuyen a los ácidos linoleico conjugados (CLA. Así los isómeros biológicamente activos ( cis -9, trans -11 (C18:2 y trans- 10, cis del ácido linoleico han sido descritos con propiedades anticarcinogénicas, antioxidantes y antiarterioscleróticas. Fuentes relativamente ricas de CLA incluyen alimentos con grasas lácteas tales como el kaymak. El kaymak es una crema concentrada elaborada de leche de búfalo o vaca principalmente en Turquía. El objetivo de este estudio fue la determinación de la concentración de CLA durante la producción de kaymak. El kaymak objeto de estudio fue elaborado a partir de leche de vaca que fue enriquecida con crema no fermentada. Los isómeros biológicamente activos del CLA fueron analizados por cromatografía gaseosa en leche cruda, crema y kaymak. El método empleado fue rápido, reproducible y sensible. Se encontraron diferencias significativas en las concentraciones de ambos isómeros y de CLA total durante el proceso de producci

  1. Co-treatment with conjugated linoleic acid and nitrite protects against myocardial infarction

    Directory of Open Access Journals (Sweden)

    Natia Qipshidze-Kelm

    2014-01-01

    Full Text Available According to the CDC, the most common type of heart disease is coronary artery disease, which commonly leads to myocardial infarction (MI. Therapeutic approaches to lessen the resulting cardiovascular injury associated with MI are limited. Recently, MicroRNAs (miRNAs have been shown to act as negative regulators of gene expression by inhibiting mRNA translation and/or stimulating mRNA degradation. A single miRNA can modulate physiological or disease phenotypes by regulating whole functional systems. Importantly, miRNAs can regulate cardiac function, thereby modulating heart muscle contraction, heart growth and morphogenesis. MicroRNA-499 (miRNA-499 is a cardiac-specific miRNA that when elevated causes cardiomyocyte hypertrophy, in turn preventing cardiac dysfunction during MI. Previous studies revealed that combination treatment with conjugated linoleic acid (cLA and nitrite preserved cardiovascular function in mice. Therefore, it was hypothesized that cLA and nitrite may regulate miRNA-499, thus providing cardiac protection during MI. To test this hypothesis, 12-week old mice were treated with cLA (10 mg/kg/d-via osmotic mini-pump or cLA and nitrite (50 ppm-drinking water 3 days prior to MI (ligation of the left anterior descending artery. Echocardiography and pressure–volume (PV-loop analysis revealed that cLA and nitrite-treated MI mice had improved heart function (10 days following MI compared to untreated MI mice. Treatment with cLA and nitrite significantly induced levels of miRNA-499 compared to untreated MI mice. In addition, treatment with cLA and nitrite abolished MI-induced protein expression of p53 and dynamin-related protein-1 (DRP-1. Moreover, the antioxidant enzyme expression of heme oxygenase-1 (HO-1 was elevated in MI mice treated with cLA and nitrite compared to untreated MI mice. Confocal imaging on heart tissue confirmed expression the levels of HO-1 and p53. Taken together, these results suggest that therapeutic

  2. The effect of conjugated linoleic acid supplementation on the nutritional status of COPD patients

    Directory of Open Access Journals (Sweden)

    Ghobadi H

    2016-10-01

    Full Text Available Hassan Ghobadi,1 Somaieh Matin,2 Ali Nemati,3 Abbas Naghizadeh-baghi4 1Pulmonary Division, 2Internal Medicine Department, 3Biochemistry and Nutrition Department, 4Basic Sciences Department, Ardabil University of Medical Sciences, Ardabil, Iran Background: COPD patients are susceptible to anorexia, reduction of caloric intake, weight loss, and malnutrition. One of the possible mechanisms is the increase of inflammatory markers such as interleukin 1β (IL1β, is highly correlated with anorexia. Considering the anti-inflammatory role of conjugated linoleic acid (CLA, this study aimed to investigate the effect of CLA supplementation on the nutritional status of COPD patients.Patients and methods: In a double-blind clinical trial, 93 COPD patients who volunteered to participate in the study and who filled out a written consent form, were randomly assigned to control or supplementation groups. The patients in the supplementation group received 3.2 g of CLA on a daily basis for 6 weeks, while those in the control group received placebo on a daily basis for 6 weeks. For IL1β assessment, the patients’ anthropometric indices and appetite score were checked and their blood samples were collected both before and after the treatment. Moreover, in order to investigate the changes in the caloric intake trend during the study, their dietary intake levels were assessed using 24-hour dietary recall, 3 days a week at the onset, in the 4th week, and at the end of the study. Eventually, 90 patients completed the study.Results: The results demonstrated a significant increase in appetite score (P=0.001, average caloric intake (P=0.01, and macronutrient intake (P<0.05, while a significant decrease was observed in the serum level of IL1β among the patients of the supplementation group (P=0.008. Meanwhile, although the supplementation group’s body mass index was also higher on completion, compared to their own initial state as well as to that in the control

  3. Dietary supplementation with conjugated linoleic acid plus n-3 polyunsaturated fatty acid increases food intake and brown adipose tissue in rats.

    Science.gov (United States)

    Sneddon, Alan A; Rayner, D Vernon; Mitchell, Sharon E; Bashir, Shabina; Ha, Jung-Heun; Wahle, Klaus W; Morris, Amanda C; Williams, Lynda M

    2009-02-01

    The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3) was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose tissue and uncoupling protein-1 expression were increased. Plasma adiponectin, triglyceride and cholesterol levels were reduced while leptin, ghrelin and liver weight and lipid content were unchanged. Hypothalamic gene expression measurements revealed increased expression of orexigenic and decreased expression of anorexigenic signals. Thus, CLA/n-3 increases food intake without affecting body weight potentially through increasing BAT size and up-regulating UCP-1 in rats.

  4. Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.

    Science.gov (United States)

    Tutone, Marco; Chinnici, Aurora; Almerico, Anna Maria; Perricone, Ugo; Sutera, Flavia Maria; De Caro, Viviana

    2016-11-29

    The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two new conjugates (DA-Trp 2C, and DA-Leu 3C) have been identified as the most promising candidates, and consequently synthesized. Preliminary evaluation in terms of distribution coefficient (D(pH7.4)), stability in rat brain homogenate, and in human plasma confirmed that DA-Trp (2C), and DA-Leu (3C) could be considered as very valuable candidates for further in vivo studies as new dopaminergic drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles.

    Science.gov (United States)

    Dehshahri, Ali; Sadeghpour, Hossein; Keykhaee, Maryam; Khalvati, Bahman; Sheikhsaran, Fatemeh

    2016-05-01

    Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100-180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers.

  6. Production of trans and conjugated fatty acids in dairy ruminants and their putative effects on human health: A review.

    Science.gov (United States)

    Ferlay, Anne; Bernard, Laurence; Meynadier, Annabelle; Malpuech-Brugère, Corinne

    2017-08-10

    Consumption of milk and dairy products is important in Western industrialised countries. Fat content is an important constituent contributing to the nutritional quality of milk and dairy products. In order to improve the health of consumers, there is high interest in improving their fatty acid (FA) composition, which depends principally on rumen and mammary metabolism. This paper reviews the lipid metabolism in ruminants, with a particular focus on the production of trans and conjugated linoleic acids (CLA) and conjugated linolenic acids (CLnA) in the rumen. After the lipolysis of dietary lipids, an extensive biohydrogenation of unsaturated FA occurs by rumen bacteria, leading to numerous cis and trans isomers of 18:1, non-conjugated of 18:2, CLA and CLnA. The paper examines the different putative pathways of ruminal biohydrogenation of cis9-18:1, 18:2n-6, 18:3n-3 and long-chain FA and the bacteria implicated. Then mechanisms relative to the de novo mammary synthesis are presented. Ruminant diet is the main factor regulating the content and the composition of milk fat. Effects of nature of forage and lipid supplementation are analysed in cows and small ruminants species. Finally, the paper briefly presents the effects of these FA on animal models and human cell lines. We describe the properties of ruminant trans 18:1, when compared to industrial trans 18:1, CLA and CLnA on human health from meta-analyses of intervention studies and then explore the underlying mechanisms. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  7. Enhanced cellular delivery of cell-penetrating peptide-peptide nucleic acid conjugates by photochemical internalization

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2011-01-01

    (antisense activity) is still limited by endocytotic entrapment. We have shown that this low bioavailability can be greatly improved by combining CPP-PNA conjugate administration with a photochemical internalization technique using photosensitizers such as aluminum phthalocyanine (AlPcS(2a...

  8. Cellular delivery and antisense effects of peptide nucleic acid conjugated to polyethyleneimine via disulfide linkers

    DEFF Research Database (Denmark)

    Berthold, Peter R; Shiraishi, Takehiko; Nielsen, Peter E

    2010-01-01

    for PNA due to the (inherent) charge neutrality of PNA. However, PEI could function as an efficient scaffold for PNA via chemical conjugation. Accordingly, we modified PEI with the amine-reactive heterobifunctional linker agent N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) (with and without a PEG...

  9. Functionalization of Fatty Acid Vesicles through Newly Synthesized Bolaamphiphile-DNA Conjugates

    DEFF Research Database (Denmark)

    Wamberg, M. C.; Wieczorek, R.; Brier, S. B.

    2014-01-01

    of these structures, only one novel bola-amphiphile DNA conjugate could interact efficiently with or spontaneously pierce into the vesicle bilayers without jeopardizing their self-assembly or stability. This molecule was synthesized via a Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition (click reaction...

  10. Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-01-01

    We have explored the merits of a novel delivery strategy for the antisense oligomers based on cell penetrating peptide (CPP) conjugated to a carrier PNA with sequence complementary to part of the antisense oligomer. The effect of these carrier CPP-PNAs was evaluated by using antisense PNA targeting...... splicing correction of the mutated luciferase gene in the HeLa pLuc705 cell line, reporting cellular (nuclear) uptake of the antisense PNA via luciferase activity measurement. Carrier CPP-PNA constructs were studied in terms of construct modification (with octaarginine and/or decanoic acid) and carrier PNA...

  11. A Novel Thin Film Resistive Humidity Sensor Based on Soluble Conjugated Polymer: (propionic acid)-co-(propargyl alcohol)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A novel soluble conjugated copolymer (propionic acid)-co-(propargyl alcohol) (PA-co-OHP) has been synthesized for the first time using a new palladium acetylide catalyst Pd(PPh3)2 (CoCC(CH3)2OH)2 (PPB). Thin film resistive humidity sensor based on the copolymer doped with HClO-4 was prepared. The impedance of the sensor changed from 103~107 W in 95%~30%RH, and the response of that is very quick (<6 sec.). Preliminary results show the copolymer is a promising humidity sensitive material.

  12. Oligo-aspartic acid conjugates with benzo[c][2,6]naphthyridine-8-carboxylic acid scaffold as picomolar inhibitors of CK2.

    Science.gov (United States)

    Vahter, Jürgen; Viht, Kaido; Uri, Asko; Enkvist, Erki

    2017-02-28

    Structurally diverse inhibitors of the protein kinase CK2 are required for regulation of this ubiquitous protein to establish biological roles of the enzyme which catalyzes the phosphorylation of a vast number of substrate proteins. In this article we disclose a series of new bisubstrate inhibitors of CK2 that are structurally represented by the oligo(l-Asp) peptide conjugates of benzo[c][2,6]naphthyridine-8-carboxylic acid. This fragment originated from CX-4945, the first in class inhibitor taken to clinical trials. The most potent conjugates possessed two-digit picomolar affinity and clear selectivity for CK2α in a panel of 140 protein kinases. Labeling of the inhibitors with a fluorescent dye yielded probes for a fluorescence anisotropy-based binding/displacement assay which can be used for analysis of CK2 and precise determination of affinity of the highly potent (tight-binding) CK2-targeting inhibitors.

  13. Positional distribution of fatty acids in triacylglycerols from subcutaneous adipose tissue of pigs fed diets enriched with conjugated linoleic acid, corn oil, or beef tallow.

    Science.gov (United States)

    King, D A; Behrends, J M; Jenschke, B E; Rhoades, R D; Smith, S B

    2004-08-01

    This study was conducted to determine the effects of dietary beef tallow, corn oil, and conjugated linoleic acid (CLA) on the distribution of fatty acids among positions within triacylglycerols. Crossbred barrows (n=6 per treatment group) received diets containing 1.5% beef tallow, 1.5% corn oil, or 1.5% CLA for 5 weeks. Subcutaneous adipose tissue samples were obtained immediately postmortem. The fatty acid composition was determined for the sn-2 positions of the triacylglycerols by digestion with Rhizopus arrhizus lipase. Fatty acids in the sn-1/3 position were calculated from these data. Feeding CLA increased (Ptallow-fed pigs. These data suggest that dietary CLA increases the melting point of lipids in porcine adipose tissue by increasing the proportion of SFA at the sn-1/3 position of lipids.

  14. Health information impact on the relative importance of beef attributes including its enrichment with polyunsaturated fatty acids (omega-3 and conjugated linoleic acid).

    Science.gov (United States)

    Kallas, Zein; Realini, Carolina E; Gil, José Maria

    2014-08-01

    This paper uses Choice Experiments (CE) to investigate Spanish consumers' preferences towards beef meat enriched with polyunsaturated fatty acids (omega-3 and conjugated linoleic acid). Data were gathered from self-completed questionnaires in a controlled environment with two different samples (320 and 322 consumers) differentiated by the information received. The surveys were carried out in three main Spanish cities (Barcelona, Zaragoza and Pamplona), representing the average consumer. A variation of the "Dual Response Choice Experiments" (DRCE) design was used due to its ability to emphasize the purchase context. Results showed that consumers who received information attach higher preference for enriched meat with polyunsaturated fatty acids. The utility associated with the higher content of fat increase for informed consumers, showing a substitute effect. Informed consumers are willing to accept meat with a higher amount of visible fat if it is enriched with beneficial fatty acids.

  15. The effect of trans-10, cis-12 conjugated linoleic acid on gene expression profiles related to lipid metabolism in human intestinal-like Caco-2 cells

    NARCIS (Netherlands)

    Murphy, E.F.; Hooiveld, G.J.E.J.; Müller, M.R.; Calogero, R.A.; Cashman, K.D.

    2009-01-01

    We conducted an in-depth investigation of the effects of conjugated linoleic acid (CLA) on the expression of key metabolic genes and genes of known importance in intestinal lipid metabolism using the Caco-2 cell model. Cells were treated with 80 mu mol/L of linoleic acid (control), trans-10, cis-12

  16. Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid blend on the human platelet proteome

    NARCIS (Netherlands)

    Bachmair, E.-M.; Bots, M.L.; Mennen, L.I.; Kelder, T.; Evelo, C.T.; Horgan, G.W.; Ford, I.; Roos, B. de

    2012-01-01

    Scope: The dietary fatty acid cis9,trans11 conjugated linoleic acid (cis9,trans11 CLA) has been shown to modify the function of endothelial cells, monocytes, and platelets, all of which are involved in the development of atherosclerosis. Potential mechanisms for the platelet effects have not been as

  17. In Vitro Antioxidant-Activity Evaluation of Gallic-Acid-Grafted Chitosan Conjugate Synthesized by Free-Radical-Induced Grafting Method.

    Science.gov (United States)

    Hu, Qiaobin; Wang, Taoran; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

    2016-07-27

    The major objective of this work was to develop a green and facile process to prepare gallic acid-chitosan conjugate and comprehensively evaluate the physicochemical properties and biological activities of an as-prepared water-soluble chitosan derivative. A free-radical-induced grafting approach using an ascorbic acid-hydrogen peroxide redox pair was adopted. The obtained conjugate was characterized by Fourier transform infrared spectroscopy, UV-vis, X-ray diffraction, and pKa analysis. The antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulphonic acid (ABTS), reducing power, and oxygen-radical antioxidant-capacity assays. The results showed that the mass ratio of gallic acid to chitosan played a vital role in determining the grafting degree and ζ potential of the conjugates, with the ratio of 0.5:1 being the optimal ratio that resulted in the highest grafting degree. The antioxidant assays demonstrated that conjugation significantly improved the antioxidant activities, being dramatically higher than that of free chitosan. It was notable that the DPPH- and ABTS-scavenging activities of conjugate at 0.4 mg/mL reached the same level as the free gallic acid at the equivalent concentration. Our study demonstrated a green and facile synthesis approach to preparing a novel water-soluble chitosan derivative that may have promising potentials in the food industry.

  18. Synthesis of Hexagonal ZnO-PQ7 Nano Disks Conjugated with Folic Acid to Image MCF - 7 Cancer Cells.

    Science.gov (United States)

    Sureshkumar, S; Jothimani, B; Sridhar, T M; Santhosh, Arul; Venkatachalapathy, B

    2017-01-01

    Surface modified ZnO nanomaterial is widely used in the field of bioimaging worldwide due to its optical properties, electronic characteristics and biocompatibility. Fluorescent enhanced, Polyquaternium-7(PQ7) capped, ZnO hexagonal nano disks (ZnO-PQ7) were synthesised by simple wet chemical method. The structural and optical properties of ZnO-PQ7 hexagonal nano disks were characterized using XRD, UV-Visible, Fluorescence, HRTEM, EDAX and FTIR studies. The size of synthesised ZnO-PQ7 were around 30-45 nm as confirmed by HRTEM studies. Fluorescence emission intensity increased with increase in PQ7 concentration. ZnO-PQ7 was further conjugated with folic acid (FA) to target human breast cancer cell line (MCF-7) via EDC/NHS coupling chemistry. Conjugation of folic acid with ZnO-PQ7 was confirmed by FTIR studies. The cell viability study using Methyl thiazolyltetrazolium(MTT) assay has demonstrated that the ZnO-PQ7 conjugated FA composites (ZnO-PQ7-FA) exhibit low toxicity towards MCF-7 up to a concentration of 125 μg/mL. Confocal laser scanning microscopic images confirmed the uptake of ZnO-PQ7-FA nanoparticles by MCF-7 cells. This study reveals ZnO-PQ7-FA nano disks as a potential imaging agent for detection of cancer cells. The synthesis route reported in this article is simple and easy to follow for the synthesis of ZnO-PQ7-FA in bulk quantities with high purity.

  19. Synthesis and carbonic anhydrase inhibitory properties of amino acid - coumarin/quinolinone conjugates incorporating glycine, alanine and phenylalanine moieties.

    Science.gov (United States)

    Küçükbay, F Zehra; Küçükbay, Hasan; Tanc, Muhammet; Supuran, Claudiu T

    2016-12-01

    N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid-coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (KIs > 50 μM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92 nM and 1.19 μM for hCA IV, and between 0.11 and 0.79 μM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.

  20. Preparation and characterization of 1-naphthylacetic acid-silica conjugated nanospheres for enhancement of controlled-release performance

    Science.gov (United States)

    Ao, Mingming; Zhu, Yuncong; He, Shun; Li, Deguang; Li, Pingliang; Li, Jianqiang; Cao, Yongsong

    2013-01-01

    Chemical pesticides have been widely used to increase the yield and quality of agricultural products as they are efficient, effective, and easy to apply. However, the rapid degradation and low utilization ratio of conventional pesticides has led to environmental pollution and resource waste. Nano-sized controlled-release formulations (CRFs) can provide better penetration through the plant cuticle and deliver the active ingredients efficiently to the targeted tissue. In this paper we reported novel conjugated nanospheres derived from 1-naphthylacetic acid (NNA), 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate and their application as a controlled-release plant growth regulator. The NNA and APTES conjugate was prepared through a covalent cross-linking reaction and subsequent hydrolyzation and polycondensation to synthesize NNA-silica nanospheres. The release data indicated that the release of NNA was by non-Fickian transport and increased as particle size decreased. It was also found that the acidity-alkalinity was enhanced and as the temperature increased, the release of the active ingredient was faster. The nanoconjugate displayed a better efficacy in promoting root formation than NNA technical. The present study provides a novel synthesis route for CRFs comprising a pesticide, with long-duration sustained-release performance and good environmental compatibility. This method may be extended to other pesticides that possess a carboxyl group.

  1. The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

    Science.gov (United States)

    Palombo, John D; Ganguly, Aniruddha; Bistrian, Bruce R; Menard, Michael P

    2002-03-28

    The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

  2. Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugated nanoparticles loaded with mitoxantrone

    Institute of Scientific and Technical Information of China (English)

    王炜; 童春义; 刘星言; 李涛; 刘斌; 熊炜

    2015-01-01

    Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), and then used as a template to prepare folic acid-chitosan (FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles (FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48−58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride (MTX) is (77.5±1.9)%, and the drug loading efficiency is (18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.

  3. Lactobacillus plantarum as source of conjugated linoleic acid: Effect of pH, incubation Temperature and inulin incorporation.

    Directory of Open Access Journals (Sweden)

    Carmen Soto

    2013-07-01

    Full Text Available The effect of pH and temperature, and inulin use, on the growth andthe fatty acid profile of Lactobacillus plantarum strain wereevaluated. The best results were obtained at 6.5 pH broth, producing3.2 g/L of biomass and about 20% of conjugated linoleic acid(CLA in the cell lipids. Similar growth was observed with 37 and45ºC, but a low CLA content (10.6% was achieved at 45°C. In thecase of inulin incorporation, a low biomass concentration (1 g/Land low production of CLA (12.4% were observed. These resultssuggest a pH and temperature dependence on CLA production bythe microorganism.

  4. Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression

    Directory of Open Access Journals (Sweden)

    Diwakar Vyas

    2012-01-01

    Full Text Available Objective. To summarize the recent studies on effect of conjugated linoleic acid (CLA on hepatic steatosis and hepatic and adipose lipid metabolism highlighting the potential regulatory mechanisms. Methods. Sixty-four published experiments were summarized in which trans-10, cis-12 CLA was fed either alone or in combination with other CLA isomers to mice, rats, hamsters, and humans were compared. Summary and Conclusions. Dietary trans-10, cis-12 CLA induces a severe hepatic steatosis in mice with a more muted response in other species. Regardless of species, when hepatic steatosis was present, a concurrent decrease in body adiposity was observed, suggesting that hepatic lipid accumulation is a result of uptake of mobilized fatty acids (FA from adipose tissue and the liver's inability to sufficiently increase FA oxidation and export of synthesized triglycerides. The potential role of liver FA composition, insulin secretion and sensitivity, adipokine, and inflammatory responses are discussed as potential mechanisms behind CLA-induced hepatic steatosis.

  5. Effect of dietary alpine butter rich in conjugated linoleic acid on milk fat composition of lactating sows.

    Science.gov (United States)

    Schmid, Alexandra; Collomb, Marius; Bee, Giuseppe; Bütikofer, Ulrich; Wechsler, Daniel; Eberhard, Pius; Sieber, Robert

    2008-07-01

    Multiparous sows (n 17) were included in a controlled cross-over-study in order to investigate the influence of a natural source of conjugated linoleic acid (CLA) (alpine butter) on the milk fatty acid composition of lactating sows (as an animal model for lactating women) and on the growth performance of their progeny. The usual fat source of a standard lactation diet was replaced by either CLA-rich alpine butter or margarine (control diet). Compared with the margarine diet, feeding the alpine butter-supplemented diet increased (P 0.05) affected. Growth performance of the progeny was similar for both dietary treatments. In summary, the findings show that adding alpine butter to the diet does not provoke a milk fat depression and does not alter the composition of total SFA, MUFA and PUFA in sow milk but increases its CLA concentration.

  6. Hyaluronic Acid Conjugates as Vectors for the Active Targeting of Drugs, Genes and Nanocomposites in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Silvia Arpicco

    2014-03-01

    Full Text Available Hyaluronic acid (HA is a naturally-occurring glycosaminoglycan and a major component of the extracellular matrix. Low levels of the hyaluronic acid receptor CD44 are found on the surface of epithelial, hematopoietic, and neuronal cells; it is overexpressed in many cancer cells, and in particular in tumor-initiating cells. HA has recently attracted considerable interest in the field of developing drug delivery systems, having been used, as such or encapsulated in different types of nanoassembly, as ligand to prepare nano-platforms for actively targeting drugs, genes, and diagnostic agents. This review describes recent progress made with the several chemical strategies adopted to synthesize conjugates and prepare novel delivery systems with improved behaviors.

  7. Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

    Science.gov (United States)

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.

  8. Conjugate addition of isocyanides to chromone 3-carboxylic acid: an efficient one-pot synthesis of chroman-4-one 2-carboxamides.

    Science.gov (United States)

    Neo, Ana G; Díaz, Jesús; Marcaccini, Stefano; Marcos, Carlos F

    2012-05-07

    We report a novel Lewis acid catalysed tandem reaction of isocyanides, chromone 3-carboxylic acid and nucleophiles. An experimentally very simple procedure, involving the use of microwave irradiation in the presence of a Lewis acid catalyst, affords a representative collection of chromone-2-carboxamides and chromone-2-carboxamido-3-esters in high yields, in just a few minutes. Such an unprecedented strategy is formally equivalent to a conjugate addition of isocyanides to Michael acceptors.

  9. Effects of deoxycholylglycine, a conjugated secondary bile acid, on myogenic tone and agonist-induced contraction in rat resistance arteries.

    Directory of Open Access Journals (Sweden)

    Sandeep Khurana

    Full Text Available BACKGROUND: Bile acids (BAs regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT, a key determinant of systemic vascular resistance (SVR, have not been examined. METHODOLOGY/PRINCIPAL FINDINGS: Fourth-order mesenteric arteries (170-250 µm isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 µM, a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and -denuded arteries. DCG reduced the myogenic response to stepwise increase in pressure (20 to 100 mmHg. Neither atropine nor the combination of L-NAME (a NOS inhibitor plus indomethacin altered DCG-mediated reduction of MT. K(+ channel blockade with glibenclamide (K(ATP, 4-aminopyradine (K(V, BaCl(2 (K(IR or tetraethylammonium (TEA, K(Ca were also ineffective. In Fluo-2-loaded arteries, DCG markedly reduced vascular smooth muscle cell (VSM Ca(2+ fluorescence (∼50%. In arteries incubated with DCG, physiological salt solution (PSS with high Ca(2+ (4 mM restored myogenic response. DCG reduced vascular tone and VSM cytoplasmic Ca(2+ responses (∼50% of phenylephrine (PE- and Ang II-treated arteries, but did not affect KCl-induced vasoconstriction. CONCLUSION: In rat mesenteric resistance arteries DCG reduces pressure- and agonist-induced vasoconstriction and VSM cytoplasmic Ca(2+ responses, independent of muscarinic receptor, NO or K(+ channel activation. We conclude that BAs alter vasomotor responses, an effect favoring reduced SVR. These findings are likely pertinent to vascular dysfunction in cirrhosis and other conditions associated with elevated serum BAs.

  10. The effect of commercial conjugated linoleic acid products on experimental periodontitis and diabetes mellitus in Wistar rats.

    Science.gov (United States)

    Balci Yuce, Hatice; Akbulut, Nihat; Ocakli, Seda; Kayir, Omer; Elmastas, Mahfuz

    2017-01-01

    The aim of present study was to determine the effects of conjugated linoleic acid enriched milk on alveolar bone loss, hyperglycaemia, oxidative stress and apoptosis in ligature-induced periodontal disease in diabetic rat model. Wistar rats were divided into six experimental groups: 1; non-ligated (NL, n = 6) group, 2; ligature only (LO, n = 6) group, 3; streptozotocin only (STZ, n = 8) group, 4; STZ and ligature (STZ + L, n = 8) group, 5; ligature and conjugated linoleic acid (CLA) (L + CLA, n = 8) group, 6; STZ, ligature and CLA group (STZ + L + CLA, n = 8) group. Diabetes mellitus was induced by 60 mg/kg streptozotocin. Rats were fed with CLA enriched milk for four weeks. Silk ligatures were placed at the gingival margin of lower first molars of mandibular quadrant. The study duration was four weeks after diabetes induction and the animals were sacrificed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined. Inducible nitric oxide synthase (iNOS) and Bax protein expressions, serum interleukin-1β (IL-1β), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels and tartrate resistant acid phosphatase (TRAP)+ osteoclast numbers were also evaluated. At the end of four weeks, alveolar bone loss was significantly higher in the STZ + LO group compared to the other groups (p Diabetes and CLA increased Bax protein levels (p  .05). Within the limits of this study, commercial CLA product administration in addition to diet significantly reduced alveolar bone loss, increased osteoblastic activity and decreased osteoclastic activity in the diabetic Wistar rats.

  11. Metabolic profile of mephedrone: Identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites.

    Science.gov (United States)

    Linhart, Igor; Himl, Michal; Židková, Monika; Balíková, Marie; Lhotková, Eva; Páleníček, Tomáš

    2016-01-01

    Metabolic profile of mephedrone (4-methylmethcathinone, 4-MMC), a frequently abused recreational drug, was determined in rats in vivo. The urine of rats dosed with a subcutaneous bolus dose of 20mg 4-MMC/kg was analysed by LC/MS. Ten phase I and five phase II metabolites were identified by comparison of their retention times and MS(2) spectra with those of authentic reference standards and/or with the MS(2) spectra of previously identified metabolites. The main metabolic pathway was N-demethylation leading to normephedrone (4-methylcathinone, 4-MC) which was further conjugated with succinic, glutaric and adipic acid. Other phase I metabolic pathways included oxidation of the 4-methyl group, carbonyl reduction leading to dihydro-metabolites and ω-oxidation at the position 3'. Five of the metabolites detected, namely, 4-carboxynormephedrone (4-carboxycathinone, 4-CC), 4-carboxydihydronormephedrone (4-carboxynorephedrine, 4-CNE), hydroxytolyldihydro-normephedrone (4-hydroxymethylnorephedrine, 4-OH-MNE) and conjugates of 4-MC with glutaric and adipic acid, have not been reported as yet. The last two conjugates represent a novel, hitherto unexploited, type of phase II metabolites in mammals together with an analogous succinic acid conjugate of 4-MC identified by Pozo et al. (2015). These conjugates might be potentially of great importance in the metabolism of other psychoactive amines.

  12. Spectrophotometric determination and removal of unchelated europium ions from solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates.

    Science.gov (United States)

    Elshan, N G R Dayan; Patek, Renata; Vagner, Josef; Mash, Eugene A

    2014-11-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination as well as the success of metal ion removal on attempted purification. We compared the use of Empore chelating disks and Chelex 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore chelating disks were found to give much higher recoveries of the probes under the conditions used. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin.

  13. Quantitative assays of the amount of diethylenetriaminepentaacetic acid conjugated to water-soluble polymers using isothermal titration calorimetry and colorimetry.

    Science.gov (United States)

    Gouin, S; Winnik, F M

    2001-01-01

    The level of conjugation of diethylenetriaminepentaacetic acid (DTPA) to the polysaccharide sodium hyaluronan (HA) has been measured by a colorimetric assay, isothermal titration calorimetry (ITC), and (1)H NMR spectroscopy. The colorimetric assay is based on the red shift, upon complexation with gadolinium ion (Gd3+), of the wavelength of maximum absorption of the dye arsenazo III. It can be performed in a few minutes using as little as 10 microg of polymer with a detection limit of approximately 0.03 mmol of DTPA (gram of polymer)-1. The ITC measurements yield values of the amount of DTPA linked to HA identical to those obtained by colorimetry. The levels of DTPA conjugation calculated by integration of signals at 3.1-3.2 ppm (DTPA protons) and at 2.0 ppm (HA acetamide protons) in the 1H NMR spectrum of HA-DTPA are consistently overestimated by a factor of approximately 2, compared to the data obtained by ITC and colorimetry. The longer relaxation times of protons of the polymer backbone, compared to those of protons attached to the freely moving DTPA side-chains may account for the discrepancy.

  14. Beef tallow increases the potency of conjugated linoleic acid in the reduction of mouse mammary tumor metastasis.

    Science.gov (United States)

    Hubbard, Neil E; Lim, Debora; Erickson, Kent L

    2006-01-01

    Animal studies consistently show that dietary conjugated linoleic acid (CLA) reduces mammary tumorigenesis including metastasis. Relatively low concentrations of CLA are required for those effects, and a threshold level exists above which there is no added reduction. We reasoned that the concentration of CLA required to effectively alter mammary tumor metastasis may be dependent on the type of dietary fat because select fatty acids can enhance or suppress normal or malignant cell growth and metastasis. For this study, the diets (a total of 12 different groups) differed in fatty acid composition but not in energy from fat (40%). In experiments involving spontaneous metastasis, mice were fed for 11 wk; in experiments in which mice were injected i.v. with tumor cells, they were fed for 7 wk. Mice were then assessed for the effect of CLA concentration on mammary tumorigenesis. Mammary tumor growth was not altered, but metastasis was significantly decreased when beef tallow (BT) replaced half of a defined vegetable fat blend (VFB). That blend reflects the typical fat content of a Western diet. In addition, that same VFB:BT diet lowered the concentration of CLA required to significantly decrease mammary tumor metastasis from 0.1% of the diet to 0.05%. A diet in which corn oil replaced half of the VFB did not lower the threshold from 0.1 to 0.05%. In vitro, the main fatty acid in vegetable oil, linoleic acid, reduced the efficacy of CLA toxicity on mammary tumor cells in culture. Alternatively, fatty acids normally found in BT, such as oleic, stearic, and palmitic acids, either did not change or enhanced the cytolytic effects of CLA isomers on mouse mammary tumor cells in culture. These data provide evidence that dietary BT, itself with negligible levels of CLA, may increase the efficacy of dietary CLA in reducing mammary tumorigenesis.

  15. Engineering the production of conjugated fatty acids in Arabidopsis thaliana leaves

    Science.gov (United States)

    The seeds of many non-domesticated plant species synthesize oils containing high amounts of a single unusual fatty acid, many of which have potential usage in industry. Despite the identification of enzymes for unusual oxidized fatty acid synthesis, the production of these fatty acids in engineered ...

  16. Identification of ellagic acid conjugates and other polyphenolics in muscadine grapes by HPLC-ESI-MS.

    Science.gov (United States)

    Lee, Joon-Hee; Johnson, Jodie V; Talcott, Stephen T

    2005-07-27

    Ellagic acid, ellagic acid glycosides, and ellagitannins found in various fruits and nuts, including muscadine grape, are reported to have potential health-promoting benefits and antioxidant properties. This study isolated and identified several ellagic acid derivatives present in muscadine grapes and determined their relative antioxidant properties (AOX). Compounds were extracted from grape skins and pulp using methanol, and the solvent was evaporated. Isolates were dissolved in citric acid buffer (pH 3.5) and absorbed onto C18 cartridges. Nonretained polyphenolics were collected separately and again partitioned from Sephadex LH-20, whereas retained polyphenolics were first eluted with ethyl acetate followed by methanol. Ellagic acid derivatives were identified on the basis of UV and mass spectra, and the presence of ellagitannins was confirmed by a significant increase in free ellagic acid with HPLC followed by acid hydrolysis. Muscadine grapes contained phenolic acids, flavonols, anthocyanins, ellagic acid, and numerous ellagic acid derivatives. AOX varied in the order ethyl acetate > methanol > C18 nonretained fractions; each correlated to both total phenolics (r = 0.90) and total ellagic acid (r = 0.99) contents. Results of this study revealed previously unidentified ellagic acid derivatives in muscadine grapes.

  17. Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

    Directory of Open Access Journals (Sweden)

    Nabil A. Siddiqui

    2016-10-01

    Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

  18. Effects of Conjugated Linoleic Acid (CLA on the Reproductive Axis Pituitary, Thyroid, Testes of Ram in Non-reproductive Season

    Directory of Open Access Journals (Sweden)

    Behnaz Mahdavi

    2014-10-01

    Full Text Available Conjugated Linoleic Acid is a group of long-chain unsaturated fatty acids with more than one double bond and a mixture of 28 isomers of Linoleic acid (C 18:2 and it is counted as one of the essential acids. The main purpose of this study was to investigate the effect of CLA on some reproductive hormones in rams. In this study, six rams 3 to 4 years old with an average weight of 90 kg were selected. Rams were randomly divided into 3 groups and were treated by CLA treatment for 30 days. The first group (as a control group didn’t receive CLA, The second group received 0.5 g and the third group received 1 g of CLA. The blood testing was done on rams every 15 days using a 20 mL syringe. Data analysis was performed by SAS software. Also mean comparison was done using Duncan's test method (p<0.05. Obtained results showed that the serum concentration of testosterone hormone was decreased numerically as well as the concentration of FSH hormone however the concentration of LH was increased. Also the CLA had a significant effect on Leptin concentration. CLA in oral form can reduce the concentration of testosterone in rams.

  19. Preparation of highly conjugated water-dispersible graphene-butyric acid for the enhancement of electron transfer within polyamic acid-benzoxazole: potential applications in electrochemical sensing.

    Science.gov (United States)

    Chen, Hsiao-Chien; Chen, Yen-Hsuan; Chen, Shi-Liang; Chern, Yaw-Terng; Tsai, Rung-Ywan; Hua, Mu-Yi

    2013-08-15

    To break through the long time and complex procedures for the preparation of highly conjugated reduced graphene oxide (r-GO) in developing electrochemical sensor, a time-saving and simple method is investigated in this study. One novel step of the exfoliated accompanying carboxylated graphene sheet from pristine is achieved via Friedel-Crafts acylation. By electrophilic aromatic substitution, the succinic anhydride ring is opened and attaches covalently to the graphene sheet (Gs) to form exfoliated graphene with grafted 1-one-butyric acid (Gs-BA). The grafting chain converts anions in aqueous solution to maintain Gs-BA in a stable dispersion and noticeably decreases the π-π stacking of the exfoliated Gs during the drying process. The analytical results of the absorption spectroscopy demonstrate that the conjugation of Gs-BA is not significantly destroyed by this chemical modification; Gs-BA retains the Gs electrical properties favorable for developing electrochemical sensors. When polyamic acid-benzoxazole (PAA-BO), a hydrogen peroxide (H₂O₂)-sensitive probe, hybridizes with Gs-BA to form Gs-BA-PAA-BO, the electron transfer rate relating to the response time improves markedly from 1.09 s(-1) to 38.8 s(-1). Additionally, it offers a high performance for H₂O₂ sensing in terms of sensitivity and response time, making this method applicable for developing glucose and choline biosensors.

  20. Toward "stable-on-the-table" enzymes: improving key properties of catalase by covalent conjugation with poly(acrylic acid).

    Science.gov (United States)

    Riccardi, Caterina M; Cole, Kyle S; Benson, Kyle R; Ward, Jessamyn R; Bassett, Kayla M; Zhang, Yiren; Zore, Omkar V; Stromer, Bobbi; Kasi, Rajeswari M; Kumar, Challa V

    2014-08-20

    Several key properties of catalase such as thermal stability, resistance to protease degradation, and resistance to ascorbate inhibition were improved, while retaining its structure and activity, by conjugation to poly(acrylic acid) (PAA, Mw 8000) via carbodiimide chemistry where the amine groups on the protein are appended to the carboxyl groups of the polymer. Catalase conjugation was examined at three different pH values (pH 5.0, 6.0, and 7.0) and at three distinct mole ratios (1:100, 1:500, and 1:1000) of catalase to PAA at each reaction pH. The corresponding products are labeled as Cat-PAA(x)-y, where x is the protein to polymer mole ratio and y is the pH used for the synthesis. The coupling reaction consumed about 60-70% of the primary amines on the catalase; all samples were completely water-soluble and formed nanogels, as evidenced by gel electrophoresis and electron microscopy. The UV circular dichroism (CD) spectra indicated substantial retention of protein secondary structure for all samples, which increased to 100% with increasing pH of the synthesis and polymer mole fraction. Soret CD bands of all samples indicated loss of ∼50% of band intensities, independent of the reaction pH. Catalytic activities of the conjugates increased with increasing synthesis pH, where 55-80% and 90-100% activity was retained for all samples synthesized at pH 5.0 and pH 7.0, respectively, and the Km or Vmax values of Cat-PAA(100)-7 did not differ significantly from those of the free enzyme. All conjugates synthesized at pH 7.0 were thermally stable even when heated to ∼85-90 °C, while native catalase denatured between 55 and 65 °C. All conjugates retained 40-90% of their original activities even after storing for 10 weeks at 8 °C, while unmodified catalase lost all of its activity within 2 weeks, under similar storage conditions. Interestingly, PAA surrounding catalase limited access to the enzyme from large molecules like proteases and significantly increased

  1. Pyrene appended bile acid conjugates: Synthesis and a structure-gelation property study

    Indian Academy of Sciences (India)

    Shreedhar Bhat; Arto Valkonen; Juha Koivukorpi; Anupama Ambika; Erkki Kolehmainen; Uday Maitra; Kari Rissanen

    2011-07-01

    A wide variety of novel compounds obtained by combining two types of known organogelators, viz., bile acid alkyl amides and pyrene alkanoic acids, were synthesized and screened for their gelation ability. The 3 esters of 1-pyrene butyric acid (PBA) of alkylamides of deoxycholic acid (DCA) turned out to be effective in the gel formation with many organic solvents although the gelation has to be triggered by the addition of a charge transfer (CT) agent 2,4,7-trinitrofluorenone (TNF). The special feature of these molecules is that the organogelation is achieved only after derivatizing the acid moiety of the 1-pyrenealkanoic acids. Additionally, the gelation properties can be fine-tuned by inserting different functional groups at the bile acid side chain. The gels obtained are deep red in colour and optically transparent up to 2% w/v. The SEM studies of the obtained xerogels revealed bundled rod-like morphology without specialized branching.

  2. Dietary Supplementation with Conjugated Linoleic Acid Plus n-3 Polyunsaturated Fatty Acid Increases Food Intake and Brown Adipose Tissue in Rats

    Directory of Open Access Journals (Sweden)

    Amanda C. Morris

    2009-11-01

    Full Text Available The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3 was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose tissue and uncoupling protein-1 expression were increased. Plasma adiponectin, triglyceride and cholesterol levels were reduced while leptin, ghrelin and liver weight and lipid content were unchanged. Hypothalamic gene expression measurements revealed increased expression of orexigenic and decreased expression of anorexigenic signals. Thus, CLA/n-3 increases food intake without affecting body weight potentially through increasing BAT size and up-regulating UCP-1 in rats.

  3. Metal halide hydrates as lewis acid catalysts for the conjugated friedel-crafts reactions of indoles and activated olefins

    Energy Technology Data Exchange (ETDEWEB)

    Schwalm, Cristiane S.; Ceschi, Marco Antonio; Russowsky, Dennis, E-mail: dennis@iq.ufrgs.b [Universidade Federal do Rio Grande do Sul (IQ/UFRGS), Porto Alegre, RS (Brazil). Inst. de Quimica

    2011-07-01

    Metal halide hydrates such as SnCl{sub 2{center_dot}}2H{sub 2}O, MnCl{sub 2{center_dot}}4H{sub 2}O, SrCl{sub 2{center_dot}}6H{sub 2}O, CrCl{sub 2{center_dot}}6H{sub 2}O, CoCl{sub 2{center_dot}}6H{sub 2}O e CeCl{sub 3{center_dot}}7H{sub 2}O were investigated as mild Lewis acids catalysts for the conjugate Friedel-Crafts reaction between indoles and activated olefins. The reactions were carried out with aliphatic unsaturated ketones over a period of days at room temperature, while chalcones reacted only under reflux conditions. The reactions with nitrostyrene s were either performed in solvent or under solventless conditions. In all cases reasonable to good yields were obtained. (author)

  4. In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin

    Science.gov (United States)

    Alvarez-Berríos, Merlis P; Vivero-Escoto, Juan L

    2016-01-01

    The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death. PMID:27920531

  5. Metabolic and growth inhibitory effects of conjugated fatty acids in the cell line HT-29 with special regard to the conversion of t11,t13-CLA.

    Science.gov (United States)

    Degen, Christian; Ecker, Josef; Piegholdt, Stefanie; Liebisch, Gerhard; Schmitz, Gerd; Jahreis, Gerhard

    2011-12-01

    Conjugated fatty acids (CFAs) exhibit growth inhibitory effects on colon cancer in vitro and in vivo. To investigate whether the anticancerogenic potency depends on number or configuration of the conjugated double bonds, the effect of conjugated linoleic acid (CLA; C18:2) isomers and conjugated linolenic acid (CLnA; C18:3) isomers on viability and growth of HT-29 cells were compared. Low concentrations of CLnAs (t11,t13-CLA≥t9,t11-CLA>c9,t11-CLA. The mRNA expression analysis of important genes associated with fatty acid metabolism showed an absence of ∆5-/∆6-desaturases and elongases in HT-29 cells, which was confirmed by fatty acid analysis. Using time- and dose-dependent stimulation experiments several metabolites were determined. Low concentrations of all trans-CFAs (5-20μM) led to dose-dependent increase of conjugated t/t-C16:2 formed by β-oxidation of C18 CFAs, ranging from 1-5% of total FAME. Importantly, it was found that CLnA is converted to CLA and that CLA is inter-converted (t11,t13-CLA is metabolized to c9,t11-CLA) by HT-29 cells. In summary, our study shows that growth inhibition of human cancer cells is associated with a specific cellular transcriptomic and metabolic profile of fatty acid metabolism, which might contribute to the diversified ability of CFAs as anti-cancer compounds.

  6. 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species.

    Science.gov (United States)

    den Hartigh, Laura J; Han, Chang Yeop; Wang, Shari; Omer, Mohamed; Chait, Alan

    2013-11-01

    Conjugated linoleic acid (CLA) is a naturally occurring dietary trans fatty acid found in food from ruminant sources. One specific CLA isomer, 10E,12Z-CLA, has been associated with health benefits, such as reduced adiposity, while simultaneously promoting deleterious effects, such as systemic inflammation, insulin resistance, and dyslipidemia. The precise mechanisms by which 10E,12Z-CLA exerts these effects remain unknown. Despite potential health consequences, CLA continues to be advertised as a natural weight loss supplement, warranting further studies on its effects on lipid metabolism. We hypothesized that 10E,12Z-CLA impairs lipid storage in adipose tissue by altering the lipid metabolism of white adipocytes. We demonstrate that 10E,12Z-CLA reduced triglyceride storage due to enhanced fatty acid oxidation and lipolysis, coupled with diminished glucose uptake and utilization in cultured adipocytes. This switch to lipid utilization was accompanied by a potent proinflammatory response, including the generation of cytokines, monocyte chemotactic factors, and mitochondrial superoxide. Disrupting fatty acid oxidation restored glucose utilization and attenuated the inflammatory response to 10E,12Z-CLA, suggesting that fatty acid oxidation is critical in promoting this phenotype. With further investigation into the biochemical pathways involved in adipocyte responses to 10E,12Z-CLA, we can discern more information about its safety and efficacy in promoting weight loss.

  7. The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters.

    Science.gov (United States)

    Zabala, Amaia; Churruca, Itziar; Macarulla, M Teresa; Rodríguez, Víctor M; Fernández-Quintela, Alfredo; Martínez, J Alfredo; Portillo, María P

    2004-09-01

    Conjugated linoleic acid (CLA) refers to the positional and geometric dienoic isomers of linoleic acid. The dietary intake of CLA has been associated with changes in lipid metabolism. The aim of the present work was to assess the effects of the two main isomers of CLA on sterol regulatory element binding protein (SREBP)-1a and SREBP-1c mRNA levels, as well as on mRNA levels and the activities of several lipogenic enzymes in liver. For this purpose hamsters were fed an atherogenic diet supplemented with 5 g linoleic acid, cis-9,trans-11 or trans-10,cis-12 CLA/kg diet for 6 weeks. The trans-10,cis-12 isomer intake produced significantly greater liver weight, but also significantly decreased liver fat accumulation. No changes in mRNA levels of SREBP-1a, SREBP-1c and lipogenic enzymes, or in the activities of these enzymes, were observed. There was no effect of feeding cis-9,trans-11 CLA. These results suggest that increased fat accumulation in liver does not occur on the basis of liver enlargement produced by feeding the trans-10,cis-12 isomer of CLA in hamsters. The reduction in hepatic triacylglycerol content induced by this isomer was not attributable to changes in lipogenesis.

  8. Bioconversion enhancement of conjugated linoleic acid by Lactobacillus plantarum using the culture media manipulation and numerical optimization.

    Science.gov (United States)

    Khosravi, Azin; Safari, Mohammad; Khodaiyan, Faramarz; Gharibzahedi, Seyed Mohammad Taghi

    2015-09-01

    The ability of different Lactobacillus strains to produce conjugated linoleic acid (CLA) from linoleic acid was evaluated. Preliminary experiments revealed that L. plantarum among the screened strains had the highest CLA-producing potential (95.25 μg/mL). The cell growth of this bacterium was studied in three media of MRS broth, skim milk and skim milk supplemented with yeast extract and glucose. Results showed that the use of yeast extract and glucose could significantly increase the cell growth and CLA production. Response surface methodology (RSM) was applied to investigate the effects of three independent variables; linoleic acid (LA), yeast extract concentrations and inoculum size on the CLA formation. A second-order polynomial model with high R (2) value (0.981) was developed using multiple linear regression analysis. The optimum conditions to achieve the highest CLA production (240.69 μg/mL) was obtained using 3 mg/mL LA, 4 g/L yeast extract and inoculum size of 4 % v/v. CLA concentration of the optimal sample was analyzed by Gas Chromatography (GC). The cis-9, trans-11 CLA was the major CLA isomer of total CLA detected.

  9. Variations in conjugated linoleic acid (CLA) content of processed cheese by lactation time, feeding regimen, and ripening.

    Science.gov (United States)

    Kim, Jun Ho; Kwon, O-Jun; Choi, Nag-Jin; Oh, Se Jong; Jeong, Ha-Yeon; Song, Man-Kang; Jeong, Inhye; Kim, Young Jun

    2009-04-22

    Dairy products are major sources of conjugated linoleic acid (CLA); thus, an increase in CLA content can improve the quality value of dairy products. The objective of this work was to determine the effects of lactation time, feeding regimen, and ripening period on the level of CLA in processed cheese. CLA content in milk varied with the period of lactation; high in spring (April and May, about 6.8 mg CLA/g fat) and relatively low in mid summer and winter (about 4.3 mg CLA/g fat). The effects of dietary regimen and ripening period were determined in milk, which was obtained from March to May. After aging for 4 months, the cheese made from milk obtained from cows fed on pasture contained relatively higher levels of CLA compared to cheese made from milk obtained from cows fed indoors (8.12 mg CLA/g fat vs 6.76 mg CLA/g fat), but there was no difference in 7 month-aged cheeses. In both pasture and indoor feeding, 7 month-aged cheeses showed higher CLA content than 4 month-aged cheeses. The contents of stearic acid (C18:0) and linolenic acid (C18:3) were significantly higher in cheese from pasture fed cows compared to those in cows fed indoors. These findings should be helpful for the efficient production of functional dairy products with high CLA contents.

  10. Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates.

    Science.gov (United States)

    Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

    2015-03-19

    Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.

  11. Production of conjugated linoleic acid (CLA) by Bifidobacterium breve LMC520 and its compatibility with CLA-producing rumen bacteria.

    Science.gov (United States)

    Park, Hui Gyu; Heo, Wan; Kim, Sang Bum; Kim, Hyun Seop; Bae, Gui Seck; Chung, Soo Hyun; Seo, Ho-Chan; Kim, Young Jun

    2011-02-09

    This study was performed to characterize the ability of an active Bifidobacterium strain to produce conjugated linoleic acid (CLA) and to test its possible utilization as a probiotic compatible to the ruminal condition. Bifidobacterium breve LMC520 can actively convert linoleic acid (LA) to cis-9,trans-11-CLA, which is a major isomer derived from microbial conversion. LMC520 showed reasonable tolerance under acidic conditions (pH 2.5 with 1% pepsin) and in the presence of oxgall (0-3%). The growth and CLA production of LMC520 were tested under ruminal conditions and compared with those of Butyrivibrio fibrisolvens A38, which is a major CLA producer in the rumen as an intermediate in the biohydrogenation (BH) process. LMC520 converted 15% of LA to CLA under ruminal conditions, which was 2 times higher activity than that of A38, and there was no decline in CLA level during prolonged incubation of 48 h. The BH activity of LMC520 was comparable to that of A38. When LMC520 was cocultured with A38, even with slight decrease of CLA due to high BH activity by A38, but the level of CLA was maintained by the high CLA-producing activity of LMC520. This comparative study shows the potential of this strain to be applied as a functional probiotic not only for humans but also for ruminants as well as to increase CLA production.

  12. Dietary conjugated linoleic acids increase intramuscular fat deposition and decrease subcutaneous fat deposition in Yellow Breed × Simmental cattle.

    Science.gov (United States)

    Zhang, Haibo; Dong, Xianwen; Wang, Zhisheng; Zhou, Aiming; Peng, Quanhui; Zou, Huawei; Xue, Bai; Wang, Lizhi

    2016-04-01

    This study was conducted to estimate the effect of dietary conjugated linoleic acids (CLA) on intramuscular and subcutaneous fat deposition in Yellow Breed × Simmental cattle. The experiment was conducted for 60 days. The results showed that the average backfat thickness, (testicles + kidney + pelvic) fat percentage and subcutaneous fat percentage in dietary CLA were significantly lower than in the control group, while intramuscular the fat percentage was significantly higher. Compared to the control group, the Longissimus muscle enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC) in dietary CLA and the subcutaneous fat enzyme activities of LPL, hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) were significantly increased. Similarly, compared to the control group, the Longissimus muscle sterol regulatory element binding protein 1 (SREBP-1), FAS, stearoyl-coenzyme A desaturase (SCD), ACC, peroxisome proliferator-activated receptor γ (PPARγ), heart fatty-acid binding protein (H-FABP) and LPL gene expression in dietary CLA were significant increased, as were the subcutaneous fat of PPARγ, H-FABP, LPL, CPT-1 and HSL in dietary CLA. These results indicated that dietary CLA increases IMF deposition mainly by the up-regulation of lipogenic gene expression, while decreasing subcutaneous fat deposition mainly by the up-regulation of lipolytic gene expression.

  13. Enantioselective conjugate addition of phenylboronic acid to enones catalysed by a chiral tropos/atropos rhodium complex at the coalescence temperature.

    Science.gov (United States)

    Monti, Chiara; Gennari, Cesare; Piarulli, Umberto

    2005-11-14

    A highly enantioselective rhodium-catalysed conjugate addition of phenylboronic acid to cyclic enones has been achieved using a dynamic library of chiral phosphorus ligands; the tropos/atropos nature of the ligands in the rhodium complex has been characterised via 31P-NMR.

  14. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention:

  15. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: Seventy

  16. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: Seventy

  17. Self-aggregated nanoparticles of linoleic acid-modified glycol chitosan conjugate as delivery vehicles for paclitaxel: preparation, characterization and evaluation.

    Science.gov (United States)

    Yu, Jingmou; Liu, Yonghua; Zhang, Lei; Zhao, Jianguo; Ren, Jin; Zhang, Lifang; Jin, Yi

    2015-01-01

    A series of linoleic acid-modified glycol chitosan (LAGC) conjugates were synthesized and characterized by FTIR and (1)H NMR. The effect of the amount of linoleic acid (LA) on the physicochemical properties of LAGC conjugates was investigated. The mean diameters of three LAGC nanoparticles determined by dynamic light scattering ranged from 204 to 289 nm. The critical aggregation concentration values of LAGC conjugates in aqueous solution were 0.0148, 0.0348, and 0.0807 mg/ml, respectively. Paclitaxel (PTX) was physically loaded into the LAGC nanoparticles by a dialysis method. The drug loading content and encapsulation efficiency of PTX-loaded LAGC (PTX-LAGC) nanoparticles increased with an increasing ratio of the hydrophobic LA to hydrophilic glycol chitosan in the conjugates. PTX-LAGC nanoparticles were almost spherical in shape observed by transmission electron microscopy. In vitro release revealed that PTX release from the nanoparticles was reduced as the LA substitution degree of LAGC conjugates increased. Compared with the commercial formulation Taxol, PTX-LAGC-1 nanoparticles exhibited comparable cellular uptake and cytotoxicity against HepG2 cells in vitro. Importantly, PTX-LAGC-1 nanoparticles demonstrated the stronger antitumor efficacy against hepatic H22 tumor-bearing mice than Taxol (p delivery vehicles for tumor therapy.

  18. Influence of dietary conjugated linoleic acid on growth, fatty acid composition and hepatic lipogenesis in large yellow croaker (Pseudosciaena crocea R.)

    Institute of Scientific and Technical Information of China (English)

    Zhan-yu ZHAO; Tian-xing WU; Hong-gang TANG; Ji-ze ZHANG

    2008-01-01

    We examined the effects of conjugated linoleic acid (CLA) on growth, fatty acid composition and enzyme activity of fatty acid oxidation in the liver of large yellow croaker. We divided 1600 fish (average initial weight 150 g) into 4 groups and reared them in 8 cages. Four dietary treatments were formulated to contain 0%, 1%, 2% and 4% (w/w) CLA, respectively. The fish were fed for 10 weeks ad libitum twice daily. We found that the dietary CLA had no effect on growth, biometric parameters and whole body proximate (P>0.05), but showed some significant effects on the fatty acid composition in both muscle and the liver.The activities oflipogenic enzymes were slightly depressed in fish fed with increasing levels of CLA when compared with control (P>0.05). Dietary CLA supplementation had no effects on liver lipid content, but significantly increased the contents of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) (P<0.05) and decreased monounsaturated fatty acid (MUFA) content in both muscle and the liver. Dietary CLA inclusion resulted in significant increases of the biologically active cis-9, trans-11 and trans-10, cis-12 isomers in both tissues (P<0.05). The total accumulation of CLA was higher in the liver (3.83%, w/w) than in muscle (3.77%, w/w) when fed with 4% (w/w) CLA. This study demonstrates that large yellow croakers are capable of absorbing and depositing CLA and long-chain n-3 PUFA in the liver and muscle, showing that this species fed with CLA could be an important human food source for these healthful fatty acids.

  19. Effects of butter naturally enriched with conjugated linoleic acid and vaccenic acid on blood lipids and LDL particle size in growing pigs

    Directory of Open Access Journals (Sweden)

    Haug Anna

    2008-08-01

    Full Text Available Abstract Background Cow milk is a natural source of the cis 9, trans 11 isomer of conjugated linoleic acid (c9,t11-CLA and trans vaccenic acid (VA. These fatty acids may be considered as functional foods, and the concentration in milk can be increased by e.g. sunflower oil supplementation to the dairy cow feed. The objective of this study was to compare the effects of regular butter with a special butter naturally enriched in c9,t11-CLA and VA on plasma lipids in female growing pigs. The experimental period lasted for three weeks and the two diets provided daily either 5.0 g c9,t11-CLA plus 15.1 g VA or 1.3 g c9,t11-CLA plus 3.6 g VA. Results The serum concentrations of c9,t11-CLA, VA and alpha-linolenic acid were increased and myristic (14:0 and palmitic acid (16:0 were reduced in the pigs fed the CLA+VA-rich butter-diet compared to regular butter, but no differences in plasma concentrations of triacylglycerol, cholesterol, HDL-cholesterol, LDL-cholesterol, LDL particle size distribution or total cholesterol/HDL cholesterol were observed among the two dietary treatment groups. Conclusion Growing pigs fed diets containing butter naturally enriched in about 20 g c9,t11-CLA plus VA daily for three weeks, had increased serum concentrations of alpha-linolenic acid and decreased myristic and palmitic acid compared to pigs fed regular butter, implying a potential benefit of the CLA+VA butter on serum fatty acid composition. Butter enriched in CLA+VA does not appear to have significant effect on the plasma lipoprotein profile in pigs.

  20. Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands.

    Science.gov (United States)

    Rist, Lukas; Mueller, André; Barthel, Christiane; Snijders, Bianca; Jansen, Margje; Simões-Wüst, A Paula; Huber, Machteld; Kummeling, Ischa; von Mandach, Ursula; Steinhart, Hans; Thijs, Carel

    2007-04-01

    The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50-90 % organic dairy/meat, 0.29 wt%, n 33, P = 0.02) and to a strict organic diet (>90 % organic dairy/meat, 0.34 wt%, n 37, P acid). Hence, the levels of CLA and TVA in human milk can be modulated if breastfeeding mothers replace conventional dairy and/or meat products by organic ones. A potential contribution of CLA and TVA to health improvement is briefly discussed.

  1. Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-Mercaptopropionic Acid and CdTe-Mercaptosuccinic Acid Quantum Dots.

    Science.gov (United States)

    Singh, Gurpal; Kumar, Manoj; Soni, Udit; Arora, Vikas; Bansal, Vivek; Gupta, Dikshi; Bhat, Madhusudan; Dinda, Amit K; Sapra, Sameer; Singh, Harpal

    2016-01-01

    CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

  2. Synthesis and isolation of trans-7,cis-9 octadecadienoic acid and other CLA isomers by base conjugation of partially hydrogenated gamma-linolenic acid.

    Science.gov (United States)

    Delmonte, Pierluigi; Roach, John A G; Mossoba, Magdi M; Morehouse, K M; Lehmann, Lutz; Yurawecz, Martin P

    2003-05-01

    CLA is of considerable interest because of reported potentially beneficial effects in animal studies. CLA, while not yet unambiguously defined, is a mixture of octadecadienoic acids with conjugated double bonds. The major isomer in natural products is generally considered to be cis-9,trans-11-octadecadienoic acid (c9,t11), which represents > 75% of the total CLA in most cases. Other isomers are drawing increased attention. The t7,c9 isomer, which is often the second-most prevalent CLA in natural products, has been reported to represent as much as 40% of total CLA in milk from cows fed a high-fat diet. The need for a reference material became apparent in a recent study directed specifically at measuring t7,c9-CLA in milk, plasma, and rumen. A suitable standard mixture was produced by stirring 0.5 g of gamma-linolenic acid (all cis-6,9,12-C18.3) with 100 mL of 10% hydrazine hydrate in methanol for 2.5 h at 45 degrees C. The solution was diluted with H2O and acidified with HCI. The resulting partially hydrogenated FA were extracted with ether/petroleum ether, dried with Na2SO4, and conjugated by adding of 6.6% KOH in ethlylene glycol and heating for 1.5 h at 150-160 degrees C. Approximately 20 mg each of cis-6,trans-8; trans-7,cis-9; cis-9,trans-11; and trans- 10,cis-12 were obtained along with other FA. Methyl esters (FAME) of these four cis/trans isomers were resolved by Ag+ HPLC (UV 233) and partially resolved by GC/(MS or FID) (CP-Sil 88). Treatment of these FAME with 12 yielded all possible cis/trans (geometric) isomers for the four positions 6,8; 7,9; 9,11; and 10,12.

  3. Molecular targets of omega 3 and conjugated linoleic fatty acids – micromanaging cellular response

    Directory of Open Access Journals (Sweden)

    Francesco eVisioli

    2012-02-01

    Full Text Available Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and CLA, as paradigmatic molecules that can be explored both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.

  4. Effect of dietary conjugated linoleic acid (CLA) on the growth and ...

    African Journals Online (AJOL)

    p4208528

    depots, specifically retroperitoneal and epididymal white adipose tissue masses and ... et al., 2001; Oku et al., 2003) and increased lipolysis and fatty acid oxidation .... (HDL-C), total triglyceride (TG) concentrations and lipoprotein lipase (LPL) ...

  5. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

    Directory of Open Access Journals (Sweden)

    Suriya Kumari Ramiah

    2015-09-01

    Full Text Available Since conjugated linoleic acid (CLA has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR and liver fatty acid binding protein (LFABP in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

  6. Design of antimicrobial peptides conjugated biodegradable citric acid derived hydrogels for wound healing.

    Science.gov (United States)

    Xie, Zhiwei; Aphale, Nikhil V; Kadapure, Tejaswi D; Wadajkar, Aniket S; Orr, Sara; Gyawali, Dipendra; Qian, Guoying; Nguyen, Kytai T; Yang, Jian

    2015-12-01

    Wound healing is usually facilitated by the use of a wound dressing that can be easily applied to cover the wound bed, maintain moisture, and avoid bacterial infection. In order to meet all of these requirements, we developed an in situ forming biodegradable hydrogel (iFBH) system composed of a newly developed combination of biodegradable poly(ethylene glycol) maleate citrate (PEGMC) and poly(ethylene glycol) diacrylate (PEGDA). The in situ forming hydrogel systems are able to conform to the wound shape in order to cover the wound completely and prevent bacterial invasion. A 2(k) factorial analysis was performed to examine the effects of polymer composition on specific properties, including the curing time, Young's modulus, swelling ratio, and degradation rate. An optimized iFBH formulation was achieved from the systematic factorial analysis. Further, in vitro biocompatibility studies using adult human dermal fibroblasts (HDFs) confirmed that the hydrogels and degradation products are not cytotoxic. The iFBH wound dressing was conjugated and functionalized with antimicrobial peptides as well. Evaluation against bacteria both in vitro and in vivo in rats demonstrated that the peptide-incorporated iFBH wound dressing offered excellent bacteria inhibition and promoted wound healing. These studies indicated that our in situ forming antimicrobial biodegradable hydrogel system is a promising candidate for wound treatment.

  7. Relationship between osmotic stress and polyamines conjugated to the deoxyribonucleic acid-protein in wheat seedling roots

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The contents of covalently conjugated polyamines (CC-PAs) and noncovalently conjugated polyamines (NCC-PAs) to deoxyribonucleic acid-protein (DNP) isolated from wheat (Triticum aestivum L.) seedling roots under osmotic stress were detected. Results showed that after osmotic stress treatment for 7 d, the levels in NCC-spermine (NCC-Spm) and NCC-spermidine (NCC-Spd) of drought-tolerant Yumai No. 18 cv. increased more markedly than that of drought-sensitive Yangmai No. 9 cv., while the NCC-putrescine (NCC-Put) could not be statistically detected in two cultivars. Exogenous Spm treatment alleviated osmotic stress injury to Yangmai No. 9 cv. seedlings, coupled with marked increases of NCC-Spm and NCC-Spd levels of this cultivar. Under PEG osmotic stress, the concomitant treatment of drought-tolerant Yumai No. 18 cv.seedlings with methylglyoxyl-bis (guanylhydrazone) (MGBG), an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), aggravated osmotic stress injury to this cultivar, coupled with market decreases of the NCC-Spm and NCC- Spd levels. The levels in CC-Put and CC-Spd of drought-tolerant Yumai No. 18 cv. increased more markedly than that of drought-sensitive Yangmai No. 9 cv. Under osmotic stress. The treatment of drought-tolerant Yumai No. 18 cv. seedlings with phenanthrolin (o-Phen), an inhibitor of transglutaminase (TGase), aggravated osmotic stress injury to this cultivar, coupled with a reduction of sum contents of CC-Put+CC-Spd. These results suggested that NCC-Spm and NCC-Spd, together with CC-Put and CC-Spd, in DNP of roots could enhance tolerance of the wheat seedlings to osmotic stress.

  8. Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.

    Science.gov (United States)

    Donazzolo, Elena; Gucciardi, Antonina; Mazzier, Daniela; Peggion, Cristina; Pirillo, Paola; Naturale, Mauro; Moretto, Alessandro; Giordano, Giuseppe

    2017-04-01

    Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3-TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Conjugates of amino acids and peptides with 5-o-mycaminosyltylonolide and their interaction with the ribosomal exit tunnel.

    Science.gov (United States)

    Shishkina, Anna; Makarov, Gennady; Tereshchenkov, Andrey; Korshunova, Galina; Sumbatyan, Nataliya; Golovin, Andrey; Svetlov, Maxim; Bogdanov, Alexey

    2013-11-20

    During protein synthesis the nascent polypeptide chain (NC) extends through the ribosomal exit tunnel (NPET). Also, the large group of macrolide antibiotics binds in the nascent peptide exit tunnel. In some cases interaction of NC with NPET leads to the ribosome stalling, a significant event in regulation of translation. In other cases NC-ribosome interactions lead to pauses in translation that play an important role in cotranslational folding of polypeptides emerging from the ribosome. The precise mechanism of NC recognition in NPET as well as factors that determine NC conformation in the ribosomal tunnel are unknown. A number of derivatives of the macrolide antibiotic 5-O-mycaminosyltylonolide (OMT) containing N-acylated amino acid or peptide residues were synthesized in order to study potential sites of NC-NPET interactions. The target compounds were prepared by conjugation of protected amino acids and peptides with the C23 hydroxyl group of the macrolide. These OMT derivatives showed high although varying abilities to inhibit the firefly luciferase synthesis in vitro. Three glycil-containing derivatives appeared to be strong inhibitors of translation, more potent than parental OMT. Molecular dynamics (MD) simulation of complexes of tylosin, OMT, and some of OMT derivatives with the large ribosomal subunit of E. coli illuminated a plausible reason for the high inhibitory activity of Boc-Gly-OMT. In addition, the MD study detected a new putative site of interaction of the nascent polypeptide chain with the NPET walls.

  10. Effects of Lactation Stage and Individual Performance on Milk -9, -11 Conjugated Linoleic Acids Content in Dairy Cows

    Directory of Open Access Journals (Sweden)

    T. Wang

    2013-02-01

    Full Text Available The goal of this study was to evaluate the effects of lactation stage and individual performance on milk cis-9, trans-11 conjugated linoleic acid (CLA content in dairy cows. In experiment 1, the milk cis-9, trans-11 CLA content from dairy cows in early (0.33±0.014%, middle (0.37±0.010%, and late stages (0.44±0.020% showed significant differences (p<0.05; and the individual contents of the major fatty acids, especially cis-9, trans-11 CLA in cows of the same lactation were also variable. In the second experiment design as a validation test, our results once again showed that the individual contents of cis-9, trans-11 CLA were various, and a difference of about 2-fold (0.55% vs 0.95% was observed, although the animals were offered same diet. These data demonstrated that lactation stage and individual performance have considerable effects on milk cis-9, trans-11 CLA contents.

  11. Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity.

    Science.gov (United States)

    Withey, Jeffrey H; Nag, Drubhajyoti; Plecha, Sarah C; Sinha, Ritam; Koley, Hemanta

    2015-12-01

    The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Isolation, molecular characterization and screening of indigenous lactobacilli for their abilities to produce bioactive conjugated linoleic acid (CLA).

    Science.gov (United States)

    Dahiya, Dinesh Kumar; Puniya, Anil Kumar

    2017-03-01

    Ingestion of conjugated linoleic acid poised many health benefits; however, amount of CLA one can get through generalized diet in is inadequate in exerting the desired benefits. Therefore, presence of CLA producing lactobacilli in dairy fermented foods has a tremendous potential to increase the CLA content. Therefore, present study was focused to isolate and characterize CLA producing lactobacilli from different dairy products and human faeces. Arguably, 283 lactobacilli were isolated from various sources and tested for CLA production. Fifty-seven CLA producing (≥20 µg/ml) lactobacilli were selected from screening in de Man, Rogosa and Sharpe (MRS) broth and reconstituted with skim milk (SM), supplemented with 0.5 mg/ml of linoleic acid. Positive strains were classified into-L. plantarum (44%), L. gasseri (30%), L. fermentum (21%) and L. salivarius (5%) species. Nineteen most efficient strains (CLA ≥25 µg/ml) were further assessed in SM for CLA production. Total 08 strains produced significantly higher CLA in SM than MRS and also produced cis 9, trans 11, trans 10, cis 12 and trans 9, trans 11 isomers. Overall, L. plantarum HIF15 was reported as the best producer of CLA and other 08 lactobacilli may be utilized for the formulation of CLA-enriched functional foods to support these bacteria to synthesize CLA in the human gut.

  13. Effects of supplemental conjugated linoleic acids (CLA) on fresh and post-thaw sperm quality of Holstein bulls.

    Science.gov (United States)

    Karimi, R; Towhidi, A; Zeinoaldini, S; Rezayazdi, K; Mousavi, M; Safari, H; Martinez-Pastor, F

    2017-02-07

    This study was designed to investigate the effects of feeding-protected conjugated linoleic acid (CLA) on the semen production and sperm freezability in Holstein bulls. Twelve bulls were randomly assigned to two groups (n = 6 per group). Bulls received the normal diet (control group) or the normal diet top-dressed with 50 g of CLA (treated group) for 10 weeks. The control group received 40 g/day calcium soap of fatty acid. Fresh and post-thaw semen quality was assessed on ejaculates collected at the 0, 4, 6, 8 and 10 week of supplementation. Semen evaluations including sperm concentration, motion characteristics (subjective and computer-assisted), viability (Eosin-Nigrosin), membrane integrity (hypo-osmotic swelling test) and abnormality were conducted. Semen volume, sperm concentration and total sperm output were not affected by dietary treatment (p > .05). The proportion of spermatozoa with abnormal morphology in fresh semen significantly increased (p CLA-fed group compared to control group. Also, in CLA-fed group, the proportion of post-thaw spermatozoa with abnormal morphology at week 10 of trial was significantly higher in CLA than control group (p CLA-fed group, although dietary supplementation did not affect other CASA parameters or viability in fresh and frozen-thawed sperm. In this study, CLA supplementation had little positive effect on fresh or post-thaw sperm quality of Holstein bulls.

  14. Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity

    Science.gov (United States)

    Nag, Drubhajyoti; Plecha, Sarah C.; Sinha, Ritam; Koley, Hemanta

    2015-01-01

    The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival. PMID:26392502

  15. Supramolecular assemblies of a conjugate of nucleobase, amino acids, and saccharide act as agonists for proliferation of embryonic stem cells and development of zygotes.

    Science.gov (United States)

    Du, Xuewen; Zhou, Jie; Guvench, Olgun; Sangiorgi, Frank O; Li, Xinming; Zhou, Ning; Xu, Bing

    2014-06-18

    The synthetic challenges in glycobiology and glycochemistry hamper the development of glycobiomaterials for biomedicine. Here we report the use of molecular self-assembly to sidestep the laborious synthesis of complex glycans for promoting the proliferation of murine embryonic stem (mES) cells. Our study shows that the supramolecular assemblies of a small molecule conjugate of nucleobase, amino acids, and saccharide, as a de novo glycoconjugate, promote the proliferation of mES cells and the development of zygotes into blastocysts of mouse. Molecular engineering confirms that each motif (i.e., adenine, Arg-Gly-Asp (RGD) domain, and glucosamine) is indispensable for the observed activity of the conjugate. As the first example of using assemblies of the molecular conjugates of multiple fundamental biological building blocks to control cell behaviors, this work illustrates an unprecedented approach to use supramolecular assemblies as multifunctional mimics of glycoconjugates.

  16. p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Swami, Rajan; Singh, Indu [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India); Kulhari, Hitesh [CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry & Pharmacology Division (India); Jeengar, Manish Kumar [National Institute of Pharmaceutical Education & Research (NIPER), Departmentof Pharmacology (India); Khan, Wahid, E-mail: wahid@niperhyd.ac.in; Sistla, Ramakrishna, E-mail: sistla@iict.res.in, E-mail: rksistla@yahoo.com [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India)

    2015-06-15

    Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by {sup 1}HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere{sup ®}). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

  17. Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles

    Science.gov (United States)

    Teow, Yiwei; Valiyaveettil, Suresh

    2010-12-01

    Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized viareduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 μg ml-1 for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

  18. Colon-specific drug delivery systems based on cyclodextrin prodrugs: In vivo evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates

    Institute of Scientific and Technical Information of China (English)

    Mei-Juan Zou; Gang Cheng; Hirokazu Okamoto; Xiu-Hua Hao; Feng An; Fu-De Cui; Kazumi Danjo

    2005-01-01

    AIM: To investigate the release of cyclodextrin-5-amino salicylic acid (CyD-5-ASA) in cecum and colon.METHODS: An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cyclodextrins (CyDs) through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat' s gastrointestinal tract after the oral administration was investigated.RESULTS: The 5-ASA concentration in the rat's stomach and small intestine after the oral administration of CyD5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate throughthe stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-5-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone.CONCLUSION: CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.

  19. Enantioselective conjugate additions of α-amino radicals via cooperative photoredox and Lewis acid catalysis.

    Science.gov (United States)

    Ruiz Espelt, Laura; McPherson, Iain S; Wiensch, Eric M; Yoon, Tehshik P

    2015-02-25

    We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

  20. Preclinical Evaluation to Specifically Target Ovarian Cancer with Folic Acid-Conjugated Nanoceria

    Science.gov (United States)

    2014-08-01

    due, in part, to the valence structure of the cerium atom combined with inherent defects in the crystal lattice structure, which are magnified at the...aspartate aminotransferase, AST; alanine aminotransferase, ALT; albumin) and kidney function (creatinine; urea ; albumin, uric acid) in plasma collected...labelled as FA) treated mice as per the manufacturer’s instructions, ALT ( Alanine Transaminase), AST (Aspartate Transaminase), Albumin

  1. Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates

    DEFF Research Database (Denmark)

    Hansen, Anna Mette; Bonke, Gitte; Larsen, Camilla Josephine

    2016-01-01

    Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the p...

  2. Synthesis and cytotoxic activity of two novel 1-dodecylthio-2-decyloxypropyl-3-phosphatidic acid conjugates with gemcitabine and cytosine arabinoside.

    Science.gov (United States)

    Alexander, Richard L; Morris-Natschke, Susan L; Ishaq, Khalid S; Fleming, Ronald A; Kucera, Gregory L

    2003-09-11

    Cytosine arabinoside (ara-C) and gemcitabine (dFdC) are two standard chemotherapy drugs used in the treatment of patients with various cancers. To alter the pharmacokinetic and pharmacodynamic properties of these molecules, we conjugated a synthetic phospholipid to both ara-C and dFdC and investigated their chemotherapeutic potential. The dFdC conjugate had greater cytotoxic activity compared with the ara-C conjugate and demonstrated notable cytotoxicity against all human cell lines tested.

  3. Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates

    Science.gov (United States)

    Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

    2015-03-01

    Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE

  4. Microencapsulated conjugated linoleic acid associated with hypocaloric diet reduces body fat in sedentary women with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Carvalho RF

    2012-12-01

    Full Text Available Roberta F Carvalho,1 Sofia K Uehara,2 Glorimar Rosa1,21Medicine Department, Federal University of Rio de Janeiro, Brazil; 2Nutrition and Dietetic Department, Josué de Castro Institute of Nutrition, Federal University of Rio de Janeiro, BrazilBackground: Animal studies have suggested beneficial effects of conjugated linoleic acid (CLA in reducing body fat mass and improvement in the serum lipid profile and glycemia. However, these effects are controversial in humans. The purpose of this study was to investigate the effects of microencapsulated CLA supplementation on body composition, body mass index, waist circumference, and blood pressure in sedentary women with metabolic syndrome.Methods: This study was a placebo-controlled and randomized clinical trial. Fourteen women diagnosed with metabolic syndrome received light strawberry jam enriched or not with microencapsulated CLA (3 g/day as a mixture of 38.57% cis-9, trans-11, and 39.76% trans-10, cis-12 CLA isomers associated with a hypocaloric diet for 90 days. The subjects were monitored to assess variables associated with the metabolic syndrome, in addition to assessing adherence with the intervention.Results: There were no significant effects of microencapsulated CLA on the lipid profile or blood pressure. Mean plasma insulin concentrations were significantly lower in women supplemented with microencapsulated CLA (Δ T90 – T0 = −12.87 ± 4.26 µU/mL, P = 0.02. Microencapsulated CLA supplementation did not alter the waist circumference, but there was a reduction in body fat mass detected after 30 days (Δ = −2.68% ± 0.82%, P = 0.02, which was maintained until the 90-day intervention period (Δ = −3.32% ± 1.41%, P = 0.02 in the microencapsulated CLA group. The placebo group showed this effect only after 90 days (Δ = −1.97% ± 0.60%, P = 0.02, but had a reduced waist circumference (Δ T90 – T0 = −4.25 ± 1.31 cm, P = 0.03.Conclusion: Supplementation with mixed

  5. Effects of trans-10,cis-12 conjugated linoleic acid on body fat and serum lipids in young and adult hamsters.

    Science.gov (United States)

    Navarro, V; Miranda, J; Churruca, I; Fernández-Quintela, A; Rodríguez, V M; Portillo, M P

    2006-06-01

    The aim of the present work was to determine whether t-10, c-12 conjugated linoleic acid (CLA) feeding was able to reduce body fat accumulation and improve the serum lipid profile in adult hamsters fed an atherogenic diet, in order to compare these effects with those observed in young growing hamsters. Young and adult hamsters were fed semi-purified atherogenic diets supplemented with 0.5 % linoleic acid or 0.5% t-10, c-12 CLA for 6 weeks. Body weight and food intake were measured every two days. Adipose tissue from different anatomical locations, liver and gastrocnemious muscle were dissected and weighed. Cholesterol, triacylglycerols, non-esterified fatty acids and proteins were determined spectrophotometrically and water content by gravimetry. In young hamsters, no significant differences were found in food intake, final body weight and gastrocnemious muscle weight. White adipose tissue weights were reduced, liver weight was increased and cholesterol and triacyl-glycerols in both serum and liver were reduced. In adult hamsters, CLA feeding decreased food intake and adipose tissue weights. No changes were observed in other parameters. The present study demonstrates that age has an influence in hamster responsiveness to t-10, c-12 CLA because, although when this isomer is added to an atherogenic diet it reduces body fat accumulation in both young and adults hamsters, the lessening of the effects on serum lipids brought about by atherogenic feeding is only observed in young animals. Moreover, it is clear that liver is a target for CLA in young but not in adult hamsters.

  6. Gene expression profiles in rat mesenteric lymph nodes upon supplementation with Conjugated Linoleic Acid during gestation and suckling

    Directory of Open Access Journals (Sweden)

    Rivero Montserrat

    2011-04-01

    Full Text Available Abstract Background Diet plays a role on the development of the immune system, and polyunsaturated fatty acids can modulate the expression of a variety of genes. Human milk contains conjugated linoleic acid (CLA, a fatty acid that seems to contribute to immune development. Indeed, recent studies carried out in our group in suckling animals have shown that the immune function is enhanced after feeding them with an 80:20 isomer mix composed of c9,t11 and t10,c12 CLA. However, little work has been done on the effects of CLA on gene expression, and even less regarding immune system development in early life. Results The expression profile of mesenteric lymph nodes from animals supplemented with CLA during gestation and suckling through dam's milk (Group A or by oral gavage (Group B, supplemented just during suckling (Group C and control animals (Group D was determined with the aid of the specific GeneChip® Rat Genome 230 2.0 (Affymettrix. Bioinformatics analyses were performed using the GeneSpring GX software package v10.0.2 and lead to the identification of 89 genes differentially expressed in all three dietary approaches. Generation of a biological association network evidenced several genes, such as connective tissue growth factor (Ctgf, tissue inhibitor of metalloproteinase 1 (Timp1, galanin (Gal, synaptotagmin 1 (Syt1, growth factor receptor bound protein 2 (Grb2, actin gamma 2 (Actg2 and smooth muscle alpha actin (Acta2, as highly interconnected nodes of the resulting network. Gene underexpression was confirmed by Real-Time RT-PCR. Conclusions Ctgf, Timp1, Gal and Syt1, among others, are genes modulated by CLA supplementation that may have a role on mucosal immune responses in early life.

  7. The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid*♦

    Science.gov (United States)

    Turell, Lucía; Vitturi, Darío A.; Coitiño, E. Laura; Lebrato, Lourdes; Möller, Matías N.; Sagasti, Camila; Salvatore, Sonia R.; Woodcock, Steven R.; Alvarez, Beatriz; Schopfer, Francisco J.

    2017-01-01

    Nitroalkene fatty acids are formed in vivo and exert protective and anti-inflammatory effects via reversible Michael addition to thiol-containing proteins in key signaling pathways. Nitro-conjugated linoleic acid (NO2-CLA) is preferentially formed, constitutes the most abundant nitrated fatty acid in humans, and contains two carbons that could potentially react with thiols, modulating signaling actions and levels. In this work, we examined the reactions of NO2-CLA with low molecular weight thiols (glutathione, cysteine, homocysteine, cysteinylglycine, and β-mercaptoethanol) and human serum albumin. Reactions followed reversible biphasic kinetics, consistent with the presence of two electrophilic centers in NO2-CLA located on the β- and δ-carbons with respect to the nitro group. The differential reactivity was confirmed by computational modeling of the electronic structure. The rates (kon and koff) and equilibrium constants for both reactions were determined for different thiols. LC-UV-Visible and LC-MS analyses showed that the fast reaction corresponds to β-adduct formation (the kinetic product), while the slow reaction corresponds to the formation of the δ-adduct (the thermodynamic product). The pH dependence of the rate constants, the correlation between intrinsic reactivity and thiol pKa, and the absence of deuterium solvent kinetic isotope effects suggested stepwise mechanisms with thiolate attack on NO2-CLA as rate-controlling step. Computational modeling supported the mechanism and revealed additional features of the transition states, anionic intermediates, and final neutral products. Importantly, the detection of cysteine-δ-adducts in human urine provided evidence for the biological relevance of this reaction. Finally, human serum albumin was found to bind NO2-CLA both non-covalently and to form covalent adducts at Cys-34, suggesting potential modes for systemic distribution. These results provide new insights into the chemical basis of NO2-CLA

  8. Effect of conjugated linoleic acid mixtures and different edible oils on body composition and lipid regulation in mice

    Directory of Open Access Journals (Sweden)

    María Victoria Scalerandi

    2014-03-01

    Full Text Available Introduction: Evidences suggest that commercial and natural conjugated linoleic acids (CLA differentially affect nutritional status and lipid metabolism. Objective: To investigate the differential effect of two types of CLA preparations supplemented to dietary fats containing different proportions of n-9, n-6 and n-3 fatty acids (FA on body composition, triacylglycerol (TG levels and lipid metabolism in mice. Methods: Growing mice were fed diets containing olive, maize and rapeseed oils supplemented with an equimolecular mixture of CLA (mix-CLA or a rumenic acid (RA-rich oil for 30 days. Body weight gain, carcass composition, tissue weights, plasma and tissue TG levels, and lipid regulation parameters were evaluated. Results: Independently of the dietary fats, mix-CLA decreased body weight gain and fat depots related to lower energy efficiency, hepatomegaly, increase of serum TG and decrease of muscle TG. Rapeseed oil prevented the hepatic steatosis observed with mix-CLA supplementation to olive and maize oils by increasing TG secretion. RA-rich oil supplementation decreased fat depots without hepatomegaly, hepatic steatosis and hypertriglyceridemia. Olive oil, by an equilibrium between FA uptake/oxidation, prevented the increase of muscle TG induced by the RA-rich oil supplementation to maize and rapeseed oils. Discussion and conclusion: The proportions of dietary unsaturated FA modulated the different mix-CLA and RA-rich oil response to lipid metabolism in mice. Finally, rapeseed oil prevented the hepatic steatosis induced by mix-CLA, and the most beneficial effects of RA-rich oil were observed when supplemented to olive oil, due to the reduced lipid accretion without changes in TG levels.

  9. Effect of Safflower Oil on Concentration of Conjugated Linoleic Acid of Kefir Prepared by Low-fat Milk.

    Science.gov (United States)

    Farsad-Naeimi, Alireza; Imani, Saeid; Arefhosseini, Seyed R; Alizadeh, Mohammad

    2015-01-01

    Conjugated linoleic acid (CLA) is a special fatty acid in dairy products with unique antioxidant and anti-cancerous effects. Kefir, a milk product, comprises normalized homogenized cow's milk, the fructose and lactulose syrup as well as a symbiotic starter which has improved probiotic characteristics. The study was aimed to discuss patents and to examine the effect of different safflower oil concentrations on CLA content of the kefir drink prepared by low-fat milk. Safflower oil was added at 0.1, 0.3 and 0.5% (V/V) to low-fat cow's milk and six formulations of kefir samples were prepared. The CLA content of the kefir products was measured at pH=6.0 and pH=6.8 by gas chromatography. Acid and bile tolerance of bacterial microenvironment in the products were also determined. Substitution of natural fat content of milk with safflower oil resulted in proportional increase in the CLA contents of kefir in a dose dependent manner. The highest concentration of CLA was found under 0.5% (V/V) of safflower oil at pH 6.0 and temperature of 37 °C. Adding the Safflower oil into milk used for kefir production, increased CLA content from 0.123 (g/100 g) in pure safflower free samples to 0.322 (g/100 g) in samples with 0.5% (V/V) of safflower oil. The current study revealed that substitution of safflower oil with natural fat of cow's milk may help the production of kefir samples with remarkable increase in CLA content of final product.

  10. A conjugated linoleic acid (CLA supplement containing trans-10, cis-12 CLA reduces milk fat synthesis in lactating goats

    Directory of Open Access Journals (Sweden)

    D. Bauman

    2010-04-01

    Full Text Available The efficacy of a lipid-encapsulated trans-10, cis-12 conjugated linoleic acid supplement (LE-CLA on milk production and milk fatty acid (FA profile was investigated. Thirty multiparous Alpine lactating goats (50 ± 7.4 kg in late lactation were used in a 3 × 3 Latin square design. Does were fed a diet of bermudagrass hay, dehydrated alfalfa pellets, and concentrate. Does were randomly allocated to three treatments; A unsupplemented (Control, B supplemented with 30 g/d LE-CLA (low-dose; LLE, and C supplemented with 60 g/d LE-CLA (high-dose; HLE. Milk yield, DMI, and milk protein content and yield were unaffected by treatment (P > 0.05. Compared with Control, milk fat yield was reduced 8.1% by the LLE treatment and 21.2% by the HLE treatment (P < 0.001, with milk fat content reduced 4.8 and 17.6% by the LLE and HLE treatments, respectively (P < 0.001. Milk fat content of trans-10, cis-12 CLA was 0.03, 0.09 and 0.19 g/100 g of fatty acids for the Control, LLE and HLE treatments, respectively. The transfer efficiency of trans-10, cis-12 CLA from the two levels of CLA supplement into milk fat was not different between treatments and averaged 1.85%. In conclusion, trans-10, cis- 12 CLA reduced milk fat synthesis in lactating goats in a manner similar to that observed for lactating dairy cows and sheep. However, dose-response comparisons suggest that the degree of reduction in milk fat synthesis is less in goats compared with sheep and dairy cows.

  11. The influence of dietary nitrogen reduction and conjugated linoleic acid supply to dairy cows on fatty acids in milk and their transfer to ripened cheese.

    Science.gov (United States)

    Schiavon, S; Cesaro, G; Cecchinato, A; Cipolat-Gotet, C; Tagliapietra, F; Bittante, G

    2016-11-01

    The aim of this study was to investigate the consequences of reducing the dietary crude protein content, with or without a supply of protected conjugated linoleic acid (CLA), on the milk fatty acid (FA) yield and recovery in 90d ripened cheese. Twenty mid-lactation Friesian dairy cows were reared for 4 periods of 3wk each in groups of 5, following a 4×4 Latin square design. Cows were fed 4 different rations, consisting of a combination of the 2 dietary crude protein levels [150 (CP15) or 123 (CP12) g of crude protein/kg of dry matter], with or without a conjugated linoleic acid supply (80g/d, providing 5.57 and 5.40g/d of C18:2 cis-9,trans-11 and C18:2 trans-10,cis-12, respectively). Milk yield was recorded. Twice in each period, milk samples were analyzed for protein, fat, and lactose content, and 10 L milk samples (pooled by group) were processed to produce 96 cheeses, which were ripened for 90d. Milk and cheese fat were analyzed for their FA profiles. Milk and cheese FA were expressed as daily yields and relative proportions, and nutrient recoveries were computed. Dietary crude protein reduction had small or no effects on the yield and relative presence of FA in milk and cheese, except for a small increase in mid-chain branched saturated fatty acids. The CLA supply strongly reduced the yield of various categories of FA, and had major effects on short-chain FA of de novo synthesis, leading to changes in the relative proportions of the various FA in milk and cheese. The addition of CLA tended to reduce uniformly the recovery of all milk constituents and of short-, medium-, and long-chain FA groups, but we observed large differences among individual FA with apparent recoveries ranging between 640 and 1,710g/kg. The highest recoveries were found for polyunsaturated long-chain FA, the lowest for saturated or monounsaturated short- or medium-chain FA. A notable rearrangement of these FA components, particularly the minor ones, took place during ripening.

  12. Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics.

    Science.gov (United States)

    Low, Stewart A; Yang, Jiyuan; Kopeček, Jindřich

    2014-11-19

    Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.

  13. Phytosynthesis of gold nanoparticles using Mappia foetida leaves extract and their conjugation with folic acid for delivery of doxorubicin to cancer cells.

    Science.gov (United States)

    Yallappa, S; Manjanna, J; Dhananjaya, B L; Vishwanatha, U; Ravishankar, B; Gururaj, H

    2015-09-01

    Mappia foetida leaves extract is used as bioreductant for the synthesis of gold nanoparticles and their application in the efficient delivery of doxorubicin to human cancer cells is reported here. The formation of gold nanoparticles is evident from their characteristic optical absorption at ~560 nm. X-ray diffraction pattern of gold nanoparticles confirmed their fcc structure. Fourier transform infrared spectroscopy shows the bioactive molecules from plant extract capped on the surface of gold nanoparticles and conjugation of doxorubicin along with activated folic acid as navigational molecules for targeted drug delivery. Such a conjugation of gold nanoparticles is characterized by their weight loss, ~35-40 %, due to thermal degradation of plant biomass and conjugated drug along with receptor, as observed in thermogravimetric analysis. The spherical shaped gold nanoparticles (Φ 10-20 nm) are observed by field emission scanning electron microscopy and transmission electron microscopy images and the expected elemental composition by energy dispersive X-ray spectroscopy. Gold nanoparticles conjugated with activated folic acid and doxorubicin complex is found to be toxic for human cancer cells viz., MDA-MB-231, HeLa, SiHa and Hep-G2. Furthermore, the amount of drug released was maximum at pH 5.3 (an ambient condition for intravenous cancer drugs) followed by pH 7.2 and pH 6.8.

  14. Elevated salicylic acid levels conferred by increased expression of ISOCHORISMATE SYNTHASE 1 contribute to hyperaccumulation of SUMO1 conjugates in the Arabidopsis mutant early in short days 4.

    Science.gov (United States)

    Villajuana-Bonequi, Mitzi; Elrouby, Nabil; Nordström, Karl; Griebel, Thomas; Bachmair, Andreas; Coupland, George

    2014-07-01

    Post-translational modification of proteins by attachment of small ubiquitin-like modifier (SUMO) is essential for plant growth and development. Mutations in the SUMO protease early in short days 4 (ESD4) cause hyperaccumulation of conjugates formed between SUMO and its substrates, and phenotypically are associated with extreme early flowering and impaired growth. We performed a suppressor mutagenesis screen of esd4 and identified a series of mutants called suppressor of esd4 (sed), which delay flowering, enhance growth and reduce hyperaccumulation of SUMO conjugates. Genetic mapping and genome sequencing indicated that one of these mutations (sed111) is in the gene salicylic acid induction-deficient 2 (SID2), which encodes ISOCHORISMATE SYNTHASE I, an enzyme required for biosynthesis of salicylic acid (SA). Analyses showed that compared with wild-type plants, esd4 contains higher levels of SID2 mRNA and about threefold more SA, whereas sed111 contains lower SA levels. Other sed mutants also contain lower SA levels but are not mutant for SID2, although most reduce SID2 mRNA levels. Therefore, higher SA levels contribute to the small size, early flowering and elevated SUMO conjugate levels of esd4. Our results support previous data indicating that SUMO homeostasis influences SA biosynthesis in wild-type plants, and also demonstrate that elevated levels of SA strongly increase the abundance of SUMO conjugates.

  15. Selective detection of carbohydrates and their peptide conjugates by ESI-MS using synthetic quaternary ammonium salt derivatives of phenylboronic acids.

    Science.gov (United States)

    Kijewska, Monika; Kuc, Adam; Kluczyk, Alicja; Waliczek, Mateusz; Man-Kupisinska, Aleksandra; Lukasiewicz, Jolanta; Stefanowicz, Piotr; Szewczuk, Zbigniew

    2014-06-01

    We present new tags based on the derivatives of phenylboronic acid and apply them for the selective detection of sugars and peptide-sugar conjugates in mass spectrometry. We investigated the binding of phenylboronic acid and its quaternary ammonium salt (QAS) derivatives to carbohydrates and peptide-derived Amadori products by HR-MS and MS/MS experiments. The formation of complexes between sugar or sugar-peptide conjugates and synthetic tags was confirmed on the basis of the unique isotopic distribution resulting from the presence of boron atom. Moreover, incorporation of a quaternary ammonium salt dramatically improved the efficiency of ionization in mass spectrometry. It was found that the formation of a complex with phenylboronic acid stabilizes the sugar moiety in glycated peptides, resulting in simplification of the fragmentation pattern of peptide-derived Amadori products. The obtained results suggest that derivatization of phenylboronic acid as QAS is a promising method for sensitive ESI-MS detection of carbohydrates and their conjugates formed by non-enzymatic glycation or glycosylation.

  16. Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-MPA and CdTe-MSA Quantum Dots.

    Science.gov (United States)

    Singh, Gurpal; Kumar, Manoj; Soni, Udit; Arora, Vikas; Bansal, Vivek; Gupta, Dikshi; Bhat, Madhusudan; Dinda, Amit K; Sapra, Sameer; Singh, Harpal

    2015-12-01

    CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

  17. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs

    DEFF Research Database (Denmark)

    Tous, Nuria; Theil, Peter Kappel; Lauridsen, Charlotte

    2012-01-01

    in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1......, both P muscle and reduced (P increased (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P ... (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography...

  18. Influence of fish oil in the concentration of conjugated linoleic acid and omega 6 and 3 in buffalo milk

    Directory of Open Access Journals (Sweden)

    E.M. Patiño

    2012-04-01

    Full Text Available The aim of this research work was to investigate the influence of fish oil supplementation on the concentration of conjugated linoleic acid (CLA and omega 6 and 3 in samples of buffalo milk. A total of 24 female buffaloes separated at random into three groups were fed for 49 days with: natural pasture (group I, supplemented with 70mL of fish oil (group II and 140mL of fish oil (group III. In the experiment the concentration of CLA showed differences (P<0.05 among the three groups, with a maximum of 7.14mg/g fat in group II. No significant differences were found in omega-6 among the three groups. The highest value of 3.82mg/g fat corresponded to group I, whicht had not been supplemented with fish oil. Significant differences were observed in omega 3 (P<0.05 in groups II and III with respect to group I. The highest average value of 2.42mg/g fat was obtained in group III. The closest relationship omega 6/3 (1.37:1 was observed in group III. As a result, the diets of groups II and III, which included fish oil, increased significantly the content of CLA and omega 3 with reductions in levels of omega 6.

  19. Counterion distribution surrounding spherical nucleic acid-Au nanoparticle conjugates probed by small-angle x-ray scattering.

    Science.gov (United States)

    Kewalramani, Sumit; Zwanikken, Jos W; Macfarlane, Robert J; Leung, Cheuk-Yui; Olvera de la Cruz, Monica; Mirkin, Chad A; Bedzyk, Michael J

    2013-12-23

    The radial distribution of monovalent cations surrounding spherical nucleic acid-Au nanoparticle conjugates (SNA-AuNPs) is determined by in situ small-angle x-ray scattering (SAXS) and classical density functional theory (DFT) calculations. Small differences in SAXS intensity profiles from SNA-AuNPs dispersed in a series of solutions containing different monovalent ions (Na(+), K(+), Rb(+), or Cs(+)) are measured. Using the "heavy ion replacement" SAXS (HIRSAXS) approach, we extract the cation-distribution-dependent contribution to the SAXS intensity and show that it agrees with DFT predictions. The experiment-theory comparisons reveal the radial distribution of cations as well as the conformation of the DNA in the SNA shell. The analysis shows an enhancement to the average cation concentration in the SNA shell that can be up to 15-fold, depending on the bulk solution ionic concentration. The study demonstrates the feasibility of HIRSAXS in probing the distribution of monovalent cations surrounding nanoparticles with an electron dense core (e.g., metals).

  20. Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/MpJ-Fas(lpr) mice.

    Science.gov (United States)

    Bergamo, Paolo; Luongo, Diomira; Maurano, Francesco; Mazzarella, Giuseppe; Stefanile, Rosita; Rossi, Mauro

    2006-11-01

    Conjugated linoleic acid (CLA), a naturally occurring peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, exhibits proapoptotic, immunomodulatory, and anticancer properties. In this study, we examined the biological effects of CLA administration in the MRL/MpJ-Fas(lpr) mouse, an animal model of systemic lupus erythematosus (SLE). We found that CLA exerted apparently opposed activities in in vitro experiments, depending on its concentration: 100 microM CLA downregulated IFN gamma synthesis and cell proliferation of splenocytes, in association with apoptosis induction and a decrease of intracellular thiols (GSH + GSSG), whereas 25 microM CLA did not significantly influence cell proliferation but enhanced the expression of gamma-glutamylcysteine ligase catalytic subunit (GCLC) and intracellular GSH concentration. Interestingly, the antiproliferative effect at 100 microM was not inhibited by the PPAR gamma antagonist GW9662. In vivo, CLA administration drastically reduced SLE signs (splenomegaly, autoantibodies, and cytokine synthesis), a condition paralleled by the enhancement of GCLC expression and intracellular GSH content. Moreover, CLA administration significantly downregulated nuclear factor kappaB activity independent of PPAR gamma activation and apoptosis induction. In conclusion, enhanced GSH content and GCLC expression in CLA-treated mice suggest a novel biochemical mechanism underlying its immunomodulatory activity and the beneficial effects on murine SLE signs.

  1. Design and synthesis of chiral 2H-chromene-N-imidazolo-amino acid conjugates as aldose reductase inhibitors.

    Science.gov (United States)

    Gopinath, Gudipudi; Sankeshi, Venu; Perugu, Shaym; Alaparthi, Malini D; Bandaru, Srinivas; Pasala, Vijay K; Chittineni, Prasad Rao; Krupadanam, G L David; Sagurthi, Someswar R

    2016-11-29

    Aldose reductase (ALR2) inhibitors provide a viable mode to fight against diabetic complications. ALR2 exhibit plasticity in the active site vicinities and possible shifts in the nearby two supporting alpha helices. Therefore, a novel series of amino acid conjugates of chromene-3-imidazoles (13-15) were designed and synthesized based on natural isoflavonoids. The compounds were identified on the basis of spectral ((1)H NMR, (13)C NMR and MS) data and tested in vitro for ALR2 inhibitory activity with an IC50 value ranges from 0.031 ± 0.082 μM to 4.29 ± 0.55 μM. Our in silico and biochemical studies confirmed that 15e has the best inhibition activity among the synthesized compounds with a high selective index against the Aldehyde reductase (ALR1). Supplementation of 15e to STZ induced rats decreased the blood glucose levels and delayed the progression of cataract in a dose-dependent manner. The present study thus provides novel series of compounds with a promising inhibitor to prevent or delay the cataract progression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice.

    Science.gov (United States)

    Chaplin, Alice; Parra, Pilar; Serra, Francisca; Palou, Andreu

    2015-01-01

    The gastrointestinal tract constitutes a physiological interface integrating nutrient and microbiota-host metabolism. Conjugated linoleic acids (CLA) have been reported to contribute to decreased body weight and fat accretion. The modulation by dietary CLA of stomach proteins related to energy homeostasis or microbiota may be involved, although this has not been previously analysed. This is examined in the present study, which aims to underline the potential mechanisms of CLA which contribute to body weight regulation. Adult mice were fed either a normal fat (NF, 12% kJ content as fat) or a high-fat (HF, 43% kJ content as fat) diet. In the latter case, half of the animals received daily oral supplementation of CLA. Expression and content of stomach proteins and specific bacterial populations from caecum were analysed. CLA supplementation was associated with an increase in stomach protein expression, and exerted a prebiotic action on both Bacteroidetes/Prevotella and Akkermansia muciniphila. However, CLA supplementation was not able to override the negative effects of HF diet on Bifidobacterium spp., which was decreased in both HF and HF+CLA groups. Our data show that CLA are able to modulate stomach protein expression and exert a prebiotic effect on specific gut bacterial species.

  3. Endurance exercise and conjugated linoleic acid (CLA supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

    Directory of Open Access Journals (Sweden)

    Rosario Barone

    Full Text Available A new role for fat supplements, in particular conjugated linoleic acid (CLA, has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

  4. Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans.

    Science.gov (United States)

    Coleman, Hannah; Quinn, Paul; Clegg, Miriam E

    2016-06-01

    Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (Pintake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Stability assessment of conjugated linoleic acid (CLA) oil-in-water beverage emulsion formulated with acacia and xanthan gums.

    Science.gov (United States)

    Nikbakht Nasrabadi, Maryam; Goli, Sayed Amir Hossein; Nasirpour, Ali

    2016-05-15

    The development of a conjugated linoleic acid (CLA) oil-in-water beverage emulsion containing acacia gum (AG) and xanthan gum (XG) was investigated. D-optimal design and response surface method was used and 10% w/w AG, 3.5% w/w CLA and 0.3% w/w XG was introduced as the optimum formula. Afterward the effect of storage time on the physicochemical properties of selected formulation including specific gravity, turbidity, viscosity, average droplet size, span, size index, creaming index, oxidation measurements and stability in its diluted form, were determined. Findings revealed that the size of oil droplets increased after six weeks and resulted in instability of the emulsion concentrate. Peroxide value increased until 21 days and then decreased dramatically, whereas TBA and Totox values began to increase after this time. Turbidity loss rate was low demonstrating the good stability of the diluted emulsion. The results revealed that it is possible to produce a stable CLA oil-in-water emulsion for using in beverages.

  6. Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

    Science.gov (United States)

    Barone, Rosario; Macaluso, Filippo; Catanese, Patrizia; Marino Gammazza, Antonella; Rizzuto, Luigi; Marozzi, Paola; Lo Giudice, Giuseppe; Stampone, Tomaso; Cappello, Francesco; Morici, Giuseppe; Zummo, Giovanni; Farina, Felicia; Di Felice, Valentina

    2013-01-01

    A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

  7. Conjugated linoleic acid (CLA) promotes endurance capacity via peroxisome proliferator-activated receptor δ-mediated mechanism in mice.

    Science.gov (United States)

    Kim, Yoo; Kim, Daeyoung; Park, Yeonhwa

    2016-12-01

    Previously, it was reported that conjugated linoleic acid (CLA) with exercise training potentially improved endurance capacity via the peroxisome proliferator-activated receptor δ (PPARδ)-mediated mechanism in mice. This study determined the role of exercise and/or CLA in endurance capacity and PPARδ-associated regulators. Male 129Sv/J mice were fed either control (soybean oil) or CLA (0.5%) containing diets for 4 weeks and were further divided into sedentary or training regimes. CLA supplementation significantly reduced body weight and fat mass independent of exercise during the experimental period. Endurance capacity was significantly improved by CLA supplementation, while no effect of exercise was observed. Similarly, CLA treatment significantly increased expressions of sirtuin 1 and PPARγ coactivator-1α, up-stream regulators of PPARδ, in both sedentary and trained animals. With respect to downstream markers of PPARδ, CLA up-regulated the key biomarker needed to stimulate mitochondrial biogenesis, nuclear respiratory factor 1. Moreover, CLA supplementation significantly induced overall genes associated with muscle fibers, such as type I (slow-twitch) and type II (fast twitch). Taken together, it suggests that CLA improves endurance capacity independent of mild-intensity exercise via PPARδ-mediated mechanism.

  8. Domino-Like Intercellular Delivery of Undecylenic Acid-Conjugated Porous Silicon Nanoparticles for Deep Tumor Penetration.

    Science.gov (United States)

    Yong, Tuying; Hu, Jun; Zhang, Xiaoqiong; Li, Fuying; Yang, Hao; Gan, Lu; Yang, Xiangliang

    2016-10-05

    Improving the intratumoral distribution of anticancer agents remains the critical challenge for developing efficient cancer chemotherapy. Luminescent porous silicon nanoparticles (PSiNPs) have attracted considerable attention in the biomedical field especially in drug delivery. Here, we described the lysosomal exocytosis-mediated domino-like intercellular delivery of undecylenic acid-conjugated PSiNPs (UA-PSiNPs) for deep tumor penetration. UA-PSiNPs with significantly improved stability in physiological conditions were internalized into tumor cells by macropinocytosis-, caveolae-, and clathrin-mediated endocytosis and mainly colocalized with Golgi apparatus and lysosomes. Substantial evidence showed that UA-PSiNPs was excreted from cells via lysosomal exocytosis after cellular uptake. The exocytosed UA-PSiNPs induced a domino-like infection of adjacent cancer cells and allowed encapsulated doxorubicin (DOX) to deeply penetrate into both three-dimensional tumor spheroids and in vivo tumors. In addition, DOX-loaded UA-PSiNPs exhibited strong antitumor activity and few side effects in vivo. This study demonstrated that UA-PSiNPs as a drug carrier might be applied for deep tumor penetration, offering a new insight into the design of more efficient delivery systems of anticancer drugs.

  9. Accurate pKa calculation of the conjugate acids of alkanolamines, alkaloids and nucleotide bases by quantum chemical methods.

    Science.gov (United States)

    Gangarapu, Satesh; Marcelis, Antonius T M; Zuilhof, Han

    2013-04-02

    The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum model (CPCM) and universal solvation models (SMD, SM8). G3, SCS-MP2 and M11-L methods coupled with SMD and SM8 solvation models perform well for alkanolamines with mean unsigned errors below 0.20 pKa units, in all cases. Extending this method to the pKa calculation of 35 nitrogen-containing compounds spanning 12 pKa units showed an excellent correlation between experimental and computational pKa values of these 35 amines with the computationally low-cost SM8/M11-L density functional approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Regulatory issues related to functional foods and natural health products in Canada: possible implications for manufacturers of conjugated linoleic acid.

    Science.gov (United States)

    Fitzpatrick, Kelley C

    2004-06-01

    The Canadian Food and Drugs Act and Regulations, through its definitions of food and drug, currently restricts health-related claims for foods, food ingredients, and natural health products (NHPs). Over the past few decades, scientific research has led to a large body of information that demonstrates the benefits for health of many food and NHP ingredients. Health Canada recognized the constraints of the current regulatory environment and started to develop regulations related to the allowance of health claims for functional foods and NHPs, including those foods and NHPs that would contain conjugated linoleic acid isomers. Health Canada has 3 initiatives under way in the area of health claims for foods: 1) to adopt the generic health claims of the United States within a Canadian context, 2) to develop scientific standards of evidence and a guidance document for supporting the validity of product-specific claims, and 3) to develop an overall regulatory framework for functional foods. In 2000, Health Canada announced approval for the use of 5 generic diet-related health claims: sodium and hypertension, calcium and osteoporosis, saturated and trans fat and cholesterol and coronary artery disease, fruits and vegetables and cancer, and sugar alcohols and dental caries. Under a separate initiative, Natural Health Products Regulations were published in the Canada Gazette Part II on June 18, 2003. The NHP Regulations came into force on January 1, 2004, with a transition period ranging from 2 y (for site licensing) to 6 y (for product licensing, for products already issued a drug identification number).

  11. Microwave-assisted degradation of acid orange using a conjugated polymer, polyaniline, as catalyst

    Directory of Open Access Journals (Sweden)

    Ufana Riaz

    2014-01-01

    Full Text Available Microwave-assisted photocatalytic degradation of dyes is one of the emerging technologies for waste water remediation. Microwave effectively accelerates photocatalytic degradation, when microwave electrodeless lamp (MEL substitutes traditional UV lamp as light source. This setup can be extremely simplified if MEL and photocatalyst can be replaced by a catalyst which can work under microwave irradiation in the absence of any light source. The present work reports for the first time degradation of acid orange 7 (AO under microwave irradiation using polyaniline (PANI as catalyst in the absence of any UV lamp as light source. The degradation/decolourization was carried out in neutral acidic and basic media and was monitored spectrophotometrically to evaluate the ability of microwave irradiation to degrade AO. Microwave irradiation showed excellent performance as it completely decolourizes AO dye solution in 10 min. With the advantages of low cost and rapid processing, this novel catalyst is expected to gain promising application in the treatment of various dyestuff wastewaters on a large scale.

  12. Effect of dose of calcium salts of conjugated linoleic acid (CLA) on percentage and fatty acid content of milk fat in midlactation holstein cows.

    Science.gov (United States)

    Giesy, J G; McGuire, M A; Shafii, B; Hanson, T W

    2002-08-01

    Increasing conjugated linoleic acid (CLA) content of milk fat from lactating dairy cattle has become a research interest due to the possible health benefits afforded humans consuming CLA. Dietary supplementation of CLA to lactating dairy cows is one potential method by which CLA content of milk and dairy products may be enhanced. Feeding CLA in calcium salt form could potentially deliver CLA to the lower digestive tract through prevention of biohydrogenation by rumen microbes. Milk fat depression (MFD) occurs when cows receive CLA-60, a commercially available CLA source containing numerous CLA isomers, abomasally. Our objectives were to determine the quantity of CLA as calcium salts required to elicit maximal MFD and to evaluate the effects of CLA supplementation on fatty acid composition of milk fat. Five Holstein cows at approximately 93 DIM were utilized in a 5 x 5 balanced Latin square crossover design. Periods were 14-d in length with a 5-d treatment phase and 9-d rest phase. Treatments were 5-d supplementation of 0, 12.5, 25, 50, and 100 g of CLA-60 in calcium salt form. Milk samples were collected on d 5 of CLA supplementation and analyzed for composition and fatty acid profile. Regression analysis of milk fat data suggested that MFD was not maximized over the dose levels investigated, despite delivery of 34.5 g of trans-10, cis-12 CLA in the 100-g dose of CLA. Supplementation with 50 and 100 g of CLA per day resulted in a reduction of milk fat percent of 29 and 34%, respectively. Trend analysis indicated a linear decrease in the milk fat content of caprylic, capric, and lauric acids as the dose of CLA increased. Milk fat content of cis-9, trans-11, and trans-10, cis-12 CLA increased at an increasing rate as dose increased.

  13. Weak effect of trans-10, cis-12-conjugated linoleic acid on body fat accumulation in adult hamsters.

    Science.gov (United States)

    Miranda, Jonatan; Churruca, Itziar; Fernández-Quintela, Alfredo; Rodríguez, Victor Manuel; Macarulla, María Teresa; Simón, Edurne; Portillo, María Puy

    2009-12-01

    It has been proposed that young animals and subjects are more responsive to conjugated linoleic acid (CLA) than the adults. Nevertheless, there is very little information concerning the effectiveness of CLA in adult animals. In the present study we aimed to explore the effects of trans-10, cis-12-CLA on body fat accumulation in adult hamsters, as well as on some of the molecular mechanisms described in young animals as responsible for the CLA body fat-lowering effect, such as lipogenesis, lipoprotein lipase (LPL)-mediated fat uptake and thermogenesis. The experiment was conducted with sixteen adult male Syrian Golden hamsters (aged 8 months) fed a high-fat diet supplemented or not with 0.5 % trans-10, cis-12-CLA for 6 weeks. Acetyl-CoA carboxylase (ACX), fatty acid synthase (FAS), LPL, PPARgamma, sterol regulatory element-binding protein (SREBP)-1a and SREBP-1c expressions were assessed in subcutaneous and perirenal adipose tissues by real-time RT-PCR. Total and heparin-releasable LPL activities were determined in subcutaneous adipose tissue by fluorimetry and FAS activity by spectrophotometry. Uncoupling protein-1 (UCP1) expression in interscapular brown adipose tissue was assessed by Western blot. Hamsters fed the trans-10, cis-12-CLA diet showed a significant reduction in subcutaneous adipose tissue. No changes were observed in the expression of ACX, FAS, LPL, SREBP-1a, SREBP-1c and PPARgamma, nor in total and heparin-releasable LPL and FAS activities. Trans-10, cis-12-CLA induced a significant increase in the amount of UCP1. These results suggest a low responsiveness to trans-10, cis-12-CLA in adults, lower than that in young hamsters. One of the reasons explaining this difference is the lack of effect on LPL.

  14. trans-10,cis-12 conjugated linoleic acid prevents adiposity but not insulin resistance induced by an atherogenic diet in hamsters.

    Science.gov (United States)

    Simón, Edurne; Macarulla, M Teresa; Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, María P

    2006-02-01

    While conjugated linoleic acid (CLA) has received a great deal of attention as a supplement that can favourably modify body composition, its potential impact on insulin sensitivity has not received equal attention. The aim of the present work was to analyse the effects of trans-10,cis-12 CLA isomer on insulin sensitivity in hamsters fed an atherogenic diet. Hamsters were divided into three groups: one group was fed a chow diet (control) and the other two a semipurified atherogenic diet supplemented with 0.5% linoleic acid (LA) or trans-10,cis-12 CLA, respectively. Serum glucose, FFAs, insulin, leptin and adiponectin were measured using commercial kits. HOMA-IR was calculated using the formula of Matthews et al. PPARgamma mRNA was assessed in epididymal adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). After 6 weeks, atherogenic feeding produced an increase in body fat accumulation as compared with control feeding. The addition of trans-10,cis-12 CLA to the atherogenic diet avoided this feature. Atherogenic feeding also led to significantly higher serum concentrations of glucose, insulin, FFAs, as well as greater HOMA-IR values. trans-10,cis-12 CLA did not prevent these effects. No significant differences were found among experimental groups in serum leptin and adiponectin concentrations, nor in PPARgamma expression. In summary, although the addition of trans-10,cis-12 CLA to an atherogenic diet reduces fat accumulation, it does not improve the impairment of insulin action associated with this feeding. The maintenance of insulin resistance in hamsters fed the atherogenic CLA-enriched diet is probably due to the high serum FFA concentration observed in these animals.

  15. Effect of conjugated linoleic acids from beef or industrial hydrogenation on growth and adipose tissue characteristics of rats

    Directory of Open Access Journals (Sweden)

    He Mao L

    2009-04-01

    Full Text Available Abstract Background The conjugated linoleic acid (CLA content of beef can be increased by supplementing appropriate beef cattle diets with vegetable oil or oil seed. Yet the effect of consumption of such beef on adipose tissue characteristics is unclear, thus the study was conducted to compare adipose tissue responses of rats to diets containing beef from steers either not provided or provided the oil supplements to alter CLA composition of the fat in muscle. Methods Effects of feeding synthetic (industrial hydrogenation CLA or CLA from beef on growth and adipose tissue responses of weanling, male, Wistar rats (n = 56; 14 per treatment diet were investigated in a completely randomized design experiment. Diets were: control (CON diet containing casein and soybean oil, synthetic CLA (SCLA diet; where 1.69% synthetic CLA replaced soybean oil, two beef-diets; CONM and CLAM, containing freeze dried beef from steers either not fed or fed 14% sunflower seeds to increase CLA content of beef. Diets were isonitrogenous (20% protein and isocaloric. Rat weights and ad libitum intakes were recorded every 2 wk. After 9 wk, rats were fasted for 24 h, blood sampled by heart puncture, sacrificed, tissue and organs were harvested and weights recorded. The adipose tissue responses with regard to cellularity and fatty acid compositions of retroperitoneal and inguinal adipose tissue were determined. Results Body weights and gains were comparable, but organ weights as percent of body weight were greater for rats fed SCLA than CONM. Fasting blood glucose concentration was lower (p 7 cells/g and 8.03 × 108 cells than those fed CONM (28.88 × 107 cells/g and 32.05 × 108 cells, respectively. Conclusion Study suggests that dietary CLA either as synthetic or high CLA-beef may alter adipose tissue characteristics by decreasing the number of adipocytes and by decreasing the size of the tissue.

  16. The conjugated linoleic acid isomer trans-9,trans-11 is a dietary occurring agonist of liver X receptor {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Josef; Liebisch, Gerhard [Institute of Clinical Chemistry, University of Regensburg (Germany); Patsch, Wolfgang [Department of Laboratory Medicine, Hospital of Salzburg (Austria); Schmitz, Gerd, E-mail: gerd.schmitz@klinik.uni-regensburg.de [Institute of Clinical Chemistry, University of Regensburg (Germany)

    2009-10-30

    Conjugated linoleic acid (CLA) isomers are dietary fatty acids that modulate gene expression in many cell types. We have previously reported that specifically trans-9,trans-11 (t9,t11)-CLA induces expression of genes involved in lipid metabolism of human macrophages. To elucidate the molecular mechanism underlying this transcriptional activation, we asked whether t9,t11-CLA affects activity of liver X receptor (LXR) {alpha}, a major regulator of macrophage lipid metabolism. Here we show that t9,t11-CLA is a regulator of LXR{alpha}. We further demonstrate that the CLA isomer induces expression of direct LXR{alpha} target genes in human primary macrophages. Knockdown of LXR{alpha} with RNA interference in THP-1 cells inhibited t9,t11-CLA mediated activation of LXR{alpha} including its target genes. To evaluate the effective concentration range of t9,t11-CLA, human primary macrophages were treated with various doses of CLA and well known natural and synthetic LXR agonists and mRNA expression of ABCA1 and ABCG1 was analyzed. Incubation of human macrophages with 10 {mu}M t9,t11-CLA led to a significant modulation of ABCA1 and ABCG1 transcription and caused enhanced cholesterol efflux to high density lipoproteins and apolipoprotein AI. In summary, these data show that t9,t11-CLA is an agonist of LXR{alpha} in human macrophages and that its effects on macrophage lipid metabolism can be attributed to transcriptional regulations associated with this nuclear receptor.

  17. The body fat-lowering effect of conjugated linoleic acid: a comparison between animal and human studies.

    Science.gov (United States)

    Navarro, V; Fernández-Quintela, A; Churruca, I; Portillo, M P

    2006-06-01

    Different reasons which justify differences between rodents and humans in body fat reduction produced by conjugated linoleic acid (CLA) could be proposed. The doses used in humans are lower than those used in rodents. Human experiments have been performed with CLA isomer mixtures instead of isolated isomers. The variable dilution of t-10, c-12, the active isomer, among different preparations might explain the reduced responsiveness in humans. Diet composition may modulate CLA effects on body fat accumulation. As far as human studies are concerned, a specific dietary pattern has not been established. As a result differences among studies and also among subjects in the same study are likely. In rodents, the effects of CLA vary with genotype, suggesting that genetic predisposition to fat accumulation can play an important role in the effectiveness of CLA. Human volunteers with different body mass index have participated in the published studies and even in the same experiment. So, differences in lipid metabolism among subjects could help to explain the discrepancies observed in the literature. Age and maturity may also be crucial. Experiments using rodents have been conducted with growing animals and there is little evidence of CLA effectiveness in adult animals. By contrast, human studies have been performed with adults. Inhibition of lipogenesis in white adipose tissue is one of the mechanisms which have been proposed to explain the body-fat lowering effect of CLA, but lipogenesis in this tissue is very low in humans. Another mechanism suggested is increased fatty acid oxidation in the liver associated with peroxisome proliferation, but humans are relatively insensitive to this effect.

  18. Diets rich in conjugated linoleic acid and vaccenic acid have no effect on blood pressure and isobaric arterial elasticity in healthy young men

    DEFF Research Database (Denmark)

    Raff, M.; Tholstrup, T.; Sejrsen, K.

    2006-01-01

    The objective of this study was to examine the effect on blood pressure (BP) and isobaric arterial elasticity (AE), as a measure of arterial health, of a commercial mixture of conjugated linoleic acids (CLA) and of milk fat produced through livestock feeding to have a high content of vaccenic acid...... of the test diets did not differ on any outcome variable: e.g., systolic- and diastolic blood pressure (SBP and DBP), pulse pressure (PP), isobaric arterial compliance (AC), distensibility (AD), or volume (AV). In conclusion, diets rich in milk fat and either CLA or VA have no effect on BP or AE indices...... (VA). Healthy young men (n = 60) with a BMI of 22.5 +/- 2 kg/m(2) (mean +/- SD) participated in this double-blind, randomized, 5-wk, parallel intervention study. The participants substituted 115 g of their daily fat intake with fat from 1 of 3 test diets: 1) CLA-diet rich in CLA (4.7 g/d of c9, t11...

  19. Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profile during protein repletion in rats.

    Science.gov (United States)

    Andreoli, María F; Illesca, Paola G; González, Marcela A; Bernal, Claudio A

    2010-11-01

    Protein depletion is associated with hepatic steatosis and decreased circulating triacylglycerol (TAG). Since conjugated linoleic acid (CLA) increases lean body mass, protects against muscle catabolism, and modulates lipid metabolism, the aim of this work was to investigate the effects of CLA with two different amounts of dietary fat on the regulation of plasma and hepatic TAG concentration, and its possible connections with changes in fatty acid (FA) profile in plasma, liver and adipose tissue and hepatic oxidative status during protein repletion. Rats were fed a low protein diet (14 days) and then a protein repletion diet (30 days), supplemented or not with CLA, containing 7% (w/w) or 20% (w/w) of fat. Hepatic TAG secretion and removal by muscle and adipose tissue lipoprotein lipase, FA profile and liver oxidative status were evaluated. Protein depletion affected hepatic TAG secretion and peripheral removal, decreasing plasma and increasing liver TAG concentration, whereas protein repletion with CLA improved these abnormalities independently of the amount of dietary fat by increasing hepatic TAG secretion. This prevention in the absence of CLA was not observed. CLA was incorporated in plasma and tissues (adipose > liver > plasma, and c9,t11-CLA > t10,c12-CLA), accompanied by alterations in FA composition, mainly in adipose tissue. The hepatic oxidative stress was overcome by protein repletion. CLA had a beneficial impact on TAG metabolism in protein repleted animals, preventing hepatic steatosis through higher hepatic TAG secretion.

  20. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Eysturskard, Jonhard; Nielsen, Peter E

    2010-01-01

    ABSTRACT: BACKGROUND: Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human ca...... method to evaluate the cellular function of MDM2 splice variants as well as a promising approach for discovery of mdm2 targeted anticancer drugs.......ABSTRACT: BACKGROUND: Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human...

  1. Rh-catalyzed enantioselective conjugate addition of arylboronic acids with a dynamic library of chiral tropos phosphorus ligands.

    Science.gov (United States)

    Monti, Chiara; Gennari, Cesare; Piarulli, Umberto

    2007-01-01

    A library of 19 chiral tropos phosphorus ligands, based on a free-to-rotate (tropos) biphenol unit and a chiral P-bonded alcohol (11 phosphites, 1-P(O)(2)O to 11-P(O)(2)O) or secondary amine (8 phosphoramidites, 12-P(O)(2)N to 19-P(O)(2)N), were screened, individually and in combinations of two, in the rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and enoates. High enantioselectivities (up to 99 % ee) and excellent yields were obtained in the addition to either cyclic or acyclic substrates. The flexible biphenolic P ligands outperformed the analogous rigid binaphtholic P ligands. Variable-temperature (31)P NMR studies revealed that the biphenolic ligands are tropos even at low temperature. Only below 190 K was a coalescence observed; upon further cooling, two atropisomers were detected. The Rh homocomplexes ([Rh(L(a))(2)](+)) were also studied: in general, a single doublet (P-Rh coupling) was observed in the case of the biphenolic phosphite ligands, over the temperature range 380-230 K, demonstrating their tropos nature in the rhodium complexes even at low temperatures. On the other hand, the phosphoramidites showed different behaviors depending on the structure of the ligand and on the nature of the rhodium source. The spectrum at 230 K of the mixture of [Rh(acac)(eth)(2)] (eth=C(2)H(4)) with phosphite 6-P(O)(2)O and phosphoramidite 19-P(O)(2)N (the most enantioselective ligand combination in the conjugate addition reaction) revealed the presence of four homocomplexes (total approximately 40 %: [Rh{6-P(O)(2)O}(2)], [Rh{(aR)-19-P(O)(2)N}(2)], [Rh{(aS)-19-P(O)(2)N}(2)], [Rh{(aR)-19-P(O)(2)N}{(aS)-19-P(O)(2)N}]) and one heterocomplex, [Rh{6-P(O)(2)O}{(aR)-19-P(O)(2)N}] (approximately 60 %) In the heterocomplex, the biphenol-derived phosphite is free to rotate (tropos) while the biphenol-derived phosphoramidite shows a temperature-dependent tropos/atropos behavior (coalescence temperature=310 K).

  2. Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type

    Directory of Open Access Journals (Sweden)

    Kristina Pavić

    2016-11-01

    Full Text Available In this paper design and synthesis of a scaffold comprising primaquine (PQ motif and cinnamic acid derivatives (CADs bound directly (compounds 3a–k or via a spacer (compounds 7a–k are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a–k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A or benzotriazolides 2 (method B. The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g and nanomolar (7j levels. Acylsemicarbazide derivatives with trifluoromethyl group(s 7i, 7j and 7k showed specific activity against human coronavirus (229E at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e, benzodioxole (7f, p-Cl (7g and m-CF3 (7i acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%. The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μΜ. The performed biological tests gave evidence of

  3. Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type.

    Science.gov (United States)

    Pavić, Kristina; Perković, Ivana; Gilja, Petra; Kozlina, Filip; Ester, Katja; Kralj, Marijeta; Schols, Dominique; Hadjipavlou-Litina, Dimitra; Pontiki, Eleni; Zorc, Branka

    2016-11-28

    In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a-k) or via a spacer (compounds 7a-k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a-k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a-k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c-e), benzodioxole (7f), p-Cl (7g) and m-CF₃ (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%-89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μΜ). The performed biological tests gave evidence of

  4. Measurement of conjugated linoleic acid (CLA) in CLA-rich potato chips by ATR-FTIR spectroscopy.

    Science.gov (United States)

    Kadamne, Jeta V; Castrodale, Chelsey L; Proctor, Andrew

    2011-03-23

    A conjugated linoleic acid (CLA)-rich soy oil has been produced by photoisomerization of soy oil linoleic acid. Nutritional studies have shown that CLA possesses health benefits in terms of reducing certain heart disease and diabetes risk factors. Potato chips are snacks that are readily produced in the CLA-rich soy oil containing CLA levels similar to those of the oil used for frying. The objective of this study was to develop an FTIR method to rapidly determine the CLA content of oil in potato chips. Photoirradiated soy oil samples with ∼25% total CLA were mixed with control soy oil, and 100 soy oil samples with total CLA levels ranging from 0.89 to 24.4% were made. Potato chips were fried using each of these 300 g CLA rich soy oil mixtures at 175 °C for approximately 3 min. Duplicate GC-FID fatty acid analyses were conducted on oil extracted from each batch of potato chips. The chip samples were ground and then scanned using ATR-FTIR spectroscopy with the aid of a high-pressure clamp, and duplicate spectra of each sample were averaged to obtain an average spectrum. Calibration models were developed using PLS regression analysis. These correlated the CLA isomer concentrations of potato chips obtained by GC-FID fatty acid analysis with their corresponding FTIR spectral features. The calibration models were fully cross validated and tested using samples that were not used in the calibration sample set. Calibrations for total CLA, trans,trans CLA, trans-10,cis-12 CLA, trans-9,cis-11 CLA, cis-10,trans-12 CLA, and cis-9,trans-11 CLA had coefficients of determinations (R2v) between 0.91 and 0.96 and corresponding root-mean-square error of prediction (RMSEP) ranging from 0.005 to 1.44. The ATR-FTIR technique showed potential as a method for the determination of the CLA levels in unknown potato chip samples.

  5. trans-10, cis-12 Conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet

    OpenAIRE

    Zabala, Amaia; Churruca Ortega, Itziar; Fernández Quintela, Alfredo; Rodríguez Rivera, Víctor Manuel; Macarulla Arenaza, María Teresa; Martínez, J Alfredo; Portillo Baquedano, María Puy

    2006-01-01

    The aim of the present work was to investigate the effects of trans-10,cis-12conjugated linoleic acid (CLA) on the activity and expression of lipogenic enzymes and lipoprotein lipase (LPL), as well as on the expression of transcriptional factors controlling these enzymes, in adipose tissue from hamsters, and to evaluate the involvement of these changes in the body fat-reducing effect of this CLA isomer. Thirty male hamsters were divided into three groups and fed atherogenic diets supplemented...

  6. Effects of trans-10, cis-12 conjugated linoleic acid on the expression of uncoupling proteins in hamsters fed an atherogenic diet

    OpenAIRE

    Ribot, Joan; Portillo Baquedano, María Puy; Picó, Catalina; Macarulla Arenaza, María Teresa; Palou, Andreu

    2007-01-01

    It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts...

  7. Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Azam Jokar

    2016-01-01

    Full Text Available Background: Vaginal atrophy is a common complication in menopause which does not improve with time and, if untreated, can affect the quality of life for women. The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen (Premarin in treatment of vaginal atrophy. Methods: This study was a randomized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy; they were randomly allocated to two groups (recipient conjugated estrogen and hyaluronic acid. The severity of each sign of atrophy was evaluated by visual analog signals (VAS and on the basis of a four point scale. Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0-100. As to the vaginal PH, we used PH marker band, the rate of which was divided into 4 degrees. Data were analyzed using SPSS, version 20, and P≤0.05 was considered as significant. Results: The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups. Dryness, itching, maturation index, PH and composite score of the vaginal symptoms were relieved significantly in both groups (P<0.001. Dyspareunia in Premarin (P<0.05 and hyaluronic acid (P<0.001 decreased compared with pre-treatment. Urinary incontinence only showed improvement in the hyaluronic acid group (P<0.05. Improvement in urinary incontinence, dryness, maturation index (P<0.05 and composite score of vaginal symptoms (P<0.001 in the hyaluronic acid group was better than those in the Premarin group. Conclusion: According to the results of the present study, hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy. But hyaluronic acid was more effective and this drug is suggested for those who do not want to or cannot take local hormone treatment.

  8. OX26 modified hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) nanoparticles: synthesis, characterization and evaluation of its brain delivery ability.

    Science.gov (United States)

    Bao, Hanmei; Jin, Xu; Li, Ling; Lv, Feng; Liu, Tianjun

    2012-08-01

    A novel nanoparticles-based brain drug delivery system made of hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) which was surface functionalized with transferrin antibody (OX26) was prepared. Hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) was synthesized, characterized and applied to prepare nanoparticles by means of double emulsion solvent evaporation technique. Transmission electron micrograph and dynamic light scattering showed that nanoparticles had a round and regular shape with a mean diameter of 170 ± 20 nm. Surface chemical composition was detected by X-ray photoelectron spectroscopy. Endomorphins, as a model drug, was encapsulated in the nanoparticles. In vitro drug release study showed that endomorphins was released continuously for 72 h. Cellular uptake study showed that the uptake of nanoparticles by the brain microvascular endothelial cells was both time- and concentration-dependant. Further uptake inhibition study indicated that the uptake of nanoparticles was via a caveolae-mediated endocytic pathway. In vivo endomorphins brain delivery ability was evaluated based upon the rat model of chronic constriction injury of sciatic nerve. OX26 modified nanoparticles had achieved better analgesic effects, compared with other groups. Thus, OX26 modified hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) nanoparticles may be a promising brain drug delivery carrier.

  9. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Science.gov (United States)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  10. Folic acid conjugated guar gum nanoparticles for targeting methotrexate to colon cancer.

    Science.gov (United States)

    Sharma, Monika; Malik, Ritu; Verma, Ashwni; Dwivedi, Pankaj; Banoth, Gabbar Singh; Pandey, Nagendra; Sarkar, Jayant; Mishra, Prabhat Ranjan; Dwivedi, Anil Kumar

    2013-01-01

    It was envisaged to develop surface modified Guar Gum Nanoparticles (GGNP) with Folic acid (FA) charged with methotrexate (MTX) to target the colon specifically. The MTX loaded FA functionalized GGNP (MTX-FA-GGNP) have been prepared by emulsion crosslinking method. These surface modified nanoparticles were compared with unmodified MTX loaded GGNP (MTX-GGNP). The developed formulations were evaluated for size and size distribution, zeta potential, Differential Scanning Calorimetry (DSC), release profile and uptake studies. The nanoparticles have been found to have average size of 325 nm in diameter having polydispersity index (PDI) 0.177 indicating mono-disperse particles. The zeta potential of the particles was found to be -36.9 mV. The percent growth inhibition of Caco 2 cells with MTX-FA-GGNP was found to be better than MTX-GGNP indicating folate receptor mediated uptake. The MTX-GGNP protects the release of MTX in upper gastrointestinal tract while maximum release of MTX occurred in simulated colonic fluids of pH 6.8. The in vivo uptake studies revealed preferential uptake of nanoparticles formulation in the colon. These studies provide evidences that MTX-FA-GGNP holds promise to address colorectal cancer over-expressing folate receptors. This prototype formulation enjoys dual advantage of having propensity to release the drug in the colon and in the conditions of colorectal carcinoma; it could be better localized and targeted with improved therapy due to over-expression of folate receptors.

  11. Hydroxycinnamate Conjugates as Potential Monolignol Replacements: In vitro Lignification and Cell Wall Studies with Rosmarinic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Yuki, Tobimatsu; Sasikumar, Elumalai; Grabber, John H.; Davidson, Christy L.; Xuejun, Pan; John, Ralph

    2012-04-01

    The plasticity of lignin biosynthesis should permit the inclusion of new compatible phenolic monomers, such as rosmarinic acid (RA) and analogous catechol derivatives, into cell-wall lignins that are consequently less recalcitrant to biomass processing. In vitro lignin polymerization experiments revealed that RA readily underwent peroxidase-catalyzed copolymerization with monolignols and lignin oligomers to form polymers with new benzodioxane inter-unit linkages. Incorporation of RA permitted extensive depolymerization of synthetic lignins by mild alkaline hydrolysis, presumably by cleavage of ester intra-unit linkages within RA. Copolymerization of RA with monolignols into maize cell walls by in situ peroxidases significantly enhanced alkaline lignin extractability and promoted subsequent cell wall saccharification by fungal enzymes. Incorporating RA also improved cell wall saccharification by fungal enzymes and by rumen microflora even without alkaline pretreatments, possibly by modulating lignin hydrophobicity and/or limiting cell wall cross-linking. Consequently, we anticipate that bioengineering approaches for partial monolignol substitution with RA and analogous plant hydroxycinnamates would permit more efficient utilization of plant fiber for biofuels or livestock production.

  12. Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis.

    Science.gov (United States)

    Puttaswamy, Naveen; Pavan Kumar, G S; Al-Ghorbani, Mohammed; Vigneshwaran, V; Prabhakar, B T; Khanum, Shaukath Ara

    2016-05-23

    Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compound's effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future.

  13. Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

    Directory of Open Access Journals (Sweden)

    Mona Mosayebnia

    2014-01-01

    Full Text Available Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. Materials and Methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2 cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO, a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay as well. Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems. Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage.

  14. Hydrophilic azlactone-functionalized magnetite nanoparticle for conjugation with folic acid

    Science.gov (United States)

    Pray-in, Yingrak; Rutnakornpituk, Boonjira; Wichai, Uthai; Vilaivan, Tirayut; Rutnakornpituk, Metha

    2014-04-01

    Herein, we report the synthesis of magnetite nanoparticles (MNPs) grafted with poly(poly(ethylene glycol) methyl ether methacrylate- stat-2-vinyl-4,4-dimethylazlactone) copolymers (poly(PEGMA- stat-VDM)) prepared via a surface-initiated atom transfer radical polymerization (ATRP) and used for the immobilization of folic acid (FA). The MNPs were synthesized using a thermal decomposition method and surface functionalized to obtain ATRP-initiating sites. The particle size was in the range of 5-10 nm with the average of 8.0 ± 1.2 nm in diameter. Molar ratio of PEGMA to VDM was systematically varied (0/100, 30/70, 50/50, and 70/30, respectively) in the copolymerization to obtain water dispersible MNP with various amounts of azlactone rings, an electrophilic moiety, on its surface. Grafting density of VDM on the particle surface increased with increased VDM loading in the copolymerization reaction. These copolymer-coated MNPs were well dispersible in water with some nano-scale aggregation after FA functionalization due to hydrophobic character of FA. Since FA is a cancer cell targeting agent, it is anticipated that these novel FA-functionalized MNPs could be used as magnetically guidable vehicle for drug delivery, particularly for cancer treatment. The results of this study warrant a future investigation of this promising system.

  15. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Andhariya, Nidhi, E-mail: nidhiandhariya@gmail.com [Thapar University, School of Physics and Materials Science (India); Upadhyay, Ramesh [Charotar University of Science and Technology, P.D. Patel Institute of Applied Sciences (India); Mehta, Rasbindu [Maharaja Krishnakumarsinhji Bhavnagar University, Department of Physics (India); Chudasama, Bhupendra, E-mail: bnchudasama@gmail.com [Thapar University, School of Physics and Materials Science (India)

    2013-01-15

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor-folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  16. Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates.

    Science.gov (United States)

    Chou, Danny Hung-Chieh; Webber, Matthew J; Tang, Benjamin C; Lin, Amy B; Thapa, Lavanya S; Deng, David; Truong, Jonathan V; Cortinas, Abel B; Langer, Robert; Anderson, Daniel G

    2015-02-24

    Since its discovery and isolation, exogenous insulin has dramatically changed the outlook for patients with diabetes. However, even when patients strictly follow an insulin regimen, serious complications can result as patients experience both hyperglycemic and hypoglycemic states. Several chemically or genetically modified insulins have been developed that tune the pharmacokinetics of insulin activity for personalized therapy. Here, we demonstrate a strategy for the chemical modification of insulin intended to promote both long-lasting and glucose-responsive activity through the incorporation of an aliphatic domain to facilitate hydrophobic interactions, as well as a phenylboronic acid for glucose sensing. These synthetic insulin derivatives enable rapid reversal of blood glucose in a diabetic mouse model following glucose challenge, with some derivatives responding to repeated glucose challenges over a 13-h period. The best-performing insulin derivative provides glucose control that is superior to native insulin, with responsiveness to glucose challenge improved over a clinically used long-acting insulin derivative. Moreover, continuous glucose monitoring reveals responsiveness matching that of a healthy pancreas. This synthetic approach to insulin modification could afford both long-term and glucose-mediated insulin activity, thereby reducing the number of administrations and improving the fidelity of glycemic control for insulin therapy. The described work is to our knowledge the first demonstration of a glucose-binding modified insulin molecule with glucose-responsive activity verified in vivo.

  17. Functionalities of conjugated compounds of γ-aminobutyric acid with salicylaldehyde or cinnamaldehyde.

    Science.gov (United States)

    Liu, Tai-Ti; Tseng, Yi-Wei; Yang, Tsung-Shi

    2016-01-01

    Aldehydes or ketones can react with amino compounds to form Schiff base adducts, which have been widely studied and shown to exhibit antimicrobial, antioxidant or antiviral activity. Salicylaldehyde (SA) and cinnamaldehyde (CA) are components of plant essential oils. γ-Aminobutyric acid (GA) is an important substance in the mammalian central nervous system and responsible for many bioactivities. This study aimed to synthesize functional Schiff base adducts using GA and SA or CA; to study the antimicrobial activity, antioxidant activity and tyrosinase-inhibition activity of these adducts (SA-GA and CA-GA) and their metal complexes--SA-GA-Cu (or Zn) and CA-GA-Cu (or Zn); and to find their applications in food systems. SA-GA and CA-GA both exhibited good antibacterial effects, and so did their Cu complexes. As for antioxidant activity, SA-GA and CA-GA were superior to their metal complexes in most tests. Regarding inhibition of enzymatic browning of mushrooms, both SA-GA-Cu and CA-GA-Cu could inhibit tyrosinase activity effectively.

  18. Role of SbmA in the Uptake of Peptide Nucleic Acid (PNA)-Peptide Conjugates in E. coli

    DEFF Research Database (Denmark)

    Ghosal, Anubrata; Vitali, Ally; Stach, James E M

    2013-01-01

    Antisense PNA oligomers targeting essential genes (acpP or ftsZ) and conjugated to the delivery peptide L((KFF)(3)K) show complete growth inhibition of wild type E. coli strain (MG1655) with submicromolar MIC. In this study we show that resistant mutants generated against such PNA......-peptide conjugates had disruptions in the region of sbmA, a gene encoding an inner membrane peptide transporter. The wild type sensitivity to the PNA conjugates was re-established in the resistance mutants by complementation with sbmA. Furthermore, deletion of sbmA in E. coli AS19, a strain that is sensitive...

  19. Folic acid-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles for hyperthermia and MRI in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Q.L.; Zheng, S.W. [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); Hong, R.Y., E-mail: rhong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); Deng, S.M.; Guo, L. [The First Affiliated Hospital of Soochow University, Suzhou 215011 (China); Hu, R.L. [Department of Thoracic Surgery, Hangzhou First People' s Hospital, Hangzhou 310006 (China); Gao, B.; Huang, M.; Cheng, L.F. [College of Medicine, Soochow University, SIP, Suzhou 215123 (China); Liu, G.H. [Respiration Department, Suzhou Municipal Hospital (East-Section), Suzhou 215001 (China); Wang, Y.Q. [Key Laboratory of Environmental Materials and Engineering of Jiangsu Province, Yangzhou University, Yangzhou 225002 (China)

    2014-07-01

    The folic acid (FA)-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs) were synthesized by co-precipitation of Fe{sup 3+} and Fe{sup 2+} solution followed by surface modification with carboxymethyl dextran (CMD) to form carboxymethyl group terminated MNPs, then FA was conjugated with the carboxyl group functionalized MNPs. The morphology and properties of obtained nanoparticles were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV–visible spectra (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The FA-conjugated MNPs exhibited relatively high saturation magnetization and fast magneto-temperature response which could be applied to hyperthermia therapy. To determine the accurate targeting effect of FA, we chose FA-conjugated MNPs as MRI contrast enhancement agent for detection of KB cells with folate receptor over-expression in vitro and in vivo. The results show that these magnetic nanoparticles appear to be the promising materials for local hyperthermia and MRI.

  20. The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5

    Science.gov (United States)

    Lopez-Abarrategui, Carlos; Figueroa-Espi, Viviana; Lugo-Alvarez, Maria B; Pereira, Caroline D; Garay, Hilda; Barbosa, João ARG; Falcão, Rosana; Jiménez-Hernández, Linnavel; Estévez-Hernández, Osvaldo; Reguera, Edilso; Franco, Octavio L; Dias, Simoni C; Otero-Gonzalez, Anselmo J

    2016-01-01

    Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid-modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 µg/mL. However, the nanoparticles were not capable of inhibiting Gram-negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 µg/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity. PMID:27563243

  1. Combining disulfiram and poly(l-glutamic acid)-cisplatin conjugates for combating cisplatin resistance.

    Science.gov (United States)

    Song, Wantong; Tang, Zhaohui; Shen, Na; Yu, Haiyang; Jia, Yanjie; Zhang, Dawei; Jiang, Jian; He, Chaoliang; Tian, Huayu; Chen, Xuesi

    2016-06-10

    A poly(l-glutamic acid) graft polyethylene glycol-cisplatin complex (PGA-CisPt) performs well in reducing the toxicity of free cisplatin and greatly enhances the accumulation and retention of cisplatin in solid tumors. However, there is a lack of effective treatment options for cisplatin-resistant tumors. A major reason for this is the dense PEG shell, which ensures that the PGA-CisPt maintains a long retention time in the blood that may result in it bypassing the tumor cells or failing to be endocytosed within the tumor microenvironment. Consequently, the cisplatin from PGA-CisPt is released to the extracellular space in the presence of cisplatin-resistant tumor cells and the resistant problem to free cisplatin still valid. Therefore, we devised a strategy to combat the resistance of cisplatin in the tumor microenvironment using nanoparticles-loaded disulfiram (NPs-DSF) as a modulator. In vitro, cisplatin, in combination with DSF, had a synergistic effect and decreased cell survival rate of cisplatin-resistant A549DDP cells. This effect was also observed when combining PGA-CisPt with NPs-DSF. Similarly, in Balb/C nude mice with A549DDP xenografts, NPs-DSF improved PGA-CisPt effectiveness in inhibiting tumor growth while maintaining low toxicity. Our data demonstrate that DSF reduces intracellular glutathione (GSH) levels, inhibits NFκB activity, and modulates the expression of apoptosis-related proteins Bcl-2 and Bax, thereby improves the effectiveness of cisplatin in resistant cell lines. Here, we provide a promising method for overcoming cisplatin resistance in tumors, while maintaining the in vivo benefits of the PGA-CisPt complex.

  2. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

    Directory of Open Access Journals (Sweden)

    Francesca Selmin

    2015-01-01

    Full Text Available This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C. By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE, suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%. Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs.

  3. Conjugation of Hyaluronic Acid onto Surfaces via the Interfacial Polymerization of Dopamine to Prevent Protein Adsorption.

    Science.gov (United States)

    Huang, Renliang; Liu, Xia; Ye, Huijun; Su, Rongxin; Qi, Wei; Wang, Libing; He, Zhimin

    2015-11-10

    A versatile, convenient, and cost-effective method that can be used for grafting antifouling materials onto different surfaces is highly desirable in many applications. Here, we report the one-step fabrication of antifouling surfaces via the polymerization of dopamine and the simultaneous deposition of anionic hyaluronic acid (HA) on Au substrates. The water contact angle of the Au surfaces decreased from 84.9° to 24.8° after the attachment of a highly uniform polydopamine (PDA)/HA hybrid film. The results of surface plasmon resonance analysis showed that the Au-PDA/HA surfaces adsorbed proteins from solutions of bovine serum albumin, lysozyme, β-lactoglobulin, fibrinogen, and soybean milk in ultralow or low amounts (4.8-31.7 ng/cm(2)). The hydrophilicity and good antifouling performance of the PDA/HA surfaces is attributable to the HA chains that probably attached onto their upper surface via hydrogen bonding between PDA and HA. At the same time, the electrostatic repulsion between PDA and HA probably prevents the aggregation of PDA, resulting in the formation of a highly uniform PDA/HA hybrid film with the HA chains (with a stretched structure) on the upper surface. We also developed a simple method for removing this PDA/HA film and recycling the Au substrates by using an aqueous solution of NaOH as the hydrolyzing agent. The Au surface remained undamaged, and a PDA/HA film could be redeposited on the surface, with the surface exhibiting good antifouling performance even after 10 such cycles. Finally, it was found that this grafting method is applicable to other substrates, including epoxy resins, polystyrene, glass, and steel, owing to the strong adhesion of PDA with these substrates.

  4. Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.

    Science.gov (United States)

    Wang, Han; Xu, Renyang; Shi, Yongying; Si, Longlong; Jiao, Pingxuan; Fan, Zibo; Han, Xu; Wu, Xingyu; Zhou, Xiaoshu; Yu, Fei; Zhang, Yongmin; Zhang, Liangren; Zhang, Lihe; Zhou, Demin; Xiao, Sulong

    2016-03-03

    Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43). Moreover, we evaluated these novel compounds for their anti-influenza activities against A/WSN/33 virus in MDCK cells. Among all evaluated compounds, the 2,3-O,O-dibenzyl-6-deoxy-l-ascorbic acid-betulinic acid conjugate (30) showed the most significant anti-influenza activity with an EC50 of 8.7 μM, and no cytotoxic effects on MDCK cells were observed. Time-of-addition assay indicated that compound 30 acted at an early stage of the influenza life cycle. Further analyses revealed that influenza virus-induced hemagglutination of chicken red blood cells was inhibited by treatment of compound 30, and the interaction between the influenza hemagglutinin (HA) and compound 30 was determined by surface plasmon resonance (SPR) with a dissociation constant of KD = 3.76 μM. Finally, silico docking studies indicated that compound 30 and its derivative 31 were able to occupy the binding pocket of HA for sialic acid receptor. Collectively, these results suggested that l-ascorbic acid-conjugated pentacyclic triterpenes were promising anti-influenza entry inhibitors, and HA protein associated with viral entry was a promising drug target.

  5. Iridium-catalyzed ortho-selective C-H silylation of aromatic compounds directed toward the synthesis of π-conjugated molecules with Lewis acid-base interaction.

    Science.gov (United States)

    Wakaki, Takayuki; Kanai, Motomu; Kuninobu, Yoichiro

    2015-04-03

    We successfully developed an iridium-catalyzed ortho-selective C-H silylation of aromatic compounds. The reaction exhibited a wide substrate scope, and a variety of π-conjugated molecules were synthesized in good to excellent yields, even in gram scale. Several silyl groups could also be introduced into the products. The experimental results indicated that the regioselectivity could be controlled by a Lewis acid-base interaction between the Lewis acidic silicon atoms of fluorinated hydrosilanes and the Lewis basic nitrogen atoms of aromatic compounds.

  6. Molecular docking of Anopheles gambiae and Aedes aegypti glutathione S-transferases epsilon 2 (GSTE2 against usnic acid: an evidence of glutathione conjugation

    Directory of Open Access Journals (Sweden)

    Rafael Trindade Maia

    2014-10-01

    Full Text Available The aim of this study was to develop a theoretical model using Anopheles gambiae GSTE2 structure as template for Aedes aegypti GSTE2 by homology modeling Docking simulations were performed for both the enzymes against usnic acid in neutral and anionic forms. Ramachandran plot revealed that 93.9% of the GSTE2 model residues were located on most favored regions. Model evaluation was made by the ANOLEA and GROMOS analysis. Docking results indicated that the enzymes were able to form glutathione-conjugate with usnic acid in both the forms (anionic and neutral.

  7. Trans-10, cis-12-conjugated linoleic acid does not increase body fat loss induced by energy restriction.

    Science.gov (United States)

    Lasa, Arrate; Churruca, Itziar; Simón, Edurne; Fernández-Quintela, Alfredo; Rodríguez, Victor Manuel; Portillo, María Puy

    2008-12-01

    Very little evidence exists concerning the effects of conjugated linoleic acid (CLA) on body fat reduction induced by energy restriction. Moreover, although an effect of trans-10, cis-12-CLA on lipolysis has been suggested, it has not been consistently shown. The aims of the present study were to determine whether trans-10, cis-12-CLA increases the reduction of body fat induced by energy restriction, and to analyse its effect on lipolysis and adipose tissue lipase expression (hormone-sensitive lipase (HSL) and adipose tissue TAG lipase (ATGL)). Male Syrian Golden hamsters were fed a high-fat diet during 7 weeks in order to make them fatter. Then they were submitted to a mild energy restriction (25 %) without or with supplementation of 0.5 % trans-10, cis-12-CLA for 3 weeks. Basal glycerol release and lipolysis stimulated by several drugs acting at different levels of the lipolytic cascade were measured in epididymal adipose tissue. The expression of HSL and ATGL was assessed by real-time RT-PCR. No differences were found in adipose tissues size between the experimental groups. Medium adipocyte size and total number of adipocytes were similar in both experimental groups. Animals fed the CLA-enriched diet showed similar lipolytic rates as well as HSL and ATGL expressions to the controls. In conclusion, trans-10, cis-12-CLA does not promote adipose tissue lipid mobilisation nor does it heighten body fat reduction induced by energy restriction. Consequently, this CLA isomer does not seem to be a useful tool to be included in body weight-loss strategies followed in obesity treatment.

  8. Carboxymethyl-β-cyclodextrin conjugated nanoparticles facilitate therapy for folate receptor-positive tumor with the mediation of folic acid.

    Science.gov (United States)

    Su, Chang; Li, Hongdan; Shi, Yijie; Wang, Guan; Liu, Liwei; Zhao, Liang; Su, Rongjian

    2014-10-20

    Currently, clinical operation treatments, chemotherapy and radiotherapy just could eliminate local tumor cells. However, chemotherapy and radiotherapy also injury normal cells and lead to serious side effects and toxicities. So, it is necessary to find an effective target cancer carrier that delivers the anticancer agents into tumor cells and reduces normal cells' injury. Folic acid (FA) is a classical targeting agent mediates internalization of chemical drugs into tumor cells which over-express folate receptor (FR) on their surface. We herein report that based on host-guest interaction, NPs decorated by novel folate enhance antitumor drug delivery. BSA-NPs were prepared by desolvation method and carboxymethyl-β-cyclodextrin (CM-β-CD) was conjugated to the surface of NPs by carbodiimide coupling to hold FA. From in vitro cytotoxicity assay, cell apoptosis study, intracellular ATP level assay and western blot, we can see that FA-CM-β-CD-BSA NPs as good monodispersity, negative charge, and homogenous particle size have a high encapsulation efficiency. The results showed that MTT and cell apoptosis demonstrated that FA-decorated NPs exhibit stronger inhibition rate and induce obvious apoptosis in FR positive Hela cells as compared to free drug and FA undecorated NPs. Moreover, 5-fluorouracil (5-Fu) loaded FA-CM-β-CD-BSA NPs down-regulate ATP levels and increase the expression of caspase-3. Taken together, FA-CM-β-CD-BSA NPs enhance FR receptor-mediated endocytosis and lead to more intracellular uptake of drug, inducing the higher apoptosis ratio of cells than free 5-Fu.

  9. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40*

    Science.gov (United States)

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole; Grundmann, Manuel; Mielenz, Manfred; Sauerwein, Helga; Christiansen, Elisabeth; Due-Hansen, Maria E.; Ulven, Trond; Ullrich, Susanne; Gomeza, Jesús; Drewke, Christel; Kostenis, Evi

    2011-01-01

    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1−/− knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes. PMID:21339298

  10. Expression Pattern and Regulatory Role of microRNA-23a in Conjugated Linoleic Acids-Induced Apoptosis of Adipocytes

    Directory of Open Access Journals (Sweden)

    Renli Qi

    2016-11-01

    Full Text Available Background/Aims: Conjugated linoleic acids (CLAs are known to induce apoptosis in adipocytes; however, the cellular mechanisms involved remained illdefined. We explored the different apoptotic induction effects of two CLA isomers on adipocytes and then investigated the expression and function of microRNAs (miRNAs related to the apoptosis. Methods: TUNEL and FCM assays were used to detect CLAs-induced adipocyte apoptosis. Microarrays were used to compare the differential expression of miRNAs. MiR-23a, a miRNA that showed significant changes in expression in the CLA-treated cells, was selected for the subsequent functional studies via over-expression and knock down in in vivo and in vitro experiments. Results: C9, t11-CLA exhibited a stronger induction of apoptosis in the differentiated 3T3-L1 adipocytes than t10, c12-CLA. However, t10, c12-CLA could rapidly activate NF-κB, which may have caused their different apoptotic effects. MiR-23a was markedly down-regulated by the CLAs treatment and miR-23a over-expression attenuated CLA-induced apoptosis. Apoptosis protease-activating factor 1 (APAF1 was identified as a target gene of miR-23a. In an in vivo experiment endogenous miR-23a was down-regulated in mice fed with a mixture of both CLAs. The mice also exhibited less fat deposition and more apoptotic fat cells in adipose tissue. Moreover, endogenous miR-23a was suppressed in mice via intravenous injection with an antagomir which resulted in decreased body weight, increased number of apoptotic fat cells and increased APAF1 expression in adipose tissue. Conclusion: Taken together, our results suggest that miR-23a plays a critical role in CLA-induced apoptosis in adipocytes via controlling APAF1 expression.

  11. Enhancement of ajoene-induced apoptosis by conjugated linoleic acid in 3T3-L1 adipocytes.

    Science.gov (United States)

    Yang, Jeong-Yeh; Della-Fera, Mary Anne; Hausman, Dorothy B; Baile, Clifton A

    2007-06-01

    Ajoene has been shown to induce apoptosis in 3T3-L1 adipocytes. In this report the effects on apoptosis of combinations of ajoene and trans-10, cis-12 conjugated linoleic acid (t10,c12CLA) in 3T3-L1 adipocytes were investigated. Although t10,c12CLA alone had no effect, ajoene plus t10,c12CLA reduced cell viability more than ajoene alone at 24 h (59.1 vs. 85.9% of control, respectively; p<0.05). Compared to treatment with t10,c12CLA, ajoene increased apoptosis 218% after 24 h (p<0.01), whereas ajoene plus t10,c12CLA increased apoptosis 122% over that caused by ajoene alone (p<0.01). Immunoblotting analysis also indicated that ajoene plus t10,c12CLA caused a greater increase in phosphorylation of c-Jun N-terminal kinase (JNK) and Bax expression and a greater release of mitochondrial proteins (cytochrome c, AIF) than additive responses to each compound alone. Ajoene plus t10,c12CLA also increased ROS production more than that resulting from ajoene treatment alone (264 vs 204% after 40 min, respectively; p<0.01). Furthermore, the antioxidant NAC prevented ROS generation and apoptosis by ajoene plus t10,c12CLA. Interestingly, the combination of ajoene and t10,c12CLA increased NF-kappaB activation and decreased the level of phosphorylated Akt more than each compound alone. Altogether, our observations indicate that t10,c12CLA potentiates the effect of ajoene on apoptosis in 3T3-L1 adipocytes.

  12. GX1-conjugated poly(lactic acid nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment

    Directory of Open Access Journals (Sweden)

    Du Y

    2015-05-01

    Full Text Available Yang Du,1,* Qian Zhang,1,* Lijia Jing,2 Xiaolong Liang,2 Chongwei Chi,1 Yaqian Li,1 Xin Yang,1 Zhifei Dai,2 Jie Tian1 1Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Biomedical Engineering, College of Engineering, Peking University, Beijing People’s Republic of China *These authors contributed equally to this work Abstract: Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid nanoparticles encapsulating Endostar (GPENs and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo

  13. In vitro study of the effect of diesterified alkoxyglycerols with conjugated linoleic acid on adipocyte inflammatory mediators

    Directory of Open Access Journals (Sweden)

    Reglero Guillermo

    2010-04-01

    Full Text Available Abstract Background Adipocytes contribute to inflammation and the innate immune response through expression of inflammatory mediators. High levels of these mediators have been related to chronic inflammation state and insulin resistance, cardiovascular diseases and diabetes type 2, among other disorders. 3-octadecylglycerol (batyl alcohol has been described as an inflammatory agent, whereas Conjugated Linoleic Acid (CLA is considered effective against obesity. In this study we examined the anti-inflammatory activity and mechanisms of modified alkoxyglycerols. Tumor necrosis factor (TNF-α activated mature adipocytes were used as cellular model of inflammation. Secreted levels and gene expressions of some inflammatory mediators, such as the adipokines, interleukin (IL-1β, IL-6 and IL-10; and the levels of leptin and adiponectin hormones were quantified in presence and absence of alkoxyglycerols and when human adipocyte cells were or not activated by TNF-α. The aim of this study is to describe the effects of nonesterified alkoxyglycerols, CLA and diesterified alkoxyglycerols with CLA (DEA-CLA and check if they present beneficial properties using an in vitro model of some chronic diseases related to the inflammatory process, such as obesity, using human mature adipocytes activated with TNF-α. Results Our data suggest that DEA-CLA, product of the esterification between the CLA and batyl alcohol, present beneficial effects on adipocytes close to observed and described for CLA (i.e. decrease of IL-1β and no adverse effects as observed for batyl alcohol (i.e. decrease of IL-10. In addition, DEA-CLA presented similar activity to CLA showing a trend to increase the secreted levels of adiponectin and decreasing the secreted levels of leptin. Conclusions CLA and DEA-CLA modify adipocyte inflammatory mediators and also could play a role on energy homeostasis through depletion of leptin levels.

  14. Interaction of hexa-His tag with acidic amino acids results in facilitated refolding of halophilic nucleoside diphosphate kinase.

    Science.gov (United States)

    Ishibashi, Matsujiro; Ida, Keiko; Tatsuda, Shuhei; Arakawa, Tsutomu; Tokunaga, Masao

    2011-11-01

    We have previously reported that amino-terminal extension sequence containing hexa-His facilitated refolding and assembly of hexameric nucleoside diphosphate kinase from extremely halophilic archaeon Halobacterium salinarum (NDK). In this study, we made various mutations in both the tag sequence and within NDK molecule. SerNDK, in which hexa-His was replaced with hexa-Ser, showed no facilitated folding. In addition, HisD58GD63G, in which both Asp58 and Asp63 in NDK were replaced with Gly, also showed no refolding enhancement. These results suggest that hexa-His in His-tag interact cooperatively with either Asp58 or Asp63 or both. Furthermore, G114D mutant, which formed a dimer in low salt solution, was strongly stabilized by His-tag to form a stable hexamer.

  15. Role of SbmA in the uptake of peptide nucleic acid (PNA)-peptide conjugates in E. coli.

    Science.gov (United States)

    Ghosal, Anubrata; Vitali, Ally; Stach, James E M; Nielsen, Peter E

    2013-02-15

    Antisense PNA oligomers targeting essential genes (acpP or ftsZ) and conjugated to the delivery peptide L((KFF)(3)K) show complete growth inhibition of wild type E. coli strain (MG1655) with submicromolar MIC. In this study we show that resistant mutants generated against such PNA-peptide conjugates had disruptions in the region of sbmA, a gene encoding an inner membrane peptide transporter. The wild type sensitivity to the PNA conjugates was re-established in the resistance mutants by complementation with sbmA. Furthermore, deletion of sbmA in E. coli AS19, a strain that is sensitive to unmodified PNA, resulted in resistance to PNA. Finally, PNA conjugated with the corresponding non-biological H-D((KFF)(3)K) peptide retained antibacterial activity in sbmA deletion strains, whereas the same conjugate with a protease-sensitive linker did not. These results clearly identify SbmA as a carrier of naked PNA over the inner bacterial membrane and thereby infer that the peptide is transporting the PNA conjugates over the outer membrane. Strains lacking SbmA were used to screen novel peptide-PNA carriers that were SbmA-independent. Four such PNA-peptide conjugates, H-D((KFF)(3)K), H-(RFR)(4)-Ahx-βAla, H-(R-Ahx-R)(4)-Ahx-βAla, and H-(R-Ahx)(6)-βAla, were identified that utilize an alternative uptake mechanism but retain their antimicrobial potency. In addition SbmA is the first protein identified to recognize PNA.

  16. Folic acid-conjugated MnO nanoparticles as a T1 contrast agent for magnetic resonance imaging of tiny brain gliomas.

    Science.gov (United States)

    Chen, Ning; Shao, Chen; Qu, Yanming; Li, Shuai; Gu, Wei; Zheng, Tingting; Ye, Ling; Yu, Chunjiang

    2014-11-26

    Detection of brain gliomas at the earliest stage is of great importance to improve outcomes, but it remains a most challenging task. In this study, oleic acid capped manganese oxide (MnO) nanoparticles (NPs) were prepared by the thermal decomposition of manganese oleate precursors and then transformed to water-dispersible MnO NPs by replacing oleic acid with N-(trimethoxysilylpropyl) ethylene diamine triacetic acid (TETT) silane. The covalently bonded TETT silane offers MnO NPs colloidal stability and abundant carboxylic functional groups allowing the further conjugation of the glioma-specific moiety, folic acid (FA). Moreover, the thin layer of TETT silane ensures a short distance between external Mn ion and water proton, which endows the FA-conjugated, TETT modified MnO (MnO-TETT-FA) NPs a longitudinal relaxivity as high as 4.83 mM(-1) s(-1). Accordingly, the in vivo magnetic resonance (MR) images demonstrated that MnO-TETT-FA NPs could efficiently enhance the MRI contrast for tiny brain gliomas. More importantly, due to the specificity of FA, MnO-TETT-FA NPs led to a clearer margin of the tiny glioma. This together with the good biocompatibility discloses the great potential of MnO-TETT-FA NPs as effective MRI contrast agents for the early diagnosis of brain gliomas.

  17. Conjugated fatty acids and methane production by rumen microbes when incubated with linseed oil alone or mixed with fish oil and/or malate.

    Science.gov (United States)

    Li, Xiang Z; Gao, Qing S; Yan, Chang G; Choi, Seong H; Shin, Jong S; Song, Man K

    2015-08-01

    We hypothesized that manipulating metabolism with fish oil and malate as a hydrogen acceptor would affect the biohydrogenation process of α-linolenic acid by rumen microbes. This study was to examine the effect of fish oil and/or malate on the production of conjugated fatty acids and methane (CH4 ) by rumen microbes when incubated with linseed oil. Linseed oil (LO), LO with fish oil (LO-FO), LO with malate (LO-MA), or LO with fish oil and malate (LO-FO-MA) was added to diluted rumen fluid, respectively. The LO-MA and LO-FO-MA increased pH and propionate concentration compared to the other treatments. LO-MA and LO-FO-MA reduced CH4 production compared to LO. LO-MA and LO-FO-MA increased the contents of c9,t11-conjugated linoleic acid (CLA) and c9,t11,c15-conjugated linolenic acid (CLnA) compared to LO. The content of malate was rapidly reduced while that of lactate was reduced in LO-MA and LO-FO-MA from 3 h incubation time. The fold change of the quantity of methanogen related to total bacteria was decreased at both 3 h and 6 h incubation times in all treatments compared to the control. Overall data indicate that supplementation of combined malate and/or fish oil when incubated with linseed oil, could depress methane generation and increase production of propionate, CLA and CLnA under the conditions of the current in vitro study. © 2015 Japanese Society of Animal Science.

  18. Transcriptomic Changes in Liver of Young Bulls Caused by Diets Low in Mineral and Protein Contents and Supplemented with n-3 Fatty Acids and Conjugated Linoleic Acid

    Science.gov (United States)

    Pegolo, Sara; Cecchinato, Alessio; Mach, Núria; Babbucci, Massimiliano; Pauletto, Marianna; Bargelloni, Luca; Schiavon, Stefano; Bittante, Giovanni

    2016-01-01

    The aim of the present study was to identify transcriptional modifications and regulatory networks accounting for physiological and metabolic responses to specific nutrients in the liver of young Belgian Blue × Holstein bulls using RNA-sequencing. A larger trial has been carried out in which animals were fed with different diets: 1] a conventional diet; 2] a low-protein/low-mineral diet (low-impact diet) and 3] a diet enriched in n-3 fatty acids (FAs), conjugated linoleic acid (CLA) and vitamin E (nutraceutical diet). The initial hypothesis was that the administration of low-impact and nutraceutical diets might influence the transcriptional profiles in bovine liver and the resultant nutrient fluxes, which are essential for optimal liver function and nutrient interconversion. Results showed that the nutraceutical diet significantly reduced subcutaneous fat covering in vivo and liver pH. Dietary treatments did not affect overall liver fat content, but significantly modified the liver profile of 33 FA traits (out of the total 89 identified by gas-chromatography). In bulls fed nutraceutical diet, the percentage of n-3 and CLA FAs increased around 2.5-fold compared with the other diets, whereas the ratio of n6/n3 decreased 2.5-fold. Liver transcriptomic analyses revealed a total of 198 differentially expressed genes (DEGs) when comparing low-impact, nutraceutical and conventional diets, with the nutraceutical diet showing the greatest effects on liver transcriptome. Functional analyses using ClueGo and Ingenuity Pathway Analysis evidenced that DEGs in bovine liver were variously involved in energy reserve metabolic process, glutathione metabolism, and carbohydrate and lipid metabolism. Modifications in feeding strategies affected key transcription factors regulating the expression of several genes involved in fatty acid metabolism, e.g. insulin-induced gene 1, insulin receptor substrate 2, and RAR-related orphan receptor C. This study provides noteworthy insights into

  19. Effects of milk supplementation with conjugated linoleic acid on weight control and body composition in healthy overweight people

    Directory of Open Access Journals (Sweden)

    Brida López-Plaza

    2013-12-01

    Full Text Available Introduction: Conjugated linoleic acids (CLAs have shown beneficial effects in weight control therapy however this relation is not clear. Objetive: The aim of the study was to examine the effects and safety of 3 g of a 1:1 mix of c9-t11 and t10-c12 on weight control and body composition in healthy overweight individuals. Methods: A prospective, placebo-controlled, randomised double-blind, parallel clinical trial lasting 24 weeks was carried out in 38 volunteers (29w, 9m aged 30-55 years and BMI ≥ 27 -<30 kg/m² who consumed 200 ml/day of skimmed milk with 3g of CLAs or 3g olive oil (placebo. Anthropometric, biochemical and dual x-ray absorptiometry (DXA tests were measured. Diet and physical activity were assessed. Results: Subjects maintained their habitual dietary and exercise patterns over the study. Only CLA group showed a significant decrease in weight (74.43 ± 10.45 vs 73.54 ± 11.66 kg, p = 0.029 and waist circumference (91.45 ± 10.33 vs 90.65 ± 9.84 cm, p = 0.012 between baseline and end of the study. BMI and waist height ratio decreased (28.44 ± 1.08 vs 27.81 ± 1.43 kg/m², p = 0.030 and 0.57 ± 0.05 vs 0.56 ± 0.04 p = 0.013 respectively in CLA group at the end. CLA group experienced a reduction in total fat mass after 24 weeks (38.62 ± 5.02 vs 36.65 ± 5.64%, p = 0.035. No decrease was observed in Control group. HOMA index had no changes. Conclusions: The consumption of skimmed milk enriched with 3g of a 1:1 mixture of c9-t11 and t10-c12 for 24 weeks led to a decrease in body weight and total fat mass in healthy, overweight subjects who maintained habitual diets and exercise patterns. No adverse effects were observed. Registered under ClinicalTrials.gov Identifier No. NCT01503047.

  20. [Effects of conjugated linoleic acid and exercise on RBP4 of liver and adipose tissues in adolescent obese rats].

    Science.gov (United States)

    Cui, Jianfei; Bai, Youping; Li, Meng; Xu, Xiaodong; Dai, Yuanyuan; Zhang, Jing

    2015-01-01

    To exploer effects of conjugated linoleic acid and exercise on RBP4 of liver and adipose tissues in adolescent obese rats. 8 adolescent SD rats were selected as blank control (C) with normal diet. Obese rats were modeled with high fat feeding for 7 weeks. 32 obese rats were selected and randomly divided into 4 groups: control group (OC), CLA group ( OCC), exercise group (OM), exercise combined with CLA group (OMC). Exercise treatment were performed on animal treadmill with running speed of 21 - 25 m/min, 60 min/every time. For CLA treatment, each rat was fed 1.6 g/kg, one time/day, 5 times/week, for 8 weeks. Animals were anesthesia treated after experiment, blood and body tissues were collected. The content of blood glucose was measured, the insulin sensitivity was calculated, testing the expression of RBP4 mRNA in visceral adipose tissue, expression of RBP4 protein in liver cells and plasma RBP4 concentration. (1) Weight, weight growth rate and body fat percentage of OM, OMC groups were lower than OC, OCC groups (P OMC groups were significantly lower than OC, OCC groups (P OMC groups was higher than OC, OCC groups (P OMC groups in visceral adipose tissue was lower than OC, OCC groups (P OMC groups in liver cells was significantly lower than OC, OCC groups. RBP4 concentration in plasma of OM, OMC groups was lower than OC, OCC groups (P OMC group were higher than OM group, but the percentage of body fat, blood glucose content and the expression of RBP4 were lower than OM group, there were no significant differences between them. Simple exercise and exercise combined with CLA conld significantly reduced adolescent obese rats weight, weight growth rate, percentage of body fat, blood glucose content and also reduced RBP4 mRNA expression in visceral adipose tissue, RBP4 protein expression in liver tissue, RBP4 level in plasma,but can increase sensitivity to insulin, in a word, the treatment of exercise and exercise combine with CLA is better than the simple complement

  1. EFFECT OF CIS-9, TRANS-11-CONJUGATED LINOLEIC ACID ON CELL CYCLE OF MAMMARY ADENOCARCINOMA CELLS(MCF-7)

    Institute of Scientific and Technical Information of China (English)

    刘家仁; 陈炳卿; 韩晓辉; 杨艳梅; 郑玉梅; 刘瑞海

    2002-01-01

    Objective: To determine the effect of cis-9, trans-1 1-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and the possible mechanism of the inhibitory effect of c9,t11-CLA. Methods: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA , cyclin A, B1, D1, p16ink4a and p21cip/waf1 of MCF-7 cells at various c9,t11-CLA concentrations (25μM, 50μM, 100μM and 200μM), at 24h and 48h. 96% ethand was used as negative control. Results: The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9,t11-CLA. After treatment with various doses of c9,t11-CLA mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively. Inhibitory effect of c9,t11-CLA on DNA synthesis (except for 25μM, 24h) was demonstrated by significantly less incorporation of 3H-TdR than the negative control (P<0.05 and P<0.01). To further investigate the influence of the cell cycle progression, we found that c9,t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that incubation with different concentration of c9,t11-CLA at various times significantly decreased the expression of PCNA, Cyclin A, B1, D1 in MCF-7 cells compared to the negative control (P<0.01), whereas the expression of p16ink4a and p21cip/waf1, cyclin-dependent kinases inhibitors (CDKI), were increased. Conclusions: The cell growth and proliferation of MCF-7 cells is inhibited by c9,t11-CLA via blocking cell cycle, accompanying reduced expression of cyclin A, B1, D1 and enhanced expression of CDKI (p16ink4a and p21cip/wafl).

  2. Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice

    Directory of Open Access Journals (Sweden)

    Razjouyan Javad

    2015-07-01

    Full Text Available To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato iron (III to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl triethoxysilane (APTES, and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG through amine group of (3-aminopropyl triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR overexpressing KB (established from a HeLa cell contamination and mouse fibroblast cell (MFB lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB. Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.

  3. Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG-poly(glutamic acid)2 copolymers via hydrazone linkers.

    Science.gov (United States)

    Sui, Bowen; Xu, Hui; Jin, Jian; Gou, Jingxin; Liu, Jingshuo; Tang, Xing; Zhang, Yu; Xu, Jinghua; Zhang, Hongfeng; Jin, Xiangqun

    2014-08-11

    In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.

  4. Docosahexaenoic Acid and Eicosapentaenoic Acid Did not Alter trans-10,cis-12 Conjugated Linoleic Acid Incorporation into Mice Brain and Eye Lipids.

    Science.gov (United States)

    Vemuri, Madhuri; Adkins, Yuriko; Mackey, Bruce E; Kelley, Darshan S

    2017-09-01

    trans 10,cis 12-CLA has been reported to alter fatty acid composition in several non-neurological tissues, but its effects are less known in neurological tissues. Therefore, the purpose of this study was to determine if CLA supplementation would alter brain and eye fatty acid composition and if those changes could be prevented by concomitant supplementation with docosahexaenoic acid (DHA; 22:6n3) or eicosapentaenoic acid (EPA; 20:5n3). Eight-week-old, pathogen-free C57BL/6N female mice (n = 6/group) were fed either the control diet or diets containing 0.5% (w/w) t10,c12-CLA in the presence or absence of either 1.5% DHA or 1.5% EPA for 8 weeks. CLA concentration was significantly (P < 0.05) greater in the eye but not in the brain lipids of the CLA group when compared with the control group. The sums of saturated, monounsaturated, polyunsaturated fatty acids, and n3:n6 ratio did not differ between these two groups for both tissues. The n3:n6 ratio and concentrations of 20:5n3 and 22:5n3 were significantly greater, and those of 20:4n6, 22:4n6, and 22:5n6 were lesser in the CLA + DHA and CLA + EPA groups than in the control and CLA groups for either tissue. DHA concentration was higher in the CLA + DHA group only but not in the CLA + EPA group when compared with the CLA group for both tissues. The dietary fatty acids generally induced similar changes in brain and eye fatty acid concentration and at the concentrations used both DHA and EPA fed individually with CLA were more potent than CLA alone in altering the tissue fatty acid concentration.

  5. Folic Acid Conjugated Chitosan for Targeted Delivery of siRNA to Activated Macrophages in vitro and in vivo

    DEFF Research Database (Denmark)

    Yang, Chuanxu; Gao, Shan; Kjems, Jørgen

    2014-01-01

    was conjugated to chitosan (FA–CS) and used to formulate siRNA into nanoparticles capable of cell specific delivery. The physiochemical properties of the nanoparticles, including size, zeta-potential and encapsulation efficiency, were characterized and the intracellular uptake and gene silencing efficiency were...

  6. Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells

    OpenAIRE

    Beppu, Fumiaki; Hosokawa, Masashi; Tanaka, Leo; Kohno, Hiroyuki; Tanaka, Takuji; Miyashita, Kazuo

    2006-01-01

    This study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers [cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA] on human colon cancer cell lines (Caco-2, HT-29 and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 μM, each isomer, even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time-dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t...

  7. Contents of conjugated linoleic acid isomers cis9,trans11 and trans10,cis12 in ruminant and non-ruminant meats available in the Italian market

    OpenAIRE

    Francesca M. Cicognini; Filippo Rossi; Samantha Sigolo; Antonio Gallo; Aldo Prandini

    2014-01-01

    Conjugated linoleic acid (CLA) isomers are considered healthy factors due to their anticarcinogenic, anti-atherosclerotic and lipolytic effect. A recommended daily intake from 0.8 to 3 g CLA/day/person has been proposed to obtain biological effects in humans. The aim of this work was to provide data on cis9,trans11 (c9,t11 CLA) and trans10,cis12 (t10,c12 CLA) contents in meats collected from Italian largescale retail trade and completing a food CLA database. In a first trial, beef loin meats ...

  8. Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yang R

    2014-09-01

    Full Text Available Rui Yang,1 YanLi An,2 FengQin Miao,1 MengFei Li,1 PeiDang Liu,1 QiuSha Tang1 1School of Medicine, Southeast University, 2Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, Jiangsu Province, People’s Republic of China Background: This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored. Methods: FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid was conjugated to the surface of albumin nanospheres via amino groups.Results: Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells.Conclusion: Folic acid-conjugated bovine serum albumin nanospheres composed of mixed

  9. Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

    Science.gov (United States)

    Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

    2014-01-01

    Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

  10. Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

    Science.gov (United States)

    Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

    2015-01-01

    In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

  11. Conjugated linoleic acid and fatty acid binding protein as antioxidants Ácido linoleico conjugado y proteína transportadora de ácidos grasos como antioxidantes

    Directory of Open Access Journals (Sweden)

    V.A. Piergiacomi

    2006-12-01

    Full Text Available Studies were carried out to determine the effect of conjugated linoleic acid (CLA and rat liver cytosolic protein enriched in fatty acid binding protein (FABP on the non-enzymatic lipid peroxidation of rat liver microsomes. The inhibition of lipid peroxidation was more evident when the FABP containing fraction obtained from CLA-group was used with either kind of microsomes (CLA and control. The chemiluminescence and polyunsaturated fatty acid composition of rat liver microsomes changed after CLA treatment. When native and peroxidized microsomes obtained from control group were compared, the most affected polyunsaturated fatty acids were: C18:2, C18:3 and C20:4, while in CLA-group C20:4 was mainly peroxidized The simultaneous analysis of chemiluminescence and fatty acid composition demonstrated that CLA and FABP play a role protecting rat liver microsomes against the harmful effect of lipid peroxidation.El objetivo del trabajo fue determinar el efecto del ácido linoleico conjugado (ALC y de la proteína citosólica de hígado de rata enriquecida en Proteína Transportadora de Ácidos Grasos (PTAG, sobre la peroxidación no enzimática de lípidos de microsomas hepáticos de rata. Luego de la incubación de éstos en un sistema ascorbato-Fe++ se observó que el total de cpm/mg de proteina originada por quimioluminiscencia fue menor en los microsomas obtenidos de las ratas del grupo ALC respecto a los del grupo control. Cuando la fracción PTAG obtenida del grupo ALC fue agregada a la peroxidación de microsomas de ambos grupos de animales ALC y control, la inhibición de la lipoperoxidación fue más evidente. Además se encontró que ambas fracciones PTAG, tanto la obtenida de animales del grupo ALC como la obtenida del grupo control, tuvieron mayor efecto como antioxidantes cuando se usaron microsomas ALC respecto a microsomas control. La composición de ácidos grasos de los microsomas cambió luego del tratamiento con ALC. Comparando

  12. Mining the bitter melon (momordica charantia l.) seed transcriptome by 454 analysis of non-normalized and normalized cDNA populations for conjugated fatty acid metabolism-related genes

    Science.gov (United States)

    Seeds of Momordica charantia (bitter melon) produce high levels of eleostearic acid, an unusual conjugated fatty acid with industrial value. Deep sequencing of non-normalized and normalized cDNAs from developing bitter melon seeds was conducted to uncover key genes required for biotechnological tran...

  13. Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with α-linolenic acid and the transport mechanism of the conjugates.

    Science.gov (United States)

    Xiao, Yuliang; Li, Pingli; Cheng, Yanna; Zhang, Xinke; Sheng, Juzheng; Wang, Decai; Li, Juan; Zhang, Qian; Zhong, Chuanqing; Cao, Rui; Wang, Fengshan

    2014-04-25

    The purpose of this report was to demonstrate the effect of amphiphilic polysaccharides-based self-assembling micelles on enhancing the oral absorption of low molecular weight chondroitin sulfate (LMCS) in vitro and in vivo, and identify the transepithelial transport mechanism of LMCS micelles across the intestinal barrier. α-Linolenic acid-low molecular weight chondroitin sulfate polymers(α-LNA-LMCS) were successfully synthesized, and characterized by FTIR, (1)HNMR, TGA/DSC, TEM, laser light scattering and zeta potential. The significant oral absorption enhancement and elimination half-life (t₁/₂) extension of LNA-LMCS2 in rats were evidenced by intragastric administration in comparison with CS and LMCS. Caco-2 transport studies demonstrated that the apparent permeability coefficient (Papp) of LNA-LMCS2 was significantly higher than that of CS and LMCS (p<0.001), and no significant effects on the overall integrity of the monolayer were observed during the transport process. In addition, α-LNA-LMCS micelles accumulated around the cell membrane and intercellular space observed by confocal laser scanning microscope (CLSM). Furthermore, evident alterations in the F-actin cytoskeleton were detected by CLSM observation following the treatment of the cell monolayers with α-LNA-LMCS micelles, which further certified the capacity of α-LNA-LMCS micelles to open the intercellular tight junctions rather than disrupt the overall integrity of the monolayer. Therefore, LNA-LMCS2 with low cytotoxicity and high bioavailability might be a promising substitute for CS in clinical use, such as treating osteoarthritis, atherosclerosis, etc.

  14. Changes in conjugated linoleic acid and C18:1 isomers profile during the ripening of Pecorino Toscano cheese produced with raw milk

    Directory of Open Access Journals (Sweden)

    Marcello Mele

    2012-10-01

    Full Text Available The aim of the present study was to investigate the evolution of the fatty acid profile, with particular attention to conjugated linoleic acid (CLA and to C18:1 isomers, during ripening of sheep cheese (Pecorino Toscano cheese produced with raw milk. After 60 days of ripening the total concentration of C18:1 isomers and that of CLA pool content decreased. In particular, if isomers profile is considered, the percentage of trans11 C18:1, trans10 C18:1 and cis9, trans11 CLA decreased as consequence of biohydrogenation or of double bonds isomerisation, while the concentration of trans10, cis12 CLA increased.

  15. N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced Activation of Microglia and Macrophages via COX-2.

    Science.gov (United States)

    Wang, Ya; Plastina, Pierluigi; Vincken, Jean-Paul; Jansen, Renate; Balvers, Michiel; Ten Klooster, Jean Paul; Gruppen, Harry; Witkamp, Renger; Meijerink, Jocelijn

    2017-03-15

    Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another amine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine significantly suppressed the production of nitric oxide (NO), the cytokine interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds, dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 (COX-2) mRNA level and production of prostaglandin E2 (PGE2) were concentration-dependently inhibited in macrophages. In activated BV-2 cells, PGE2 production was also reduced, without changes in COX-2 mRNA levels. In addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous endocannabinoid, may be an additional member of the group of immune-modulating n-3 fatty acid-derived lipid mediators.

  16. Intercalator conjugates of pyrimidine locked nucleic acid-modified triplex-forming oligonucleotides: improving DNA binding properties and reaching cellular activities

    Science.gov (United States)

    Brunet, Erika; Corgnali, Maddalena; Perrouault, Loïc; Roig, Victoria; Asseline, Ulysse; Sørensen, Mads D.; Babu, B. Ravindra; Wengel, Jesper; Giovannangeli, Carine

    2005-01-01

    Triplex-forming oligonucleotides (TFOs) are powerful tools to interfere sequence-specifically with DNA-associated biological functions. (A/T,G)-containing TFOs are more commonly used in cells than (T,C)-containing TFOs, especially C-rich sequences; indeed the low intracellular stability of the non-covalent pyrimidine triplexes make the latter less active. In this work we studied the possibility to enhance DNA binding of (T,C)-containing TFOs, aiming to reach cellular activities; to this end, we used locked nucleic acid-modified TFOs (TFO/LNAs) in association with 5′-conjugation of an intercalating agent, an acridine derivative. In vitro a stable triplex was formed with the TFO-acridine conjugate: by SPR measurements at 37°C and neutral pH, the dissociation equilibrium constant was found in the nanomolar range and the triplex half-life ∼10 h (50-fold longer compared with the unconjugated TFO/LNA). Moreover to further understand DNA binding of (T,C)-containing TFO/LNAs, hybridization studies were performed at different pH values: triplex stabilization associated with pH decrease was mainly due to a slower dissociation process. Finally, biological activity of pyrimidine TFO/LNAs was evaluated in a cellular context: it occurred at concentrations ∼0.1 μM for acridine-conjugated TFO/LNA (or ∼2 μM for the unconjugated TFO/LNA) whereas the corresponding phosphodiester TFO was inactive, and it was demonstrated to be triplex-mediated. PMID:16049028

  17. A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA.

    Science.gov (United States)

    Mero, Anna; Campisi, Monica; Favero, Marta; Barbera, Carlo; Secchieri, Cynthia; Dayer, Jean M; Goldring, Mary B; Goldring, Steven R; Pasut, Gianfranco

    2014-08-10

    Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP). High molecular weight hyaluronic acid (HA) is used as a lubricant in OA therapy, and, interestingly, HA polymers may normalize the levels of MMP-1, -3 and -13. We demonstrated that sCT rapidly clears from the knee joint of rat animal model, after intra-articular (i.a.) administration, and it induces systemic effects. Here, sCT was conjugated to HA (200kDa) with the aim of prolonging the residence time of the polypeptide in the joint space by reducing its clearance. An aldehyde derivative of HA was used for N-terminal site-selective coupling of sCT. The activity of sCT was preserved, both in vitro and in vivo, after its conjugation and the i.a. injection of HA-sCT did not trigger any systemic effects in rats. The efficacy of HA-sCT treatment was tested in a rabbit OA model and clear chondro-protective effect was proven by macro- and microscopic assessments and histological findings. Our results indicate that HAylation of sCT increases the size of the polypeptide in a stable covalent manner and delays its passage into the blood stream. We conclude that HA conjugation prolongs the anti-catabolic effects of sCT in joint tissues, including the synovial membrane and cartilage.

  18. Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound.

    Science.gov (United States)

    Varga, Gabriella; Lajkó, Norbert; Ugocsai, Melinda; Érces, Dániel; Horváth, Gyöngyi; Tóth, Gábor; Boros, Mihály; Ghyczy, Miklós

    2016-06-15

    Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim was to develop a new compound from ASA and Tris precursors and to characterize the biological effects of ASA-Tris and the derivatives ASA-bis- and mono-hydroxymethyl-aminomethane (ASA-Bis, ASA-Mono, respectively) using in vivo and in vitro test systems. ASA or ASA conjugates (0.55mmol/kg, each) were administered intragastrically to Sprague-Dawley rats. Changes in the mucosal structure and in the serosal microcirculation were detected by in vivo imaging techniques, the plasma TNF-alpha, tissue xanthine oxidoreductase and myeloperoxidase activities, and liver cytochrome c changes were also determined. In two separate series, platelet aggregation and carrageenan arthritis-induced inflammatory pain were measured in control, ASA and ASA-Tris-treated groups. Severe mucosal injury and a significant decrease in serosal red blood cell velocity developed in the ASA-treated group and an ~2-fold elevation in proinflammatory mediator levels evolved. ASA-Tris did not cause bleeding, microcirculatory dysfunction, mucosal injury or an elevation in proinflammatory markers. The ASA-Mono and ASA-Bis conjugates did not cause macroscopic bleeding, but the inflammatory activation was apparent. ASA-Tris did not influence the cyclooxygenase-induced platelet aggregation significantly, but the inflammatory pain was reduced as effectively as in the case of equimolar ASA doses. ASA-Tris conjugation is an effective approach through which the GI side-effects of ASA are controlled by decreasing the cytokine-mediated progression of pro-inflammatory events.

  19. Drimane Sesquiterpene-Conjugated Amino Acids from a Marine Isolate of the Fungus Talaromyces minioluteus (Penicillium Minioluteum

    Directory of Open Access Journals (Sweden)

    Suthatip Ngokpol

    2015-06-01

    Full Text Available Four new sesquiterpene lactones (3, 4, 6 and 7 and three known compounds, purpuride (1, berkedrimane B (2 and purpuride B (5, were isolated from the marine fungus, Talaromyces minioluteus (Penicillium minioluteum. New compounds were drimane sesquiterpenes conjugated with N-acetyl-l-valine, and their structures were elucidated by analysis of spectroscopic data, as well as by single crystal X-ray analysis. The isolated compounds could not inhibit the apoptosis-regulating enzyme, caspase-3, while three of the compounds (2, 3 and 7 exhibited weak cytotoxic activity.

  20. Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication.

    Directory of Open Access Journals (Sweden)

    V Haridas

    Full Text Available BACKGROUND: Japanese encephalitis virus (JEV is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties. METHODOLOGY/PRINCIPAL FINDINGS: In this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis.

  1. Cytotoxicity of folic acid conjugated hollow silica nanoparticles toward Caco2 and 3T3 cells, with and without encapsulated DOX.

    Science.gov (United States)

    Patel, Kunal; Sundara Raj, Behin; Chen, Yan; Lou, Xia

    2016-04-01

    Hollow silica nanoparticles of two sizes with and without a folic acid targeting ligand were synthesized. Fickian diffusion of the antitumor drug doxorubicin hydrochloride (DOX) was demonstrated by the produced nanoparticles, achieving a cumulative release of 73% and 45% for 215 nm and 430 nm particles respectively over a period of 500 h. The hollow silica nanoparticles presented a time and dose dependent toxicity, selective to human epithelial colorectal adenocarcinoma (Caco2) cells, over mouse embryonic fibroblast (3T3) cells. At 24h Caco2 cell viability was reduced to 66% using pure hollow silica at a concentration of 50 μg mL(-1), while that of 3T3 cells remained at 94% under the same conditions. The selective cytotoxicity of hollow silica nanoparticles was further enhanced by conjugation of folic acid and incorporation of DOX: at 24h and an equivalent DOX concentration of 0.5 μg mL(-1), viable Caco2 cells were reduced to 45% while 3T3 cells were reduced to 83%. Interestingly the equivalent dose of free DOX was more toxic to 3T3 than to Caco2 cells, reducing the 3T3 viability to 72% and the Caco2 viability to 80%, which is likely due to the presence of the p-glycoprotein pumps in Caco2 cells. Folic acid conjugation served to enhance the viability of both cell lines in this work. Careful optimization of the folate content should further improve the cell specificity of the hollow silica nanoparticles, thus providing a viable targeting platform for cancer therapy.

  2. Incorporation of a lauric acid-conjugated GRGDS peptide directly into the matrix of a poly(carbonate-urea)urethane polymer for use in cardiovascular bypass graft applications.

    Science.gov (United States)

    Kidane, Asmeret G; Punshon, Geoffrey; Salacinski, Henryk J; Ramesh, Bala; Dooley, Audrey; Olbrich, Michael; Heitz, Johannes; Hamilton, George; Seifalian, Alexander M

    2006-12-01

    Gly-Arg-Gly-Asp-Ser (GRGDS) was modified by conjugation to lauric acid (LA) to facilitate incorporation into the matrix of a poly(carbonate-urea)urethane (PCU) used in vascular bypass grafts. GRGDS and LA-GRGDS were synthesized using solid phase Fmoc chemistry and characterized by high performance liquid chromatography and Fourier transform infrared spectroscopy. LA-GRGDS was passively coated and incorporated as nanoparticle dispersion on the PCU films. Biocompatibility of the modified surfaces was investigated. Endothelial cells seeded on LA-GRGDS coated and incorporated PCU showed after 48 h and 72 h a significant (p < 0.05) increase in metabolism compared with unmodified PCU. The platelet adhesion and hemolysis studies showed that the modification of PCU had no adverse effect. In conclusion, LA-conjugated RGD derivatives, such as LA-GRGDS, that permit solubility into solvents used in solvent casting methodologies should have wide applicability in polymer development for use in coronary, vascular, and dialysis bypass grafts, and furthermore scaffolds utilized for tissue regeneration and tissue engineering.

  3. Identification of conjugated linoleic acid (CLA) isomers by silver ion-liquid chromatography/in-line ozonolysis/mass spectrometry (Ag+-LC/O3-MS).

    Science.gov (United States)

    Sun, Chenxing; Black, Brenna A; Zhao, Yuan-Yuan; Gänzle, Michael G; Curtis, Jonathan M

    2013-08-06

    A novel method for the identification of conjugated linoleic acid (CLA) isomers has been developed in which silver ion liquid chromatography is coupled to in-line ozonolysis/mass spectrometry (Ag(+)-LC/O3-MS). The mobile phase containing CLA isomers eluting from the Ag(+)-LC column flows through a length of gas-permeable tubing within an ozone rich environment. Ozone penetrating the tubing wall reacts with the conjugated double bonds forming ozonolysis product aldehydes. These, and their corresponding methanol loss fragment ions formed within the atmospheric pressure photoionization (APPI) source, were detected by in-line MS and used for the direct assignment of double bond positions. Assignment of positional isomers is based entirely on the two pairs of diagnostic ions seen in the in-line O3-MS mass spectra. In this way, de novo identification of CLA positional isomers, i.e. without requiring comparison to CLA standards, was achieved. The Ag(+)-LC/O3-MS method was applied to the analysis of CLA isomers in a commercial CLA supplement, milk fat, and the lipid extract from a Lactobacillus plantarum TMW1460 culture. The results demonstrate how Ag(+)-LC/O3-MS can be used for the direct and fast determination of CLA isomers at low concentrations and in complex lipid mixtures.

  4. Effect of different types of fibre supplemented with sunflower oil on ruminal fermentation and production of conjugated linoleic acids in vitro.

    Science.gov (United States)

    Li, Yanling; Meng, Qingxiang

    2006-10-01

    An in vitro study was conducted to determine the effect of different types of fibre supplemented with sunflower oil on ruminal fermentation and formation of conjugated linoleic acids (CLA) by mixed ruminal microorganisms. Cell wall components extracted from wheat straw (representing lignified fibre), soybean hulls (representing easily digestible fibre), and purified cellulose were used as substrates. Sunflower oil was supplemented at the same level for all three types of fibre. After 24 h of incubation, ruminal fermentation parameters (including 24 h gas production, pH value, concentration of ammonia nitrogen and volatile fatty acids) and the concentration of long chain fatty acids in the culture fluid were determined. Results showed that the type of fibre influenced ruminal fermentation traits and the biohydrogenation of unsaturated C18 fatty acids in vitro. Composition of LCFA and profile of CLA were altered by the fibre type. Compared to the digestible fibre and purified cellulose, lignified fibre significantly increased the production of cis-9, trans-11 CLA and total CLA (sum of cis-9, trans-11 CLA, trans-10, cis-12 CLA, trans-9, trans-11 CLA, and cis-9, cis-11 CLA) by ruminal microorganisms. It was concluded that ruminal fermentation and production of CLA can be affected by the type of dietary fibre.

  5. Biliary bile acids in birds of the Cotingidae family: taurine-conjugated (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid and two epimers (25R and 25S) of 3α,7α-dihydroxy-5β-cholestan-27-oic acid.

    Science.gov (United States)

    Hagey, Lee R; Iida, Takashi; Ogawa, Shoujiro; Adachi, Yuuki; Une, Mizuho; Mushiake, Kumiko; Maekawa, Masamitsu; Shimada, Miki; Mano, Nariyasu; Hofmann, Alan F

    2011-01-01

    Three C(27) bile acids were found to be major biliary bile acids in the capuchinbird (Perissocephalus tricolor) and bare-throated bellbird (Procnias nudicollis), both members of the Cotingidae family of the order Passeriformes. The individual bile acids were isolated by preparative RP-HPLC, and their structures were established by RP-HPLC, LC/ESI-MS/MS and NMR as well as by a comparison of their chromatographic properties with those of authentic reference standards of their 12α-hydroxy derivatives. The most abundant bile acid present in the capuchinbird bile was the taurine conjugate of C(27) (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid, a diastereomer not previously identified as a natural bile acid. The four diastereomers of taurine-conjugated (24ξ,25ξ)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid could be distinguished by NMR and were resolved by RP-HPLC. The RRT of the diastereomers (with taurocholic acid as 1.0) were found to be increased in the following order: (24R,25R)taurine conjugates) in both bird species. Epimers of the two compounds could be distinguished by their NMR spectra and resolved by RP-HPLC with the (25S)-epimer eluting before the (25R)-epimer. Characterization of the taurine-conjugated (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid and two epimers (25R and 25S) of 3α,7α-dihydroxy-5β-cholestan-27-oic acid should facilitate their detection in peroxisomal disease and inborn errors of bile acid biosynthesis.

  6. Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

    DEFF Research Database (Denmark)

    Kennedy, Arion; Martinez, Kristina; Chung, Soonkyu

    2010-01-01

    10,12 CLA-mediated production of reactive oxygen species (ROS), activation of ERK1/2 and cJun-NH2-terminal kinase (JNK), and induction of inflammatory genes. 10,12 CLA-mediated binding of NFkappaB to the promoters of interleukin (IL)-8 and cyclooxygenase (COX)-2 and induction of calcium......We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) induced inflammation and insulin resistance in primary human adipocytes by activating nuclear factor kappaB (NFkappaB) and extracellular signal-related kinase (ERK) signaling. In this study, we demonstrated...... that the initial increase in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8, an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor. Moreover, BAPTA, TMB-8, and D609 attenuated...

  7. Effect of whole linseed and rumen-protected conjugated linoleic acid enriched diets on feedlot performance, carcass characteristics, and adipose tissue development in young Holstein bulls.

    Science.gov (United States)

    Albertí, P; Gómez, I; Mendizabal, J A; Ripoll, G; Barahona, M; Sarriés, V; Insausti, K; Beriain, M J; Purroy, A; Realini, C

    2013-06-01

    Forty-eight young Holstein bulls (slaughtered at 458.6±9.79 kg body weight) were used to evaluate the effect of whole linseed and conjugated linoleic acid (CLA) supplementation on animal performance, adipose tissue development, and carcass characteristics. The animals were fed with one of four isoenergetic and isoproteic diets: control (0% linseed, 0% CLA), linseed (10% linseed, 0% CLA), CLA (0% linseed, 2% CLA), and linseed plus CLA (10% linseed, 2% CLA). Animal performance and carcass characteristics were unaffected by diet composition. Adding linseed or CLA to the concentrate diet did not result in significant differences in adipocyte size and number or lipogenic enzyme activity. However, while the frequency distribution of subcutaneous adipocyte diameters followed a normal distribution, the frequency distribution of intramuscular adipocyte diameters was not normal in any dietary group (skewness coefficients: 0.8, 1.2, 0.9, 0.8 for control, linseed, CLA, and linseed plus CLA, respectively; Padipose tissue.

  8. Use of immobilized phospholipase A1-catalyzed acidolysis for the production of structured phosphatidylcholine with an elevated conjugated linoleic acid content

    Energy Technology Data Exchange (ETDEWEB)

    Baeza-Jimenez, R.; Gonzalez-Rodriguez, J.; Kim, I. H.; Gracia, H. S.; Otero, C.

    2012-11-01

    Structured phosphatidylcholine (SPC) was successfully produced via immobilized phospholipase A1 (PLA1) catalyzed acidolysis of phosphatidylcholine (PC) with conjugated linoleic acid (CLA). The effects of enzyme loading (2, 5, 10, 15 and 20%, with respect to the weight of substrates), temperature (20, 30, 40, 50 and 60 degree centigrade) and the molar ratio of substrates (1:2, 1:4, 1:6, 1:8 and 1:10, PC/CLA) were evaluated to maximize the incorporation of CLA into PC. The maximum incorporation of CLA achieved was ca. 90% for 24 h of reaction at 50 degree centigrade and 200 rpm, using a 1:4 substrate molar ratio and an enzyme loading of 15%. (Author) 30 refs.

  9. Influence of α-tocopherol supplementation on trans-18:1 and conjugated linoleic acid profiles in beef from steers fed a barley-based diet.

    Science.gov (United States)

    Mapiye, C; Dugan, M E R; Juárez, M; Basarab, J A; Baron, V S; Turner, T; Yang, X; Aldai, N; Aalhus, J L

    2012-11-01

    The current study was conducted to determine the effect of different α-tocopherol (vitamin E) inclusion levels on trans(t)-18:1 and conjugated linoleic acid (CLA) profiles in subcutaneous and intramuscular fat of steers fed a barley-based diet. Fifty-six feedlot steers were offered a barley-based finisher diet (73% steam rolled barley, 22% barley silage and 5% supplement as-fed basis) with four levels of supplementary dl-α-tocopheryl acetate (340, 690, 1040 or 1740 IU/steer per day) for 120 days. Adding vitamin E to the diet had little effect on the overall fatty acid composition of intramuscular fat. The proportion of individual and total t,t- and cis(c),t-CLA, n-3 fatty acids, total polyunsaturated fatty acids (PUFA), mono-unsaturated fatty acids and saturated fatty acids to PUFA ratio in subcutaneous fat were not influenced (P > 0.05) by dietary vitamin E supplementation. Increasing levels of vitamin E led to linear reductions in t6-/t7-/t8-18:1 and t10-18:1 (P < 0.05), and linear increase in t11-/t10-18:1 ratio (P < 0.05) in subcutaneous fat. The content of 20:3n-6 and total n-6 in subcutaneous fat decreased (P < 0.05) linearly with increasing amounts of vitamin E. The subcutaneous fat n-6:n-3 ratio showed a quadratic (P < 0.05) response to vitamin E. In conclusion, although vitamin E supplementation has some potential to reduce t10-18:1 formation and increase t11-/t10-18:1 ratio in subcutaneous fat of cattle fed barley-based diets, the changes in the present study were limited and may not have been sufficient to impact on human health.

  10. Fabrication and spectroscopic studies of folic acid-conjugated Fe3O4@Au core-shell for targeted drug delivery application

    Science.gov (United States)

    Karamipour, Sh.; Sadjadi, M. S.; Farhadyar, N.

    2015-09-01

    Gold coated magnetite core shell is a kind of nanoparticle that include magnetic iron oxide core with a thin layer nanogold. Fe3O4-gold core-shell nanostructure can be used in biomedical applications such as magnetic bioseparation, bioimaging, targeting drug delivery and cancer treatment. In this study, the synthesis and characterization of gold coated magnetite nanoparticles were discussed. Magnetite nanoparticles with an average size of 6 nm in diameter were synthesized by the chemical co-precipitation method and gold-coated Fe3O4 core-shell nanostructures were produced with an average size of 11.5 nm in diameter by reduction of Au3+ with citrate ion in the presence of Fe3O4. Folate-conjugated gold coated magnetite nanoparticles were synthesized to targeting folate receptor that is overexpressed on the surface of cancerous cells. For this purpose, we used L-cysteine, as a bi-functional linker for attachment to gold surface and it was linked to the gold nanoparticles surface through its thiol group. Then, we conjugated amino-terminated nanoparticles to folic acid with an amide-linkage formation. These gold magnetic nanoparticles were characterized by various techniques such as X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrometer (FT-IR), UV-visible spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dispersive analysis of X-ray (EDAX) and vibrating sample magnetometer (VSM) analysis. The magnetic and optical properties of Fe3O4 nanostructure were changed by gold coating and attachment of L-cysteine and folic acid to Fe3O4@Au nanoparticles.

  11. Arabidopsis Acetyl-Amido Synthetase GH3.5 Involvement in Camalexin Biosynthesis through Conjugation of Indole-3-Carboxylic Acid and Cysteine and Upregulation of Camalexin Biosynthesis Genes

    Institute of Scientific and Technical Information of China (English)

    Mu-Yang Wang; Xue-Ting Liu; Ying Chen; Xiao-Jing Xu; Biao Yu; Shu-Qun Zhang; Qun Li; Zu-Hua He

    2012-01-01

    Camalexin (3-thiazol-2'-yl-indole) is the major phytoalexin found in Arabidopsis thaliana.Several key intermediates and corresponding enzymes have been identified in camalexin biosynthesis through mutant screening and biochemical experiments.Camalexin is formed when indole-3-acetonitrile (IAN)is catalyzed by the cytochrome P450 monooxygenase CYP71A13.Here,we demonstrate that the Arabidopsis GH3.5 protein,a multifunctional acetyl-amido synthetase,is involved in camalexin biosynthesis via conjugating indole-3-carboxylic acid (ICA) and cysteine (Cys) and regulating camalexin biosynthesis genes.Camalexin levels were increased in the activation-tagged mutant gh3.5-1D in both Col-0 and cyp71A13-2 mutant backgrounds after pathogen infection.The recombinant GH3.5 protein catalyzed the conjugation of ICA and Cys to form a possible intermediate indole-3-acyl-cysteinate (ICA(Cys)) in vitro.In support of the in vitro reaction,feeding with ICA and Cys increased camalexin levels in Col-0 and gh3.5-1D.Dihydrocamalexic acid (DHCA),the precursor of camalexin and the substrate for PAD3,was accumulated in gh3.5-1Dlpad3-1,suggesting that ICA(Cys) could be an additional precursor of DHCA for camalexin biosynthesis.Furthermore,expression of the major camalexin biosynthesis genes CYP79B2,CYP71A12,CYP71A13 and PAD3 was strongly induced in gh3.5-1D.Our study suggests that GH3.5 is involved in camalexin biosynthesis through direct catalyzation of the formation of ICA(Cys),and upregulation of the major biosynthetic pathway genes.

  12. DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice.

    Science.gov (United States)

    Müller, Cristina; Struthers, Harriet; Winiger, Christian; Zhernosekov, Konstantin; Schibli, Roger

    2013-01-01

    The folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates. However, using folate-based radiopharmaceuticals for therapy has long been regarded as an unattainable goal because of their considerable renal accumulation. Herein, we present a novel strategy in which a DOTA-folate conjugate with an albumin-binding entity (cm09) was designed with the aim of prolonging circulation in the blood and therewith potentially improving tumor-to-kidney ratios. The folate conjugate cm09 was radiolabeled with (177)LuCl(3), and stability experiments were performed in plasma. Cell uptake studies were performed on FR-positive KB tumor cells, and an ultrafiltration assay was used to determine the plasma protein-binding properties of (177)Lu-cm09. In vivo, (177)Lu-cm09 was tested in KB tumor-bearing mice using SPECT/CT. The therapeutic anticancer effect of (177)Lu-cm09 (20 MBq) applied as a single injection or as fractionated injections was investigated in different groups of mice (n = 5) by monitoring tumor size and the survival time of treated mice, compared with untreated controls. Compound cm09 was radiolabeled at a specific activity of 40 MBq/nmol, a radiochemical yield of more than 98%, and a stability of more than 99% over 5 d in plasma. Ultrafiltration revealed significant binding of (177)Lu-cm09 to serum proteins (∼91%) in plasma, compared with folate radioconjugate without an albumin-binding entity. Cell uptake and internalization of (177)Lu-cm09 was FR-specific and comparable to other folate radioconjugates. In vivo studies resulted in high tumor uptake (17.56 percentage injected dose per gram [%ID/g] at 4 h after injection), which was almost completely retained for at least 72 h. Renal accumulation was significantly reduced (28 %ID/g at 4 h after injection), compared with folate conjugates that lack an albumin-binding entity (∼70 %ID/g at 4 h after injection). These circumstances enabled SPECT imaging of exce