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Sample records for caffeic acid oligomers

  1. Butylated caffeic acid: An efficient novel antioxidant

    Directory of Open Access Journals (Sweden)

    G. Shi

    2017-09-01

    Full Text Available A novel antioxidant, butylated caffeic acid (BCA was rationally designed by adding a tert-butyl group to caffeic acid, which was synthesized at a high yield (36.2% from 2-methoxy-4-methylphenol by a four-step reaction including Friedel-Crafts alkylation, bromine oxidation, ether bond hydrolysis and Knoevenagel condensation. Its antioxidant capacity was much stronger than common commercial antioxidant tert-butyl hydroquinone (TBHQ and its mother compound, caffeic acid, in both rancimat and deep frying tests. When investigated via the DPPH method, the antioxidant capacity of BCA was almost equal to TBHQ, but lower than caffeic acid. BCA could be a potentially strong antioxidant, especially for food processing at high temperatures such as deep frying and baking.

  2. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  3. Toxicity and biodegradability of caffeic acid in anaerobic digesting ...

    African Journals Online (AJOL)

    ... to treat waste caffeic acid by anaerobic digestion and adsorption of its derivates, in order to reduce the contribution to global warming and to protect the environment. Keywords: anaerobes, anaerobic digestion, biogas, biomass, caffeic acid, graphene, inhibition, polyphenols, renewable energy, toxicity, wastewater ...

  4. Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of ...

    African Journals Online (AJOL)

    Purpose: To describe caffeic acid-based pharmacokinetics of methanol extract of seed of Syzygium cumini L. in rats. Methods: A dose of the extract (500 mg, equivalent to 37.135 mg caffeic acid) was administered orally to 6 male Wister rats, weighing 200 ± 10 g. Blood samples (0.5 mL), collected from the tail vein at 0, 15,.

  5. Toxicity and biodegradability of caffeic acid in anaerobic digesting ...

    African Journals Online (AJOL)

    ABSTRACT. Caffeic acid in waste comes from a variety of industries, and its disposal is likely to increase due to emerging processes such as graphene production and use in healthcare products. The current sustainable option to treat waste caffeic acid and prevent its natural transformation in soil to greenhouse gases, ...

  6. Inhibition of multiplication of herpes simplex virus by caffeic acid.

    Science.gov (United States)

    Ikeda, Keiko; Tsujimoto, Kazuko; Uozaki, Misao; Nishide, Mitsunori; Suzuki, Yukiko; Koyama, A Hajime; Yamasaki, Hisashi

    2011-10-01

    Hot water extracts of coffee grinds and commercial instant coffee solutions have been shown to exhibit marked antiviral and virucidal activities against herpes simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N-methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The present study examined the virological properties and the antiviral activity of caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not. These reagents did not have a direct virucidal effect. The one-step growth curve of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.) did not significantly affect the formation of progeny viruses. An analysis of the influence of the time of caffeic acid addition, revealed that addition at an early time post infection remarkably inhibited the formation of progeny infectious virus in the infected cells, but its addition after 6 h p.i. (i.e., the time of the completion of viral genome replication) did not efficiently inhibit this process. These results indicate that caffeic acid inhibits HSV-1 multiplication mainly before the completion of viral DNA replication, but not thereafter. Although caffeic acid showed some cytotoxicity by prolonged incubation, the observed antiviral activity is likely not the secondary result of the cytotoxic effect of the reagent, because the inhibition of the virus multiplication was observed before appearance of the notable cytotoxicity.

  7. Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of ...

    African Journals Online (AJOL)

    Purpose: To describe caffeic acid-based pharmacokinetics of methanol extract of seed of Syzygium cumini L. in rats. Methods: A dose of the extract (500 mg, equivalent to 37.135 mg caffeic acid) was administered orally to 6 male Wister rats, weighing 200 ± 10 g. Blood samples (0.5 mL), collected from the tail vein at 0, 15, ...

  8. Novel Caffeic Acid Nanocarrier: Production, Characterization, and Release Modeling

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    Milad Fathi

    2013-01-01

    Full Text Available This paper deals with the development of novel nanocarriers using layer by layer carbohydrate coating of caffeic acid loaded solid lipid nanoparticles (SLNs to improve stability and colon delivery of the poorly water-soluble caffeic acid. Three biopolymers (chitosan, alginate, and pectin in different concentrations (0.1, 0.25, and 0.5% were electrostatically coated over the SLN surface. The size and zeta potential of produced nanocarriers were measured using photon correlation spectroscopy. Mathematical models (i.e., zero-order, first-order, Higuchi, Ritger-Peppas, reciprocal powered time, Weibull, and quadratic models were used to describe the release and kinetic modeling in gastrointestinal solution (GIS. Also, antioxidant activity of caffeic acid during the release in GIS was investigated using DPPH and reducing activity methods. The prepared treatments coated by alginate-chitosan as well as pectin-chitosan coated SLN at the concentration of 0.1% showed nanosized bead; the latter efficiently retarded the release of caffeic acid in gastric media up to 2.5 times higher than that of SLN. Zeta potential values of coated samples were found to significantly increase in comparison to SLN indicating the higher stability of produced nanocarriers. Antioxidant activity of caffeic acid after gastric release did not result in the same trend as observed for caffeic acid release from different treatments; however, in line with less caffeic acid release in the intestine solution by the effect of coating, lower antioxidant activity was determined at the end stage of the experiment.

  9. Caffeic Acid Derivatives in Dried Lamiaceae and Echinacea purpurea Products

    Science.gov (United States)

    The concentrations of caffeic acid derivatives within Lamiaceae and Echinacea (herb, spice, tea, and dietary supplement forms) readily available in the U.S. marketplace (n=72) were determined. After the first identification of chicoric acid in Ocimum basilicum (basil), the extent to which chicoric a...

  10. Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation

    National Research Council Canada - National Science Library

    Lee, Shih-Yi; Ku, Hui-Chun; Kuo, Yueh-Hsiung; Yang, Kai-Chien; Tu, Ping-Chen; Chiu, His-Lin; Su, Ming-Jai

    2015-01-01

    .... Caffeic acid ethanolamide (CAEA), a synthesized derivative from caffeic acid that exerted antioxidative properties, was thus applied in this study to explore its effects on the pathogenesis of heart failure...

  11. Caffeic Acid Induces Apoptosis in Human Cervical Cancer Cells Through the Mitochondrial Pathway

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    Wei-Chun Chang

    2010-12-01

    Conclusion: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

  12. Separation and purification of the antioxidant compounds, caffeic acid phenethyl ester and caffeic acid from mushrooms by molecularly imprinted polymer.

    Science.gov (United States)

    Li, Ning; Ng, Tzi Bun; Wong, Jack Ho; Qiao, Ji Xuan; Zhang, Ye Ni; Zhou, Rong; Chen, Rong Rong; Liu, Fang

    2013-08-15

    Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA), two naturally occurring phenolic antioxidants, have been reported to have a diversity of biological activities. In this investigation, a novel approach to separate and enrich CAPE and CA from 25 species of mushrooms using molecularly imprinted polymers (MIPs) as the sorbent material is reported. The MIPs were synthesized using CAPE as the template, and its adsorption behavior was investigated in detail. In comparison with C18-solid phase extraction (SPE), MIP-SPE displayed high selectivity and good affinity for CAPE and CA. The antioxidant potential of the mushroom extracts, before and after preconcentration using MIPs, was assayed by inhibition of erythrocyte hemolysis and lipid peroxidation. Application of MIPs with a high affinity toward CAPE and CA provides a novel method for obtaining active compounds from natural products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues

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    Zhiqian Liu

    2014-05-01

    Full Text Available A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  14. Synthesis and Functional Characterization of Caffeic Acid Glucoside Using Leuconostoc mesenteroides Dextransucrase.

    Science.gov (United States)

    Nam, Seung-Hee; Kim, Young-Min; Walsh, Marie K; Wee, Young-Jung; Yang, Kwang-Yeol; Ko, Jin-A; Han, Songhee; Thanh Hanh Nguyen, Thi; Kim, Ji Young; Kim, Doman

    2017-04-05

    Caffeic acid was modified via transglucosylation using sucrose and dextransucrase from Leuconostoc mesenteroides B-512FMCM. Following enzymatic modification, a caffeic acid glucoside was isolated by butanol separation, silica gel chromatography, and preparative HPLC. The synthesized caffeic acid glucoside had a molecular mass-to-charge ratio of 365 m/z, and its structure was identified as caffeic acid-3-O-α-d-glucopyranoside. The production of this caffeic acid-3-O-α-d-glucopyranoside at a concentration of 153 mM was optimized using 325 mM caffeic acid, 355 mM sucrose, and 650 mU mL-1 dextransucrase in the synthesis reaction. In comparison with the caffeic acid, the caffeic acid-3-O-α-d-glucopyranoside displayed 3-fold higher water solubility, 1.66-fold higher antilipid peroxidation effect, 15% stronger inhibition of colon cancer cell growth, and 11.5-fold higher browning resistance. These results indicate that this caffeic acid-3-O-α-d-glucopyranoside may be a suitable functional component of food and pharmaceutical products.

  15. Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk

    DEFF Research Database (Denmark)

    Alemán, Mercedes; Bou, Ricard; Guardiola, Francesc

    2015-01-01

    The antioxidative effect of lipophilized caffeic acid was assessed in two different fish oil enriched food products: mayonnaise and milk. In both emulsion systems, caffeic acid esterified with fatty alcohols of different chain lengths (C1–C20) were better antioxidants than the original phenolic c...

  16. Caffeic Acid Inhibits NFkappaB Activation of Osteoclastogenesis Signaling Pathway

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    Ferry Sandra

    2011-12-01

    Full Text Available BACKGROUND: Caffeic acid (3,4-dihydroxycinnamic acids is involved in various green plants. Based on our previous report, a major component of sweet potato extracts, possibly caffeic acid, was shown as a promising inhibitor of osteoclastogenesis. However, the effect of caffeic acid in inhibiting osteoclastogenesis needs to be confirmed. The underlying mechanism needs to be disclosed as well. METHODS: Caffeic acid in various concentrations was added to in vitro osteoclastogenesis of receptor activator nuclear factor kB ligand (RANKL-tumor necrosis factor alpha (TNF-α-macrophage colony stimulating factor (M-CSF-induced bone marrow-derived monocyte/macrophage precursor cells (BMMs and RANKL-TNF-α-induced RAW264 cells D-Clone (RAW-D cells. Tartrate resistant acid phosphatase (TRAP staining was performed and TRAP-positive polynucleated cells (PNCs were counted. For apoptosis analysis, caffeic acid-treated BMMs, RAW-D cells and osteoclast-like PNCs were subjected to Sub-G1 Apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays. To measure NFkB activity, RAW-D cells were transfected with pNFkB-TA-Luc and subjected to Dual Luciferase Reporter Assay System. RESULTS: Caffeic acid inhibited osteoclastogenesis of RANKL-TNF-α-M-CSF-induced BMMs as well as RANKL-TNF-α-induced RAW-D cells in a dose dependent manner. Caffeic acid did not induce apoptosis in BMMs, RAW-D cells and osteoclast-like PNCs. RANKL-TNF-α-induced NFkB activity in RAW-D was diminished by caffeic acid in a dose dependent manner. Significant NFkB activity inhibtion was observed starting from 1µg/mL caffeic acid. CONCLUSIONS: Caffeic acid could be a potent osteoclastogenesis inhibitor through inhibition of NFkB activity. Our present study should be further followed up to disclose caffeic acid's possible overlying signaling pathways in inhibiting osteoclastogenesis. KEYWORDS: caffeic acid, osteoclastogenesis, NFkB, RANKL, TNF-α.

  17. Modulatory effect of caffeic acid on cholinesterases inhibitory properties of donepezil.

    Science.gov (United States)

    Agunloye, Odunayo Michael; Oboh, Ganiyu

    2017-09-22

    Background Donepezil hydrochloride commonly used in the management of Alzheimer's disease (AD), exhibiting its inhibitory effects on acetylcholinesterase and butyrylcholinesterase activity thereby enhance cognitive function. Caffeic acid member of hydroxycinnamic acid is widely present in human diet. This study aims to investigate influence of caffeic acid on acetylcholinesterase and butyrylcholinesterase inhibitory properties of donepezil (in vitro). Methods 5 mg of donepezil was dissolved in 50 mL distilled water while 10 mg of caffeic acid was dissolved in 100 mL distilled water. Therefore, mixtures of samples were prepared as follows: A2=donepezil 0.075 mg/mL+caffeic acid 0.025 mg/mL; A3=donepezil 0.050 mg/mL+caffeic acid 0.050 mg/mL; A4=donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL. All samples were kept in the refrigerator at 4 °C for subsequent analysis. Results The result showed that all the combinations show an inhibitory effect on acetylcholinesterase and butyrylcholinesterase activity in vitro, with the combination A4=donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL had significant (pdonepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL and A3=donepezil 0.050 mg/mL+caffeic acid 0.050 mg/mL had highest inhibitory effect against FeSO4 and SNP induced lipid peroxidation in rat brain homogenate in vitro respectively. Moreover, all the samples exhibit antioxidant properties as typified by their ability to chelate iron (II) ion (Fe2+), hydroxyl radical (OH٭) radical scavenging ability and ferric reducing property (FRAP). Conclusions Therefore, the combination of caffeic acid with donepezil enhances the antioxidant properties of donepezil. The combination of caffeic acid with donepezil could be a therapeutic aid in the management of AD, possibly with fewer side effects of donepezil. Nevertheless, the combination donepezil 0.025 mg/mL+caffeic acid 0.075 mg/mL acid look promising.

  18. Activity of caffeic acid in different fish lipid matrices: A review

    DEFF Research Database (Denmark)

    Medina, Isabel; Undeland, Ingrid; Larsson, Karin

    2012-01-01

    was however clearly dependent on the lipid to antioxidant ratio. In these systems, an important redox cycle between caffeic acid and the endogenous reducing agents ascorbic acid and tocopherol were further thought to play an important role for the protective effects. The effect of caffeic acid was also highly......Caffeic acid, a hydroxycinnamic acid common in different vegetable sources, has been employed as a natural antioxidant for inhibiting oxidation of fish lipids present in different food matrices. The aim of this review is to discuss the mechanisms involved in the antioxidative and prooxidative...... effects of caffeic acid found in different model systems containing fish lipids. These model systems include bulk fish oils, liposomes from cod roe phospholipids, fish oil emulsions, washed cod mince, regular horse mackerel mince and a fish oil fortified fitness bar. The data reported show...

  19. Formation of volatile chemicals from thermal degradation of less volatile coffee components: quinic acid, caffeic acid, and chlorogenic acid.

    Science.gov (United States)

    Moon, Joon-Kwan; Shibamoto, Takayuki

    2010-05-12

    The less volatile constituents of coffee beans (quinic acid, caffeic acid, and chlorogenic acid) were roasted under a stream of nitrogen, air, or helium. The volatile degradation compounds formed were analyzed by gas chromatography and gas chromatography-mass spectrometry. Caffeic acid produced the greatest amount of total volatiles. Quinic acid and chlorogenic acid produced a greater number of volatiles under the nitrogen stream than under the air stream. These results suggest that the presence of oxygen does not play an important role in the formation of volatile compounds by the heat degradation of these chemicals. 2,5-Dimethylfuran formed in relatively large amounts (59.8-2231.0 microg/g) in the samples obtained from quinic acid and chlorogenic acid but was not found in the samples from caffeic acid. Furfuryl alcohol was found in the quinic acid (259.9 microg/g) and caffeic acid (174.4 microg/g) samples roasted under a nitrogen stream but not in the chlorogenic sample. The three acids used in the present study do not contain a nitrogen atom, yet nitrogen-containing heterocyclic compounds, pyridine, pyrrole, and pyrazines, were recovered. Phenol and its derivatives were identified in the largest quantities. The amounts of total phenols ranged from 60.6 microg/g (quinic acid under helium) to 89893.7 microg/g (caffeic acid under helium). It was proposed that phenol was formed mainly from quinic acid and that catechols were formed from caffeic acid. Formation of catechol from caffeic acid under anaerobic condition indicates that the reaction participating in catechol formation was not oxidative degradation.

  20. Caffeic acid production by simultaneous saccharification and fermentation of kraft pulp using recombinant Escherichia coli.

    Science.gov (United States)

    Kawaguchi, Hideo; Katsuyama, Yohei; Danyao, Du; Kahar, Prihardi; Nakamura-Tsuruta, Sachiko; Teramura, Hiroshi; Wakai, Keiko; Yoshihara, Kumiko; Minami, Hiromichi; Ogino, Chiaki; Ohnishi, Yasuo; Kondo, Ahikiko

    2017-07-01

    Caffeic acid (3,4-dihydroxycinnamic acid) serves as a building block for thermoplastics and a precursor for biologically active compounds and was recently produced from glucose by microbial fermentation. To produce caffeic acid from inedible cellulose, separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) reactions were compared using kraft pulp as lignocellulosic feedstock. Here, a tyrosine-overproducing Escherichia coli strain was metabolically engineered to produce caffeic acid from glucose by introducing the genes encoding a 4-hydroxyphenyllactate 3-hydroxylase (hpaBC) from Pseudomonas aeruginosa and tyrosine ammonia lyase (fevV) from Streptomyces sp. WK-5344. Using the resulting recombinant strain, the maximum yield of caffeic acid in SSF (233 mg/L) far exceeded that by SHF (37.9 mg/L). In the SSF with low cellulase loads (≤2.5 filter paper unit/g glucan), caffeic acid production was markedly increased, while almost no glucose accumulation was detected, indicating that the E. coli cells experienced glucose limitation in this culture condition. Caffeic acid yield was also negatively correlated with the glucose concentration in the fermentation medium. In SHF, the formation of by-product acetate and the accumulation of potential fermentation inhibitors increased significantly with kraft pulp hydrolysate than filter paper hydrolysate. The combination of these inhibitors had synergistic effects on caffeic acid fermentation at low concentrations. With lower loads of cellulase in SSF, less potential fermentation inhibitors (furfural, 5-hydroxymethyfurfural, and 4-hydroxylbenzoic acid) accumulated in the medium. These observations suggest that glucose limitation in SSF is crucial for improving caffeic acid yield, owing to reduced by-product formation and fermentation inhibitor accumulation.

  1. Preparation and characterization of SPION functionalized via caffeic acid

    Energy Technology Data Exchange (ETDEWEB)

    Baykal, A. [Department of Chemistry, Fatih University, B.Çekmece, 34500 Istanbul (Turkey); Amir, Md., E-mail: mda.fatih@gmail.com [Department of Chemistry, Fatih University, B.Çekmece, 34500 Istanbul (Turkey); Günerb, S. [Department of Physics, Fatih University, B.Çekmece, 34500 Istanbul (Turkey); Sözeri, H. [TUBITAK-UME, National Metrology Institute, 41470 Gebze, Kocaeli (Turkey)

    2015-12-01

    Caffeic acid coated superparamagnetic iron oxide nanoparticles (SPION-CFA) was synthesized by reflux method. The structural, spectroscopic and magnetic properties were studied by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), and Vibrating sample magnetometer (VSM) techniques. Thermal gravimetric analysis (TG) and Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of CA on the surface of SPION. The theoretical analyzes performed on recorded room temperature VSM spectrum confirmed the formation of superparamagnetic nature of SPION-CFA. The particle size dependent Langevin function was applied to determine the average magnetic particle dimension (D{sub mag}) around 11.93 nm. In accordance, the average crystallite and particle sizes were obtained as 11.40 nm and ~12.00 nm from XRD and TEM measurements. The extrapolated specific saturation magnetization (σ{sub s}) is 44.11 emu/g and measured magnetic moment is 1.83 µ{sub B}. These parameters assign small order of magnetization for NPs with respect to bulk Fe{sub 3}O{sub 4}. Magnetic anisotropy was offered as uniaxial and calculated effective anisotropy constant (K{sub eff}) is 34.82×10{sup 4} Erg/g. The size-dependent saturation magnetization suggests the existence of a magnetically inactive layer as 1.035 nm for SPION-CFA. - Highlights: • The effects of CFA on the microstructure and magnetic properties of SPION have been investigated. • Product was structurally and magnetically characterized. • Product presented superparamagnetic behavior at room temperature.

  2. Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases.

    Science.gov (United States)

    Monien, Bernhard H; Henry, Brian L; Raghuraman, Arjun; Hindle, Michael; Desai, Umesh R

    2006-12-01

    Thrombin and factor Xa, two important procoagulant enzymes, have been prime targets for regulation of clotting through the direct and indirect mechanism of inhibition. Our efforts on exploiting the indirect mechanism led us to study a carboxylic acid-based scaffold, which displayed major acceleration in the inhibition of these enzymes [J. Med. Chem.2005, 48, 1269, 5360]. This work advances the study to chemo-enzymatically prepared oligomers of 4-hydroxycinnamic acids, DHPs, which display interesting anticoagulant properties. Oligomers, ranging in size from tetramers to pentadecamers, were prepared through peroxidase-catalyzed oxidative coupling of caffeic, ferulic, and sinapic acids, and sulfated using triethylamine-sulfur trioxide complex. Chromatographic, spectroscopic, and elemental studies suggest that the DHPs are heterogeneous, polydisperse preparations composed of inter-monomer linkages similar to those found in natural lignins. Measurement of activated thromboplastin and prothrombin time indicates that both the sulfated and unsulfated derivatives of the DHPs display anticoagulant activity, which is dramatically higher than that of the reference polyacrylic acids. More interestingly, this activity approaches that of low-molecular-weight heparin with the sulfated derivative showing approximately 2- to 3-fold greater potency than the unsulfated parent. Studies on the inhibition of factor Xa and thrombin indicate that the oligomers exert their anticoagulant effect through both direct and indirect inhibition mechanisms. This dual inhibition property of 4-hydroxycinnamic acid-based DHP oligomers is the first example in inhibitors of coagulation. This work puts forward a novel, non-heparin structure, which may be exploited for the design of potent, dual action inhibitors of coagulation through combinatorial virtual screening on a library of DHP oligomers.

  3. Quantitative analysis of caffeic and ferulic acids in oatmeal. Comparison of a conventional method with a stable isotope dilution assay.

    Science.gov (United States)

    Guth, H; Grosch, W

    1994-09-01

    [13C]Caffeic acid and [13C]ferulic acid were synthesized and then used as internal standards for the determination of these acids (free and esterified) in oatmeal. A comparative study indicated that 84% of the ferulic acid, but only 32% of the caffeic acid, which is more susceptible to oxidation than the former, could be found by a conventional analytical approach.

  4. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Natarelli

    Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

  5. Biosynthesis of caffeic acid in Escherichia coli using its endogenous hydroxylase complex

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    Lin Yuheng

    2012-04-01

    Full Text Available Abstract Background Caffeic acid (3,4-dihydroxycinnamic acid is a natural phenolic compound derived from the plant phenylpropanoid pathway. Caffeic acid and its phenethyl ester (CAPE have attracted increasing attention for their various pharmaceutical properties and health-promoting effects. Nowadays, large-scale production of drugs or drug precursors via microbial approaches provides a promising alternative to chemical synthesis and extraction from plant sources. Results We first identified that an Escherichia coli native hydroxylase complex previously characterized as the 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H was able to convert p-coumaric acid to caffeic acid efficiently. This critical enzymatic step catalyzed in plants by a membrane-associated cytochrome P450 enzyme, p-coumarate 3-hydroxylase (C3H, is difficult to be functionally expressed in prokaryotic systems. Moreover, the performances of two tyrosine ammonia lyases (TALs from Rhodobacter species were compared after overexpression in E. coli. The results indicated that the TAL from R. capsulatus (Rc possesses higher activity towards both tyrosine and L-dopa. Based on these findings, we further designed a dual pathway leading from tyrosine to caffeic acid consisting of the enzymes 4HPA3H and RcTAL. This heterologous pathway extended E. coli native tyrosine biosynthesis machinery and was able to produce caffeic acid (12.1 mg/L in minimal salt medium. Further improvement in production was accomplished by boosting tyrosine biosynthesis in E. coli, which involved the alleviation of tyrosine-induced feedback inhibition and carbon flux redirection. Finally, the titer of caffeic acid reached 50.2 mg/L in shake flasks after 48-hour cultivation. Conclusion We have successfully established a novel pathway and constructed an E. coli strain for the production of caffeic acid. This work forms a basis for further improvement in production, as well as opens the possibility of microbial synthesis

  6. Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus.

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    Hui Shen

    Full Text Available Caffeic acid phenethyl ester (CAPE has been reported as a multifunctional compound. In this report, we tested the effect of CAPE and its derivatives on hepatitis C virus (HCV replication in order to develop an effective anti-HCV compound. CAPE and CAPE derivatives exhibited anti-HCV activity against an HCV replicon cell line of genotype 1b with EC50 values in a range from 1.0 to 109.6 µM. Analyses of chemical structure and antiviral activity suggested that the length of the n-alkyl side chain and catechol moiety are responsible for the anti-HCV activity of these compounds. Caffeic acid n-octyl ester exhibited the highest anti-HCV activity among the tested derivatives with an EC50 value of 1.0 µM and an SI value of 63.1 by using the replicon cell line derived from genotype 1b strain Con1. Treatment with caffeic acid n-octyl ester inhibited HCV replication of genotype 2a at a similar level to that of genotype 1b irrespectively of interferon signaling. Caffeic acid n-octyl ester could synergistically enhance the anti-HCV activities of interferon-alpha 2b, daclatasvir, and VX-222, but neither telaprevir nor danoprevir. These results suggest that caffeic acid n-octyl ester is a potential candidate for novel anti-HCV chemotherapy drugs.

  7. Anti-inflammatory activity of caffeic acid derivatives isolated from the roots of Salvia miltiorrhiza Bunge.

    Science.gov (United States)

    Choi, Hyun Gyu; Tran, Phuong Thao; Lee, Jeong-Hyung; Min, Byung Sun; Kim, Jeong Ah

    2017-11-09

    Ten caffeic acid derivatives (1-10) were isolated from the roots of Salvia miltiorrhiza by using various chromatographic methods and their chemical structures were spectroscopically elucidated. The absolute configurations of chiral centers were determined by comparison with reported coupling constants, optical rotation values, and CD techniques. Anti-inflammatory activities were evaluated using nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 inhibition assays, and by determining the expression of heme oxygenase (HO)-1. Two new caffeic acid derivatives, 8-epiblechnic acid 9-methyl ester (4) and 8-epiblechnic acid 9'-methyl ester (5), and eight known derivatives, caffeic acid methyl ester (1), shimobashiric acid B (2), rosmarinic acid methyl ester (3), salvianolic acid C (6), methyl salvianolate C (7), lithospermic acid monomethyl ester (8), lithospermic acid dimethyl ester (9), and dimethyl lithospermate B (10), were isolated from the ethyl acetate fraction of S. miltiorrhiza. All caffeic acid derivatives were evaluated for their inhibitory effect on NO production. Compounds 2 and 3 inhibited NO production with IC50 values of 1.4 and 0.6 μM, respectively. These compounds also strongly inhibited the production of iNOS and COX-2. In addition, compound 3 induced the expression HO-1 in a concentration-dependent manner at 0.1, 0.3, and 1.0 μM.

  8. [Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid].

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    Obertreis, B; Giller, K; Teucher, T; Behnke, B; Schmitz, H

    1996-01-01

    Urtica dioica extract is a traditionary used adjuvant therapeutic in rheumatoid arthritis. The antiphlogistic effects of the urtica dioica folia extract IDS 23 (Extractum Urticae dioicae foliorum) and the main phenolic ingredient caffeic malic acid were tested concerning the inhibitory potential on biosynthesis of arachidonic acid metabolites in vitro. The caffeic malic acid was isolated from Urtica folia extract using gel exclusion- and high performance liquid chromatography and identified by mass spectroscopy and nuclear magnetic resonance. Concerning the 5-lipoxygenase products IDS 23 showed a partial inhibitory effect. The isolated phenolic acid inhibited the synthesis of the leukotriene B4 in a concentration dependent manner. The concentration for halfmaximal inhibition (IC50) was 83 microns/ml in the used assay. IDS 23 showed a strong concentration dependent inhibition of the synthesis of cyclooxygenase derived reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38 micrograms/ml for the caffeic malic acid. Calculating the content in IDS 23 the caffeic malic acid is a possible but not the only active ingredient of the plant extract in the tested assay systems. It is demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23. The antiphlogistic effects observed in vitro may give an explanation for the pharmacological and clinical effects of IDS 23 in therapie of rheumatoid diseases.

  9. The timing of caffeic acid treatment with cisplatin determines sensitization or resistance of ovarian carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    R. Sirota

    2017-04-01

    The use of caffeic acid as adjuvant for cisplatin should be carefully examined due to different pharmacokinetic profiles of caffeic acid and cisplatin. Thus, it is questionable if the two agents can reach the tumors at the right time frame in vivo.

  10. Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol.

    Science.gov (United States)

    Lima, Valéria N; Oliveira-Tintino, Cícera D M; Santos, Enaide S; Morais, Luís P; Tintino, Saulo R; Freitas, Thiago S; Geraldo, Yuri S; Pereira, Raimundo L S; Cruz, Rafael P; Menezes, Irwin R A; Coutinho, Henrique D M

    2016-10-01

    The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 μg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 μg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 μg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Determination of caffeic acid in root and rhizome of Black cohosh (Cimicifuga racemosa (L. Nutt.

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    Zapala Karolina

    2014-06-01

    Full Text Available Cimicifuga racemosa, is a plant with a diverse and long history of medicinal use. Caffeic acid, bioactive compound, which often occurs with other polyphenols can influence the biological activity of this plant. The aim of our work was quantitative analysis of caffeic acid in roots and rhizomes of two varieties of C. racemosa. Analysis was performed by HPLC method. The extracts were separated on C18 reversed-phase column using mixture of methanol, water and formic acid (25:75:0.5 v/v/v as a mobile phase. The flow rate of eluent was 1.0 ml·min-1. The obtained validation parameters such as linearity, linear regression equation and precision expressed as a relative standard deviation were adequate for quantitative determination. Caffeic acid was found in all tested extracts. The highest total amount of caffeic acid was determined in C. racemosa var. racemosa (255.3 μg·g-1 while its concentration in C. racemosa var. cordifolia was significantly lower (213.0 μg·g-1.

  12. Effect of high pressure on peanut allergens in the presence of polyphenol oxidase and caffeic acid

    Science.gov (United States)

    High pressure (HP) enhances enzymatic reactions. Because polyphenol oxidase (PPO) is an enzyme, and reduces IgE binding of peanut allergens in presence of caffeic acid (CA), we postulated that a further reduction in IgE binding can be achieved, using HP together with PPO and CA. Peanut extracts cont...

  13. Functional characterization of cinnamyl alcohol dehydrogenase and caffeic acid O-methyltransferase in Brachypodium distachyon.

    Science.gov (United States)

    Lignin is a significant recalcitrant in the conversion of plant biomass to bioethanol. Cinnamyl alcohol dehydrogenase (CAD) and caffeic acid O-methyltransferase (COMT) catalyze key steps in the pathway of lignin monomer biosynthesis. Brown midrib mutants in Zea mays and Sorghum bicolor with impaired...

  14. Grape skins (Vitis vinifera L.) catalyze the in vitro enzymatic hydroxylation of p-coumaric acid to caffeic acid

    DEFF Research Database (Denmark)

    Arnous, Anis; Meyer, Anne S.

    2009-01-01

    The ability of grape skins to catalyze in vitro conversion of p-coumaric acid to the more potent antioxidant caffeic acid was studied. Addition of different concentrations of p-coumaric to red grape skins (Cabernet Sauvignon) resulted in formation of caffeic acid. This caffeic acid formation (Y......) correlated positively and linearly to p-coumaric acid consumption (X): Y = 0.5 X + 9.5; R 2 = 0.96, P skin concentrations, indicated that the grape skins harboured an o......-hydroxylation activity, proposedly a monophenol- or a flavonoid 3′-monooxygenase activity (EC 1.14.18.1 or EC 1.14.13.21). The K m of this crude o-hydroxylation activity in the red grape skin was 0.5 mM with p-coumaric acid....

  15. HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC DETERMINATION OF CAFFEIC ACID AND ROSMARINIC ACID FROM THE LEAVES OF Orthosiphon stamineus

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    M. Amzad Hossain

    2010-06-01

    Full Text Available This paper presents the studies performed on extraction of Orthosiphon stamineus, Benth by using different solvent for the identification and quantification of the caffeic acid derivatives such as caffeic acid  and rosmarinic acid which confers to the leaves of this plant with remarkable pharmaceutical properties. High performance thin-layer chromatographic (HPTLC allows the identification and the quantification of more than 20 samples in the same chromatographic run. The analysis of the samples requires 15-30 min compared with more than 2 h using a typical HPLC method. Using the techniques of the HPTLC and the UV-VIS spectra we have found that the extraction of this herb plant contain, the caffeic acid and rosmarinic acid ranging between 0.029% up to 0.506% and up to 0.24% to 2.24% respectively.     Keywords: Caffice acid derivatives, quantification, Malaysian Orthosiphon stamineus, HPTLC

  16. Ameliorative Effects of Caffeic Acid on Lead Accumulation and Oxidative Stress in Lead-Exposed Mice

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    Maryam Lotfi-Ghahramanloo

    2016-05-01

    Full Text Available Background The currently approved treatment for lead toxicity is chelation therapy to reduce the burden of the toxic effects of lead, but the safety and efficacy of the various chelating agents may be questioned. Objectives This study was aimed to evaluate the effects of caffeic acid, a dietary non-flavonoid phenolic acid, on lead accumulation and lead-induced oxidative stress in mice. Materials and Methods In this experimental study, 24 mice were divided into four groups. Group 1 served as control. Mice in group 2 received water containing 1000 ppm lead acetate. Group 3 animals received caffeic acid (60 mg/kg body weight i.p. during lead treatment. Mice in group 4 only received caffeic acid. At the end of the experiment (18 days, blood samples were drawn and the levels of lead and some oxidative-stress related parameters were measured. Results Blood Pb concentration increased significantly in group 2 as compared to control group. Lead exposure caused significant increase of malondialdehyde and decrease of glutathione concentrations in erythrocyte haemolysate as compared to control group. Although caffeic acid was effective in normalization of the attenuated levels of erythrocytic glutathione, its administration had no significant effect in decreasing the augmented levels of erythrocytic malondialdehyde in group 3. Values of other measured parameters including erythrocytic activities of glutathione peroxidase and superoxide dismutase did not change significantly among experimental groups. Conclusions Present results show some beneficial effects of caffeic acid against lead poisoning and it can be thus proposed as a potential prophylactic treatment for amelioration of lead toxicity.

  17. Protective effect of dietary polyphenol caffeic acid on ethylene glycol-induced kidney stones in rats.

    Science.gov (United States)

    Yasir, Fauzia; Wahab, Atia-Tul-; Choudhary, M Iqbal

    2017-06-14

    Dietary polyphenol caffeic acid (1) has been reported for various pharmacological activities. The aim of the current study was to investigate the effect of caffeic acid (1) on ethylene glycol-induced renal stones in rats. For the study, male Wistar rats were divided into seven groups; normal, pathological, and standard drug controls, and preventive and curative groups. Normal control group received drinking water for 8 weeks. Pathological, standard drug, preventive, and curative groups received 0.75% ethylene glycol in drinking water for the induction of calcium oxalate stone formation, along with the regular diet. Standard drug group received Urocit-K by gavage from day 1, while preventive and curative groups received caffeic acid (1) by gavage at doses of 20 and 40 mg/kg on day 1 and day 14, respectively. At the end of the experiment, urine analysis and kidney histopathology were performed. Real-time PCR was performed to evaluate the renal expression of the most important genes involved in urolithiasis, i.e., osteopontin, Tamm-Horsfall, prothrombin fragment 1, and bikunin genes. The results indicated that in both the preventive and curative groups, treatment of rats with caffeic acid (1) significantly regulated the altered biochemical parameters, along with the remarkable reduction of calcium oxalate deposits in the kidneys, as compared to the pathological group. Treatment with compound 1 also resulted in down-regulation of the osteopontin gene, and up-regulation of the prothrombin fragment 1, Tamm-Horsfall, and bikunin genes. These results suggest that caffeic acid (1) can be further investigated for the prevention, and treatment of kidney stones.

  18. Inhibitory Effects of Caffeic Acid, a Coffee-Related Organic Acid, on the Propagation of Hepatitis C Virus.

    Science.gov (United States)

    Tanida, Isei; Shirasago, Yoshitaka; Suzuki, Ryosuke; Abe, Ryo; Wakita, Takaji; Hanada, Kentaro; Fukasawa, Masayoshi

    2015-01-01

    Multipurpose cohort studies have demonstrated that coffee consumption reduces the risk of hepatocellular carcinoma (HCC). Given that one of the main causes of HCC is hepatitis C virus (HCV) infection, we examined the effect of caffeic acid, a major organic acid derived from coffee, on the propagation of HCV using an in vitro naïve HCV particle-infection and production system within human hepatoma-derived Huh-7.5.1-8 cells. When cells were treated with 1% coffee extract or 0.1% caffeic acid for 1-h post HCV infection, the amount of HCV particles released into the medium at 3 and 4 days post-infection considerably decreased. In addition, HCV-infected cells cultured with 0.001% caffeic acid for 4 days, also released less HCV particles into the medium. Caffeic acid treatment inhibited the initial stage of HCV infection (i.e., between virion entry and the translation of the RNA genome) in both HCV genotypes 1b and 2a. These results suggest that the treatment of cells with caffeic acid may inhibit HCV propagation.

  19. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Development and validation of an LCMS method to determine the pharmacokinetic profiles of caffeic acid phenethyl amide and caffeic acid phenethyl ester in male Sprague-Dawley rats.

    Science.gov (United States)

    Yang, John; Bowman, Phillip D; Kerwin, Sean M; Stavchansky, Salomon

    2014-02-01

    A validated LCMS method was developed for the quantitative determination of caffeic acid phenethyl amide (CAPA) and caffeic acid phenethyl ester (CAPE) from rat plasma. Separation was achieved using a reverse-phase C12 HPLC column (150 × 2.00 mm, 4 µm) with gradient elution running water (A) and acetonitrile (B). Mass spectrometry was performed with electrospray ionization in negative mode. This method was used to determine the pharmacokinetic profiles of CAPA and CAPE in male Sprague-Dawley rats following intravenous bolus administration of 5, 10 and 20 mg/kg of CAPA and 20 mg/kg of CAPE. The pharmacokinetic analysis suggests the lack of dose proportionality in the dose range of 5-20 mg/kg of CAPA. Total clearance values for CAPA ranged from 45 to 156 mL/min and decreased with increasing dose of CAPA. The volume of distribution for CAPA ranged from 17,750 to 52,420 mL, decreasing with increasing dose. The elimination half-life for CAPA ranged from 243.1 to 295.8 min and no statistically significant differences were observed between dose groups in the range of 5-20 mg/kg (p > 0.05). The elimination half-life for CAPE was found to be 92.26 min. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Possible molecular targets for therapeutic applications of caffeic acid phenethyl ester in inflammation and cancer

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    Ghulam Murtaza

    2015-03-01

    Full Text Available Of the various derivatives of caffeic acid, caffeic acid phenethyl ester (CAPE is a hydrophobic, bioactive polyphenolic ester obtained from propolis extract. The objective in writing this review article was to summarize all published studies on therapeutics of CAPE in inflammation and cancer to extract direction for future research. The possible molecular targets for the action of CAPE, include various transcription factors such as nuclear factor-κB, tissue necrosis factor-α, interleukin-6, cyclooxygenase-2, Nrf2, inducible nitric oxide synthase, nuclear factor of activated T cells, hypoxia-inducible factor-1α, and signal transducers and activators of transcription. Based on the valuable data on its therapeutics in inflammation and cancer, clinical studies of CAPE should also be conducted to explore its toxicities, if any.

  2. Binding of caffeic acid to human serum albumin by the retention data and frontal analysis.

    Science.gov (United States)

    An, Yuxin; Li, Qian; Chen, Jiejun; Gao, Xiaokang; Chen, Hongwei; Xiao, Chaoni; Bian, Liujiao; Zheng, Jianbin; Zhao, Xinfeng; Zheng, Xiaohui

    2014-12-01

    A new mathematical model and frontal analysis were used to characterize the binding behavior of caffeic acid to human serum albumin (HSA) based on high-performance affinity chromatography. The experiments were carried out by injecting various mole amounts of the drug onto an immobilized HSA column. They indicated that caffeic acid has only one type of binding site to HSA on which the association constant was 2.75 × 10(4) /m. The number of the binding site involving the interaction between caffeic acid and HSA was 69 nm. The data obtained by the frontal analysis appeared to present the same results for both the association constant and the number of binding sites. This new model based on the relationship between the mole amounts of injection and capacity factors assists understanding of drug-protein interaction. The proposed model also has the advantages of ligand saving and rapid operation. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Molecularly imprinted polymer for caffeic acid by precipitation polymerization and its application to extraction of caffeic acid and chlorogenic acid from Eucommia ulmodies leaves.

    Science.gov (United States)

    Miura, Chitose; Matsunaga, Hisami; Haginaka, Jun

    2016-08-05

    Molecularly imprinted polymers (MIPs) for caffeic acid (CA) were prepared using 4-vinylpyridine and methacrylamide (MAM) as functional monomers, divinylbenzene as a crosslinker and acetonitrile-toluene (3:1, v/v) as a porogen by precipitation polymerization. The use of MAM as the co-monomer resulted in the formation of microsphere MIPs and non-imprinted polymers (NIPs) with ca. 3- and 5-μm particle diameters, respectively. Binding experiments and Scatchard analyses revealed that the binding capacity and affinity of the MIP to CA are higher than those of the NIP. The retention and molecular-recognition properties of the prepared MIPs were evaluated using water-acetonitrile and sodium phosphate buffer-acetonitrile as mobile phases in hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography, respectively. In HILIC mode, the MIP showed higher molecular-recognition ability for CA than in reversed-phase mode. In addition to shape recognition, hydrophilic interactions seem to work for the recognition of CA on the MIP in HILIC mode, while hydrogen bonding and hydrophobic interactions seem to work for the recognition of CA in reversed-phase mode. The MIP had a specific molecular-recognition ability for CA in HILIC mode, while other structurally related compounds, such as chlorogenic acid (CGA), gallic acid, protocatechuic acid and vanillic acid, could not be recognized by the MIP. Furthermore, the MIP was successfully applied for extraction of CA and CGA in the leaves of Eucommia ulmodies in HILIC mode. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Mechanism and kinetics in reactions of caffeic acid with radicals by pulse radiolysis and calculation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xifeng; Cai, Zhongli; Katsumura, Yosuke [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab

    2000-03-01

    The interaction of caffeic acid with e{sub aq}{sup -}, (CH{sub 3}){sub 2}(OH) CCH{sub 2}{sup {center_dot}}, CO{sub 2}{sup {center_dot}}{sup -}, H{sup {center_dot}}, {center_dot}OH and N{sub 3}{sup {center_dot}} radicals were studied by {gamma}-, pulse radiolysis and molecular orbital calculation. UV-visible spectra of electron/{center_dot}OH adducts, semi-quinone radicals of caffeic ions, and the stable products from the reactions were derived. The rate constants were determined. The attacked sites and the most favorable structures of the transient radicals were predicted. Reaction mechanisms were proposed. (author)

  5. Green synthesis of gold-chitosan nanocomposites for caffeic acid sensing.

    Science.gov (United States)

    Di Carlo, Gabriella; Curulli, Antonella; Toro, Roberta G; Bianchini, Chiara; De Caro, Tilde; Padeletti, Giuseppina; Zane, Daniela; Ingo, Gabriel M

    2012-03-27

    In this work, colloidal gold nanoparticles (AuNPs) stabilized into a chitosan matrix were prepared using a green route. The synthesis was carried out by reducing Au(III) to Au(0) in an aqueous solution of chitosan and different organic acids (i.e., acetic, malonic, or oxalic acid). We have demonstrated that by varying the nature of the acid it is possible to tune the reduction rate of the gold precursor (HAuCl(4)) and to modify the morphology of the resulting metal nanoparticles. The use of chitosan, a biocompatible and biodegradable polymer with a large number of amino and hydroxyl functional groups, enables the simultaneous synthesis and surface modification of AuNPs in one pot. Because of the excellent film-forming capability of this polymer, AuNPs-chitosan solutions were used to obtain hybrid nanocomposite films that combine highly conductive AuNPs with a large number of organic functional groups. Herein, Au-chitosan nanocomposites are successfully proposed as sensitive and selective electrochemical sensors for the determination of caffeic acid, an antioxidant that has recently attracted much attention because of its benefits to human health. A linear response was obtained over a wide range of concentration from 5.00 × 10(-8) M to 2.00 × 10(-3) M, and the limit of detection (LOD) was estimated to be 2.50 × 10(-8) M. Moreover, further analyses have demonstrated that a high selectivity toward caffeic acid can be achieved without interference from catechin or ascorbic acid (flavonoid and nonphenolic antioxidants, respectively). This novel synthesis approach and the high performances of Au-chitosan hybrid materials in the determination of caffeic acid open up new routes in the design of highly efficient sensors, which are of great interest for the analysis of complex matrices such as wine, soft drinks, and fruit beverages. © 2012 American Chemical Society

  6. Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study

    Directory of Open Access Journals (Sweden)

    Agata Kabała-Dzik

    2017-10-01

    Full Text Available One of the deadliest cancers among women is a breast cancer. Research has shown that two natural substances occurring in propolis, caffeic acid (CA and caffeic acid phenethyl ester (CAPE, have significant anticancer effects. The purpose of our in vitro study was to compare cytotoxic activity and migration rate inhibition using CA and CAPE (doses of 50 and 100 µm against triple-negative, MDA-MB-231 breast adenocarcinoma line cells, drawn from Caucasian women. Viability was measured by XTT-NR-SRB assay (Tetrazolium hydroxide-Neutral Red-Sulforhodamine B for 24 h and 48 h periods. Cell migration for wound healing assay was taken for 0 h, 8 h, 16 h, and 24 h periods. CAPE displayed more than two times higher cytotoxicity against MDA-MB-231 cells. IC50 values for the XTT assay were as follows: CA for 24 h and 48 h were 150.94 µM and 108.42 µM, respectively, while CAPE was 68.82 µM for 24 h and 55.79 µM for 48 h. For the NR assay: CA was 135.85 µM at 24 h and 103.23 µM at 48 h, while CAPE was 64.04 µM at 24 h and 53.25 µM at 48 h. For the SRB assay: CA at 24 h was 139.80 µM and at 48 h 103.98 µM, while CAPE was 66.86 µM at 24 h and 47.73 µM at 48 h. Both agents suspended the migration rate; however, CAPE displayed better activity. Notably, for the 100 µM CAPE dose, motility of the tested breast carcinoma cells was halted.

  7. Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study

    Science.gov (United States)

    Rzepecka-Stojko, Anna; Kubina, Robert; Jastrzębska-Stojko, Żaneta; Stojko, Rafał; Wojtyczka, Robert Dariusz; Stojko, Jerzy

    2017-01-01

    One of the deadliest cancers among women is a breast cancer. Research has shown that two natural substances occurring in propolis, caffeic acid (CA) and caffeic acid phenethyl ester (CAPE), have significant anticancer effects. The purpose of our in vitro study was to compare cytotoxic activity and migration rate inhibition using CA and CAPE (doses of 50 and 100 µm) against triple-negative, MDA-MB-231 breast adenocarcinoma line cells, drawn from Caucasian women. Viability was measured by XTT-NR-SRB assay (Tetrazolium hydroxide-Neutral Red-Sulforhodamine B) for 24 h and 48 h periods. Cell migration for wound healing assay was taken for 0 h, 8 h, 16 h, and 24 h periods. CAPE displayed more than two times higher cytotoxicity against MDA-MB-231 cells. IC50 values for the XTT assay were as follows: CA for 24 h and 48 h were 150.94 µM and 108.42 µM, respectively, while CAPE was 68.82 µM for 24 h and 55.79 µM for 48 h. For the NR assay: CA was 135.85 µM at 24 h and 103.23 µM at 48 h, while CAPE was 64.04 µM at 24 h and 53.25 µM at 48 h. For the SRB assay: CA at 24 h was 139.80 µM and at 48 h 103.98 µM, while CAPE was 66.86 µM at 24 h and 47.73 µM at 48 h. Both agents suspended the migration rate; however, CAPE displayed better activity. Notably, for the 100 µM CAPE dose, motility of the tested breast carcinoma cells was halted. PMID:29048370

  8. Adsorption of Acid Red 114 onto Fe3O4@Caffeic acid recycable magnetic nanocomposite

    Directory of Open Access Journals (Sweden)

    Aylin YILDIZ

    2016-11-01

    Full Text Available In this study, the adsorption capacity of caffeic acid (CFA functionalized Fe3O4 magnetic recyclable nanocomposite (Fe3O4@CFA MNCs for removal of industrial dye Acid Red 114 (AR 114 was investigated. The max. adsorption (qm of the Fe3O4@CFA MNCs for AR114 was 333 mg/g without pH correction of the solution. Compared with other studies these adsorbent possess very adsorption capacity for AR114 dye. The adsorption isotherm data and the process of adsorption kinetics were fitted using the Langmuir equation and a pseudo-second-order kinetic model that showed chemisorption may be the rate controlling step in the adsorption processes. It was proved which the magnetic NMs technology was contributed by this study which can be a new and covetable alternative for organic contaminant adsorption. Furthermore, the reusability of the Fe3O4@CFA MNCs was investigated and significant removal of AR114 obtained even after five cycles

  9. The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability.

    Science.gov (United States)

    Qian, Bing-Jun; Liu, Jian-Hua; Zhao, Shu-Juan; Cai, Jian-Xiong; Jing, Pu

    2017-08-01

    The mechanism by which copigments stabilize colour, by protecting anthocyanin chromophores from nucleophilic attack, seems well accepted. This study was to determine effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability. Molecular dynamics simulations were applied to explore molecular interactions. Phenolic acids intensified the colour by 19%∼27%. Colour fading during heating followed first-order reactions with half-lives of 3.66, 9.64, 3.50, and 3.39h, whereas anthocyanin degradation, determined by the pH differential method (or HPLC-PDA), followed second-order reactions with half-lives of 3.29 (3.40), 3.43 (3.39), 2.29 (0.39), and 2.72 (0.32)h alone or with gallic/ferulic/caffeic acids, respectively, suggesting that anthocyanin degradation was faster than the colour fading. The strongest protection of gallic acids might be attributed to the shortest distance (4.37Å) of its aromatic ring to the anthocyanin (AC) panel. Hyperchromic effects induced by phenolic acids were pronounced and they obscured the accelerated anthocyanin degradation due to self-association interruption. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Protective Effects of Caffeic Acid Phenethyl Ester on Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

    Science.gov (United States)

    Uysal, Ersin; Yılmaz, H Ramazan; Ugan, Yunus; Altuntas, Atila; Dogru, Atalay; Kutlucan, Ali; Tunc, Sevket Ercan

    2015-12-01

    We investigated the protective effect of caffeic acid phenethyl ester (CAPE) on cyclophosphamide-induced hemorrhagic cystitis in rats in comparison with 2-mercaptoethane sulfonate (MESNA). Forty male rats were randomized into four groups: group 1 (control), group 2 (cyclophosphamide), group 3 (cyclophosphamide + MESNA), group 4 (cyclophosphamide + CAPE). Cyclophosphamide injection increased malondialdehyde levels indicating oxidative stress, whereas CAPE and MESNA ameliorated malondialdehyde levels in the bladder (p hemorrhagic cystitis, we suggest that it would be more beneficial to use MESNA with CAPE to prevent histological damage. © 2015 Wiley Periodicals, Inc.

  11. Can propolis and caffeic acid phenethyl ester (CAPE be promising agents against cyclophosphamide toxicity?

    Directory of Open Access Journals (Sweden)

    Sumeyya Akyol

    2016-03-01

    Full Text Available Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE. They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide has been used to treat a broad of malignancies including Hodgkin's and non-Hodgking's lymphoma, Burkitt's lymphoma, chronic lymphocytic leukemia, Ewing's sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against cyclophosphamide-induced injuries. [J Intercult Ethnopharmacol 2016; 5(1.000: 105-107

  12. Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model

    OpenAIRE

    Kim, Ji Hyun; Wang, Qian; Choi, Ji Myung; Lee, Sanghyun; Cho, Eun Ju

    2015-01-01

    BACKGROUND/OBJECTIVES Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide (Aβ) and oxidative stress in the brain are the most common causes of AD. MATERIALS/METHODS Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an Aβ25-35-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavi...

  13. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    Directory of Open Access Journals (Sweden)

    Martin J. G. Hébert

    2015-01-01

    Full Text Available Two novel boron compounds containing caffeic acid phenethyl ester (CAPE derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  14. Polydopamine-coated magnetic molecularly imprinted polymer for the selective solid-phase extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample.

    Science.gov (United States)

    Yin, Yuli; Yan, Liang; Zhang, Zhaohui; Wang, Jing; Luo, Ningjing

    2016-04-01

    We describe novel cinnamic acid polydopamine-coated magnetic imprinted polymers for the simultaneous selective extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample. The novel magnetic imprinted polymers were synthesized by surface imprinting polymerization using magnetic multi-walled carbon nanotubes as the support material, cinnamic acid as the template and dopamine as the functional monomer. The magnetic imprinted polymers were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometry. The results revealed that the magnetic imprinted polymers had outstanding magnetic properties, high adsorption capacity, selectivity and fast kinetic binding toward cinnamic acid, ferulic acid and caffeic acid. Coupled with high-performance liquid chromatography, the extraction conditions of the magnetic imprinted polymers as a magnetic solid-phase extraction sorbent were investigated in detail. The proposed imprinted magnetic solid phase extraction procedure has been used for the purification and enrichment of cinnamic acid, ferulic acid and caffeic acid successfully from radix scrophulariae extraction sample with recoveries of 92.4-115.0% for cinnamic acid, 89.4-103.0% for ferulic acid and 86.6-96.0% for caffeic acid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Synthesis and Antiradical/Antioxidant Activities of Caffeic Acid Phenethyl Ester and Its Related Propionic, Acetic, and Benzoic Acid Analoguesc

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    Mohamed Touaibia

    2012-12-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is a bioactive component isolated from propolis. A series of CAPE analogues was synthesized and their antiradical/antioxidant effects analyzed. The effect of the presence of the double bond and of the conjugated system on the antioxidant effect is evaluated with the analogues obtained from 3-(3,4-dihydroxyphenyl propanoic acid. Those obtained from 2-(3,4-dihydroxyphenyl acetic acid and 3,4-dihydroxybenzoic acid allow the evaluation of the effect of the presence of two carbons between the carbonyl and aromatic system.

  16. Synthesis and antiradical/antioxidant activities of caffeic acid phenethyl ester and its related propionic, acetic, and benzoic acid analogues.

    Science.gov (United States)

    LeBlanc, Luc M; Paré, Aurélie F; Jean-François, Jacques; Hébert, Martin J G; Surette, Marc E; Touaibia, Mohamed

    2012-12-10

    Caffeic acid phenethyl ester (CAPE) is a bioactive component isolated from propolis. A series of CAPE analogues was synthesized and their antiradical/antioxidant effects analyzed. The effect of the presence of the double bond and of the conjugated system on the antioxidant effect is evaluated with the analogues obtained from 3-(3,4-dihydroxyphenyl) propanoic acid. Those obtained from 2-(3,4-dihydroxyphenyl) acetic acid and 3,4-dihydroxybenzoic acid allow the evaluation of the effect of the presence of two carbons between the carbonyl and aromatic system.

  17. Regulatory Effects of Caffeic Acid Phenethyl Ester on Neuroinflammation in Microglial Cells

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    Cheng-Fang Tsai

    2015-03-01

    Full Text Available Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE, a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties. Accordingly, the current study intended to probe the effects of CAPE on microglia activation by using in vitro and in vivo models. Western blot and Griess reaction assay revealed CAPE significantly inhibited the expressions of inducible nitric oxide synthase (NOS, cyclooxygenase (COX-2 and the production of nitric oxide (NO. Administration of CAPE resulted in increased expressions of hemeoxygenase (HO-1and erythropoietin (EPO in microglia. The phosphorylated adenosine monophosphate-activated protein kinase (AMPK-α was further found to regulate the anti-inflammatory effects of caffeic acid. In vivo results from immunohistochemistry along with rotarod test also revealed the anti-neuroinflammatory effects of CAPE in microglia activation. The current study has evidenced several possible molecular determinants, AMPKα, EPO, and HO-1, in mediating anti-neuroinflammatory responses in microglial cells.

  18. Choline chloride-based deep eutectic solvents as additives for optimizing chromatographic behavior of caffeic acid

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    Li, Guizhen; Zhu, Tao; Lei, Yingjie [Tianjin University of Technology, Tianjin (China)

    2015-10-15

    A series of deep eutectic solvents (DESs) were prepared using glycerol and choline chloride (ChCl), and Fourier transform infrared spectrometer (FT-IR) was used to analyze the spectra of glycerol, choline chloride and DESs based on glycerol and choline chloride. Then DESs were used as the additives of mobile phase to optimize chromatographic behavior of caffeic acid in high performance liquid chromatography (HPLC). A 17-run Box-Behnken design (BBD) was employed to evaluate effect of DESs as additives by analyzing the maximum theoretical plate number. Three factors, reaction temperature (60 .deg. C, 80 .deg. C, 100 .deg. C), molar ratio of glycerol and choline chloride (2 : 1, 3 : 1, 4 : 1, n/n), and volume percent of additives (0.05%, 0.10%, 0.15%, v/v), were investigated in BBD. The optimum experiment condition was that of reaction temperature (80 .deg. C), molar ratio of glycerol and ChCl (3 : 1, n/n), and volume percent of additive (0.10%, v/v). The mean chromatographic theoretical plate number of the caffeic acid this condition was 1567.5, and DESs as additives shorten the retention time and modify the chromatogram shape, proving DESs as additives for effective theoretical plate number and column efficiency in HPLC.

  19. Radio-Modulatory Potential ofCaffeic Acid Phenethyl Ester: A Therapeutic Perspective.

    Science.gov (United States)

    Anjaly, Km; Tiku, Ashu

    2017-11-13

    Use of natural agents is an upcoming area of research in cancer biology. Caffeic acid phenethyl ester has received great attention because of its therapeutic potential in various conditions including cancer. It is an active/abundant component of propolis. Propolis is a honey bee hive product produced by bees using their enzyme-rich digestive secretions on resinous mix, bee wax and pollen from plants. It is used to protect the beehive against bacteria and other infections.Although a lot of work has been done on chemotherapeutic aspects of CAPE, its role as a radiomodulator is yet to be delineated. It can act both as radioprotector and radiosensitizer. Depending on the tissue type it can modulate the radiation response by following different mechanisms. This review will focus on the differential radiomodulatory effects of Caffeic Acid Phenethyl Ester in normal and cancer cells.Besides chemistry and bioavailability,it's potential as a therapeutic agent against radiation induced damage will also be discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Thermal transformation of bioactive caffeic acid on fumed silica seen by UV-Vis spectroscopy, thermogravimetric analysis, temperature programmed desorption mass spectrometry and quantum chemical methods.

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    Kulik, Tetiana V; Lipkovska, Natalia O; Barvinchenko, Valentyna M; Palyanytsya, Borys B; Kazakova, Olga A; Dudik, Olesia O; Menyhárd, Alfréd; László, Krisztina

    2016-05-15

    Thermochemical studies of hydroxycinnamic acid derivatives and their surface complexes are important for the pharmaceutical industry, medicine and for the development of technologies of heterogeneous biomass pyrolysis. In this study, structural and thermal transformations of caffeic acid complexes on silica surfaces were studied by UV-Vis spectroscopy, thermogravimetric analysis, temperature programmed desorption mass spectrometry (TPD MS) and quantum chemical methods. Two types of caffeic acid surface complexes are found to form through phenolic or carboxyl groups. The kinetic parameters of the chemical reactions of caffeic acid on silica surface are calculated. The mechanisms of thermal transformations of the caffeic chemisorbed surface complexes are proposed. Thermal decomposition of caffeic acid complex chemisorbed through grafted ester group proceeds via three parallel reactions, producing ketene, vinyl and acetylene derivatives of 1,2-dihydroxybenzene. Immobilization of phenolic acids on the silica surface improves greatly their thermal stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Analysis of Caffeic Acid Extraction From Ocimum gratissimum Linn. by High Performance Liquid Chromatography and its Effects on a Cervical Cancer Cell Line

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    Je-Chiuan Ye

    2010-09-01

    Conclusion: This paper shows that high performance liquid chromatography is a suitable analytical method for determining caffeic acid levels in O. gratissimum, Ju ZenTa, and several vegetable oils. Caffeic acid can suppress the proliferation of HeLa cells.

  2. Product analysis of caffeic acid oxidation by on-line electrochemistry/electrospray ionization mass spectrometry.

    Science.gov (United States)

    Arakawa, Ryuichi; Yamaguchi, Masashi; Hotta, Hiroki; Osakai, Toshiyuki; Kimoto, Takashi

    2004-08-01

    On-line electrochemistry/electrospray ionization mass spectrometry (EC/ESI-MS) was developed using a microflow electrolytic cell. This technique was applied to electrochemical oxidation of caffeic acid (CAF) which is known to be a highly antioxidative agent. Effects of electrolytic potentials on ion intensities of product ions and on electrolytic currents were examined at different pHs. Dimer products were detected at electrolytic potentials of E = 0.7 V (vs. Ag/AgCl) and trimer products at 1.0 V at pH 9. Dimer products were distinguished from hydrogen-bonded complexes by MS/MS experiments. Hydrogen/deuterium exchange experiments determined the number of hydroxyl and carboxyl groups in the Dimers formed by electrolysis. The mechanism of oxidative polymerization of CAF is discussed with speculation as to the structure of the dimer product.

  3. Antiviral Properties of Caffeic Acid Phenethyl Ester and Its Potential Application

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    Haci Kemal Erdemli

    2015-12-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is found in variety of plants and well known active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature. [J Intercult Ethnopharmacol 2015; 4(4.000: 344-347

  4. Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction.

    Science.gov (United States)

    Nader, Manar A

    2013-04-01

    Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis extracts. The results of the current study demonstrate that CAPE attenuated immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE effectively reduced both histamine and serotonin (5-HT)-induced vascular permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction induced by histamine (3 × 10(-8)-3 × 10(-5) M), 5-HT (3 × 10(-9)-10(-6) M) and adenosine (3 × 10(-8)-10(-5) M) in guinea pig tracheal zigzag. These findings provide evidence that CAPE may serve as an effective therapeutic agent for allergic diseases.

  5. Engineering alfalfa to accumulate useful caffeic acid derivatives and characterization of hydroxycinnamoyl-CoA transferases from legumes

    Science.gov (United States)

    Some forages crops, such as red clover, accumulate high levels of caffeic acid derivatives. Oxidation of these o-diphenols to quinones by endogenous polyphenol oxidases (PPOs) and the subsequent reactions of these quinones (probably with endogenous plant proteases) result in a significant reduction ...

  6. Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL-induced EGF-receptor activation

    Science.gov (United States)

    Vacaresse, Nathalie; Vieira, Otília; Robbesyn, Fanny; Jürgens, Günther; Salvayre, Robert; Negre-Salvayre, Anne

    2001-01-01

    Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among them 4-hydroxynonenal, 4-HNE) contained in oxLDL.The use of phenolic antioxidants, such as trolox, alpha-tocopherol, caffeic acid and tyrphostins A-25, A-46 or A-1478, showed that the oxLDL-induced EGFR activation is constituted by two separate components, the first (early) one being antioxidant-insensitive, the second (late) being antioxidant-sensitive.4-HNE derivatization of EGFR and EGFR activation induced by exogenous 4-HNE, suggest that the early (0.5 – 3 h) component of oxLDL-induced EGFR activation is mediated (at least in part) by 4-HNE (and possibly by other oxidized lipids). This early component is antioxidant-insensitive.The second component (4 – 5 h) of the oxLDL-induced EGFR activation is antioxidant-sensitive, since it is blocked by antioxidants such as trolox, caffeic acid or PDTC, which act by blocking the cellular oxidative stress (H2O2 generation) evoked by oxLDL. Conversely, exogenous H2O2 induced EGFR autophosphorylation (thus mimicking the second component) and was also inhibited by antioxidants. This effect is mediated in part through inhibition by oxidative stress of protein tyrosine phosphatases involved in EGFR dephosphorylation. PMID:11309250

  7. Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture

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    Kazancioglu HO

    2015-12-01

    Full Text Available Hakki Oguz Kazancioglu,1 Sertac Aksakalli,2 Seref Ezirganli,1 Muhammet Birlik,2 Mukaddes Esrefoglu,3 Ahmet Hüseyin Acar1 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, Faculty of Dentistry, 3Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new application has been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE on new bone formation in rat midpalatal suture after RME.Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess of new bone formation.Results: New bone formation was significantly greater in CAPE group than the control group (P<0.05. CAPE enhances new bone formation in midpalatal suture after RME.Conclusion: These results show that CAPE may decrease the time needed for retention. Keywords: rapid maxillary expansion, bone formation, caffeic acid phenethyl ester, midpalatal suture, histopathology

  8. Inhibitory effect of caffeic acid on human organic anion transporters hOAT1 and hOAT3: a novel candidate for food-drug interaction.

    Science.gov (United States)

    Uwai, Yuichi; Ozeki, Yukihiro; Isaka, Tomonori; Honjo, Hiroaki; Iwamoto, Kikuo

    2011-01-01

    Several kinds of food have been shown to influence the absorption and metabolism of drugs, although there is little information about their effect on the renal excretion of drugs. In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effects of chlorogenic acid, caffeic acid and quinic acid, which are contained in coffee, fruits and vegetables, on human organic anion transporters hOAT1 and hOAT3; these transporters mediate renal tubular uptake of anionic drugs from blood. Injection of hOAT1 and hOAT3 cRNA into oocytes stimulated uptake of typical substrates of hOAT1 and hOAT3 (p-aminohippurate and estrone sulfate, respectively); among the three compounds tested, caffeic acid most strongly inhibited these transporters. The apparent 50% inhibitory concentrations of caffeic acid were estimated to be 16.6 µM for hOAT1 and 5.4 µM for hOAT3. Eadie-Hofstee plot analysis showed that caffeic acid inhibited both transporters in a competitive manner. In addition to the transport of p-aminohippurate and estrone sulfate, that of antifolates and antivirals was inhibited by caffeic acid. These findings show that caffeic acid has inhibitory potential against hOAT1 and hOAT3, suggesting that renal excretion of their substrates could be affected in patients consuming a diet including caffeic acid.

  9. Fungal biotransformation of chlorogenic and caffeic acids by Fusarium graminearum: New insights in the contribution of phenolic acids to resistance to deoxynivalenol accumulation in cereals.

    Science.gov (United States)

    Gauthier, Léa; Bonnin-Verdal, Marie-Noelle; Marchegay, Gisèle; Pinson-Gadais, Laetitia; Ducos, Christine; Richard-Forget, Florence; Atanasova-Penichon, Vessela

    2016-03-16

    Fusarium Head Blight and Gibberella Ear Rot, mainly caused by the fungi Fusarium graminearum and Fusarium culmorum, are two of the most devastating diseases of small-grain cereals and maize. In addition to yield loss, these diseases frequently result in contamination of kernels with toxic type B trichothecenes. The potential involvement of chlorogenic acid in cereal resistance to Fusarium Head Blight and Gibberella Ear Rot and to trichothecene accumulation was the focus of this study. The effects of chlorogenic acid and one of its hydrolyzed products, caffeic acid, on fungal growth and type B trichothecenes biosynthesis were studied using concentrations close to physiological amounts quantified in kernels and a set of F. graminearum and F. culmorum strains. Both chlorogenic and caffeic acids negatively impact fungal growth and mycotoxin production, with caffeic acid being significantly more toxic. Inhibitory efficiencies of both phenolic acids were strain-dependent. To further investigate the antifungal and anti "mycotoxin" effect of chlorogenic and caffeic acids, the metabolic fate of these two phenolic acids was characterized in supplemented F. graminearum broths. For the first time, our results demonstrated the ability of F. graminearum to degrade chlorogenic acid into caffeic, hydroxychlorogenic and protocatechuic acids and caffeic acid into protocatechuic and hydroxycaffeic acids. Some of these metabolic products can contribute to the inhibitory efficiency of chlorogenic acid that, therefore, can be compared as a "pro-drug". As a whole, our data corroborate the contribution of chlorogenic acid to the chemical defense that cereals employ to counteract F. graminearum and its production of mycotoxins. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

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    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.

  11. Impact of caffeic acid addition on phenolic composition of tempranillo wines from different winemaking techniques.

    Science.gov (United States)

    Aleixandre-Tudó, José Luis; Alvarez, I; Lizama, Victoria; García, María José; Aleixandre, José Luis; Du Toit, Wessel J

    2013-12-11

    The effect of prefermentative and postfermentative caffeic acid (CFA) addition, prefermentative cold maceration, and a simulation of the micro-oxygenation technique through acetaldehyde addition on the phenolic and color composition of Tempranillo wines was investigated. Cold soaking and dry ice addition were performed as prefermentative techniques. Wines were analyzed after the end of the malolactic fermentation and after 6 and 12 months' storage. The results showed an important effect in wines to which CFA had been added, suggesting intramolecular copigmentation reactions through direct interaction between anthocyanins and free phenolic acids, thereby increasing the acylated anthocyanin fraction with an increase in color stability. The higher concentration of total phenols and lower hue values in CFA-added wines also contributed to the stability of these compounds during storage. Prefermentative cold maceration was shown to be influenced by the vintage. Phenolic acids, the acylated anthocyanin fraction, and total phenolics showed higher values in CFA-added and acetaldehyde-added wines. No differences were found in color density between the control wines and both the prefermentative and postfermentative CFA-added wines. However, a higher anthocyanin polymeric fraction and higher acylated anthocyanins, phenolic acids, and total phenols were observed in the CFA-added wines. The implications of this for the color stability of Tempranillo are also discussed.

  12. Simulation of force spectroscopy experiments on galacturonic acid oligomers.

    Science.gov (United States)

    Cybulska, Justyna; Brzyska, Agnieszka; Zdunek, Artur; Woliński, Krzysztof

    2014-01-01

    Pectins, forming a matrix for cellulose and hemicellulose, determine the mechanics of plant cell walls. They undergo salient structural changes during their development. In the presence of divalent cations, usually calcium, pectins can form gel-like structures. Because of their importance they have been the subject of many force spectroscopy experiments, which have examined the conformational changes and molecular tensions due to external forces. The most abundant unit present in the pectin backbone is polygalacturonic acid. Unfortunately, experimental force spectroscopy on polygalacturonic acid molecules is still not a trivial task. The mechanism of the single-molecule response to external forces can be inferred by theoretical methods. Therefore, in this work we simulated such force spectroscopy experiments using the Enforced Geometry Optimization (EGO) method. We examined the oligomeric (up to hexamer) structures of α-D-galacturonic acid exposed to external stretching forces. The EGO simulation of the force spectroscopy appropriately reproduced the experimental course of the enforced conformational transition: chair →inverted chair via the twisted boat conformation(s) in the pyranose ring of α-D-galacturonic acid. Additionally, our theoretical approach also allowed to determine the minimum oligomer size adequate for the description of nano-mechanical properties of (poly)-α-D-galacturonic acid.

  13. Simulation of force spectroscopy experiments on galacturonic acid oligomers.

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    Justyna Cybulska

    Full Text Available Pectins, forming a matrix for cellulose and hemicellulose, determine the mechanics of plant cell walls. They undergo salient structural changes during their development. In the presence of divalent cations, usually calcium, pectins can form gel-like structures. Because of their importance they have been the subject of many force spectroscopy experiments, which have examined the conformational changes and molecular tensions due to external forces. The most abundant unit present in the pectin backbone is polygalacturonic acid. Unfortunately, experimental force spectroscopy on polygalacturonic acid molecules is still not a trivial task. The mechanism of the single-molecule response to external forces can be inferred by theoretical methods. Therefore, in this work we simulated such force spectroscopy experiments using the Enforced Geometry Optimization (EGO method. We examined the oligomeric (up to hexamer structures of α-D-galacturonic acid exposed to external stretching forces. The EGO simulation of the force spectroscopy appropriately reproduced the experimental course of the enforced conformational transition: chair →inverted chair via the twisted boat conformation(s in the pyranose ring of α-D-galacturonic acid. Additionally, our theoretical approach also allowed to determine the minimum oligomer size adequate for the description of nano-mechanical properties of (poly-α-D-galacturonic acid.

  14. Chlorogenic acid versus amaranth's caffeoylisocitric acid - Gut microbial degradation of caffeic acid derivatives.

    Science.gov (United States)

    Vollmer, Maren; Schröter, David; Esders, Selma; Neugart, Susanne; Farquharson, Freda M; Duncan, Sylvia H; Schreiner, Monika; Louis, Petra; Maul, Ronald; Rohn, Sascha

    2017-10-01

    The almost forgotten crop amaranth has gained renewed interest in recent years due to its immense nutritive potential. Health beneficial effects of certain plants are often attributed to secondary plant metabolites such as phenolic compounds. As these compounds undergo significant metabolism after consumption and are in most cases not absorbed very well, it is important to gain knowledge about absorption, biotransformation, and further metabolism in the human body. Whilst being hardly found in other edible plants, caffeoylisocitric acid represents the most abundant low molecular weight phenolic compound in many leafy amaranth species. Given that this may be a potentially bioactive compound, gastrointestinal microbial degradation of this substance was investigated in the present study by performing in vitro fermentation tests using three different fecal samples as inocula. The (phenolic) metabolites were analyzed using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Furthermore, quantitative polymerase chain reaction (qPCR) analyses were carried out to study the influence on the microbiome and its composition. The in vitro fermentations led to different metabolite profiles depending on the specific donor. For example, the metabolite 3-(4-hydroxyphenyl)propionic acid was observed in one fermentation as the main metabolite, whereas 3-(3-hydroxyphenyl)propionic acid was identified in the other fermentations as important. A significant change in selected microorganisms of the gut microbiota however was not detected. In conclusion, caffeoylisocitric acid from amaranth, which is a source of several esterified phenolic acids in addition to chlorogenic acid, can be metabolized by the human gut microbiota, but the metabolites produced vary between individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Caffeic Acid Phenethyl Ester from the Twigs of Cinnamomum cassia Inhibits Malignant Cell Transformation by Inducing c-Fos Degradation.

    Science.gov (United States)

    Shin, Seung Ho; Lee, Seoung Rak; Lee, Eunjung; Kim, Ki Hyun; Byun, Sanguine

    2017-07-28

    The twigs of Cinnamomum cassia, commonly referred to as Cinnamomi Ramulus, are widely used as one of the primary ingredients in Chinese/Korean traditional medicines that have anticancer effects. However, the active constituents responsible for its anticancer effects and their molecular mechanisms still remain to be elucidated. Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA) were isolated for the first time from C. cassia using LC-MS-guided phytochemical isolation methods. CAPE significantly suppressed EGF- and TPA-induced cell transformation of JB6 P+ cells at sub-micromolar concentrations, whereas CA, a structurally similar compound to CAPE, had no such effect. The antiproliferative and chemopreventive activity of CAPE was found to arise through the inhibition of AP-1 transcriptional activity via the promotion of c-Fos degradation. These findings demonstrate that CAPE may contribute to the chemopreventive/chemotherapeutic effects of C. cassia through downregulating c-Fos.

  16. Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester on Nephrotoxicity Caused by Dichlorvos in Rats

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    Muhammet Murat Celik

    2015-01-01

    Full Text Available The protective effects of Caffeic Acid Phenethyl Ester (CAPE and intralipid (IL on nephrotoxicity caused by acute Dichlorvos (D toxicity were investigated in this study. Forty-eight Wistar Albino rats were divided into 7 groups as follows: Control, D, CAPE, intralipid, D + CAPE, D + IL, and D + CAPE + IL. When compared to D group, the oxidative stress index (OSI values were significantly lower in Control, CAPE, and D + IL + CAPE groups. When compared to D + IL + CAPE group, the TOS and OSI values were significantly higher in D group (P<0.05. When mitotic cell counts were assessed in the renal tissues, it was found that mitotic cell count was significantly higher in the D group while it was lower in the D + CAPE, D + IL, and D + IL + CAPE groups when compared to the control group (P<0.05. Also, immune reactivity showed increased apoptosis in D group and low profile of apoptosis in the D + CAPE group when compared to the Control group. The apoptosis level was significantly lower in D + IL + CAPE compared to D group (P<0.05 in the kidneys. As a result, we concluded that Dichlorvos can be used either alone or in combination with CAPE and IL as supportive therapy or as facilitator for the therapeutic effect of the routine treatment in the patients presenting with pesticide poisoning.

  17. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

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    Ying-Yu Kuo

    2015-05-01

    Full Text Available Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC. The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs, epidermal growth factor receptor (EGFR, and Cyclooxygenase-2 (COX-2. Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K/protein kinase B (Akt signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.

  18. Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells

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    Tarek K. Motawi

    2016-01-01

    Full Text Available Although Tamoxifen (TAM is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

  19. Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models.

    Science.gov (United States)

    Lutfi, Esmail; Babin, Patrick J; Gutiérrez, Joaquim; Capilla, Encarnación; Navarro, Isabel

    2017-01-01

    Some natural products, known sources of bioactive compounds with a wide range of properties, may have therapeutic values in human health and diseases, as well as agronomic applications. The effect of three compounds of plant origin with well-known dietary antioxidant properties, astaxanthin (ATX), caffeic acid (CA) and hydroxytyrosol (HT), on zebrafish (Danio rerio) larval adiposity and rainbow trout (Onchorynchus mykiss) adipocytes was assessed. The zebrafish obesogenic test (ZOT) demonstrated the anti-obesogenic activity of CA and HT. These compounds were able to counteract the obesogenic effect produced by the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone (RGZ). CA and HT suppressed RGZ-increased PPARγ protein expression and lipid accumulation in primary-cultured rainbow trout adipocytes. HT also significantly reduced plasma triacylglycerol concentrations, as well as mRNA levels of the fasn adipogenic gene in the adipose tissue of HT-injected rainbow trout. In conclusion, in vitro and in vivo approaches demonstrated the anti-obesogenic potential of CA and HT on teleost fish models that may be relevant for studying their molecular mode of action. Further studies are required to evaluate the effect of these bioactive components as food supplements for modulating adiposity in farmed fish.

  20. Caffeic Acid Phenethyl Ester Regulates PPAR’s Levels in Stem Cells-Derived Adipocytes

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    Luca Vanella

    2016-01-01

    Full Text Available Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ, considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape, isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration.

  1. Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice

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    Radia Belkhelfa-Slimani

    2017-04-01

    Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.

  2. Terpenoids, flavonoids and caffeic acid derivatives from Salvia viridis L. cvar. Blue Jeans.

    Science.gov (United States)

    Rungsimakan, Supattra; Rowan, Michael G

    2014-12-01

    Three diterpenoids, 1-oxomicrostegiol (1), viroxocin (2), viridoquinone (3), were isolated from the roots of Salvia viridis L. cvar. Blue Jeans. Five known diterpenoids, microstegiol (4), 7α-acetoxy-14-hydroxy-8,13-abietadiene-11,12-dione (5; 7-O-acetylhorminone tautomer), 7α,14-dihydroxy-8,13-abietadiene-11,12-dione (6; horminone tautomer), ferruginol and salvinolonyl 12-methyl ether (7) were also found in the roots together with 1-docosyl ferulate (8), and a mixture of 2-(4'-alkoxyphenyl) ethyl alkanoates (9). Two lupane triterpenoids, 2α-acetoxy-lup-20(29)-en-3β-ol (10), and 3β-acetoxy-lup-20(29)-en-2α-ol (11) were found in the aerial parts together with known compounds, lup-20(29)-ene-2α,3β-diol (12), ursolic acid, oleanolic acid, β-sitosterol and β-sitosterol glucoside. A known phenylpropanoid, trans-verbascoside (or acteoside; 13), was the main constituent in the polar fraction of the aerial part, and it is now reported in the genus Salvia for the first time. Other polyphenolic compounds were cis-verbascoside (14), leucosceptoside A (15), martynoside (16), caffeic acid, 6-O-caffeoyl-glucose (18), rosmarinic acid, salidroside, luteolin-7-O-α-rhamnopyranosyl-(1→6)-β-galactopyranoside, luteolin-7-O-β-galactopyranoside, luteolin-7-O-α-rhamnopyranosyl-(1→6)-β-glucopyranoside, luteolin-7-O-β-glucopyranoside, and apigenin-7-O-β-glucopyranoside. The structures were determined by 1D-, 2D-NMR and HR-ESI-MS techniques. Compounds 6, 10, ferruginol, ursolic acid and oleanolic acid exhibited antibacterial activity against Enterococcus faecalis (ATCC 775) with MIC 50 μM, 25 μM, 50 μM, 12.5 μM, 12.5 μM respectively. Ferruginol, ursolic acid and oleanolic acid were also active against Staphylococcus aureus (ATCC 6571), and Bacillus cereus (ATCC 2599) with MIC 12.5-50 μM. 4 was also active against S.aureus (ATCC 6571) with MIC 50 μM. These values are consistent with previous studies on the antimicrobial activity of Salvia diterpenoids. Copyright

  3. Detoxification Processes from Vanadate at the Root Apoplasm Activated by Caffeic and Polygalacturonic Acids.

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    Giovanni Garau

    Full Text Available In the root apoplasm, V(V and V(IV toxicity can be alleviated through redox and complexation reactions involving phenolic substances and the polyuronic components. In such context we report the role of polygalacturonic acid (PGA on the reducing activity of caffeic acid (CAF towards V(V. The redox reaction was particularly effective at pH 2.8 leading to the formation of oxidation products with redox activity towards V(V. An o-quinone was identified as the first product of the reaction which is further involved in the formation of CAF dimers. At pH ≥ 3.6 the redox activity decreased and a yield in V(IV equal to 38, 31, 21 and 14% was found at pH 3.6, 4.0. 5.0 and 6.0 respectively compared with that obtained at pH 2.8. The redox reaction was faster in the presence of PGA and a higher yield of V(IV was found in the 4.0-6.0 pH range with respect to the CAF-V(V binary system. The higher efficiency of the redox reaction in the presence of PGA was related with the ability of PGA to bind V(IV. The biological significance of the redox reaction between CAF and V(V, as well as the role of PGA in such reaction, was established "in vivo" using triticale plants. Results showed that PGA reduced significantly the phytotoxic effects of the V(V-CAF system.

  4. Caffeic Acid Phenethyl Ester Protects against Amphotericin B Induced Nephrotoxicity in Rat Model

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    Altuntaş, Atila; Yılmaz, H. Ramazan; Altuntaş, Ayşegül; Uz, Efkan; Demir, Murat; Gökçimen, Alparslan; Aksu, Oğuzhan; Bayram, Dilek Şenol; Sezer, Mehmet Tuğrul

    2014-01-01

    The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 μmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 μmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models. PMID:25032223

  5. Functional characterization of cinnamyl alcohol dehydrogenase and caffeic acid O-methyltransferase in Brachypodium distachyon

    Science.gov (United States)

    2013-01-01

    Background Lignin is a significant barrier in the conversion of plant biomass to bioethanol. Cinnamyl alcohol dehydrogenase (CAD) and caffeic acid O-methyltransferase (COMT) catalyze key steps in the pathway of lignin monomer biosynthesis. Brown midrib mutants in Zea mays and Sorghum bicolor with impaired CAD or COMT activity have attracted considerable agronomic interest for their altered lignin composition and improved digestibility. Here, we identified and functionally characterized candidate genes encoding CAD and COMT enzymes in the grass model species Brachypodium distachyon with the aim of improving crops for efficient biofuel production. Results We developed transgenic plants overexpressing artificial microRNA designed to silence BdCAD1 or BdCOMT4. Both transgenes caused altered flowering time and increased stem count and weight. Downregulation of BdCAD1 caused a leaf brown midrib phenotype, the first time this phenotype has been observed in a C3 plant. While acetyl bromide soluble lignin measurements were equivalent in BdCAD1 downregulated and control plants, histochemical staining and thioacidolysis indicated a decrease in lignin syringyl units and reduced syringyl/guaiacyl ratio in the transgenic plants. BdCOMT4 downregulated plants exhibited a reduction in total lignin content and decreased Maule staining of syringyl units in stem. Ethanol yield by microbial fermentation was enhanced in amiR-cad1-8 plants. Conclusion These results have elucidated two key genes in the lignin biosynthetic pathway in B. distachyon that, when perturbed, may result in greater stem biomass yield and bioconversion efficiency. PMID:23902793

  6. The protective effects of caffeic acid phenethyl ester against toluene-induced nephrotoxicity in rats.

    Science.gov (United States)

    Meydan, Sedat; Nacar, Ahmet; Oztürk, Hasan Oktay; Tas, Ufuk; Köse, Evren; Zararsiz, Ismail; Yılmaz, Nigar; Kus, Ilter

    2016-01-01

    Caffeic acid phenethyl ester (CAPE) has antioxidant and anti-inflammatory properties. The aim of this study is to examine the negative effects of toluene on kidney tissues and functions and to investigate the protective effects of CAPE against toluene-induced nephrotoxicity in rats. A total of 21 male Wistar rats were divided into three groups of equal number in each. The rats in group I were the controls. Toluene was intraperitoneally injected into the rats in group II with a dose of 500 mg/kg. Rats in group III received CAPE daily while exposed to toluene. After 14 days of experimental period, all rats were killed by decapitation. Enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and malondialdehyde (MDA) levels were studied in the rat kidneys. Blood urea nitrogen (BUN) and serum creatinine levels were measured for renal function. The CAT and SOD enzyme activities and serum creatinine levels were significantly increased in rats treated with toluene when compared with the controls. But GSH-Px activity, MDA, and BUN levels showed statistically nonsignificant changes. However, increased CAT and SOD enzyme activities and decreased serum creatinine levels were detected in the rats that received CAPE while exposed to toluene. The GSH-Px activity and MDA and BUN levels in the same group did not show statistically significant changes. The results of our study demonstrated that toluene damages kidney tissue and is a nephrotoxic substance. CAPE was able to prevent the renal damage as antioxidant, antitoxic, and nephroprotective agent. © The Author(s) 2013.

  7. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    Science.gov (United States)

    Genaro-Mattos, Thiago C; Maurício, Ângelo Q; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its beneficial effects

  8. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation—A Chemical Approach

    Science.gov (United States)

    Genaro-Mattos, Thiago C.; Maurício, Ângelo Q.; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here—in association with its reported signaling effects—could be an explanation to its beneficial effects

  9. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    Directory of Open Access Journals (Sweden)

    Thiago C Genaro-Mattos

    Full Text Available Caffeic acid (CA is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its

  10. Pharmacokinetics of Caffeic Acid, Ferulic Acid, Formononetin, Cryptotanshinone, and Tanshinone IIA after Oral Administration of Naoxintong Capsule in Rat by HPLC-MS/MS

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    Jin Li

    2017-01-01

    Full Text Available Naoxintong capsule (NXTC was a famous patent medicine of Traditional Chinese Medicine (TCM to treat cerebrovascular diseases in China. An LC-MS/MS method was developed for simultaneous determination of 11 major ingredients (paeoniflorin, ecdysterone, amygdalin, mulberroside A, caffeic acid, ferulic acid, salvianolic acid B, astragaloside IV, formononetin, cryptotanshinone, and tanshinone IIA in NXTC in rat plasma. All analytes were separated on an Eclipse plus C18 column using a gradient mobile phase system of acetonitrile-0.1% formic acid aqueous solution. The lower limits of quantification of 11 ingredients were between 0.075 and 10 ng mL−1. The precision was less than 15% and the accuracies were between 85% and 115%. The results showed that caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA could be detected after oral administration of NXTC. The validated method was successfully applied to pharmacokinetic study of the caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA in rats after oral administration of NXTC at single and triple dose.

  11. Ternary choline chloride/caffeic acid/ethylene glycol deep eutectic solvent as both a monomer and template in a molecularly imprinted polymer.

    Science.gov (United States)

    Fu, Najing; Liu, Xiao; Li, Liteng; Tang, Baokun; Row, Kyung Ho

    2017-05-01

    A molecularly imprinted polymer based on a ternary deep eutectic solvent comprised of choline chloride/caffeic acid/ethylene glycol was prepared. The caffeic acid in the ternary deep eutectic solvent was used as both a monomer and template. The molecularly imprinted polymer based on the ternary deep eutectic solvent was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, field-emission scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, atomic force microscopy, and elemental analysis. A series of molecularly imprinted polymers based on choline chloride/caffeic acid/ethylene glycol with different molar ratios was prepared and applied to the molecular recognition of polyphenols. A comparison of the recognition ability of molecularly imprinted polymers to polyphenols revealed that the choline chloride/caffeic acid/ethylene glycol (1:0.4:1, molar ratio) molecularly imprinted polymer had the best molecular recognition effect with 132 μg/g of protocatechuic acid, 104 μg/g of catechins, 80 μg/g of epicatechin, and 123 μg/g of caffeic acid in 6 h, as well as good molecular recognition ability for polyphenols from a Radix Asteris sample. These results show that the ternary deep eutectic solvent based molecularly imprinted polymer is a potential medium that can be applied to drug purification, drug delivery, and drug analysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester.

    Science.gov (United States)

    Oktem, Faruk; Ozguner, Fehmi; Sulak, Osman; Olgar, Seref; Akturk, Onur; Yilmaz, H Ramazan; Altuntas, Irfan

    2005-09-01

    Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 microM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

  13. Development of an Electrochemical Sensor for NADH Determination Based on a Caffeic Acid Redox Mediator Supported on Carbon Black

    Directory of Open Access Journals (Sweden)

    Chiara Zanardi

    2015-04-01

    Full Text Available Screen-printed electrode (SPE modified with carbon black nanoparticles (CB has been tested as a new platform for the stable deposition of caffeic acid (CFA on the electrode surface. The electrochemical performance from varying the amount of CFA/CB composite has been tested with respect to NADH determination. The electrocatalytic activity of CFA/CB has also been compared with that of SPEs modified by a single component of the coating, i.e., either CFA or CB. Finally, glycerol dehydrogenase, a typical NADH-dependent enzyme, was deposited on the CFA/CB coating in order to test the applicability of the sensor in glycerol determination.

  14. Caffeic acid: potential applications in nanotechnology as a green reducing agent for sustainable synthesis of gold nanoparticles.

    Science.gov (United States)

    Seo, Yu Seon; Cha, Song-Hyun; Yoon, Hye-Ran; Kang, Young-Hwa; Park, Youmie

    2015-04-01

    The sustainable synthesis of gold nanoparticles from gold ions was conducted with caffeic acid as a green reducing agent. The formation of gold nanoparticles was confirmed by spectroscopic and microscopic methods. Spherical nanoparticles with an average diameter of 29.99 ± 7.43 nm were observed in high- resolution transmission electron microscopy and atomic force microscopy images. The newly prepared gold nanoparticles exhibited catalytic activity toward the reduction of 4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. This system enables the preparation of green catalysts using plant natural products as reducing agents, which fulfills the growing need for sustainability initiatives.

  15. Effect of pH on the antimicrobial activity and oxidative stability of oil-in-water emulsions containing caffeic acid.

    Science.gov (United States)

    Almajano, M P; Carbó, R; Delgado, M E; Gordon, M H

    2007-06-01

    Antioxidant properties in food are dependent on various parameters. These include the pH value and interactions with food components, including proteins or metal ions. Food components affect antioxidant stability and also influence the properties of microorganisms and their viability. This paper describes an investigation of the effect of pH on the antioxidant and antibacterial properties of caffeic acid in different media. The pH values studied, using an oil-in-water emulsion as model system, were 3, 5 (with and without phosphate buffer), and 9. Effects of mixtures of caffeic acid, bovine serum albumin (BSA), and Fe (III) on oxidative deterioration in the emulsion samples were studied. The results show that the antioxidant activity of caffeic acid was increased by the presence of BSA. This effect was pH dependent and was affected by the presence of iron ions. Antibacterial properties were also pH dependent. The minimum concentration of caffeic acid required to inhibit some microorganisms in the pH range of 5 to 7 was determined. A concentration of 0.4% (w/w) caffeic acid was enough to inhibit the growth of some of the studied microorganisms in the pH range of 5 to 7. However, near-neutral pH concentrations higher than 0.4% were needed to inhibit some microorganisms, including Listeria monocytogenes, E. coli, and Staphylococcus aureus, in the medium.

  16. Comparison of Two Components of Propolis: Caffeic Acid (CA and Caffeic Acid Phenethyl Ester (CAPE Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231

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    Agata Kabała-Dzik

    2017-09-01

    Full Text Available Studies show that caffeic acid (CA and caffeic acid phenethyl ester (CAPE are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human caucasian breast adenocarcinoma line cells (MDA-MB-231. MDA-MB-231 cells were treated by CA and CAPE with doses of from 10 to 100 µM, for periods of 24 h and 48 h. Cytotoxicity MTT tests, apoptosis by Annexin V, and cell cycle with Dead Cell Assays were performed. Cytotoxic activity was greater for CAPE compared to CA (both incubation times, same dosage. IC50 values for CAPE were 27.84 µM (24 h and 15.83 µM (48 h and for CA > 10,000 µM (24 h and > 1000 µM (48 h. Polyphenols induced apoptosis, while CAPE (dose dependently, induced a higher apoptotic effect. CAPE also induced cell cycle arrest in S phase (time and dose dependently, CA did it only for 50 and 100 µM. A dose dependent decline was seen for the G0/G1 phase (CAPE, 48 h, as well as elimination of phase G2/M by 100 µM of CAPE (only mild effect for CA. Comparing CA and CAPE activity on MDA-MB-231, CAPE clearly showed better activity for the same dosages and experiment times.

  17. Enzymatic Browning in Sugar Beet Leaves (Beta vulgaris L.): Influence of Caffeic Acid Derivatives, Oxidative Coupling, and Coupled Oxidation.

    Science.gov (United States)

    Vissers, Anne; Kiskini, Alexandra; Hilgers, Roelant; Marinea, Marina; Wierenga, Peter Alexander; Gruppen, Harry; Vincken, Jean-Paul

    2017-06-21

    Sugar beet (Beta vulgaris L.) leaves of 8 month (8m) plants showed more enzymatic browning than those of 3 month (3m). Total phenolic content increased from 4.6 to 9.4 mg/g FW in 3m and 8m, respectively, quantitated by reverse-phase-ultrahigh-performance liquid chromatography-ultraviolet-mass spectrometry (RP-UHPLC-UV-MS). The PPO activity was 6.7 times higher in extracts from 8m than from 3m leaves. Substrate content increased from 0.53 to 2.45 mg/g FW in 3m and 8m, respectively, of which caffeic acid glycosyl esters were most important, increasing 10-fold with age. Caffeic acid glycosides and vitexin derivatives were no substrates. In 3m and 8m, nonsubstrate-to-substrate ratios were 8:1 and 3:1, respectively. A model system showed browning at 3:1 ratio due to formation of products with extensive conjugated systems through oxidative coupling and coupled oxidation. The 8:1 ratio did not turn brown as oxidative coupling occurred without much coupled oxidation. We postulate that differences in nonsubstrate-to-substrate ratio and therewith extent of coupled oxidation explain browning.

  18. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Wells, P.G.; Zubovits, J.T.; Wong, S.T.; Molinari, L.M.; Ali, S.

    1989-02-01

    Teratogenicity of the anticonvulsant drug phenytoin is thought to involve its bioactivation by cytochromes P-450 to a reactive arene oxide intermediate. We hypothesized that phenytoin also may be bioactivated to a teratogenic free radical intermediate by another enzymatic system, prostaglandin synthetase. To evaluate the teratogenic contribution of this latter pathway, an irreversible inhibitor of prostaglandin synthetase, acetylsalicylic acid (ASA), 10 mg/kg intraperitoneally (ip), was administered to pregnant CD-1 mice at 9:00 AM on Gestational Days 12 and 13, 2 hr before phenytoin, 65 mg/kg ip. Other groups were pretreated 2 hr prior to phenytoin administration with either the antioxidant caffeic acid or the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). Caffeic acid and PBN were given ip in doses that respectively were up to 1.0 to 0.05 molar equivalents to the dose of phenytoin. Dams were killed on Day 19 and the fetuses were assessed for teratologic anomalies. A similar study evaluated the effect of ASA on the in vivo covalent binding of radiolabeled phenytoin administered on Day 12, in which case dams were killed 24 hr later on Day 13. ASA pretreatment produced a 50% reduction in the incidence of fetal cleft palates induced by phenytoin (p less than 0.05), without significantly altering the incidence of resorptions or mean fetal body weight. Pretreatment with either caffeic acid or PBN resulted in dose-related decreases in the incidence of fetal cleft palates produced by phenytoin, with maximal respective reductions of 71 and 82% at the highest doses of caffeic acid and PBN (p less than 0.05).

  19. A Comparative Study of the Radical-scavenging Activity of the Phenolcarboxylic Acids Caffeic Acid, p-Coumaric Acid, Chlorogenic Acid and Ferulic Acid, With or Without 2-Mercaptoethanol, a Thiol, Using the Induction Period Method

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    Seiichiro Fujisawa

    2008-10-01

    Full Text Available Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione, a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME, as a substitute for GSH, was investigated by the induction period (IP method for polymerization of methyl methacrylate (MMA initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radicals, R. and benzoyl peroxide (BPO, a source of peroxy radicals, PhCOO. using differential scanning calorimetry (DSC. Upon PhCOO. radical scavenging, the stoichiometric factors (n, number of free radical trapped by one mole of antioxidant for caffeic acid, ferulic acid, p-coumaric acid and chlorogenic acid were 2.4, 1.8, 1.7 and 0.9, whereas upon R. radical scavenging, the corresponding values were 1.3, 1.2, 1.0 and 0.8, respectively. Antioxidants with n values close to 2 suggest the stepwise formation of semiquinone radicals and quinones. By contrast, those with n values close to 1 suggest the formation of dimers after single-electron oxidation, possibly due to recombination of corresponding aryloxy radicals. The ratio of the rate constant of inhibition to that of propagation (kinh/kp declined in the order chlorogenic acid > p-coumaric acid > ferulic acid > caffeic acid. The ratio of the observed IP for the phenolcarboxylic acid/2-mercapto-ethanol (ME mixture (1:1 molar ratio (A to the calculated IP (the simple sum of phenol acid antioxidant and ME (B was investigated. Upon R. scavenging, the caffeic acid or p-coumaric acid/ME mixture was A/B > 1, particularly the former was 1.2, suggesting a synergic effect. By contrast, upon PhCOO. scavenging, the corresponding mixture was A/B < 1, particularly the latter was 0.7, suggesting an antagonistic effect. Upon both radicals scavenging, the A/B for the ferulic acid or chlorogenic acid

  20. Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol

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    VANDERSON S. BISPO

    Full Text Available ABSTRACT Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM, caffeic acid (1.1 µM, methyl caffeate (0.03 µM, quercetin (0.08 µM and ferulic acid (0.02 µM isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05. Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

  1. Efficacy of various naturally occurring caffeic acid derivatives in preventing post-harvest protein losses in forages.

    Science.gov (United States)

    Sullivan, Michael L; Zeller, Wayne E

    2013-01-01

    In red clover, oxidation of endogenous o-diphenols by polyphenol oxidase (PPO) inhibits post-harvest proteolyis. This system is transferable to alfalfa by providing PPO (via a transgene) and o-diphenol PPO substrates (via exogenous application). To exploit the PPO system for protein protection, it would be advantageous to produce PPO substrates in alfalfa, which lacks them. We assessed the extent of PPO-mediated proteolytic inhibition by phenolic compounds, especially those whose biosynthesis could be engineered into alfalfa. Tested compounds included o-diphenols (caffeic acid, phaselic acid, chlorogenic acid, clovamide) and monophenols (p-coumaric acid, p-coumaroyl-malic acid). In the presence of PPO, 2 mmol o-diphenol g⁻¹ protein reduced 24 h proteolysis 68-87% (P < 0.001) and as little as 0.25 mmol g⁻¹ protein still decreased 24 h proteolysis 43-60% (P < 0.001). At high concentrations, clovamide inhibited 24 h proteolysis 50% (P < 0.001) in the absence of PPO, likely due to non-PPO oxidation. Monophenol p-coumaric acid did not inhibit 24 h proteolyis, although high levels of its malate ester did exhibit PPO- and oxygen-independent inhibition (37%, P < 0.001). For PPO-mediated proteolytic inhibition, pathways for both phaselic acid and chlorogenic acid may be good targets for engineering into alfalfa. Clovamide may be useful for inhibiting proteolysis without PPO. Published 2012 by John Wiley & Sons, Ltd.

  2. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

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    Sumeyya Akyol

    2014-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R. In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

  3. Effects of propolis, caffeic acid phenethyl ester, and pollen on renal injury in hypertensive rat: An experimental and theoretical approach.

    Science.gov (United States)

    Salmas, Ramin Ekhteiari; Gulhan, Mehmet Fuat; Durdagi, Serdar; Sahna, Engin; Abdullah, Huda I; Selamoglu, Zeliha

    2017-08-01

    The objective of this study was to evaluate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE; active compound in propolis), and pollen on biochemical oxidative stress biomarkers in rat kidney tissue inhibited by Nω -nitro-L-arginine methyl ester (L-NAME). The biomarkers evaluated were paraoxonase (PON1), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), asymmetric dimethylarginine (ADMA), and nuclear factor kappa B (NF-κB). TAS levels and PON1 activity were significantly decreased in kidney tissue samples in the L-NAME-treated group (P propolis, CAPE, and pollen groups compared with the L-NAME-treated group. TOS, ADMA, and NF-κB levels were significantly increased in the kidney tissue samples of the L-NAME-treated group (P propolis, CAPE, and pollen groups (P propolis, CAPE administration. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Amine-modified SBA-15 and MCF mesoporous molecular sieves as promising sorbents for natural antioxidant. Modeling of caffeic acid adsorption.

    Science.gov (United States)

    Moritz, Michał; Geszke-Moritz, Małgorzata

    2016-04-01

    This work presents a detailed study of caffeic acid adsorption on mesoporous SBA-15 and MCF silicas functionalized with (3-aminopropyl)triethoxysilane (APTES) and 3-[2-(aminoethylamino)propyl]trimethoxysilane (AEAPTMS). Synthesized mesoporous adsorbents were characterized using different analytical techniques such as N2 sorption, XRD, TEM, SEM and FT-IR. The adsorption studies of caffeic acid were conducted in various organic solvents. Moreover, the effect of water content in 2-propanol-water mixture on adsorption efficiency was investigated. The experimental data were best fitted to the Langmuir equation, followed by the Temkin, Dubinin-Radushkevich and Freundlich models. The maximum adsorption capacity values calculated from the Langmuir model demonstrated that SBA-15 and MCF silicas modified with AEAPTMS revealed better adsorption properties toward caffeic acid (192.3 and 161.3mg/g, respectively) as compared to the materials modified with APTES (125.0 and 113.6 mg/g, respectively). The obtained results indicate that both SBA-15 and MCF silicas functionalized with AEAPTMS and APTES are promising materials for the entrapment of caffeic acid. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Caffeic Acid Reduces the Viability and Migration Rate of Oral Carcinoma Cells (SCC-25 Exposed to Low Concentrations of Ethanol

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    Arkadiusz Dziedzic

    2014-10-01

    Full Text Available Alcohol increases the risk of carcinoma originated from oral epithelium, but the biological effects of ultra-low doses of ethanol on existing carcinoma cells in combination with natural substances are still unclear. A role for ethanol (EtOH, taken in small amounts as an ingredient of some beverages or mouthwashes to change the growth behavior of established squamous cell carcinoma, has still not been examined sufficiently. We designed an in vitro study to determine the effect of caffeic acid (CFA on viability and migration ability of malignant oral epithelial keratinocytes, exposed to ultra-low concentrations (maximum 100 mmol/L EtOH. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide and LDH (lactate dehydrogenase assays were used to assess the cytotoxic effect of EtOH/CFA and the viability of squamous carcinoma SCC-25 cells (ATCC CRL-1628, mobile part of the tongue. Tested EtOH concentrations were: 2.5, 5, 10, 25, 50, and 100 mmol/L, along with an equal CFA concentration of 50 μmol/L. Carcinoma cells’ migration was investigated by monolayer “wound” healing assay. We demonstrated that very low concentrations of EtOH ranging between 2.5 and 10 mmol/L may induce the viability of oral squamous cell carcinoma cells, while the results following addition of CFA reveal an antagonistic effect, attenuating pro-proliferative EtOH activity. The migration rate of oral squamous carcinoma cells can be significantly inhibited by the biological activity of caffeic acid.

  6. A simple procedure for preparing chitin oligomers through acetone precipitation after hydrolysis in concentrated hydrochloric acid.

    Science.gov (United States)

    Kazami, Nao; Sakaguchi, Masayoshi; Mizutani, Daisuke; Masuda, Tatsuhiko; Wakita, Satoshi; Oyama, Fumitaka; Kawakita, Masao; Sugahara, Yasusato

    2015-11-05

    Chitin oligomers are of interest because of their numerous biologically relevant properties. To prepare chitin oligomers containing 4-6 GlcNAc units [(GlcNAc)4-6], α- and β-chitin were hydrolyzed with concentrated hydrochloric acid at 40 °C. The reactant was mixed with acetone to recover the acetone-insoluble material, and (GlcNAc)4-6 was efficiently recovered after subsequent water extraction. Composition analysis using gel permeation chromatography and MALDI-TOF mass spectrometry indicated that (GlcNAc)4-6 could be isolated from the acetone-insoluble material with recoveries of approximately 17% and 21% from the starting α-chitin and β-chitin, respectively. The acetone precipitation method is highly useful for recovering chitin oligomers from the acid hydrolysate of chitin. The changes in the molecular size and higher-order structure of chitin during the course of hydrolysis were also analyzed, and a model that explains the process of oligomer accumulation is proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Nonenzymatic synthesis of RNA and DNA oligomers on hexitol nucleic acid templates: the importance of the A structure

    Science.gov (United States)

    Kozlov, I. A.; Politis, P. K.; Van Aerschot, A.; Busson, R.; Herdewijn, P.; Orgel, L. E.; Bada, J. L. (Principal Investigator); Dolan, M. (Principal Investigator)

    1999-01-01

    Hexitol nucleic acid (HNA) is an analogue of DNA containing the standard nucleoside bases, but with a phosphorylated 1,5-anhydrohexitol backbone. HNA oligomers form duplexes having the nucleic acid A structure with complementary DNA or RNA oligomers. The HNA decacytidylate oligomer is an efficient template for the oligomerization of the 5'-phosphoroimidazolides of guanosine or deoxyguanosine. Comparison of the oligomerization efficiencies on HNA, RNA, and DNA decacytidylate templates under various conditions suggests strongly that only nucleic acid double helices with the A structure support efficient template-directed synthesis when 5'-phosphoroimidazolides of nucleosides are used as substrates.

  8. Comparison of chicoric acid, and its metabolites caffeic acid and caftaric acid: In vitro protection of biological macromolecules and inflammatory responses in BV2 microglial cells

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    Qian Liu

    2017-12-01

    Full Text Available Chicoric acid (CA, a natural phenolic acid, has been used as a nutraceutical food ingredient due to its powerful antioxidant, anti-HIV and anti-diabetic bioactivities. CA could be partly metabolized into caffeic acid (CFA and caftaric acid (CTA on cytochrome P450s in rat liver microsomes. To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses, oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed. Results showed that CA, CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals, and suppressed hemin/nitrite/H2O2 triggered-nitration. Moreover, CA, CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner, and restrained the oxidation of herring sperm DNA, as well as the breakage of pBR322 plasmid DNA. Furthermore, CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS. However, bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range. This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants. Keywords: Chicoric acid and its metabolites, Oxidative damage, Biomolecules, Microglia, Inflammation

  9. Evaluation of Chemical Constituents and Antioxidant Activity of Coconut Water (Cocus nucifera L. and Caffeic Acid in Cell Culture

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    JOAO L.A. SANTOS

    2013-09-01

    Full Text Available Coconut water contains several uncharacterized substances and is widely used in the human consumption. In this paper we detected and quantified ascorbic acid and caffeic acid and total phenolics in several varieties of coconut using HPLS/MS/MS (25.8 ± 0.6 µg/mL and 1.078 ± 0.013 µg/mL and 99.7 µg/mL, respectively, in the green dwarf coconut water, or 10 mg and 539 µg and 39.8 mg for units of coconut consumed, 500 ± 50 mL. The antioxidant potential of four coconut varieties (green dwarf, yellow dwarf, red dwarf and yellow Malaysian was compared with two industrialized coconut waters and the lyophilized water of the green dwarf variety. All varieties were effective in scavenging the DPPH radical (IC50=73 µL and oxide nitric (0.1 mL with an IP of 29.9% as well as in inhibiting the in vitro production of thiobarbituric acid reactive substances (1 mL with an IP of 34.4%, highlighting the antioxidant properties of the green dwarf which it is the most common used. In cell culture, the green dwarf water was efficient in protecting against oxidative damages induced by hydrogen peroxide.

  10. Size-Dependent Affinity of Glycine and Its Short Oligomers to Pyrite Surface: A Model for Prebiotic Accumulation of Amino Acid Oligomers on a Mineral Surface

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    Rehana Afrin

    2018-01-01

    Full Text Available The interaction strength of progressively longer oligomers of glycine, (Gly, di-Gly, tri-Gly, and penta-Gly, with a natural pyrite surface was directly measured using the force mode of an atomic force microscope (AFM. In recent years, selective activation of abiotically formed amino acids on mineral surfaces, especially that of pyrite, has been proposed as an important step in many origins of life scenarios. To investigate such notions, we used AFM-based force measurements to probe possible non-covalent interactions between pyrite and amino acids, starting from the simplest amino acid, Gly. Although Gly itself interacted with the pyrite surface only weakly, progressively larger unbinding forces and binding frequencies were obtained using oligomers from di-Gly to penta-Gly. In addition to an expected increase of the configurational entropy and size-dependent van der Waals force, the increasing number of polar peptide bonds, among others, may be responsible for this observation. The effect of chain length was also investigated by performing similar experiments using l-lysine vs. poly-l-lysine (PLL, and l-glutamic acid vs. poly-l-glutamic acid. The results suggest that longer oligomers/polymers of amino acids can be preferentially adsorbed on pyrite surfaces.

  11. Dietary phenolic antioxidants, caffeic acid and Trolox, protect rainbow trout gill cells from nitric oxide-induced apoptosis.

    Science.gov (United States)

    Chung, Mi Ja; Walker, Paul A; Hogstrand, Christer

    2006-12-30

    Caffeic acid (CA) and Trolox are phenolic acids that have beneficial antioxidant effect, but the underlying mechanisms involved are not fully understood. The extent to which CA and Trolox protect against sodium nitroprusside (SNP)-induced oxidative cell injury was investigated in cultured rainbow trout gill cells. The cells exposed to SNP for 24 h displayed a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability as indicated by the MTT assay (mitochondrial dehydrogenase activity). Both effects were prevented by treatment with 50 microM CA or Trolox. CA or Trolox, protected against SNP-induced caspase-3 activation and DNA fragmentation, indicating a reduction of apoptosis. Thus, the results indicate that SNP induced cell death is caspase-3 related apoptosis and the treatment with CA inhibited the apoptotic pathway. In addition, we studied the effect of CA and Trolox on expression of zinc-responsive antioxidant genes such as metallothioneins (MT), glutathione-S-transferase (GST Class pi) and glucose-6-phosphate dehydrogenase (G6PD) in cultured gill cells. CA, 100 microM, increased accumulation of mRNA for MTA, MTB, GST and G6PD in cells. Thus, in addition to its ability to sequester free radicals, CA may protect against oxidative stress through expression of zinc-induced antioxidant proteins. Because of these properties we suggest that CA could be a beneficial additive to fish feeds in aquaculture.

  12. Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NFκB transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee; Kang, Dong Woo [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of); Jung, Yunjin [College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Choi, Kang-Yell [Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of)

    2013-12-06

    Highlights: •We found CAFÉ, a natural product that suppresses expression and activity of PLD1. •CAPE decreased PLD1 expression by inhibiting NFκB transactivation. •CAPE rapidly inhibited PLD activity via its binding to a Cys837 of PLD1. •PLD1 downregulation by CAPE inhibited invasion and proliferation of glioma cells. -- Abstract: Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition of binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.

  13. Caffeic Acid Derivatives in Market Available Lamiaceae and Echinacea purpurea Products

    Science.gov (United States)

    Fresh basil leaves contain chicoric acid, the principal phenolic compound of Echinacea purpurea and purportedly the active ingredient in its dietary supplements. Our group discovered and first reported chicoric acid in basil. This following study examined the distribution of chicoric acid within the...

  14. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid and methylglyoxal

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    Y. Tan

    2012-01-01

    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including pyruvate, oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid plays a central role in the aqueous oxidation of methylglyoxal and it is a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid (20 μM–10 mM was oxidized by OH radicals, and pyruvic acid and methylglyoxal experimental samples were analyzed using new analytical methods, in order to better understand the formation of SOA from acetic acid and methylglyoxal. Glyoxylic, glycolic, and oxalic acids formed from acetic acid and OH radicals. In contrast to the aqueous OH radical oxidation of methylglyoxal, the aqueous OH radical oxidation of acetic acid did not produce succinic acid and oligomers. This suggests that the methylgloxal-derived oligomers do not form through the acid catalyzed esterification pathway proposed previously. Using results from these experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  15. Structural Characterization of Poly-l-lactic Acid (PLLA) and Poly(glycolic acid)(PGA) Oligomers

    Science.gov (United States)

    Casalini, Tommaso; Rossi, Filippo; Santoro, Marco; Perale, Giuseppe

    2011-01-01

    Structural characterization of poly-l-lactic acid (PLLA) and poly(glycolic acid) (PGA) oligomers containing three units was carried out with an atomistic approach. Oligomer structures were first optimized through quantum chemical calculations, using density functional theory (DFT); rotational barriers concerning dihedral angles along the chain were then investigated. Diffusion coefficients of l-lactic acid and glycolic acid in pure water were estimated through molecular dynamic (MD) simulations. Monomer structures were obtained with quantum chemical computation in implicit water using DFT method; atomic charges were fitted with Restrained Electrostatic Potentials (RESP) formalism, starting from electrostatic potentials calculated with quantum chemistry. MD simulations were carried out in explicit water, in order to take into account solvent presence. PMID:21747712

  16. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2009-01-01

    The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...... storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil...

  17. Protective Effects of Intralipid and Caffeic Acid Phenyl Esther (CAPE) on Neurotoxicity Induced by Ethanol in Rats.

    Science.gov (United States)

    Basarslan, Seyit Kagan; Osun, Arif; Senol, Serkan; Korkmaz, Murat; Ozkan, Umit; Kaplan, Ibrahim

    2017-01-01

    Ethanol causes oxidative degradation of the mitochondrial genome in the brain. This effect could contribute to the development of brain injury in some alcoholic patients. We investigated the protective effect of caffeic acid phenyl esther (CAPE) and intralipid (IL) on oxidative stress and neurotoxicity induced by ethanol intake. The forty-eight rats were randomly divided into seven groups. Ethanol was administered for acute toxicity. IL and CAPE were administered immediately after ethanol intake. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative status index (OSi) were evaluated and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immuno-histochemical dyes was performed. In the ethanol group, TAS levels were significantly lower than the other groups and this finding indicates that the toxic effect of ethanol reduces antioxidant levels. In the ethanol group, TOS levels were significantly higher than the other groups. These results showed that ethanol induced oxidative stress. IL treatment increased TAS levels, and CAPE decreased TOS levels against ethanol toxicity. There was correlation between TAS and TOS levels. Also, histopathologic results confirmed these biochemical results. CAPE and IL treatment could be effective course of therapy to enhance therapeutic efficacy and may provide a promising approach for the treatment of neurotoxicity and oxidative stress induced by ethanol in clinic.

  18. Enhanced antioxidant effect of caffeic acid phenethyl ester and Trolox in combination against radiation induced-oxidative stress.

    Science.gov (United States)

    Bai, Hua; Liu, Rui; Chen, Hong-Li; Zhang, Wei; Wang, Xin; Zhang, Xiao-Di; Li, Wen-Li; Hai, Chun-Xu

    2014-01-25

    Combinations of antioxidants are believed to be more effective than single antioxidant because when antioxidants are combined they support each other synergistically to create a magnified effect. Discovering the enhancer effects or synergies between bioactive components is valuable for resisting oxidative stress and improving health benefits. The aim of this study was to investigate a possible cooperation of natural antioxidant caffeic acid phenethyl ester (CAPE) with synthetic antioxidant Trolox in the model systems of chemical generation of free radicals, lipid peroxidation of microsomes and radiation-induced oxidative injury in L929 cells. Based on the intermolecular interaction between CAPE and Trolox, the present study shows a synergistic effect of CAPE and Trolox in combination on elimination of three different free radicals and inhibition of lipid peroxidation initiated by three different systems. CAPE and Trolox added simultaneously to the L929 cells exerted an enhanced preventive effect on the oxidative injury induced by radiation through decreasing ROS generation, protecting plasma membrane and increasing the ratios of reduced glutathione/oxidized glutathione and the expression of key antioxidant enzymes mediated by nuclear factor erythroid 2 p45-related factor 2 (Nrf2). Our results showed for the first time that administration of CAPE and Trolox in combination may exert synergistic antioxidant effects, and further indicate that CAPE and Trolox combination functions mainly through scavenging ROS directly, inhibiting lipid peroxidation and promoting redox cycle of GSH mediated by Nrf2-regulated glutathione peroxidase and glutathione reductase expression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

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    Mi-Sook Lee

    2014-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST and forced swim (FST tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234, resulting in an increased pGR(S220/S234 ratio. We also observed negative correlations between pGR(S220/(S234 and p38 mitogen-activated protein kinase (p38MAPK phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.

  20. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

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    Abuzar Elnager

    2015-01-01

    Full Text Available Background. Caffeic acid phenethyl ester (CAPE has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM. After 3 hours, D-dimer (DD levels and WB clot weights were measured for each concentration. Thromboelastography (TEG parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM. The 50% effective dose (ED50 of CAPE (based on DD was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

  1. Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

    Directory of Open Access Journals (Sweden)

    Aburrahman Gun

    2016-01-01

    Full Text Available Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS. HFCS (6 weeks, 30% fed with drinking water caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

  2. Development of a Mitochondriotropic Antioxidant Based on Caffeic Acid: Proof of Concept on Cellular and Mitochondrial Oxidative Stress Models.

    Science.gov (United States)

    Teixeira, José; Cagide, Fernando; Benfeito, Sofia; Soares, Pedro; Garrido, Jorge; Baldeiras, Inês; Ribeiro, José A; Pereira, Carlos M; Silva, António F; Andrade, Paula B; Oliveira, Paulo J; Borges, Fernanda

    2017-08-24

    Targeting mitochondrial oxidative stress is an effective therapeutic strategy. In this context, a rational design of mitochondriotropic antioxidants (compounds 22-27) based on a dietary antioxidant (caffeic acid) was performed. Jointly named as AntiOxCINs, these molecules take advantage of the known ability of the triphenylphosphonium cation to target active molecules to mitochondria. The study was guided by structure-activity-toxicity-property relationships, and we demonstrate in this work that the novel AntiOxCINs act as mitochondriotropic antioxidants. In general, AntiOxCINs derivatives prevented lipid peroxidation and acted as inhibitors of the mitochondrial permeability transition pore. AntiOxCINs toxicity profile was found to be dependent on the structural modifications performed on the dietary antioxidant. On the basis of mitochondrial and cytotoxicity/antioxidant cellular data, compound 25 emerged as a potential candidate for the development of a drug candidate with therapeutic application in mitochondrial oxidative stress-related diseases. Compound 25 increased GSH intracellular levels and showed no toxicity on mitochondrial morphology and function.

  3. Poly(3-hydroxybutyrate)/caffeic acid electrospun fibrous materials coated with polyelectrolyte complex and their antibacterial activity and in vitro antitumor effect against HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ignatova, Milena G. [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Manolova, Nevena E., E-mail: manolova@polymer.bas.bg [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Rashkov, Iliya B. [Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia (Bulgaria); Markova, Nadya D. [Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Bl. 26, BG-1113 Sofia (Bulgaria); Toshkova, Reneta A.; Georgieva, Ani K.; Nikolova, Elena B. [Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev St, bl. 25, BG-1113 Sofia (Bulgaria)

    2016-08-01

    The purpose of this work was to investigate the possibility for the preparation of new poly(3-hydroxybutyrate) (PHB)/poly(ethylene glycol) (PEG)-based fibrous materials containing natural phenolic compound caffeic acid (CA) of diverse architectures, as well as to study the impact of the fiber composition on the in vitro CA release profile and on the biological properties of the fibrous materials. The application of the one-pot electrospinning enabled the fabrication of nanofibrous materials from PHB and PEG loaded with the CA. Materials with targeted design were obtained by coating with polyelectrolyte complex of alginate (Alg) and N,N,N-trimethylchitosan (TMCh). Three different processing paths were used to obtain coated mats: (i) with CA incorporated in the PHB/PEG core; (ii) with CA embedded in the Alg layer; and (iii) with CA included in the TMCh layer. The in vitro release of CA was modulated by controlling the composition and the architecture of the nanofibrous mats. The performed microbiological screening and MTT cell viability studies revealed that in contrast to the bare mats, the CA-containing nanofibrous materials were effective in suppressing the growth of the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli and displayed good cytotoxicity against human cervical HeLa tumor cells. In addition, the proliferation of murine spleen lymphocytes and peritoneal macrophages was increased by the prepared CA-containing nanofibrous materials. The obtained materials are promising for antibacterial wound dressing applications as well as for application in local treatment of cervical tumors. - Highlights: • New caffeic acid-loaded materials from PHB and PEG were prepared by electrospinning. • Different design is achieved by coating and formation of polyelectrolyte complexes. • The control on the architecture of the mats enables modulating caffeic acid release. • The caffeic acid-loaded mats suppress the growth of

  4. Structure and Oligomers Distribution of Commercial Tara (Caesalpina spinosa Hydrolysable Tannin

    Directory of Open Access Journals (Sweden)

    Samuele GIOVANDO

    2013-03-01

    Full Text Available Solvent extracted commercial Tara tanninextract have been examined by Matrix Assisted LaserDesorption/Ionisation Time-of-Flight (MALDI-TOFmass spectrometry and by High Pressure LiquidChromatography (HPLC. The Tara extract has beenfound to be composed of a series of oligomers ofpolygallic acid attached by an ester link to one quinicacid. They constitute the oligomers in higherproportion in the extract. Other polygallic chains linkedto one only or two repeating units such as caffeic acidand methylated quinic, methylated gallic andmethylated caffeic acids are also present. Negativeion mode MALDI-TOF showed that somecarbohydrate residues appear to still be present,linked to the polyphenolic material of the extract buttheir proportion is very low as would be expected of asolvent extracted tannin.

  5. Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass reveals a novel monolignol analog

    Directory of Open Access Journals (Sweden)

    Tschaplinski Timothy J

    2012-09-01

    Full Text Available Abstract Background Down-regulation of the caffeic acid 3-O-methyltransferase EC 2.1.1.68 (COMT gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography–mass spectrometry (GCMS-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors. Results GCMS confirmed the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of microbial fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol in both non-pretreated, as well as hot water pretreated samples. iso-Sinapyl alcohol and its glucoside were subsequently generated by organic synthesis and the identity of natural and synthetic materials were confirmed by mass spectrometric and NMR analyses. The additional novel presence of iso-sinapic acid, iso-sinapyl aldehyde, and iso-syringin suggest the increased activity of a para-methyltransferase, concomitant with the reduced COMT activity, a strict meta-methyltransferase. Quantum chemical calculations were used to predict the most likely homodimeric lignans generated from dehydration reactions, but these products were not evident in plant samples. Conclusions Down-regulation of COMT activity in switchgrass resulted in the accumulation of previously undetected metabolites resembling sinapyl alcohol and its related metabolites, but that are derived from para

  6. Preparation and properties of poly(acrylic acid) oligomer stabilized superparamagnetic ferrofluid.

    Science.gov (United States)

    Lin, Chia-Lung; Lee, Chia-Fen; Chiu, Wen-Yen

    2005-11-15

    Ferrofluids, which are stable dispersions of magnetic particles, behave as liquids that have strong magnetic properties. Nanoparticles of magnetite with a mean diameter of 10-15 nm, which are in the range of superparamagnetism, are usually prepared by the traditional method of co-precipitation from ferrous and ferric electrolyte solution. When diluted, the ferrofluid dispersions are not stable if anionic or cationic surfactants are used as the stabilizer. This work presents an efficient way to prepare a stable aqueous nanomagnetite dispersion. A stable ferrofluid containing Fe3O4 nanoparticles was synthesized via co-precipitation in the presence of poly(acrylic acid) oligomer. The mechanism, microstructure, and properties of the ferrofluid were investigated. The results indicate that the PAA oligomers promoted the nucleation and inhibited the growth of the magnetic iron oxide, and the average diameter of each individual Fe3O4 particle was smaller than 10 nm. In addition, the PAA oligomers provided both electrostatic and steric repulsion against particle aggregation, and the stability of dispersions could be controlled by adjusting the pH value of solution. A small amount of Fe2O3 was found in the nanoparticles but the superparamagnetic behavior of the nanoparticles was not affected.

  7. Effect of propolis and caffeic acid phenethyl ester (CAPE) on NFκB activation by HTLV-1 Tax.

    Science.gov (United States)

    Shvarzbeyn, Jenny; Huleihel, Mahmoud

    2011-06-01

    HTLV-1 is the etiological agent of aggressive malignancy of the CD4(+) T-cells, adult T-cell leukemia (ATL), and other severe clinical disorders. The viral Tax protein is a key factor in HTLV-1 pathogenicity. A major part of Tax oncogenic potential is accounted for by its capacity of inducing the transcriptional activity of the NFκB factors, which regulate the expression of numerous cellular genes. Propolis (PE), a natural product produced by honeybees, has been used for a long time in folk medicine. One of PE active components, caffeic acid phenylethyl ester (CAPE), was well characterized and found to be a potent inhibitor of NFκB activation. Therefore, the aim of this study was to pursue the possibility of blocking Tax oncogenic effects by treatment with these natural products. Human T-cell lines were used in this study since these cells are the main targets of HTLV-1 infections. We tried to determine which step of Tax-induced NFκB activation is blocked by these products. Our results showed that both tested products substantially inhibited the activation of NFκB-dependent promoter by Tax. However, only PE could efficiently inhibit also the Tax-induced activation of SRF- and CREB-dependent promoters. Our results showed also that PE and CAPE strongly prevented both Tax binding to IκBα and its induced degradation by Tax. However, both products did not interfere in the nuclear transport of Tax or NFκB proteins. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Behavioral and genotoxic evaluation of rosmarinic and caffeic acid in acute seizure models induced by pentylenetetrazole and pilocarpine in mice.

    Science.gov (United States)

    Coelho, Vanessa Rodrigues; Vieira, Caroline Gonçalves; de Souza, Luana Pereira; da Silva, Lucas Lima; Pflüger, Pricila; Regner, Gabriela Gregory; Papke, Débora Kuck Mausolff; Picada, Jaqueline Nascimento; Pereira, Patrícia

    2016-11-01

    The goal of this study was to investigate the effects of rosmarinic acid (RA) and caffeic acid (CA) in the acute pentylenetetrazole (PTZ) and pilocarpine (PIL) seizure models. We also evaluated the effect of RA and CA on the diazepam (DZP)-induced sleeping time test and its possible neuroprotective effect against the genotoxic damage induced by PTZ and PIL. Mice were treated intraperitoneally (i.p.) with saline, RA (2 or 4 mg/kg), or CA (4 or 8 mg/kg) alone or associated to low-dose DZP. After, mice received a single dose of PTZ (88 mg/kg) or PIL (250 mg/kg) and were monitored for the percentage of seizures and the latency to first seizure (LFS) >3 s. Vigabatrin and DZP were used as positive controls. In the DZP-induced sleeping time test, mice were treated with RA and CA and 30 min after receiving DZP (25 mg/kg, i.p.). The alkaline comet assay was performed after acute seizure tests to evaluate the antigenotoxic profiles of RA and CA. The doses of RA and CA tested alone did not reduce the occurrence of seizures induced by PTZ or PIL. The association of 4 mg/kg RA + low-dose DZP was shown to increase LFS in the PTZ model, compared to the group that received only the DZP. In the DZP-induced sleeping time test, the latency to sleep was reduced by 4 mg/kg RA and 8 mg/kg CA. The PTZ-induced genotoxic damage was not prevented by RA or CA, but the PIL-induced genotoxic damage was decreased by pretreatment with 4 mg/kg RA (in cortex) and 4 mg/kg CA (in hippocampus). In conclusion, RA and CA presented neuroprotective effect against PIL-induced genotoxic damage and reduced the latency to DZP-induced sleep. Of the rosmarinic acid, 4 mg/kg enhanced the DZP effect in the increase of latency to clonic PTZ-induced seizures.

  9. Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer.

    Science.gov (United States)

    Rosendahl, Ann H; Perks, Claire M; Zeng, Li; Markkula, Andrea; Simonsson, Maria; Rose, Carsten; Ingvar, Christian; Holly, Jeff M P; Jernström, Helena

    2015-04-15

    Epidemiologic studies indicate that dietary factors, such as coffee, may influence breast cancer and modulate hormone receptor status. The purpose of this translational study was to investigate how coffee may affect breast cancer growth in relation to estrogen receptor-α (ER) status. The influence of coffee consumption on patient and tumor characteristics and disease-free survival was assessed in a population-based cohort of 1,090 patients with invasive primary breast cancer in Sweden. Cellular and molecular effects by the coffee constituents caffeine and caffeic acid were evaluated in ER(+) (MCF-7) and ER(-) (MDA-MB-231) breast cancer cells. Moderate (2-4 cups/day) to high (≥5 cups/day) coffee intake was associated with smaller invasive primary tumors (Ptrend = 0.013) and lower proportion of ER(+) tumors (Ptrend = 0.018), compared with patients with low consumption (≤1 cup/day). Moderate to high consumption was associated with lower risk for breast cancer events in tamoxifen-treated patients with ER(+) tumors (adjusted HR, 0.51; 95% confidence interval, 0.26-0.97). Caffeine and caffeic acid suppressed the growth of ER(+) (P ≤ 0.01) and ER(-) (P ≤ 0.03) cells. Caffeine significantly reduced ER and cyclin D1 abundance in ER(+) cells. Caffeine also reduced the insulin-like growth factor-I receptor (IGFIR) and pAkt levels in both ER(+) and ER(-) cells. Together, these effects resulted in impaired cell-cycle progression and enhanced cell death. The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER(+) and ER(-) breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth. ©2015 American Association for Cancer Research.

  10. Synthesis of caffeic acid molecularly imprinted polymer microspheres and high-performance liquid chromatography evaluation of their sorption properties.

    Science.gov (United States)

    Valero-Navarro, Angel; Gómez-Romero, María; Fernández-Sánchez, Jorge F; Cormack, Peter A G; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

    2011-10-14

    In the current work, a molecularly imprinted polymer (MIP) has been synthesised and used to enable the extraction of a naturally-occurring antioxidant from complex media. More specifically, we describe the first example of a caffeic acid (CA) MIP which has been synthesised in the form of well-defined polymer microspheres, and its use for the extraction of CA from fruit juice sample. The CA MIP was synthesised by precipitation polymerisation using 4-vinylpyridine as functional monomer, divinylbenzene-80 as crosslinker and acetonitrile:toluene (75/25, v/v) as porogen. The particle sizing and morphological characterisation of the polymers was carried out by means of scanning electron microscopy (narrow particle size distribution; ∼5 and 1.5 μm particle diameters for the MIP and NIP [non-imprinted polymer], respectively) and nitrogen sorption porosimetry (specific surface areas of 340 and 350 m(2)g(-1), and specific pore volumes of 0.17 and 0.19 cm(3)g(-1) for the MIP and NIP, respectively). The polymers were evaluated further by batch rebinding experiments, and from the derived isotherms their binding capacity and binding strength were determined (number of binding sites (N(K))=0.6 and 0.3 mmol g(-1) for the MIP and NIP, respectively, and apparent average adsorption constant (K(N))=10.0 and 1.6L mmol(-1) for the MIP and NIP, respectively). To evaluate the molecular recognition character of the MIP it was packed into a stainless steel column (50 mm × 4.6 mm i.d.) and evaluated as an HPLC-stationary phase. The mobile phase composition, flow rate, and the elution profile were then optimised in order to improve the peak shape without negatively affecting the imprinting factor (IF). Very interesting, promising properties were revealed. The imprinting factor (IF) under the optimised conditions was 11.9. Finally, when the imprinted LC column was used for the selective recognition of CA over eight related compounds, very good selectivity was obtained. This outcome enabled

  11. Effects of acidic oligosaccharide sugar chain on amyloid oligomer-induced impairment of synaptic plasticity in rats.

    Science.gov (United States)

    Chang, Lan; Li, Fushun; Chen, Xiaowei; Xu, Shujun; Wang, Chuang; Chen, Hongzhuan; Wang, Qinwen

    2014-09-01

    Soluble amyloid-β protein (Aβ) oligomers have been recognized to be early and key intermediates in Alzheimer's disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, with oligomeric Aβ. We found that the inhibition of long-term potentiation (LTP) induced by Aβ oligomers can be dose dependently reversed by the application of AOSC, whereas AOSC alone did not alter normal LTP induction. Interestingly, treatment with Aβ monomers with or without AOSC did not affect LTP induction. Additionally, when fresh-made Aβ was co-incubated with AOSC before in vitro testing, there was no impairment of LTP induction. The results from Western blots demonstrated that AOSC prevent the aggregation of Aβ oligomers. These findings indicate that AOSC may reverse Aβ oligomer-mediated cytotoxicity by directly disrupting the amyloid oligomer aggregation, and this action is concentration dependent. Thus, we propose that AOSC might be a potential therapeutic drug for Alzheimer's disease due to its protection against oligomeric Aβ-induced dysfunction of synaptic plasticity.

  12. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

    Science.gov (United States)

    Burgos-Morón, Estefanía; Calderón-Montaño, José Manuel; Orta, Manuel Luis; Guillén-Mancina, Emilio; Mateos, Santiago; López-Lázaro, Miguel

    2016-01-01

    Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee. PMID:27399778

  13. Photo-Crosslinked Biodegradable Hydrogels Prepared From Fumaric Acid Monoethyl Ester-Functionalized Oligomers for Protein Delivery

    NARCIS (Netherlands)

    Jansen, Janine; Mihov, George; Feijen, Jan; Grijpma, Dirk W.

    Photo-crosslinkable, fumaric acid monoethyl ester-functionalized triblock oligomers are synthesized and copolymerized with N-vinyl-2-pyrrolidone to form biodegradable photo-crosslinked hydrogels. Poly(ethylene glycol) is used as the middle hydrophilic segment and the hydrophobic segments are based

  14. Linear and cyclic ester Oligomers of succinic acid and 1,4-butanediol: Biocatalytic synthesis and characterization

    NARCIS (Netherlands)

    Habeych Narvaez, D.I.; Eggink, G.; Boeriu, C.G.

    2011-01-01

    The lipase-catalyzed synthesis of cyclic ester oligomers from non-activated succinic acid (A) and 1,4-butanediol (B) in the presence of immobilized Candida antarctica lipase B was investigated. Batch and pulse fed-batch systems were implemented to increase the formation of cyclic ester products. The

  15. Kinetic properties of two Rhizopus exo-polygalacturonase enzymes hydrolyzing galacturonic acid oligomers using isothermal titration calorimetry

    Science.gov (United States)

    The kinetic characteristics of two Rhizopus oryzae exo-polygalacturonases acting on galacturonic acid oligomers (GalpA) were determined using isothermal titration calorimetry (ITC). RPG15 hydrolyzing (GalpA)2 demonstrated a Km of 55 uM and kcat of 10.3 s^-1^ while RPG16 was shown to have greater af...

  16. High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers

    DEFF Research Database (Denmark)

    Hansen, Mads E; Bentin, Thomas; Nielsen, Peter E

    2009-01-01

    substitution, in combination with (oligo)lysine or 9-aminoacridine conjugation, homopyrimidine PNA oligomers bind complementary dsDNA targets via triplex formation with (sub)nanomolar affinities (at pH 7.2, 150 mM Na(+)). Binding affinity can be modulated more than 1000-fold by changes in pH, PNA oligomer...

  17. Effects of dilute acid pretreatment conditions on enzymatic hydrolysis monomer and oligomer sugar yields for aspen, balsam, and switchgrass.

    Science.gov (United States)

    Jensen, Jill R; Morinelly, Juan E; Gossen, Kelsey R; Brodeur-Campbell, Michael J; Shonnard, David R

    2010-04-01

    The effects of dilute acid hydrolysis conditions were investigated on total sugar (glucose and xylose) yields after enzymatic hydrolysis with additional analyses on glucose and xylose monomer and oligomer yields from the individual hydrolysis steps for aspen (a hardwood), balsam (a softwood), and switchgrass (a herbaceous energy crop). The results of this study, in the form of measured versus theoretical yields and a severity analysis, show that for aspen and balsam, high dilute acid hydrolysis xylose yields were obtainable at all acid concentrations (0.25-0.75 wt.%) and temperatures (150-175 degrees C) studied as long as reaction time was optimized. Switchgrass shows a relatively stronger dependence on dilute acid hydrolysis acid concentration due to its higher neutralizing mineral content. Maximum total sugar (xylose and glucose; monomer plus oligomer) yields post-enzymatic hydrolysis for aspen, balsam, and switchgrass, were 88.3%, 21.2%, and 97.6%, respectively. In general, highest yields of total sugars (xylose and glucose; monomer plus oligomer) were achieved at combined severity parameter values (log CS) between 2.20 and 2.40 for the biomass species studied. Copyright 2009 Elsevier Ltd. All rights reserved.

  18. Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects.

    Science.gov (United States)

    Tolba, Mai F; Azab, Samar S; Khalifa, Amani E; Abdel-Rahman, Sherif Z; Abdel-Naim, Ashraf B

    2013-08-01

    Caffeic acid phenethyl ester (CAPE) is an important active component of honey bee propolis that possesses a plethora of biological activities. Propolis is used safely in traditional medicine as a dietary supplement for its therapeutic benefits. This review highlights the recently published data about CAPE bioavailability, anti-inflammatory, neuroprotective; hepatoprotective and cardioprotective activities. CAPE showed promising efficacy both in vitro and in vivo studies in animal models with minimum adverse effects. Its effectiveness was demonstrated in multiple target organs. Despite this fact, it has not been yet investigated as a protective agent or a potential therapy in humans. Investigation of CAPE efficacy in clinical trials is strongly encouraged to elucidate its therapeutic benefit for different human diseases after performing full preclinical toxicological studies and gaining more insights into its pharmacokinetics. © 2013 International Union of Biochemistry and Molecular Biology.

  19. Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues.

    Science.gov (United States)

    Narongchai, Paitoon; Niwatananun, Kanokporn; Narongchai, Siripun; Kusirisin, Winthana; Jaikang, Churdsak

    2016-01-01

    Caffeic acid (CAF) and its amide analogues, ethyl 1-(3',4'-dihydroxyphenyl) propen amide (EDPA), phenethyl 1-(3',4'-dihydroxyphenyl) propen amide (PEDPA), phenmethyl 1- (3',4'-dihydroxyphenyl) propen amide (PMDPA) and octyl 1-(3',4'-dihydroxyphenyl) propen amide (ODPA) were investigated for the inhibition of procarcinogen activating enzyme. CYP1A2 and scavenging activity on formation of nitric oxide, superoxide anion, DPPH radical and hydroxyl radical. It was found that they inhibited CYP1A2 enzyme by uncompetitive inhibition. Apparent Ki values of CAF, EDPA, PEDPA, PMDPA and ODPA were 0.59, 0.39, 0.45, 0.75 and 0.80 µM, respectively suggesting potent inhibitors of CYP1A2. Moreover, they potentially scavenged nitric oxide radical with IC 50 values of 0.12, 0.22, 0.28, 0.22 and 0.51 mM, respectively. The IC50 values of superoxide anion scavenging were 0.20, 0.22, 0.44, 2.18 and 2.50 mM, respectively. 1, 1- diphenyl-2- picrylhydrazyl (DPPH) radical-scavenging ability, shown as IC50 values, were 0.41, 0.29, 0.30, 0.89 and 0.84 mM, respectively. Moreover, the hydroxyl radical scavenging in vitro model was shown as IC50 values of 23.22, 21.06, 17.10, 17.21 and 15.81 µM, respectively. From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis.

  20. Preparation and applications of novel fluoroalkyl end-capped acrylic acid oligomers/silica nanocomposites-encapsulated fullerenes.

    Science.gov (United States)

    Kasai, Remi; Yaegashi, Hideaki; Yokoyama, Hiroshi; Yamanaka, Masahiko; Sawada, Hideo

    2007-01-01

    Fluoroalkyl end-capped acrylic acid oligomers/fullerenes nanocomposites reacted smoothly with tetraethoxysilane (TEOS) and silica nanoparticles under alkaline conditions to give fluoroalkyl end-capped oligomers/silica composites-encapsulated fullerenes. Interestingly, these isolated fluorinated composites were found to afford nanometer size-controlled colloidal particles with a good dispersibility in a variety of organic solvents including water. More interestingly, these fluorinated silica nanocomposites-encapsulated fullerenes were applied to a new type of surface modification agent, and these nanocomposites were able to disperse well above the poly(methyl methacrylate) films to exhibit not only surface active property imparted by fluorine but also a unique characteristic related to fullerenes in the nanocomposites on the surface, effectively.

  1. Structural studies on HCN oligomers.

    Science.gov (United States)

    Ferris, J P; Edelson, E H; Auyeung, J M; Joshi, P C

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  2. Preventative Effects of Caffeic Acid Phenyl Ester on Cadmium Intoxication Induced Hematological and Blood Coagulation Disturbances and Hepatorenal Damage in Rats

    Science.gov (United States)

    Ashour, Tariq Helal

    2014-01-01

    The preventative effect of caffeic acid phenyl ester (CAPE) against hematological, blood coagulation, and hepatorenal disturbances in cadmium (Cd) intoxication was investigated in rats. Male Wistar rats were randomly assigned into control group, Cd-group, and Cd + CAPE group. Cd intoxication was induced by intraperitoneal injection (i.p.) of CdCl2 (1 mg/kg/day) for 21 days, and CAPE was daily given (10 micromol/kg; i.p.) for also 21 days. The results showed that Cd intoxication impaired hepatorenal function and significantly prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen level, red blood cells and platelets counts, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Interestingly, all these hematological, blood coagulation, and hepatorenal deteriorations of Cd toxicity were significantly prevented by CAPE. Additionally, CAPE significantly reversed the significant decreases in levels of total reduced glutathione and superoxide dismutase and increases in levels of thiobarbituric acid reactive substances that were observed in the sera and liver and kidney homogenates of Cd group. It is concluded that CAPE is a promising compound that can counteract the hematological and blood coagulation disturbances, oxidative stress, and hepatorenal damages in Cd intoxication. However, further studies are crucially needed to improve this treatment in patients. PMID:25006475

  3. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

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    Hee Soon Shin

    2017-02-01

    Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  4. Novel and economic acid-base indicator based on (p-toluidine) oligomer: Synthesis; characterization and solvatochromism applications

    Science.gov (United States)

    Zoromba, M. Sh.

    2017-12-01

    A new (p-toluidine) oligomer (PTO) was facile synthesized and economically routed via chemical oxidative polymerization by potassium dichromate as an initiator in an acidic aqueous medium at room temperature. The characterization of (p-toluidine) oligomer (PTO) has been described by various techniques including Fourier transform infra-red (FTIR), UV-Visible measurements, Mass spectra, H NMR, and thermal gravimetric analysis (TGA). Solvatochromism of PTO was studied in different polaritiy solvents such as acetic acid, acetone, dimethyl formamide, ethanol, isopropanol, chloroform, p-xylene, dichloromethane and carbon teterachloride. The absorption bands were bathochromically shifted with increased polarity of the solvent (positive solvatochromism). PTO shows three isosbestic points at 333, 388 and 472 nm in a binary mixture of acetone and chloroform. The deprotonation constants of PTO were found to be 3.1 and 5.8, based on spectrophotometric calculations. PTO was successfully used as an acid-base indicator; the acid solution color sharply turned from pink (acidic medium) to yellow (basic medium) at the end point.

  5. Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats.

    Science.gov (United States)

    Gou, Jing; Yao, Xiaofang; Tang, Hao; Zou, Kaili; Liu, Yujia; Zuo, Hua; Zhao, Xiaoyan; Li, Zhubo

    2016-12-01

    Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO2), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO2 are related to their absorption properties. To understand the pharmacokinetic profiles of CAPE and CAPE-NO2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. The pharmacokinetic profiles of CAPE and CAPE-NO2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO2 (5, 10, 20 μM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO2 (5, 20 μM) for 48 and 72 h. The AUC(0-t) of CAPE-NO2 (3239.9 ± 352 ng × h/mL) was two-time greater than CAPE (1659.6 ± 152 ng × h/mL) in rats. The Papp values of CAPE and CAPE-NO2 were (4.86 ± 0.90) × 10(-6 )cm/s and (12.34 ± 1.6) × 10(-6 )cm/s, respectively. The accumulation of rhodamine 123 was increased by 1.3- to 1.9-fold and 1.4- to 2.3-fold in CAPE and CAPE-NO2 groups after 1 h administration, respectively. However, CAPE and CAPE-NO2 increased the P-gp levels by 2.1- and 1.7-fold, respectively. The absorption of CAPE-NO2 can be enhanced in rats and Caco-2 cells compared with CAPE. The two compounds are potential inhibitors of P-gp. The increased P-gp levels generated by CAPE and CAPE-NO2 played a role as a defense mechanism by limiting intracellular xenobiotic levels.

  6. Caffeic Acid Phenylethyl Ester and MG-132 Have Apoptotic and Antiproliferative Effects on Leukemic Cells But Not on Normal Mononuclear Cells12

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    Cavaliere, Victoria; Papademetrio, Daniela L; Lorenzetti, Mario; Valva, Pamela; Preciado, María Victoria; Gargallo, Patricia; Larripa, Irene; Monreal, Mariela B; Pardo, María Laura; Hajos, Silvia E; Blanco, Guillermo AC; Álvarez, Élida MC

    2009-01-01

    Chemotherapy aims to limit proliferation and induce apoptotic cell death in tumor cells. Owing to blockade of signaling pathways involved in cell survival and proliferation, nuclear factor κB (NF-κB) inhibitors can induce apoptosis in a number of hematological malignancies. The efficacy of conventional chemotherapeutic drugs, such as vincristine (VCR) and doxorubicine (DOX), may be enhanced with combined therapy based on NF-κB modulation. In this study, we evaluated the effect of caffeic acid phenylethyl ester (CAPE) and MG-132, two nonspecific NF-κB inhibitors, and conventional chemotherapeutics drugs DOX and VCR on cell proliferation and apoptosis induction on a lymphoblastoid B-cell line, PL104, established and characterized in our laboratory. CAPE and MG-132 treatment showed a strong antiproliferative effect accompanied by clear cell cycle deregulation and apoptosis induction. Doxorubicine and VCR showed antiproliferative effects similar to those of CAPE and MG-132, although the latter drugs showed an apoptotic rate two-fold higher than DOX and VCR. None of the four compounds showed cytotoxic effect on peripheral mononuclear cells from healthy volunteers. CAPE- and MG-132-treated bone marrow cells from patients with myeloid and lymphoid leukemias showed 69% (P < .001) and 25% decrease (P < .01) in cell proliferation and 42% and 34% (P < .01) apoptosis induction, respectively. Overall, our results indicate that CAPE and MG-132 had a strong and selective apoptotic effect on tumor cells that may be useful in future treatment of hematological neoplasias. PMID:19252751

  7. Caffeic Acid Phenethyl Ester and Ethanol Extract of Propolis Induce the Complementary Cytotoxic Effect on Triple-Negative Breast Cancer Cell Lines

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    Anna Rzepecka-Stojko

    2015-05-01

    Full Text Available Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP and its derivative caffeic acid phenethyl ester (CAPE towards two triple-negative breast cancer (TNBC cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  8. In vitro effect of caffeic acid phenethyl ester on matrix metalloproteinases (MMP-1 and MMP-9) and their inhibitor (TIMP-1) in lipopolysaccharide-activated human monocytes.

    Science.gov (United States)

    Vilela, Polyana das Graças Figueiredo; de Oliveira, Jonatas Rafael; de Barros, Patrícia Pimentel; Leão, Mariella Vieira Pereira; de Oliveira, Luciane Dias; Jorge, Antonio Olavo Cardoso

    2015-09-01

    The role of matrix metalloproteinases (MMPs) in tissue degradation has become evident in many diseases and great interest therefore exists in the pharmacological control of the activity of these enzymes. This study evaluated the effect of caffeic acid phenethyl ester (CAPE) on the production of MMPs and their inhibitor (TIMP) in monocytes activated by lipopolysaccharide (LPS). The human monocytic cell line (THP-1) was treated with non-cytotoxic concentrations of CAPE (10 and 60μM) combined with 1μg/mL of LPS. The gene expression of MMP-1, MMP-9 and TIMP-1 was evaluated by quantitative real-time polymerase chain reaction. The protein secretion into the culture medium was assessed via enzyme-linked immunosorbent assay and the gelatinolytic activity of MMP-9 by zymography. CAPE, especially at the highest concentration, down-regulated MMP-1 and MMP-9 gene expression but up-regulated the gene expression of TIMP-1. Furthermore, CAPE reduced the secreted protein level of MMP-1 and MMP-9 as well as the gelatinolytic activity of MMP-9. CAPE was able to inhibit the gene expression, production and the activity of MMPs induced by LPS and also increased the gene expression of TIMP-1. The present observations suggest that CAPE exerted a positive effect on the regulatory mechanism between MMPs and TIMP, which is important for the control of different diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer.

    Science.gov (United States)

    Wu, Jing; Omene, Coral; Karkoszka, Jerzy; Bosland, Maarten; Eckard, Jonathan; Klein, Catherine B; Frenkel, Krystyna

    2011-09-01

    Breast cancer (BC) patients use alternative and natural remedies more than patients with other malignancies. Specifically, 63-83% use at least one type of alternative medicine and 25-63% use herbals and vitamins. Propolis is a naturopathic honeybee product, and CAPE (caffeic acid phenethyl ester), is a major medicinal component of propolis. CAPE, in a concentration dependent fashion, inhibits MCF-7 (hormone receptor positive, HR+) and MDA-231 (a model of triple negative BC (TNBC) tumor growth, both in vitro and in vivo without much effect on normal mammary cells and strongly influences gene and protein expression. It induces cell cycle arrest, apoptosis and reduces expression of growth and transcription factors, including NF-κB. Notably, CAPE down-regulates mdr-1 gene, considered responsible for the resistance of cancer cells to chemotherapeutic agents. Further, CAPE dose-dependently suppresses VEGF formation by MDA-231 cells and formation of capillary-like tubes by endothelial cells, implicating inhibitory effects on angiogenesis. In conclusion, our results strongly suggest that CAPE inhibits MDA-231 and MCF-7 human breast cancer growth via its apoptotic effects, and modulation of NF-κB, the cell cycle, and angiogenesis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Effect of caffeic acid phenethyl ester on oxidant and anti-oxidant status of liver and serum in a rat model with acute methanol intoxication.

    Science.gov (United States)

    Yazgan, Ü C; Elbey, B; Kuş, S; Baykal, B; Keskin, I; Yılmaz, A; Şahin, A

    2017-05-01

    Methanol toxicity is one of the major public health problems because it can cause severe morbidity and mortality. Methanol intoxication causes changes in the balance between the production of free radicals and antioxidant capacity. We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on the total oxidant status, total antioxidant status (TAS), and oxidative stress index (OSI) parameters of the liver and the serum in a rat model of acute methanol intoxication. Rats were treated with intraperitoneal (i.p.) Methotrexate (MTX) for 7 days. On the 8th day, i.p. Methanol was administered in the methanol, ethanol and CAPE groups. Four hours after methanol treatment, ethanol was injected i.p. in the ethanol group; CAPE (i.p.) in the CAPE group; serum physiologic i.p. in other groups. After 8 hours, rats were killed and the serum and the liver samples were obtained for biochemical analyses. The OSI value was significantly higher in the methanol group compared to the ethanol and CAPE groups. Serum TAS levels of the methanol group were significantly different compared to the control group, but not compared to the MTX group. The amelioration of oxidative stress was greater in the CAPE group compared to the ethanol group but was not statistically significant. This study demonstrates that CAPE treatment ameliorates oxidative stress in the serum and liver in a rat model of acute methanol intoxication.

  11. Development of novel antibacterial active, HaCaT biocompatible and biodegradable CA-g-P(3HB-EC biocomposites with caffeic acid as a functional entity

    Directory of Open Access Journals (Sweden)

    H. M. N. Iqbal

    2015-09-01

    Full Text Available We have developed novel composites by grafting caffeic acid (CA onto the P(3HB-EC based material and laccase from Trametes versicolor was used for grafting purposes. The resulting composites were designated as CA-g-P(3HB-EC i.e., P(3HB-EC (control, 5CA-g-P(3HB-EC, 10CA-g-P(3HB-EC, 15CA-g-P(3HB-EC and 20CA-g-P(3HB-EC. FT-IR (Fourier-transform infrared spectroscopy was used to examine the functional and elemental groups of the control and laccase-assisted graft composites. Evidently, 15CA-g-P(3HB-EC composite exhibited resilient antibacterial activity against Gram-positive and Gram-negative bacterial strains. Moreover, a significant level of biocompatibility and biodegradability of the CA-g-P(3HB-EC composites was also achieved with the human keratinocytes-like HaCaT cells and soil burial evaluation, respectively. In conclusion, the newly developed novel composites with multi characteristics could well represent the new wave of biomaterials for medical applications, and more specifically have promising future in the infection free would dressings, burn and/or skin regeneration field due to their sophisticated characteristics.

  12. Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Han, Eun Hee [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Im, Ji Hye; Lee, Eun Ji; Jin, Sun Woo [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2015-09-25

    Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported to have anticarcinogenic properties, although its precise chemopreventive mechanism remains unclear. In this study, we examined the effects of CAPE on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1α (HIF-1α) protein level and HIF-1α responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1α induction. - Highlights: • CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. • CAPE inhibited 3-MC-induced CYP1A1 expression. • CAPE induced HIF-1α induction. • CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 expression.

  13. The colorimetric determination of selectively cleaved adenosines and guanosines in DNA oligomers using bicinchoninic acid and copper.

    Science.gov (United States)

    Thomas, Elizabeth M; Testa, Stephen M

    2017-01-01

    Colorimetric methods combined with color-changing chemical probes are widely used as simple yet effective tools for identifying and quantifying a wide variety of molecules in solution. For nucleic acids (DNA and RNA), perhaps the most commonly used colorimetric probe is potassium permanganate, which can be used to identify single-stranded pyrimidines (thymine and cytosine) in polymers. Unfortunately, permanganate is not an effective probe for identifying purines (adenine and guanine), especially in the presence of the more reactive pyrimidines. Therefore, robust methods for discriminating between the purines remain elusive, thereby creating a barrier toward developing more complex colorimetric applications. In this proof-of-principle study, we demonstrate that bicinchoninic acid (BCA) and copper, when combined with purine-specific chemical cleavage reactions, can be a colorimetric probe for the identification and quantification of adenosines and/or guanosines in single-stranded DNA oligomers, even in the presence of pyrimidines. Furthermore, the reactions are stoichiometric, which allows for the quantification of the number of adenosines and/or guanosines in these oligomers. Because the BCA/copper reagent detects the reducing sugar, 2-deoxyribose, that results from the chemical cleavage of a given nucleotide's N-glycosidic bond, these colorimetric assays are effectively detecting apurinic sites in DNA oligomers, which are known to occur via DNA damage in biological systems. We demonstrate that simple digital analysis of the color-changing chromophore (BCA/copper) is all that is necessary to obtain quantifiable and reproducible data, which indicates that these assays should be broadly accessible.

  14. Establishment of hairy root cultures of Rhaponticum carthamoides (Willd.) Iljin for the production of biomass and caffeic acid derivatives.

    Science.gov (United States)

    Skała, Ewa; Kicel, Agnieszka; Olszewska, Monika A; Kiss, Anna K; Wysokińska, Halina

    2015-01-01

    The aim of the study was to obtain transformed roots of Rhaponticum carthamoides and evaluate their phytochemical profile. Hairy roots were induced from leaf explants by the transformation of Agrobacterium rhizogenes strains A4 and ATCC 15834. The best response (43%) was achieved by infection with A4 strain. The effects of different liquid media (WPM, B5, SH) with full and half-strength concentrations of macro- and micronutrients on biomass accumulation of the best grown hairy root line (RC3) at two different lighting conditions (light or dark) were investigated. The highest biomass (93 g L(-1) of the fresh weight after 35 days) was obtained in WPM medium under periodic light. UPLC-PDA-ESI-MS(3) and HPLC-PDA analyses of 80% aqueous methanol extracts from the obtained hairy roots revealed the presence of eleven caffeoylquinic acids and their derivatives and five flavonoid glycosides. The production of caffeoylquinic acids and their derivatives was elevated in hairy roots grown in the light. Only light-grown hairy roots demonstrated the capability for the biosynthesis of such flavonoid glycosides as quercetagetin, quercetin, luteolin, and patuletin hexosides. Chlorogenic acid, 3,5-di-O-caffeoylquinic acid and a tentatively identified tricaffeoylquinic acid derivative were detected as the major compounds present in the transformed roots.

  15. Establishment of Hairy Root Cultures of Rhaponticum carthamoides (Willd. Iljin for the Production of Biomass and Caffeic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Ewa Skała

    2015-01-01

    Full Text Available The aim of the study was to obtain transformed roots of Rhaponticum carthamoides and evaluate their phytochemical profile. Hairy roots were induced from leaf explants by the transformation of Agrobacterium rhizogenes strains A4 and ATCC 15834. The best response (43% was achieved by infection with A4 strain. The effects of different liquid media (WPM, B5, SH with full and half-strength concentrations of macro- and micronutrients on biomass accumulation of the best grown hairy root line (RC3 at two different lighting conditions (light or dark were investigated. The highest biomass (93 g L−1 of the fresh weight after 35 days was obtained in WPM medium under periodic light. UPLC-PDA-ESI-MS3 and HPLC-PDA analyses of 80% aqueous methanol extracts from the obtained hairy roots revealed the presence of eleven caffeoylquinic acids and their derivatives and five flavonoid glycosides. The production of caffeoylquinic acids and their derivatives was elevated in hairy roots grown in the light. Only light-grown hairy roots demonstrated the capability for the biosynthesis of such flavonoid glycosides as quercetagetin, quercetin, luteolin, and patuletin hexosides. Chlorogenic acid, 3,5-di-O-caffeoylquinic acid and a tentatively identified tricaffeoylquinic acid derivative were detected as the major compounds present in the transformed roots.

  16. An unusual caffeic acid derived bicyclic [2.2.2] octane lignan and other constituents from Cordia rufescens.

    Science.gov (United States)

    do Vale, Ademir E; David, Jorge M; dos Santos, Edlene O; David, Juceni P; e Silva, Lidercia C R C; Bahia, Marcus V; Brandão, Hugo N

    2012-04-01

    This work reports isolation of an unusual lignan with a bicyclic [2.2.2] octene skeleton, named rufescenolide (1), from stems of Cordia rufescens, along with β-sitosterol, stigmasterol, syringaldehyde, 3-β-O-D-glucopyranosyl-sitosterol, methyl caffeate, 4-methoxy-protocatechuic acid and methyl rosmarinate. Structural characterizations employed IR spectroscopic, ESIHRMS and mono and dimensional NMR spectroscopy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Nitrogen Limited Red and Green Leaf Lettuce Accumulate Flavonoid Glycosides, Caffeic Acid Derivatives, and Sucrose while Losing Chlorophylls, Β-Carotene and Xanthophylls.

    Directory of Open Access Journals (Sweden)

    Christine Becker

    Full Text Available Reduction of nitrogen application in crop production is desirable for ecological and health-related reasons. Interestingly, nitrogen deficiency can lead to enhanced concentrations of polyphenols in plants. The reason for this is still under discussion. The plants' response to low nitrogen concentration can interact with other factors, for example radiation intensity. We cultivated red and green leaf lettuce hydroponically in a Mediterranean greenhouse, supplying three different levels of nitrogen (12 mM, 3 mM, 0.75 mM, either in full or reduced (-50% radiation intensity. In both red and green lettuce, we found clear effects of the nitrogen treatments on growth characteristics, phenolic and photosynthetic compounds, nitrogen, nitrate and carbon concentration of the plants. Interestingly, the concentrations of all main flavonoid glycosides, caffeic acid derivatives, and sucrose increased with decreasing nitrogen concentration, whereas those of chlorophylls, β-carotene, neoxanthin, lactucaxanthin, all trans- and cis-violaxanthin decreased. The constitutive concentrations of polyphenols were lower in the green cultivar, but their relative increase was more pronounced than in the red cultivar. The constitutive concentrations of chlorophylls, β-carotene, neoxanthin, all trans- and cis-violaxanthin were similar in red and green lettuce and with decreasing nitrogen concentration they declined to a similar extent in both cultivars. We only detected little influence of the radiation treatments, e.g. on anthocyanin concentration, and hardly any interaction between radiation and nitrogen concentration. Our results imply a greater physiological plasticity of green compared to the red lettuce regarding its phenolic compounds. They support the photoprotection theory regarding anthocyanins as well as the theory that the deamination activity of phenylalanine ammonia-lyase drives phenylpropanoid synthesis.

  18. Nitrogen Limited Red and Green Leaf Lettuce Accumulate Flavonoid Glycosides, Caffeic Acid Derivatives, and Sucrose while Losing Chlorophylls, Β-Carotene and Xanthophylls

    Science.gov (United States)

    Becker, Christine; Urlić, Branimir; Jukić Špika, Maja; Kläring, Hans-Peter; Krumbein, Angelika; Baldermann, Susanne; Goreta Ban, Smiljana; Perica, Slavko; Schwarz, Dietmar

    2015-01-01

    Reduction of nitrogen application in crop production is desirable for ecological and health-related reasons. Interestingly, nitrogen deficiency can lead to enhanced concentrations of polyphenols in plants. The reason for this is still under discussion. The plants’ response to low nitrogen concentration can interact with other factors, for example radiation intensity. We cultivated red and green leaf lettuce hydroponically in a Mediterranean greenhouse, supplying three different levels of nitrogen (12 mM, 3 mM, 0.75 mM), either in full or reduced (-50%) radiation intensity. In both red and green lettuce, we found clear effects of the nitrogen treatments on growth characteristics, phenolic and photosynthetic compounds, nitrogen, nitrate and carbon concentration of the plants. Interestingly, the concentrations of all main flavonoid glycosides, caffeic acid derivatives, and sucrose increased with decreasing nitrogen concentration, whereas those of chlorophylls, β-carotene, neoxanthin, lactucaxanthin, all trans- and cis-violaxanthin decreased. The constitutive concentrations of polyphenols were lower in the green cultivar, but their relative increase was more pronounced than in the red cultivar. The constitutive concentrations of chlorophylls, β-carotene, neoxanthin, all trans- and cis-violaxanthin were similar in red and green lettuce and with decreasing nitrogen concentration they declined to a similar extent in both cultivars. We only detected little influence of the radiation treatments, e.g. on anthocyanin concentration, and hardly any interaction between radiation and nitrogen concentration. Our results imply a greater physiological plasticity of green compared to the red lettuce regarding its phenolic compounds. They support the photoprotection theory regarding anthocyanins as well as the theory that the deamination activity of phenylalanine ammonia-lyase drives phenylpropanoid synthesis. PMID:26569488

  19. Cooperative Reinforcement of Ionic Liquid and Reactive Solvent on Enzymatic Synthesis of Caffeic Acid Phenethyl Ester as an In Vitro Inhibitor of Plant Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2017-01-01

    Full Text Available It is widely believed that lipases in ionic liquids (ILs possess higher enzyme activity, stability and selectivity; however, reaction equilibrium is always limited by product inhibition, and the product is difficult to separate from non-volatile ILs using distillation. To solve this problem, using trialkylphosphine oxide (TOPO as a complexing agent, a novel biphase of reactive solvent and IL was firstly reported for caffeic acid phenethyl ester (CAPE production from methyl caffeate (MC and 2-phenylethanol (PE catalyzed by lipase via transesterification. The effects of the reaction parameters and their action mechanism were investigated, and the inhibition of CAPE against bacterial wilt pathogen Ralstonia solanacearum was firstly measured. The MC conversion of 98.83% ± 0.76% and CAPE yield of 96.29% ± 0.07% were obtained by response surface methodology in the 25 g/L TOPO-cyclohexane/[Bmim][Tf2N] (1:1, v/v; the complex stoichiometry calculation and FTIR spectrum confirmed that the reversible hydrogen-bond complexation between TOPO and caffeates significantly enhances the cooperative effect of two phases on the lipase-catalyzed reaction. The temperature was reduced by 14 °C; the MC concentration increased by 3.33-fold; the ratio of catalyst to donor decreased by 4.5-fold; and Km decreased 1.08-fold. The EC50 of CAPE against R. solanacearum was 0.17–0.75 mg/mL, suggesting that CAPE is a potential in vitro inhibitor of plant pathogenic bacteria.

  20. Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on Cadmium-Induced Testicular Toxicity in Rats.

    Science.gov (United States)

    Erboga, Mustafa; Kanter, Mehmet; Aktas, Cevat; Bozdemir Donmez, Yeliz; Fidanol Erboga, Zeynep; Aktas, Emel; Gurel, Ahmet

    2016-05-01

    Cadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 μmol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.

  1. Radiolysis of linear model compounds of polyamide. 1. Formation of stable products of radiolysis of the oligomers of epsilon-aminocaproic acid

    Energy Technology Data Exchange (ETDEWEB)

    Szymanski, W.; Truszkowski, S. (Uniwersytet Mikolaja Kopernika, Torun (Poland). Inst. Chemii)

    1985-07-01

    Polyamide oligomers of epsilon-aminocaproic acid (ACA) were used as model compounds. Six oligomers with the number of mers, 2-7, designated as K/sub 2/-K/sub 7/ were synthesized. The ACA oligomers were irradiated with /sup 60/Co gamma rays in an atmosphere of nitrogen and in air in a dose range from 0 to 1300 kGy. The concentration of the CHO, NH/sub 2/ and COOH groups formed and the yields of gaseous products, hydrogen and carbon monoxide, as well as the absorption of oxygen, were determined. The polycaprolactam PA6 in the form of unstabilized fibres was investigated for comparison. The number of CHO groups increases with the dose for all oligomers; this value is, in air, for K/sub 5/-K/sub 7/ three times, for K/sub 3/-K/sub 4/ six times, and for K/sub 2/ nine times as large as in the atmosphere of nitrogen. The number of NH/sub 2/ groups goes through a maximum with increasing dose; in air the maximum is smaller and occurs at lower doses. The number of COOH groups changes only slightly with the dose; in air the number of COOH groups increases for longer oligomers (K/sub 5/-K/sub 7/). The concentration of hydrogen increases linearly with the dose both in the atmosphere of nitrogen and in air. In the latter case the radiation yields Gsub((H/sub 2/)) are lower.

  2. From lignocellulosic biomass to lactic- and glycolic-acid oligomers: a gram-scale microwave-assisted protocol.

    Science.gov (United States)

    Carnaroglio, Diego; Tabasso, Silvia; Kwasek, Beata; Bogdal, Dariusz; Gaudino, Emanuela Calcio; Cravotto, Giancarlo

    2015-04-24

    The conversion of lignocellulosic biomass into platform chemicals is the key step in the valorization of agricultural waste. Of the biomass-derived platform chemicals currently produced, lactic acid plays a particularly pivotal role in modern biorefineries as it is a versatile commodity chemical and building block for the synthesis of biodegradable polymers. Microwave-assisted processes that furnish lactic acid avoid harsh depolymerization conditions while cutting down reaction time and energy consumption. We herein report a flash catalytic conversion (2 min) of lignocellulosic biomass into lactic and glycolic acids under microwave irradiation. The batch procedure was successfully adapted to a microwave-assisted flow process (35 mL min(-1) ), with the aim of designing a scalable process with higher productivity. The C2 and C4 units recovered from the depolymerization were directly used as the starting material for a solvent and catalyst-free microwave-assisted polycondensation that afforded oligomers in good yields. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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 targeti...

  4. Reuse of Organomineral Substrate Waste from Hydroponic Systems as Fertilizer in Open-Field Production Increases Yields, Flavonoid Glycosides, and Caffeic Acid Derivatives of Red Oak Leaf Lettuce (Lactuca sativa L.) Much More than Synthetic Fertilizer.

    Science.gov (United States)

    Dannehl, Dennis; Becker, Christine; Suhl, Johanna; Josuttis, Melanie; Schmidt, Uwe

    2016-09-28

    Effects of organic waste from a hydroponic system added with minerals (organomineral fertilizer) and synthetic fertilizer on major polyphenols of red oak leaf lettuce using HPLC-DAD-ESI-MS(3) were investigated. Interestingly, contents of the main flavonoid glycosides and caffeic acid derivatives of lettuce treated with organomineral fertilizer were equal to those synthesized without soil additives. This was found although soil nutrient concentrations, including that of nitrogen, were much lower without additives. However, lettuce treated with synthetic fertilizer showed a significant decrease in contents of caffeic acid derivatives and flavonoid glycosides up to 78.3 and 54.2%, respectively. It is assumed that a negative effect of a high yield on polyphenols as described in the growth-differentiation balance hypothesis can be counteracted by (i) a higher concentration of Mg or (ii) optimal physical properties of the soil structure. Finally, the organomineral substrate waste reused as fertilizer and soil improver resulted in the highest yield (+78.7%), a total fertilizer saving of 322 kg ha(-1) and waste reduction in greenhouses.

  5. Structural Characterization of Monomers and Oligomers of D-Amino Acid-Containing Peptides Using T-Wave Ion Mobility Mass Spectrometry.

    Science.gov (United States)

    Pang, Xueqin; Jia, Chenxi; Chen, Zhengwei; Li, Lingjun

    2017-01-01

    The D-residues are crucial to biological function of D-amino acid containing peptides (DAACPs). Previous ion mobility mass spectrometry (IM-MS) studies revealing oligomerization patterns of amyloid cascade demonstrated conversion from native soluble unstructured assembly to fibril ß-sheet oligomers, which has been implicated in amyloid diseases, such as Alzheimer's disease and type 2 diabetes. Although neuropeptides are typically present at very low concentrations in circulation, their local concentrations could be much higher in large dense core vesicles, forming dimers or oligomers. We studied the oligomerization of protonated and metal-adducted achatin I and dermorphin peptide isomers with IM-MS. Our results suggested that dimerization, oligomerization, and metal adduction augment the structural differences between D/L peptide isomers compared to protonated monomers. Dimers and oligomers enhanced the structural differences between D/L peptide isomers in both aqueous and organic solvent system. Furthermore, some oligomer forms were only observed for either D- or L-isomers, indicating the importance of chiral center in oligomerization process. The oligomerization patterns of D/L isomers appear to be similar. Potassium adducts were detected to enlarge the structural differences between D/L isomers. Graphical Abstract ᅟ.

  6. Structural Characterization of Monomers and Oligomers of D-Amino Acid-Containing Peptides Using T-Wave Ion Mobility Mass Spectrometry

    Science.gov (United States)

    Pang, Xueqin; Jia, Chenxi; Chen, Zhengwei; Li, Lingjun

    2017-01-01

    The D-residues are crucial to biological function of D-amino acid containing peptides (DAACPs). Previous ion mobility mass spectrometry (IM-MS) studies revealing oligomerization patterns of amyloid cascade demonstrated conversion from native soluble unstructured assembly to fibril ß-sheet oligomers, which has been implicated in amyloid diseases, such as Alzheimer's disease and type 2 diabetes. Although neuropeptides are typically present at very low concentrations in circulation, their local concentrations could be much higher in large dense core vesicles, forming dimers or oligomers. We studied the oligomerization of protonated and metal-adducted achatin I and dermorphin peptide isomers with IM-MS. Our results suggested that dimerization, oligomerization, and metal adduction augment the structural differences between D/L peptide isomers compared to protonated monomers. Dimers and oligomers enhanced the structural differences between D/L peptide isomers in both aqueous and organic solvent system. Furthermore, some oligomer forms were only observed for either D- or L-isomers, indicating the importance of chiral center in oligomerization process. The oligomerization patterns of D/L isomers appear to be similar. Potassium adducts were detected to enlarge the structural differences between D/L isomers.

  7. Depolymerization and de-N-acetylation of chitin oligomers in hydrochloric acid.

    Science.gov (United States)

    Einbu, Aslak; Vårum, Kjell M

    2007-01-01

    The monosaccharide 2-amino-2-deoxy-D-glucose (glucosamine, GlcN) has recently drawn much attention in relation to its use to treat or prevent osteoarthritis in humans. Glucosamine is prepared from chitin, a process that is performed in concentrated acid, such as hydrochloric acid. This process involves two acid-catalyzed processes, that is, the hydrolysis of the glycosidic linkages (depolymerization) and of the N-acetyl linkages (de-N-acetylation). The depolymerization reaction has previously been found to be much faster compared to the deacetylation, with the consequence that the chitin chain will first be hydrolyzed to the monomer 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine, GlcNAc) which is subsequently deacetylated. We have found that the chitin disaccharide GlcNAc(1-->4)GlcNAc could be completely hydrolyzed to the monosaccharide GlcNAc with negligible concomitant de-N-acetylation, and the chitin disaccharide and monosaccharide were further used to study the depolymerization reaction and the de-N-acetylation reaction, respectively. The reactions were performed in hydrochloric acid as a function of acid concentration (3-12 M) and temperature (20-35 degrees C), and 1H-NMR spectroscopy was used to monitor the reaction rates. The 1H NMR spectrum of GlcNAc in concentrated (12 M) and deuterated hydrochloric acid at 25 degrees C was assigned. The glucofuranosyl oxazolinium (3) ion was found to exist in equilibrium with the alpha- and beta-anomers of the pyranose form of GlcNAc, where 3 was present in half the total molar concentrations of the two anomeric forms of GlcNAc. At lower acid concentration (3-6 M), only trace concentrations of 3 could be detected. The rate of de-N-acetylation of GlcNAc was determined as a function of hydrochloric acid concentration, showing a maximum at 6 M and decreasing by a factor of 2 upon decreasing or increasing the acid concentration to 3 or 12 M. The activation energy for hydrolysis of the N-acetyl linkage of GlcNAc was

  8. Monounsaturated fatty acid ether oligomers formed during heating of virgin olive oil show agglutination activity against human red blood cells.

    Science.gov (United States)

    Patrikios, Ioannis S; Mavromoustakos, Thomas M

    2014-01-29

    The present work focuses on the characterization of molecules formed when virgin olive oil is heated at 130 °C for 24 h open in air, which are found to be strong agglutinins. The hemagglutinating activity of the newly formed molecule isolated from the heated virgin olive oil sample was estimated against human red blood cells (RBCs). Dimers and polymers (high molecular weight molecules) were identified through thin layer chromatography (TLC) of the oil mixture. (1)H and (13)C nuclear magnetic resonance (NMR) and gas chromatography-mass spectroscopy (GC-MS) were the methods used for structural characterization. Among others, oligomerization of at least two monounsaturated fatty acids (FA) by an ether linkage between the hydrocarbon chains is involved. Light microscopy was used to characterize and visualize the agglutination process. Agglutination without fusion or lysis was observed. It was concluded that the heating of virgin olive oil open in air, among other effects, produces oligomerization as well as polymerization of unsaturated FA, possibly of monohydroxy, monounsaturated FA that is associated with strong hemagglutinating activity against human RBCs. The nutritional value and the effects on human health of such oligomers are not discussed in the literature and remain to be investigated.

  9. Crystal structure of a partly self-complementary peptide nucleic acid (PNA) oligomer showing a duplex-triplex network

    DEFF Research Database (Denmark)

    Petersson, Britt; Nielsen, Bettina Bryde; Rasmussen, Hanne

    2005-01-01

    of the decamer (G(4)A(5)T(6)C(7)). One right- and one left-handed Watson-Crick duplex are formed. The two PNA units C(9)T(10) change helical handedness, so that each PNA strand contains both a right- and a left-handed section. The changed handedness in C(9)T(10) allows formation of Hoogsteen hydrogen bonding...... Hoogsteen type. The structural diversity of this PNA demonstrates how the PNA backbone is able to adapt to structures governed by the stacking and hydrogen-bonding interactions between the nucleobases. The crystal structure further shows how PNA oligomers containing limited sequence complementarity may form......The X-ray structure of a partly self-complementary peptide nucleic acid (PNA) decamer (H-GTAGATCACT-l-Lys-NH(2)) to 2.60 A resolution is reported. The structure is mainly controlled by the canonical Watson-Crick base pairs formed by the self-complementary stretch of four bases in the middle...

  10. Kinetic characteristics of polygalacturonase enzymes hydrolyzing galacturonic acid oligomers using isothermal titration calorimetry

    Science.gov (United States)

    Polygalacturonase enzymes hydrolyze the polygalacturonic acid chains found in pectin. Interest in polygalacturonase enzymes continues as they are useful in a number of industrial processes and conversely, detrimental, as they are involved in maceration of economically important crops. While a good...

  11. Prediction of protein homo-oligomer types by pseudo amino acid composition: Approached with an improved feature extraction and Naive Bayes Feature Fusion.

    Science.gov (United States)

    Zhang, S-W; Pan, Q; Zhang, H-C; Shao, Z-C; Shi, J-Y

    2006-06-01

    The interaction of non-covalently bound monomeric protein subunits forms oligomers. The oligomeric proteins are superior to the monomers within the scope of functional evolution of biomacromolecules. Such complexes are involved in various biological processes, and play an important role. It is highly desirable to predict oligomer types automatically from their sequence. Here, based on the concept of pseudo amino acid composition, an improved feature extraction method of weighted auto-correlation function of amino acid residue index and Naive Bayes multi-feature fusion algorithm is proposed and applied to predict protein homo-oligomer types. We used the support vector machine (SVM) as base classifiers, in order to obtain better results. For example, the total accuracies of A, B, C, D and E sets based on this improved feature extraction method are 77.63, 77.16, 76.46, 76.70 and 75.06% respectively in the jackknife test, which are 6.39, 5.92, 5.22, 5.46 and 3.82% higher than that of G set based on conventional amino acid composition method with the same SVM. Comparing with Chou's feature extraction method of incorporating quasi-sequence-order effect, our method can increase the total accuracy at a level of 3.51 to 1.01%. The total accuracy improves from 79.66 to 80.83% by using the Naive Bayes Feature Fusion algorithm. These results show: 1) The improved feature extraction method is effective and feasible, and the feature vectors based on this method may contain more protein quaternary structure information and appear to capture essential information about the composition and hydrophobicity of residues in the surface patches that buried in the interfaces of associated subunits; 2) Naive Bayes Feature Fusion algorithm and SVM can be referred as a powerful computational tool for predicting protein homo-oligomer types.

  12. Synthesis and characterization of MnO2/NiO nanocomposites for photocatalysis of tetracycline antibiotic and modification with guanidine for carriers of Caffeic acid phenethyl ester-an anticancer drug.

    Science.gov (United States)

    Gupta, Vinod Kumar; Fakhri, Ali; Agarwal, Shilpi; Ahmadi, Elham; Nejad, Pedram Afshar

    2017-09-01

    In the present studies, modified NiO nanoparticles and MnO 2 /NiO nanocomposites with guanidine were synthesized by anchoring method for carriers of anticancer drug "Caffeic acid phenethyl ester". The prepared nanocomposites were characterized by using Scanning Electron Microscopy, Raman and Fourier transform infrared spectroscopy, X-ray diffraction, Vibrating sample magnetometer. The results from XRD indicated that the crystalline size of NiO nanoparticles and MnO 2 /NiO nanocomposites are 12 and 15nm, respectively. Saturation magnetization (Ms) for NiO NPs and MnO 2 /NiO nanocomposites was to be 0.60, and 0.68emu/g indicating that these are superparamagnetic and ferromagnetic properties in nature. The prepared nanocomposites were evaluated as catalyst for degradation of antibiotics in photocatalysis process. Particularly, the MnO 2 /NiO composite demonstrated the higher degradation rate (89.55%) of tetracycline antibiotic under UV light irradiation than the NiO (67.80%). Drug load on and release from nanopowders was investigated by using UV-Vis spectroscopy method. Time of drug loading was 100min and the drug release in 1-10h with 20-80% drug release were found, and then, it's applicable to in-vivo drug delivery. Therefore, the NiO nanoparticles and MnO 2 /NiO nanocomposites are promising for targeted Caffeic acid phenethyl ester anticancer drug delivery applications. The anticancer drug loaded on guanidine-NiO and guanidine-MnO 2 /NiO in high concentration has an antioxidant property. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. From the X-rays to a reliable “low cost” computational structure of caffeic acid: DFT, MP2, HF and integrated molecular dynamics-X-ray diffraction approach to condensed phases

    Science.gov (United States)

    Lombardo, Giuseppe M.; Portalone, Gustavo; Colapietro, Marcello; Rescifina, Antonio; Punzo, Francesco

    2011-05-01

    The ability of caffeic acid to act as antioxidant against hyperoxo-radicals as well as its recently found therapeutic properties in the treatment of hepatocarcinoma, still make this compound, more than 20 years later the refinement of its crystal structure, object of study. It belongs to the vast family of humic substances, which play a key role in the biodegradation processes and easily form complexes with ions widely diffused in the environment. This class of compounds is therefore interesting for potential environmental chemistry applications concerning the possible complexation of heavy metals. Our study focused on the characterization of caffeic acid as a starting necessary step, which will be followed in the future by the application of our findings on the study of the properties of caffeate anion interaction with heavy metal ions. To reach this goal, we applied a low cost approach - in terms of computational time and resources - aimed at the achievement of a high resolution, robust and trustable structure using the X-ray single crystal data, recollected with a higher resolution, as touchstone for a detailed check. A comparison between the calculations carried out with density functional theory (DFT), Hartree-Fock (HF) method and post SCF second order Møller-Plesset perturbation method (MP2), at the 6-31G ** level of the theory, molecular mechanics (MM) and molecular dynamics (MD) was performed. As a consequence we explained on one hand the possible reasons for the pitfalls of the DFT approach and on the other the benefits of using a good and robust force field developed for condensed phases, as AMBER, with MM and MD. The reliability of the latter, highlighted by the overall agreement extended up to the anisotropic displacement parameters calculated by means of MD and the ones gathered by X-ray measurements, makes it very promising for the above-mentioned goals.

  14. Activity of chalcones derived from 2,4,5-trimethoxybenzaldehyde against Meloidogyne exigua and in silico interaction of one chalcone with a putative caffeic acid 3-O-methyltransferase from Meloidogyne incognita.

    Science.gov (United States)

    Nunes, Alexandro Silva; Campos, Vicente Paulo; Mascarello, Alessandra; Stumpf, Taisa Regina; Chiaradia-Delatorre, Louise Domenghini; Machado, Alan Rodrigues Teixeira; Santos Júnior, Helvécio Martins; Yunes, Rosendo Augusto; Nunes, Ricardo José; Oliveira, Denilson Ferreira

    2013-12-01

    Meloidogyne exigua is a parasitic nematode of plants that causes great losses to coffee farmers. In an effort to develop parasitic controls, 154 chalcones were synthesized and screened for activity against this nematode. The best results were obtained with (2E)-1-(4'-nitrophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (6) with a 50% lethal concentration (LC50) of 171 μg/ml against M. exigua second-stage juveniles, in comparison to the commercially-available nematicide carbofuran which had an LC50 of 260 μg/ml under the same conditions. When coffee plants were used, 6 reduced the nematode population to ~50% of that observed in control plants. To investigate the mechanism of action of 6, an in silico study was carried out, which indicated that 6 may act against M. exigua through inhibition of a putative caffeic acid 3-O-methyltransferase homodimer, the amino acid sequence of which was determined by examining the genome of Meloidogyne incognita. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Characterization of the Interunit Bonds of Lignin Oligomers Released by Acid-Catalyzed Selective Solvolysis of Cryptomeria japonica and Eucalyptus globulus Woods via Thioacidolysis and 2D-NMR.

    Science.gov (United States)

    Saito, Kaori; Kaiho, Atsushi; Sakai, Ryo; Nishimura, Hiroshi; Okada, Hitomi; Watanabe, Takashi

    2016-12-07

    Acid-catalyzed degradation of lignin in toluene containing methanol selectively yields C6-C2 lignin monomers and releases lignin oligomers, a potential raw feedstock for epoxy resins. We herein characterize the structures of the lignin oligomers by focusing on the changes in the interunit linkage types during solvolysis. The oligomeric lignin products were analyzed via thioacidolysis and 2D-HSQC-NMR. The results show that lignin oligomers ranging from monomers to tetramers are released through considerable cleavage of the β-O-4 linkages. The lignin oligomers from Cryptomeria japonica (softwood) mainly comprise β-5, β-1, and tetrahydrofuran β-β linkages, whereas Eucalyptus globulus (hardwood) yields oligomers rich in β-1 and syringaresinol β-β linkages. Both wood samples exhibit selective release of β-β dimers and a relative decrease in 5-5 and 4-O-5 bonds during solvolysis. The method presented for the separation of lignin oligomers without β-O-4 linkages and with linkages unique to each wood species will be useful for the production of lignin-based materials.

  16. A direct correlation between the antioxidant efficiencies of caffeic acid and its alkyl esters and their concentrations in the interfacial region of olive oil emulsions. The pseudophase model interpretation of the "cut-off" effect.

    Science.gov (United States)

    Costa, Marlene; Losada-Barreiro, Sonia; Paiva-Martins, Fátima; Bravo-Díaz, Carlos; Romsted, Laurence S

    2015-05-15

    Recently published results for a series of homologous antioxidants, AOs, of increasing alkyl chain length show a maximum in AO efficiency followed by a significant decrease for the more hydrophobic AOs, typically called the "cut-off" effect. Here we demonstrate that in olive oil emulsions both antioxidant efficiencies and partition constants for distributions of AOs between the oil and interfacial regions, PO(I), show a maximum at the C8 ester. A reaction between caffeic acid, CA, and its specially synthesised C1-C16 alkyl esters, and a chemical probe is used to estimate partition constants for AO distributions and interfacial rate constants, kI, in intact emulsions based on the pseudophase kinetic model. The model provides a natural interpretation for both the maximum and the "cut-off" effect. More than 70% of the CA esters are in the interfacial region even at low surfactant volume fraction, ΦI=0.005. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Caffeic Acid Phenethyl Ester (Propolis Extract) Ameliorates Insulin Resistance by Inhibiting JNK and NF-κB Inflammatory Pathways in Diabetic Mice and HepG2 Cell Models.

    Science.gov (United States)

    Nie, Jiarui; Chang, Yaning; Li, Yujia; Zhou, Yingjun; Qin, Jiawen; Sun, Zhen; Li, Haibin

    2017-10-18

    Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.

  18. Verbascoside is not genotoxic in the ST and HB crosses of the Drosophila wing spot test, and its constituent, caffeic acid, decreases the spontaneous mutation rate in the ST cross.

    Science.gov (United States)

    Santos-Cruz, Luis Felipe; Ávila-Acevedo, José Guillermo; Ortega-Capitaine, Diego; Ojeda-Duplancher, Jesús Clemente; Perdigón-Moya, Juana Laura; Hernández-Portilla, Luis Barbo; López-Dionicio, Héctor; Durán-Díaz, Angel; Dueñas-García, Irma Elena; Castañeda-Partida, Laura; García-Bores, Ana María; Heres-Pulido, María Eugenia

    2012-03-01

    Verbascoside (VB) is a phenylpropanoid isolated from Buddleja species, some of which originate in Mexico, and was first described in the sixteenth century in the codices of Mexican traditional medicine. VB is present in alcohol extracts and is widely used in the north of Mexico as a sunscreen. VB absorbs UV-A and UV-B radiation and has high antioxidant and anti-inflammatory capacities. VB and its constituent caffeic acid (CA) were screened to determine their genotoxic activity using the Drosophila wing spot test. Third instar larvae (72±4 h) of the standard (ST) and high bioactivation (HB) crosses, with regulated and high levels of cytochrome P450s (Cyp450s), respectively, were exposed to VB or CA (0, 27, 57, 81, 135, and 173 mM). VB was not genotoxic at any of the concentrations tested in both crosses. The amount of VB residue as determined by HPLC in the adult flies that were fed with VB indicated a low metabolism of this compound, which explains the absence of genotoxicity. CA decreased the spontaneous frequencies of small and total spots and showed putative toxicity in the ST cross. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Caffeic Acid Phenethyl Ester Induces Adrenoleukodystrophy (Abcd2) Gene in Human X-ALD Fibroblasts and Inhibits the Proinflammatory Response in Abcd1/2 Silenced Mouse Primary Astrocytes

    Science.gov (United States)

    Singh, Jaspreet; Khan, Mushfiquddin; Singh, Inderjit

    2013-01-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derrangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans. PMID:23318275

  20. Carbon nanotube reinforced hollow fiber solid/liquid phase microextraction: a novel extraction technique for the measurement of caffeic acid in Echinacea purpurea herbal extracts combined with high-performance liquid chromatography.

    Science.gov (United States)

    Es'haghi, Zarrin; Golsefidi, Mazyar Ahmadi; Saify, Ali; Tanha, Ali Akbar; Rezaeifar, Zohre; Alian-Nezhadi, Zahra

    2010-04-23

    A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was developed for the determination of caffeic acid in medicinal plants samples as Echinacea purpure. The membrane extraction with sorbent interface used in this research is a three-phase supported liquid membrane consisting of an aqueous (donor phase), organic solvent/nano sorbent (membrane) and aqueous (acceptor phase) system operated in direct immersion sampling mode. The multi-walled carbon nanotube dispersed in the organic solvent is held in the pores of a porous membrane supported by capillary forces and sonification. It is in contact with two aqueous phases: the donor phase, which is the aqueous sample, and the acceptor phase, usually an aqueous buffer. All microextraction experiments were supported using an Accurel Q3/2 polypropylene hollow fiber membrane (600 microm I.D., 200 microm wall thicknesses, and 0.2 microm pore size). The experimental setup is very simple and highly affordable. The hollow fiber is disposable, so single use of the fiber reduces the risk of cross-contamination and carry-over problems. The proposed method allows the very effective and enriched recuperation of an acidic analyte into one single extract. In order to obtain high enrichment and extraction efficiency of the analyte using this novel technique, the main parameters were optimized. Under the optimized extraction conditions, the method showed good linearity (0.0001-50 microg/L), repeatability, low limits of detection (0.00005 microg/L) and excellent enrichment (EF=2108). Copyright 2010 Elsevier B.V. All rights reserved.

  1. Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes.

    Science.gov (United States)

    Jackson, Alexis; Jani, Saumya; Sala, Carol Davies; Soler-Bistué, Alfonso J C; Zorreguieta, Angeles; Tolmasky, Marcelo E

    2016-03-01

    EGSs (external guide sequences) are short antisense oligoribonucleotides that elicit RNase P-mediated cleavage of a target mRNA, which results in inhibition of gene expression. EGS technology is used to inhibit expression of a wide variety of genes, a strategy that may lead to development of novel treatments of numerous diseases, including multidrug-resistant bacterial and viral infections. Successful development of EGS technology depends on finding nucleotide analogs that resist degradation by nucleases present in biological fluids and the environment but still elicit RNase P-mediated degradation when forming a duplex with a target mRNA. Previous results suggested that locked nucleic acids (LNA)/DNA chimeric oligomers have these properties. LNA are now considered the first generation of compounds collectively known as bridged nucleic acids (BNA), modified ribonucleotides that contain a bridge at the 2',4'-position of the ribose. LNA and the second generation BNA, known as BNANC, differ in the chemical nature of the bridge. Chimeric oligomers containing LNA or BNANC and deoxynucleotide monomers in different configurations are nuclease resistant and could be excellent EGS compounds. However, not all configurations may be equally active as EGSs. RNase P cleavage assays comparing LNA/DNA and BNANC/DNA chimeric oligonucleotides that share identical nucleotide sequence but with different configurations were carried out using as target the amikacin resistance aac(6')-Ib mRNA. LNA/DNA gapmers with 5 and 3/4 LNA residues at the 5'- and 3'-ends, respectively, were the most efficient EGSs while all BNANC/DNA gapmers showed very poor activity. When the most efficient LNA/DNA gapmer was covalently bound to a cell penetrating peptide (CPP), the hybrid compound conserved the EGS activity as determined by RNase P cleavage assays and reduced the levels of resistance to amikacin when added to Acinetobacter baumannii cells in culture, an indication of cellular uptake and biological

  2. Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.

    Science.gov (United States)

    Goldberg, Joel S

    2011-02-15

    It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.

  3. Structural studies on HCN oligomers. [catalysts for prebiotic processes

    Science.gov (United States)

    Ferris, J. P.; Edelson, E. H.; Auyeung, J. M.; Joshi, P. C.

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  4. 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability.

    Science.gov (United States)

    Takahashi, Hideaki; Nguyen, Binh Cao Quan; Uto, Yoshihiro; Shahinozzaman, Md; Tawata, Shinkichi; Maruta, Hiroshi

    2017-05-30

    Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1. However, mainly due to their COOH moiety, cell-permeability of these herbal compounds is rather limited. Thus, in this study, in an attempt to increase their cell-permeability without any significant loss of their water-solubility, we have esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through Click Chemistry. We found that this esterization boosts the anti-cancer activity of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent growth of A549 lung cells, but show no effect on the PAK1-independent growth of B16F10 melanoma cells. Confirming this "selective" toxicity, these esters are still capable of blocking the kinase PAK1 strongly in cell culture (with IC 50 around 5 µM), and the anti-PAK1 activity of 15A (ARC ester) and 15C (CA ester) appears to be 30-fold and 140-fold higher than ARC and CA, respectively. The 15A and 15C are 8-fold and 70-fold more cell-permeable (through the multi-drug resistant cell line EMT6) than ARC and CA, respectively. These data altogether suggest that both 15A and 15C would be far more useful than propolis for the treatment of a wide variety of PAK1-dependent diseases/disorders such as cancers, Alzheimer's diseases (AD), hypertension, diabetes (type 2), and hyper-pigmentation.

  5. Highly Stable Foams from Block Oligomers Synthesized by Enzymatic Reactions

    NARCIS (Netherlands)

    Sagis, L.M.C.; Boeriu, C.G.; Frissen, A.E.; Schols, H.A.; Wierenga, P.A.

    2008-01-01

    We have synthesized a new amphiphilic block oligomer by the enzymatic linking of a fatty acid (lauric acid) to a fructan oligomer (inulin) and tested the functionality of this carbohydrate derivative in foam stabilization. The structure of the modified oligosaccharide was found to be

  6. Inhibition of low-density lipoprotein oxidation and oxidative burst in polymorphonuclear neutrophils by caffeic acid and hispidin derivatives isolated from sword brake fern (Pteris ensiformis Burm.).

    Science.gov (United States)

    Wei, Hsiu-An; Lian, Tzi-Wei; Tu, Yi-Chen; Hong, Jing-Ting; Kou, Mei-Chun; Wu, Ming-Jiuan

    2007-12-26

    Several antioxidant compounds have been previously identified from sword brake fern (Pteris ensiformis Burm.) by DPPH bleaching and Trolox equivalent antioxidant capacity (TEAC) analyses. Among the isolates, 7-O-caffeoylhydroxymaltol 3-O-beta-D-glucopyranoside and hispidin 4-O-beta- D-glucopyranoside [6-(3,4-dihydroxystyryl)-4-O-beta-D-glucopyranoside-2-pyrone] were two new compounds. The aim of this study is to elucidate the possible effect of the aqueous extract of sword brake fern (SBF) and these two compounds in preventing atherosclerosis. The results demonstrated that SBF and these two compounds strongly inhibited Cu2+-mediated low-density lipoprotein (LDL) oxidation measured by thiobarbituric acid-reactive substances assay (TBARS), conjugated diene production, and relative electrophoretic mobility. The commercial antioxidant dl-alpha-tocopherol showed lower antioxidant activity than these two compounds at the same molecular concentration. SBF and these two compounds also suppressed N-formylmethionyl-leucylphenylalanine (fMLP)-stimulated reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN). These findings indicate that sword brake fern may prevent atherosclerosis via inhibition of both LDL oxidation and ROS production.

  7. Label-free impedimetric sensor for a ribonucleic acid oligomer specific to hepatitis C virus at a self-assembled monolayer-covered electrode.

    Science.gov (United States)

    Park, Jin-Young; Lee, Yoon-suk; Chang, Byoung-Yong; Kim, Byeang Hyean; Jeon, Sangmin; Park, Su-Moon

    2010-10-01

    A ribonucleic acid (RNA) sensor based on hybridization of its peptide nucleic acid (PNA) molecule with a target RNA oligomer of the internal ribosome entry site sequence specific to the hepatitis C virus (HCV) and the electrochemical impedance detection is described. This RNA is one of the most conservative molecules of the whole HCV RNA genome. The ammonium ion terminated PNA molecule was immobilized via its host-guest interactions with the diaza crown ring of 3-thiophene-acetamide-diaza-18-crown-6 synthesized by a simple two-step method, which forms a well-defined self-assembled monolayer (SAM) on gold. Hybridization events of the probe PNA with the target RNA were monitored by measuring charge-transfer resistances for the Fe(CN)(6)(3-/4-) redox probe using Fourier transform electrochemical impedance spectroscopy. The ratio of the resistances of the SAM-covered electrode measured before and after hybridization increased linearly with log[RNA] in the rat liver lysate with a detection limit of about 23 pM.

  8. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy.

    Science.gov (United States)

    Chang, Huasong; Wang, Yuehua; Yin, Xusheng; Liu, Xinying; Xuan, Hongzhuan

    2017-09-26

    Propolis and its major constituent - caffeic acid phenethyl ester (CAPE) have good abilities on antitumor and anti-inflammation. However, little is known about the actions of propolis and CAPE on tumor in inflammatory microenvironment, and inflammatory responses play decisive roles at different stages of tumor development. To understand the effects and mechanisms of ethanol-extracted Chinese propolis (EECP) and its major constituent - CAPE in inflammation-stimulated tumor, we investigated their effects on Toll-like receptor 4 (TLR4) signaling pathway which plays a crucial role in breast cancer MDA-MB-231 cell line. 80% confluent breast cancer MDA-MB-231 cells were stimulated with 1 μg/mL lipopolysaccaride (LPS). Then the cells were divided for treatment by CAPE (25 μg/mL) and EECP (25, 50 and 100 μg/mL), respectively. Cell viability, nitric oxide (NO) production and cell migration were measured by sulforhodamine B assay, chemical method and scratch assay. The levels of TLR4, MyD88, IRAK4, TRIF, caspase 3, PARP, LC3B and p62 were investigated through western blotting. The expression of TLR4, LC3B and nuclear factor-κB p65 (NF-κB p65) were tested by immunofluorescence microscopy assay. Treatment of different concentrations of EECP (25, 50 and 100 μg/mL) and CAPE (25 μg/mL) significantly inhibited LPS-stimulated MDA-MB-231 cell line proliferation, migration and NO production. Furthermore, EECP and CAPE activated caspase3 and PARP to induce cell apoptosis, and also upregulated LC3-II and decreased p62 level to induce autophagy during the process. TLR4 signaling pathway molecules such as TLR4, MyD88, IRAK4, TRIF and NF-κB p65 were all down-regulated after EECP and CAPE treatment in LPS-stimulated MDA-MB-231 cells. These findings indicated that EECP and its major constituent - CAPE inhibited breast cancer MDA-MB-231 cells proliferation in inflammatory microenvironment through activating apoptosis, autophagy and inhibiting TLR4 signaling pathway. EECP and

  9. Structural Characterization of Formaldehyde-induced Cross-links Between Amino Acids and Deoxynucleosides and Their Oligomers

    Science.gov (United States)

    Lu, Kun; Ye, Wenjie; Zhou, Li; Collins, Leonard B.; Chen, Xian

    2010-01-01

    Exposure to formaldehyde results in the formation of DNA-protein cross-links (DPCs) as a primary genotoxic effect. Although DPCs are biologically important and eight amino acids have been reported to form stable adducts with formaldehyde, the structures of these cross-links have not yet been elucidated. We have characterized formaldehyde-induced cross-links of Lys, Cys, His and Trp with dG, dA and dC. dT formed no cross-links, nor did Arg, Gln, Tyr or Asn. Reaction of formaldehyde with Lys and dG gave the highest yield of cross-linked products, followed by reaction with Cys and dG. Yields from the other coupling reactions were lower by a factor of 10 or more. Detailed structural examination by NMR and mass spectrometry established that the cross-links between amino acids and single nucleosides involve a formaldehyde-derived methylene bridge. Lys yielded two additional products with dG in which the linking structure is a 1,N2-fused triazino ring. The Lys cross-linked products were unstable at ambient temperature. Reactions between the reactive Nα-Boc-protected amino acids and the trinucleotides d(T1B2T3) where B2 is the target base G, A or C and reactions between dG, dA and dC and 8-mer peptides containing a single reactive target residue at position 5 yielded cross-linked products with structures inferred from high resolution mass spectrometry and fragmentation patterns that are consistent with those between Nα-Boc-protected amino acids and single nucleotides rigorously determined by NMR studies. These structures will provide a basis for investigation of the characteristics and properties of DPCs formed in vivo and will be helpful in identifying biomarkers for the evaluation of formaldehyde exposure both at site of contact and at distant sites. PMID:20178313

  10. The role of 2-methylglyceric acid and oligomer formation in the multiphase processing of secondary organic aerosol from isoprene and methacrolein photooxidation (CUMULUS project)

    Science.gov (United States)

    Giorio, Chiara; Brégonzio-Rozier, Lola; Siekmann, Frank; Cazaunau, Mathieu; Temime-Roussel, Brice; Langley DeWitt, Helen; Gratien, Aline; Michoud, Vincent; Pangui, Edouard; Morales, Sébastien; Ravier, Sylvain; Zielinski, Arthur T.; Tapparo, Andrea; Vermeylen, Reinhilde; Claeys, Magda; Voisin, Didier; Salque-Moreton, Guillaume; Kalberer, Markus; Doussin, Jean-François; Monod, Anne

    2017-04-01

    Biogenic volatile organic compounds (BVOCs) undergo atmospheric processing and form a wide range of oxidised and water-soluble compounds. These compounds could partition into atmospheric water droplets, and react within the aqueous phase producing higher molecular weight and less volatile compounds which could remain in the particle phase after water evaporation (Ervens et al., 2011). The aim of this work was the molecular characterisation of secondary organic aerosol (SOA) formed from the photooxidation of isoprene and methacrolein during cloud evapo-condensation cycles. The experiments were performed within the CUMULUS project (CloUd MULtiphase chemistry of organic compoUndS in the troposphere), at the 4.2 m3 stainless steel CESAM chamber at LISA (Brégonzio-Rozier et al., 2016). In each experiment, isoprene or methacrolein was photooxidised with HONO and clouds have been produced to study oxidation processes in a multiphase environment that well simulates the interactions between VOCs, SOA particles and cloud droplets. During all the experiments, SOA was characterised online with a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and offline with gas chromatography mass spectrometry (GC-MS) and direct infusion nanoelectrospray ionisation high resolution mass spectrometry (nanoESI-HRMS). We observed that the main SOA compound in all experiments was 2-methylglyceric acid which undergoes oligomerisation reactions. A large number of long homologous series of oligomers were detected in all experiments, together with a complex co-oligomerised system made of monomers with a large variety of different structures. Comparison of SOA from multiphasic (smog chamber) experiments and samples from aqueous phase oxidation of methacrolein with •OH radical pointed out different types of oligomerisation reactions dominating the two different systems. Ervens et al. (2011) Atmos. Chem. Phys. 11, 11069 11102. Brégonzio-Rozier et al. (2016) Atmos. Chem. Phys

  11. PIPERIDINE OLIGOMERS AND COMBINATORIAL LIBRARIES THEREOF

    DEFF Research Database (Denmark)

    1999-01-01

    The present invention relates to piperidine oligomers, methods for the preparation of piperidine oligomers and compound libraries thereof, and the use of piperidine oligomers as drug substances. The present invention also relates to the use of combinatorial libraries of piperidine oligomers...... in libraries (arrays) of compounds especially suitable for screening purposes....

  12. Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers

    Directory of Open Access Journals (Sweden)

    Yeung Stephen

    2010-12-01

    Full Text Available Abstract Background Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates. Results We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological analysis of a number of different prefibrillar Aβ oligomer preparations show that structural polymorphisms exist in Aβ prefibrillar oligomers that can be distinguished on the basis of their reactivity with monoclonal antibodies. Western blot analysis demonstrates that the conformers defined by the monoclonal antibodies have distinct size distributions, indicating that oligomer structure varies with size. The different conformational types of Aβ prefibrillar oligomers can serve as they serve as templates for monomer addition, indicating that they seed the conversion of Aβ monomer into more prefibrillar oligomers of the same type. Conclusions These results indicate that distinct structural variants or conformers of prefibrillar Aβ oligomers exist that are capable of seeding their own replication. These conformers may be analogous to different strains of prions.

  13. Imide Oligomers Endcapped with Phenylethynl Phthalic Anhydrides and Polymers Therefrom

    Science.gov (United States)

    Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1998-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N.N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or cheznicauy to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydxide(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  14. Imide oligomers endcapped with phenylethynyl phthalic anhydrides and polymers therefrom

    Science.gov (United States)

    Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or chemically to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydride(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  15. Targeting α-synuclein oligomers

    DEFF Research Database (Denmark)

    van Diggelen, Femke

    2017-01-01

    Parkinson’s Disease (PD) is a complex disease, characterised by degeneration of neocortical, limbic and nigrostriatal neurons. It is unknown what initiates neurodegeneration, but soluble oligomers of the protein α-synuclein (αSn) seem to be particularly toxic, compared to insoluble fibrils....... Although there is currently no cure for PD, αSn oligomers (αSOs) are a potential therapeutic target, but a major drawback it that little is known about the nature of PD-associated αSOs. The scientific literature describes a wide variety of protocols to generate αSOs in vitro, with a subsequent...

  16. SAXS fingerprints of aldehyde dehydrogenase oligomers

    Directory of Open Access Journals (Sweden)

    John J. Tanner

    2015-12-01

    Full Text Available Enzymes of the aldehyde dehydrogenase (ALDH superfamily catalyze the nicotinamide adenine dinucleotide-dependent oxidation of aldehydes to carboxylic acids. ALDHs are important in detoxification of aldehydes, amino acid metabolism, embryogenesis and development, neurotransmission, oxidative stress, and cancer. Mutations in genes encoding ALDHs cause metabolic disorders, including alcohol flush reaction (ALDH2, Sjögren–Larsson syndrome (ALDH3A2, hyperprolinemia type II (ALDH4A1, γ-hydroxybutyric aciduria (ALDH5A1, methylmalonic aciduria (ALDH6A1, pyridoxine dependent epilepsy (ALDH7A1, and hyperammonemia (ALDH18A1. We previously reported crystal structures and small-angle X-ray scattering (SAXS analyses of ALDHs exhibiting dimeric, tetrameric, and hexameric oligomeric states (Luo et al., Biochemistry 54 (2015 5513–5522; Luo et al., J. Mol. Biol. 425 (2013 3106–3120. Herein I provide the SAXS curves, radii of gyration, and distance distribution functions for the three types of ALDH oligomer. The SAXS curves and associated analysis provide diagnostic fingerprints that allow rapid identification of the type of ALDH oligomer that is present in solution. The data sets provided here serve as a benchmark for characterizing oligomerization of ALDHs.

  17. Targeting Cancer with Antisense Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes

  18. Anti-Aβ Oligomer IgG and Surface Sialic Acid in Intravenous Immunoglobulin: Measurement and Correlation with Clinical Outcomes in Alzheimer’s Disease Treatment

    Science.gov (United States)

    Kwon, Hyewon; Finke, John M.

    2015-01-01

    The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer’s Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment. PMID:25826319

  19. Preparation of Chito-Oligomers by Hydrolysis of Chitosan in the Presence of Zeolite as Adsorbent

    Directory of Open Access Journals (Sweden)

    Khalid A. Ibrahim

    2016-07-01

    Full Text Available An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as immuno-enhancing effects on animals. Conventional depolymerization methods of chitosan to chito-oligomers are either chemical by acid-hydrolysis under harsh conditions or by enzymatic degradation. In this work, hydrolysis of chitosan to chito-oligomers has been achieved by applying adsorption-separation technique using diluted HCl in the presence of different types of zeolite as adsorbents. The chito-oligomers were retrieved from adsorbents and characterized by differential scanning calorimetry (DSC, liquid chromatography/mass spectroscopy (LC/MS, and ninhydrin test.

  20. Amyloid protofibrils of lysozyme nucleate and grow via oligomer fusion.

    Science.gov (United States)

    Hill, Shannon E; Robinson, Joshua; Matthews, Garrett; Muschol, Martin

    2009-05-06

    The mechanisms linking deposits of insoluble amyloid fibrils to the debilitating neuronal cell death characteristic of neurodegenerative diseases remain enigmatic. Recent findings implicate transiently formed intermediates of mature amyloid fibrils as the principal toxic agent. Hence, determining which intermediate aggregates represent on-pathway precursors or off-pathway side branches is critical for understanding amyloid self-assembly, and for devising therapeutic approaches targeting relevant toxic species. We examined amyloid fibril self-assembly in acidic solutions, using the model protein hen egg-white lysozyme. Combining in situ dynamic light scattering with calibrated atomic-force microscopy, we monitored the nucleation and growth kinetics of multiple transient aggregate species, and characterized both their morphologies and physical dimensions. Upon incubation at elevated temperatures, uniformly sized oligomers formed at a constant rate. After a lag period of several hours, protofibrils spontaneously nucleated. The nucleation kinetics of protofibrils and the tight match of their widths and heights with those of oligomers imply that protofibrils both nucleated and grew via oligomer fusion. After reaching several hundred nanometers in length, protofibrils assembled into mature fibrils. Overall, the amyloid fibril assembly of lysozyme followed a strict hierarchical aggregation pathway, with amyloid monomers, oligomers, and protofibrils forming on-pathway intermediates for assembly into successively more complex structures.

  1. Beta-Amyloid Oligomers Activate Apoptotic BAK Pore for Cytochrome c Release

    Science.gov (United States)

    Kim, Jaewook; Yang, Yoosoo; Song, Seung Soo; Na, Jung-Hyun; Oh, Kyoung Joon; Jeong, Cherlhyun; Yu, Yeon Gyu; Shin, Yeon-Kyun

    2014-01-01

    In Alzheimer’s disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (Aβ) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic Aβ of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 family protein BAK is suppressed by siRNA, Aβ oligomer-induced cell death was reduced. Furthermore, significant reduction of cytochrome c release was observed with mitochondria isolated from BAK siRNA-treated HT-22 cells. Our in vitro experiments demonstrate that Aβ oligomers bind to BAK on the membrane and induce apoptotic BAK pores and cytochrome c release. Thus, the results suggest that Aβ oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death. PMID:25296312

  2. Cyclic oligomers in polyamide for food contact material: quantification by HPLC-CLND and single-substance calibration.

    Science.gov (United States)

    Heimrich, M; Bönsch, M; Nickl, H; Simat, T J

    2012-01-01

    Cyclic oligomers are the major substances migrating from polyamide (PA) food contact materials. However, no commercial standards are available for the quantification of these substances. For the first time the quantification of cyclic oligomers was carried out by HPLC coupled with a chemiluminescence nitrogen detector (CLND) and single-substance calibration. Cyclic monomer (MW = 226 Da) and dimer (MW = 452 Da) of PA66 were synthesised and equimolar N detection of CLND to synthesised oligomers, caprolactam, 6-aminohexanoic acid (monomers of PA6) and caffeine (a typical nitrogen calibrant) was proven. Relative response factors (UVD at 210 nm) referring to caprolactam were determined for cyclic PA6 oligomers from dimer to nonamer, using HPLC-CLND in combination with a UVD. A method for quantification of cyclic oligomer content in PA materials was introduced using HPLC-CLND analysis and caffeine as a single nitrogen calibrant. The method was applied to the quantification of cyclic PA oligomers in several PA granulates. For two PA6 granulates from different manufacturers markedly different oligomer contents were analysed (19.5 versus 13.4 g kg⁻¹). The elution pattern of cyclic oligomers offers the possibility of identifying the PA type and differentiating between PA copolymers and blends.

  3. Self-propagative replication of Aβ oligomers suggests potential transmissibility in Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available The aggregation of amyloid-β (Aβ peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD. The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates a transmissible nature of Aβ aggregates and implicates a prion-like mechanism of oligomer propagation, which manifests as the dissemination and proliferation of Aβ toxicity. Despite accumulating evidence in support of a transmissible nature of Aβ aggregates, a clear, molecular-level understanding of this intriguing mechanism is lacking. Recently, we reported the characterization of unique replicating oligomers of Aβ42 (12-24 mers in vitro called Large Fatty Acid-derived Oligomers (LFAOs (Kumar et al., 2012, J. Biol. Chem. In the current report, we establish that LFAOs possess physiological activity by activating NF-κB in human neuroblastoma cells, and determine the experimental parameters that control the efficiency of LFAO replication by self-propagation. These findings constitute the first detailed report on monomer - oligomer lateral propagation reactions that may constitute potential mechanism governing transmissibility among Aβ oligomers. These data support the previous reports on transmissible mechanisms observed in transgenic animal models.

  4. Electrochemical behavior of antioxidants: Part 3. Electrochemical studies of caffeic Acid–DNA interaction and DNA/carbon nanotube biosensor for DNA damage and protection

    Directory of Open Access Journals (Sweden)

    Refat Abdel-Hamid

    2016-05-01

    Full Text Available Multi-walled carbon nanotubes-modified glassy carbon electrode biosensor was used for electrochemical studies of caffeic acid–dsDNA interaction in phosphate buffer solution at pH 2.12. Caffeic acid, CAF, shows a well-defined cyclic voltammetric wave. Its anodic peak current decreases and the peak potential shifts positively on the addition of dsDNA. This behavior was ascribed to an interaction of CAF with dsDNA giving CAF–dsDNA complex by intercalative binding mode. The apparent binding constant of CAF–dsDNA complex was determined using amperometric titrations. The oxidative damage caused to DNA was detected using the biosensor. The damage caused by the reactive oxygen species, hydroxyl radical (·−OH generated by the Fenton system on the DNA-biosensor was detected. It was found that CAF has the capability of scavenging the hydroxide radical and protecting the DNA immobilized on the GCE surface.

  5. Emitting oligomer containing quinoline group: Synthesis and photophysical properties of conjugated oligomer obtained by Wittig reaction

    Energy Technology Data Exchange (ETDEWEB)

    Karpagam, S., E-mail: skarpagam80@yahoo.com [Organic Chemistry Division, School of Advanced Science, VIT University, Vellore 14, Tamil Nadu (India); Guhanathan, S. [Department of Chemistry, Muthurangam Government Arts College, Vellore, Tamil Nadu (India)

    2014-01-15

    Dichloro quinoline substituted phenylene vinylene oligomer (QUI-OPV) was synthesized via Wittig route. Formation of the oligomer was characterized by spectral (FTIR, {sup 1}H and {sup 13}C NMR), elemental and gel permeation chromatography analysis. The oligomer possesses excellent thermal stability (decomposition temperature 470 °C), solubility in common organic solvents and high glass transition temperature (61 °C). The morphology of the oligomer film of one dimensional (1D) and three dimensional (3D) architectures was observed using atomic force microscopy (AFM). In CHCl{sub 3} solution, the oligomer showed the absorption maxima at 382 nm and also observed excellent photoluminescence (PL) with bluish green emission maxima at shorter wavelengths of 477 nm. The introduction of quinoline to the main chain resulted in a slight decrease of effective conjugation length and exhibited the blue shift in both the absorption and emission spectra. -- Highlights: • Simple synthesis of quinoline functionalized phenylene vinylene oligomer by Wittig route. • The materials had good organosolubility and intrinsic viscosity. • High thermal stability and good surface roughness morphology were observed. • Performance of luminescence improved via introducing quinoline into PPV. • Electrochemical and optical band gap of the oligomer were consistent with each other.

  6. MODIFICATION OLIGOMER DERIVED FROM BY-PRODUCTS OF POLYBUTADIENE USING WASTE OF PRODUCTION OF PHTHALIC ANHYDRIDE

    Directory of Open Access Journals (Sweden)

    N. S. Nikulina

    2013-01-01

    Full Text Available The modification of the oligomer synthesized from polybutadiene waste byproducts formed during the production of phthalic anhydride comprising as a main component maleic acid was studied. The influence of temperature, duration of the process and content of the waste on the properties of the resulting product was considered.

  7. Protonating polymer oligomers in the gas phase to change fragmentation pathways.

    Science.gov (United States)

    Alhazmi, Abdulrahman M; Mayer, Paul M

    2009-01-01

    Ionization of polymers in mass spectrometry is usually achieved by forming metal ion adducts. The metal ion has been shown by Wesdemiotis to often play a spectator role in the collision-induced dissociation (CID) chemistry of these species, wherein they fragment according to a free-radical mechanism similar to that found in their pyrolysis. The result is a predominance of low-mass ions in the CID mass spectrum. We have changed this behavior by generating protonated oligomers in the gas phase by first forming proton-bound complexes of the oligomers with amino acids or peptides by electrospray ionization. These complexes dissociate first by loss of the amino acid/peptide to form protonated oligomers, which then undergo a unique fragmentation chemistry. In this article we discuss the results for poly(methyl methacrylate) (PMMA) and poly(butyl acrylate) (PBA). Initially, protonated PMMA and PBA lose methanol and butanol, respectively, from the side chains of the respective monomers. The resulting PMMA-derived ion then undergoes a series of neutral losses corresponding to 32 and 28 Da, methanol and carbon monoxide. This continues as collision energy increases until a final, carbon-rich backbone ion is formed, which then undergoes a classic hydrocarbon fragmentation pattern. The PBA-derived ions are proposed to fragment by the loss of butylether molecules to form anhydride rings along the oligomer chain. The number of ether molecules lost corresponded to half the number of available side chains in the oligomer. The resulting poly-anhydride ion dissociates by small molecule loss. Mechanisms have been suggested for the fragmentation chemistry of these two classes of oligomers.

  8. 40 CFR 721.10081 - Aromatic urethane acrylate oligomer (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aromatic urethane acrylate oligomer... Specific Chemical Substances § 721.10081 Aromatic urethane acrylate oligomer (generic). (a) Chemical... as aromatic urethane acrylate oligomer (PMN P-06-26) is subject to reporting under this section for...

  9. Statistical mechanics of thermal denaturation of DNA oligomers

    Indian Academy of Sciences (India)

    Double stranded DNA chain is known to have non-trivial elasticity. We study the effect of this elasticity on the denaturation profile of DNA oligomer by constraining one base pair at one end of the oligomer to remain in unstretched (or intact) state. The effect of this constraint on the denaturation profile of the oligomer has been ...

  10. Dual Myostatin and Dystrophin Exon Skipping by Morpholino Nucleic Acid Oligomers Conjugated to a Cell-penetrating Peptide Is a Promising Therapeutic Strategy for the Treatment of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Alberto Malerba

    2012-01-01

    Full Text Available The knockdown of myostatin, a negative regulator of skeletal muscle mass may have important implications in disease conditions accompanied by muscle mass loss like cancer, HIV/AIDS, sarcopenia, muscle atrophy, and Duchenne muscular dystrophy (DMD. In DMD patients, where major muscle loss has occurred due to a lack of dystrophin, the therapeutic restoration of dystrophin expression alone in older patients may not be sufficient to restore the functionality of the muscles. We recently demonstrated that phosphorodiamidate morpholino oligomers (PMOs can be used to re-direct myostatin splicing and promote the expression of an out-of-frame transcript so reducing the amount of the synthesized myostatin protein. Furthermore, the systemic administration of the same PMO conjugated to an octaguanidine moiety (Vivo-PMO led to a significant increase in the mass of soleus muscle of treated mice. Here, we have further optimized the use of Vivo-PMO in normal mice and also tested the efficacy of the same PMO conjugated to an arginine-rich cell-penetrating peptide (B-PMO. Similar experiments conducted in mdx dystrophic mice showed that B-PMO targeting myostatin is able to significantly increase the tibialis anterior (TA muscle weight and when coadministered with a B-PMO targeting the dystrophin exon 23, it does not have a detrimental interaction. This study confirms that myostatin knockdown by exon skipping is a potential therapeutic strategy to counteract muscle wasting conditions and dual myostatin and dystrophin skipping has potential as a therapy for DMD.

  11. Template-based modeling and ab initio refinement of protein oligomer structures using GALAXY in CAPRI round 30.

    Science.gov (United States)

    Lee, Hasup; Baek, Minkyung; Lee, Gyu Rie; Park, Sangwoo; Seok, Chaok

    2017-03-01

    Many proteins function as homo- or hetero-oligomers; therefore, attempts to understand and regulate protein functions require knowledge of protein oligomer structures. The number of available experimental protein structures is increasing, and oligomer structures can be predicted using the experimental structures of related proteins as templates. However, template-based models may have errors due to sequence differences between the target and template proteins, which can lead to functional differences. Such structural differences may be predicted by loop modeling of local regions or refinement of the overall structure. In CAPRI (Critical Assessment of PRotein Interactions) round 30, we used recently developed features of the GALAXY protein modeling package, including template-based structure prediction, loop modeling, model refinement, and protein-protein docking to predict protein complex structures from amino acid sequences. Out of the 25 CAPRI targets, medium and acceptable quality models were obtained for 14 and 1 target(s), respectively, for which proper oligomer or monomer templates could be detected. Symmetric interface loop modeling on oligomer model structures successfully improved model quality, while loop modeling on monomer model structures failed. Overall refinement of the predicted oligomer structures consistently improved the model quality, in particular in interface contacts. Proteins 2017; 85:399-407. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. A quantification method for heat-decomposable methylglyoxal oligomers and its application on 1,3,5-trimethylbenzene SOA

    Science.gov (United States)

    Rodigast, Maria; Mutzel, Anke; Herrmann, Hartmut

    2017-03-01

    Methylglyoxal forms oligomeric compounds in the atmospheric aqueous particle phase, which could establish a significant contribution to the formation of aqueous secondary organic aerosol (aqSOA). Thus far, no suitable method for the quantification of methylglyoxal oligomers is available despite the great effort spent for structure elucidation. In the present study a simplified method was developed to quantify heat-decomposable methylglyoxal oligomers as a sum parameter. The method is based on the thermal decomposition of oligomers into methylglyoxal monomers. Formed methylglyoxal monomers were detected using PFBHA (o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride) derivatisation and gas chromatography-mass spectrometry (GC/MS) analysis. The method development was focused on the heating time (varied between 15 and 48 h), pH during the heating process (pH = 1-7), and heating temperature (50, 100 °C). The optimised values of these method parameters are presented. The developed method was applied to quantify heat-decomposable methylglyoxal oligomers formed during the OH-radical oxidation of 1,3,5-trimethylbenzene (TMB) in the Leipzig aerosol chamber (LEipziger AerosolKammer, LEAK). Oligomer formation was investigated as a function of seed particle acidity and relative humidity. A fraction of heat-decomposable methylglyoxal oligomers of up to 8 % in the produced organic particle mass was found, highlighting the importance of those oligomers formed solely by methylglyoxal for SOA formation. Overall, the present study provides a new and suitable method for quantification of heat-decomposable methylglyoxal oligomers in the aqueous particle phase.

  13. Electrophoretic studies of polygalacturonate oligomers and their interactions with metal ions.

    Science.gov (United States)

    Wiedmer, S K; Cassely, A; Hong, M; Novotny, M V; Riekkola, M L

    2000-09-01

    Polygalacturonic acid, a linear homopolysaccharide, was investigated by capillary electrophoresis (CE) using linear polyacrylamide-coated capillaries and laser-induced fluorescence (LIF) detection. A successful separation of its fluorescently labeled oligomers was achieved through sieving in polyacrylamide entangled matrices. The reaction conditions for the derivatization of polygalacturonic acid were optimized. In studying the interactions between polygalacturonic acid and various metal ions, the end-label, free-solution electrophoretic (ELFSE) technique, developed earlier in our laboratory (Sudor, J., Novotny, M. V., Anal. Chem. 1995, 67, 4205-4209) was found preferable to the sieving method. ELFSE is fast and convenient in that no polymer solutions are needed for the separation. The investigation showed that for the moderately large oligomers, the strongest binding occurred with calcium and cadmium ions, while the smallest interaction was observed with magnesium ions.

  14. Oligomer in polystyrene; Porisuchiren chu no origoma

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, J.

    2000-02-05

    In polystyrene used for the housing of electric appliances and cup noodle containers, it is known that oligomers such as dimers and trimers exist, and performance such as machining performance and the thermal instability of polystyrene is affected. Kawamura has evaluated the instant food keeping in the polystyrene container of 32 varieties, and the conversion of the styrene dimers and trimers from the container by cooking. Yamada has proven that the standard of styrene oligomer of about 25 samples confirmed by by-products under polystyrene manufacturing, heat decomposition, material analysis and dissolution test is synthesized, the biological evaluation is carried out for the chemical compound confirmed that dissolving from the container out, anyway does not have the estrogenicity action. In addition, Honishi has announced that the styrene extracted by ethanol which is reported in the Current State Report of the Cup Container for the Food by the Japan Styrene Industry Association, did not show the estrogenicity. (NEDO)

  15. Cure Chemistry of Phenylethynyl Terminated Oligomers

    Science.gov (United States)

    Wood, Karen H.; Orwoll, Robert A.; Young, Philip R.; Jensen, Brian J.; McNair, Harold M.

    1997-01-01

    The ability to process high performance polymers into quality, void-free composites has been significantly advanced using oligomers terminated with reactive groups which cure or crosslink at elevated temperature without the evolution of volatile byproducts. Several matrix resin systems of considerable interest to the aerospace community utilize phenylethynyl-terminated imide (PETI) technology to achieve this advantage. The present paper addresses the cure chemistry of PETI oligomers. The thermal cure of a low molecular weight model compound was studied using a variety of analytical techniques including differential scanning calorimetry, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectroscopy. The studies indicate an extremely complex cure process. Many stable products were isolated and this paper reports current work on identification of those products. The intent of this research is to provide fundamental insight into the molecular structure of the cured PETI engineering materials so that performance and durability can be more fully assessed.

  16. 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...

  17. Chicoric Acid Found in Basil (Ocimum basilicum L.) Leaves

    Science.gov (United States)

    This is the first report to identify the presence of chicoric acid (cichoric acid; also known as dicaffeoyltartaric acid) in basil leaves. Rosmarinic acid, chicoric acid, and caftaric acid (in the order of most abundant to least; all derivatives of caffeic acid) were identified in fresh basil leaves...

  18. Peptide oligomers for holographic data storage

    DEFF Research Database (Denmark)

    Berg, Rolf Henrik; Hvilsted, Søren; Ramanujam, P.S.

    1996-01-01

    chromophores-which appear particularly promising for erasable holographic data storage applications. The rationale for our approach is to use the structural properties of peptide-like molecules to impose orientational order on the chromophores, and thereby optimize the optical properties of the resulting...... materials. Here we show that holographic gratings with large first-order diffraction efficiencies (up to 80%) can be written and erased optically in oligomer films only a few micrometres thick. The holograms also exhibit good thermal stability, and are not erased after heating to 180 degrees C for one month...

  19. Biocatalytic Synthesis of Fluorescent Conjugated Indole Oligomers

    Directory of Open Access Journals (Sweden)

    Ryan M. Bouldin

    2014-12-01

    Full Text Available Fluorescent conjugated materials exhibiting reasonable biocompatibility that are capable of interacting with biological molecules are of interest for bio-sensing and imaging applications. Traditional approaches do not allow for the synthesis of conjugated materials in the presence of biologically relevant substrates. Further conjugated polymers synthesized using conventional methods are doped and not fluorescent. Here we explore the possibility of synthesizing fluorescent oligomers of indole using enzymes as catalyst under mild conditions. The peroxidase catalyzed coupling reaction presented here creates a photoluminescent material that allows for direct utilization (without purification and separation of the dopant in biosensing applications. The polymerization reaction proceeds smoothly in just deionized water and ethanol. Monitoring of the absorption and fluorescence spectra over one hour shows that the concentration of both absorbing and emitting species grows steadily over time. The presence of anionic buffers and templates is shown to effectively retard the development of light emitting species and instead leads to the formation of an electrically doped conjugated polymer. Structural characterization through FTIR and 1H-NMR analysis suggests that the oligomer is coupled through the 2 and 3 positions on the indole ring.

  20. Isolation and Quantification of Polyamide Cyclic Oligomers in Kitchen Utensils and Their Migration into Various Food Simulants.

    Science.gov (United States)

    Abe, Yutaka; Mutsuga, Motoh; Ohno, Hiroyuki; Kawamura, Yoko; Akiyama, Hiroshi

    2016-01-01

    Small amounts of cyclic monomers and oligomers are present in polyamide (PA)-based kitchen utensils. In this study, we isolated eight PA-based cyclic monomers and oligomers from kitchen utensils made from PA6 (a polymer of ε-caprolactam) and PA66 (a polymer of 1,6-diaminohexane and adipic acid). Their structures were identified using high-resolution mass spectrometry and 1H- and 13C-nuclear magnetic resonance spectroscopy, and their residual levels in PA-based kitchen utensils and degree of migration into food simulants were quantified by high-performance liquid chromatography/mass spectrometry using purchased PA6 monomer and isolated PA66 monomers, and isolated PA6 and PA66 oligomers as calibration standards. Their total residual levels among 23 PA-based kitchen utensils made from PA6, PA66, and copolymers of PA6 and PA66 (PA6/66) ranged from 7.8 to 20 mg/g. Using water, 20% ethanol, and olive oil as food simulants, the total migration levels of the PA monomers and oligomers ranged from 0.66 to 100 μg/cm2 under most examined conditions. However, the total migration levels of the PA66 monomer and oligomers from PA66 and PA6/66 kitchen utensils into 20% ethanol at 95°C were very high (1,700 and 2,200 μg/cm2, respectively) due to swelling by high-temperature ethanol.

  1. Synthesis and characterization of thermally stable oligomer-metal ...

    African Journals Online (AJOL)

    Synthesis and characterization of thermally stable oligomer-metal complexes of copper(II), nickel(II), zinc(II) and cobalt(II) derived from oligo- p - nitrophenylazomethinephenol. ... The properties of oligomer-metal complexes were studied by elemental, FT-IR and magnetic moments analyses. The thermal stabilities of the ...

  2. The Challenge of Synthesizing Oligomers for Molecular Wires

    DEFF Research Database (Denmark)

    Søndergaard, Roar; Krebs, Frederik C

    2011-01-01

    molecules with a molecular length up to 9–10 nm which allow for the introduction of aromatic thioacetate functionality in fully conjugated oligomer systems. Oligomers containing 3–15 phenyl units were synthesized by step wise Horner-Wadsworth-Emmons (HWE) reactions of a bifunctional OPV-monomer, which...

  3. Atomic View of a Toxic Amyloid Small Oligomer

    Energy Technology Data Exchange (ETDEWEB)

    Laganowsky, Arthur; Liu, Cong; Sawaya, Michael R.; Whitelegge, Julian P.; Park, Jiyong; Zhao, Minglei; Pensalfini, Anna; Soriaga, Angela B.; Landau, Meytal; Teng, Poh K.; Cascio, Duilio; Glabe, Charles; Eisenberg, David (UCI); (UCLA)

    2012-04-30

    Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein {alpha}{beta} crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: {beta}-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the {beta}-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

  4. An Open-Circuit Voltage and Power Conversion Efficiency Study of Fullerene Ternary Organic Solar Cells Based on Oligomer/Oligomer and Oligomer/Polymer.

    Science.gov (United States)

    Zhang, Guichuan; Zhou, Cheng; Sun, Chen; Jia, Xiaoe; Xu, Baomin; Ying, Lei; Huang, Fei; Cao, Yong

    2017-07-01

    Variations in the open-circuit voltage (V oc ) of ternary organic solar cells are systematically investigated. The initial study of these devices consists of two electron-donating oligomers, S2 (two units) and S7 (seven units), and the electron-accepting [6,6]-phenyl C71 butyric acid methyl ester (PC 71 BM) and reveals that the V oc is continuously tunable due to the changing energy of the charge transfer state (E ct ) of the active layers. Further investigation suggests that V oc is also continuously tunable upon change in E ct in a ternary blend system that consists of S2 and its corresponding polymer (P11):PC 71 BM. It is interesting to note that higher power conversion efficiencies can be obtained for both S2:S7:PC 71 BM and S2:P11:PC 71 BM ternary systems compared with their binary systems, which can be ascribed to an improved V oc due to the higher E ct and an improved fill factor due to the improved film morphology upon the incorporation of S2. These findings provide a new guideline for the future design of conjugated polymers for achieving higher performance of ternary organic solar cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. HAMLET forms annular oligomers when deposited with phospholipid monolayers.

    Science.gov (United States)

    Baumann, Anne; Gjerde, Anja Underhaug; Ying, Ming; Svanborg, Catharina; Holmsen, Holm; Glomm, Wilhelm R; Martinez, Aurora; Halskau, Oyvind

    2012-04-20

    Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Synthesis of a Series of Caffeic Acid Phenethyl Amide (CAPA) Fluorinated Derivatives: Comparison of Cytoprotective Effects to Caffeic Acid Phenethyl Ester (CAPE)

    Science.gov (United States)

    2010-06-11

    analysis was performed using the JMP program (SAS). Acknowledgments This project was supported by the US Army Institute of Surgical Research, the Robert ... Robert , A.; Meunier, B.; Boissier, J.; Cosledan, F.; Gornitzka, H. Eur. J. Org. Chem. 2008. 26. Kunduzova, O. R.; Bianchi, P.; Parini, A.; Cambon, C...K. L.; Olubajo, O.; Buchhold, K.; Lewandowski , G. A.; Gusovsky, F.; McCulloh, D.; Daly, J. W.; Creveling, C. R. J. Med. Chem. 1986, 29, 1982. 30. Wang

  7. Enzymatic sequencing of partially acetylated chitosan oligomers.

    Science.gov (United States)

    Hamer, Stefanie Nicole; Moerschbacher, Bruno Maria; Kolkenbrock, Stephan

    2014-06-17

    Chitosan oligosaccharides have diverse biological activities with potentially valuable applications, for example, in the fields of medicine and agriculture. These functionalities are thought to depend on their degree of polymerization and acetylation, and possibly on specific patterns of acetylation. Chitosan oligomers with fully defined architecture are difficult to produce, and their complete analysis is demanding. Analysis is typically done using MS or NMR, requiring access to expensive infrastructure, and yielding unequivocal results only in the case of rather small oligomers. We here describe a simple and cost-efficient method for the sequencing of μg amounts of chitosan oligosaccharides which is based on the sequential action of two recombinant glycosidases, namely an exo-β-N-acetylhexosaminidase (GlcNAcase) from Bacillus subtilis 168 and an exo-β-d-glucosaminidase (GlcNase) from Thermococcus kodakarensis KOD1. Starting from the non-reducing end, GlcNAcase and GlcNase specifically remove N-acetyl glucosamine (A) and glucosamine (D) units, respectively. By the sequential addition and removal of these enzymes in an alternating way followed by analysis of the products using high-performance thin-layer chromatography, the sequence of chitosan oligosaccharides can be revealed. Importantly, both enzymes work under identical conditions so that no buffer exchange is required between steps, and the enzyme can be removed conveniently using simple ultra-filtration devices. As proof-of-principle, the method was used to sequence the product of enzymatic deacetylation of chitin pentamer using a recombinant chitin deacetylase from Vibrio cholerae which specifically removes the acetyl group from the second unit next to the non-reducing end of the substrate, yielding mono-deacetylated pentamer with the sequence ADAAA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Association Thermodynamics and Conformational Stability of β-Sheet Amyloid β(17-42) Oligomers: Effects of E22Q (Dutch) Mutation and Charge Neutralization

    Science.gov (United States)

    Blinov, Nikolay; Dorosh, Lyudmyla; Wishart, David; Kovalenko, Andriy

    2010-01-01

    Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Aβ17–42 oligomers with different protonation states of Glu22, as well the E22Q (Dutch) mutants. The association free energy of small β-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the β-sheet oligomers. The charge reduction of the wild-type Aβ17–42 oligomers upon protonation of the solvent-exposed Glu22 at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type Aβ17–42 oligomers at neutral pH and the Dutch mutants, on the one hand, and the Aβ17–42 oligomers with

  9. Association thermodynamics and conformational stability of beta-sheet amyloid beta(17-42) oligomers: effects of E22Q (Dutch) mutation and charge neutralization.

    Science.gov (United States)

    Blinov, Nikolay; Dorosh, Lyudmyla; Wishart, David; Kovalenko, Andriy

    2010-01-20

    Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Abeta(17-42) oligomers with different protonation states of Glu(22), as well the E22Q (Dutch) mutants. The association free energy of small beta-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the beta-sheet oligomers. The charge reduction of the wild-type Abeta(17-42) oligomers upon protonation of the solvent-exposed Glu(22) at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type Abeta(17-42) oligomers at neutral pH and the Dutch mutants, on the one hand, and the Abeta(17

  10. Toxic species in amyloid disorders: Oligomers or mature fibrils

    Directory of Open Access Journals (Sweden)

    Meenakshi Verma

    2015-01-01

    Full Text Available Protein aggregation is the hallmark of several neurodegenerative disorders. These protein aggregation (fibrillization disorders are also known as amyloid disorders. The mechanism of protein aggregation involves conformation switch of the native protein, oligomer formation leading to protofibrils and finally mature fibrils. Mature fibrils have long been considered as the cause of disease pathogenesis; however, recent evidences suggest oligomeric intermediates formed during fibrillization to be toxic. In this review, we have tried to address the ongoing debate for these toxic amyloid species. We did an extensive literature search and collated information from Pubmed (http://www.ncbi.nlm.nih.gov and Google search using various permutations and combinations of the following keywords: Neurodegeneration, amyloid disorders, protein aggregation, fibrils, oligomers, toxicity, Alzheimer′s Disease, Parkinson′s Disease. We describe different instances showing the toxicity of mature fibrils as well as oligomers in Alzheimer′s Disease and Parkinson′s Disease. Distinct structural framework and morphology of amyloid oligomers suggests difference in toxic effect between oligomers and fibrils. We highlight the difference in structure and proposed toxicity pathways for fibrils and oligomers. We also highlight the evidences indicating that intermediary oligomeric species can act as potential diagnostic biomarker. Since the formation of these toxic species follow a common structural switch among various amyloid disorders, the protein aggregation events can be targeted for developing broad-range therapeutics. The therapeutic trials based on the understanding of different protein conformers (monomers, oligomers, protofibrils and fibrils in amyloid cascade are also described.

  11. Thermogravimetry for measuring the molecular mass distribution of perfluorinated oligomers

    Science.gov (United States)

    Kim, I. P.; Kolesnikova, A. M.

    2011-09-01

    A method for determinoffing the molecular mass distribution (MMD) in mixtures of perfluorinated oligomers based on analysis of the differential thermogravimetric (DTG) curves (temperature dependences of the rate of mass loss) is proposed. It is indicated that this method allows us to measure the MMD of oligomers whose boiling temperature is less than the temperature of their thermal decomposition, and the total portion of longer oligomers. This method was applied to the determination of MMD of products of the radiation-chemical telomerization of tetrafluoroethylene in solution.

  12. Indirubin Derivative 7-Bromoindirubin-3-Oxime (7Bio Attenuates Aβ Oligomer-Induced Cognitive Impairments in Mice

    Directory of Open Access Journals (Sweden)

    Liping Chen

    2017-11-01

    Full Text Available Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio, an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5 and glycogen synthase kinase-3β (GSK3β, two pharmacological targets of Alzheimer's disease (AD. In this study, we have discovered that 2.3–23.3 μg/kg 7Bio effectively prevented β-amyloid (Aβ oligomer-induced impairments of spatial cognition and recognition without affecting bodyweight and motor functions in mice. Moreover, 7Bio potently inhibited Aβ oligomer-induced expression of interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α. Furthermore, 7Bio significantly prevented the decreased expression of synapsin-1 and PSD-95, biomarkers of pre-synaptic and post-synaptic proteins in Aβ oligomer-treated mice. The mean optical density (OD with hyper-phosphorylated tau (pTau, glial fibrillary acidic protein (GFAP and CD45 positive staining in the hippocampus of 7Bio-treated mice were significantly decreased compared to those of Aβ oligomer-treated mice. In addition, Western blotting analysis showed that 7Bio attenuated Aβ oligomer-decreased expression of pSer9-GSK3β. Those results suggested that 7Bio could potently inhibit Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, and activation of astrocytes and microglia, which may contribute to the neuroprotective effects of 7Bio. Based on these findings, we expected that 7Bio might be developed as a novel anti-AD lead compound.

  13. Annular Protofibrils Are a Structurally and Functionally Distinct Type of Amyloid Oligomer*

    OpenAIRE

    Kayed, Rakez; Pensalfini, Anna; Margol, Larry; Sokolov, Yuri; Sarsoza, Floyd; Head, Elizabeth; Hall, James; Glabe, Charles

    2009-01-01

    Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides ...

  14. Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

    Science.gov (United States)

    Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

    2013-09-01

    Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

  15. SAXS and stability studies of iron-induced oligomers of bacterial frataxin CyaY.

    Directory of Open Access Journals (Sweden)

    Mostafa Fekry

    Full Text Available Frataxin is a highly conserved protein found in both prokaryotes and eukaryotes. It is involved in several central functions in cells, which include iron delivery to biochemical processes, such as heme synthesis, assembly of iron-sulfur clusters (ISC, storage of surplus iron in conditions of iron overload, and repair of ISC in aconitase. Frataxin from different organisms has been shown to undergo iron-dependent oligomerization. At least two different classes of oligomers, with different modes of oligomer packing and stabilization, have been identified. Here, we continue our efforts to explore the factors that control the oligomerization of frataxin from different organisms, and focus on E. coli frataxin CyaY. Using small-angle X-ray scattering (SAXS, we show that higher iron-to-protein ratios lead to larger oligomeric species, and that oligomerization proceeds in a linear fashion as a results of iron oxidation. Native mass spectrometry and online size-exclusion chromatography combined with SAXS show that a dimer is the most common form of CyaY in the presence of iron at atmospheric conditions. Modeling of the dimer using the SAXS data confirms the earlier proposed head-to-tail packing arrangement of monomers. This packing mode brings several conserved acidic residues into close proximity to each other, creating an environment for metal ion binding and possibly even mineralization. Together with negative-stain electron microscopy, the experiments also show that trimers, tetramers, pentamers, and presumably higher-order oligomers may exist in solution. Nano-differential scanning fluorimetry shows that the oligomers have limited stability and may easily dissociate at elevated temperatures. The factors affecting the possible oligomerization mode are discussed.

  16. A new source of oxygenated organic aerosol and oligomers

    Directory of Open Access Journals (Sweden)

    J. Liggio

    2013-03-01

    Full Text Available A large oxygenated organic uptake to aerosols was observed when exposing ambient urban air to inorganic acidic and non-acidic sulfate seed aerosol. For non-acidic seed aerosol the uptake was attributed to the direct dissolution of primary vehicle exhaust gases into the aqueous aerosol fraction, and was correlated to the initial seed sulphate mass. The uptake of primary oxygenated organic gases to aerosols in this study represents a significant amount of organic aerosol (OA that may be considered primary when compared to that reported for primary organic aerosol (POA, but is considerably more oxygenated (O : C ~ 0.3 than traditional POA. Consequently, a fraction of measured ambient oxygenated OA, which correlates with secondary sulphate, may in fact be of a primary, rather than secondary source. These results represent a new source of oxygenated OA on neutral aerosol and imply that the uptake of primary organic gases will occur in the ambient atmosphere, under dilute conditions, and in the presence of pre-existing SO4 aerosols which contain water. Conversely, under acidic seed aerosol conditions, oligomer formation was observed with the uptake of organics being enhanced by a factor of three or more compared to neutral aerosols, and in less than 2 min, representing an additional source of SOA to the atmosphere. This resulted in a trajectory in Van Krevelen space towards higher O : C (slope ~ −1.5, despite a lack of continual gas-phase oxidation in this closed system. The results demonstrate that high molecular weight species will form on acidic aerosols at the ambient level and mixture of organic gases, but are otherwise unaffected by subsequent aerosol neutralization, and that aerosol acidity will affect the organic O : C via aerosol-phase reactions. These two processes, forming oxygenated POA under neutral conditions and SOA under acidic conditions can contribute to the total ambient OA mass and the evolution of ambient aerosol O : C ratios

  17. Chemical Fluorescent Probe for Detection of Aβ Oligomers.

    Science.gov (United States)

    Teoh, Chai Lean; Su, Dongdong; Sahu, Srikanta; Yun, Seong-Wook; Drummond, Eleanor; Prelli, Frances; Lim, Sulgi; Cho, Sunhee; Ham, Sihyun; Wisniewski, Thomas; Chang, Young-Tae

    2015-10-28

    Aggregation of amyloid β-peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), with the soluble, Aβ oligomeric species thought to be the critical pathological species. Identification and characterization of intermediate species formed during the aggregation process is crucial to the understanding of the mechanisms by which oligomeric species mediate neuronal toxicity and following disease progression. Probing these species proved to be extremely challenging, as evident by the lack of reliable sensors, due to their heterogeneous and transient nature. We describe here an oligomer-specific fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), developed through the use of the diversity-oriented fluorescent library approach (DOFLA) and high-content, imaging-based screening. This probe enables dynamic oligomer monitoring during fibrillogenesis in vitro and shows in vivo Aβ oligomers staining possibility in the AD mice model.

  18. Breaking the Code of Amyloid-β Oligomers

    Directory of Open Access Journals (Sweden)

    Sylvain E. Lesné

    2013-01-01

    Full Text Available Departing from the original postulates that defined various neurodegenerative disorders, accumulating evidence supports a major role for soluble forms of amyloid proteins as initiator toxins in Alzheimer’s disease, Parkinson’s disease, frontotemporal dementias, and prion diseases. Soluble multimeric assemblies of amyloid-β, tau, α-synuclein, and the prion protein are generally englobed under the term oligomers. Due to their biophysical properties, soluble amyloid oligomers can adopt multiple conformations and sizes that potentially confer differential biological activities. Therein lies the problem: with sporadic knowledge and limited tools to identify, characterize, and study amyloid oligomers, how can we solve the enigma of their respective role(s in the pathogenesis of neurodegenerative disorders? To further our understanding of these devastating diseases, the code of the amyloid oligomers must be broken.

  19. GalaxyHomomer: a web server for protein homo-oligomer structure prediction from a monomer sequence or structure.

    Science.gov (United States)

    Baek, Minkyung; Park, Taeyong; Heo, Lim; Park, Chiwook; Seok, Chaok

    2017-04-06

    Homo-oligomerization of proteins is abundant in nature, and is often intimately related with the physiological functions of proteins, such as in metabolism, signal transduction or immunity. Information on the homo-oligomer structure is therefore important to obtain a molecular-level understanding of protein functions and their regulation. Currently available web servers predict protein homo-oligomer structures either by template-based modeling using homo-oligomer templates selected from the protein structure database or by ab initio docking of monomer structures resolved by experiment or predicted by computation. The GalaxyHomomer server, freely accessible at http://galaxy.seoklab.org/homomer, carries out template-based modeling, ab initio docking or both depending on the availability of proper oligomer templates. It also incorporates recently developed model refinement methods that can consistently improve model quality. Moreover, the server provides additional options that can be chosen by the user depending on the availability of information on the monomer structure, oligomeric state and locations of unreliable/flexible loops or termini. The performance of the server was better than or comparable to that of other available methods when tested on benchmark sets and in a recent CASP performed in a blind fashion. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Overall and specific migration from multilayer high barrier food contact materials - kinetic study of cyclic polyester oligomers migration.

    Science.gov (United States)

    Úbeda, Sara; Aznar, Margarita; Vera, Paula; Nerín, Cristina; Henríquez, Luis; Taborda, Laura; Restrepo, Claudia

    2017-10-01

    Most multilayer high barrier materials used in food packaging have a polyurethane adhesive layer in their structures. In order to assess the safety of these materials, it is important to determine the compounds intentionally added to the adhesives (IAS) as well as those non-intentionally added substances (NIAS). During the manufacture of polyurethane adhesives, some by-products can be formed, such as cyclic polyester oligomers coming from the reaction between dicarboxylic acids and glycols. Since these compounds are not listed in the Regulation 10/2011/EU, they should not be found in migration above 0.01 mg/kg of simulant. In this study two flexible multilayer packaging materials were used and migration was evaluated in simulant A (ethanol 10% v/v), simulant B (acetic acid 3% w/v) and simulant ethanol 95% v/v during 10 days at 60ºC. Identification and quantification of non-volatile compounds was carried out by UPLC-MS-QTOF. Most of migrants were oligomers such as cyclic polyesters and caprolactam oligomers. Overall migration and specific migration of adipic acid-diethylene glycol and phthalic acid-diethylene glycol were monitored over time and analysed by UPLC-MS-TQ. In most cases, ethanol 95% v/v was the simulant with the highest concentration values. Overall migration kinetics followed a similar pattern than specific migration kinetics.

  1. Amplifying (Im)perfection: The Impact of Crystallinity in Discrete and Disperse Block Co-oligomers.

    Science.gov (United States)

    van Genabeek, Bas; Lamers, Brigitte A G; de Waal, Bas F M; van Son, Martin H C; Palmans, Anja R A; Meijer, E W

    2017-10-25

    Crystallinity is seldomly utilized as part of the microphase segregation process in ultralow-molecular-weight block copolymers. Here, we show the preparation of two types of discrete, semicrystalline block co-oligomers, comprising an amorphous oligodimethylsiloxane block and a crystalline oligo-l-lactic acid or oligomethylene block. The self-assembly of these discrete materials results in lamellar structures with unforeseen uniformity in the domain spacing. A systematic introduction of dispersity reveals the extreme sensitivity of the microphase segregation process toward chain length dispersity in the crystalline block.

  2. Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers

    Science.gov (United States)

    Rosmarinic acid (RA), a caffeic acid derivative found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be of benefit t...

  3. A thermal-cycling method for disaggregating monoclonal antibody oligomers.

    Science.gov (United States)

    Sadavarte, Rahul H; Ghosh, Raja

    2014-03-01

    Non-native oligomeric forms of biopharmaceutical proteins are therapeutically inactive, and potentially toxic and immunogenic, and therefore undesirable in pharmaceutical formulations. Immunoglobulin G class of antibodies are known to form stable nonnative oligomers through Fab-Fab interactions. In this paper, we investigate thermal-cycling as a technique for disaggregating antibody oligomers. Aggregate containing monoclonal antibody (mAb) samples were exposed to rapid heating and cooling cycles in a thermal-cycler. The heating phase of the thermal-cycle resulted in partial unfolding of the Fab domain, leading to the release of monomer from the oligomer complexes, whereas the rapid cooling that followed led to refolding and minimized the probability of protein reaggregation. The extent of mAb oligomer disaggregation was determined by size-exclusion chromatography and hydrophobic interaction membrane chromatography, whereas protein refolding was assessed by circular dichroism spectroscopy. The thermal-cycling technique in addition to being suitable for disaggregating protein oligomer samples could also potentially be useful for studying the mechanisms of protein aggregation and disaggregation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Resveratrol Oligomers for the Prevention and Treatment of Cancers

    Directory of Open Access Journals (Sweden)

    You-Qiu Xue

    2014-01-01

    Full Text Available Resveratrol (3,4′,5-trihydroxystilbene is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers.

  5. The effect of caffeic acid phenethyl ester and thymoquinone on otitis media with effusion in rats.

    Science.gov (United States)

    Gülmez, Mehmet İhsan; Okuyucu, Şemsettin; Dokuyucu, Recep; Gökçe, Hasan

    2017-05-01

    In this study, we aimed to investigate the effect of CAPE and thymoquinone in experimental rat otitis media with effusion (OME) model. Intraoral approach of eustachian tube orifice cauterization were administered to 36 of 40 rats participating the study. After application of exclusion criterias, 22 rats with appropriate conditions were determined. Totally 26 rats (44 otitis model ears and 8 normal ears) were randomly divided into 5 groups. While group I was consisted of healthy rats, the other groups were consisted of rats with otitis model. Group I (saline + control group; n = 8 normal ears) and group II (saline + otitis model; n = 10 otitis model ears) received intraperitoneally saline solution. CAPE was given intraperitoneally to group III (CAPE + otitis model; n = 12 otitis model ears) at a concentration of 10 mg/kg for treatment of otitis media. Group IV (thymoquinone + otitis model; n = 12 otitis model ears) was treated orally with 10 mg/kg of thymoquinone. Group V (methylprednisolone + otitis model; n = 10 otitis model ears) was treated intraperitoneally with 1 mg/kg of methylprednisolone. Tympanic bulla samples were excised after 10th day of treatment and examined under light microscopy. Submucosal neutrophil leukocyte count of group I was significantly lower than other groups (II, IV, V) (respectively p < 0,0001, p < 0,001, p < 0,0001, Tukey test), while it was not significantly different from group III (p = 0,056, Tukey test). Submucosal neutrophil leukocyte count of group III was significantly lower than group II and group V (p = 0.029 ve p = 0.03, Tukey test). There was no significant difference between group IV and group V (p = 0,28, Tukey test). Based on these findings, it could be suggested that CAPE, anti inflammatory properties proven in the literature, plays an important role in OME treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Solvent-free, microwave-assisted synthesis of thiophene oligomers via Suzuki coupling.

    Science.gov (United States)

    Melucci, Manuela; Barbarella, Giovanna; Sotgiu, Giovanna

    2002-12-13

    The purpose of this study was to obtain a rapid, efficient, and environmentally friendly methodology for the synthesis of highly pure thiophene oligomers. The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, allowed us to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the targeted product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Thus, for example, quaterthiophene was obtained in 6 min by reaction of 2-bromo-2,2'-bithiophene with bis(pinacolato)diboron (isolated yield 65%), whereas quinquethiophene was obtained in 11 min by reaction of dibromoterthiophene with thienylboronic acid (isolated yield 74%). The synthesis of new chiral 2,2'-bithiophenes is reported. The detailed analysis of the byproducts of some reactions allowed us to elucidate a few aspects of reaction mechanisms. While the use of microwaves proved to be very convenient for the coupling between conventional thienyl moieties, the same was not true for the coupling of thienyl rings to thienyl-S,S-dioxide moieties. Indeed, in this case, the targeted product was obtained in low yields because of the competitive, accelerated, Diels-Alder reaction that affords a variety of condensation products.

  7. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    Science.gov (United States)

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-06-08

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

  8. Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

    DEFF Research Database (Denmark)

    Pedersen, Martin Nors; Foderà, Vito; Horvath, Istvan

    2015-01-01

    are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075), and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential...

  9. 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

  10. Statistical mechanics of thermal denaturation of DNA oligomers

    Indian Academy of Sciences (India)

    Statistical mechanics of thermal denaturation of DNA oligomers. NAVIN SINGH and YASHWANT SINGH. Department of Physics, Banaras Hindu University, Varanasi 221 005, India. Email: ysingh@bhu.ac.in. Abstract. Double stranded DNA chain is known to have non-trivial elasticity. We study the effect of this elasticity on ...

  11. Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers

    NARCIS (Netherlands)

    Cong, Yingying; Kriegenburg, Franziska; de Haan, Cornelis A. M.; Reggiori, Fulvio

    2017-01-01

    Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down

  12. Beta-strand interfaces of non-dimeric protein oligomers are characterized by scattered charged residue patterns.

    Directory of Open Access Journals (Sweden)

    Giovanni Feverati

    Full Text Available Protein oligomers are formed either permanently, transiently or even by default. The protein chains are associated through intermolecular interactions constituting the protein interface. The protein interfaces of 40 soluble protein oligomers of stœchiometries above two are investigated using a quantitative and qualitative methodology, which analyzes the x-ray structures of the protein oligomers and considers their interfaces as interaction networks. The protein oligomers of the dataset share the same geometry of interface, made by the association of two individual β-strands (β-interfaces, but are otherwise unrelated. The results show that the β-interfaces are made of two interdigitated interaction networks. One of them involves interactions between main chain atoms (backbone network while the other involves interactions between side chain and backbone atoms or between only side chain atoms (side chain network. Each one has its own characteristics which can be associated to a distinct role. The secondary structure of the β-interfaces is implemented through the backbone networks which are enriched with the hydrophobic amino acids favored in intramolecular β-sheets (MCWIV. The intermolecular specificity is provided by the side chain networks via positioning different types of charged residues at the extremities (arginine and in the middle (glutamic acid and histidine of the interface. Such charge distribution helps discriminating between sequences of intermolecular β-strands, of intramolecular β-strands and of β-strands forming β-amyloid fibers. This might open new venues for drug designs and predictive tool developments. Moreover, the β-strands of the cholera toxin B subunit interface, when produced individually as synthetic peptides, are capable of inhibiting the assembly of the toxin into pentamers. Thus, their sequences contain the features necessary for a β-interface formation. Such β-strands could be considered as 'assemblons

  13. Design, synthesis, and characterization of biomimetic oligomers

    DEFF Research Database (Denmark)

    Laursen, Jonas Striegler

    Peptides and proteins made from the 20 canonical amino acids are responsible for many processes necessary for organisms to function. Beside their composition, proteins obtain their activity and unique selectivity through an ability to display functionalities accurately in the three-dimensional sp...

  14. Isolation and identification of oligomers from partial degradation of lime fruit cutin.

    Science.gov (United States)

    Tian, Shiying; Fang, Xiuhua; Wang, Weimin; Yu, Bingwu; Cheng, Xiaofang; Qiu, Feng; Mort, Andrew J; Stark, Ruth E

    2008-11-12

    Complementary degradative treatments with low-temperature hydrofluoric acid and methanolic potassium hydroxide have been used to investigate the protective biopolymer cutin from Citrus aurantifolia (lime) fruits, augmenting prior enzymatic and chemical strategies to yield a more comprehensive view of its molecular architecture. Analysis of the resulting soluble oligomeric fragments with one- and two-dimensional NMR and MS methods identified a new dimer and three trimeric esters of primary alcohols based on 10,16-dihydroxyhexadecanoic acid and 10-oxo-16-hydroxyhexadecanoic acid units. Whereas only 10-oxo-16-hydroxyhexadecanoic acid units were found in the oligomers from hydrofluoric acid treatments, the dimer and trimer products isolated to date using diverse degradative methods included six of the seven possible stoichiometric ratios of monomer units. A novel glucoside-linked hydroxyfatty acid tetramer was also identified provisionally, suggesting that the cutin biopolymer can be bound covalently to the plant cell wall. Although the current findings suggest that the predominant molecular architecture of this protective polymer in lime fruits involves esters of primary and secondary alcohols based on long-chain hydroxyfatty acids, the possibility of additional cross-linking to enhance structural integrity is underscored by these and related findings of nonstandard cutin molecular architectures.

  15. Interpenetrating polymer networks based on cyanate ester and fluorinated ethynyl-terminated imide oligomers

    Directory of Open Access Journals (Sweden)

    Y. Wen

    2017-12-01

    Full Text Available Highly soluble fluorinated ethynyl-terminated imide (FETI oligomers were prepared via a conventional one-step method in m-cresol, using 4, 4′-(hexafluoroisopropylidene diphthalic anhydride and 2, 2′-bis(trifluoromethyl benzidine as the monomers, and ethynylphthalic anhydride as the end-capper; then interpenetrating polymer networks (IPN were formulated from FETI oligomers and bisphenol A dicyanate ester (BADCy through a solvent-free procedure, and their thermal, mechanical, and dielectric properties were fully characterized. The curing mechanism was studied by model reactions using nitrogen nuclear magnetic resonance. As evidenced by differential scanning calorimetry analysis and rheological measurements, the FETI/BADCy blends exhibited lower curing temperature and shorter gelation time in comparison with pure BADCy due to the catalytic effects of ethynyl and residue amic acid groups. The properties of IPNs were fully compared with those of polycyanurate, and the results revealed that the incorporation of FETI into cyanate ester resins could significantly improve the toughness, glass transition temperatures, mechanical and dielectric properties of the resultant IPNs.

  16. Rožmarinska kislina: Rosmarinic acid:

    OpenAIRE

    Sova, Matej

    2012-01-01

    Rosmarinic acid, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is an active component of several medicinal plants and spices. This article presents the biosynthesis of rosmarinic acid and provides a brief description of its main biological activities and potential therapeutic use. Rožmarinska kislina, ester kavne in 3,4-dihidroksifenilmlečne kisline, je aktivna sestavina številnih zdravilnih rastlin in začimb. V prispevku so predstavljeni njena biosinteza, kratek pregled gla...

  17. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    Full Text Available Amyloid beta (Abeta 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD. We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1 protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological

  18. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers II: Sigma-2/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity

    Science.gov (United States)

    Izzo, Nicholas J.; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J.; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A.; Arancio, Ottavio; Mach, Robert H.; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L.; Catalano, Susan M.

    2014-01-01

    Amyloid beta (Abeta) 1–42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  19. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    Science.gov (United States)

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  20. OH-radical induced degradation of hydroxybenzoic- and hydroxycinnamic acids and formation of aromatic products-A gamma radiolysis study

    Energy Technology Data Exchange (ETDEWEB)

    Krimmel, Birgit; Swoboda, Friederike [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Solar, Sonja, E-mail: sonja.solar@univie.ac.a [University of Vienna, Department of Nutritional Sciences, Section Radiation Biology (Austria); Reznicek, Gottfried [Department of Pharmacognosy, Althanstrasse 14, A-1090 Vienna (Austria)

    2010-12-15

    The OH-radical induced degradation of hydroxybenzoic acids (HBA), hydroxycinnamic acids (HCiA) and methoxylated derivatives, as well as of chlorogenic acid and rosmarinic acid was studied by gamma radiolysis in aerated aqueous solutions. Primary aromatic products resulting from an OH-radical attachment to the ring (hydroxylation), to the position occupied by the methoxyl group (replacement -OCH{sub 3} by -OH) as well as to the propenoic acid side chain of the cinnamic acids (benzaldehyde formations) were analysed by HPLC-UV and LC-ESI-MS. A comparison of the extent of these processes is given for 3,4-dihydroxybenzoic acid, vanillic acid, isovanillic acid, syringic acid, cinnamic acid, 4-hydroxycinnamic acid, caffeic acid, ferulic acid, isoferulic acid, chlorogenic acid, and rosmarinic acid. For all cinnamic acids and derivatives benzaldehydes were significant oxidation products. With the release of caffeic acid from chlorogenic acid the cleavage of a phenolic glycoside could be demonstrated. Reaction mechanisms are discussed.

  1. Amyloid β oligomer-induced ERK1/2-dependent serine 636/639 phosphorylation of insulin receptor substrate-1 impairs insulin signaling and glycogen storage in human astrocytes.

    Science.gov (United States)

    Zhang, Qinghua; Guo, Shougang; Zhang, Xiao; Tang, Shi; Wang, Lu; Han, Xiaojuan; Shao, Wen; Cong, Lin; Du, Yifeng

    2015-04-25

    This study is to investigate the effect of amyloid β1-42 oligomers on insulin signaling in astrocytes. Synthetic Aβ1-42 oligomers were prepared and the oligomeric form of Aβ1-42 was verified by an electron microscope. Normal human astrocytes were cultured in Dulbecco's Modified Eagle Medium. Western blotting was employed to measure the amount of lysate proteins. Immunofluorescence was performed to detect the distribution of phosphorylated insulin receptor substrate-1 and expression of P-GSK3β in astrocytes under confocal microscopy and fluorescent microscopy, respectively. Periodic Acid-Schiff staining was used to detect glycogen, the content of which was measured using glycogen assay. Our data showed that Aβ1-42 oligomers inhibited insulin-induced serine phosphorylation of Akt at 473 and GSK3β at serine 9, as well as glycogen storage. However, the levels of phosphorylated GSK3β at tyrosine 216 were significantly increased in the presence of Aβ1-42 oligomers. In addition, the levels of phosphorylated ERK1/2 and insulin receptor substrate-1 at serine 636/639 were significantly increased in response to treatment with Aβ1-42 oligomers. Of note, the responses and inhibitory effects of Aβ1-42 oligomers on insulin signaling were partially reversed by ERK1/2 upstream inhibitor PD98059. Our results demonstrated that Aβ1-42 oligomers impaired insulin signaling and suppressed insulin-induced glycogen storage in human astrocytes, probably due to ERK1/2-dependent serine phosphorylation of insulin receptor substrate-1 at 636/639 induced by Aβ1-42 oligomers. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Formation of Silver Nanoparticles Using Fluorescence Properties of Chitosan Oligomers.

    Science.gov (United States)

    Cheon, Ja Young; Lee, Hun Min; Park, Won Ho

    2018-01-03

    In this study, silver chloride nanoparticles (AgCl NPs) were prepared using chitosan oligomer (CHI) and chitosan oligomer derivatives (CHI-FITC). The CHI and CHI-FITC were used as markers to confirm the formation of AgCl NPs using their fluorescence properties as well as stabilizers. The fluorescence properties of CHI and CHI-FITC were monitored by a luminescence spectrophotometer, and the morphology of the AgCl NPs was further confirmed by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The fluorescence of CHI and CHI-FITC was quenched by the formation of AgCl NPs, and the Stern-Volmer equation was used to compare the two types of stabilizer. The CHI and CHI-FITC stabilizer were linear and nonlinear, respectively, with respect to the Stern-Volmer equation, and considered to be usable as fluorescence indicators to confirm the formation behavior of AgCl NPs through fluorescence quenching.

  3. Charge transfer in conjugated oligomers encapsulated into carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Almadori, Y.; Alvarez, L.; Michel, T.; Le Parc, R.; Bantignies, J.L.; Hermet, P.; Sauvajol, J.L. [Laboratoire Charles Coulomb UMR 5521, Universite Montpellier 2, 34095 Montpellier (France); Laboratoire Charles Coulomb UMR 5521, CNRS, 34095 Montpellier (France); Arenal, R. [Laboratoire d' Etude des Microstructures, CNRS-ONERA, 92322 Chatillon (France); Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia de Aragon, U. Zaragoza, 50018 Zaragoza (Spain); Babaa, R. [Laboratoire de Chimie des Surfaces et Interfaces, CEA, IRAMIS, SPCSI, 91191 Gif-sur-Yvette Cedex (France); Chemical Engineering Department, University of Technology PETRONAS, UTP, Ipoh-Perak (Malaysia); Jouselme, B.; Palacin, S. [Laboratoire de Chimie des Surfaces et Interfaces, CEA, IRAMIS, SPCSI, 91191 Gif-sur-Yvette Cedex (France)

    2011-11-15

    This study deals with a hybrid system consisting in quaterthiophene derivative encapsulated inside single-walled and multi-walled carbon nanotubes. Investigations of the encapsulation step are performed by transmission electron microscopy. Raman spectroscopy data point out different behaviors depending on the laser excitation energy with respect to the optical absorption of quaterthiophene. At low excitation energy (far from the oligomer resonance window) there is no significant modification of the Raman spectra before and after encapsulation. By contrast, at high excitation energy (close to the oligomer resonance window), Raman spectra exhibit a G-band shift together with an important RBM intensity loss, suggesting a significant charge transfer between the inserted molecule and the host nanotubes. Those results suggest a photo induced process leading to a significant charge transfer. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Computationally Designed Oligomers for High Contrast Black Electrochromic Polymers

    Science.gov (United States)

    2017-05-05

    AFRL-AFOSR-VA-TR-2017-0097 Computationally Designed Oligomers for High Contrast Black Electrochromic Polymers Aimee Tomlinson University Of North...Black Electrochromic FA9550-15-1-0181 Polymers 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6.AUTHO~ 5d. PROJECT NUMBER AimeeL. T . Se. TASK...neraly black neutral state. Additionally, upon oxidation these polymers would have litte to no tailing form the near IR thereby guaranteeing nearly a I

  5. Some biological actions of PEG-conjugated RNase A oligomers

    Czech Academy of Sciences Publication Activity Database

    Poučková, P.; Škvor, J.; Gotte, G.; Vottariello, F.; Slavík, Tomáš; Matoušek, Josef; Laurents, D. V.; Libonati, M.; Souček, J.

    2006-01-01

    Roč. 53, č. 1 (2006), s. 79-85 ISSN 0028-2685 R&D Projects: GA ČR GA523/04/0755; GA MZd NR8233 Grant - others:Spanish Ministerio de Ciencia y Technologia BQU2003-05227 Institutional research plan: CEZ:AV0Z50450515 Keywords : RNase A oligomers * polyethylene glycol conjugates * anti-tumour activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.247, year: 2006

  6. Incorporation of Chlorogenic Acids in Coffee Brew Melanoidins

    NARCIS (Netherlands)

    Bekedam, E.K.; Schols, H.A.; Boekel, van T.; Smit, G.

    2008-01-01

    The incorporation of chlorogenic acids (CGAs) and their subunits quinic and caffeic acids (QA and CA) in coffee brew melanoidins was studied. Fractions with different molecular weights, ionic charges, and ethanol solubilities were isolated from coffee brew. Fractions were saponified, and the

  7. Influence of thermalization on thermal conduction through molecular junctions: Computational study of PEG oligomers

    Science.gov (United States)

    Pandey, Hari Datt; Leitner, David M.

    2017-08-01

    Thermalization in molecular junctions and the extent to which it mediates thermal transport through the junction are explored and illustrated with computational modeling of polyethylene glycol (PEG) oligomer junctions. We calculate rates of thermalization in the PEG oligomers from 100 K to 600 K and thermal conduction through PEG oligomer interfaces between gold and other materials, including water, motivated in part by photothermal applications of gold nanoparticles capped by PEG oligomers in aqueous and cellular environments. Variation of thermalization rates over a range of oligomer lengths and temperatures reveals striking effects of thermalization on thermal conduction through the junction. The calculated thermalization rates help clarify the scope of applicability of approaches that can be used to predict thermal conduction, e.g., where Fourier's law breaks down and where a Landauer approach is suitable. The rates and nature of vibrational energy transport computed for PEG oligomers are compared with available experimental results.

  8. Waterborne carboxyl-terminated hyperbranched oligomer polyester ligand: Synthesis, characterization and chelation with chromium(III)

    Science.gov (United States)

    Yao, Qi; Li, Chenying; Huang, Henghui; Chen, Hualin; Liu, Bailing

    2017-09-01

    A series of carboxyl-terminated hyperbranched oligomer polyester (HBP) with different degree of branching (DB) and number average molar mass (Mbarn) have been prepared. The molecular structure, degree of branching, molecular mass and its distribution of HBP were investigated by FTIR, 1H NMR, and GPC, respectively. And the coordination number, stability constant and degree of dissociation (α) between HBP and chromium(Ⅲ) were measured via continuous variation method (Job's plot). Experimental results show that the coordination capability between HBP and chromium(Ⅲ) affected by both DB and molecular mass, and the latter plays a decisive role. Moreover HBP outperforms low molecular weight of organic acids (citric acid, acetic acid) and linear polyacrylic acid with similar molecular mass. The coordination number and stability constants of HBP-3 (Mbarn = 1713 Da, Mbarw /Mbarn (PDI) = 1.11 and DB = 0.72) can reach 4 and 6.55e+008, which demonstrated it can be selected as a good ligand to coordination with chromium(Ⅲ). Therefore HBP can be used as chrome auxiliary in chrome tanning to improve the absorption of chromium.

  9. Enzymatic Extraction of Hydroxycinnamic Acids from Coffee Pulp

    Directory of Open Access Journals (Sweden)

    Ernesto Favela-Torres

    2011-01-01

    Full Text Available Ferulic, caffeic, p-coumaric and chlorogenic acids are classified as hydroxycinnamic acids, presenting anticarcinogenic, anti-inflammatory and antioxidant properties. In this work, enzymatic extraction has been studied in order to extract high value-added products like hydroxycinnamic acids from coffee pulp. A commercial pectinase and enzyme extract produced by Rhizomucor pusillus strain 23aIV in solid-state fermentation using olive oil or coffee pulp (CP as an inducer of the feruloyl esterase activity were evaluated separately and mixed. The total content (covalently linked and free of ferulic, caffeic, p-coumaric and chlorogenic acids was 5276 mg per kg of coffee pulp. Distribution was as follows (in %: chlorogenic acid 58.7, caffeic acid 37.6, ferulic acid 2.1 and p-coumaric acid 1.5. Most of the hydroxycinnamic acids were covalently bound to the cell wall (in %: p-coumaric acid 97.2, caffeic acid 94.4, chlorogenic acid 76.9 and ferulic acid 73.4. The content of covalently linked hydroxycinnamic acid was used to calculate the enzyme extraction yield. The maximum carbon dioxide rate for the solid-state fermentation using olive oil as an inducer was higher and it was reached in a short cultivation time. Nevertheless, the feruloyl esterase (FAE activity (units per mg of protein obtained in the fermentation using CP as an inducer was 31.8 % higher in comparison with that obtained in the fermentation using olive oil as the inducer. To our knowledge, this is the first report indicating the composition of both esterified and free ferulic, caffeic, p-coumaric and chlorogenic acids in coffee pulp. The highest yield of extraction of hydroxycinnamic acids was obtained by mixing the produced enzyme extract using coffee pulp as an inducer and a commercial pectinase. Extraction yields were as follows (in %: chlorogenic acid 54.4, ferulic acid 19.8, p-coumaric acid 7.2 and caffeic acid 2.3. An important increase in the added value of coffee pulp was mainly

  10. Artificial biosynthesis of phenylpropanoic acids in a tyrosine overproducing Escherichia coli strain

    Directory of Open Access Journals (Sweden)

    Kang Sun-Young

    2012-12-01

    Full Text Available Abstract Background The phenylpropanoid metabolites are an extremely diverse group of natural products biosynthesized by plants, fungi, and bacteria. Although these compounds are widely used in human health care and nutrition services, their availability is limited by regional variations, and isolation of single compounds from plants is often difficult. Recent advances in synthetic biology and metabolic engineering have enabled artificial production of plant secondary metabolites in microorganisms. Results We develop an Escherichia coli system containing an artificial biosynthetic pathway that yields phenylpropanoic acids, such as 4-coumaric acid, caffeic acid, and ferulic acid, from simple carbon sources. These artificial biosynthetic pathways contained a codon-optimized tal gene that improved the productivity of 4-coumaric acid and ferulic acid, but not caffeic acid in a minimal salt medium. These heterologous pathways extended in E. coli that had biosynthesis machinery overproducing tyrosine. Finally, the titers of 4-coumaric acid, caffeic acid, and ferulic acid reached 974 mg/L, 150 mg/L, and 196 mg/L, respectively, in shake flasks after 36-hour cultivation. Conclusions We achieved one gram per liter scale production of 4-coumaric acid. In addition, maximum titers of 150 mg/L of caffeic acid and 196 mg/L of ferulic acid were achieved. Phenylpropanoic acids, such as 4-coumaric acid, caffeic acid, and ferulic acid, have a great potential for pharmaceutical applications and food ingredients. This work forms a basis for further improvement in production and opens the possibility of microbial synthesis of more complex plant secondary metabolites derived from phenylpropanoic acids.

  11. [Native and renatured oligomer-dependent epitopes of intracellular influenza virus nucleocapsid protein].

    Science.gov (United States)

    Semenova, N P; Prokudina, E N; Chumakov, V M; Grigor'eva, T A; Stitz, L

    2008-01-01

    Intracellular NP oligomers have been shown to react with some anti-NP monoclonal antibodies (mAbs) in radio-immnoprecipitation, immunoblotting, and dot immunoassay. Soluble NP monomers obtained after thermal dissociation of NP oligomers are not recognized by mAbs unlike the NP monomers whose concentration increased by about 100-fold due to transfer to the nitrocellulose membrane after polyacrylamide gel electrophoresis. The findings demonstrated that in the intact NP oligomers there were epitopes determined by their quaternary structure. These oligomer-dependent epitopes may be renaturated in vitro under the conditions allowing for a concentration-dependent NP-NP association.

  12. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    Science.gov (United States)

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  13. Molecular determinants of S100B oligomer formation.

    Directory of Open Access Journals (Sweden)

    Eva Thulin

    Full Text Available BACKGROUND: S100B is a dimeric protein that can form tetramers, hexamers and higher order oligomers. These forms have been suggested to play a role in RAGE activation. METHODOLOGY/PRINCIPAL FINDINGS: Oligomerization was found to require a low molecular weight trigger/cofactor and could not be detected for highly pure dimer, irrespective of handling. Imidazol was identified as a substance that can serve this role. Oligomerization is dependent on both the imidazol concentration and pH, with optima around 90 mM imidazol and pH 7, respectively. No oligomerization was observed above pH 8, thus the protonated form of imidazol is the active species in promoting assembly of dimers to higher species. However, disulfide bonds are not involved and the process is independent of redox potential. The process was also found to be independent of whether Ca(2+ is bound to the protein or not. Tetramers that are purified from dimers and imidazol by gel filtration are kinetically stable, but dissociate into dimers upon heating. Dimers do not revert to tetramer and higher oligomer unless imidazol is again added. Both tetramers and hexamers bind the target peptide from p53 with retained stoichiometry of one peptide per S100B monomer, and with high affinity (lgK = 7.3±0.2 and 7.2±0.2, respectively in 10 mM BisTris, 5 mM CaCl(2, pH 7.0, which is less than one order of magnitude reduced compared to dimer under the same buffer conditions. CONCLUSION/SIGNIFICANCE: S100B oligomerization requires protonated imidazol as a trigger/cofactor. Oligomers are kinetically stable after imidazol is removed but revert back to dimer if heated. The results underscore the importance of kinetic versus thermodynamic control of S100B protein aggregation.

  14. Structural Transitions of Solvent-Free Oligomer-Grafted Nanoparticles

    KAUST Repository

    Chremos, Alexandros

    2011-09-01

    Novel structural transitions of solvent-free oligomer-grafted nanoparticles are investigated by using molecular dynamics simulations of a coarse-grained bead-spring model. Variations in core size and grafting density lead to self-assembly of the nanoparticles into a variety of distinct structures. At the boundaries between different structures, the nanoparticle systems undergo thermoreversible transitions. This structural behavior, which has not been previously reported, deviates significantly from that of simple liquids. The reversible nature of these transitions in solvent-free conditions offers new ways to control self-assembly of nanoparticles at experimentally accessible conditions. © 2011 American Physical Society.

  15. Expression of enzymes in yeast for lignocellulose derived oligomer CBP

    Energy Technology Data Exchange (ETDEWEB)

    McBride, John E.; Wiswall, Erin; Shikhare, Indraneel; Xu, Haowen; Thorngren, Naomi; Hau, Heidi H.; Stonehouse, Emily

    2017-08-29

    The present invention provides a multi-component enzyme system that hydrolyzes hemicellulose oligomers from hardwood which can be expressed, for example, in yeast such as Saccharomyces cerevisiae. In some embodiments, this invention provides for the engineering of a series of biocatalysts combining the expression and secretion of components of this enzymatic system with robust, rapid xylose utilization, and ethanol fermentation under industrially relevant process conditions for consolidated bioprocessing. In some embodiments, the invention utilizes co-cultures of strains that can achieve significantly improved performance due to the incorporation of additional enzymes in the fermentation system.

  16. Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed

    Energy Technology Data Exchange (ETDEWEB)

    Makoveichuk, Elena; Sukonina, Valentina; Kroupa, Olessia [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden); Thulin, Petra; Ehrenborg, Ewa [Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm (Sweden); Olivecrona, Thomas [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden); Olivecrona, Gunilla, E-mail: Gunilla.Olivecrona@medbio.umu.se [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Lipoprotein lipase (LPL) activity is controlled by ANGPTL4 in THP-1 macrophages. Black-Right-Pointing-Pointer Both LPL and ANGPTL4 bind to THP-1 macrophages in a heparin-releasable fashion. Black-Right-Pointing-Pointer Only monomers of ANGPTL4 are present within THP-1 macrophages. Black-Right-Pointing-Pointer Covalent oligomers of ANGPTL4 appear on cell surface and in medium. Black-Right-Pointing-Pointer Inactivation of LPL coincide with ANGPTL4 oligomer formation on cell surfaces. -- Abstract: Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPAR{delta} agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL. Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed.

  17. Investigation of Membrane Receptors' Oligomers Using Fluorescence Resonance Energy Transfer and Multiphoton Microscopy in Living Cells

    Science.gov (United States)

    Mishra, Ashish K.

    Investigating quaternary structure (oligomerization) of macromolecules (such as proteins and nucleic acids) in living systems (in vivo) has been a great challenge in biophysics, due to molecular diffusion, fluctuations in several biochemical parameters such as pH, quenching of fluorescence by oxygen (when fluorescence methods are used), etc. We studied oligomerization of membrane receptors in living cells by means of Fluorescence (Forster) Resonance Energy Transfer (FRET) using fluorescent markers and two photon excitation fluorescence micro-spectroscopy. Using suitable FRET models, we determined the stoichiometry and quaternary structure of various macromolecular complexes. The proteins of interest for this work are : (1) sigma-1 receptor and (2) rhodopsin, are described as below. (1) Sigma-1 receptors are molecular chaperone proteins, which also regulate ion channels. S1R seems to be involved in substance abuse, as well as several diseases such as Alzheimer's. We studied S1R in the presence and absence of its ligands haloperidol (an antagonist) and pentazocine +/- (an agonist), and found that at low concentration they reside as a mixture of monomers and dimers and that they may form higher order oligomers at higher concentrations. (2) Rhodopsin is a prototypical G protein coupled receptor (GPCR) and is directly involved in vision. GPCRs form a large family of receptors that participate in cell signaling by responding to external stimuli such as drugs, thus being a major drug target (more than 40% drugs target GPCRs). Their oligomerization has been largely controversial. Understanding this may help to understand the functional role of GPCRs oligomerization, and may lead to the discovery of more drugs targeting GPCR oligomers. It may also contribute toward finding a cure for Retinitis Pigmentosa, which is caused by a mutation (G188R) in rhodopsin, a disease which causes blindness and has no cure so far. Comparing healthy rhodopsin's oligomeric structure with that

  18. Identification and bioactivities of resveratrol oligomers and flavonoids from Carex folliculata seeds.

    Science.gov (United States)

    Li, Liya; Henry, Geneive E; Seeram, Navindra P

    2009-08-26

    Plants of the Carex genus (Family: Cyperaceae) have attracted recent attention as potential food additives because they contain high levels of bioactive polyphenols commonly found in plant foods. Seven compounds, which included two resveratrol oligomers and five flavonoids, were isolated from seeds of Carex folliculata L. (northern long sedge), a forage prevalent in the northern United States. The compounds were identified by (1)H and (13)C nuclear magnetic resonance and mass spectrometry data. The resveratrol oligomers were pallidol (1), a resveratrol dimer reported to be present in levels equivalent to those of resveratrol in red wine, and kobophenol A (2), a resveratrol tetramer with a unique 2,3,4,5-tetraaryltetrahydrofuran skeleton. The flavonoids were isoorientin (3), luteolin (4), quercetin (5), 3-O-methylquercetin (6), and rutin (7). Compounds were evaluated for antioxidant activity in the diphenylpicrylhydrazyl (DPPH) radical scavenging assay; cytotoxicity activity against human colon (HCT116, HT29) and breast (MCF7, MDA-MB-231) tumor cell lines; and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The antioxidant activities of the flavonoids (3-7; IC(50) values ranging from 50 to 200 microM) were comparable to that of ascorbic acid (IC(50) = 60 microM) and superior to those of the resveratrol derivatives (1 and 2; IC(50) > 1000 microM) and butylated hydroxytoluene (BHT; IC(50) = 1500 microM), a commercial antioxidant. In the cytotoxicity and antibacterial bioassays, compounds 4 (IC(50) for HCT116 = 45 microM) and 6 (IC(50) for MRSA = 6.4 microM) were the most active, respectively. Therefore, given the wide availability and underutilization of C. folliculata, this forage may provide a source of bioactive compounds useful for nutraceutical purposes. Also, this is the first reported phytochemical investigation of C. folliculata.

  19. Organic heterostructures based on arylenevinylene oligomers deposited by MAPLE

    Science.gov (United States)

    Socol, M.; Preda, N.; Vacareanu, L.; Grigoras, M.; Socol, G.; Mihailescu, I. N.; Stanculescu, F.; Jelinek, M.; Stanculescu, A.; Stoicanescu, M.

    2014-05-01

    Organic heterostructures were fabricated by matrix assisted pulsed laser evaporation (MAPLE) method using arylenevinylene oligomers based on triphenylamine (P78)/carbazole (P13) group and tris(8-hydroxyquinolinato)aluminum salt (Alq3). Optical properties of the organic multilayer structures were characterized by spectroscopic techniques: FTIR, UV-vis and photoluminescence (PL). A good transparency (over 60%) was remarked for the structures with two organic layers in the 550-800 nm range. Photoluminescence (PL) spectra proved that the emission characteristics of the materials have been preserved. I-V characteristics of (ITO/oligomer/Alq3/Al and ITO/Alq3/Al) heterostructures were symmetrically while rectifying properties of these heterostructures have not been observed. A comparison between the heterostructures made of layers with different thickness reveals that the higher current (8 × 10-6 A at 1 V) was obtained for the ITO/P78/Alq3/Al heterostructure, which is characterized by a larger thickness of the double organic layer. AFM measurements revealed a similar topography while RMS values of the reported structures depend on the organic material.

  20. Broadband terahertz dynamics of propylene glycol monomer and oligomers

    Science.gov (United States)

    Koda, Shota; Mori, Tatsuya; Kojima, Seiji

    2016-12-01

    We investigated the broadband terahertz spectra (0.1-5.0 THz) of glass-forming liquids, propylene glycol (PG), its oligomers poly (propylene glycol)s (PPGs), and poly (propylene glycol) diglycidyl ether (PPG-de) using broadband terahertz time-domain spectroscopy and low-frequency Raman scattering. The numerical value of the dielectric loss at around 1.5 THz, which is the peak position of broad peaks in all samples, decreased as the molecular weight increased. Furthermore, the peak at around 1.5 THz is insensitive to the molecular weight. For PPGs, the side chain effect of the oligomer was observed in the terahertz region. Based on the experimental and calculation results for the PPGs and PPG-de, whose end groups are epoxy groups, the beginnings of the increases in the observed dielectric loss above 3.5 THz of the PPGs are assigned to the OH bending vibration. The higher value of the dielectric loss in the terahertz region for the PPG-de can be the tail of a broad peak located in the MHz region. The difference between the Raman susceptibility and dielectric loss reflects the difference in the observable molecular dynamics between the infrared and Raman spectroscopies.

  1. Radial distribution function of semiflexible oligomers with stretching flexibility

    Science.gov (United States)

    Zhang, Xi; Bao, Lei; Wu, Yuan-Yan; Zhu, Xiao-Long; Tan, Zhi-Jie

    2017-08-01

    The radial distribution of the end-to-end distance Ree is crucial for quantifying the global size and flexibility of a linear polymer. For semiflexible polymers, several analytical formulas have been derived for the radial distribution of Ree ignoring the stretching flexibility. However, for semiflexible oligomers, such as DNA or RNA, the stretching flexibility can be rather pronounced and can significantly affect the radial distribution of Ree. In this study, we obtained an extended formula that includes the stretch modulus to describe the distribution of Ree for semiflexible oligomers on the basis of previous formulas for semiflexible polymers without stretching flexibility. The extended formula was validated by extensive Monte Carlo simulations over wide ranges of the stretch modulus and persistence length, as well as all-atom molecular dynamics simulations of short DNAs and RNAs. Additionally, our analyses showed that the effect of stretching flexibility on the distribution of Ree becomes negligible for DNAs longer than ˜130 base pairs and RNAs longer than ˜240 base pairs.

  2. Usefulness of Alginate Lyases Derived from Marine Organisms for the Preparation of Alginate Oligomers with Various Bioactivities.

    Science.gov (United States)

    Takeshita, S; Oda, T

    Alginate-degrading enzyme, alginate lyase, catalyzes the cleavage of glycosidic 1-4 O-linkages between uronic acid residues of alginate by a β-elimination reaction leaving a 4-deoxy-l-erythro-hex-4-ene pyranosyluronate as nonreducing terminal end. The enzymes from a wide variety of sources such as marine molluscs, seaweeds, and marine bacteria have been discovered and studied not only from a point of view of enzymological interest of enzyme itself but also for elucidation of fine chemical structure of alginate, structure-activity relationship of alginate, and biological activities and physicochemical features of the enzymatic digestion products. Based on the substrate specificities, alginate lyases are classified into three groups: poly(β-d-mannuronate) lyase, poly(α-l-guluronate) lyase, and bifunctional alginate lyase, which are specific to mannuronate, guluronate, and both uronic acid residues, respectively. We have studied enzymological aspects of these three types of alginate lyases, and bioactivities of enzymatically digested alginate oligomers. In this chapter, we described the purification and characterization of three types of alginate lyases from different marine origins and overviewed the bioactivities of alginate oligomers. © 2016 Elsevier Inc. All rights reserved.

  3. Sedimentation Studies on Human Amylin Fail to Detect Low-Molecular-Weight Oligomers

    Science.gov (United States)

    Vaiana, Sara M.; Ghirlando, Rodolfo; Yau, Wai-Ming; Eaton, William A.; Hofrichter, James

    2008-01-01

    Sedimentation velocity experiments show that only monomers coexist with amyloid fibrils of human islet amyloid-polypeptide. No oligomers containing <100 monomers could be detected, suggesting that the putative toxic oligomers are much larger than those found for the Alzheimer's peptide, Aβ(1-42). PMID:18223003

  4. Aggregation Effects on the Emission Spectra and Dynamics of Model Oligomers of MEH-PPV

    NARCIS (Netherlands)

    Sherwood, Gizelle A.; Cheng, Ryan; Smith, Timothy M.; Werner, James H.; Shreve, Andrew P.; Peteanu, Linda A.; Wildeman, Jurjen

    2009-01-01

    The effects of aggregate formation on the photophysical properties of oligomers of MEH-PPV were studied in bulk solution to better understand the effects of aggregation on the emission properties of the polymer. Nanoaggregates of oligomers from 3 to 17 repeat units in length were formed using a

  5. Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease

    NARCIS (Netherlands)

    Jongbloed, W.; Bruggink, K.A.; Kester, M.I.; Visser, P.J.; Scheltens, P.; Blankenstein, M.A.; Verbeek, M.M.; Teunissen, C.E.; Veerhuis, R.

    2015-01-01

    Background: Amyloid-β (Aβ)-oligomers are neurotoxic isoforms of Aβ and are a potential diagnostic biomarker for Alzheimer's disease (AD). Objectives: 1) Analyze the potential of Aβ-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large clinical

  6. Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease

    NARCIS (Netherlands)

    Jongbloed, W.; Bruggink, K.A.; Kester, M.I.; Visser, P.J.; Scheltens, P.; Blankenstein, M.A.; Verbeek, M.M.; Teunissen, C.E.; Veerhuis, R.

    2015-01-01

    BACKGROUND: Amyloid-beta (Abeta)-oligomers are neurotoxic isoforms of Abeta and are a potential diagnostic biomarker for Alzheimer's disease (AD). OBJECTIVES: 1) Analyze the potential of Abeta-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large

  7. Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice

    Directory of Open Access Journals (Sweden)

    Jackson George R

    2011-06-01

    Full Text Available Abstract Background The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate. Results Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I, and activated caspase-9, which is related to the apoptotic mitochondrial pathway. Conclusions This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.

  8. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers I: Abeta 42 Oligomer Binding to Specific Neuronal Receptors Is Displaced by Drug Candidates That Improve Cognitive Deficits

    Science.gov (United States)

    Izzo, Nicholas J.; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F.; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M.

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1–42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors - i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD

  9. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers I: Abeta 42 Oligomer Binding to Specific Neuronal Receptors Is Displaced by Drug Candidates That Improve Cognitive Deficits

    OpenAIRE

    Izzo, Nicholas J.; Agnes Staniszewski; Lillian To; Mauro Fa; Teich, Andrew F.; Faisal Saeed; Harrison Wostein; Thomas Walko; Anisha Vaswani; Meghan Wardius; Zanobia Syed; Jessica Ravenscroft; Kelsie Mozzoni; Colleen Silky; Courtney Rehak

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1–42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures o...

  10. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers II: Sigma-2/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity

    OpenAIRE

    Izzo, Nicholas J.; Jinbin Xu; Chenbo Zeng; Kirk, Molly J.; Kelsie Mozzoni; Colleen Silky; Courtney Rehak; Raymond Yurko; Gary Look; Gilbert Rishton; Hank Safferstein; Carlos Cruchaga; Alison Goate; Cahill, Michael A.; Ottavio Arancio

    2014-01-01

    Amyloid beta (Abeta) 1–42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease ...

  11. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits.

    Directory of Open Access Journals (Sweden)

    Nicholas J Izzo

    Full Text Available Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD. Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in

  12. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits.

    Science.gov (United States)

    Izzo, Nicholas J; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models

  13. Oligomer Formation Reactions of Criegee Intermediates in the Ozonolysis of Small Unsaturated Hydrocarbons

    Science.gov (United States)

    Sakamoto, Y.; Inomata, S.; Hirokawa, J.

    2013-12-01

    Secondary organic aerosol (SOA) constitutes a substantial fraction of atmospheric fine particulate matters and has an effect on visibility, climate and human health. One of the major oxidizing processes leading to SOA formation is an ozonolysis of unsaturated hydrocarbons (UHCs).[1] Despite of its importance, the contribution of the ozonolysis of UHCs to the SOA formation in the troposphere is not sufficiently understood due to a lack of information on reaction pathways to produce low volatile compounds. While many studies have previously been focused on SOA formation from the ozonolysis of large UHCs, SOA formation from the ozonolysis of UHCs with less than six carbon atoms have been rarely investigated because their products are expected to be too volatile to contribute to the SOA formation. Very recently, a few studies have reported the SOA formation from the ozonolysis of such small UHCs but chemical mechanisms are still unclear. [2-4] In order to understand SOA formation from the ozonolysis of the small UHCs, this study investigated gas- and particle-phase products in laboratory experiments with a Teflon bag using a negative ion chemical ionization mass spectrometry (NI-CIMS) with chloride ion transfer for chemical ionization. This technique is suitable for analysis of compounds such as carboxylic acids and hydroperoxides expected to be produced in the ozonolysis of UHCs with less fragmentation, high selectivity, and high sensitivity. In the particle-phase analysis, SOAs collected on a PTFE filter were heated, and thermally desorbed compounds were analyzed. In the gas-phase analysis, series of peaks with an interval of a mass-to-charge ratio equal to the molecular weight of a Criegee intermediate formed in their ozonolysis were observed. These peaks were attributed to oligomeric hydroperoxides composed of Criegee intermediates as a chain unit. These oligomeric hydroperoxides were also observed in the particle-phase analysis, indicating that the oligomeric

  14. Photophysics and light-activated biocidal activity of visible-light-absorbing conjugated oligomers.

    Science.gov (United States)

    Parthasarathy, Anand; Goswami, Subhadip; Corbitt, Thomas S; Ji, Eunkyung; Dascier, Dimitri; Whitten, David G; Schanze, Kirk S

    2013-06-12

    The photophysical properties of three cationic π-conjugated oligomers were correlated with their visible light activated biocidal activity vs S. aureus. The oligomers contain three arylene units (terthiophene, 4a; thiophene-benzotriazole-thiophene, 4b; thiophene-benzothiadiazole-thiophene, 4c) capped on each end by cationic -(CH2)3NMe3(+) groups. The oligomers absorb in the visible region due to their donor-acceptor-donor electronic structure. Oligomers 4a and 4b have high intersystem crossing and singlet oxygen sensitization efficiency, but 4c has a very low intersystem crossing efficiency and it does not sensitize singlet oxygen. The biocidal activity of the oligomers under visible light varies in the order 4a > 4b ≈ 4c.

  15. The Adsorption of Short Single-Stranded DNA Oligomers on Mineral Surfaces

    Science.gov (United States)

    Kopstein, M.; Sverjensky, D. A.; Hazen, R. M.; Cleaves, H. J.

    2009-12-01

    Previous studies have described feasible pathways for the synthesis of simple organic building blocks such as formaldehyde and hydrogen cyanide, and their reaction to form more complex biomolecules such as nucleotide bases, amino acids and sugars (Miller and Orgel 1974, Miller and Cleaves 2006). However, the polymerization of monomers into a useful genetic material remains problematic (Orgel 2004). Organic building blocks were unlikely to polymerize from very dilute aqueous solution in the primitive oceans. Mineral surface adsorption has been suggested as a possible mechanism for concentrating the necessary building blocks (Bernal 1951). This study focused on the adsorption behavior of single-stranded DNA homo-oligomers of adenine and thymine (including the monomers, dimers, tetramers, hexamers, octomers, and decamers) with five different mineral surfaces (pyrite, rutile, hematite, olivine and calcite). Adsorption was studied in 0.1 M pH 8.1 KHCO3 with0.05 M NaCl as background electrolyte. Solutions were mixed for 24 hours at room temperature, centrifuged and the supernatants analyzed by UV/visible spectrophotometry. Equilibrium solution concentrations were measured and used to determine the number of moles adsorbed per square meter. Langmuir isotherms were constructed using the experimental data. It was found that adenine-containing molecules tend to bind much more strongly than thymine-containing molecules. It was also found that the number of moles adsorbed at saturation tends to fall with increasing chain length, while adsorption affinity tends to rise. Oligomer length appears to affect adsorption more than the mineral type. These results may have implications for the primordial organization of the first nucleic acid molecules as the persistence of extra-cellular nucleic acids in the environment. References Bernal, J. D. (1951) The Physical Basis of Life (Routledge, London). Miller S.L. and Cleaves, H.J. (2006) Prebiotic chemistry on the primitive Earth. In

  16. Structural Characteristics of the Alpha-Synuclein Oligomers Stabilized By the Flavonoid Baicalein

    Energy Technology Data Exchange (ETDEWEB)

    Hong, D.-P.; Fink, A.L.; Uversky, V.N.

    2009-05-18

    The flavonoid baicalein inhibits fibrillation of alpha-synuclein, which is a major component of Lewy bodies in Parkinson's disease. It has been known that baicalein induces the formation of alpha-synuclein oligomers and consequently prevents their fibrillation. In order to evaluate the structural properties of baicalein-stabilized oligomers, we purified oligomer species by HPLC and examined their stability and structure by CD, Fourier transform infrared spectroscopy, size exclusion chromatography HPLC, small-angle X-ray scattering, and atomic force microscopy. Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. They did not form fibrils even after very prolonged incubation. From small-angle X-ray scattering data and atomic force microscopy images, the oligomers were characterized as quite compact globular species. Oligomers were extremely stable, with a GdmCl C(m)=3.3 M. This high stability explains the previously observed inhibition properties of baicalein against alpha-synuclein fibrillation. These baicalein-stabilized oligomers, added to the solution of aggregating alpha-synuclein, were able to noticeably inhibit its fibrillation. After prolonged coincubation, short fibrils were formed, suggesting an effective interaction of oligomers with monomeric alpha-synuclein. Membrane permeability tests suggested that the baicalein-stabilized oligomers had a mild effect on the integrity of the membrane surface. This effect was rather similar to that of the monomeric protein, suggesting that targeted stabilization of certain alpha-synuclein oligomers might offer a potential strategy for the development of novel Parkinson's disease therapies.

  17. Metabolic modeling of Rosmarinic acid biosynthetic pathway

    OpenAIRE

    Sundaram, Shanthy; Tripathi, Ashutosh; Gupta, Deepak K

    2010-01-01

    Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4‐dihydroxyphenyllacticacid. It is commonly found in Coleus blumei, Salvia officinalis, Melissa officinalis and Rosmarinus officinalis. The biosynthesis of RA starts with precursor molecules L‐phenylalanine and L‐tyrosine. Simulation of RA biosynthetic pathway was done using Gepasi Software, includes the reaction kinetics of each step of the pathway and different integration methods such as Euler's method. Optimization of the significant...

  18. In situ biodegradable crosslinking of cationic oligomer coating on mesoporous silica nanoparticles for drug delivery.

    Science.gov (United States)

    Wang, Yifeng; Wang, Jine; Yang, Yang; Sun, Yi; Yuan, Yuan; Li, Yulin; Liu, Changsheng

    2017-05-01

    Although layer-by-layer assembly using anionic and cationic polymer has been a popular way to develop core-shell nanoparticles, the strong electrostatic interactions may limit shell degradability, thus hampering their application as a platform for controlled therapeutic delivery. In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-drug loading (using doxorubicin (DOX) as a model drug) into mesoporous silica nanoparticles (MSN), followed by surface functionalization with a kind of cationic oligomer (low molecular weight polyethylene imine, LPEI) and in situ crosslinking by degradable N,N'-bis(acryloyl)cystamine (BAC). The presence of LPEI shell affords the nanohybrids with charge-reversal ability, which means that the acidic tumor extracellular microenvironment can transform the negative surface charge at neutral conditions into positive-charged ones. The nanohybrids displayed a pH- and redox-dual sensitivity in DOX release under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The nanohybrids can be effectively internalized into A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their high potential as a new platform for therapeutic delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Diffusivities and Viscosities of Poly(ethylene oxide) Oligomers

    KAUST Repository

    Hong, Bingbing

    2010-10-14

    Diffusivities and viscosities of poly(ethylene oxide) (PEO) oligomer melts with 1 to 12 repeat units have been obtained from equilibrium molecular dynamics simulations using the TraPPE-UA force field. The simulations generated diffusion coefficients with high accuracy for all of the molar masses studied, but the statistical uncertainties in the viscosity calculations were significantly larger for longer chains. There is good agreement of the calculated viscosities and densities with available experimental data, and thus, the simulations can be used to bridge gaps in the data and for extrapolations with respect to chain length, temperature, and pressure. We explored the convergence characteristics of the Green-Kubo formulas for different chain lengths and propose minimal production times required for convergence of the transport properties. The chain-length dependence of the transport properties suggests that neither Rouse nor reptation models are applicable in the short-chain regime investigated. © 2010 American Chemical Society.

  20. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    Directory of Open Access Journals (Sweden)

    Rogério Barbosa Lima

    Full Text Available Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H, guaiacyl (G and syringyl (S monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway in a growth chamber for 24 h. In general, the results showed that 1 cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2 cinnamic and p-coumaric acids increased p-hydroxyphenyl (H monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G content, and sinapic acid increased sinapyl (S content; 3 when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H, cinnamic acid reduced H, G and S contents; and 4 when applied in conjunction with 3,4-(methylenedioxycinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL, p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  1. Amyloid oligomers and protofibrils, but not filaments, self-replicate from native lysozyme.

    Science.gov (United States)

    Mulaj, Mentor; Foley, Joseph; Muschol, Martin

    2014-06-25

    Self-assembly of amyloid fibrils is the molecular mechanism best known for its connection with debilitating human disorders such as Alzheimer's disease but is also associated with various functional cellular responses. There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly.

  2. Subunit conformational variation within individual GroEL oligomers resolved by Cryo-EM.

    Science.gov (United States)

    Roh, Soung-Hun; Hryc, Corey F; Jeong, Hyun-Hwan; Fei, Xue; Jakana, Joanita; Lorimer, George H; Chiu, Wah

    2017-08-01

    Single-particle electron cryo-microscopy (cryo-EM) is an emerging tool for resolving structures of conformationally heterogeneous particles; however, each structure is derived from an average of many particles with presumed identical conformations. We used a 3.5-Å cryo-EM reconstruction with imposed D7 symmetry to further analyze structural heterogeneity among chemically identical subunits in each GroEL oligomer. Focused classification of the 14 subunits in each oligomer revealed three dominant classes of subunit conformations. Each class resembled a distinct GroEL crystal structure in the Protein Data Bank. The conformational differences stem from the orientations of the apical domain. We mapped each conformation class to its subunit locations within each GroEL oligomer in our dataset. The spatial distributions of each conformation class differed among oligomers, and most oligomers contained 10-12 subunits of the three dominant conformation classes. Adjacent subunits were found to more likely assume the same conformation class, suggesting correlation among subunits in the oligomer. This study demonstrates the utility of cryo-EM in revealing structure dynamics within a single protein oligomer.

  3. Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C).

    Science.gov (United States)

    Kim, Chae; Haldiman, Tracy; Surewicz, Krystyna; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Kong, Qingzhong; Telling, Glenn C; Surewicz, Witold K; Safar, Jiri G

    2012-01-01

    The mammalian prions replicate by converting cellular prion protein (PrP(C)) into pathogenic conformational isoform (PrP(Sc)). Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrP(Sc) on conversion of PrP(C) in vitro using PrP(Sc) seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD). The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s) PrP(Sc). The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrP(Sc). The tight correlation between conversion potency of small oligomers of human sPrP(Sc) observed in vitro and duration of the disease suggests that sPrP(Sc) conformers are an important determinant of prion strain characteristics that control the progression rate of the disease.

  4. Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    Full Text Available The mammalian prions replicate by converting cellular prion protein (PrP(C into pathogenic conformational isoform (PrP(Sc. Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrP(Sc on conversion of PrP(C in vitro using PrP(Sc seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD. The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s PrP(Sc. The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrP(Sc. The tight correlation between conversion potency of small oligomers of human sPrP(Sc observed in vitro and duration of the disease suggests that sPrP(Sc conformers are an important determinant of prion strain characteristics that control the progression rate of the disease.

  5. Small Protease Sensitive Oligomers of PrPSc in Distinct Human Prions Determine Conversion Rate of PrPC

    Science.gov (United States)

    Kim, Chae; Haldiman, Tracy; Surewicz, Krystyna; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Sy, Man-Sun; Cohen, Mark; Kong, Qingzhong; Telling, Glenn C.; Surewicz, Witold K.; Safar, Jiri G.

    2012-01-01

    The mammalian prions replicate by converting cellular prion protein (PrPC) into pathogenic conformational isoform (PrPSc). Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrPSc on conversion of PrPC in vitro using PrPSc seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD). The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s) PrPSc. The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrPSc. The tight correlation between conversion potency of small oligomers of human sPrPSc observed in vitro and duration of the disease suggests that sPrPSc conformers are an important determinant of prion strain characteristics that control the progression rate of the disease. PMID:22876179

  6. Phenylethynyl Terminated Arylene Ether Oxadiazole and Triazole Oligomers and Their Cured Polymers

    Science.gov (United States)

    Thompson, C. M.; Hergenrother, P. M.

    2001-01-01

    Several novel phenylethynyl terminated arylene ether oligomers containing oxadiazole and triazole rings were prepared as part of an effort to develop high performance polymers with an attractive combination of properties (e.g. processability and mechanical performance) for future NASA applications. The oligomers displayed low melt viscosities and good solubilities. Thin films cast from solutions of the oligomers and cured for one hour at 350 C in air gave good tensile properties. Titanium to titanium (6Al-4V) tensile shear specimens were readily fabricated and provided moderate strengths. The chemistry and properties of these new materials are discussed.

  7. Effect of molecular weight of oligomer on ionic diffusion in oligomer electrolytes and its implication for dye-sensitized solar cells

    Science.gov (United States)

    Park, Jong Hyuk; Choi, Kyu Jin; Kim, Junkyung; Kang, Yong Soo; Lee, Sang-Soo

    This study measures the diffusion coefficients of I - and I 3 - in oligomer electrolytes as a function of the molecular weight of oligomers and investigates their effect on the performance of dye-sensitized solar cells (DSSCs). The high-diffusion coefficients of ions in an oligomer electrolyte with a lower molecular weight can help to promote the redox mechanism in DSSCs and thereby increase the short-circuit current density. They can also cause a decrease in the open-circuit voltage since a high-diffusion coefficient of I 3 - is capable of reducing the lifetime of electrons in TiO 2 electrodes. To offset these effects, N-methyl-benzimidazole is added to the oligomer electrolytes, thereby improving the open-circuit voltage and fill factor and, consequently, the overall energy-conversion efficiency, which increases to over 5%. A further test involving storage at a high temperature of 75 °C demonstrates that DSSCs employing the oligomer electrolytes show excellent thermal stability over 200 h.

  8. Supplementation with xylanase and β-xylosidase to reduce xylo-oligomer and xylan inhibition of enzymatic hydrolysis of cellulose and pretreated corn stover

    Directory of Open Access Journals (Sweden)

    Qing Qing

    2011-06-01

    Full Text Available Abstract Background Hemicellulose is often credited with being one of the important physical barriers to enzymatic hydrolysis of cellulose, and acts by blocking enzyme access to the cellulose surface. In addition, our recent research has suggested that hemicelluloses, particularly in the form of xylan and its oligomers, can more strongly inhibit cellulase activity than do glucose and cellobiose. Removal of hemicelluloses or elimination of their negative effects can therefore become especially pivotal to achieving higher cellulose conversion with lower enzyme doses. Results In this study, cellulase was supplemented with xylanase and β-xylosidase to boost conversion of both cellulose and hemicellulose in pretreated biomass through conversion of xylan and xylo-oligomers to the less inhibitory xylose. Although addition of xylanase and β-xylosidase did not necessarily enhance Avicel hydrolysis, glucan conversions increased by 27% and 8% for corn stover pretreated with ammonia fiber expansion (AFEX and dilute acid, respectively. In addition, adding hemicellulase several hours before adding cellulase was more beneficial than later addition, possibly as a result of a higher adsorption affinity of cellulase and xylanase to xylan than glucan. Conclusions This key finding elucidates a possible mechanism for cellulase inhibition by xylan and xylo-oligomers and emphasizes the need to optimize the enzyme formulation for each pretreated substrate. More research is needed to identify advanced enzyme systems designed to hydrolyze different substrates with maximum overall enzyme efficacy.

  9. Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers

    Science.gov (United States)

    Minsky, Burcu Baykal; Dubin, Paul L.; Kaltashov, Igor A.

    2017-04-01

    The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions.

  10. Dopamine prevents lipid peroxidation-induced accumulation of toxic α-synuclein oligomers by preserving autophagy-lysosomal function

    Science.gov (United States)

    Jiang, Peizhou; Gan, Ming; Yen, Shu-Hui C.

    2013-01-01

    The formation of Lewy bodies containing α-synuclein (α-syn), prominent loss of dopaminergic neurons and dopamine (DA) deficiency in substantia nigra and striatum are histopathological and biochemical hallmarks of Parkinson’s disease (PD). Multiple lines of evidence have indicated that a critical pathogenic factor causing PD is enhanced production of reactive oxygen species (ROS), which reacts readily with polyunsaturated fatty acids to cause lipid peroxidation (LPO). LPO products have been shown to facilitate assembly of toxic α-syn oligomers in in vitro studies. Since DA is prone to autoxidation and cause ROS, it has been suggested that interactions among DA, LPO, and α-syn play an important role in neuronal loss in PD. However, the exact mechanism(s) remains unclear. We addressed this issue using a neuronal cell model which inducibly expresses human wild-type α-syn by the tetracycline off (Tet-Off) mechanism and stably expresses high levels of DA transporter. Under retinoic acid elicited neuronal differentiation, cells with or without overexpressing α-syn and with or without exposure to LPO inducer-arachidonic acid (AA), plus 0–500 μM of DA were assessed for the levels of LPO, α-syn accumulation, cell viability, and autophagy. AA exposure elicited similar LPO levels in cells with and without α-syn overexpression, but significantly enhanced the accumulation of α-syn oligomers and monomers only in cultures with Tet-Off induction and decreased cell survival in a LPO-dependent manner. Surprisingly, DA at low concentrations (100 μM), DA exposure enhanced the toxic effects of AA. To our knowledge, this is the first report showing biphasic effects of DA on neuronal survival and α-syn accumulation. PMID:23754979

  11. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

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    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  12. Oleocanthal ameliorates amyloid-β oligomers' toxicity on astrocytes and neuronal cells: In vitro studies.

    Science.gov (United States)

    Batarseh, Yazan S; Mohamed, Loqman A; Al Rihani, Sweilem B; Mousa, Youssef M; Siddique, Abu Bakar; El Sayed, Khalid A; Kaddoumi, Amal

    2017-06-03

    Extra-virgin olive oil (EVOO) has several health promoting effects. Evidence have shown that EVOO attenuates the pathology of amyloid-β (Aβ) and improves cognitive function in experimental animal models, suggesting it's potential to protect and reduce the risk of developing Alzheimer's disease (AD). Available studies have linked this beneficial effect to oleocanthal, one of the active components in EVOO. The effect of oleocanthal against AD pathology has been linked to its ability to attenuate Aβ and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild-type and AD transgenic mice in vivo. However, the ability of oleocanthal to alter the toxic effect of Aβ on brain parenchymal cells is unknown. In the current study, we investigated oleocanthal effect on modulating Aβ oligomers (Aβo) pathological events in neurons and astrocytes. Our findings demonstrated oleocanthal prevented Aβo-induced synaptic proteins, SNAP-25 and PSD-95, down-regulation in neurons, and attenuated Aβo-induced inflammation, glutamine transporter (GLT1) and glucose transporter (GLUT1) down-regulation in astrocytes. Aβo-induced inflammation was characterized by interleukin-6 (IL-6) increase and glial fibrillary acidic protein (GFAP) upregulation that were reduced by oleocanthal. In conclusion, this study provides further evidence to support the protective effect of EVOO-derived phenolic secoiridoid oleocanthal against AD pathology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Microwave assisted synthesis of bithiophene based donor-acceptor-donor oligomers and their optoelectronic performances

    Science.gov (United States)

    Bathula, Chinna; Buruga, Kezia; Lee, Sang Kyu; Khazi, Imtiyaz Ahmed M.; Kang, Youngjong

    2017-07-01

    In this article we present the synthesis of two novel bithiophene based symmetrical π conjugated oligomers with donor-acceptor-donor (D-A-D) structures by microwave assisted PdCl2(dppf) catalyzed Suzuki coupling reaction. These molecules contain electron rich bithiophene as a donor, dithienothiadiazole[3,4-c]pyridine and phthalic anhydride units as acceptors. The shorter reaction time, excellent yields and easy product isolation are the advantages of this method. The photophysical prerequisites for electronic application such as strong and broad optical absorption, thermal stability, and compatible energy levels were determined for synthesized oligomers. Optical band gap for the oligomers is found to be 1.72-1.90 eV. The results demonstrated the novel oligomers to be promising candidates in organic optoelectronic applications.

  14. Antimicrobial Silver Chloride Nanoparticles Stabilized with Chitosan Oligomer for the Healing of Burns

    OpenAIRE

    Yun Ok Kang; Ju-Young Jung; Donghwan Cho; Oh Hyeong Kwon; Ja Young Cheon; Won Ho Park

    2016-01-01

    Recently, numerous compounds have been studied in order to develop antibacterial agents, which can prevent colonized wounds from infection, and assist the wound healing. For this purpose, novel silver chloride nanoparticles stabilized with chitosan oligomer (CHI-AgCl NPs) were synthesized to investigate the influence of antibacterial chitosan oligomer (CHI) exerted by the silver chloride nanoparticles (AgCl NPs) on burn wound healing in a rat model. The CHI-AgCl NPs had a spherical morphology...

  15. Distinct annular oligomers captured along the assembly and disassembly pathways of transthyretin amyloid protofibrils.

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    Ricardo H Pires

    Full Text Available BACKGROUND: Defects in protein folding may lead to severe degenerative diseases characterized by the appearance of amyloid fibril deposits. Cytotoxicity in amyloidoses has been linked to poration of the cell membrane that may involve interactions with amyloid intermediates of annular shape. Although annular oligomers have been detected in many amyloidogenic systems, their universality, function and molecular mechanisms of appearance are debated. METHODOLOGY/PRINCIPAL FINDINGS: We investigated with high-resolution in situ atomic force microscopy the assembly and disassembly of transthyretin (TTR amyloid protofibrils formed of the native protein by pH shift. Annular oligomers were the first morphologically distinct intermediates observed in the TTR aggregation pathway. Morphological analysis suggests that they can assemble into a double-stack of octameric rings with a 16 ± 2 nm diameter, and displaying the tendency to form linear structures. According to light scattering data coupled to AFM imaging, annular oligomers appeared to undergo a collapse type of structural transition into spheroid oligomers containing 8-16 monomers. Disassembly of TTR amyloid protofibrils also resulted in the rapid appearance of annular oligomers but with a morphology quite distinct from that observed in the assembly pathway. CONCLUSIONS/SIGNIFICANCE: Our observations indicate that annular oligomers are key dynamic intermediates not only in the assembly but also in the disassembly of TTR protofibrils. The balance between annular and more compact forms of aggregation could be relevant for cytotoxicity in amyloidogenic disorders.

  16. Annular Protofibrils Are a Structurally and Functionally Distinct Type of Amyloid Oligomer*

    Science.gov (United States)

    Kayed, Rakez; Pensalfini, Anna; Margol, Larry; Sokolov, Yuri; Sarsoza, Floyd; Head, Elizabeth; Hall, James; Glabe, Charles

    2009-01-01

    Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif. PMID:19098006

  17. Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer.

    Science.gov (United States)

    Kayed, Rakez; Pensalfini, Anna; Margol, Larry; Sokolov, Yuri; Sarsoza, Floyd; Head, Elizabeth; Hall, James; Glabe, Charles

    2009-02-13

    Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (alphaAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in alphaAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric alpha-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a beta barrel structural motif.

  18. Unique copper-induced oligomers mediate alpha-synuclein toxicity.

    Science.gov (United States)

    Wright, Josephine A; Wang, Xiaoyan; Brown, David R

    2009-08-01

    Parkinson's disease and a number of other neurodegenerative diseases have been linked to either genetic mutations in the alpha-synuclein gene or show evidence of aggregates of the alpha-synuclein protein, sometimes in the form of Lewy bodies. There currently is no clear evidence of a distinct neurotoxic species of alpha-synuclein to explain the death of neurons in these diseases. We undertook to assess the toxicity of alpha-synuclein via exogenous application in cell culture. Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Other members of the synuclein family showed no toxicity in any form and inherited point mutations did not alter the effective toxic concentration of alpha-synuclein. Through protein fractionation techniques, we were able to isolate an oligomeric species responsible for the toxicity of alpha-synuclein. This oligomeric species has a unique stellate appearance under EM and again, requires association with copper to induce cell death. The results allow us to suggest that the toxic species of alpha-synuclein in vivo could possibly be these stellate oligomers and not fibrils. Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration.

  19. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

    Science.gov (United States)

    Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

    2017-11-01

    Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

  20. Update on Phytochemistry and Pharmacology of Naturally Occurring Resveratrol Oligomers.

    Science.gov (United States)

    Shen, Jie; Zhou, Qiang; Li, Pei; Wang, Zhiqiang; Liu, Shuangshuang; He, Chunnian; Zhang, Chunhong; Xiao, Peigen

    2017-11-24

    Resveratrol oligomers (REVs), a major class of stilbenoids, are biosynthesized by regioselective oxidative coupling of two to eight units of resveratrol monomer. Due to their unique structures and pleiotropic biological activities, natural product chemists are increasingly focusing on REVs in the last few decades. This study presents a detailed and thorough examination of REVs, including chemical structures, natural resources, and biological activities, during the period of 2010-2017. Ninety-two new REVs compounds, including 39 dimers, 23 trimers, 13 tetramers, six resveratrol monomers, six hexamers, four pentamers, and one octamer, have been reported from the families of Dipterocarpaceae, Paeoniaceae, Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and Poaceae. Amongst these families, Dipterocarpaceae, with 50 REVs, accounts for the majority, and seven genera of Dipterocarpaceae are involved, including Vatica , Vateria , Shorea , Hopea , Neobalanocarpus , Dipterocarpus , and Dryobalanops . These REVs have shown a wide range of bioactivities. Pharmacological studies have mainly focused on potential efficacy on tumors, bacteria, Alzheimer's disease, cardiovascular diseases, and others. The information updated in this review might assist further research and development of novel REVs as potential therapeutic agents.

  1. Carboxybetaine methacrylate oligomer modified nylon for circulating tumor cells capture.

    Science.gov (United States)

    Dong, Chaoqun; Wang, Huiyu; Zhang, Zhuo; Zhang, Tao; Liu, Baorui

    2014-10-15

    Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Synthesis of Chitosan Oligomers/Propolis/Silver Nanoparticles Composite Systems and Study of Their Activity against Diplodia seriata

    Directory of Open Access Journals (Sweden)

    Petruta Mihaela Matei

    2015-01-01

    Full Text Available The synthesis and characterization of composites of oligomeric chitosan with propolis extract which allow the incorporation of a third component (silver nanoparticles are reported, together with their application in aqueous or hydroalcoholic solutions with a view to the formation of adhesive substances or nanofilms for the protection of vineyards against harmful xylophagous fungi. The antimicrobial properties of the association of the two biological products or those resulting from the incorporation of silver nanoparticles (NPs are studied and discussed. The efficacy of the chitosan oligomers/propolis/silver NPs ternary system is assessed in vitro for Diplodia fungi. A preliminary study on the convenience of replacing propolis with gentisic acid is also presented.

  3. Caffeic Acid Phenethyl Ester Loaded PLGA Nanoparticles: Effect of Various Process Parameters on Reaction Yield, Encapsulation Efficiency, and Particle Size

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    Serap Derman

    2015-01-01

    Full Text Available CAPE loaded PLGA nanoparticles were prepared using the oil in water (o/w single emulsion solvent evaporation methods. Five different processing parameters including initial CAPE amount, initial PLGA amount, PVA concentration in aqueous phase, PVA volume, and solvent type were screened systematically to improve encapsulation of hydrophobic CAPE molecule, simultaneously minimize particle size, and raise the reaction yield. Obtained results showed that the encapsulation efficiency of the nanoparticles significantly increased with the increase of the initial CAPE amount (p<0.05 and particle size (p<0.05. Furthermore, the particle size is significantly influenced by initial polymer amount (p<0.05 and surfactant concentration (p<0.05. By the optimization of process parameters, the nanoparticles produced 70±6% reaction yield, 89±3% encapsulation efficiency, -34.4±2.5 mV zeta potential, and 163±2 nm particle size with low polydispersity index 0.119±0.002. The particle size and surface morphology of optimized nanoparticles were studied and analyses showed that the nanoparticles have uniform size distribution, smooth surface, and spherical shape. Lyophilized nanoparticles with different CAPE and PLGA concentration in formulation were examined for in vitro release at physiological pH. Interestingly, the optimized nanoparticles showed a high (83.08% and sustained CAPE release (lasting for 16 days compared to nonoptimized nanoparticle.

  4. Efficacy of various naturally occurring caffeic acid derivatives in preventing post-harvest protein losses in forages

    Science.gov (United States)

    In red clover, oxidation of endogenous o-diphenols by polyphenol oxidase (PPO) inhibits post-harvest proteolyis. This system is transferable to alfalfa by providing PPO (via a transgene) and o-diphenol PPO substrates (via exogenous application). To exploit the PPO system for protein protection, it w...

  5. Cytoprotection of Human Endothelial Cells From Menadione Cytotoxicity by Caffeic Acid Phenethyl Ester: The Role of Heme Oxygenase-1

    Science.gov (United States)

    2008-06-08

    cells (HUVEC) to evaluate potential gene expression involvement. CAPE exhibited dose- dependent cytoprotection of HUVEC. A gene screen with...highly induced (8.25-fold) by CAPE compared to DMSO control. To validate this particular microarray screening result, quantitative real-time RT-PCR was...the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. The Journal of Biological Chemistry 279, 8919–8929. Minami, T

  6. Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids.

    Directory of Open Access Journals (Sweden)

    Carlos A H Fernandes

    Full Text Available One of the main challenges in toxicology today is to develop therapeutic alternatives for the treatment of snake venom injuries that are not efficiently neutralized by conventional serum therapy. Venom phospholipases A2 (PLA2s and PLA2-like proteins play a fundamental role in skeletal muscle necrosis, which can result in permanent sequelae and disability. This leads to economic and social problems, especially in developing countries. In this work, we performed structural and functional studies with Piratoxin-I, a Lys49-PLA2 from Bothropspirajai venom, complexed with two compounds present in several plants used in folk medicine against snakebites. These ligands partially neutralized the myotoxic activity of PrTX-I towards binding on the two independent sites of interaction between Lys49-PLA2 and muscle membrane. Our results corroborate the previously proposed mechanism of action of PLA2s-like and provide insights for the design of structure-based inhibitors that could prevent the permanent injuries caused by these proteins in snakebite victims.

  7. The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease.

    Science.gov (United States)

    Mancini, Simona; Minniti, Stefania; Gregori, Maria; Sancini, Giulio; Cagnotto, Alfredo; Couraud, Pierre-Olivier; Ordóñez-Gutiérrez, Lara; Wandosell, Francisco; Salmona, Mario; Re, Francesca

    2016-01-01

    We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Extraction of chitosan and its oligomers from shrimp shell waste, their characterization and antimicrobial effect.

    Science.gov (United States)

    Varun, Tarun Kumar; Senani, Swaraj; Jayapal, Natasha; Chikkerur, Jayaram; Roy, Sohini; Tekulapally, Vijay Bhasker; Gautam, Mayank; Kumar, Narender

    2017-02-01

    The present study was performed to utilize the shrimp shell waste for chitin and chitosan production, characterization by Fourier transform infrared (FT-IR) technique and to evaluate the antimicrobial effects of chitosan oligomers produced by depolymerization of chitosan by nitrous acid. Chitosan was extracted from the shrimp shell waste by the chemical method and characterized by FT-IR. Chitooligomers were produced by depolymerising chitosan using nitrous acid, and the chitooligomers were tested for antimicrobial effect against four gut pathogenic organisms, i.e., Enterobacter aerogen (National Collection of Dairy Culture [NCDC] 106), Enterococcus faecalis (NCDC 119), Escherichia coli (NCDC 134), and Staphylococcus aureus (NCDC 109) by well diffusion method using Muller-Hinton agar. A pure culture of pathogenic organisms was collected from NCDC, ICAR-National Dairy Research Institute, Karnal. Extracted chitosan characterized by FT-IR and chitooligomers demonstrated antimicrobial effect against four gut pathogenic organisms used in this study. Zone of inhibitions (mm) were observed in E. faecalis (13±0.20), E. coli (11.5±0.4), S. aureus (10.7±0.2), and E. aerogen (10.7±0.3). E. faecalis showed larger inhibition zone as compared to all other organisms and inhibitions zones of E. aerogen and S. aureus were comparable to each other. Shrimp waste can be utilized for chitosan production, and the chitooligomers can be used as feed additive for gut health enhancement and have potential to replace antibiotics from the feed. Along with value addition pollutant load could be reduced by waste utilization.

  9. Extraction of chitosan and its oligomers from shrimp shell waste, their characterization and antimicrobial effect

    Directory of Open Access Journals (Sweden)

    Tarun Kumar Varun

    2017-02-01

    Full Text Available Aim: The present study was performed to utilize the shrimp shell waste for chitin and chitosan production, characterization by Fourier transform infrared (FT-IR technique and to evaluate the antimicrobial effects of chitosan oligomers produced by depolymerization of chitosan by nitrous acid. Materials and Methods: Chitosan was extracted from the shrimp shell waste by the chemical method and characterized by FT-IR. Chitooligomers were produced by depolymerising chitosan using nitrous acid, and the chitooligomers were tested for antimicrobial effect against four gut pathogenic organisms, i.e., Enterobacter aerogen (National Collection of Dairy Culture [NCDC] 106, Enterococcus faecalis (NCDC 119, Escherichia coli (NCDC 134, and Staphylococcus aureus (NCDC 109 by well diffusion method using Muller-Hinton agar. A pure culture of pathogenic organisms was collected from NCDC, ICAR-National Dairy Research Institute, Karnal. Results: Extracted chitosan characterized by FT-IR and chitooligomers demonstrated antimicrobial effect against four gut pathogenic organisms used in this study. Zone of inhibitions (mm were observed in E. faecalis (13±0.20, E. coli (11.5±0.4, S. aureus (10.7±0.2, and E. aerogen (10.7±0.3. E. faecalis showed larger inhibition zone as compared to all other organisms and inhibitions zones of E. aerogen and S. aureus were comparable to each other. Conclusion: Shrimp waste can be utilized for chitosan production, and the chitooligomers can be used as feed additive for gut health enhancement and have potential to replace antibiotics from the feed. Along with value addition pollutant load could be reduced by waste utilization.

  10. Self-assembly of conjugated oligomers and polymers at the interface: structure and properties

    Science.gov (United States)

    Xu, Lirong; Yang, Liu; Lei, Shengbin

    2012-07-01

    In this review, we give a brief account on the recent scanning tunneling microscopy investigation of interfacial structures and properties of π-conjugated semiconducting oligomers and polymers, either at the solid-air (including solid-vacuum) or at the solid-liquid interface. The structural aspects of the self-assembly of both oligomers and polymers are highlighted. Conjugated oligomers can form well ordered supramolecular assemblies either at the air-solid or liquid-solid interface, thanks to the relatively high mobility and structural uniformity in comparison with polymers. The backbone structure, substitution of side chains and functional groups can affect the assembling behavior significantly, which offers the opportunity to tune the supramolecular structure of these conjugated oligomers at the interface. For conjugated polymers, the large molecular weight limits the mobility on the surface and the distribution in size also prevents the formation of long range ordered supramolecular assembly. The submolecular resolution obtained on the assembling monolayers enables a detailed investigation of the chain folding at the interface, both the structural details and the effect on electronic properties. Besides the ability in studying the assembling structures at the interfaces, STM also provides a reasonable way to evaluate the distribution of the molecular weight of conjugated polymers by statistic of the contour length of the adsorbed polymer chains. Both conjugated oligomers and polymers can form composite assemblies with other materials. The ordered assembly of oligomers can act as a template to controllably disperse other molecules such as coronene or fullerene. These investigations open a new avenue to fine tune the assembling structure at the interface and in turn the properties of the composite materials. To summarize scanning tunneling microscopy has demonstrated its surprising ability in the investigation of the assembling structures and properties of

  11. Solvent free low-melt viscosity imide oligomers and thermosetting polymide composites

    Science.gov (United States)

    Chuang, Chun-Hua (Inventor)

    2012-01-01

    .[.This invention relates to the composition and a solvent-free process for preparing novel imide oligomers and polymers specifically formulated with effective amounts of a dianhydride such as 2,3,3',4-biphenyltetra carboxylic dianydride (a-BPDA), at least one aromatic diamine and an endcapped of 4-phenylethynylphthalic anhydride (PEPA) or nadic anhydride to produce imide oligomers that possess a low-melt viscosity of 1-60 poise at 260-280.degree. C. When the imide oligomer melt is cured at about 371.degree. C. in a press or autoclave under 100-500 psi, the melt resulted in a thermoset polyimide having a glass transition temperature (T.sub.g) equal to and above 310.degree. C. A novel feature of this process is that the monomers; namely the dianhydrides, diamines and the endcaps, are melt processable to form imide oligomers at temperatures ranging between 232-280.degree. C. (450-535.degree. F.) without any solvent. These low-melt imide oligomers can be easily processed by resin transfer molding (RTM), vacuum-assisted resin transfer molding (VARTM) or the resin infusion process with fiber preforms e.g. carbon, glass or quartz preforms to produce polyimide matrix composites with 288-343.degree. C. (550-650.degree. F.) high temperature performance capability..]. .Iadd.This invention relates to compositions and a solvent-free reaction process for preparing imide oligomers and polymers specifically derived from effective amounts of dianhydrides such as 2,3,3',4'-biphenyltetracarboxylic dianhydride (a-BPDA), at least one aromatic polyamine and an end-cap such as 4-phenylethynyphthalic anhydride (PEPA) or nadic anhydride to produce imide oligomers that possess a low-melt viscosity of 1-60 poise at 260.degree. C.-280.degree. C..Iaddend.

  12. Assessing the contribution of heterogeneous distributions of oligomers to aggregation mechanisms of polyglutamine peptides.

    Science.gov (United States)

    Vitalis, Andreas; Pappu, Rohit V

    2011-11-01

    Polyglutamine aggregation is associated with neurodegeneration in nine different disorders. The effects of polyglutamine length and peptide concentration on the kinetics of aggregation were previously analyzed using a homogeneous nucleation model that assumes the presence of a single bottleneck along the free energy profile G(n), where n denotes the number of polyglutamine molecules. The observation of stable, soluble oligomers as intermediates along aggregation pathways is refractory to the assumptions of homogeneous nucleation. Furthermore, the analysis of in vitro kinetic data using a specific variant of homogeneous nucleation leads to confounding observations such as fractional and/or negative values for estimates of the critical nucleus size. Here, we show that the homogeneous nucleation model is inherently robust and is unlikely to yield fractional values if the underlying process is strictly homogeneous with a free energy profile G(n) that displays a sharp maximum at n=n*, where n* corresponds to the critical nucleus. Conversely, a model that includes oligomers of different size and different potentials for supporting turnover into fibrils yields estimates of fractional and/or negative nucleus sizes when the kinetic data are analyzed using the assumption of a homogeneous process. This model provides a route to reconcile independent observations of heterogeneous distributions of oligomers and other non-fibrillar aggregates with results obtained from analysis of aggregation kinetics using the assumption of a homogeneous nucleation model. In the new model, the mechanisms of fibril assembly are governed by the relative stabilities of two types of oligomers viz., fibril-competent and fibril-incompetent oligomers, the size of the smallest fibril competent oligomer, and rates for conformational conversion within different oligomers. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Novel Enzymatic Synthesis of 3-hydroxybutyric Acid Oligomerswith Inserted Lactobionic Acid Moieties

    NARCIS (Netherlands)

    Kakasi-Zsurka, S.; Todea, A.; But, A.; Paul, C.; Boeriu, C.G.; Nagv, A.; Davidescu, C.M.; Peter, F.

    2011-01-01

    3-Hydroxybutyric acid and lactobionic acid yielded linear and cyclic oligomers in a lipase-catalyzedcondensation polymerization reaction, performed at 80°C in bulk and organic solvent systems. Novozyme435 was the most efficient biocatalyst, and a mixture of t-butanol and dimethylsulfoxide in 80:20

  14. Enrichment of maize and triticale bran with recombinant Aspergillus tubingensis ferulic acid esterase

    CSIR Research Space (South Africa)

    Zwane, EN

    2017-03-01

    Full Text Available from maize bran and triticale bran, respectively, and also significantly increased the levels of p-coumaric and caffeic acid from triticale bran. The cost-effective production of AtFAEA could therefore allow for the enrichment of brans generally used...

  15. Ferulic acid enhances IgE binding to peanut allergens in western blots.

    Science.gov (United States)

    Phenolic compounds at high concentrations are known to form insoluble complexes with proteins. We hypothesized that this complex formation could interfere with Western blot and ELISA assays for peanut allergens. To verify this, three simple phenolic compounds (ferulic, caffeic, and chlorogenic acids...

  16. Analysis of PEG oligomers in black gel inks: Discrimination and ink dating.

    Science.gov (United States)

    Sun, Qiran; Luo, Yiwen; Xiang, Ping; Yang, Xu; Shen, Min

    2017-08-01

    Carbon-based black gel inks are common samples in forensic practice of questioned document examination in China, but there are few analytical methods for this type of ink. In this study, a liquid chromatography-.high resolution mass spectrometry (LC-HRMS) method was established for the analysis of PEG oligomers in carbon-based black gel ink entries. The coupled instruments achieve both the identification and quantification of PEG oligomers in ink entries with reproducible results. Twenty carbon-based black gel inks, whose Raman spectra appeared identical, were analyzed using the LC-HRMS method. As a result, the twenty gel inks were classified into four groups according to the distribution of PEG oligomers. Artificially aging of PEG 400 and a gel ink showed that as PEG degraded, the relative amounts of low molecular weight PEG oligomers increased, while those of high molecular weight decreased. The degradation of PEG oligomers in a naturally aged gel ink was consistent with those in the artificially aged samples, but occurred more slowly. This study not only provided a new method for discriminating carbon-based black gel ink entries, but also offered a new approach for studying the relative ink dating of carbon-based black gel ink entries. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Thin films of arylenevinylene oligomers prepared by MAPLE for applications in non-linear optics

    Energy Technology Data Exchange (ETDEWEB)

    Stanculescu, A., E-mail: sanca@infim.ro [National Institute of Materials Physics, Optics and Spectroscopy Laboratory, 105 bis Atomistilor Street, P.O. Box MG-7, Bucharest-Magurele 077125 (Romania); Vacareanu, L.; Grigoras, M. [P. Poni' Institute of Macromolecular Chemistry, 41 A Gr. Ghica Voda Alley, 700487 Iasi (Romania); Socol, M. [National Institute of Materials Physics, Optics and Spectroscopy Laboratory, 105 bis Atomistilor Street, P.O. Box MG-7, Bucharest-Magurele 077125 (Romania); Socol, G. [National Institute for Laser, Plasma and Radiation Physics, Str. Atomistilor, Nr. 409, P.O. Box MG-36, Magurele, Bucharest 077125 (Romania); Stanculescu, F. [Faculty of Physics, University of Bucharest, Str. Atomistilor nr.405, P.O. Box MG-11, Bucharest-Magurele 077125 (Romania); Preda, N.; Matei, E. [National Institute of Materials Physics, Optics and Spectroscopy Laboratory, 105 bis Atomistilor Street, P.O. Box MG-7, Bucharest-Magurele 077125 (Romania); Ionita, I. [Faculty of Physics, University of Bucharest, Str. Atomistilor nr.405, P.O. Box MG-11, Bucharest-Magurele 077125 (Romania); Girtan, M. [Laboratoire de Photonique d' Angers, Universite d' Angers, 2, Bd. Lavoisier, 49045 Angers (France); Mihailescu, I.N. [National Institute for Laser, Plasma and Radiation Physics, Str. Atomistilor, Nr. 409, P.O. Box MG-36, Magurele, Bucharest 077125 (Romania)

    2011-04-01

    This paper discusses two arylenevinylene oligomers with optical nonlinear properties. Their trans molecular structure was confirmed by Fourier Transform Infrared Spectroscopy and Nuclear Magnetic Resonance. Second Harmonic Generation and two-photon fluorescence have been observed on Matrix Assisted Pulsed Laser Evaporation-deposited thin films. We have seen two local maxima in UV-Vis spectra and a red shift of the photoluminescence peak for carbazole-based oligomer, which can be correlated with a higher conformational flexibility and with strong polarization interactions in the solid state. Scanning Electron Microscopy and Atomic Force Microscopy images have revealed a grainy morphology of the film deposited on titanium and a higher roughness for carbazole-based oligomer. Second harmonic measurements have shown nearly equal values of the second-order nonlinear optical coefficient for the triphenylamine and carbazole-based oligomers for P{sub laser} < 100 mW. z-Scan and x-scan representations of the carbazole-based oligomer film have shown strong two-photon fluorescence intensity inside the sample confirming a volume process, and a strong second harmonic at the surface of the sample determined by the surface morphology.

  18. Determination of the critical molar mass of ovalbumin oligomers degraded by ultrasound

    Directory of Open Access Journals (Sweden)

    BRATOLJUB H. MILOSAVLJEVIC

    2000-02-01

    Full Text Available An experimental method has been developed which enables the determination of the critical molar mass (Mmc of ovalbumin oligomers degraded by ultrasound of known frequency. To test the validity of the Mmc postulate, a series of ovalbumin oligomers was prepared by the radiolytic cross-linking of 1% solutions of ovalbumin monomer dissolved in 50 mM Na/K-phosphate buffer pH 7.0 saturated with N2O. Under these conditions, irradiation with 5 kGy from a 60Co source, yielded ovalbumin dimers, trimers, tetramers, and higher order oligomers. On the basis of the results obtained with the ovalbumin oligomers, it was concluded that for ultrasound of 23 kHz frequency and 5mm amplitude, the Mmc was 274000 + 14000 g/mol. Our results confirmed that the two postulates in the chemistry of polymer degradation by ultrasound are valid when ovalbumin oligomers are used as substrates, i.e., (1 that the higher the molar mass of the original macromolecule, the faster is its degradation rate, and (2 that a lower molar mass limit (LMmL exists below which the macromolecules are resistent to further degradation.

  19. Ferroelectricity and the phase transition in large area evaporated vinylidene fluoride oligomer thin films

    Science.gov (United States)

    Foreman, K.; Poddar, Shashi; Ducharme, Stephen; Adenwalla, S.

    2017-05-01

    Organic ferroelectric materials, including the well-known poly(vinylidene fluoride) and its copolymers, have been extensively studied and used for a variety of applications. In contrast, the VDF oligomer has not been thoroughly investigated and is not widely used, if used at all. One key advantage the oligomer has over the polymer is that it can be thermally evaporated in vacuum, allowing for the growth of complex heterostructures while maintaining interfacial cleanliness. Here, we report on the ferroelectric properties of high-quality VDF oligomer thin films over relatively large areas on the order of mm2. The operating temperature is identified via differential scanning calorimetry and pyroelectric measurements. Pyroelectric measurements also reveal a stable remanent polarization for these films which persists over very long time scales, an important result for non-volatile data storage. Temperature dependent pyroelectric and capacitance measurements provide compelling evidence for the phase transition in these films. Capacitance-voltage and current-voltage measurements are used to confirm ferroelectricity, quantify the dielectric loss, and calculate the spontaneous polarization. Finally, piezoresponse force microscopy is used to demonstrate large area, low-voltage ferroelectric domain reading/writing in VDF oligomer thin films. This work enables new channels for VDF oligomer applications and research.

  20. Parametrization of the Gay-Berne potential for conjugated oligomer with a high aspect ratio.

    Science.gov (United States)

    Lee, Cheng K; Hua, Chi C; Chen, Show A

    2010-08-14

    The Gay-Berne (GB) potential has been a popular semiempirical model for describing the short-range intermolecular forces for a wide variety of aspherical molecules, including liquid crystals and anisotropic colloids, with generally small molecular dimensions and low aspect ratios (<5). This study evaluates the parametrization of the GB potential for a high-aspect-ratio (=10) oligomer belonging to a model conjugated polymer. We elaborate that the semiflexibility associated with a large oligomer species demands a variant umbrella-sampling scheme in establishing the potentials of mean force (PMFs) for four pair ellipsoid arrangements typically utilized to parametrize the GB potential. The model ellipsoid so constructed is shown to capture the PMFs of essential intermediate arrangements as well, and, according to the results of simplex optimizations, recommendations are given for the minimum set of parameters to be included in the optimization of a large oligomer or particulate species. To further attest the parametrized GB potential, the coarse-grained (CG) Monte Carlo simulations employing the GB potential and the back-mapped, full-atom atomistic molecular dynamics (AMD) simulations were performed for a dense oligomer system at two representative system temperatures. The results indicated that the CG simulations can capture, with exceptional computational efficiency, the AMD predictions with good thermal transferability. In future perspectives, we remark on potential applications to construct efficient, parameter-free CG models for capturing fundamental material properties of large oligomer/particulate species as well as long-chain conjugated polymers.

  1. Migration of oligomers from PET: determination of diffusion coefficients and comparison of experimental versus modelled migration.

    Science.gov (United States)

    Hoppe, Maria; Fornari, Roberta; de Voogt, Pim; Franz, Roland

    2017-07-01

    Polyethylene terephthalate (PET) is increasingly used as food-contact material in, for example, containers for beverage such as bottles for soft drinks, mineral water, juices and beer. Mass transport of substances present in packaging materials into the packed food and beverages is monitored to verify the food law compliance of the materials. PET is known to contain or give rise to migrants that are oligomers derived from the polymeric material. Until now their actual migration potential has been investigated only poorly. A convenient way to determine their migration would be by using models. To verify existing models with experimental data, a migration kinetic study of PET oligomers was conducted. PET bottle material was submerged in 50% ethanol at 80°C for 15 h. The oligomer content in the migration solutions was determined every hour using LC-MS with the first-series cyclic PET trimer as standard. Diffusion coefficients of five PET oligomers (first-series dimer and trimer, second-series dimer and trimer, and third-series dimer) were calculated from the obtained data and compared with the calculated diffusion coefficients using the models of Welle and Piringer. This is the first study to provide diffusion characteristics of oligomers in PET other than the first-series cyclic trimer.

  2. Transesterification of PHA to oligomers covalently bonded with (bioactive compounds containing either carboxyl or hydroxyl functionalities.

    Directory of Open Access Journals (Sweden)

    Iwona Kwiecień

    Full Text Available This manuscript presents the synthesis and structural characterisation of novel biodegradable polymeric controlled-release systems of pesticides with potentially higher resistance to weather conditions in comparison to conventional forms of pesticides. Two methods for the preparation of pesticide-oligomer conjugates using the transesterification reaction were developed. The first method of obtaining conjugates, which consist of bioactive compounds with the carboxyl group and polyhydroxyalkanoates (PHAs oligomers, is "one-pot" transesterification. In the second method, conjugates of bioactive compounds with hydroxyl group and polyhydroxyalkanoates oligomers were obtained in two-step method, through cyclic poly(3-hydroxybutyrate oligomers. The obtained pesticide-PHA conjugates were comprehensively characterised using GPC, 1H NMR and mass spectrometry techniques. The structural characterisation of the obtained products at the molecular level with the aid of mass spectrometry confirmed that both of the synthetic strategies employed led to the formation of conjugates in which selected pesticides were covalently bonded to PHA oligomers via a hydrolysable ester bond.

  3. A novel glutathione-hydroxycinnamic acid product generated in oxidative wine conditions.

    Science.gov (United States)

    Bouzanquet, Quentin; Barril, Celia; Clark, Andrew C; Dias, Daniel A; Scollary, Geoffrey R

    2012-12-12

    This study characterizes a novel glutathione-substituted dihydroxyphenyl compound formed during the oxidation of white wine and model wine solutions, which may contribute to the synergistic role of glutathione and hydroxycinnamic acids in delaying oxidative coloration. The critical components for the formation of the compound were found to be hydroxycinnamic acids and glutathione, while ascorbic acid enabled the product to accumulate to higher concentrations. The presence of the wine components important in other wine oxidation mechanisms, (+)-catechin, ethanol and/or tartaric acid, was not essential for the formation of this new compound. Via LC-MS/MS, HR-MS and (1)H NMR (1D and 2D NMR) analyses, the major isomer of the compound formed from glutathione and caffeic acid was found to be 4-[(E)-2'-(S)-glutathionyl ethenyl]-catechol (GEC). Equivalent products were also confirmed via LC-MS/MS for other hydroxycinnamic acids (i.e., ferulic and coumaric acids). Only trace amounts of GEC were formed with the quinic ester of caffeic acid (i.e., chlorogenic acid), and no equivalent product was found for cinnamic acid. GEC was detected in a variety of white wines supplemented with glutathione and caffeic acid. A radical mechanism for the formation of the styrene-glutathione derivatives is proposed.

  4. The effect of thyme oil low-density polyethylene impregnated pellets in polylactic acid sachets on storage quality of ready-to-eat avocado

    CSIR Research Space (South Africa)

    Bill, M

    2018-01-01

    Full Text Available the incidence severity of anthracnose and enabled the retention of dietary phytochemicals (p-coumaric, ferulic and caffeic acid, catechin and epicatechin), fatty acids, mannoheptulose, fruit firmness and taste compared to the currently used prochloraz® fungicide...

  5. Dietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids.

    Science.gov (United States)

    Combet, Emilie; El Mesmari, Aziza; Preston, Tom; Crozier, Alan; McColl, Kenneth E L

    2010-03-15

    Acid-catalyzed nitrosation and production of potentially carcinogenic nitrosative species is focused at the gastroesophageal junction, where salivary nitrite, derived from dietary nitrate, encounters the gastric juice. Ascorbic acid provides protection by converting nitrosative species to nitric oxide (NO). However, NO may diffuse into adjacent lipid, where it reacts with O(2) to re-form nitrosative species and N-nitrosocompounds (NOC). In this way, ascorbic acid promotes acid nitrosation. Using a novel benchtop model representing the gastroesophageal junction, this study aimed to clarify the action of a range of water-soluble antioxidants on the nitrosative mechanisms in the presence or absence of lipids. Caffeic, ferulic, gallic, or chlorogenic and ascorbic acids were added individually to simulated gastric juice containing secondary amines, with or without lipid. NO and O(2) levels were monitored by electrochemical detection. NOC were measured in both aqueous and lipid phases by gas chromatography-tandem mass spectrometry. In the absence of lipids, all antioxidants tested inhibited nitrosation, ranging from 35.9 + or - 7.4% with gallic acid to 93 + or - 0.6% with ferulic acid. In the presence of lipids, the impact of each antioxidant on nitrosation was inversely correlated with the levels of NO they generated (R(2) = 0.95, pascorbic acid promoted nitrosation, whereas ferulic and caffeic acids markedly inhibited nitrosation. Copyright 2010 Elsevier Inc. All rights reserved.

  6. [Effect of procyanidolic oligomers on corneal collagen fibrillogenesis].

    Science.gov (United States)

    Robert, A M; Robert, L; Renard, G

    2005-12-01

    We showed in a previous study that procyanidolic oligomers (PCOs) from grape seeds effectively protect corneal stroma against degradation by bacterial collagenase. Here we report the study of the effect of PCOs on protein and collagen composition of cornea and on the biosynthesis of corneal collagens. Bovine corneas were used in explant cultures. We quantitatively determined total proteins and collagen as well as the incorporation of 3H-proline in separated collagen types. Collagens type I, V, and VI were separated and quantitated. In order to understand some of the results obtained, we studied the interaction of PCO with collagen type I separately. In the absence of PCOs, collagen typing and 3H-proline incorporation yielded the expected results for a normal cornea, with the usual proportion of the three major types of collagens. In presence of PCOs at 1 mg/ml and after 24 h incubation, total proteins and collagens decreased, as did papain-extractable collagens. Proteins in the final residue solubilized in 1 M KOH-80% v/v aqueous ethanol increased. The proportion of the three principal collagens was also modified: type I became preponderant, and the proportions of the two others (type V and VI) decreased. The study of the interaction of collagen type I with PCOs showed that 30% of total PCOs do not interact with collagen, 20% interact reversibly, and 50% of PCOs are strongly and irreversibly fixed. This strongly fixed fraction could not be separated from collagen by either column chromatography or collagenase or KOH in aqueous ethanol. Bovine corneas in explant cultures in presence of PCOs undergo a modification of their protein and collagen content, with a concurrent modification of the proportion of collagens types I, V, and VI. Collagen type I predominates, and the two other types decrease. Study of the collagen type I-PCO interaction showed that roughly 50% of PCOs become irreversibly fixed to collagen, resisting collagenase or other methods of separation. This

  7. Biodegradable polyester-based eco-composites containing hemp fibers modified with macrocyclic oligomers

    Science.gov (United States)

    Conzatti, Lucia; Utzeri, Roberto; Hodge, Philip; Stagnaro, Paola

    2016-05-01

    An original compatibilizing pathway for hemp fibers/poly(1,4-butylene adipate-co-terephtalate) (PBAT) eco-composites was explored exploiting the capability of macrocyclic oligomers (MCOs), obtained by cyclodepolymerization (CDP) of PBAT at high dilution, of being re-converted into linear chains by entropically-driven ring-opening polymerization (ED-ROP) that occurs simply heating the MCOS in the bulk. CDP reaction of PBAT was carried out varying solvent, catalyst and reaction time. Selected MCOs were used to adjust the conditions of the ED-ROP reaction. The best experimental conditions were then adopted to modify hemp fibers. Eco-composites based on PBAT and hemp fibers as obtained or modified with PBAT macrocyclics or oligomers were prepared by different process strategies. The best fiber-PBAT compatibility was observed when the fibers were modified with PBAT oligomers before incorporation in the polyester matrix.

  8. Resin adhesion strengths to zirconia ceramics after primer treatment with silane coupling monomer or oligomer.

    Science.gov (United States)

    Okada, Masahiro; Inoue, Kazusa; Irie, Masao; Taketa, Hiroaki; Torii, Yasuhiro; Matsumoto, Takuya

    2017-09-26

    Resin bonding to zirconia ceramics is difficult to achieve using the standard methods for conventional silica-based dental ceramics, which employ silane coupling monomers as primers. The hypothesis in this study was that a silane coupling oligomer -a condensed product of silane coupling monomers- would be a more suitable primer for zirconia. To prove this hypothesis, the shear bond strengths between a composite resin and zirconia were compared after applying either a silane coupling monomer or oligomer. The shear bond strength increased after applying a non-activated ethanol solution of the silane coupling oligomer compared with that achieved when applying the monomer. Thermal treatment of the zirconia at 110°C after application of the silane coupling agents was essential to improve the shear bond strength between the composite resin cement and zirconia.

  9. Stress relaxation following uniaxial extension of polystyrene melt and oligomer dilutions

    DEFF Research Database (Denmark)

    Huang, Qian; Rasmussen, Henrik K.

    2016-01-01

    The filament stretching rheometer has been used to measure the stress relaxation following the startup of uniaxial extensional flow, on anarrow molar mass distribution (NMMD) polystyrene melt and styrene oligomer dilutions thereof. All samples used here were characterizedin molecular weight......, mechanical spectroscopy, and constant strain rate uniaxial extension in the work of Huang et al. [Macromolecules 46,5026–5035 (2013); ACS Macro Lett. 2, 741–744 (2013)]. The stress relaxation following the steady extensional stress was measured on a285 kg/mole NMMD polystyrene and two 1.92 kg/mole styrene...... oligomer dilutions thereof {PS-285k, PS-285k/2k-72, and PS-285k/2k-44 inthe work of Huang et al. [Macromolecules 46, 5026–5035 (2013)]}. The two dilutions contained 28 and 56 wt. % oligomer, respectively.Further, the stress relaxation on a 545 kg/mole NMMD polystyrene diluted with 48 wt. % 0.972 kg...

  10. Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury.

    Science.gov (United States)

    Gatson, Joshua Wayne; Warren, Victoria; Abdelfattah, Kareem; Wolf, Steven; Hynan, Linda S; Moore, Carol; Diaz-Arrastia, Ramon; Minei, Joseph P; Madden, Christopher; Wigginton, Jane G

    2013-06-01

    Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (Aβ) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecular-weight β-amyloid oligomers were measured using Western blot analysis. Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

  11. Convenient synthesis and application of versatile nucleic acid lipid membrane anchors in the assembly and fusion of liposomes

    DEFF Research Database (Denmark)

    Ries, Oliver; Löffler, Philipp M. G.; Vogel, Stefan

    2015-01-01

    Hydrophobic moieties like lipid membrane anchors are highly demanded modifications for nucleic acid oligomers. Membrane-anchor modified oligonucleotides are applicable in biomedicine leading to new delivery strategies as well as in biophysical investigations towards assembly and fusion of liposom...

  12. The phenolic acids of some species of the Oenothera L. genus

    OpenAIRE

    Tadeusz Krzaczek; Anna Bogucka-Kocka; Renata Śnieżko

    2014-01-01

    The occurence and approximative quantitative proportions of the phenolic acids in four species of the Oenothera L. genus was determined by the method of TLC and HPLC. In all species of Oenothera L. genus the permanent occurrence of acids: 2-hydroxy-4-metoxybenzoic, salicylic, ferulic, syringic, vanillic, p-coumaric, p-hydroxybenzoic, p-hydroxyphenylacetic, γ-rezorcil, gentysic, protocatechuic, caffeic and gallic has been confirmed. Whereas the other phenolic acids: o-coumaric, o-hydroxyphenyl...

  13. Biogenesis of rosmarinic acid in Mentha

    Science.gov (United States)

    Ellis, B. E.; Towers, G. H. N.

    1970-01-01

    The biogenesis of rosmarinic acid (α-O-caffeoyl-3,4-dihydroxyphenyl-lactic acid), the second most common ester of caffeic acid in the plant kingdom, was studied in Mentha arvense and Mentha piperita. Administration of 14C-labelled compounds showed that, whereas the caffeoyl moiety was formed from phenylalanine via cinnamic acid and p-coumaric acid, the 3,4-dihydroxyphenyl-lactic acid moiety was formed from tyrosine and 3,4-dihydroxyphenylalanine. Time-course studies and the use of labelled rosmarinic acid showed that endogenous rosmarinic acid had a low turnover rate. The caffeoyl moiety did not appear to contribute to the formation of insoluble polymers, as has been suggested for chlorogenic acid in other plants. PMID:5484678

  14. Extended Ladder-Type Benzo[ k ]tetraphene-Derived Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jongbok [Department of Chemistry, Texas A& M University, 3255 TAMU College Station TX 77843-3255 USA; Li, Huanbin [MOE Key Laboratory of Macromolecular Synthesis and Functionalization, State Key Laboratory of Silicon Materials, Department of Polymer Science and Engineering, Zhejiang University, 38 Zheda Rd Hangzhou 310027 China; Kalin, Alexander J. [Department of Chemistry, Texas A& M University, 3255 TAMU College Station TX 77843-3255 USA; Yuan, Tianyu [Department of Materials Science and Engineering, Texas A& M University, 3003 TAMU College Station TX 77843-3003 USA; Wang, Chenxu [Department of Materials Science and Engineering, Texas A& M University, 3003 TAMU College Station TX 77843-3003 USA; Olson, Troy [Department of Chemistry, Texas A& M University, 3255 TAMU College Station TX 77843-3255 USA; Li, Hanying [MOE Key Laboratory of Macromolecular Synthesis and Functionalization, State Key Laboratory of Silicon Materials, Department of Polymer Science and Engineering, Zhejiang University, 38 Zheda Rd Hangzhou 310027 China; Fang, Lei [Department of Chemistry, Texas A& M University, 3255 TAMU College Station TX 77843-3255 USA; Department of Materials Science and Engineering, Texas A& M University, 3003 TAMU College Station TX 77843-3003 USA

    2017-10-02

    Well-defined, fused-ring aromatic oligomers represent promising candidates for the fundamental understanding and application of advanced carbon-rich materials, though bottom-up synthesis and structure–property correlation of these compounds remain challenging. In this work, an efficient synthetic route was employed to construct extended benzo[k]tetraphene-derived oligomers with up to 13 fused rings. The molecular and electronic structures of these compounds were clearly elucidated. Precise correlation of molecular sizes and crystallization dynamics was established, thus demonstrating the pivotal balance between intermolecular interaction and molecular mobility for optimized processing of highly ordered solids of these extended conjugated molecules.

  15. Enzymatic elongation of microsatellite oligomers for use in direct-label chemiluminescent hybridizations.

    Science.gov (United States)

    Longmire, J L; Ratliff, R L

    1994-12-01

    Short, synthetic oligonucleotide sequences representing microsatellites and other short tandem repeats can be elongated (concatamerized) using a simple method in which complementary strands are annealed, phosphorylated, primer extended and ligated. When used in direct-label chemiluminescent hybridizations, the elongated microsatellite sequences provide an approximately 30-fold increase in signal strength compared with microsatellite oligomers that have not been concatamerized. Concatamerization of simple repeat oligomers further enables the use of relatively short oligonucleotide sequences in direct-label chemiluminescent hybridization experiments, thereby reducing the overall need for radioisotopes in certain commonly performed laboratory procedures such as DNA fingerprinting and selection of clones containing microsatellite sequences.

  16. Aggregation mechanism of an IgG2 and two IgG1 monoclonal antibodies at low pH: from oligomers to larger aggregates.

    Science.gov (United States)

    Arosio, Paolo; Rima, Simonetta; Morbidelli, Massimo

    2013-03-01

    To identify the aggregation mechanism and the stability characteristics of three different monoclonal antibodies under acidic conditions. The aggregation kinetics is analyzed by a combination of light scattering, size exclusion chromatography and fluorescence techniques and the aggregation data are correlated to protein structure, hydrophobicity, charge and antibody subclass. In the investigated conditions, the antibody aggregation follows a mechanism consisting of two-steps: reversible monomer oligomerization followed by irreversible cluster-cluster aggregation. The kinetics of the two steps is differently affected by the operating conditions: mild destabilizing conditions induce formation of oligomers which are stable within weeks, while stronger denaturing conditions promote aggregation of oligomers to larger aggregates which eventually precipitate. For different antibodies significant differences in both oligomerization and growth rates are found, even for antibodies belonging to the same subclass. For all antibodies the aggregate formation is accompanied by a structure re-organization with an increase in the ordered β-sheet structures. At low pH the aggregation propensity of the investigated antibodies does not correlate with antibody subclass, surface net charge and hydrophobicity of the non-native state. The aggregation mechanism of three antibodies in acidic conditions as well as differences and analogies in their stability behavior has been characterized.

  17. Effect of particle size on the composition of lignin derived oligomers obtained by fast pyrolysis of beech wood

    NARCIS (Netherlands)

    Zhou, Shuai; Garcia-Perez, Manuel; Pecha, Brennan; McDonald, Armando G.; Westerhof, Roel Johannes Maria

    2014-01-01

    The effect of particle size on the yield and composition of lignin derived oligomers (also known as pyrolytic lignin (PL)) was studied in a fluidized bed reactor. Milled beech wood particles of sizes between 0.3 and 0.55 and cylinders of 3–14 mm were pyrolyzed at 500 °C. The lignin oligomers were

  18. RP-HPLC analysis of phenolic acids of selected Central European Carex L. (Cyperaceae) species and its implication for taxonomy.

    Science.gov (United States)

    Bogucka-Kocka, Anna; Szewczyk, Katarzyna; Janyszek, Magdalena; Janyszek, Sławomir; Cieśla, Łukasz

    2011-01-01

    Eighteen species belonging to the Carex genus were checked for the presence and the amount of eight phenolic acids (p-hydroxybenzoic, vanillic, caffeic, syringic, protocatechuic, p-coumaric, sinapic, and ferulic) by means of HPLC. Both the free and bonded phenolic acids were analyzed. The majority of the analyzed acids occurred in the studied species in relatively high amounts. The highest concentrations found were caffeic acid and p-coumaric acid, for which the detected levels were negatively correlated. A very interesting feature was the occurrence of sinapic acid, a compound very rarely detected in plant tissues. Its distribution across the analyzed set of species can be hypothetically connected with the humidity of plants' habitats. Several attempted tests of aggregative cluster analysis showed no similarity to the real taxonomical structure of the genus Carex. Thus, the phenolic acids' composition cannot be considered as the major taxonomical feature for the genus Carex.

  19. High-Resolution Studies of Hyaluronic Acid Mixtures through Capillary Gel Electrophoresis.

    Science.gov (United States)

    Hong, M; Sudor, J; Stefansson, M; Novotny, M V

    1998-02-01

    Hyaluronic acid is a negatively charged polysaccharide with a high degree of polydispersity that makes the separation of its oligomers extremely difficult. Through the use of columns filled with a highly viscous polyacrylamide matrix, the unit resolution of hyaluronate oligomers could be achieved, up to at least 80 kDa of mass, through capillary electrophoresis. As analytical application examples, the fractions of enzymatically or ultrasonically degraded hyaluronates were monitored through this method. Because of the very high resolving power, peaks additional to the regular oligomers can be observed that are assumed to be conformers of this regular, unbranched biopolymer.

  20. Supported Intrinsically Porous Oligomers as Hybrid Materials for Separations, Storage, and Sensing

    Science.gov (United States)

    Thompson, Anthony Boone

    Adsorption-desorption phenomena are often difficult to study at the molecular level because the surfaces on which they occur can be heterogeneous, giving a wide distribution of adsorption sites and associated energies. Considering that these phenomena underlie an incredibly wide variety of industrially important processes, a better understanding could aid in the development of more efficient methods. In this work, we describe an approach to designing materials with well-defined adsorption sites by covalently attaching intrinsically porous molecules to solid surfaces by a rigid multidentate linker. These cup-shaped molecules are intended to act as adsorption sites on the material, whereas the rigid attachment to the solid support serves to prevent movement and conformational changes of the sites, leading to better understanding of adsorption phenomena. As a proof-of-concept application, materials were used for adsorption of n-butanol biofuel and related compounds from dilute aqueous solution. The materials were thermally and hydrolytically stable, and adsorption phenomena were reversible. Adsorption sites containing more hydrophobic molecular area led to stronger adsorption, suggesting that it is driven by weak van der Waals forces. Likewise, adsorption sites that were strongly polarized performed poorly, possibly reflecting a greater energy penalty of removing water molecules from the cavity. Upon placing a Lewis acidic metal at the bottom of the cavity, an enhancement was seen only with the most acidic metal, which may indicate weak guest coordination. Observing that hydrophobic interactions dominate adsorption on these materials, efforts were made to develop hybrid materials with large hydrophobic area for adsorption. Glaser coupling of diethynylbenzene was used to grow oligo(phenylene butadiynylene)s from the surface of silica, resulting in materials that were more than 25% organic by weight. In addition to their potential use as adsorbents, these materials may

  1. Oligomer formation during gas-phase ozonolysis of small alkenes and enol ethers: new evidence for the central role of the Criegee Intermediate as oligomer chain unit

    Directory of Open Access Journals (Sweden)

    A. Sadezky

    2008-05-01

    Full Text Available An important fraction of secondary organic aerosol (SOA formed by atmospheric oxidation of diverse volatile organic compounds (VOC has recently been shown to consist of high-molecular weight oligomeric species. In our previous study (Sadezky et al., 2006, we reported the identification and characterization of oligomers as main constituents of SOA from gas-phase ozonolysis of small enol ethers. These oligomers contained repeated chain units of the same chemical composition as the main Criegee Intermediates (CI formed during the ozonolysis reaction, which were CH2O2 (mass 46 for alkyl vinyl ethers (AVE and C2H4O2 (mass 60 for ethyl propenyl ether (EPE. In the present work, we extend our previous study to another enol ether (ethyl butenyl ether EBE and a variety of structurally related small alkenes (trans-3-hexene, trans-4-octene and 2,3-dimethyl-2-butene.

    Experiments have been carried out in a 570 l spherical glass reactor at atmospheric conditions in the absence of seed aerosol. SOA formation was measured by a scanning mobility particle sizer (SMPS. SOA filter samples were collected and chemically characterized off-line by ESI(+/TOF MS and ESI(+/TOF MS/MS, and elemental compositions were determined by ESI(+/FTICR MS and ESI(+/FTICR MS/MS. The results for all investigated unsaturated compounds are in excellent agreement with the observations of our previous study. Analysis of the collected SOA filter samples reveal the presence of oligomeric compounds in the mass range 200 to 800 u as major constituents. The repeated chain units of these oligomers are shown to systematically have the same chemical composition as the respective main Criegee Intermediate (CI formed during ozonolysis of the unsaturated compounds, which is C3H6O2 (mass 74 for ethyl butenyl ether (EBE, trans-3-hexene, and 2,3-dimethyl-2-butene, and C4H8

  2. High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification.

    Science.gov (United States)

    Kotler, Samuel A; Brender, Jeffrey R; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M Banaszak; Marsh, E Neil G; Ramamoorthy, Ayyalusamy

    2015-07-03

    Alzheimer's disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling (1)H-(1)H NMR experiments to overcome many of these limitations. Using (1)H-(1)H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time (1)H-(1)H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils.

  3. GPCR-OKB: the G Protein Coupled Receptor Oligomer Knowledge Base.

    NARCIS (Netherlands)

    Khelashvili, G.; Dorff, K.; Shan, J.; Camacho-Artacho, M.; Skrabanek, L.; Vroling, B.; Bouvier, M.; Devi, L.A.; George, S.R.; Javitch, J.A.; Lohse, M.J.; Milligan, G.; Neubig, R.R.; Palczewski, K.; Parmentier, M.; Pin, J.P.; Vriend, G.; Campagne, F.; Filizola, M.

    2010-01-01

    SUMMARY: Rapid expansion of available data about G Protein Coupled Receptor (GPCR) dimers/oligomers over the past few years requires an effective system to organize this information electronically. Based on an ontology derived from a community dialog involving colleagues using experimental and

  4. An update on the physiological and therapeutic relevance of GPCR oligomers.

    Science.gov (United States)

    Farran, Batoul

    2017-03-01

    The traditional view on GPCRs held that they function as single monomeric units composed of identical subunits. This notion was overturned by the discovery that GPCRs can form homo- and hetero-oligomers, some of which are obligatory, and can further assemble into receptor mosaics consisting of three or more protomers. Oligomerisation exerts significant impacts on receptor function and physiology, offering a platform for the diversification of receptor signalling, pharmacology, regulation, crosstalk, internalization and trafficking. Given their involvement in the modulation of crucial physiological processes, heteromers could constitute important therapeutic targets for a wide range of diseases, including schizophrenia, Parkinson's disease, substance abuse or obesity. This review aims at depicting the current developments in GPCR oligomerisation research, documenting various class A, B and C GPCR heteromers detected in vitro and in vivo using biochemical and biophysical approaches, as well as recently identified higher-order oligomeric complexes. It explores the current understanding of dimerization dynamics and the possible interaction interfaces that drive oligomerisation. Most importantly, it provides an inventory of the wide range of physiological processes and pathophysiological conditions to which GPCR oligomers contribute, surveying some of the oligomers that constitute potential drug targets. Finally, it delineates the efforts to develop novel classes of ligands that specifically target and tether to receptor oligomers instead of a single monomeric entity, thus ameliorating their ability to modulate GPCR function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

    Directory of Open Access Journals (Sweden)

    Makoto Nakai

    2014-01-01

    Full Text Available Here, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471 and the in vitro chromosomal aberration test (OECD test guideline No. 473 under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low.

  6. High-capacity conductive nanocellulose paper sheets for electrochemically controlled extraction of DNA oligomers.

    Directory of Open Access Journals (Sweden)

    Aamir Razaq

    Full Text Available Highly porous polypyrrole (PPy-nanocellulose paper sheets have been evaluated as inexpensive and disposable electrochemically controlled three-dimensional solid phase extraction materials. The composites, which had a total anion exchange capacity of about 1.1 mol kg(-1, were used for extraction and subsequent release of negatively charged fluorophore tagged DNA oligomers via galvanostatic oxidation and reduction of a 30-50 nm conformal PPy layer on the cellulose substrate. The ion exchange capacity, which was, at least, two orders of magnitude higher than those previously reached in electrochemically controlled extraction, originated from the high surface area (i.e. 80 m(2 g(-1 of the porous composites and the thin PPy layer which ensured excellent access to the ion exchange material. This enabled the extractions to be carried out faster and with better control of the PPy charge than with previously employed approaches. Experiments in equimolar mixtures of (dT(6, (dT(20, and (dT(40 DNA oligomers showed that all oligomers could be extracted, and that the smallest oligomer was preferentially released with an efficiency of up to 40% during the reduction of the PPy layer. These results indicate that the present material is very promising for the development of inexpensive and efficient electrochemically controlled ion-exchange membranes for batch-wise extraction of biomolecules.

  7. Structural Investigations of on-pathway Oligomers of α-Synuclein

    DEFF Research Database (Denmark)

    Pedersen, Martin Nors; Horvath, Istvan; Weise, Christoph F.

    ). "Hunting the Chameleon: Structural Conformations of the Intrinsically Disordered Protein Alpha-Synuclein." Chembiochem 13(6): 761-768. Giehm, L., et al. (2011). "Low-resolution structure of a vesicle disrupting alpha-synuclein oligomer that accumulates during fibrillation." Proceedings of the National...

  8. Ultrafast Photoinduced Electron Transfer in a π-Conjugated Oligomer/Porphyrin Complex

    KAUST Repository

    Aly, Shawkat Mohammede

    2014-10-02

    Controlling charge transfer (CT), charge separation (CS), and charge recombination (CR) at the donor-acceptor interface is extremely important to optimize the conversion efficiency in solar cell devices. In general, ultrafast CT and slow CR are desirable for optimal device performance. In this Letter, the ultrafast excited-state CT between platinum oligomer (DPP-Pt(acac)) as a new electron donor and porphyrin as an electron acceptor is monitored for the first time using femtosecond (fs) transient absorption (TA) spectroscopy with broad-band capability and 120 fs temporal resolution. Turning the CT on/off has been shown to be possible either by switching from an organometallic oligomer to a metal-free oligomer or by controlling the charge density on the nitrogen atom of the porphyrin meso unit. Our time-resolved data show that the CT and CS between DPP-Pt(acac) and cationic porphyrin are ultrafast (approximately 1.5 ps), and the CR is slow (ns time scale), as inferred from the formation and the decay of the cationic and anionic species. We also found that the metallic center in the DPP-Pt(acac) oligomer and the positive charge on the porphyrin are the keys to switching on/off the ultrafast CT process.

  9. Facile Synthesis of Highly Crystalline and Large Areal Hexagonal Boron Nitride from Borazine Oligomers

    Science.gov (United States)

    Park, Sungchan; Seo, Tae Hoon; Cho, Hyunjin; Min, Kyung Hyun; Lee, Dong Su; Won, Dong-Il; Kang, Sang Ook; Kim, Myung Jong

    2017-01-01

    A novel and facile synthetic method for h-BN films from borazine oligomer (B3N3H4)x precursors has been developed. This method only includes spin-coating of borazine oligomer onto nickel catalysts and a subsequent annealing step. Large areal and highly crystalline h-BN films were obtained. The stoichiometric B/N ratio of borazine oligomer precursor was preserved in the final h-BN product such that it was close to 1 as revealed by XPS. Catalytic effect of nickel for h-BN formation was clearly demonstrated by lowering crystallization temperature compared to the growth condition in the absence of catalyst. The graphene field effect transistor (GFET) characterization has proved the high quality synthesis of h-BN films, showing the shift of neutrality point and the increase of the mobility. This method can also provide functional h-BN coating on various surfaces by annealing Ni-coated borazine oligomer films and subsequent removal of Ni catalyst. PMID:28074854

  10. Student-Driven Design of Peptide Mimetics: Microwave-Assisted Synthesis of Peptoid Oligomers

    Science.gov (United States)

    Pohl, Nicola L. B.; Kirshenbaum, Kent; Yoo, Barney; Schulz, Nathan; Zea, Corbin J.; Streff, Jennifer M.; Schwarz, Kimberly L.

    2011-01-01

    An experiment for the undergraduate organic laboratory is described in which peptide mimetic oligomers called "peptoids" are built stepwise on a solid-phase resin. Students employ two modern strategies to facilitate rapid multistep syntheses: solid-phase techniques to obviate the need for intermediate purifications and microwave irradiation to…

  11. Optimization of the All-D Peptide D3 for Aβ Oligomer Elimination.

    Directory of Open Access Journals (Sweden)

    Antonia Nicole Klein

    Full Text Available The aggregation of amyloid-β (Aβ is postulated to be the crucial event in Alzheimer's disease (AD. In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized d-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified d-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i inhibit the formation of Thioflavin T-positive fibrils; (ii bind to Aβ monomers with micromolar affinities; (iii eliminate Aβ oligomers; (iv reduce Aβ-induced cytotoxicity; and (v disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.

  12. The Volumetric Diversity of Misfolded Prion Protein Oligomers Revealed by Pressure Dissociation*

    Science.gov (United States)

    Torrent, Joan; Lange, Reinhard; Rezaei, Human

    2015-01-01

    Protein oligomerization has been associated with a wide range of diseases. High pressure approaches offer a powerful tool for deciphering the underlying molecular mechanisms by revealing volume changes associated with the misfolding and assembly reactions. We applied high pressure to induce conformational changes in three distinct β-sheet-rich oligomers of the prion protein PrP, a protein characterized by a variety of infectious quaternary structures that can propagate stably and faithfully and cause diseases with specific phenotypic traits. We show that pressure induces dissociation of the oligomers and leads to a lower volume monomeric PrP state that refolds into the native conformation after pressure release. By measuring the different pressure and temperature sensitivity of the tested PrP oligomers, we demonstrate significantly different void volumes in their quaternary structure. In addition, by focusing on the kinetic and energetic behavior of the pressure-induced dissociation of one specific PrP oligomer, we reveal a large negative activation volume and an increase in both apparent activation enthalpy and entropy. This suggests a transition state ensemble that is less structured and significantly more hydrated than the oligomeric state. Finally, we found that site-specific fluorescent labeling allows monitoring of the transient population of a kinetic intermediate in the dissociation reaction. Our results indicate that defects in atomic packing may deserve consideration as a new factor that influences differences between PrP assemblies and that could be relevant also for explaining the origin of prion strains. PMID:26126829

  13. Conformational Flexibility of Soluble Cellulose Oligomers: Chain Length and Temperature Dependence

    Science.gov (United States)

    Structures, dynamics, and stabilities of different sized cellulosic oligomers need to be considered when designing enzymatic cocktails for the conversion of biomass to biofuels since they can be both productive substrates and inhibitors of the overall process. In the present work, the conformational...

  14. Aqueous-phase oligomerization of methyl vinyl ketone through photooxidation - Part 1: Aging processes of oligomers

    Science.gov (United States)

    Renard, P.; Siekmann, F.; Salque, G.; Demelas, C.; Coulomb, B.; Vassalo, L.; Ravier, S.; Temime-Roussel, B.; Voisin, D.; Monod, A.

    2015-01-01

    It has recently been established that unsaturated water-soluble organic compounds (UWSOCs) might efficiently form oligomers in polluted fogs and wet aerosol particles, even for weakly soluble ones like methyl vinyl ketone (MVK). The atmospheric relevance of these processes is explored by means of multiphase process model studies in a companion paper. In the present study, we investigate the aging of these aqueous-phase MVK oligomers formed via •OH oxidation, as well as their ability to form secondary organic aerosol (SOA) upon water evaporation. The comparison between aqueous-phase composition and aerosol composition after nebulization of the corresponding solutions shows similar trends for oligomer formation and aging. The measurements reveal that oligomer aging leads to the formation of organic diacids. Quantification of the SOA mass formed after nebulization is performed, and the obtained SOA mass yields seem to depend on the spectral irradiance of the light used to initiate the photochemistry. Investigating a large range of initial MVK concentrations (0.2-20 mM), the results show that their •OH oxidation undergoes competition between functionalization and oligomerization that is dependent on the precursor concentration. At high initial MVK concentrations (≥ 2 mM), oligomerization prevails over functionalization, while at lower initial concentrations, oligomerization is not the major process, and functionalization dominates, resulting in small carbonyls, dicarbonyls and monoacids. The atmospheric implications of these processes are discussed.

  15. Cytotoxic helix-rich oligomer formation by melittin and pancreatic polypeptide.

    Directory of Open Access Journals (Sweden)

    Pradeep K Singh

    Full Text Available Conversion of amyloid fibrils by many peptides/proteins involves cytotoxic helix-rich oligomers. However, their toxicity and biophysical studies remain largely unknown due to their highly dynamic nature. To address this, we chose two helical peptides (melittin, Mel and pancreatic polypeptide, PP and studied their aggregation and toxicity. Mel converted its random coil structure to oligomeric helical structure upon binding to heparin; however, PP remained as helix after oligomerization. Interestingly, similar to Parkinson's associated α-synuclein (AS oligomers, Mel and PP also showed tinctorial properties, higher hydrophobic surface exposure, cellular toxicity and membrane pore formation after oligomerization in the presence of heparin. We suggest that helix-rich oligomers with exposed hydrophobic surface are highly cytotoxic to cells irrespective of their disease association. Moreover as Mel and PP (in the presence of heparin instantly self-assemble into stable helix-rich amyloidogenic oligomers; they could be represented as models for understanding the biophysical and cytotoxic properties of helix-rich intermediates in detail.

  16. Cholesterol facilitates interactions between α-synuclein oligomers and charge-neutral membranes

    DEFF Research Database (Denmark)

    van Maarschalkerweerd, Andreas; Vetri, Valeria; Vestergaard, Bente

    2015-01-01

    composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model...... of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein....

  17. Annotation of Different Dehydrocatechin Oligomers by MS/MS and Their Occurrence in Black Tea

    NARCIS (Netherlands)

    Verloop, Annewieke J.W.; Gruppen, Harry; Vincken, Jean Paul

    2016-01-01

    Dehydrocatechins (DhC's), oligomeric oxidation products of (epi)catechins, were formed in model incubations of epicatechin with mushroom tyrosinase. DhC oligomers up to tetramers were detected by reversed-phase ultrahigh-performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis.

  18. Alpha-synuclein oligomers - neurotoxic molecules in Parkinson’s disease and other Lewy body disorders

    Directory of Open Access Journals (Sweden)

    Martin Ingelsson

    2016-09-01

    Full Text Available Adverse intra- and extracellular effects of toxic α-synuclein are believed to be central to the pathogenesis in Parkinson’s disease and other disorders with Lewy body pathology in the nervous system. One of the physiological roles of α-synuclein relates to the regulation of neurotransmitter release at the presynapse, although it is still unclear whether this mechanism depends on the action of monomers or smaller oligomers. As for the pathogenicity, accumulating evidence suggest that prefibrillar species, rather than the deposits per se, are responsible for the toxicity in affected cells. In particular, larger oligomers or protofibrils of α-synuclein have been shown to impair protein degradation as well as the function of several organelles, such as the mitochondria and the endoplasmic reticulum. Accumulating evidence further suggest that oligomers/protofibrils may have a toxic effect on the synapse, which may lead to disrupted electrophysiological properties. In addition, recent data indicate that oligomeric α-synuclein species can spread between cells, either as free-floating proteins or via extracellular vesicles, and thereby act as seeds to propagate disease between interconnected brain regions. Taken together, several lines of evidence suggest that α-synuclein have neurotoxic properties and therefore should be an appropriate molecular target for therapeutic intervention in Parkinson’s disease and other disorders with Lewy pathology. In this context, immunotherapy with monoclonal antibodies against α-synuclein oligomers/protofibrils should be a particularly attractive treatment option.

  19. Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.

    Science.gov (United States)

    Kittelberger, Kara A; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G

    2012-01-01

    Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.

  20. PrP(Sc-specific antibodies with the ability to immunodetect prion oligomers.

    Directory of Open Access Journals (Sweden)

    Mourad Tayebi

    Full Text Available The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc.To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p(0/0 cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids.

  1. Natural Amyloid-Beta Oligomers Acutely Impair the Formation of a Contextual Fear Memory in Mice

    Science.gov (United States)

    Kittelberger, Kara A.; Piazza, Fabrizio; Tesco, Giuseppina; Reijmers, Leon G.

    2012-01-01

    Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss. PMID:22238679

  2. Aqueous phase oligomerization of methyl vinyl ketone through photooxidation - Part 1: Aging processes of oligomers

    Science.gov (United States)

    Renard, P.; Siekmann, F.; Salque, G.; Smaani, A.; Demelas, C.; Coulomb, B.; Vassalo, L.; Ravier, S.; Temime-Roussel, B.; Voisin, D.; Monod, A.

    2014-06-01

    Secondary organic aerosol (SOA) represents a substantial part of organic aerosol, which affects climate and human health. It is now accepted that one of the important pathways of SOA formation occurs via aqueous phase chemistry in the atmosphere. Recently, we have shown in a previous study (Renard et al., 2013) the mechanism of oligomerization of MVK (methyl vinyl ketone), and suggested that unsaturated water soluble organic compounds (UWSOC) might efficiently form SOA in wet aerosol particles, even for weakly soluble ones like MVK. The atmospheric relevance of these processes is explored by means of process model studies (in a companion paper). In the present study we investigate the aging of these aqueous phase MVK-oligomers (Part 1). We compared aqueous phase composition and SOA composition after nebulization, mainly by means of UPLC-ESI-MS and AMS, respectively. Both instruments match and show similar trend of oligomer formation and aging. The SMPS analysis performed on the nebulized solutions allow to quantify these SOA and to measure their mass yields. We have highlighted in the current study that MVK •OH-oxidation undergoes kinetic competition between functionalization and oligomerization. The SOA composition and its evolution highly depend on the precursor initial concentration. We determined the threshold of MVK concentration, i.e. 2 mM, from which oligomerization prevails over functionalization. Hence, at these concentrations, •OH-oxidation of MVK forms oligomers that are SV-OOA, with low O / C and high f43. Oligomers are then fragmented, via unidentified intermediates that have the properties of LV-OOA which then end into succinic, malonic and oxalic diacids. For lower initial MVK concentrations, the oligomerization is not the major process, and functionalization dominates, resulting in small carbonyls, dicarbonyls and mainly monoacids. The aging of these oligomers could be an explanation for the presence of a part of the diacids observed in aerosol.

  3. PrPSc-Specific Antibodies with the Ability to Immunodetect Prion Oligomers

    Science.gov (United States)

    Tayebi, Mourad; Jones, Daryl Rhys; Taylor, William Alexander; Stileman, Benjamin Frederick; Chapman, Charlotte; Zhao, Deming; David, Monique

    2011-01-01

    The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc. To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs) derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p0/0 cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids. PMID:21625515

  4. Distinct internalization pathways of human amylin monomers and its cytotoxic oligomers in pancreatic cells.

    Directory of Open Access Journals (Sweden)

    Saurabh Trikha

    Full Text Available Toxic human amylin oligomers and aggregates are implicated in the pathogenesis of type 2 diabetes mellitus (TTDM. Although recent studies have shown that pancreatic cells can recycle amylin monomers and toxic oligomers, the exact uptake mechanism and trafficking routes of these molecular forms and their significance for amylin toxicity are yet to be determined. Using pancreatic rat insulinoma (RIN-m5F beta (β-cells and human islets as model systems we show that monomers and oligomers cross the plasma membrane (PM through both endocytotic and non-endocytotic (translocation mechanisms, the predominance of which is dependent on amylin concentrations and incubation times. At low (≤ 100 nM concentrations, internalization of amylin monomers in pancreatic cells is completely blocked by the selective amylin-receptor (AM-R antagonist, AC-187, indicating an AM-R dependent mechanism. In contrast at cytotoxic (µM concentrations monomers initially (1 hour enter pancreatic cells by two distinct mechanisms: translocation and macropinocytosis. However, during the late stage (24 hours monomers internalize by a clathrin-dependent but AM-R and macropinocytotic independent pathway. Like monomers a small fraction of the oligomers initially enter cells by a non-endocytotic mechanism. In contrast a majority of the oligomers at both early (1 hour and late times (24 hours traffic with a fluid-phase marker, dextran, to the same endocytotic compartments, the uptake of which is blocked by potent macropinocytotic inhibitors. This led to a significant increase in extra-cellular PM accumulation, in turn potentiating amylin toxicity in pancreatic cells. Our studies suggest that macropinocytosis is a major but not the only clearance mechanism for both amylin's molecular forms, thereby serving a cyto-protective role in these cells.

  5. Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin

    Directory of Open Access Journals (Sweden)

    Langen Ralf

    2008-10-01

    Full Text Available Abstract Background The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD, age-related macular degeneration (AMD, atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins. Results We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation. Conclusion These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.

  6. Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.

    Directory of Open Access Journals (Sweden)

    Kara A Kittelberger

    Full Text Available Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD. It has been proposed that soluble amyloid-beta (Abeta oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.

  7. Rosmarinic acid: a potent carbonic anhydrase isoenzymes inhibitor

    OpenAIRE

    Topal, Meryem; GÜLÇİN, İlhami

    2014-01-01

    Rosmarinic acid is a water-soluble ester of caffeic acid and 3,4-dihydroxyphenyllactic acids, and is mainly found in plant species including Boraginaceae and Lamiaceae. In this research, we determined the inhibition property of rosmarinic acid on carbonic anhydrase isoenzymes I and II (hCA I and II) purified from human erythrocytes by using Sepharose-4B affinity column chromatography. hCA I and II isoenzymes were obtained with a yield of 57.9% and 67.2% and 76.5- and 509.3-fold purifica...

  8. Synthesis and Characterization of Oligomer 4-Vinylpyridine as A Corrosion Inhibitor for Mild Steel in CO2 Saturated Brine Solution

    Directory of Open Access Journals (Sweden)

    Ilim Ilim

    2016-08-01

    Full Text Available In this work, the oligomer of 4-vinylpyridine designated as O(4-VP was synthesized by hydrogen peroxide initiated chain growth polymerization and characterized in terms of molecular weight and structure by matrix assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF MS. The oligomer was tested as corrosion inhibitor of mild steel in brine solution saturated with carbon dioxide, with the main purpose to investigate the effect of inhibitor concentrations and temperatures on the inhibition activity defined in terms of corrosion rate and percent of protection. The inhibition tests were carried out using the methods of weight loss (WL and linear polarization (LP. Characterization using MALDI-TOF MS revealed that the oligomer has the mass (m/z in the range 200-2400, which corresponds to chain length of 2-22 repeating units. The results of corrosion rate measurements show that the corrosion rate with the use of oligomer is significantly lower than that without inhibitor, demonstrating that the oligomer functioned as effective corrosion inhibitor, while the 4-vinyl pyridine monomer was found to promote the corrosion. It was also found that the protection by the oligomer increased with increasing temperature and it was predicted the oligomer was chemically adsorbed by the surface of the metal.

  9. Amyloid β oligomers elicit mitochondrial transport defects and fragmentation in a time-dependent and pathway-specific manner.

    Science.gov (United States)

    Rui, Yanfang; Zheng, James Q

    2016-08-17

    Small oligomeric forms of amyloid-β (Aβ) are believed to be the culprit for declined brain functions in AD in part through their impairment of neuronal trafficking and synaptic functions. However, the precise cellular actions of Aβ oligomers and underlying mechanisms in neurons remain to be fully defined. Previous studies have identified mitochondria as a major target of Aβ toxicity contributing to early cognitive decline and memory loss in neurodegenerative diseases including Alzheimer's disease (AD). In this study, we report that Aβ oligomers acutely elicit distinct effects on the transport and integrity of mitochondria. We found that acute exposure of hippocampal neurons to Aβ oligomers from either synthetic peptides or AD brain homogenates selectively impaired fast transport of mitochondria without affecting the movement of late endosomes and lysosomes. Extended exposure of hipoocampal neurons to Aβ oligomers was found to result in mitochondrial fragmentation. While both mitochondrial effects induced by Aβ oligomers can be abolished by the inhibition of GSK3β, they appear to be independent from each other. Aβ oligomers impaired mitochondrial transport through HDAC6 activation whereas the fragmentation involved the GTPase Drp-1. These results show that Aβ oligomers can acutely disrupt mitochondrial transport and integrity in a time-dependent and pathway-specific manner. These findings thus provide new insights into Aβ-induced mitochondrial defects that may contribute to neuronal dysfunction and AD pathogenesis.

  10. Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure

    Energy Technology Data Exchange (ETDEWEB)

    Altman, Robin [Univ. of California, Davis, CA (United States). Dept. of Biochemistry and Molecular Medicine; Ly, Sonny [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Science Directorate; Hilt, Silvia [Univ. of California, Davis, CA (United States). Dept. of Biochemistry and Molecular Medicine; Petrlova, Jitka [Univ. of California, Davis, CA (United States). Dept. of Biochemistry and Molecular Medicine; Maezawa, Izumi [Univ. of California Davis, Sacramento, CA (United States). MIND Inst. and Dept. of Pathology and Laboratory Medicine; Kálai, Tamás [Univ. of Pecs (Hungary). Inst. of Organic and Medicinal Chemistry; Hideg, Kálmán [Univ. of Pecs (Hungary). Inst. of Organic and Medicinal Chemistry; Jin, Lee-Way [Univ. of California Davis, Sacramento, CA (United States). MIND Inst. and Dept. of Pathology and Laboratory Medicine; Laurence, Ted A. [Univ. of California, Davis, CA (United States). Dept. of Biochemistry and Molecular Medicine; Voss, John C. [Univ. of California, Davis, CA (United States). Dept. of Biochemistry and Molecular Medicine

    2015-12-01

    Alzheimer’s disease is characterized by the presence of extracellular plaques comprised of amyloid beta (Aβ) peptides. Soluble oligomers of the Aβ peptide underlie a cascade of neuronal loss and dysfunction associated with Alzheimer's disease. Single particle analyses of Aβ oligomers in solution by fluorescence correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes (SLFs; bi-functional small molecules that block the toxicity of Aβ) prevent and disrupt oligomeric assemblies of Aβ in solution. The FCS results, combined with electron paramagnetic resonance spectroscopy and circular dichroism spectroscopy, demonstrate SLFs can inhibit the growth of Aβ oligomers and disrupt existing oligomers while retaining Aβ in a largely disordered state. Furthermore, while the ability of SLF to block Aβ toxicity correlates with a reduction in oligomer size, our results suggest the conformation of Aβ within the oligomer determines the toxicity of the species. Attenuation of Aβ toxicity, which has been associated primarily with the soluble oligomeric form, can be achieved through redistribution of the peptides into smaller oligomers and arrest of the fractional increase in beta secondary structure.

  11. Direct observation of single amyloid-β(1-40 oligomers on live cells: binding and growth at physiological concentrations.

    Directory of Open Access Journals (Sweden)

    Robin D Johnson

    Full Text Available Understanding how amyloid-β peptide interacts with living cells on a molecular level is critical to development of targeted treatments for Alzheimer's disease. Evidence that oligomeric Aβ interacts with neuronal cell membranes has been provided, but the mechanism by which membrane binding occurs and the exact stoichiometry of the neurotoxic aggregates remain elusive. Physiologically relevant experimentation is hindered by the high Aβ concentrations required for most biochemical analyses, the metastable nature of Aβ aggregates, and the complex variety of Aβ species present under physiological conditions. Here we use single molecule microscopy to overcome these challenges, presenting direct optical evidence that small Aβ(1-40 oligomers bind to living neuroblastoma cells at physiological Aβ concentrations. Single particle fluorescence intensity measurements indicate that cell-bound Aβ species range in size from monomers to hexamers and greater, with the majority of bound oligomers falling in the dimer-to-tetramer range. Furthermore, while low-molecular weight oligomeric species do form in solution, the membrane-bound oligomer size distribution is shifted towards larger aggregates, indicating either that bound Aβ oligomers can rapidly increase in size or that these oligomers cluster at specific sites on the membrane. Calcium indicator studies demonstrate that small oligomer binding at physiological concentrations induces only mild, sporadic calcium leakage. These findings support the hypothesis that small oligomers are the primary Aβ species that interact with neurons at physiological concentrations.

  12. Synthesis of novel thiophene-phenylene oligomer derivatives with a dibenzothiophene-5,5-dioxide core for use in organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Shunjiro; Kataura, Hiromichi [Nanosystem Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8562 (Japan); JST, CREST, Kawaguchi 330-0012 (Japan); Duan, Zongfan [College of Science and Technology (CST), Nihon University, Chiba 274-8501 (Japan); School of Materials Science and Engineering, Xi' an University of Technology, Xi' an 710048 (China); Okukawa, Takanori; Yanagi, Yuichiro; Yoshida, Akira; Nishioka, Yasushiro [College of Science and Technology (CST), Nihon University, Chiba 274-8501 (Japan); Tanaka, Takeshi [Nanosystem Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8562 (Japan); Zhao, Gaoyang [School of Materials Science and Engineering, Xi' an University of Technology, Xi' an 710048 (China)

    2012-12-15

    A novel donor-acceptor-donor oligomer, 3,7-bis[5-(4-n-hexylphenyl)-2-thienyl]dibenzothiophene-5,5-dioxide (37HPTDBTSO) with a dibenzothiophene-5,5-dioxide core and end-cap phenylene-thiophene moieties, was synthesized using Stille cross-coupling reactions. The functional properties, including the optical and electrochemical properties, were investigated. Using 37HPTDBTSO and phenyl-C61-butyric acid methyl ester (PCBM) as a photoactive layer, bulk-heterojunction solar cell devices were fabricated by a spin-coating technique. 37HPTDBTSO was found to be a valuable electron donor. The device had a high open circuit voltage of 0.85 V and the highest power conversion efficiency of 0.84% when the weight ratio of 37HPTDBTSO to PCBM was 1:1.5. These results indicate that the new oligomer is a promising solution-processable photovoltaic material. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Formation of secondary organic aerosol and oligomers from the ozonolysis of enol ethers

    Directory of Open Access Journals (Sweden)

    A. Sadezky

    2006-01-01

    Full Text Available Formation of secondary organic aerosol has been observed in the gas phase ozonolysis of a series of enol ethers, among them several alkyl vinyl ethers (AVE, ROCH=CH2, such as ethyl, propyl, n-butyl, iso-butyl, t-butyl vinyl ether, and ethyl propenyl ether (EPE, C2H5OCH=CHCH3. The ozonolysis has been studied in a 570 l spherical glass reactor at ambient pressure (730 Torr and room temperature (296 K. Gas phase reaction products were investigated by in-situ FTIR spectroscopy, and secondary organic aerosol (SOA formation was monitored by a scanning mobility particle sizer (SMPS. The chemical composition of the formed SOA was analysed by a hybrid mass spectrometer using electrospray ionization (ESI. The main stable gas phase reaction product is the respective alkyl formate ROC(OH, formed with yields of 60 to 80%, implying that similar yields of the corresponding excited Criegee Intermediates (CI CH2O2 for the AVE and CH3CHO2 for EPE are generated. Measured SOA yields are between 2 to 4% for all enol ethers. Furthermore, SOA formation is strongly reduced or suppressed by the presence of an excess of formic acid, which acts as an efficient CI scavenger. Chemical analysis of the formed SOA by ESI(+/MS-TOF allows to identify oligomeric compounds in the mass range 200 to 800 u as its major constituents. Repetitive chain units are identified as CH2O2 (mass 46 for the AVE and C2H4O2 (mass 60 for EPE and thus have the same chemical compositions as the respective major Criegee Intermediates formed during ozonolysis of these ethers. The oligomeric structure and chain unit identity are confirmed by HPLC/ESI(+/MS-TOF and ESI(+/MS/MS-TOF experiments, whereby successive and systematic loss of a fragment with mass 46 for the AVE (and mass 60 for EPE is observed. It is proposed that the oligomer has the following basic structure of an oligoperoxide, -[CH(R-O-O]n-, where R=H for the AVE and R=CH3 for the EPE. Oligoperoxide formation is thus suggested to be another

  14. Synthesis of Cycloveratrylene Macrocycles and Benzyl Oligomers Catalysed by Bentonite under Microwave/Infrared and Solvent-Free Conditions

    Directory of Open Access Journals (Sweden)

    Manuel Salmón

    2013-10-01

    Full Text Available Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation of cycloveratrylene macrocycles and benzyl oligomers from the corresponding benzyl alcohols in good yields under microwave heating and infrared irradiation in the absence of solvent in both cases. The catalytic reaction is sensitive to the type of substituent on the aromatic ring. Thus, when benzyl alcohol was substituted with a methylenedioxy, two methoxy or three methoxy groups, a cyclooligomerisation process was induced. Unsubstituted, methyl and methoxy benzyl alcohols yielded linear oligomers. In addition, computational chemistry calculations were performed to establish a validated mechanistic pathway to explain the growth of the obtained linear oligomers.

  15. Constant interchain pressure effect in extensional flows of oligomer diluted polystyrene and poly(methyl methacrylate) melts

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Koblitz; Huang, Qian

    2017-01-01

    The constant ‘interchain pressure’ idea has been addressed, to evaluate if it is an adequate quantitative assumption to describe the fluid mechanics of oligomer diluted entangled NMMD polymer systems. The molecular stress function constitutive framework has been used with the constant interchain ......)s and almost all published oligomer diluted NMMD polystyrenes. The only deviation is on the most diluted and largest molecular weight case of an 18% 1880 kg/mol polystyrene in oligomer diluent. In this case, the maximal extensibility is not needed....

  16. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via π-π interactions.

    Science.gov (United States)

    Fan, Hailong; Yu, Xiang; Liu, Yang; Shi, Zujin; Liu, Huihui; Nie, Zongxiu; Wu, Decheng; Jin, Zhaoxia

    2015-06-21

    Recent research has indicated that polydopamine and synthetic eumelanins are optoelectronic biomaterials in which one-dimensional aggregates composed of ordered-stacking oligomers have been proposed as unique organic semiconductors. However, improving the ordered-stacking of oligomers in polydopamine nanostructures is a big challenge. Herein, we first demonstrate how folic acid molecules influence the morphology and nanostructure of polydopamine via tuning the π-π interactions of oligomers. MALDI-TOF mass spectrometry reveals that porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA) nanofibers. X-ray diffraction combined with simulation studies indicate that these oligomers favour aggregation into graphite-like ordered nanostructures via strong π-π interactions. High-resolution TEM characterization of carbonized FA-PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains is over 100 nm. The addition of folic acid in polydopamine enhances the ordered stacking of oligomers in its nanostructure. Our study steps forward to discover the mystery of the structure-property relationship of FA-PDA hybrids. It paves a way to optimize the properties of PDA through the design and selection of oligomer structures.

  17. Nanomolar Cellular Antisense Activity of Peptide Nucleic Acid (PNA) Cholic Acid ("Umbrella") and Cholesterol Conjugates Delivered by Cationic Lipids

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-01-01

    of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 µM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs...... volume improved transfection efficiency, suggesting that accumulation (condensation) of the PNA/lipid complex on the cellular surface is part of the uptake mechanism. These results provide a novel, simple method for very efficient cellular delivery of PNA oligomers, especially using PNA-cholic acid...

  18. Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Taneo, Jun; Adachi, Takumi [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Yoshida, Aiko; Takayasu, Kunio [Responses to Environmental Signals and Stresses, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Kyoto 606-8501 (Japan); Takahara, Kazuhiko, E-mail: ktakahar@zoo.zool.kyoto-u.ac.jp [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0081 (Japan); Inaba, Kayo [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0081 (Japan)

    2015-03-13

    Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia. We prepared Aβ oligomer and fibril from Aβ (1–42) peptide in vitro. We analyzed the characteristics of these oligomers and fibrils by electrophoresis and atomic force microscopy. Interestingly, Aβ oligomers but not Aβ monomers or fibrils induced robust IL-1β production in the presence of lipopolysaccharide. Moreover, Aβ oligomers induced endo/phagolysosome rupture, which released cathepsin B into the cytoplasm. Aβ oligomer-induced IL-1β production was inhibited not only by the cathepsin B inhibitor CA-074-Me but also by the reactive oxygen species (ROS) inhibitor N-acetylcysteine. Random chemical crosslinking abolished the ability of the oligomers to induce IL-1β. Thus, multimerization and fibrillization causes Aβ oligomers to lose the ability to induce IL-1β. These results indicate that Aβ oligomers, but not fibrils, induce IL-1β production in primary microglia in a cathepsin B- and ROS-dependent manner. - Highlights: • We prepared amyloid β (Aβ) fibrils with minimum contamination of Aβ oligomers. • Primary microglia (MG) produced IL-1β in response to Aβ oligomers, but not fibrils. • Only Aβ oligomers induced leakage of cathepsin B from endo/phagolysosomes. • IL-1β production in response to Aβ oligomers depended on both cathepsin B and ROS. • Crosslinking reduced the ability of the Aβ oligomers to induce IL-1β from MG.

  19. Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson's disease brain.

    Science.gov (United States)

    Roberts, Rosalind F; Wade-Martins, Richard; Alegre-Abarrategui, Javier

    2015-06-01

    Oligomeric forms of alpha-synuclein are emerging as key mediators of pathogenesis in Parkinson's disease. Our understanding of the exact contribution of alpha-synuclein oligomers to disease is limited by the lack of a technique for their specific detection. We describe a novel method, the alpha-synuclein proximity ligation assay, which specifically recognizes alpha-synuclein oligomers. In a blinded study with post-mortem brain tissue from patients with Parkinson's disease (n = 8, age range 73-92 years, four males and four females) and age- and sex-matched controls (n = 8), we show that the alpha-synuclein proximity ligation assay reveals previously unrecognized pathology in the form of extensive diffuse deposition of alpha-synuclein oligomers. These oligomers are often localized, in the absence of Lewy bodies, to neuroanatomical regions mildly affected in Parkinson's disease. Diffuse alpha-synuclein proximity ligation assay signal is significantly more abundant in patients compared to controls in regions including the cingulate cortex (1.6-fold increase) and the reticular formation of the medulla (6.5-fold increase). In addition, the alpha-synuclein proximity ligation assay labels very early perikaryal aggregates in morphologically intact neurons that may precede the development of classical Parkinson's disease lesions, such as pale bodies or Lewy bodies. Furthermore, the alpha-synuclein proximity ligation assay preferentially detects early-stage, loosely compacted lesions such as pale bodies in patient tissue, whereas Lewy bodies, considered heavily compacted late lesions are only very exceptionally stained. The alpha-synuclein proximity ligation assay preferentially labels alpha-synuclein oligomers produced in vitro compared to monomers and fibrils, while stained oligomers in human brain display a distinct intermediate proteinase K resistance, suggesting the detection of a conformer that is different from both physiological, presynaptic alpha

  20. Microflora dynamics in earthworms casts in an artificial soil (biosynthesol containing lactic acid oligomers

    Directory of Open Access Journals (Sweden)

    Alauzet Nathalie

    2001-01-01

    Full Text Available Studies were performed to appreciate the presence of micro-organisms able to degrade OLA, in earthworms casts or in the surroundings. Worms were grown in biosynthesol, an artificial soil. The counting of bacteria and fungi in earthworms casts and in biosynthesol without earthworms suggested that earthworms ate some of the micro-organisms. The main filamentous fungi genera found were Aspergillus, Trichoderma, Fusarium and Penicillium. Previous results in the literature have shown that some species from the Aspergillus and Fusarium genera were able to degrade OLA and other aliphatic esters. It could be suggested that these two genera and some bacteria were responsible for the pre-degradation of OLA, and that earthworms might eat them.

  1. Kinetic properties of Rhizopus oryzae RPG1 endo-polygalacturonase hydrolyzing galacturonic acid oligomers

    Science.gov (United States)

    Future fuel and specialty chemical production will benefit from the use of agricultural biomass. Efficient and effective use of agricultural biomass requires conversion to simple sugars by chemical pre-treatments and enzymes into simple sugars. Rhizopus oryzae, a filamentous fungus, makes enzymes ca...

  2. Electrospray mass spectrometry of NeuAc oligomers associated with the C fragment of the tetanus toxin

    Energy Technology Data Exchange (ETDEWEB)

    Prieto, M C; Whittal, R M; Baldwin, M A; Burlingame, A L; Balhorn, R

    2005-04-03

    The Clostridial neurotoxins, botulinum and tetanus, gain entry into neuronal cells by protein recognition involving cell specific binding sites. The sialic or N-acetylneuraminic acid (NeuAc) residues of gangliosides attached to the surface of motor neurons are the suspected recognition and interaction points with Clostridial neurotoxins, although not necessarily the only ones. We have used electrospray ionization mass spectrometry (ESIMS) to examine formation of complexes between the tetanus toxin C fragment, or targeting domain, and carbohydrates containing NeuAc groups to determine how NeuAc residues contribute to ganglioside binding. ESI-MS was used to rapidly and efficiently measure dissociation constants for a number of related NeuAc-containing carbohydrates and NeuAc oligomers, information that has helped identify the structural features of gangliosides that determine their binding to tetanus toxin. The strength of the interactions between the C fragment and (NeuAc){sub n}, are consistent with the topography of the targeting domain of tetanus toxin and the nature of its carbohydrate binding sites. The results suggest that the targeting domain of tetanus toxin contains two binding sites that can accommodate NeuAc (or a dimer). This study also shows that NeuAc must play an important role in ganglioside binding and molecular recognition, a process critical for normal cell function and one frequently exploited by toxins, bacteria and viruses to facilitate their entrance into cells.

  3. Oligomers, organosulfates, and nitrooxy organosulfates in rainwater identified by ultra-high resolution electrospray ionization FT-ICR mass spectrometry

    Directory of Open Access Journals (Sweden)

    K. E. Altieri

    2009-04-01

    Full Text Available Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50% of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS. Elemental compositions of 552 unique molecular species were determined in the mass range 50–500 Da in the rainwater. Four main groups of organic compounds were identified: compounds containing carbon, hydrogen, and oxygen (CHO only, sulfur (S containing CHOS compounds, nitrogen (N containing CHON compounds, and S- and N- containing CHONS compounds. Organic acids commonly identified in precipitation were detected in the rainwater. Within the four main groups of compounds detected in the rainwater, oligomers, organosulfates, and nitrooxy-organosulfates were assigned based on elemental formula comparisons. The majority of the compounds identified are products of atmospheric reactions and are known contributors to secondary organic aerosol (SOA formed from gas phase, aerosol phase, and in-cloud reactions in the atmosphere. It is suggested that the large uncharacterized component of SOA is the main contributor to the large uncharacterized component of rainwater organic matter.

  4. HCT2, a Novel Hydroxycinnamoyl-Malate Transferase, is Responsible for Phaselic Acid (2-O-Caffeoyl-L-Malate) Biosynthesis in Red Clover

    Science.gov (United States)

    In red clover, post-harvest oxidation of o-diphenol caffeic acid derivatives to o-quinones by an endogenous polyphenol oxidase (PPO) prevents breakdown of forage protein during storage (1). Agronomically important forages like alfalfa lack both PPO and o-diphenols. Consequently, breakdown of their p...

  5. Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on Hyperuricemia and Inflammation

    Directory of Open Access Journals (Sweden)

    Zilma Schimith Ferraz-Filha

    2017-01-01

    Full Text Available Tabebuia species (Bignoniaceae have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL of Tabebuia roseoalba (Ridl. Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species.

  6. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life

    Science.gov (United States)

    Ferris, James P

    2006-01-01

    Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30–50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0–4.5 Ga. PMID:17008218

  7. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life.

    Science.gov (United States)

    Ferris, James P

    2006-10-29

    Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30-50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0-4.5Ga.

  8. Self-Assembly of Cellulose Oligomers into Nanoribbon Network Structures Based on Kinetic Control of Enzymatic Oligomerization.

    Science.gov (United States)

    Serizawa, Takeshi; Fukaya, Yuka; Sawada, Toshiki

    2017-10-27

    The ability to chemically synthesize desired molecules followed by their in situ self-assembly in reaction solution has attracted much attention as a simple and environmentally friendly method to produce self-assembled nanostructures. In this study, α-D-glucose 1-phosphate monomers and cellobiose primers were subjected to cellodextrin phosphorylase-catalyzed reverse phosphorolysis reactions in aqueous solution in order to synthesize cellulose oligomers, which were then in situ self-assembled into crystalline nanoribbon network structures. The average degree-of-polymerization (DP) values of the cellulose oligomers were estimated to be approximately 7-8 with a certain degree of DP distribution. The cellulose oligomers crystallized with the cellulose II allomorph appeared to align perpendicularly to the base plane of the nanoribbons in an anti-parallel manner. Detailed analyses of reaction time dependence suggested that the production of nanoribbon network structures was kinetically controlled by the amount of water-insoluble cellulose oligomers produced.

  9. Soluble Aβ oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes

    National Research Council Canada - National Science Library

    Hong, Soyon; Ostaszewski, Beth L; Yang, Ting; O'Malley, Tiernan T; Jin, Ming; Yanagisawa, Katsuhiko; Li, Shaomin; Bartels, Tim; Selkoe, Dennis J

    2014-01-01

    .... Here, we found that soluble Aβ oligomers were sequestered from brain interstitial fluid onto brain membranes much more rapidly than nontoxic monomers and were recovered in part as bound to GM1 ganglioside on membranes. Aβ...

  10. Detergent-dispersing properties of succinamide additives with an oligomer ethylene base

    Energy Technology Data Exchange (ETDEWEB)

    Ostroverkhov, V.G.; Glavati, O.L.; Glavati, Ye.V.; Klimenko, P.L.; Konovich, L.G.

    1980-01-01

    Bis-succinamide additives (SA) with different branching characteristics and saturation level (with diethylenetriamine) were derived on an oligomer ethylene (OE) fraction base of C/sub 18/-C/sub 26/, C/sub 20/-C/sub 26/, C/sub 26/, C/sub 18/-C/sub 40/. With dispersing properties at 250/sup 0/C (coal tar in vaseline oil), and detergent properties (PEV method) principal part of SA on the OE base is better than SA with an oligomer isobutylene base with a mol. mass 900, which is industrial SA. With respect to corrosion aggressiveness to Pb, thermo-oxidizing stability and oil stability of the M-11 to oxidation in the DK-2 apparatus, these additives are similar. It is presumed that the detergent-dispersion properties of SA on an OE base is better than in SA derived on more narrow OE fractions that are included in the mixture.

  11. "Nail" and "comb" effects of cholesterol modified NIPAm oligomers on cancer targeting liposomes

    KAUST Repository

    Li, Wengang

    2014-01-01

    Thermosensitive liposomes are a promising approach to controlled release and reduced drug cytotoxicity. Low molecular weight N-isopropylacrylamide (NIPAm) oligomers (NOs) with different architectures (main chain NOs (MCNOs) and side chain NOs (SCNOs)) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and radical polymerization and then separately used to prepare thermosensitive liposomes. A more controlled and enhanced release was observed for both NO liposomes compared to pristine ones. Two release mechanisms depending on the oligomer architecture, namely "nail" for MCNOs and "comb" for SCNOs, are proposed. In addition to thermosensitivity, the cancer targeting property of NO liposomes was achieved by further biotinylation of the delivery system. © The Royal Society of Chemistry.

  12. Liquid Crystalline Thermosets from Ester, Ester-imide, and Ester-amide Oligomers

    Science.gov (United States)

    Dingemans, Theodorus J. (Inventor); Weiser, Erik S. (Inventor); St. Clair, Terry L. (Inventor)

    2009-01-01

    Main chain thermotropic liquid crystal esters, ester-imides, and ester-amides were prepared from AA, BB, and AB type monomeric materials and end-capped with phenylacetylene, phenylmaleimide, or nadimide reactive end-groups. The end-capped liquid crystal oligomers are thermotropic and have, preferably, molecular weights in the range of approximately 1000-15,000 grams per mole. The end-capped liquid crystaloligomers have broad liquid crystalline melting ranges and exhibit high melt stability and very low melt viscosities at accessible temperatures. The end-capped liquid crystal oli-gomers are stable forup to an hour in the melt phase. They are highly processable by a variety of melt process shape forming and blending techniques. Once processed and shaped, the end-capped liquid crystal oigomers were heated to further polymerize and form liquid crystalline thermosets (LCT). The fully cured products are rubbers above their glass transition temperatures.

  13. Studies of Third-Order Nonlinear Optical Properties of Polyazine and Its Oligomers

    Science.gov (United States)

    Nalwa, Hari Singh; Hamada, Tomoyuki; Kakuta, Atsushi; Mukoh, Akio

    1993-02-01

    The third-order nonlinear optical properties of a polyazine and its oligomers are reported for the first time. Third-harmonic generation measurements revealed a nonresonant third-order nonlinear optical susceptibility χ(3)(-3ω; ω, ω, ω) of 1.53× 10-12 esu for a pentamer and 8.0× 10-12 esu for propylmethylpolyazine at 1.5 μm. Dipole polarizability (α) and second hyperpolarizability (γ) of oligomer model compounds were also calculated by employing the ab initio coupled-perturbed Hartee-Fock (CPHF) theory. Both polarizabilities and χ(3)(-3ω; ω, ω, ω) increase significantly as the length of π-electron delocalization increases in the polyazine backbone.

  14. Two-Photon Absorption in a Conformationally Twisted D-π-A Oligomer : A Synergic Photosensitizing Approach for Multiphoton Lithography

    OpenAIRE

    Malval, Jean-Pierre; Achelle, Sylvain; Bodiou, Loïc; Spangenberg, Arnaud; Chia Gomez, Laura; Soppera, Olivier; Robin-Le Guen, Françoise

    2014-01-01

    International audience; A comparative study of the linear and nonlinear optical properties of a novel triphenylamine–pyrimidine alternated oligomer and its corresponding V-shaped quadrupolar monomer is presented. Both chromophores strikingly exhibit the same spectral shape when considering their respective one- and two-photon absorption spectra. This effect was attributed to a weak interchromophore coupling within the oligomer which exhibits a highly distorted geometry resulting in a strong r...

  15. Co-oligomers Based on 2-Methoxy, 5-(2’-ethylhexyloxy) phenylene and Thienylenevinylene for Organic Solar Cells

    OpenAIRE

    A. El Alamy; mohamed bouzzine; Hamidi, M.; Bouachrine, M.

    2016-01-01

    Thanks to their optoelectronic properties and specific applications such as organic solar cells, the research on the lower band gap of organic p-conjugated materials encompassing both polymers and oligomers have been widely studied over the last years. The control of the band gap of these materials is a research issue of ongoing interest. In this study, theoretical study using the DFT method on four oligomers based on 2-methoxy, 5-(2’-ethylhexyloxy) phenylene and thienylenevinylene is reporte...

  16. Quarternization of 3-azido-1-propyne oligomers obtained by copper(I-catalyzed azide–alkyne cycloaddition polymerization

    Directory of Open Access Journals (Sweden)

    Shun Nakano

    2015-06-01

    Full Text Available 3-Azido-1-propyne oligomer (oligoAP samples, prepared by copper(I-catalyzed azide–alkyne cycloaddition (CuAAC polymerization, were quarternized quantitatively with methyl iodide in sulfolane at 60 °C to obtain soluble oligomers. The conformation of the quarternized oligoAP in dilute DMSO-d6 solution was examined by pulse-field-gradient spin-echo NMR based on the touched bead model.

  17. Synthesis of polymers and oligomers containing fluorinated side groups for the construction of hydrophobic surfaces

    OpenAIRE

    Zhuang, Rong-Chuan

    2005-01-01

    Oligomers and polymers based on functionalized Rf-amides were successfully synthesized for the fabrication of hydrophobic surfaces with either linear or network structure. Firstly, new functionalized Rf-amides (RfCONH-, Rf is a perfluoroalkyl segment) were developed in most cases by a one step reaction and a simple work-up procedure. The reaction behaviors of synthesized Rf-amides in polyreactions were well understood. New fluorinated oligoester polyols, blocked IPDI's, and end-hydroxyl termi...

  18. A foldamer-dendrimer conjugate neutralizes synaptotoxic β-amyloid oligomers.

    Directory of Open Access Journals (Sweden)

    Lívia Fülöp

    Full Text Available BACKGROUND AND AIMS: Unnatural self-organizing biomimetic polymers (foldamers emerged as promising materials for biomolecule recognition and inhibition. Our goal was to construct multivalent foldamer-dendrimer conjugates which wrap the synaptotoxic β-amyloid (Aβ oligomers with high affinity through their helical foldamer tentacles. Oligomeric Aβ species play pivotal role in Alzheimer's disease, therefore recognition and direct inhibition of this undruggable target is a great current challenge. METHODS AND RESULTS: Short helical β-peptide foldamers with designed secondary structures and side chain chemistry patterns were applied as potential recognition segments and their binding to the target was tested with NMR methods (saturation transfer difference and transferred-nuclear Overhauser effect. Helices exhibiting binding in the µM region were coupled to a tetravalent G0-PAMAM dendrimer. In vitro biophysical (isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy and size-exclusion chromatography and biochemical tests (ELISA and dot blot indicated the tight binding between the foldamer conjugates and the Aβ oligomers. Moreover, a selective low nM interaction with the low molecular weight fraction of the Aβ oligomers was found. Ex vivo electrophysiological experiments revealed that the new material rescues the long-term potentiation from the toxic Aβ oligomers in mouse hippocampal slices at submicromolar concentration. CONCLUSIONS: The combination of the foldamer methodology, the fragment-based approach and the multivalent design offers a pathway to unnatural protein mimetics that are capable of specific molecular recognition, and has already resulted in an inhibitor for an extremely difficult target.

  19. The Volumetric Diversity of Misfolded Prion Protein Oligomers Revealed by Pressure Dissociation.

    Science.gov (United States)

    Torrent, Joan; Lange, Reinhard; Rezaei, Human

    2015-08-14

    Protein oligomerization has been associated with a wide range of diseases. High pressure approaches offer a powerful tool for deciphering the underlying molecular mechanisms by revealing volume changes associated with the misfolding and assembly reactions. We applied high pressure to induce conformational changes in three distinct β-sheet-rich oligomers of the prion protein PrP, a protein characterized by a variety of infectious quaternary structures that can propagate stably and faithfully and cause diseases with specific phenotypic traits. We show that pressure induces dissociation of the oligomers and leads to a lower volume monomeric PrP state that refolds into the native conformation after pressure release. By measuring the different pressure and temperature sensitivity of the tested PrP oligomers, we demonstrate significantly different void volumes in their quaternary structure. In addition, by focusing on the kinetic and energetic behavior of the pressure-induced dissociation of one specific PrP oligomer, we reveal a large negative activation volume and an increase in both apparent activation enthalpy and entropy. This suggests a transition state ensemble that is less structured and significantly more hydrated than the oligomeric state. Finally, we found that site-specific fluorescent labeling allows monitoring of the transient population of a kinetic intermediate in the dissociation reaction. Our results indicate that defects in atomic packing may deserve consideration as a new factor that influences differences between PrP assemblies and that could be relevant also for explaining the origin of prion strains. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Interchain tube pressure effect in extensional flows of oligomer diluted nearly monodisperse polystyrene melts

    DEFF Research Database (Denmark)

    Rasmussen, Henrik K.; Huang, Qian

    2014-01-01

    times and entanglements have been established based on published extensional experiments on nearly monodisperse polystyrene melts. The constitutive equation has shown agreement with the experimental startup of and steady extension data from Huang et al. (Macromolecules 46:5026–5035, 2013a) based on 285...... and 545 kg/mol polystyrenes diluted in styrene oligomers containing 3.3 (1.92 kg/mol) and 7.3 (4.29 kg/mol) Kuhn steps....

  1. Intrahippocampal Administration of Amyloid-β1–42 Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C.

    2017-01-01

    Increasing evidence suggests that abnormal brain accumulation of amyloid-β1–42 (Aβ1–42) oligomers plays a causal role in Alzheimer’s disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ1–42 oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ1–42 oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ1–42 oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ1–42 oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ1–42 oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ1–42 leads to cognitive impairment via interference with hippocampal insulin signaling. PMID:22430529

  2. Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism.

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C

    2012-01-01

    Increasing evidence suggests that abnormal brain accumulation of amyloid-β(1-42) (Aβ(1-42)) oligomers plays a causal role in Alzheimer's disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ(1-42) oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ(1-42) oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ(1-42) oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ(1-42) oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ(1-42) oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ(1-42) leads to cognitive impairment via interference with hippocampal insulin signaling.

  3. A lifespan observation of a novel mouse model: in vivo evidence supports aβ oligomer hypothesis.

    Directory of Open Access Journals (Sweden)

    Yichi Zhang

    Full Text Available Transgenic mouse models are powerful tools in exploring the mechanisms of AD. Most current transgenic models of AD mimic the memory impairment and the main pathologic features, among which the formation of beta-amyloid (Aβ plaques is considered a dominant pathologic event. Recently, Aβ oligomers have been identified as more neurotoxic than Aβ plaques. However, no ideal transgenic mouse model directly support Aβ oligomers as a neurotoxic species due to the puzzling effects of amyloid plaques in the more widely-used models. Here, we constructed a single-mutant transgenic (Tg model harboring the PS1V97L mutation and used Non-Tg littermates as a control group. Employing the Morris water maze, electrophysiology, immunohistochemistry, biochemistry, and electron microscopy, we investigated behavioral changes and pathology progression in our single-mutant transgenic model. We discovered the pathological alteration of intraneuronal accumulation of Aβ oligomers without Aβ plaques in the PS1V97L-Tg mouse model, which might be the result of PS1 gene mutation. Following Aβ oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for Aβ oligomers in the onset of AD and suggests that Aβ plaques may not be the only prerequisite. This model provides a useful tool for studying the role of Aβ oligomers in AD pathogenesis.

  4. Amyloid-β oligomers are sequestered by both intracellular and extracellular chaperones.

    Science.gov (United States)

    Narayan, Priyanka; Meehan, Sarah; Carver, John A; Wilson, Mark R; Dobson, Christopher M; Klenerman, David

    2012-11-20

    The aberrant aggregation of the amyloid-β peptide into β-sheet rich, fibrillar structures proceeds via a heterogeneous ensemble of oligomeric intermediates that have been associated with neurotoxicity in Alzheimer's disease (AD). Of particular interest in this context are the mechanisms by which molecular chaperones, part of the primary biological defenses against protein misfolding, influence Aβ aggregation. We have used single-molecule fluorescence techniques to compare the interactions between distinct aggregation states (monomers, oligomers, and amyloid fibrils) of the AD-associated amyloid-β(1-40) peptide, and two molecular chaperones, both of which are upregulated in the brains of patients with AD and have been found colocalized with Aβ in senile plaques. One of the chaperones, αB-crystallin, is primarily found inside cells, while the other, clusterin, is predominantly located in the extracellular environment. We find that both chaperones bind to misfolded oligomeric species and form long-lived complexes, thereby preventing both their further growth into fibrils and their dissociation. From these studies, we conclude that these chaperones have a common mechanism of action based on sequestering Aβ oligomers. This conclusion suggests that these chaperones, both of which are ATP-independent, are able to inhibit potentially pathogenic Aβ oligomer-associated processes whether they occur in the extracellular or intracellular environment.

  5. Dynamics in coarse-grained models for oligomer-grafted silica nanoparticles

    KAUST Repository

    Hong, Bingbing

    2012-01-01

    Coarse-grained models of poly(ethylene oxide) oligomer-grafted nanoparticles are established by matching their structural distribution functions to atomistic simulation data. Coarse-grained force fields for bulk oligomer chains show excellent transferability with respect to chain lengths and temperature, but structure and dynamics of grafted nanoparticle systems exhibit a strong dependence on the core-core interactions. This leads to poor transferability of the core potential to conditions different from the state point at which the potential was optimized. Remarkably, coarse graining of grafted nanoparticles can either accelerate or slowdown the core motions, depending on the length of the grafted chains. This stands in sharp contrast to linear polymer systems, for which coarse graining always accelerates the dynamics. Diffusivity data suggest that the grafting topology is one cause of slower motions of the cores for short-chain oligomer-grafted nanoparticles; an estimation based on transition-state theory shows the coarse-grained core-core potential also has a slowing-down effect on the nanoparticle organic hybrid materials motions; both effects diminish as grafted chains become longer. © 2012 American Institute of Physics.

  6. Aβ40 oligomers identified as a potential biomarker for the diagnosis of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Carol Man Gao

    Full Text Available Alzheimer's Disease (AD is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42 from cerebrospinal fluid (CSF. Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.

  7. KARAKTERISASI ENZIM KITOSANASE DAR] ISOLAT BAKTERI KPU 2123 DAN APLIKASINYA UNTUK PRODUKS1 OLIGOMER KITOSAN

    Directory of Open Access Journals (Sweden)

    Yusro Nuri Fawzya

    2009-06-01

    Full Text Available Penelitian ini merupakan sebagian dari rangkaian penelitian mengenai eksplorasi enzim kitinolitik dari mikroba lingkungan laut, khususnya dari limbah udang. Tujuan penelitian ini adalah untuk mengidentifikasi isolat bakteri KPU 2123 dari limbah udang, mengkarakterisasi dan mengaplikasikan enzim kitosanase yang dihasilkan oleh bakteri tersebut untuk produksi oligomer kitosan dan menguji bioaktivitas oligomer kitosan tersebut sebagai antitumor dan antibakteri. Karakterisasi enzim dilakukan dengan menguji aktivitas enzim pada berbagai suhu dan pH. Selain itu juga ditentukan besarnya aktivitas yang tersisa setelah enzim diinkubasi pada suhu dan lama waktu tertentu. Pengaruh ion logam terhadap aktivitas enzim juga dilihat dengan mereaksikan enzim dengan 1 mM ion logam dalam bentuk larutan khlorida. Hasil penelitian menunjukkan bahwa berdasarkan analisis gen 16S-rRNA, isolat bakteri KPU 2123 memiliki kemiripan 95% dengan Stanotrophomonas maltophilia. Enzim kitosanase dari isolat ini bekerja optimal pada suhu 50 ºC dan pH 6. Enzim ini cukup stabil pada suhu 37 ºC selama 120 menit. Penambahan ion logam berpengaruh terhadap aktivitas enzim. Ion logam Zn²+ (sebagai garam klorida 1 mM menghambat 100% aktivitas enzim tersebut. Penggunaan enzim kitosanase dalam menghidrolisis substrat kitosan, menghasilkan oligomer kitosan yang mengandung tetramer, pentamer dan heksamer Oligor kitosan tersebut mampu menghambat pertumbuhan bakteri Staphylococcus aureus sebesar 10,06% dan dapat menyebabkan kematian sel HeLa dengan LC50 pada dosis 120 ppm.

  8. Tumor delivery of antisense oligomer using trastuzumab within a streptavidin nanoparticle

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Yale University, Yale PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Liu, Xinrong; Chen, Ling; Cheng, Dengfeng; Rusckowski, Mary [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Hnatowich, Donald J. [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Umass Medical School, Department of Radiology, Worcester, MA (United States)

    2009-12-15

    Trastuzumab (Herceptin trademark) is often internalized following binding to Her2+ tumor cells. The objective of this study was to investigate whether trastuzumab can be used as a specific carrier to deliver antisense oligomers into Her2+ tumor cells both in vitro and in vivo. A biotinylated MORF oligomer antisense to RhoC mRNA and its biotinylated sense control were labeled with either lissamine for fluorescence detection or {sup 99m}Tc for radioactivity detection and were linked to biotinylated trastuzumab via streptavidin. The nanoparticles were studied in SUM190 (RhoC+, Her2+) study and SUM149 (RhoC+, Her2-) control cells in culture and as xenografts in mice. As evidence of unimpaired Her2+ binding of trastuzumab within the nanoparticle, accumulations were clearly higher in SUM190 compared to SUM149 cells and, by whole-body imaging, targeting of SUM190 tumor was similar to that expected for a radiolabeled trastuzumab. As evidence of internalization, fluorescence microscopy images of cells grown in culture and obtained from xenografts showed uniform cytoplasm distribution of the lissamine-MORF. An invasion assay showed decreased RhoC expression in SUM190 cells when incubated with the antisense MORF nanoparticles at only 100 nM. Both in cell culture and in animals, the nanoparticle with trastuzumab as specific carrier greatly improved tumor delivery of the antisense oligomer against RhoC mRNA into tumor cells overexpressing Her2 and may be of general utility. (orig.)

  9. Predicting oligomer/polymer compatibility and the impact on nanoscale segregation in thin films.

    Science.gov (United States)

    Sabattié, Elise F D; Tasche, Jos; Wilson, Mark R; Skoda, Maximilian W A; Hughes, Arwel; Lindner, Torsten; Thompson, Richard L

    2017-05-21

    Compatibility between oligomers and polymers was systematically assessed using differential scanning calorimetry (DSC) and was correlated with similarity in saturation and solubility parameter. These measurements enabled validation of detailed volume of mixing calculations using Statistical Association Fluid Theory (SAFT-γ Mie) and molecular dynamics (MD) simulations, which can be used to predict behaviour beyond the experimentally accessible conditions. These simulations confirmed that squalane is somewhat more compatible with poly(isoprene), "PI" than poly(butadiene), "PB", and further enabled prediction of the temperature dependence of compatibility. Surface and interfacial segregation of a series of deuterated oligomers was quantified in rubbery polymer films: PI, PB and hydrogenated poly(isoprene) "hPI". A striking correlation was established between surface wetting transition and mixtures of low compatibility, such as oligo-dIB in PB or PI. Segregation was quantified normal to the surface by ion beam analysis and neutron reflectometry and in some cases lateral segregation was observable by AFM. While surface segregation is driven by disparity in molecular weight in highly compatible systems this trend reverses as critical point is approached, and surface segregation increases with increasing oligomer molecular weight.

  10. Structural Properties of HIV Integrase. Lens Epithelium-derived Growth Factor Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, K.; Diamond, T; Hwang, Y; Bushman, F; Van Duyne, G

    2010-01-01

    Integrase (IN) is the catalytic component of the preintegration complex, a large nucleoprotein assembly critical for the integration of the retroviral genome into a host chromosome. Although partial crystal structures of human immunodeficiency virus IN alone and its complex with the integrase binding domain of the host factor PSIP1/lens epithelium-derived growth factor (LEDGF)/p75 are available, many questions remain regarding the properties and structures of LEDGF-bound IN oligomers. Using analytical ultracentrifugation, multiangle light scattering, and small angle x-ray scattering, we have established the oligomeric state, stoichiometry, and molecular shapes of IN {center_dot} LEDGF complexes in solution. Analyses of intact IN tetramers bound to two different LEDGF truncations allow for placement of the integrase binding domain by difference analysis. Modeling of the small angle x-ray scattering envelopes using existing structural data suggests domain arrangements in the IN oligomers that support and extend existing biochemical data for IN {center_dot} LEDGF complexes and lend new insights into the quaternary structure of LEDGF-bound IN tetramers. These IN oligomers may be involved in stages of the viral life cycle other than integration, including assembly, budding, and early replication.

  11. NMR studies of DNA oligomers and their interactions with minor groove binding ligands

    Energy Technology Data Exchange (ETDEWEB)

    Fagan, Patricia A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I•C base pairs are functional analogs of A•T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

  12. Macroscopic Strain-Induced Transition from Quasi-infinite Gold Nanoparticle Chains to Defined Plasmonic Oligomers.

    Science.gov (United States)

    Steiner, Anja Maria; Mayer, Martin; Seuss, Maximilian; Nikolov, Svetoslav; Harris, Kenneth D; Alexeev, Alexander; Kuttner, Christian; König, Tobias A F; Fery, Andreas

    2017-09-26

    We investigate the formation of chains of few plasmonic nanoparticles-so-called plasmonic oligomers-by strain-induced fragmentation of linear particle assemblies. Detailed investigations of the fragmentation process are conducted by in situ atomic force microscopy and UV-vis-NIR spectroscopy. Based on these experimental results and mechanical simulations computed by the lattice spring model, we propose a formation mechanism that explains the observed decrease of chain polydispersity upon increasing strain and provides experimental guidelines for tailoring chain length distribution. By evaluation of the strain-dependent optical properties, we find a reversible, nonlinear shift of the dominant plasmonic resonance. We could quantitatively explain this feature based on simulations using generalized multiparticle Mie theory (GMMT). Both optical and morphological characterization show that the unstrained sample is dominated by chains with a length above the so-called infinite chain limit-above which optical properties show no dependency on chain length-while during deformation, the average chain length decrease below this limit and chain length distribution becomes more narrow. Since the formation mechanism results in a well-defined, parallel orientation of the oligomers on macroscopic areas, the effect of finite chain length can be studied even using conventional UV-vis-NIR spectroscopy. The scalable fabrication of oriented, linear plasmonic oligomers opens up additional opportunities for strain-dependent optical devices and mechanoplasmonic sensing.

  13. Oligomers Modulate Interfibril Branching and Mass Transport Properties of Collagen Matrices

    Science.gov (United States)

    Whittington, Catherine F.; Brandner, Eric; Teo, Ka Yaw; Han, Bumsoo; Nauman, Eric; Voytik-Harbin, Sherry L.

    2013-01-01

    Mass transport within collagen-based matrices is critical to tissue development, repair, and pathogenesis as well as the design of next generation tissue engineering strategies. This work shows how collagen precursors, specified by intermolecular cross-link composition, provide independent control of collagen matrix mechanical and transport properties. Collagen matrices were prepared from tissue-extracted monomers or oligomers. Viscoelastic behavior was measured in oscillatory shear and unconfined compression. Matrix permeability and diffusivity were measured using gravity-driven permeametry and integrated optical imaging, respectively. Both collagen types showed an increase in stiffness and permeability hindrance with increasing collagen concentration (fibril density); however, different physical property-concentration relationships were noted. Diffusivity wasn’t affected by concentration for either collagen type over the range tested. In general, oligomer matrices exhibited a substantial increase in stiffness and only a modest decrease in transport properties when compared to monomer matrices prepared at the same concentration. The observed differences in viscoelastic and transport properties were largely attributed to increased levels of interfibril branching within oligomer matrices. The ability to relate physical properties to relevant microstructure parameters, including fibril density and interfibril branching, is expected to advance the understanding of cell-matrix signaling as well as facilitate model-based prediction and design of matrix-based therapeutic strategies. PMID:23842082

  14. Some aspects of nanomodification of mineral dispersions by oligomers based on trifunctional oxyphenyl

    Directory of Open Access Journals (Sweden)

    : Shapovalov Nikolay Afanasyevich

    2016-12-01

    Full Text Available te size of the dispersion phase and other colloid-chemical characteristics of suspensions used in the building industry are determined by the peculiarities of the boundary layer structure. The authors have identified the adsorption parameters of resole oligomers synthesized on the base of trifunctionl oxyphenyls on the following adsorbents: CaCO3, ZnO. The most potential adsorption pattern of phloroglucinefurfural nanomodificator molecules on the surface of chalk particles have been suggested in the work. It has been stated that the molecules of oxyphenyl oligomers are adsorbed on the surface of disperse material particles forming monomolecular layer. The adsorption on the particles surface is provided by the ionic interaction of negative oxy groups of the phloroglicine unit or resocine with positively charged active centers of dispersion phase surface and dispersion forces of interaction between the system of oligomer aromatic rings and particles surface. It has been proved that the injection of optimal dose of phloroglucinefurfural nanomodificator into the chalk and zink oxide suspensions decreases the number average radius of nanomodified particles to the size of initial particles of the dispersions under study – from 7 to 1 mcm for chalk and from 5 mcm to 50 nm for zink oxide. It demonstrates the peptizing effect of the nanomodificator.

  15. Template-directed synthesis of linear porphyrin oligomers: classical, Vernier and mutual Vernier.

    Science.gov (United States)

    Kamonsutthipaijit, Nuntaporn; Anderson, Harry L

    2017-04-01

    Three different types of template-directed syntheses of linear porphyrin oligomers are presented. In the classical approach the product has the same number of binding sites as the template, whereas in Vernier reactions the product has the lowest common multiple of the numbers of binding sites in the template and the building block. Mutual Vernier templating is like Vernier templating except that both strands of the Vernier complex undergo coupling simultaneously, so that it becomes impossible to say which is the 'template' and which is the 'building block'. The template-directed synthesis of monodisperse linear oligomers is more difficult than that of cyclic oligomers, because the products of linear templating have reactive ends. All three types of templating are demonstrated here, and used to prepare a nickel(ii) porphyrin dodecamer with 4-pyridyl substituents on all twelve porphyrin units. The stabilities and cooperativities of the double-strand complexes involved in these reactions were investigated by UV-vis-NIR titration. The four-rung ladder duplex has a stability constant of about 2 × 1018 M-1 in dichloromethane at 298 K.

  16. Identification of Phenolic Acids and Changes in their Content during Fermentation and Ageing of White Wines Pošip and Rukatac

    Directory of Open Access Journals (Sweden)

    Tomislav Lovrić

    2002-01-01

    Full Text Available Identification of phenolic acids was performed and changes in their content during the production of autochthonous Croatian white wines Pošip and Rukatac (Vitis vinifera, L. were registered. In both varieties (Pošip, Rukatac the following phenolic acids were identified: gallic, protocatechuic and vanillic acids as hydroxybenzoic acids; and caffeic, p-coumaric and ferulic acids as hydroxycinnamic acids. It was found that there is a difference between hydroxybenzoic acid group and hydroxycinnamic acid group content and between their influences on the wine colour (colour intensity and hue.

  17. Modulating gene function with peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E.; Crooke, Stanley T.

    2008-01-01

    A review on peptide nucleic acid (PNA) oligomers as modulators of gene expression ranging from gene silencing at the mRNAor the dsDNA (antigene) level, and redirection of mRNA splicing to gene activation through transcription bubble mimicking. PNA chem., anti-infective agents, cellular delivery, ......, and in vivo bioavailability of PNA are briefly discussed. [on SciFinder (R)]...

  18. Hydroxycinnamic acids in cooked potato tubers fromSolanum tuberosumgroup Phureja.

    Science.gov (United States)

    Piñeros-Niño, Clara; Narváez-Cuenca, Carlos-Eduardo; Kushalappa, Ajjamada C; Mosquera, Teresa

    2017-05-01

    Hydroxycinnamic acids are phenolic compounds and are considered to have health promotion properties due to their antioxidant activity. Potato tubers of 113 genotypes of Solanum tuberosum group Phureja belonging to the Colombian Central Collection, landraces of potatoes, and commercial cultivars were evaluated for their hydroxycinnamic acids content. The composition of these compounds was analyzed using cooked tubers in two different agro-climatic conditions. The genotypes were analyzed for chlorogenic acid, neo -chlorogenic acid, crypto -chlorogenic acid, and caffeic acid by ultrahigh-performance liquid chromatography (UHPLC). Chlorogenic acid was the major representative and varied between 0.77 to 7.98 g kg -1  DW (dry weight) followed by crypto -chlorogenic acid (from 0.09 to 1.50 g kg -1  DW). Under moorland agro-climatic conditions even though the chlorogenic acid levels increased with respect to flatland agro-climatic conditions, the related isomer neo -chlorogenic acid decreased as compared to flatland conditions. The correlation between chlorogenic acid with the isomers, and with caffeic acid was positive. This study demonstrated that there is a wide variation in hydroxycinnamic acids contents in the germplasm studied, which can be exploited in breeding programs to contribute to human health.

  19. Sustainable hydrogen from bio-oil - Catalytic steam reforming of acetic acid as a model oxygenate

    NARCIS (Netherlands)

    Takanabe, Kazuhiro; Seshan, K.; Lefferts, Leon; Aika, Ken-ichi

    2004-01-01

    Steam reforming of acetic acid as a model oxygenate present in bio-oil over Pt/ZrO2 catalysts has been studied. Pt/ZrO2 catalysts are very active, completely converting acetic acid and give hydrogen yield close to thermodynamic equilibrium. The catalyst deactivated by formation of oligomers, which

  20. Sustainable hydrogen from bio-oil - Steam reforming of acetic acid as a model oxygenate

    NARCIS (Netherlands)

    Takanabe, K.; Aika, Ken-ichi; Seshan, Kulathuiyer; Lefferts, Leonardus

    2004-01-01

    Steam reforming of acetic acid over Pt/ZrO2 catalysts has been investigated. Pt/ZrO2 catalysts are very active, completely converting acetic acid, and give a hydrogen yield close to thermodynamic equilibrium. The catalyst deactivated by formation of oligomers which block the active sites. The

  1. Structure/Property Relationships of Poly(L-lactic Acid/Mesoporous Silica Nanocomposites

    Directory of Open Access Journals (Sweden)

    Javier Gudiño-Rivera

    2013-01-01

    Full Text Available Biodegradable poly(L-lactic acid (PLLA/mesoporous silica nanocomposites were prepared by grafting L-lactic acid oligomer onto silanol groups at the surface of mesoporous silica (SBA-15. The infrared results showed that the lactic acid oligomer was grafted onto the mesoporous silica. Surface characterization of mesoporous silica proved that the grafted oligomer blocked the entry of nitrogen into the mesopores. Thermal analysis measurements showed evidence that, once mixed with PLLA, SBA-15 not only nucleated the PLLA but also increased the total amount of crystallinity. Neat PLLA and its nanocomposites crystallized in the same crystal habit and, as expected, PLLA had a defined periodicity compared with the nanocomposites. This was because the grafted macromolecules on silica tended to cover the lamellar crystalline order. The g-SBA-15 nanoparticles improved the tensile moduli, increasing also the tensile strength of the resultant nanocomposites. Overall, the silica concentration tended to form a brittle material.

  2. ENVIRONMENTAL ENRICHMENT STRENGTHENS CORTICOCORTICAL INTERACTIONS AND REDUCES AMYLOID-β OLIGOMERS IN AGED MICE

    Directory of Open Access Journals (Sweden)

    Marco eMainardi

    2014-01-01

    Full Text Available Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE, a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.

  3. Human taste detection of glucose oligomers with low degree of polymerization.

    Science.gov (United States)

    Pullicin, Alexa J; Penner, Michael H; Lim, Juyun

    2017-01-01

    Studies have reported that some animals, including humans, can taste mixtures of glucose oligomers (i.e., maltooligosaccharides, MOS) and that their detection is independent of the known T1R2/T1R3 sweet taste receptor. In an effort to understand potential mechanisms underlying the taste perception of glucose oligomers in humans, this study was designed to investigate: 1) the variability of taste sensitivity to MOS with low degree-of-polymerization (DP), and 2) the potential role of hT1R2/T1R3 in the MOS taste detection. To address these objectives, a series of food grade, narrow-DP-range MOS were first prepared (DP 3, 3-4, 5-6, and 6-7) by fractionating disperse saccharide mixtures. Subjects were then asked to discriminate these MOS stimuli as well as glucose (DP 1) and maltose (DP 2) from blanks after the stimuli were swabbed on the tongue. All stimuli were presented at 75 mM with and without a sweet taste inhibitor (lactisole). An α-glucosidase inhibitor (acarbose) was added to all test stimuli to prevent oral digestion of glucose oligomers. Results showed that all six stimuli were detected with similar discriminability in normal tasting conditions. When the sweet receptor was inhibited, DP 1, 2, and 3 were not discriminated from blanks. In contrast, three higher-DP paired MOS stimuli (DP 3-4, 5-6, and 6-7) were discriminated from blanks at a similar degree. Overall, these results support the presence of a sweet-independent taste perception mechanism that is stimulated by MOS greater than three units.

  4. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  5. Flavonoid oligomers from Chinese dragon’s blood, the red resins of Dracaena cochinchinensis

    OpenAIRE

    Zheng, Qing-An; Xu, Min; Yang, Chong-Ren; Wang, Dong; Li, Hai-Zhou; Zhu, Hong-Tao; Zhang, Ying-Jun

    2012-01-01

    A detailed chemical investigation of the red resins from Dracaena cochinchinensis (Chinese dragon’s blood) yielded five new flavonoid oligomers, named cochinchinenins D-H (1–5), together with a known biflavonoid, cinnabarone (6), and a mixture of two known biflavonoids, socotrin-4′-ol (7) and homoisosocotrin-4′-ol (8). Of these new compounds, 1–3 were biflavonoids and 4 and 5 were triflavonoids. Their structures were determined on the basis of spectroscopic analysis. The isolated compounds we...

  6. Simulations of fluorescence solvatochromism in substituted PPV oligomers from excited state molecular dynamics with implicit solvent

    Science.gov (United States)

    Bjorgaard, J. A.; Nelson, T.; Kalinin, K.; Kuzmenko, V.; Velizhanin, K. A.; Tretiak, S.

    2015-07-01

    An efficient method of treating solvent effects in excited state molecular dynamics (ESMD) is implemented and tested by exploring the solvatochromic effects in substituted p-phenylene vinylene oligomers. A continuum solvent model is used which has very little computational overhead. This allows simulations of ESMD with solvent effects on the scale of hundreds of picoseconds for systems of up to hundreds of atoms. At these time scales, solvatochromic shifts in fluoresence spectra can be described. Solvatochromic shifts in absorption and fluorescence spectra from ESMD are compared with time-dependent density functional theory calculations and experiments.

  7. Synthetic oligomer analysis using atmospheric pressure photoionization mass spectrometry at different photon energies

    Energy Technology Data Exchange (ETDEWEB)

    Desmazières, Bernard [Global Bioenergies, 5 rue Henri Desbruyeres, 91030 Evry (France); Legros, Véronique [CNRS, UMR8587, Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry (France); Giuliani, Alexandre [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, 91192 Gif-sur-Yvette (France); UAR1008, CEPIA, INRA, Rue de la Geraudiere, F-44316 Nantes (France); Buchmann, William, E-mail: william.buchmann@univ-evry.fr [CNRS, UMR8587, Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry (France)

    2014-01-15

    Graphical abstract: Atmospheric pressure photoIonization mass spectra of synthetic oligomers were recorded in the negative mode by varying the photon energy using synchrotron radiation. Photon energy required for an efficient ionization of the polymer was correlated to ionization potential of the solvent (for example 9.4 eV for tetrahydrofuran). -- Highlights: •Atmospheric pressure photoionization was performed using synchrotron radiation. •Photoionization of oligomers in THF with 10% CH{sub 2}Cl{sub 2} produces intact [M + Cl]{sup −} ions. •The photon energy required corresponds to ionization potential of the solvent. •Polymer distributions depend on source parameters such T °C and applied voltages. •Liquid chromatography was coupled to MS using an APPI interface for polymer analysis. -- Abstract: Atmospheric pressure photoionization (APPI) followed by mass spectrometric detection was used to ionize a variety of polymers: polyethylene glycol, polymethyl methacrylate, polystyrene, and polysiloxane. In most cases, whatever the polymer or the solvent used (dichloromethane, tetrahydrofuran, hexane, acetone or toluene), only negative ion mode produced intact ions such as chlorinated adducts, with no or few fragmentations, in contrast to the positive ion mode that frequently led to important in-source fragmentations. In addition, it was shown that optimal detection of polymer distributions require a fine tuning of other source parameters such as temperature and ion transfer voltage. Series of mass spectra were recorded in the negative mode, in various solvents (dichloromethane, tetrahydrofuran, hexane, toluene, and acetone), by varying the photon energy from 8 eV up to 10.6 eV using synchrotron radiation. To these solvents, addition of a classical APPI dopant (toluene or acetone) was not necessary. Courtesy of the synchrotron radiation, it was demonstrated that the photon energy required for an efficient ionization of the polymer was correlated to the

  8. Unraveling the degradation of artificial amide bonds in nylon oligomer hydrolase: from induced-fit to acylation processes.

    Science.gov (United States)

    Baba, Takeshi; Boero, Mauro; Kamiya, Katsumasa; Ando, Hiroyuki; Negoro, Seiji; Nakano, Masayoshi; Shigeta, Yasuteru

    2015-02-14

    To elucidate how the nylon oligomer hydrolase (NylB) acquires its peculiar degradation activity towards non-biological amide bonds, we inspected the underlying enzymatic processes going from the induced-fit upon substrate binding to acylation. Specifically we investigated the mutational effects of two mutants, Y170F and D181G, indicated in former experiments as crucial systems because of their specific amino acid residues. Therefore, by adopting first-principles molecular dynamics complemented with metadynamics we provide a detailed insight into the underlying acylation mechanism. Our results show that while in the wild type (WT) the Tyr170 residue points the NH group towards the proton-acceptor site of an artificial amide bond, hence ready to react, in the Y170F this does not occur. The reason is ascribed to the absence of Tyr170 in the mutant, which is replaced by phenylalanine, which is unable to form hydrogen bond with the amide bond; thus, resulting in an increase in the activation barrier of more than 10 kcal mol(-1). Nonetheless, despite the lack of hydrogen bonding between the Y170F and the substrate, the highest free energy barrier for the induced-fit is similar to that of WT. This seems to suggest that in the induced-fit process, kinetics is little affected by the mutation. On the basis of additional structural homology analyses on the enzymes of the same family, we suggest that natural selection is responsible for the development of the peculiar hydrolytic activity of Arthrobacter sp. KI72.

  9. DNA-Grafted Supramolecular Polymers: Helical Ribbon Structures Formed by Self-Assembly of Pyrene-DNA Chimeric Oligomers.

    Science.gov (United States)

    Vyborna, Yuliia; Vybornyi, Mykhailo; Rudnev, Alexander V; Häner, Robert

    2015-06-26

    The controlled arraying of DNA strands on adaptive polymeric platforms remains a challenge. Here, the noncovalent synthesis of DNA-grafted supramolecular polymers from short chimeric oligomers is presented. The oligomers are composed of an oligopyrenotide strand attached to the 5'-end of an oligodeoxynucleotide. The supramolecular polymerization of these oligomers in an aqueous medium leads to the formation of one-dimensional (1D) helical ribbon structures. Atomic force and transmission electron microscopy show rod-like polymers of several hundred nanometers in length. DNA-grafted polymers of the type described herein will serve as models for the development of structurally and functionally diverse supramolecular platforms with applications in materials science and diagnostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Characterizing the dynamics of alpha-synuclein oligomers using hydrogen/deuterium exchange monitored by mass spectrometry

    DEFF Research Database (Denmark)

    Mysling, Simon; Betzer, Cristine; Jensen, Poul H

    2013-01-01

    SN (residues 94-140) underwent isotopic exchange very rapidly, demonstrating a highly dynamic region in the oligomeric state. Three regions (residues 4-17, 39-54, and 70-89) were strongly protected against isotopic exchange in the oligomers, indicating the presence of a stable hydrogen-bonded or solvent...... hydrogen/deuterium exchange monitored by mass spectrometry (HDX-MS), we have analyzed the structural dynamics of soluble αSN oligomers. The analyzed oligomers were metastable, slowly dissociating to monomers over a period of 21 days, after excess monomer had been removed. The C-terminal region of α...... analyses performed on αSN fibrils and indicated a possible zipperlike maturation mechanism for αSN aggregates. We find the protected N-terminus (residues 4-17) to be of particular interest, as this region has previously been observed to be highly dynamic for both monomeric and fibrillar αSN. This region...

  11. Induction of Covalently Crosslinked p62 Oligomers with Reduced Binding to Polyubiquitinated Proteins by the Autophagy Inhibitor Verteporfin.

    Directory of Open Access Journals (Sweden)

    Elizabeth Donohue

    Full Text Available Autophagy is a cellular catabolic process responsible for the degradation of cytoplasmic constituents, including organelles and long-lived proteins, that helps maintain cellular homeostasis and protect against various cellular stresses. Verteporfin is a benzoporphyrin derivative used clinically in photodynamic therapy to treat macular degeneration. Verteporfin was recently found to inhibit autophagosome formation by an unknown mechanism that does not require exposure to light. We report that verteporfin directly targets and modifies p62, a scaffold and adaptor protein that binds both polyubiquitinated proteins destined for degradation and LC3 on autophagosomal membranes. Western blotting experiments revealed that exposure of cells or purified p62 to verteporfin causes the formation of covalently crosslinked p62 oligomers by a mechanism involving low-level singlet oxygen production. Rose bengal, a singlet oxygen producer structurally unrelated to verteporfin, also produced crosslinked p62 oligomers and inhibited autophagosome formation. Co-immunoprecipitation experiments demonstrated that crosslinked p62 oligomers retain their ability to bind to LC3 but show defective binding to polyubiquitinated proteins. Mutations in the p62 PB1 domain that abolish self-oligomerization also abolished crosslinked oligomer formation. Interestingly, small amounts of crosslinked p62 oligomers were detected in untreated cells, and other groups noted the accumulation of p62 forms with reduced SDS-PAGE mobility in cellular and animal models of oxidative stress and aging. These data indicate that p62 is particularly susceptible to oxidative crosslinking and lead us to propose a model whereby oxidized crosslinked p62 oligomers generated rapidly by drugs like verteporfin or over time during the aging process interfere with autophagy.

  12. Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease.

    Science.gov (United States)

    Deas, Emma; Cremades, Nunilo; Angelova, Plamena R; Ludtmann, Marthe H R; Yao, Zhi; Chen, Serene; Horrocks, Mathew H; Banushi, Blerida; Little, Daniel; Devine, Michael J; Gissen, Paul; Klenerman, David; Dobson, Christopher M; Wood, Nicholas W; Gandhi, Sonia; Abramov, Andrey Y

    2016-03-01

    Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity. We first demonstrate excessive free radical production in a human induced pluripotent stem-derived α-S triplication model at basal levels and on application of picomolar doses of β-sheet-rich α-S oligomers. We probed the effects of different structural species of α-S in wild-type rat neuronal cultures and show that both oligomeric and fibrillar forms of α-S are capable of generating free radical production, but that only the oligomeric form results in reduction of endogenous glutathione and subsequent neuronal toxicity. We dissected the mechanism of oligomer-induced free radical production and found that it was interestingly independent of several known cellular enzymatic sources. The oligomer-induced reactive oxygen species (ROS) production was entirely dependent on the presence of free metal ions as addition of metal chelators was able to block oligomer-induced ROS production and prevent oligomer-induced neuronal death. Our findings further support the causative role of soluble amyloid oligomers in triggering neurodegeneration and shed light into the mechanisms by which these species cause neuronal damage, which, we show here, can be amenable to modulation through the use of metal chelation.

  13. Effect of Conjugation Length on Photoinduced Charge-Transfer in π-Conjugated Oligomer-Acceptor Dyads

    KAUST Repository

    Jiang, Junlin

    2017-05-25

    A series of -conjugated oligomer-acceptor dyads were synthesized that feature oligo(phenylene ethynylene) (OPE) conjugated backbones end-capped with a naphthalene diimide (NDI) acceptor. The OPE segments vary in length from 4 to 8 phenylene ethynene units (PEn-NDI, where n = 4, 6 and 8). Fluorescence and transient absorption spectroscopy reveals that intramolecular OPE NDI charge transfer dominates the deactivation of excited states of the PEn-NDI oligomers. Both charge separation (CS) and charge recombination (CR) are strongly exothermic (G0CS ~ -1.1 and G0CR ~ -2.0 eV), and the driving forces do not vary much across the series because the oxidation and reduction potentials and singlet energies of the OPEs do not vary much with their length. Bimolecular photoinduced charge transfer between model OPEs that do not contain the NDI acceptors with methyl viologen was studied, and the results reveal that the absorption of the cation radical state (OPE+•) remains approximately constant ( ~ 575 nm) regardless of oligomer length. This finding suggests that the cation radical (polaron) of the OPE is relatively localized, effectively occupying a confined segment of n 4 repeat units in the longer oligomers. Photoinduced intramolecular electron transfer dynamics in the PEn-NDI series was investigated by UV-visible femtosecond transient absorption spectroscopy with visible and mid-infrared probes. Charge separation occurs on the 1 – 10 ps timescale, with the rates decreasing slightly with increased oligomer length (βCS ~ 0.15 Å-1). The rate for charge-recombination decreases in the sequence PE4-NDI > PE6-NDI ~ PE8-NDI. The discontinuous distance dependence in the rate for charge recombination may be related to the spatial localization of the positive polaron state in the longer oligomers.

  14. Self-assembly of soluble unlinked and cross-linked fibrin oligomers.

    Science.gov (United States)

    Rosenfeld, M A; Leonova, V B; Biryukova, M I; Vasileva, M V

    2011-10-01

    Self-assembly of soluble unlinked and cross-linked fibrin oligomers formed from desA-fibrin monomer under the influence of factor XIIIa was studied in the presence of non-denaturing urea concentrations. By methods of elastic and dynamic light scattering combined with analytical ultracentrifugation, desA-fibrin oligomers formed in both the presence and absence of the factor XIIIa were shown to be ensembles consisting of soluble rod-like double-stranded protofibrils with diverse weight and size. Unlinked and cross-linked soluble double-stranded protofibrils can reach the length of 350-450 nm. The structure of soluble covalently-linked protofibrils is stabilized by isopeptide γ-dimers. Electrophoretic data indicate a complete absence of isopeptide bonds between α-chains of desA-fibrin molecules. The molecular mechanism of formation of soluble rod-like fibrin structures and specific features of its covalent stabilization under the influence of factor XIIIa are discussed.

  15. Enhanced Solubilization of Fluoranthene by Hydroxypropyl β-Cyclodextrin Oligomer for Bioremediation

    Directory of Open Access Journals (Sweden)

    Kyeong Hui Park

    2018-01-01

    Full Text Available Fluoranthene (FT is a polycyclic aromatic hydrocarbon (PAH, consisting of naphthalene and benzene rings connected by a five-member ring. It is widespread in the environment. The hydrophobicity of FT limits its availability for biological uptake and degradation. In this study, hydroxypropyl β-cyclodextrin oligomers (HP-β-CD-ol were synthesized with epichlorohydrin (EP, while the solubility enhancement of FT by HP-β-CD-ol was investigated in water. The synthesized HP-β-CD-ol was characterized by MALDI-TOF mass spectrometry (MS, 1H NMR, and 13C NMR spectroscopy. The solubility of FT increased 178-fold due to the complex formation with HP-β-CD oligomers. The inclusion complexes of FT/HP-β-CD-ol were analyzed using Fourier-Transform Infrared (FT-IR, Differential Scanning Calorimetry (DSC, Scanning Electron Microscope (SEM, and Nuclear Overhauser Effect Spectroscopy Nuclear magnetic resonance (NOESY NMR spectroscopy. On the basis of these results, HP-β-CD-ol is recommended as a potential solubilizer for the development of PAH removal systems.

  16. Green synthesis and antimicrobial activity of silver chloride nanoparticles stabilized with chitosan oligomer.

    Science.gov (United States)

    Kang, Yun Ok; Lee, Taek Seung; Park, Won Ho

    2014-12-01

    Nanocrystalline silver (Ag) and Ag containing nanostructure synthesized using various methods have been studied for their antimicrobial, wound healing, and anti-inflammatory efficacy. Among these, crystalline silver chloride (AgCl) nanostructures exhibit desirable properties for biological and biomedical applications. However, most of them are synthesized using hazardous agents and organic solvents, which has been limited for application in the biological field. A simple and environmentally friendly method was demonstrated for AgCl nanoparticles stabilized with chitosan oligomer (CHI-AgCl NPs) as both a resource of Cl ions and stabilizing agent with expectations of synergistic effects. The CHI-AgCl NPs stabilized by the chitosan oligomer had spherical morphology with a mean diameter of 42 ± 15 nm. Ag ions precipitated as AgCl in presence of Cl ions, which remained in the protonated amine group after HCl hydrolysis of the chitosan. Moreover, much of the amine and hydroxyl group bound to the AgCl NPs for growth and stabilization. These nanoparticles were characterized via various spectroscopic techniques, including UV-Vis spectrophotometry, X-ray photoelectron spectrometry, X-ray diffractometry, and transmission electron microscopy.

  17. Antimicrobial Silver Chloride Nanoparticles Stabilized with Chitosan Oligomer for the Healing of Burns

    Directory of Open Access Journals (Sweden)

    Yun Ok Kang

    2016-03-01

    Full Text Available Recently, numerous compounds have been studied in order to develop antibacterial agents, which can prevent colonized wounds from infection, and assist the wound healing. For this purpose, novel silver chloride nanoparticles stabilized with chitosan oligomer (CHI-AgCl NPs were synthesized to investigate the influence of antibacterial chitosan oligomer (CHI exerted by the silver chloride nanoparticles (AgCl NPs on burn wound healing in a rat model. The CHI-AgCl NPs had a spherical morphology with a mean diameter of 42 ± 15 nm. The burn wound healing of CHI-AgCl NPs ointment was compared with untreated group, Vaseline ointment, and chitosan ointment group. The burn wound treated with CHI-AgCl NPs ointment was completely healed by 14 treatment days, and was similar to normal skin. Particularly, the regenerated collagen density became the highest in the CHI-AgCl NPs ointment group. The CHI-AgCl NPs ointment is considered a suitable healing agent for burn wounds, due to dual antibacterial activity of the AgCl NPs and CHI.

  18. Atomistic simulation of CO 2 solubility in poly(ethylene oxide) oligomers

    KAUST Repository

    Hong, Bingbing

    2013-10-02

    We have performed atomistic molecular dynamics simulations coupled with thermodynamic integration to obtain the excess chemical potential and pressure-composition phase diagrams for CO2 in poly(ethylene oxide) oligomers. Poly(ethylene oxide) dimethyl ether, CH3O(CH 2CH2O)nCH3 (PEO for short) is a widely applied physical solvent that forms the major organic constituent of a class of novel nanoparticle-based absorbents. Good predictions were obtained for pressure-composition-density relations for CO2 + PEO oligomers (2 ≤ n ≤ 12), using the Potoff force field for PEO [J. Chem. Phys. 136, 044514 (2012)] together with the TraPPE model for CO2 [AIChE J. 47, 1676 (2001)]. Water effects on Henrys constant of CO2 in PEO have also been investigated. Addition of modest amounts of water in PEO produces a relatively small increase in Henrys constant. Dependence of the calculated Henrys constant on the weight percentage of water falls on a temperature-dependent master curve, irrespective of PEO chain length. © 2013 Taylor & Francis.

  19. Self-Healable and Reprocessable Polysulfide Sealants Prepared from Liquid Polysulfide Oligomer and Epoxy Resin.

    Science.gov (United States)

    Gao, Wentong; Bie, Mengyao; Liu, Fu; Chang, Pengshan; Quan, Yiwu

    2017-05-10

    Polysulfide sealants have been commercially applied in many industrial fields. In this article, we study the self-healing property of the epoxy resin-cured polysulfide sealants for the first time. The obtained sealants showed a flexible range of ultimate elongation of 157-478% and a tensile strength of 1.02-0.75 MPa corresponding to different polysulfide oligomers. By taking advantage of the dynamic reversible exchange of disulfide bonds, polysulfide sealants exhibited good self-healing ability under a moderate thermal stimulus. A higher molecular weight and a lower degree of cross-linking of polysulfide oligomer were helpful in improving the ultimate elongation and healing efficiency of the polysulfide sealants. After subjecting to a temperature of 75 °C for 60 min, both the tensile strength and ultimate elongation of a fully cut sample, LP55-F, were restored to 91% of the original values, without affecting the sealing property. Furthermore, the sample exhibited excellent reshaping and reprocessing abilities. These outcomes offer a paradigm toward sustainable industrial applications of the polysulfide-based sealants.

  20. Identification of chlorinated oligomers formed during anodic oxidation of phenol in the presence of chloride

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Linxi; Campo, Pablo; Kupferle, Margaret J., E-mail: margaret.kupferle@uc.edu

    2015-02-11

    Graphical abstract: - Highlights: • By-products from anodic oxidation of phenol in the presence of chloride are investigated. • Chlorinated oligomer formation is demonstrated by LC-QTOF-MS. • They have structures similar to triclosan and polychlorinated dibenzo-p-dioxins. - Abstract: Chlorinated oligomer intermediates formed during the anodic electrochemical oxidation of phenol with a boron-doped diamond electrode were studied at two different concentrations of chloride (5 mM and 50 mM). Under the same ionic strength, with sodium sulfate being the make-up ion, a 10-fold increase in Cl{sup −} led to removal rates 10.8, 1.5, and 1.4 times higher for phenol, TOC, and COD, respectively. Mono-, di- and trichlorophenols resulting from electrophilic substitution were the identified by-products. Nevertheless, discrepancies between theoretical and measured TOC values along with gaps in the mass balance of chlorine-containing species indicated the formation of unaccounted-for chlorinated by-products. Accurate mass measurements by liquid chromatography quadrupole time-of-flight mass spectrometry and MS-MS fragmentation spectra showed that additional compounds formed were dimers and trimers of phenol with structures similar to triclosan and polychlorinated dibenzo-p-dioxins.

  1. The RNA-dependent RNA polymerase of Citrus tristeza virus forms oligomers.

    Science.gov (United States)

    Cevik, Bayram

    2013-12-01

    The RNA-dependent RNA polymerases (RdRp) from Citrus tristeza virus (CTV) were tagged with HA and FLAG epitopes. Differentially tagged proteins were expressed either individually or concomitantly in Escherichia coli. Immunoprecipitation of the expressed proteins with anti-FLAG antibody followed by Western blot with anti-HA antibody demonstrated that molecules of RdRp from CTV interact to form oligomers. Yeast two-hybrid assays showed that molecules of RdRp interact in eukaryotic cells. Co-immunoprecipitation with anti-FLAG antibody of truncated HA-tagged RdRps (RdRpΔ1-166-HA, RdRpΔ1-390-HA, RdRp1-169-HA) co-expressed with full-length RdRp-FLAG showed that only RdRp1-169-HA interacted with the full-length FLAG-RdRp. Yeast two-hybrid assays with truncated RdRp constructs confirmed that the oligomerization site resides in the N-terminal region and that the first 169 aa of CTV RdRp are necessary and sufficient for oligomerization both in bacterial and yeast cells. Development of control strategies targeting viral RdRp oligomer formation may inhibit virus replication and prove useful in control of CTV. © 2013 Elsevier Inc. All rights reserved.

  2. Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala

    Science.gov (United States)

    Chen, Liang; Yang, Yang; Yuan, Pulong; Yang, Yifu; Chen, Kaixian; Jia, Qi; Li, Yiming

    2014-01-01

    Cinnamon barks extracts have been reported to regulate immune function; however, the component(s) in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s) that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F) and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD-1), parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB) induced delayed-type hypersensitivity (DTH) response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-γ and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases. PMID:25530780

  3. Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2014-01-01

    Full Text Available Cinnamon barks extracts have been reported to regulate immune function; however, the component(s in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD-1, parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB induced delayed-type hypersensitivity (DTH response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-γ and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases.

  4. Length dependence of rectification in organic co-oligomer spin rectifiers

    Science.gov (United States)

    Gui-Chao, Hu; Zhao, Zhang; Ying, Li; Jun-Feng, Ren; Chuan-Kui, Wang

    2016-05-01

    The rectification ratio of organic magnetic co-oligomer diodes is investigated theoretically by changing the molecular length. The results reveal two distinct length dependences of the rectification ratio: for a short molecular diode, the charge-current rectification changes little with the increase of molecular length, while the spin-current rectification is weakened sharply by the length; for a long molecular diode, both the charge-current and spin-current rectification ratios increase quickly with the length. The two kinds of dependence switch at a specific length accompanied with an inversion of the rectifying direction. The molecular ortibals and spin-resolved transmission analysis indicate that the dominant mechanism of rectification suffers a change at this specific length, that is, from asymmetric shift of molecular eigenlevels to asymmetric spatial localization of wave functions upon the reversal of bias. This work demonstrates a feasible way to control the rectification in organic co-oligomer spin diodes by adjusting the molecular length. Project supported by the National Natural Science Foundation of China (Grant No. 11374195), the Natural Science Foundation of Shandong Province, China (Grant No. ZR2014AM017), the Taishan Scholar Project of Shandong Province, China, and the Excellent Young Scholars Research Fund of Shandong Normal University, China.

  5. Probing the Nucleus Model for Oligomer Formation during Insulin Amyloid Fibrillogenesis

    Science.gov (United States)

    Pease, Leonard F.; Sorci, Mirco; Guha, Suvajyoti; Tsai, De-Hao; Zachariah, Michael R.; Tarlov, Michael J.; Belfort, Georges

    2010-01-01

    We find evidence for a direct transition of insulin monomers into amyloid fibrils without measurable concentrations of oligomers or protofibrils, suggesting that fibrillogenesis may occur directly from assembly of denaturing insulin monomers rather than by successive transitions through protofibril nuclei. To support our finding, we obtain size distributions using electrospray differential mobility analysis (ES-DMA), which provides excellent resolution to clearly distinguish among small oligomers and rapidly generates statistically significant size distributions. The distributions detect an absence of significant peaks between 6 nm and 17 nm as the monomer reacts into fibers—exactly the size range observed by others for small-angle-neutron-scattering-measured intermediates and for circular supramolecular structures. They report concentrations in the nanomolar range, whereas our limit of detection remains three-orders-of-magnitude lower (<5 pmol/L). This finding, along with the lack of significant increases in the β-sheet content of monomers using circular dichroism, suggests monomers do not first structurally rearrange and accumulate in a β-rich state but react and reorganize at the growing fiber's tip. These results quantitatively inform reaction-based theories of amyloid fiber formation and have implications for neurodegenerative, protein conformation ailments including Alzheimer's disease and bovine spongiform encephalopathy. PMID:21156140

  6. Change of electric dipole moment in charge transfer transitions of ferrocene oligomers studied by ultrafast two-photon absorption

    Science.gov (United States)

    Mikhaylov, Alexander; Arias, Eduardo; Moggio, Ivana; Ziolo, Ronald; Uudsemaa, Merle; Trummal, Aleksander; Cooper, Thomas; Rebane, Aleksander

    2017-02-01

    Change of permanent electric dipole moment in the lower-energy charge transfer transitions for a series of symmetrical and non-symmetrical ferrocene-phenyleneethynylene oligomers were studied by measuring the corresponding femtosecond two-photon absorption cross section spectra, and were determined to be in the range Δμ = 3 - 10 D. Quantum-chemical calculations of Δμ for the non-symmetrical oligomers show good quantitative agreement with the experimental results, thus validating two-photon absorption spectroscopy as a viable experimental approach to study electrostatic properties of organometallics and other charge transfer systems.

  7. Noncovalent intramolecular interactions in the monomers and oligomers of the acceptor and donor type of low band gap conducting polymers

    OpenAIRE

    Özen, Alimet Sema; Ozen, Alimet Sema; Atılgan, Canan; Atilgan, Canan; Sönmez, Gürsel; SONMEZ, Gursel

    2007-01-01

    Intramolecular interactions of non-covalent nature in the conjugated oligomers of co- thiophene-thieno [3,4-b] pyrazine-thiophene and co-thiophene-benzo [c] 1,2,5-thiadiazole-thiophene are studied quantum mechanically. S…N contacts are identified by the existence of topological bond critical points (bcp) along the bond path by means of Atoms-in-molecules (AIM) theory. The planarity of the oligomers is attributed to the observed ring critical points among the thiophene and pyrazine or thiadiaz...

  8. α-Synuclein Oligomers Stabilize Pre-Existing Defects in Supported Bilayers and Propagate Membrane Damage in a Fractal-Like Pattern

    NARCIS (Netherlands)

    Chaudhary, Himanshu; Iyer, Aditya; Subramaniam, Vinod; Claessens, Mireille M A E

    2016-01-01

    Phospholipid vesicles are commonly used to get insights into the mechanism by which oligomers of amyloidogenic proteins damage membranes. Oligomers of the protein α-synuclein (αS) are thought to create pores in phospholipid vesicles containing a high amount of anionic phospholipids but fail to

  9. Identification/quantification of free and bound phenolic acids in peel and pulp of apples (Malus domestica) using high resolution mass spectrometry (HRMS).

    Science.gov (United States)

    Lee, Jihyun; Chan, Bronte Lee Shan; Mitchell, Alyson E

    2017-01-15

    Free and bound phenolic acids were measured in the pulp and peel of four varieties of apples using high resolution mass spectrometry. Twenty-five phenolic acids were identified and included: 8 hydroxybenzoic acids, 11 hydroxycinnamic acids, 5 hydroxyphenylacetic acids, and 1 hydoxyphenylpropanoic acid. Several phenolics are tentatively identified for the first time in apples and include: methyl gallate, ethyl gallate, hydroxy phenyl acetic acid, three phenylacetic acid isomers, 3-(4-hydroxyphenyl)propionic acid, and homoveratric acid. With exception of chlorogenic and caffeic acid, most phenolic acids were quantified for the first time in apples. Significant varietal differences (ppeel and pulp. The levels of total phenolic acids were higher in the pulp as compared to apple peel (dry weight) in all varieties. Coumaroylquinic, protocatechuic, 4-hydroxybenzoic, vanillic and t-ferulic acids were present in free forms. With exception of chlorogenic acid, all other phenolic acids were present only as bound forms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Diverse mechanisms of antidiabetic effects of the different procyanidin oligomer types of two different cinnamon species on db/db mice.

    Science.gov (United States)

    Chen, Liang; Sun, Peng; Wang, Ting; Chen, Kaixian; Jia, Qi; Wang, Heyao; Li, Yiming

    2012-09-12

    The procyanidin oligomers are thought to be responsible for the antidiabetic activity of cinnamon. To investigate the hypoglycemic effects of different procyanidin oligomer types, the procyanidin oligomer-rich extracts were prepared from two different cinnamon species. Using high-performance liquid chromatography with purified procyanidin oligomers as reference compounds, we found that the Cinnamomum cassia extract (CC-E) and Cinnamomum tamala extract (CT-E) were rich in B- and A-type procyanidin oligomers, respectively. In the experiment, 8-week-old diabetic (db/db) mice were gavaged with CC-E and CT-E (both 200 mg/kg per day) for 4 weeks. Both CC-E and CT-E exhibited antidiabetic effects. Moreover, histopathological studies of the pancreas, liver, and adipose tissue showed that CC-E promoted lipid accumulation in the adipose tissue and liver, whereas CT-E mainly improved the insulin concentration in the blood and pancreas.

  11. Synthesis and characterization of thermally stable oligomer-metal complexes of copper(II), nickel(II), zinc(II) and cobalt(II) derived from oligo-p-nitrophenylazomethinephenol

    OpenAIRE

    Ufuk S. Vural; Hasan Mart; H. Okkes Demir; Ozlem Sarıöz; Vefa Muradoğlu; M. Cihangir Koç

    2006-01-01

    Thermally stable metal complexes based on oligomers were prepared by the reaction between oligo-p-nitrophenilazomethinephenol (ONPAP) and Cu(II), Ni(II), Zn(II) and Co(II) ions. The properties of oligomer-metal complexes were studied by elemental, FT-IR and magnetic moments analyses. The thermal stabilities of the oligomer-metal complexes were compared by thermogravimetric (TG) and differential thermal (DTA) analyses. According to TG, oligomer-metal complexes were stable against to temperatur...

  12. Determination of free and bounded phenolic acids in the rhizomes and herb of Sanguisorba officinalis L.

    Directory of Open Access Journals (Sweden)

    Biernasiuk Anna

    2015-12-01

    Full Text Available An analysis of the fractions of free acids and phenolic acids liberated by way of hydrolysis in the rhizomes and herbaceous tissues of Sanguisorba officinalis L. was conducted through utilizing the 2D-TLC method. Fifteen phenolic acids were identified. Our work showed that ellagic, protocatechuic, gentisic, p-hydroxybenzoic, syringic, vannilic and ferulic acids were common in all tested fractions, and gallic and protocatechuic acids were dominant in fractions obtained from the rhizomes, while caffeic, p-coumaric, syringic, vannilic and ferulic acids were abundant in the herbaceous tissues. However, α and β - resorcylic acids were detected only in rhizome phenolic acid fractions liberated from their conjunction with sugars and alcohols. Furthermore, chlorogenic acid was present only in a free form in the herbaceous tissues, while p-hydroxyphenylacetic acid was liberated from conjunction from a herbaceous extract.

  13. Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer's and Parkinson's diseases.

    Directory of Open Access Journals (Sweden)

    Igor F Tsigelny

    Full Text Available BACKGROUND: Misfolding and pathological aggregation of neuronal proteins has been proposed to play a critical role in the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD and Parkinson's disease (PD are frequent neurodegenerative diseases of the aging population. While progressive accumulation of amyloid beta protein (Abeta oligomers has been identified as one of the central toxic events in AD, accumulation of alpha-synuclein (alpha-syn resulting in the formation of oligomers and protofibrils has been linked to PD and Lewy body Disease (LBD. We have recently shown that Abeta promotes alpha-syn aggregation and toxic conversion in vivo, suggesting that abnormal interactions between misfolded proteins might contribute to disease pathogenesis. However the molecular characteristics and consequences of these interactions are not completely clear. METHODOLOGY/PRINCIPAL FINDINGS: In order to understand the molecular mechanisms involved in potential Abeta/alpha-syn interactions, immunoblot, molecular modeling, and in vitro studies with alpha-syn and Abeta were performed. We showed in vivo in the brains of patients with AD/PD and in transgenic mice, Abeta and alpha-synuclein co-immunoprecipitate and form complexes. Molecular modeling and simulations showed that Abeta binds alpha-syn monomers, homodimers, and trimers, forming hybrid ring-like pentamers. Interactions occurred between the N-terminus of Abeta and the N-terminus and C-terminus of alpha-syn. Interacting alpha-syn and Abeta dimers that dock on the membrane incorporated additional alpha-syn molecules, leading to the formation of more stable pentamers and hexamers that adopt a ring-like structure. Consistent with the simulations, under in vitro cell-free conditions, Abeta interacted with alpha-syn, forming hybrid pore-like oligomers. Moreover, cells expressing alpha-syn and treated with Abeta displayed increased current amplitudes and calcium influx consistent with the

  14. Efficient Cleavage of Lignin–Carbohydrate Complexes and Ultrafast Extraction of Lignin Oligomers from Wood Biomass by Microwave‐Assisted Treatment with Deep Eutectic Solvent

    Science.gov (United States)

    Liu, Yongzhuang; Chen, Wenshuai; Xia, Qinqin; Guo, Bingtuo; Wang, Qingwen; Liu, Shouxin; Liu, Yixing; Li, Jian

    2017-01-01

    Abstract Lignocellulosic biomass is an abundant and renewable resource for the production of biobased value‐added fuels, chemicals, and materials, but its effective exploitation by an energy‐efficient and environmentally friendly strategy remains a challenge. Herein, a facile approach for efficiently cleaving lignin–carbohydrate complexes and ultrafast fractionation of components from wood by microwave‐assisted treatment with deep eutectic solvent is reported. The solvent was composed of sustainable choline chloride and oxalic acid dihydrate, and showed a hydrogen‐bond acidity of 1.31. Efficient fractionation of lignocellulose with the solvent was realized by heating at 80 °C under 800 W microwave irradiation for 3 min. The extracted lignin showed a low molecular weight of 913, a low polydispersity of 1.25, and consisted of lignin oligomers with high purity (ca. 96 %), and thus shows potential in downstream production of aromatic chemicals. The other dissolved matter mainly comprised glucose, xylose, and hydroxymethylfurfural. The undissolved material was cellulose with crystal I structure and a crystallinity of approximately 75 %, which can be used for fabricating nanocellulose. Therefore, this work promotes an ultrafast lignin‐first biorefinery approach while simultaneously keeping the undissolved cellulose available for further utilization. This work is expected to contribute to improving the economics of overall biorefining of lignocellulosic biomass. PMID:28054749

  15. Efficient Cleavage of Lignin-Carbohydrate Complexes and Ultrafast Extraction of Lignin Oligomers from Wood Biomass by Microwave-Assisted Treatment with Deep Eutectic Solvent.

    Science.gov (United States)

    Liu, Yongzhuang; Chen, Wenshuai; Xia, Qinqin; Guo, Bingtuo; Wang, Qingwen; Liu, Shouxin; Liu, Yixing; Li, Jian; Yu, Haipeng

    2017-04-22

    Lignocellulosic biomass is an abundant and renewable resource for the production of biobased value-added fuels, chemicals, and materials, but its effective exploitation by an energy-efficient and environmentally friendly strategy remains a challenge. Herein, a facile approach for efficiently cleaving lignin-carbohydrate complexes and ultrafast fractionation of components from wood by microwave-assisted treatment with deep eutectic solvent is reported. The solvent was composed of sustainable choline chloride and oxalic acid dihydrate, and showed a hydrogen-bond acidity of 1.31. Efficient fractionation of lignocellulose with the solvent was realized by heating at 80 °C under 800 W microwave irradiation for 3 min. The extracted lignin showed a low molecular weight of 913, a low polydispersity of 1.25, and consisted of lignin oligomers with high purity (ca. 96 %), and thus shows potential in downstream production of aromatic chemicals. The other dissolved matter mainly comprised glucose, xylose, and hydroxymethylfurfural. The undissolved material was cellulose with crystal I structure and a crystallinity of approximately 75 %, which can be used for fabricating nanocellulose. Therefore, this work promotes an ultrafast lignin-first biorefinery approach while simultaneously keeping the undissolved cellulose available for further utilization. This work is expected to contribute to improving the economics of overall biorefining of lignocellulosic biomass. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  16. Unified approach to catechin hetero-oligomers: first total synthesis of trimer EZ-EG-CA isolated from Ziziphus jujuba.

    Science.gov (United States)

    Yano, Takahisa; Ohmori, Ken; Takahashi, Haruko; Kusumi, Takenori; Suzuki, Keisuke

    2012-10-14

    A catechin hetero-trimer isolated from Ziziphus jujuba has been synthesized. Among three constituent monomers, (-)-epiafzelechin and (-)-epigallocatechin were prepared by de novo synthesis. Trimer formation relied on the unified approach to oligomers based on the bromo-capping and the orthogonal activation, reaching the reported structure of the natural product.

  17. Far-red fluorescence : A direct spectroscopic marker for LHCII oligomer formation in non-photochemical quenching

    NARCIS (Netherlands)

    Miloslavina, Yuliya; Wehner, Antje; Lambrev, Petar H.; Wientjes, Emilie; Reus, Michael; Garab, Gyozo; Croce, Roberta; Holzwarth, Alfred R.; Garab, Győző

    2008-01-01

    Time-resolved fluorescence on oligomers of the main light-harvesting complex from higher plants indicate that in vitro oligomerization leads to the formation of a weakly coupled inter-trimer chlorophyll-chlorophyll (Chl) exciton state which converts in tens of ps into a state which is spectrally

  18. Detecting the Formation and Transformation of Oligomers during Insulin Fibrillation by a Dendrimer Conjugated with Aggregation-Induced Emission Molecule.

    Science.gov (United States)

    Huang, Qin; Xie, Jing; Liu, Yanpeng; Zhou, Anna; Li, Jianshu

    2017-04-19

    The fibrillation of protein is harmful and impedes the use of protein drugs. It also relates to various debilitating diseases such as Alzheimer's diseases. Thus, investigating the protein fibrillation process is necessary. In this study, poly(amido amine) dendrimers (PAMAM) of generation 3 (G3) and generation 4 (G4) were synthesized and conjugated with 4-aminobiphenyl, an aggregation-induced emission (AIE) moiety, at varied grafting ratios. Among them, one fluorescence probe named G3-biph-3 that was grafted average 3.25 4-aminobiphenyl to the G3, can detect the transformations both from native insulin to oligomers and from oligomers to fibrils. The size difference of native insulin, oligomers, and fibrils was proposed to be the main factor leading to the detection of the above transformations. Different molecular weights of sodium polyacrylate (PAAS) were also applied as a model to interact with G3-biph-3 to further reveal the mechanism. The results indicated that PAMAM with a certain generation and grafted with appropriate AIE groups can detect the oligomer formation and transformation during the insulin fibrillation process.

  19. Charge-carrier selective electrodes for organic bulk heterojunction solar cell by contact-printed siloxane oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hyun-Sik; Khang, Dahl-Young, E-mail: dykhang@yonsei.ac.kr

    2015-08-31

    ‘Smart’ (or selective) electrode for charge carriers, both electrons and holes, in organic bulk-heterojunction (BHJ) solar cells using insertion layers made of hydrophobically-recovered and contact-printed siloxane oligomers between electrodes and active material has been demonstrated. The siloxane oligomer insertion layer has been formed at a given interface simply by conformally-contacting a cured slab of polydimethylsiloxane stamp for less than 100 s. All the devices, either siloxane oligomer printed at one interface only or printed at both interfaces, showed efficiency enhancement when compared to non-printed ones. The possible mechanism that is responsible for the observed efficiency enhancement has been discussed based on the point of optimum symmetry and photocurrent analysis. Besides its simplicity and large-area applicability, the demonstrated contact-printing technique does not involve any vacuum or wet processing steps and thus can be very useful for the roll-based, continuous production scheme for organic BHJ solar cells. - Highlights: • Carrier-selective insertion layer in organic bulk heterojunction solar cells • Simple contact-printing of siloxane oligomers improves cell efficiency. • Printed siloxane layer reduces carrier recombination at electrode surfaces. • Siloxane insertion layer works equally well at both electrode surfaces. • Patterned PDMS stamp shortens the printing time within 100 s.

  20. Single-channel electrophysiology reveals a distinct and uniform pore complex formed by α-synuclein oligomers in lipid membranes.

    Directory of Open Access Journals (Sweden)

    Felix Schmidt

    Full Text Available Synucleinopathies such as Parkinson's disease, multiple system atrophy and dementia with Lewy bodies are characterized by deposition of aggregated α-synuclein. Recent findings indicate that pathological oligomers rather than fibrillar aggregates may represent the main toxic protein species. It has been shown that α-synuclein oligomers can increase the conductance of lipid bilayers and, in cell-culture, lead to calcium dyshomeostasis and cell death. In this study, employing a setup for single-channel electrophysiology, we found that addition of iron-induced α-synuclein oligomers resulted in quantized and stepwise increases in bilayer conductance indicating insertion of distinct transmembrane pores. These pores switched between open and closed states depending on clamped voltage revealing a single-pore conductance comparable to that of bacterial porins. Pore conductance was dependent on transmembrane potential and the available cation. The pores stably inserted into the bilayer and could not be removed by buffer exchange. Pore formation could be inhibited by co-incubation with the aggregation inhibitor baicalein. Our findings indicate that iron-induced α-synuclein oligomers can form a uniform and distinct pore species with characteristic electrophysiological properties. Pore formation could be a critical event in the pathogenesis of synucleinopathies and provide a novel structural target for disease-modifying therapy.

  1. In Silico Study of Full-Length Amyloid β 1-42 Tri- and Penta-Oligomers in Solution

    NARCIS (Netherlands)

    Masman, Marcelo F.; Eisel, Ulrich L. M.; Csizmadia, Imre G.; Penke, Botond; Enriz, Ricardo D.; Marrink, Siewert Jan; Luiten, Paul G. M.

    2009-01-01

    Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length A beta(1-42)

  2. Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a

    Directory of Open Access Journals (Sweden)

    Yoosoo Yang

    2015-08-01

    Full Text Available Alzheimer’s disease (AD is closely associated with synaptic dysfunction, and thus current treatments often aim to stimulate neurotransmission to improve cognitive impairment. Whereas the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE complex is essential for synaptic transmission, the correlation between SNAREs and AD neuropathology is unknown. Here, we report that intracellular amyloid-β (Aβ oligomers directly inhibit SNARE-mediated exocytosis by impairing SNARE complex formation. We observe abnormal reduction of SNARE complex levels in the brains of APP/PS1 transgenic (TG mice compared to age-matched wild-types. We demonstrate that Aβ oligomers block SNARE complex assembly through the direct interaction with a target membrane (t-SNARE syntaxin 1a in vitro. Furthermore, the results of the in vitro single-vesicle content-mixing assay reveal that Aβ oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular Aβ oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions.

  3. Identification and quantification of oligomers as potential migrants in plastics food contact materials with a focus in polycondensates - A review

    NARCIS (Netherlands)

    Hoppe, M.; de Voogt, P.; Franz, R.

    2016-01-01

    Background: Over the last years the variety of food and beverage packaging has increased with the development of new plastic materials and (co)polymer modifications. Oligomers which are always present in polymers evoke attention as potential migrants, from a qualitatively and quantitatively

  4. The phenolic acids of some species of the Oenothera L. genus

    Directory of Open Access Journals (Sweden)

    Tadeusz Krzaczek

    2014-01-01

    Full Text Available The occurence and approximative quantitative proportions of the phenolic acids in four species of the Oenothera L. genus was determined by the method of TLC and HPLC. In all species of Oenothera L. genus the permanent occurrence of acids: 2-hydroxy-4-metoxybenzoic, salicylic, ferulic, syringic, vanillic, p-coumaric, p-hydroxybenzoic, p-hydroxyphenylacetic, γ-rezorcil, gentysic, protocatechuic, caffeic and gallic has been confirmed. Whereas the other phenolic acids: o-coumaric, o-hydroxyphenylacetic and pirocatechuic were found in some species of the Oenothera L. genus only.

  5. Release of phenolic acids from defatted rice bran by subcritical water treatment.

    Science.gov (United States)

    Fabian, Cynthia; Tran-Thi, Ngoc Yen; Kasim, Novy S; Ju, Yi-Hsu

    2010-12-01

    Oil production from rice bran, an undervalued by-product of rice milling, produces defatted rice bran (DRB) as a waste material. Although it is considered a less valuable product, DRB still contains useful substances such as phenolic compounds with antioxidant, UV-B-protecting and anti-tumour activities. In this study the phenolic acids in DRB were extracted with subcritical water at temperatures of 125, 150, 175 and 200 °C. Analysis of total phenolics using Folin-Ciocalteu reagent showed about 2-20 g gallic acid equivalent kg(-1) bran in the extracts. High-performance liquid chromatography analysis showed low contents of phenolic acids (about 0.4-2 g kg(-1) bran). Ferulic, p-coumaric, gallic and caffeic acids were the major phenolic acids identified in the extracts. Thermal analysis of the phenolic acids was also done. The thermogravimetric curves showed that p-coumaric, caffeic and ferulic acids started to decompose at about 170 °C, while gallic acid did not start to decompose until about 200 °C. Subcritical water can be used to hydrolyse rice bran and release phenolic compounds, but the high temperatures used in the extraction can also cause the decomposition of phenolic acids. Copyright © 2010 Society of Chemical Industry.

  6. Targeting β-amyloid plaques and oligomers: development of near-IR fluorescence imaging probes.

    Science.gov (United States)

    Liu, Hongwu; Yang, Jian; Wang, Letian; Xu, Yungen; Zhang, Siyuan; Lv, Jie; Ran, Chongzhao; Li, Yuyan

    2017-02-01

    Evidence indicated that shifting treatment to a presymptomatic stage may produce significant benefits to prevent/alleviate the progression of Alzheimer's disease (AD); in particular, early incorporation of noninvasive imaging and biomarker testing will be significantly beneficial for AD drug development. Based on amyloid cascade hypothesis and its revised version, both β-amyloid deposition and soluble oligomeric species could be good diagnostic biomarkers for AD. Near-IR fluorescence (NIRF) imaging, which so far is limited to animal studies, is a promising method for its incomparable advantages such as low cost, high-throughput and easy operation. This review focuses on recent reported NIRF probes that showed excellent binding to plaques and oligomers. We hope that this review will shed light on the future of NIRF probes' discovery.

  7. Torsional Barriers to Rotation and Planarization in Heterocyclic Oligomers of Value in Organic Electronics.

    Science.gov (United States)

    Lin, Janice B; Jin, Yu; Lopez, Steven A; Druckerman, Nathaniel; Wheeler, Steven E; Houk, K N

    2017-11-14

    In order to understand the conformational behavior of organic components in organic electronic devices, we have computed the torsional potentials for a library of thiophene-based heterodimers. The accuracy and efficiencies of computational methods for these organic materials were benchmarked for 11 common density functionals with three Pople basis sets against a Focal Point Analysis (FPA) on a model oligothiophene 2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]-thiophene (BTTT) system. This study establishes a set of general trends in regards to conformational preferences, as well as planarization and rotational barriers for a library comprised of common fragments found in organic materials. These gas phase structures are compared to experimental crystal structures to determine the effect of crystal packing on geometry. Finally, we analyze the structure of hole-transporting material DERDTS-TBDT and design a new oligomer likely to be planar in the solid state.

  8. The transition between undiluted and oligomer-diluted states of nearly monodisperse polystyrenes in extensional flow

    DEFF Research Database (Denmark)

    Huang, Qian; Rasmussen, Henrik K.

    2017-01-01

    We have measured the startup and steady extensional viscosity of two narrow molar mass distributed (NMMD) polystyrenes, a 910 kg/mole and a 545 kg/mole, diluted in a NMMD 4.29 kg/mole styrene oligomer, with a wide concentration range from 90 down to 17%. The constant interchain pressure model......, proposed by Rasmussen and Huang (Rheol Acta 53(3):199–208 (2014a)), predicts the extensional viscosity well for the dilutions with lower concentrations. However, for the 70 and 90% 545 kg/mole samples which represent the transition between the diluted and undiluted states, the model predictions are less...... satisfactory. Another concept based on interchain pressure, proposed by Wagner (Rheol Acta 53(10):765–777 (2014)), also shows agreement with the measured data....

  9. A new assessment of the crystalline structure of undoped and doped aniline oligomers and polymers

    Energy Technology Data Exchange (ETDEWEB)

    Lux, F. [School of Chemistry, University of Bristol, Cantock`s Close, Bristol BS8 1TS (United Kingdom); Samuelsen, E.J. [Department of Physics and Mathematics, University of Trondheim, Norwegian Institute of Technology, 7034 Trondheim (Norway); Kang, E.T. [Department of Chemical Engineering, National University of Singapore, Kent Ridge, 0511 Singapore (Singapore)

    1995-03-01

    We describe here the crystalline structure of aniline oligomers and polymers, derived from the aniline dimer, p-aminodiphenylamine, and aniline. It is shown that while the crystalline structure of the undoped samples is generally in reasonable accord with the findings of Pouget et al. for their EBII-structure, especially the crystalline arrangement of the doped materials does not fit the picture, given by these authors for the ESII-salt. The latter fact might be rationalized by the simple exchange of the two main peaks of the ESII arrangement, thus giving the P2{sub 1}22{sub 1} arrangement, proposed by Pouget et al. but not found in their experimental studies. (orig.)

  10. De novo design of protein homo-oligomers with modular hydrogen bond network-mediated specificity

    Science.gov (United States)

    Boyken, Scott E.; Chen, Zibo; Groves, Benjamin; Langan, Robert A.; Oberdorfer, Gustav; Ford, Alex; Gilmore, Jason; Xu, Chunfu; DiMaio, Frank; Pereira, Jose Henrique; Sankaran, Banumathi; Seelig, Georg; Zwart, Peter H.; Baker, David

    2017-01-01

    In nature, structural specificity in DNA and proteins is encoded quite differently: in DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen bond networks with atomic accuracy is a milestone for protein design and enables the programming of protein interaction specificity for a broad range of synthetic biology applications. PMID:27151862

  11. Structure, wettability and thermal degradation of new fluoro-oligomer modified nanoclays.

    Science.gov (United States)

    Valsecchi, R; Viganò, M; Levi, M; Turri, S

    2008-04-01

    Quaternary ammonium salts based on monofunctionalized Perfluoropolyether (PFPE) oligomers were synthesized and used for the cation exchange process of sodium Montmorillonite nanoclays. The new fluoromodified nanoclays were characterized through X-rays diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), termogravimetric analysis (TGA), differential scanning calorimetry (DSC), electronic microscopy (SEM-EDS), and contact angle measurements (CA). In particular XRD showed rather complex patterns (presence of higher order reflections) which allowed the calculation of basal spacings, regularly increasing with the molecular weight of the fluorinated macrocation. Both IR and SEM confirmed the presence of fluorinated segments at clays interface, while TGA showed a limited thermal stability with an onset of degradation temperature which seems not dependent on the molecular weight of the macrocation. CA measurements showed a peculiar behaviour, with evident dynamic hysteresis phenomena and surface tension components quite different from those of commercially available, organomodified clays.

  12. Charge generation in polymer:fullerene and oligomer:fullerene blends for organic photovoltaics

    Science.gov (United States)

    Banerji, Natalie

    Polymer:fullerene blends have attracted attention as efficient organic photovoltaic (OPV) materials promising over 10% power conversion efficiency. It has recently been shown that the polymers can be replaced by small molecules or oligomers, which have better chemical reproducibility. In this talk, I present results obtained with a variety of ultrafast spectroscopic techniques (transient absorption, terahertz and electro-modulated differential absorption spectroscopy) that have allowed to correlate the mechanism of charge generation in donor:acceptor blends to