Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells

Alzheimer’s disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8–40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production.     

Fatty acid modified polyurethane dispersion for surface coatings: Effect of fatty acid content and ionic content

The higher molecular weight fatty acid modified polyurethane–urea dispersions (PUDs) were prepared with effective utilization of fatty acid and ionic emulsifier. The PUDs were prepared using oligomer of linoleic fatty acid, dimethylol propionic acid (DMPA), linear polyester diol, isophorone diisocyanate (IPDI), triethylamine (TEA) and ethylenediamine (EDA) by prepolymer mixing method. Resultant PUDs had so-called controlled branched polymer structures. To incorporate fatty acid residues in the backbone of the polyurethane two types of oligomers were used which were synthesized by esterifying linoleic acid and phthalic anhydride (PA) with different monomers having different hydroxyl functionality i.e. trimethylol propane (TMP), pentaerythritol and neopentyl glycol (NPG). The oligomers were mixed with linear polyester diol in different proportions and used as polyol part in prepolymer for PUDs. Various compositional variations such as type of oligomer, content of oligomer and ionic emulsifier were studied for stability and compatibility with water. The PUDs were also examined by FTIR, AFM, GPC, particle size analyzer, viscometer, TGA, DMA and tensile tester to analyze structures and properties. Chemical, water and corrosion resistances of the dried films were also evaluated to study the effect of oligomer content in modified PUDs. These properties are found to be significantly affected by the content and type of oligomer as well as ionic content in the polymer.     

Synthesis of polypropylene oligomer—clay intercalation compounds

The synthesis of polypropylene (PP) oligomer—clay intercalation compounds was studied by using three kinds of PP oligomers and organophylic clay. PP oligomers were two types of maleic-anhydride-modified PP oligomers containing different amount of maleic anhydride groups and one type of hydroxy modified PP oligomer. Organophylic clay was sodium-ion-exchanged montmorillonite with octadecylammonium ion (C18—Mt). PP oligomer was mixed with C18—Mt at 200°C. Maleic-anhydride-modified PP oligomer, which was of high acid value type, and hydroxy-modified PP oligomer were intercalated between silicate layers of clay; and PP oligomer—clay intercalation compounds were synthesized successfully. But maleic-anhydride-modified PP oligomer, which was of low acid value type, was not intercalated. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1781–1785, 1997     

Evaluating The Extent of Bio-Polyester Polymerization in Solid Wood by Thermogravimetric Analysis

In this study, the thermogravimetric analysis (TGA) technique has been applied to determine the extent of in situ polymerization achievable in solid wood on treating with bio-polyester oligomers. Low-molecular-weight oligomers of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(butylene succinate) (PBS), and poly(butylene adipate) (PBA) were impregnated and then thermally polymerized within solid wood to enhance the physical properties of wood. TGA revealed a similar degree of oligomer polymerization was achieved either with pure oligomers or within the wood structure. The influence of relatively acidic treatments, such as low-molecular-weight PGA oligomers, was observed to lead to degradation of the hemicellulose wood component. Polymerization of PLA and PGA oligomer treatments which penetrate the wood cell wall gave relatively lower wood thermal stability. Treatment and polymerization of lumen filling PBS and PBA oligomers contributed to increased wood thermal stability.     

用液态含羧基丙烯酸酯低聚物改性环氧树脂

采用溶液聚合法合成了以丙烯酸丁酯、丙烯腈为主链结构的液态含羧基丙烯酸酯低聚物,用其对环氧树脂进行增韧改性,讨论了丙烯腈、丙烯酸以及丙烯酸酯低聚物质量分数对改性环氧树脂力学性能的影响,并研究了改性环氧树脂的微观形态和动态力学性能。结果表明,丙烯酸酯低聚物质量分数为5％时,丙烯酸丁酯／丙烯腈／丙烯酸（质量比）为75／20／5的改性环氧树脂的拉伸强度比纯环氧树脂提高4．3％;丙烯酸酯低聚物质量分数为10％时,该改性环氧树脂的冲击强度比纯环氧树脂提高近4倍,同时体系的耐热性能保持不变;环氧树脂改性体系呈两相结构,丙烯酸酯低聚物质量分数达到30％时,对环氧树脂的增韧效果变差;随着丙烯酸酯低聚物质量分数的增加,改性环氧树脂的玻璃化转变温度先升高后降低,其质量分数不超过10％时,改性环氧树脂的玻璃化转变温度高于纯环氧树脂。     

Cytotoxicity of Selected Water-Soluble Polymer–cis-Diaminedichloroplatinum(II) Conjugates Against the Human HeLa Cancer Cell Line

Several polymer-platinum conjugates comprising the square-planar cis-diaminedichloroplatinum(II) complex system of cisplatin-type anticancer drugs are screened for antiproliferative activity in cell culture tests. The water-soluble conjugates prepared in this study or taken from preceding investigations are obtained by platination of aliphatic polyamide carriers containing ethylenediamine segments as side-group or main-chain components. These segments, coordinating to the metal as cis-diamine chelating ligands, are bound to, or into, the carrier backbone through biofissionable amide links permitting drug release from the carrier. In vitro tests are performed against a HeLa human cervix carcinoma cell line. IC₅₀ data, expressed as the concentration of Pt in the conjugates (μg/ml), causing 50% inhibition of cell growth, show the highest activity, with IC₅₀=14 μg/ml, to be associated with a conjugate derived from a polyaspartamide carrier that contains the platinum complex as a side group in proximity to the main chain and, additionally, contains dimethylaminopropyl side groups as solubilizing functions. At the low end of the performance spectrum is a conjugate, with IC₅₀>120 μg/ml, possessing a similar backbone and metal-binding structure, yet comprising long poly(ethylene oxide) grafts. The latter apparently shield the complex-binding tether from enzymatic attack and thus prevent efficient intracellular release of the monomeric complex. Selected conjugates will be submitted for toxicological evaluation.     

Poly(acrylic acid)-grafted magnetic nanoparticle for conjugation with folic acid

Poly(acrylic acid) (poly(AA))-grafted magnetite nanoparticles (MNPs) prepared via surface-initiated atom transfer radical polymerization (ATRP) of t-butyl acrylate, followed by acid-catalyzed deprotection of t-butyl groups, is herein presented. In addition to serve as both steric and electrostatic stabilizers, poly(AA) grafted on MNP surface also served as a platform for conjugating folic acid, a cancer cell targeting agent. Fourier transform infrared spectroscopy (FTIR) was used to monitor the reaction progress in each step of the syntheses. The particle size was 8 nm in diameter without significant aggregation during the preparation process. Photocorrelation spectroscopy (PCS) indicated that, as increasing pH of the dispersions, their hydrodynamic diameter was decreased and negatively charge surface was obtained. According to thermogravimetric analysis (TGA), up to 14 wt% of folic acid (about 400 molecules of folic acid per particle) was bound to the surface-modified MNPs. This novel nanocomplex is hypothetically viable to efficiently graft other affinity molecules on their surfaces and thus might be suitable for use as an efficient drug delivery vehicle particularly for cancer treatment.     

Voltammetric behavior study of folic acid at phosphomolybdic-polypyrrole film modified electrode

The electrochemical behavior of folic acid at the Keggin-type phosphomolybdate (PMo₁₂) doped polypyrrole (PPy) film modified glassy carbon electrode (PMo₁₂-PPy/GCE) was studied. PMo₁₂ doped PPy modified electrodes were achieved during the electrochemical preparation of the polymer films in aqueous solution. The redox behavior of the modified electrode was described by cyclic voltammetry. The electrochemical behavior of folic acid at PMo₁₂-PPy/GCE was studied by 0.5 order differential voltammetry. Numerous factors affecting the reduction peak currents of folic acid at PMo₁₂-PPy/GCE were optimized to maximize the sensitivity. The results showed that folic acid had high inhibitory activity toward the reduction of modified electrode in 0.01 M H₂SO₄. The reduction peak currents were directly proportional to the concentration of folic acid from 1.0 × 10⁻⁸ to 1 × 10⁻⁷ M with correlation coefficient of 0.9976, a detection limit of 1.0 × 10⁻¹⁰ M of folic acid was estimated. From the inhibitory effect of folic acid on PMo₁₂-PPy/GCE, the apparent formation constant of folic acid with the modified film was estimated. This modified electrode showed excellent sensitivity and stability for the determination of folic acid. The response mechanism of folic acid at PMo₁₂-PPy/GCE was discussed in detail.     

磷钨酸铈催化合成棕榈酸和硬脂酸混合酸甲酯

采用磷钨酸铈作为催化剂,在反应温度67 ℃合成棕榈酸和硬脂酸混合酸甲酯反应,研究酸醇物质的量比、催化剂用量和反应时间对酯化反应的影响,并在最佳反应条件基础上研究催化剂的循环利用工艺。结果表明,在酸醇物质的量比1∶10、催化剂用量为棕榈酸和硬脂酸混合酸质量的8%、反应时间4 h和催化剂重结晶后循环利用10次条件下,棕榈酸和硬脂酸混合酸转化率均≥96.0%,催化剂反应前后的IR和XRD表征发现,催化剂均为Keggin型结构,未发生变化,表现出良好的催化活性。     

Allanblackia Oil: Phytochemistry and Use as a Functional Food

The consumption and commercial exploitation of Allanblackia (Clusiaceae) seed oils is of current interest. The favorable physicochemical characteristics of Allanblackia oil (solid at room temperature; high stearic acid content) lend food products that contain it (i.e., vegetable-based dairy products, ice cream, spreads) health advantages over others that contain higher levels of lauric, myristic, and/or palmitic acids, which can increase blood cholesterol levels. Such considerations are important for individuals prone to cardiovascular disease or with hypercholesterolemia. Domestication projects of several Allanblackia species in tropical Africa are underway, but wildcrafting of fruits to meet the seed demand still occurs. Proper species authentication is important, since only authenticated oil can be deemed safe for human consumption. The chemical constituency of Allanblackia seed oils, and potential roles of these phytochemicals in preventive strategies (e.g., as part of a healthy diet) and as pharmacological agents used to treat chronic disease were examined in this review. The primary and secondary metabolite constituency of the seed oils of nearly all Allanblackia species is still poorly known. The presence, identity, and quantity of potentially bioactive secondary metabolites in the seed oils, and pharmacological testing of isolated compounds were identified as important directions for future research.     

Macromolecular Conjugates of 4- and 8-Aminoquinoline Compounds

Some members of 4-aminoquinolines and 8-aminoquinolines have been found to provide adjuvant effects when used in combination with anti-cancer drugs. The clinical co-administration of active anti-cancer drugs with other drugs acting as potentiating agents has shown considerable merits when compared to a single-drug administration. Anti-cancer drugs are often toxic when delivered straight, but the bio-reversible drug conjugation of anticancer drugs to water-soluble macromolecular carriers has proved to enhance the therapeutic effectiveness of anticancer drugs. Following facilitated pharmacokinetics pathways, the conjugates, acting as pro-drugs, will release the active drug species in the transformed target cells and their designs are geared towards reducing pharmacological barriers of toxicity, drug resistance and poor bioavailability encountered with currently used anti-cancer drugs. This paper describes the synthesis of water-soluble macromolecular carriers containing 4- and 8-aminoquinolines that are bio-reversibly anchored with cytotoxic drugs. The conjugates and co-conjugates are isolated as water soluble solids and characterized by NMR-spectroscopy.     

Synthesis and characteristics of aqueous reactive urethane oligomer containing sulfoisophthalate sodium salt

This research studied urethane oligomers, which contains the sulfonic acid group and different reactive groups. First, the transesterification of dimethyl 5‐sulfoisophthalate sodium salt were performed with ethylene glycol or polyethylene glycol of different molecular weights to produce PEG soft chains possessing sulfonic acid group. Subsequently, isophorone diisocyanate used as a hard chain was connected to the two terminals of the sulfonated diols, which finally were blocked by methyl ethyl ketoxime or hydroxyethyl methacrylate or 2, 3‐Epoxy‐1‐propanol to form three kinds of aqueous reactive urethane oligomers (MSE, HSE, and OSE). The MSE oligomer had the greatest particle diameter, particle variance, and streaming current readings; the HSE oligomer, and the OSE oligomer had the second large and the smallest readings of the aforementioned measurements, respectively; whereas the contact angle and surface tension appeared with an opposite trend. Within the thermal properties of oligomer, the T_g of oligomer followed the trend: OSE < HSE < MSE; however, T_m and ΔH show an opposite tendency. With regard to the reactivity of the oligomers toward PET fabric, the add‐on for the variety of oligomers was in the quantity order of MSE > HSE > OSE series, and the washing durability was rated in the order of HSE > MSE > OSE series. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Foliate-Targeting Quantum Dots-β-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells

Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and β-cyclodextrin (β-CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with β-CD. The effect of using FA in QDs-β-CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs-β-CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs-β-CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QD_green-β-CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.     

Dietary fat and fatty acids modulate cholesterol cholelithiasis in the hamster

We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein, corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil, corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones entirely (groups 2–4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional 4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2% palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model.     

稀土复合固体酸催化合成棕榈酸生物柴油的研究

用溶胶凝胶法制备稀土复合固体酸催化剂SO₄^2-/TiO₂/Ce⁴⁺,将其用于棕榈酸与甲醇的加压酯化反应.考察了不同制备条件对催化剂性能的影响,并对其结构进行表征.结果表明,在Ce⁴⁺浓度0.05 mol/L、H₂SO₄浓度1.38 mol/L、煅烧温度450 ℃和煅烧时间3 h的制备条件下,催化剂活性最高.棕榈酸与甲醇的加压酯化反应最佳工艺条件为:醇酸物质的量之比10:1、反应温度110 ℃、反应时间30 min、催化剂用量3%,此时转化率可达到96.33%.催化剂在重复使用4次后,转化率仍在50%以上.     

Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions

γ-oryzanol (Orz), a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol metabolism, and associated chronic inflammation. Previous studies have shown the direct action of Orz when downregulating the expression of genes that encode proteins related to adiposity (CCAAT/enhancer binding proteins (C/EBPs)), inflammatory responses (nuclear factor kappa-B (NF-κB)), and metabolic syndrome (peroxisome proliferator-activated receptors (PPARs)). It is likely that this wide range of beneficial activities results from a complex network of interactions and signals triggered, and/or inhibited by its antioxidant properties. This review focuses on the significance of Orz in metabolic disorders, which feature remarkable oxidative imbalance, such as impaired glucose metabolism, obesity, and inflammation.     

Antiproliferative Activity of β-Hydroxy-β-Arylalkanoic Acids

Article describes the synthesis of fifteen β-hydroxy-β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2-bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC₅₀ values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4- biphenylyl)-butanoic acid, having the IC₅₀ value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC₅₀ > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity.     

Conjugation with Phospholipids as a Modification Increasing Anticancer Activity of Phenolic Acids in Metastatic Melanoma—In Vitro and In Silico Studies

Phenolic acids possess many beneficial biological activities, including antioxidant and anti-inflammatory properties. Unfortunately, their low bioavailability restricts their potential medical uses, as it limits the concentration of phenolic acids achievable in the organism. The conjugation with phospholipids constitutes one of the most effective strategies to enhance compounds bioavailability in biological systems. In the present study, the conjugates of anisic (ANISA) and veratric acid (VA) with phosphatidylcholine (PC) were investigated. Since both ANISA and VA are inhibitors of tyrosinase, a melanocyte enzyme, the expression of which increases during tumorigenesis, anticancer potential of the conjugates was tested in several metastatic melanoma cell lines. The conjugates proved to be antiproliferative, apoptosis-inducing and cell-cycle-affecting agents, selective for cancerous cells and not affecting normal fibroblasts. The conjugates substituted by ANISA and VA, respectively, at both the sn-1 and sn-2 positions of PC, appeared the most promising, since they were effective against the vast majority of metastatic melanoma cell lines. Additionally, the conjugation of phenolic acids to PC increased their antioxidant activity. Molecular modeling was employed for the first time to estimate the features of the investigated conjugates relevant to their anticancer properties and membrane permeation. Again, the conjugates substituted by phenolic acid at both the sn-1 and sn-2 positions of PC seemed to be presumably most bioavailable.     

Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding

Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% Oenothera biennis Linn oil (OBLO, linoleic acid +γ-linolenic acid) from a wild plant, evening primrose oil (EPO, linoleic acid +γ-linolenic acid) from a cultivated plant, bio-γ-linolenic acid oil from mold (BIO, palmitic acid+oleic acid+linoleic acid+γ-linolenic acid), safflower oil (linoleic acid), palm oil (PLO, palmitic acid+oleic acid+linoleic acid), or soybean oil (linoleic acid+α-linolenic acid) with 0.5% cholesterol for 13 wk. Though there were no significant differences in the food intake among the groups, the body weight gain of the OBLO group was significantly lower than that of other groups except for the BIO and PLO groups, and that of the EPO and SPO groups were the highest among the groups. The liver weight of the OBLO group was significantly lower than that of other groups, and that of the PLO group was the highest among the groups. The serum total cholesterol and very low density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low density lipoprotein (LDL) cholesterol concentrations of the OBLO and EPO groups were consistently lower than those in the other groups. However, those of the BIO group were higher than those in the OBLO and EPO groups. The liver cholesterol concentration of the PLO group was the highest among all groups except for the EPO group. The fecal neutral sterol and bile acid extraction of the BIO group tended to increase compared to other groups. The results of this study demonstrate that OBLO and EPO inhibit the increasing of serum total cholesterol and VLDL+IDL+LDL-cholesterol concentrations in the presence of excess cholesterol in the diet compared with the other dietary oils.     

Isolation and Structural Elucidation of Antiproliferative Compounds of Lipidic Fractions from White Shrimp Muscle (Litopenaeus vannamei)

Shrimp is one of the most popular seafood items worldwide, and has been reported as a source of chemopreventive compounds. In this study, shrimp lipids were separated by solvent partition and further fractionated by semi-preparative RP-HPLC and finally by open column chromatography in order to obtain isolated antiproliferative compounds. Antiproliferative activity was assessed by inhibition of M12.C3.F6 murine cell growth using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. The methanolic fraction showed the highest antiproliferative activity; this fraction was separated into 15 different sub-fractions (M1–M15). Fractions M8, M9, M10, M12, and M13 were antiproliferative at 100 µg/mL and they were further tested at lower concentrations. Fractions M12 and M13 exerted the highest growth inhibition with an IC₅₀ of 19.5 ± 8.6 and 34.9 ± 7.3 µg/mL, respectively. Fraction M12 was further fractionated in three sub-fractions M12a, M12b, and M12c. Fraction M12a was identified as di-ethyl-hexyl-phthalate, fraction M12b as a triglyceride substituted by at least two fatty acids (predominantly oleic acid accompanied with eicosapentaenoic acid) and fraction M12c as another triglyceride substituted with eicosapentaenoic acid and saturated fatty acids. Bioactive triglyceride contained in M12c exerted the highest antiproliferative activity with an IC₅₀ of 11.33 ± 5.6 µg/mL. Biological activity in shrimp had been previously attributed to astaxanthin; this study demonstrated that polyunsaturated fatty acids are the main compounds responsible for antiproliferative activity.