低聚水溶性壳聚糖修饰阿魏酸及细胞毒活性研究

阿魏酸（Ferulic acid,FA）,化学学名为4-羟基3-甲氧基苯丙烯酸,是当归、川芎、木贼、升麻、樟白皮等中药材水溶性提取物中主要的单体活性成份,属天然酚酸类化合物,由于其优良的抗氧化性,故对一些肿瘤表现出抑制作用,但活性不是很好。另外,由于FA的稳定性差,在人体内不参与肝肠循环等缺陷也影响其药效的发挥。     

Effect of the Folate Ligand Density on the Targeting Property of Folated‐Conjugated Polymeric Nanoparticles

Targeted drug delivery systems have attracted increasing attention due to their ability for delivering anticancer drugs selectively to tumor cells. Folic acid (FA)‐conjugated targeted block copolymers, FA‐Pluronic‐polycaprolactone (FA‐Pluronic‐PCL) are synthesized in this study. The anticancer drug paclitaxel (PTX) is loaded in FA‐Pluronic‐PCL nanoparticles by nanoprecipitation method. The in vitro release of PTX from FA‐Pluronic‐PCL nanoparticles shows slow and sustained release behaviors. The effect of FA ligand density of FA‐Pluronic‐PCL nanoparticles on their targeting properties is examined by both cytotoxicity and fluorescence methods. It is shown that FA‐Pluronic‐PCL nanoparticles indicated better targeting ability than non‐targeted PCL‐Pluronic‐PCL nanoparticles. Furthermore, FA‐F127‐PCL nanoparticle with 10% FA molar content has more effective antitumor activity and higher cellular uptake than those with 50% and 91% FA molar content. These results prove that FA‐F127‐PCL nanoparticle with 10% FA molar content can be a better candidate as the drug carrier in targeted drug delivery systems.     

Study on the condensation and crosslinking reactions of furfuryl alcohol and tris(2-hy-droxyethyl)isocyanurate by thermal methods

Condensation and crosslinking reactions of furfuryl alcohol (FA) and FA with tris (2-hydroxyethyl )isocyanurate (THEIC) are studied by means of DSC, TG, TBA, NMR and elemental analysis. Four exothermic peaks are observed on the DSC curves of thermal condensation of FA and FA with THEIC in the presence of sulfuric acid. The peaks I, II (50–80°C), III (110–130°C) and IV (150–190°C) correspond to linear polycondensation of FA through head-to-tail condensation, head-to-head etherification, crosslinking dehydration reaction between methylene group and terminal hydroxy group of FA polymeric chain and to further crosslinking reaction at higher temperature, respectively. The reactivity of FA and THEIC increases sharply at 130–150°C and THEIC is reacted completely at 150°C. Addition of THEIC raises the initial decomposition temperature of FA polymer by 60°C.     

Femtosecond transient absorption, nanosecond time-resolved resonance Raman, and density functional theory study of fenofibric acid in acetonitrile and isopropyl alcohol solvents

Hydrogen abstraction reaction of fenofibric acid (FA) in acetonitrile and isopropyl alcohol solvents was studied by femtosecond transient absorption (fs-TA) and nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy experiments. The singlet excite state ((1)FA) (nπ*) with a maximum transient absorption at 352 nm observed in the fs-TA experiments undergoes efficient intersystem crossing (ISC) to convert into a nπ* triplet state FA ((3)FA) that exhibits two transient absorption bands at 345 and 542 nm. The nπ* (3)FA species does not decay obviously within 3000 ps. In the ns-TR(3) experiments, the nπ* (3)FA is also observed and completely decays by 120 ns. Compared with the triplet states of benzophenone (BP) and ketoprofen (KP), the nπ* (3)FA species seems to have a much higher hydrogen abstraction reactivity so that (3)FA decays fast and generates a FA ketyl radical like species. In isopropyl alcohol solvent, the nπ* (3)FA exhibits similar reactivity and promptly abstracts a hydrogen from the strong hydrogen donor isopropyl alcohol solvent to generate a ketyl radical intermediate. With the decay of the FA ketyl radical, no light absorption transient (LAT) intermediate is observed in isopropyl alcohol solvent although such a LAT species was observed after similar experiments for BP and KP. Comparison of the ns-TR(3) spectra for the species of interest with results from density functional theory calculations were used to elucidate the identity, structure, properties, and major spectral features of the intermediates observed in the ns-TR(3) spectra. This comparison provides insight into the structure and hydrogen abstraction reactivity of the triplet states of BP derivatives.     

Interaction of formic acid with solid water

The interaction of formic acid (HCOOH) with solid water, deposited on tungsten at 80 K, was investigated. We have prepared and annealed formic acid (FA)/water interfaces (FA layers on thin films of solid water and H(2)O adlayers on thin FA films). Metastable impact electron spectroscopy and ultraviolet photoemission spectroscopy (He I and II) were utilized to study the electron emission from the 10a' to 6a' molecular orbitals (MOs) of FA, and the 1b(1), 3a(1), and 1b(2) MOs of H(2)O. These spectra were compared with results of density-functional theory calculations on FA-H(2)O complexes reported in Ref. 14 [A. Allouche, J. Chem. Phys. 122, 234703(2005), (preceding paper)]. Temperature programmed desorption was applied for information on the desorption kinetics. Initially, FA is adsorbed on top of the water film. The FA spectra are distorted with respect to those from FA monomers; it is concluded that a strong interaction exists between the adsorbates. Even though partial solvation of FA species takes place during annealing, FA remains in the top layer up to the desorption of the water film. When H(2)O molecules are offered to FA films at 80 K, no water network is formed during the initial stage of water exposure; H(2)O molecules interact individually via H bonds with the formic acid network. Experiment and theory agree that no water-induced deprotonation of the formic acid molecules takes place.     

Stability and Anti-Aging of Encapsulated Ferulic Acid in Phosphorylated Rice Starch

Ferulic acid (FA) provides broad biological functions that have been used in cosmetics formulation as a photoprotection, anti-aging, and brightening agent. However, its application is limited by its tendency to deteriorate by exposure to heat, humidity, and light. This study aimed to enhance the stability of FA by encapsulation in phosphorylated rice starch (PRS) and evaluate its effect on improving human skin. First, FA was encapsulated in PRS and characterized by FTIR, SEM, XRD, and DSC. Then, its stability when exposed to a temperature of 45 °C and light and its anti-aging effect on 16 volunteers were investigated. The results indicated that FA was successfully encapsulated in PRS with an encapsulation yield of 77%, EE (73%) and LE (65%). After 1 month at the high temperature/80%RH, the encapsulated FA retained its quantity (70%), whereas free FA was retained at only 50%. Under light exposure conditions, the encapsulated FA was retained at 65%, which was higher than FA (35%). Franz diffusion cell was used and demonstrated that PRS provided the controlled release of FA. Application of encapsulated FA and FA creams showed an absence of skin irritation in all volunteers. After 1 month, the encapsulated FA cream was found to be better than the FA cream on skin lightening, elasticity, smoothness, roughness, scaliness, and wrinkle. The results indicated that PRS is a potential wall material for enhancing the stability of FA, resulting in more efficacious skin lightening and anti-aging properties.     

Marine macroalgae analyzed by mass spectrometry are rich sources of polyunsaturated fatty acids

Algae from cold water (Canada) and warm water (China) were analyzed for their total lipid content, and for their fatty acid (FA) composition and content. The major findings are that FA from Canadian algae are generally richer in polyunsaturated FA (PUFA), with a higher n-3/n-6 FA ratio, and a higher degree of total unsaturation. The 18 C, 4 double bonds FA (18 : 4 stearidonic acid, morotic acid as synonym) was detected in greater amounts in cold water samples. The high levels of total PUFA, and especially of n-3 FA in Canadian algae, suggests their possible utilizations for nutritional purposes.     

Influence of human serum albumin on photodegradation of folic acid in solution

It has been proposed that photodegradation of folates may be the reason for the pigmentation of races living under high fluence rates of ultraviolet radiation. The photodegradation of folic acid (FA) induced by ultraviolet-A (UV-A) radiation, in solution and in the presence of human serum albumin (HSA), was studied with absorption and fluorescence spectroscopy. FA photodegradation, with formation of p-aminobenzoyl-l-glutamic acid, 6-formylpterin and pterin-6-carboxylic acid, was found to follow an exponential trend. A scheme of FA photodegradation, which involves photosensitization of FA degradation by its photoproducts, was proposed. The rate of FA photodegradation decreased drastically in the presence of HSA, whereas the spectral characteristics of the photoproducts remained constant. The reduction of the FA photodegradation rate by HSA was accompanied by degradation of tryptophan in HSA. Tryptophan, when added to solutions of FA, had a similar effect as HSA. In solutions of FA and HSA the FA photoproducts cause photodamage mainly to HSA rather than to FA itself. The oxygen dependence of FA photodegradation and the inhibition of this process by sodium azide indicate that singlet oxygen may participate in the photosensitizing activity of FA photoproducts.     

Anodic Oxidation Behaviors of Formaldehyde at Boron‐Doped Diamond Electrodes

The electrochemical behaviors of formaldehyde (FA) at boron‐doped diamond (BDD) electrodes are investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and linear scanning voltammetry (LSV) techniques. The CV results show that the oxidation reaction of FA is influenced by the hydroxyl concentration in the solution, and the peak current response with the FA concentration is linear at the range from 10 to 100 mM. The differential capacitance from EIS results indicate that the FA molecules adsorb at the BDD electrode surface at low potential (from 1.0 to 1.4 V). The kinetic studies have been examined with the various concentrations of FA, pH, and temperature. The activation energy of FA oxidation is also calculated. The results of kinetic study indicate that the adsorption of FA molecules at the BDD electrode is the rate‐determining step at low potential (from 1.0 to 1.40 V).     

Activity‐Based Genetically Encoded Fluorescent and Luminescent Probes for Detecting Formaldehyde in Living Cells

Formaldehyde (FA) is endogenously produced in living systems through a variety of biological processes and has been implicated in many pathological conditions. Detection tools for biological FA are therefore of great interest. Reported here are novel activity‐based genetically encoded fluorescent and luminescent probes for detecting FA in aqueous solutions and living mammalian cells. A FA‐reactive lysine analogue, PrAK, was site‐specifically incorporated into the essential lysine sites of enhanced green fluorescent protein (EGFP) and firefly luciferase (fLuc) to afford fluorescent and luminescent FA probes, respectively. FA selectively reacts with PrAK residues on EGFP and fLuc through a 2‐aza‐Cope rearrangement, resulting in fluorescence and luminescence turn‐on responses, respectively, to FA selectively over potentially interfering reactive species in aqueous buffer. Moreover, the genetically encoded probes are capable of visualizing FA at physiologically relevant levels in living mammalian cells by fluorescence and luminescence imaging, demonstrating their potential as new tools to explore FA biology.     

Activity-Based Genetically Encoded Fluorescent and Luminescent Probes for Detecting Formaldehyde in Living Cells

Formaldehyde (FA) is endogenously produced in living systems through a variety of biological processes and has been implicated in many pathological conditions. Detection tools for biological FA are therefore of great interest. Reported here are novel activity-based genetically encoded fluorescent and luminescent probes for detecting FA in aqueous solutions and living mammalian cells. A FA-reactive lysine analogue, PrAK, was site-specifically incorporated into the essential lysine sites of enhanced green fluorescent protein (EGFP) and firefly luciferase (fLuc) to afford fluorescent and luminescent FA probes, respectively. FA selectively reacts with PrAK residues on EGFP and fLuc through a 2-aza-Cope rearrangement, resulting in fluorescence and luminescence turn-on responses, respectively, to FA selectively over potentially interfering reactive species in aqueous buffer. Moreover, the genetically encoded probes are capable of visualizing FA at physiologically relevant levels in living mammalian cells by fluorescence and luminescence imaging, demonstrating their potential as new tools to explore FA biology.     

Real structure of formamide entrapped by AOT nonaqueous reverse micelles: FT-IR and 1H NMR studies

Noninvasive techniques such as FT-IR and (1)H NMR spectroscopy have been employed to investigate the solubilization of formamide, FA, and its aqueous solution, FA-water, by sodium 1,4-bis(2-ethylhexyl)sulfosuccinate, AOT, in heptane or isooctane reverse micelles, respectively. Partially deuterated FA (FADH) was used in the FT-IR experiments and nu(OD), n(ND) were analyzed. Also, the nu(C=O) band of FA was investigated. For AOT, the changes of the SO(3)(-) group's symmetric, nu(s), and asymmetric, nu(a), bands were also studied. The results are showing that FA is interacting strongly with the Na+ counterions of the surfactant through electrostatic interactions maintaining their hydrogen bond network present in the FA bulk. Accordingly, partially deuterated FA is "frozen" inside the aggregates and it is possible to detect, by FT-IR technique, the cis and trans isomers. Curve fitting of the nu(OD) (in the FA-water mixture) band requires use of two peaks because the band is asymmetric, not because the solubilizate molecules are present in layers of different structure. The chemical shifts of the (1)H bound to N and C of FA were studied by (1)H NMR. The comparison of the chemical shift of AOT in reverse micelles with FA and the FA-water mixture in the polar core of the aggregate shows that there is a strong preferential solvation of Na+ by FA (through electrostatic interaction) and the AOT's sulfonate group by water (through hydrogen bond interaction).     

Enhanced percutaneous penetration of flufenamic acid using lipid disperse systems containing glycosylceramides

The usefulness of lipid disperse systems, containing soybean phosphatidylcholine (PC) and glycosylceramide (GC) as lipid components, to enhance the percutaneous penetration of flufenamic acid (FA) through rat abdominal skin was examined by both in vitro permeation and in vivo absorption studies. The penetration of FA from a simple buffer suspension (pH 3.0) containing no lipid component was poor, but was markedly enhanced when FA was incorporated in PC-dispersions. However, this enhancing effect disappeared when the PC concentration in the preparation exceeded 40 mumol/ml. Enhanced penetration of FA from PC-dispersions could also be recognized when 30% propylene glycol or 30% glycerol was used as the dispersing medium instead of the aqueous buffer solution. Addition of GC to the PC-dispersions brought further enhancement of FA penetration through the skin. The maximal effect was observed when FA was incorporated in a 10%-GC system, and the cumulative amount of FA penetrating through the skin in 24 h from this system was approximately 6-fold larger than that from the simple buffer suspension. Enhanced absorption of FA from lipid disperse systems was also confirmed by in vivo application of these preparations.     

甲酰胺与正负离子表面活性剂有序溶液的研究

对羧酸钠与烷基三甲基溴化铵1：1混合体系的研究表明：常温下各体系在不同比例甲酰胺（FA）／水混合溶剂中，表面张力随浓度变化均有明显的转折点，显示了混合体系中胶团的存在．实验中发现随混合溶剂中FA比例增加，各体系的临界胶团浓度（cmc）增大．在较高温度下发现在甲酰胺中亦存在着因胶团形成而产生的表面张力-浓度对数（γ－logc）曲线的转折点，利用相分离模型对体系胶团热力学参数进行了计算．并探讨了FA对正负离子表面活性剂囊泡的影响．     

Release kinetics of nicotinamide from fatty acid-nicotinamide equimolar complexes. II. Activation thermodynamic quantities.

The rates of release of nicotinamide (NAA) from fatty acid (FA)-NAA complexes, FA-NAA, were determined at various temperatures, and the thermodynamic quantities for the release of NAA were estimated. The results were compared with the previous results obtained for FA-thiamine disulfide (TDS) complexes, (FA)6(TDS). The values of activation enthalpy (delta H ++) and activation entropy (delta S ++) for the release of NAA from FA-NAA were positive and negative, respectively, indicating that the release of NAA is disadvantageous from not only enthalpic but also entropic viewpoints. The plots of delta H++ against the carbon number (n) in the constituent FA showed a zig-zag line with an upward convex at an odd-numbered position and the plots of the absolute values of (-delta S++) showed a zig-zag line with a downward convex at an odd-numbered position, though the positive value of delta H++ increases and the negative value of delta S++ decreases with an increasing n for either even-numbered or odd-numbered FA. It was found that the release of NAA from FA-NAA formed with odd-numbered FA is more disadvantageous enthalpically but more advantageous entropically as compared with that from FA-NAA formed with even-numbered FA. This phenomenon was similar to that observed for (FA)6(TDS). Furthermore, it is suggested that FA-NAA is formed at least by van der Waals forces and hydrophobic interactions and that van der Waals forces are dominant for the formation of FA-NAA formed with odd-numbered FA and that hydrophobic interactions are dominant for the formation of FA-NAA formed with even-numbered FA.     

硝酸氧解法提高泥炭中黄腐酸的产率

硝酸氧解法提高泥炭中黄腐酸的产率;腐植酸;硝酸氧化降解     

MODIFICATION OF MEMBRANE COMPOSITION, EICOSANOID METABOLISM, AND IMMUNORESPONSIVENESS BY DIETARY OMEGA-3 AND OMEGA-6 FATTY ACID SOURCES, MODULATORS OF ULTRAVIOLET-CARCINOGENESIS

Dietary sources of lipids containing predominantly n-3 or n-6 fatty acids (FA) have been examined for effect upon several potential pathophysiologic parameters. Epidermal, plasma, and red blood cell (RBC) membrane FA composition exhibited marked differences between animals fed the respective dietary lipid sources. Reduced levels of 18:1, 20:3 and 20:4 occurred in the n-3 FA fed animals which exhibited significantly higher levels of 20:5 and 22:6. Approximately equal levels of 18:2 were present in animals fed either diet. Despite marked differences in RBC membrane FA composition, only marginal effect upon osmotic fragility occurred. Lower levels of 20:3 and 20:4 found in n-3 fed animals could result from a deficit of elongase and/or delta 5-desaturase activity. Whether lower 20:4 levels in n-3 fed animals could rate-limit eicosanoid metabolism is unknown, but epidermal capacity to metabolise arachidonic acid in these animals was found to be closely related to n-6 FA intake. Animals fed n-3 FA exhibited markedly lower levels of plasma PGE2, even when the diet was supplemented with n-6 FA. In addition, UV-radiated animals receiving the n-3 FA source demonstrated a reduced (approximately 30%) response to inflammatory stimulus and a greater (4.5-fold) delayed hypersensitivity (DH) to dinitrochlorobenzene than animals fed the n-6 FA source. These data demonstrate that dietary lipid strongly influences tissue FA composition, eicosanoid metabolism, and, in the case of DH, at least one type of T-cell mediated immune response in UV-irradiated animals.     

Development of a Two‐Photon Fluorescent Probe for Imaging of Endogenous Formaldehyde in Living Tissues

Investigation of the physiological and pathological functions of formaldehyde (FA) are largely restricted by a lack of useful FA imaging agents, in particular, those that allow detection of FA in the context of living tissues. Herein, we present the rational design, synthesis, and photophysical property studies of the first two‐photon fluorescent FA probe, Na‐FA . Importantly, the highly desirable attributes of the probe Na‐FA (such as a very large turn‐on signal (up to 900‐fold), a low detection limit, and a very fast onset imparted by the unique design aspects of the probe), make it possible to monitor endogenous FA in living tissues for the first time. Furthermore, sodium bisulfite was identified as a simple and convenient inhibitor of FA within biological environments.     

Effective diameters for collisions of fractal-like aggregates: recommendations for improved aerosol coagulation frequency predictions

Fractal-like aggregate (FA-) drag has been previously calculated/correlated/reported, but "mobility diameter" information is not sufficient to make rational calculations of Brownian coagulation rates (for, say, population-balance modeling). Indeed, until now, only conjectures about gyration-radius scaling behavior have been used to predict FA-FA collision cross sections! But such "scaling relations" are untrustworthy even for FA momentum-, energy-, and mass-transfer purposes, and improved FA-collision rate constants (appearing as "kernels" in the coagulation balance integro-PDE) are overdue. Our premise is that FA collision rates in the free-molecule regime can be predicted using a gas-kinetic type formulation. If (a) carrier gas mean free path and FA persistence length are much larger than any characteristic FA size, (b) FA number density is low, (c) FA velocity and position are uncorrelated, and (d) there is a "hard-sphere" interaction between primary particles of different FAs, such a theory is developed/applied here. We introduce an effective collision diameter, , depending on the geometries of the two participating FAs. Quasi-MC calculations are reported for large ensembles of pairs of FAs, each computer-generated using a tunable cluster-cluster (CC)-algorithm. Our results differ from frequently used theoretical estimates based only on FA gyration (or mobility) radii and D(f). They also confirm that, if the size disparity of the colliding FAs is large, obtained by simply assigning individual diameters to each FA are significantly overestimated. Modified collision rate expressions for FA-coagulation modeling are suggested.     

Surface modification of RGD-liposomes for selective drug delivery to monocytes/neutrophils in brain

In the present study, RGD peptide was coupled with ferulic acid (FA) liposomes for binding to monocytes and neutrophils in peripheral blood for brain targeting in response to leukocyte recruitment. Cholesterol (Ch) was esterified with succinic anhydride to introduce a carboxylic end group (Ch-COOH). Soybean phosphatidylcholine, cholesterol and Ch-COOH were in a molar ratio of 1 : 0.23 : 0.05. FA was loaded into liposomes with 80.2+/-5.2% entrapment efficiency (EE) using a calcium acetate gradient method since it was difficult to load FA by other methods. RGD peptide was a novel compound coupled with Ch-COOH via carbodiimide and N-hydroxysulfosuccinimide. The results of the in vitro flow cytometric study showed that RGD conjugation liposomes (RGD-liposomes) could bind to monocytes/neutrophils efficiently. The rats were subjected to intrastriatal microinjections of 100 microl of human recombinant IL-1beta to produce brain inflammation and subsequently sacrificed after 15, 30, 60 and 120 min of administration of three formulations (FA solution, FA liposome, RGD-coated FA liposome). The body distribution results showed that RGD-liposomes could be directed to the target site, i.e. the brain, by cell selectivity in case of an inflammatory response. For RGD coated liposomes, the concentration of FA in brain was 6-fold higher than that of FA solution and 3-fold higher than that of uncoated liposomes. MTT assay and flow cytometry were used in the pharmacodynamic studies where it was found that FA liposomes exhibited greater antioxidant activity to FA solution on U937 cell.