Metabolomic-based investigation of Yinlan alleviating hyperlipidemia by inhibiting blood stasis and phlegm turbidity through the PXR-CYP3A4-ABCB1-FXR pathway

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.     

Controlled phase separations in solutions of soluble polyelectrolyte complex of DIVEMA (copolymer of divinyl ether and maleic anhydride)

Copolymer of divinyl ether and maleic anhydride (DIVEMA) is known to possess some anti-tumor and immune-stimulating activity and use as a drug carrier in anti-tumor drug delivery systems. Samples of DIVEMA of different degrees of polymerization were synthesized and characterized. Interaction of the hydrolyzed water-soluble DIVEMA polyanions with poly(N-ethyl-4-vinylpyridinium) cations (PEVP) has been studied. According to the potentiometry data, almost all carboxylic groups of the polyanions were able to form ion pairs with PEVP. In aqueous and water-salt solutions, formation of either soluble or insoluble polyelectrolyte complexes occurred depending on pH, ratio of the oppositely charged groups, and degree of polymerization of PEVP and/or DIVEMA. The phase separations followed general rules revealed by studying mixtures of PEVP and polycarboxylic acids. However in the case of DIVEMA, a significant broadening of the region for insoluble complexes at the expense of the region of soluble complexes was established. The data obtained demonstrate plausible advantages of the complex formation as the non-covalent modification of the polymeric carrier that endow DIVEMA with the ability for reversible soluble-insoluble transformation, in particular at physiological pH and ionic strength.     

Electrophoretic mobility of the polymer-like micelles of tetradecyldimethylamine oxide hemihydrochloride

Effects of the surfactant concentration C_d and the NaCl concentration C_s on the electrophoretic mobilities U of the well-characterized polymer-like micelles have been investigated by the electrophoretic light scattering, using tetradecyldimethylamine oxide hemihydrochloride (C14DMAO·1/2HCl). At the high ionic strength of 0.1 mol kg⁻¹ NaCl, the electrophoretic mobilities were independent of C_d (5 mM < C_d < 100 mM), despite the concentration-dependent micelle growth of the polymer-like micelles. This suggests that the electrophoretic mobility of the polymer-like micelle at high ionic strengths is independent of the contour length (i.e., the molecular weight), as found on linear polyelectrolytes. Somewhat surprisingly, the entanglements of the polymer-like micelles gave small effect on the electrophoretic mobilities in the examined range of the surfactant concentration above an overlap concentration. The mobilities of the polymer-like micelle decreased with √C_s in a single exponential manner in the range of C_s from 0.02 to 0.3 mol kg⁻¹. It is suggested that the cylinder model can be applied to the electrophoretic mobilities of the polymer-like micelles at high ionic strengths (i.e. a free-draining behavior), since the persistence length of the polymer-like micelle (20 nm) is much larger than the Debye length at high ionic strength.     

Fractal metal nanoparticle aggregates morphology formation mediated by polyelectrolyte/surfactant complex films at interfaces

In this work, the gold nanoparticle self-assembly behavior of mica-surface-confined polyelectrolyte/surfactant complex films was investigated. First, modified partially hydrated polyacrylamide (MHPAM)/hexadecyltrimethylammonium bromide (CTAB) complex films were deposited on the mica surface using Langmuir–Blodgett technique. Then, the preadsorbed MHPAM/CTAB complex film mica plate was dipped into the gold aqueous solution and the interesting fractal nanostructured gold network was formed. In addition, the effect of dipping time on gold nanoparticle self-assembly morphology was studied. The mechanism of formation process is briefly proposed.     

有机分子与聚电解质静电吸附成膜特性研究

选取多种有机分子及聚电解质，采用静电吸附自组装法制备了聚电解质，聚电解质、聚电解质，有机分子、有机分子，有机分子的复合薄膜，讨论了这些体系的静电吸附成膜特性及其成膜机理．     

聚电解质-磺化聚砜溶液的光散射

本文采用激光小角光散射法,测定了聚电解质-磺化聚砜(钠盐),在分别舍有NaNO_3、LiNO_3、LiCl、NaBr和NaI的DMF中各试样的表现分子量。结果表明,在含有0.07N NaNO_3的DMF中,磺化聚砜的表观分子量接近于试样的真实分子量。     

聚电解质──壳聚糖浓溶液流变学性质研究：浓度、温度、溶剂pH值和外加盐对粘度及流动性的影响

本工作用日本岩本ＲＰＸ－７０５多功能流变仪测定了在不同浓度、温度、溶剂ｐＨ值和外加盐浓度对壳聚糖在甲酸水溶液中其浓溶液粘度η随剪切速率γ的变化关系．讨论了浓度、温度等对溶液粘度、流动活化能Ｅ_γ和流动指数ｎ的影响．发现溶剂ｐＨ值减小或溶液中外加盐浓度增加，溶液粘度变小，ｎ增大，表明非牛顿流动性减弱，并且进一步讨论了零剪切粘度η_０和外加盐浓度Ｃ_ｓ的依赖关系．     

Fluorescence decay and quenching of pyrene labeled on sulfonate polyelectrolytes in salt-free aqueous solutions

Fluorescence decay and quenching of pyrene labels on copolymers of 2-acrylamido-2-methylpropanesulphonic acid (AMPS) and N,N-dimethylacrylamide were observed in dilute salt-free aqueous solutions as a function of the mole fraction F_AMPS of AMPS from 0 to 0.896. Monoexponential decay was found for the samples of F_AMPS<0.35 and biexponential decay for the samples of F_AMPS>0.35. The fast decay component is 80%, and the averaged lifetime 〈τ〉 and lifetime τ₁ of the fast decay is decreased with increasing F_AMPS. Quenching efficiency of Cu²⁺, I⁻, CH₃NO₂, and dinitrobenzene to the pyrene label was investigated in the framework of Stern-Volmer plot. With increasing F_AMPS the quenching efficiency of Cu²⁺ is increased while that of I⁻ decreased. For the neutral quenchers, the quenching rate constant k_q increases when F_AMPS<0.449 then decreases, showing a decline of accessibility to the pyrene label. These results were interpreted consistently with the counterion condensation concept, where condensed counterions caused the polyelectrolyte chains to aggregate. The existence of less-polar “temporal aggregated domain” in highly charged polyelectrolytes appears to lead to the slower decay and lower accessibility of the pyrene labels.     

A method to construct polyelectrolyte multilayers film containing gold nanoparticles

Gold nanoparticles in polyelectrolyte multilayers film can be easily prepared by repeating immersion of a substrate in poly(diallyl dimethylammonium) chloride (PDDA)-AuCl₄⁻ complexes solution followed by reduction Au³⁺ through heating. UV-vis spectroscopy, cyclic voltammetry (CV) and tapping-mode atomic force microscopy (AFM) are used to confirm the successful construction of the polyelectrolyte multilayers film and the formation of gold nanoparticles. The multilayers film shows electrocatalytic activity to dioxygen reduction.     

Stable Hydrogen-Bonded Spherical Capsules Formed from Self-Assembly of Pyrogallol[4]arenes

The self-assemblies of two pyrogallol[4]arenes held together by 48 intermolecular hydrogen bonds stably associate in the form of spherical hexameric capsules. The molecular structures of two hexameric capsules with large interior space were analyzed by single crystal X-ray crystallography.