Studies on metabolites and metabolic pathways of bulleyaconitine A in rat liver microsomes using LC‐MSn combined with specific inhibitors

Bulleyaconitine A (BLA) from Aconitum bulleyanum plants is usually used as anti‐inflammatory drug in some Asian countries. It has a variety of bioactivities, and at the same time some toxicities. Since the bioactivities and toxicities of BLA are closely related to its metabolism, the metabolites and the metabolic pathways of BLA in rat liver microsomes were investigated by HPLC–MSⁿ. In this research, the 12 metabolites of BLA were identified according to the results of HPLC‐MSⁿ data and the relevant literature. The results showed that there are multiple metabolites of BLA in rat liver microsomes, including demethylation, deacetylation, dehydrogenation deacetylation and hydroxylation. The major metabolic pathways of BLA in rat liver microsomes were clarified by HPLC‐MS combined with specific inhibitors of CYP450 isoforms. As a result, CYP3A and 2C were found to be the principal CYP isoforms contributing to the metabolism of BLA. Moreover, CYP2D6 and 2E1 are also more important CYP isoforms for the metabolism of BLA. While CYP1A2 only affected the formation rate of M11, its effect on the metabolism of BLA is very small. Copyright © 2014 John Wiley & Sons, Ltd.     

Asymptotic Behavior of Least Energy Solutions for a Fractional Laplacian Eigenvalue Problem on ℝN

Acta Mathematica Sinica, English Series - We are interested in the existence and asymptotic behavior for the least energy solutions of the following fractional eigenvalue problem $$\left({\rm{P}}...     

蛋白质-多糖复合体系在活性物质传递中的应用

蛋白质-多糖复合体系作为生物活性物质传递系统的壁材,有着人工合成聚合物或无机物等其他材料不可比拟的多重优势。本文就蛋白质和多糖之间的连接方式及蛋白质-多糖复合体系形成传递系统的多种形式进行了综述,以及对此领域的发展趋势进行了展望。结合蛋白质和多糖的结构特点,二者之间的链接方式分为非共价结合的物理共聚,和共价结合的美拉德偶联、化学交联、酶催化交联等方式,文中分别对各种连接方式的原理和机理,以及其影响因素做了深入阐述。以蛋白质-多糖复合体系为壁材对活性物质的传递形式大体上分成乳化系统、胶束、纳米凝胶、分子复合物以及壳核结构等系统。不同的活性物质的特征和传递需求,可针对性地选择合适结构的蛋白质和多糖种类以及二者的连接方式和传递系统的形式。并且,随着研究的逐步发展和推进,此领域的发展趋势朝着智能化和靶向性的方向进行。目前活性物质的蛋白质-多糖复合体系的传递系统,还依然面临着系统设计、评价和应用等多方面的挑战,这就要求我们在更全面更深入了解认识其对活性物质影响和功效的基础上,安全合理地设计和深入细致地评价活性成分的传递系统。     

Recent advances and challenges in the recovery and purification of cellular exosomes

Exosomes are nanovesicles secreted by most cellular types that carry important biochemical compounds throughout the body with different purposes, playing a preponderant role in cellular communication. Because of their structure, physicochemical properties and stability, recent studies are focusing in their use as nanocarriers for different therapeutic compounds for the treatment of different diseases ranging from cancer to Parkinson's disease. However, current bioseparation protocols and methodologies are selected based on the final exosome application or intended use and present both advantages and disadvantages when compared among them. In this context, this review aims to present the most important technologies available for exosome isolation while discussing their advantages and disadvantages and the possibilities of being combined with other strategies. This is critical since the development of novel exosome‐based therapeutic strategies will be constrained to the effectiveness and yield of the selected downstream purification methodologies for which a thorough understanding of the available technological resources is needed.     

Separation and analysis of triazine herbcide residues by capillary electrophoresis

Triazines are widely used in agriculture around the world as selective pre‐ and post‐emergence herbicides for the control of broad leaf and grassy weeds. With high toxicity and persistence, triazines can contaminate the environment and crops, so the development of rapid and sensitive methods for the determination of different triazines is necessary. Capillary electrophoresis comprises a group of techniques used to separate chemical mixtures. Analytical separation is based on different electrophoretic mobilities. This review focuses on the analysis of triazine herbicides with different modes of capillary electrophoresis, including capillary zone electrophoresis, micellar electrokinetic capillary electrophoresis, capillary electrochromatography and nonaqueous capillary electrophoresis. Determinations of triazines in various matrices such as surface water, groundwater, vegetables, soil and grains are emphasized. Copyright © 2014 John Wiley & Sons, Ltd.     

An improved LC–MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients

Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC–MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid-phase extraction-protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C₁₈ column using water containing 0.05% acetic acid along with 20 μM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m/z 830.3 → 548.8 and m/z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1–500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from −4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.     

Lipase‐Supported Metal–Organic Framework Bioreactor Catalyzes Warfarin Synthesis

A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase‐supported metal–organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors.     

Polymer nanoparticles with a sensitive CO2‐responsive hydrophilic/hydrophobic surface

Poly(methyl methacrylate) (PMMA) nanoparticles with a sensitive CO₂‐responsive hydrophilic/hydrophobic surface that confers controlled dispersion and aggregation in water were prepared by emulsion polymerization at 50 °C under CO₂ bubbling using amphiphilic diblock copolymers of 2‐dimethylaminoethyl methacrylate (DMAEMA) and N‐isopropyl acrylamide (NIPAAm) as an emulsifier. The amphiphilicity of the hydrophobic–hydrophilic diblock copolymer at 50 °C was triggered by CO₂ bubbling in water and enabled the copolymer to serve as an emulsifier. The resulting PMMA nanoparticles were spherical, approximately 100 nm in diameter and exhibited sensitive CO₂/N₂‐responsive dispersion/aggregation in water. Using copolymers with a longer PNIPAAm block length as an emulsifier resulted in smaller particles. A higher concentration of copolymer emulsifier led to particles with a stickier surface. Given its simple preparation and reversible CO₂‐triggered amphiphilic behavior, this newly developed block copolymer emulsifier offers a highly efficient route toward the fabrication of sensitive CO₂‐stimuli responsive polymeric nanoparticle dispersions. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2149–2156     

Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites

Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing [U-¹³C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.