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Pancreatic cancer stem cells:Perspectives on potential therapeutic approaches of pancreatic ductal adenocarcinoma

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World Journal of Stem Cells 2018年第11期10卷 172-182页

作者： Claudia Di Carlo Jessica Brandi Daniela Cecconi Department of Biotechnology Proteomics and Mass Spectrometry Laboratory University of Verona

Pancreatic ductal adenocarcinoma is one of the most aggressive solid tumours of the pancreas, characterised by a fve-year survival rate less than 8%. Recent reports that pancreatic cancer stem cells （PCSCs） contribute to the tumorigenesis, progression, and chemoresistance of pancreatic cancer have prompted the investigation of new therapeutic approaches able to directly target PCSCs. In the present paper the non-cancer related drugs that have been proposed to target CSCs that could potentially combat pancreatic cancer are revi-ewed and evaluated. The role of some pathways and deregulated proteins in PCSCs as new therapeutic tar-gets are also discussed with a focus on selected speci-fic inhibitors. Finally, advances in the development of nanoparticles for targeting PCSCs and site-specifc drug delivery are highlighted, and their limitations considered.

关键词： Pancreatic cancer stem cells Pancreatic cancer Therapeutic approaches Pancreas Treatment

Screening the anti-gout traditional herbs from TCM using an in vitro method

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Chinese Chemical Letters 2016年第11期27卷 1701-1707页

作者： Wei-Jia Chen Yi Wu Xin Zhao Shu Liu Feng-Rui Song Zhong-Ying Liu Zhi-Qiang Liu School of Pharmaceutical Sciences Jilin University National Center of mass spectrometry in Changchun & Jilin Province Key laboratory of Chinese Medicine Chemistry and mass spectrometry Changchun Institute of Applied ChemistryChinese Academy of Sciences

The aim of this work was to evaluate the ability of 33 herbal extracts in inhibiting the acute inflammation and xanthine oxidase （XOD） activity. The anti-inflammation effects of the herbal extracts were detected by an in vitro cell model, which was established by stimulating human umbilical vein endothelial cells （HUVEC） using sodium urate （MSU）. In this model, the intercellular adhesion molecule-1 （ICAM-1） and interleukin-1 beta （IL-1β） were expressed, and the anti-inflammation effects of herbal extracts were evaluated by detecting the content changes of ICAM-1 and IL-1β in cell lysates and cell culture supernates using an enzyme-linked immunosorbent assay （ELISA）. Moreover, an ultrahigh performance liquid chromatography and tandem mass spectrometry （UPLC-MS/MS） method was used for the detection of XOD activity and the screening of XOD inhibitors in this research. The amount of uric acid from each analyte was directly detected using the multiple reaction monitoring mode and the uric acid level could be reduced via the addition of an inhibitor. Results indicated that Salviae Miltiorrhizae Radix et Rhizome, Rhei Radix et Rhizoma, Polygoni Cuspidati Rhizoma et Radix, Selaginellae Herba, Paeoniae Radix Rubra, especially Ginkgo Folium seemed to be more effective in anti-inflammation and inhibiting XOD activity. The anti-inflammation and enzyme inhibitory activities of the herbal extracts may be correlated with their bioactive components. And the differences between the herbal extracts were correlated with the amount of flavonoid and anthraquinone components. In our study, we have investigated the potential anti-inflammation bioactivity of 33 herbal extracts in vitro, which could provide a reference for further in vivo research in the orevention and treatment of gout.

关键词： Gout Inflammation Human umbilical vein endothelial cells Xanthine oxidase UPLC-MS/MS

Quantitative analysis of urinary endogenous markers for the treatment effect of Radix Scutellariae on type 2 diabetes rats

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Chinese Chemical Letters 2017年第6期28卷 1214-1219页

作者： Guang-Yue Hou Li-Hui Men Lu Wang Zhong Zheng Zhi-Qiang Liu Feng-Rui Song Zhong-Ying Liu National Center for mass spectrometry in Changchun & Jilin Province Key laboratory of Chinese Medicine Chemistry and mass spectrometry Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Pharmaceutical Sciences Jilin University

The effect of Radix Scutellariae treated on type 2 diabetic rats has been investigated by a liquid chromatography coupled with tandem mass spectrometry（LC-MS/MS） based urinary quantitative *** this research,multiple reactions monitoring mode of MS/MS in LC-MS/MS analysis was used to quantitatively analyze the concentrations of 7 endogenous compounds in urine of normal control group,type 2 diabetic model group and Radix Scutellariae-treated group,and multivariate statistical analysis was utilized for MS data *** above-mentioned three groups can be distinguished via pattern *** obtained results indicated that Radix Scutellariae affect the urinary metabolic profiling of type 2 diabetic rats on the polyol pathway,protein glycation reaction and amino acids metabolism *** to these results,Radix Scutellariae should have the pharmacological effect on preventing or delaying the onset and progression of diabetes and its complications.

关键词： LC-MS/MS Endogenous markers Multivariate statistical analysis Type 2 diabetic complications Radix Scutellariae

Effects of the ambient fine particulate matter(PM2.5) exposure on urinary metabolic profiles in rats using UPLC-Q-TOF-MS

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Chinese Chemical Letters 2019年第1期30卷 90-94页

作者： Lin Zhang Tengfei Xu Zifeng Pi Meizhu Zheng Fengrui Song Zhiqiang Liu Changchun Institute of Applied Chemistry Chinese Academy of Science Changchun Center of Mass Spectrometry Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry School of Pharmaceutical Sciences Jilin University The Central laboratory Changchun Normal University

In order to study the damage of ambient fine particulate matter(PM2.5) to organism in the environment,the method of urinary metabolomics was used to detect the potential endogenous metabolites and their related metabolic pathways to clarify the toxicity mechanisms. Particles of PM2.5 collected from the fibrous membrane were extracted ultrasonically and dissolved in physiological saline to prepare PM2.5 suspension. The solution of saline and fine particular matter was injected into the trachea of rats respectively. The rats were injected two times a week for four weeks. Samples of 24-h urine were collected at the 14 th day after the end of exposure, and the ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used for the metabolomics detection. Principal component analysis(PCA) was used to investigate the global metabolomic alterations and a clear separation in the scatter diagram were observed. 17 potential endogenous metablites were identified from urinary samples in rats by UPLC-Q-TOF-MS. The primary metabolism pathways involved pentose and glucuronate interconversions, starch and sucrose metabolism, tryptophan metabolism, tyrosine metabolism, phenylalanine metabolism, purine metabolism, acetaminophen metabolism pathway, retinol metabolism and valproic acid metabolism *** results are helpful to understand the toxicological mechanisms of PM2.5 and screened out potential biomarkers of rats which exposure to PM2.5.

关键词： Ambient fine particulate matter UPLC -Q-TOF-MS Metabolomics Urine

Studies of the intestinal absorption of the alkaloids in the Wu-tou decoction combined with different incompatible medicinal herbs in a Caco-2 cell culture system using UPLC-MS/MS

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Chinese Chemical Letters 2015年第5期26卷 590-594页

作者： Hong Kan Wen-Yue Jiang Ru Ding Zhong-Ying Liu Zi-Feng Pi Zhi-Qiang Liu School of Pharmacy Jilin University National Centre of mass spectrometry in Changchun & Jilin Province Key laboratory of Chinese Medicine Chemistry and mass spectrometry Changchun Institute of Applied ChemistryChinese Academy of Science

In this study, seven alkaloids were detected in Wu-tou decoction using ultra performance liquid chromatography coupled with tandem mass spectrometry （UPLC-MSn）. The aim of this study was to investigate the effect of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, Pinelliae Rhizoma in different ratios with Wu-tou decoction （2：1, 1：1, 1：2） by measuring the therapeutic effects in Wu-tou decoction of main seven alkaloids including benzoylaconitine （BA）, benzoylmesaconitine （BM）, benzoylhypaconitine （BH）, hypaconitine （HA）, fuziline （FU）, niaolin （NE） and deoxyaconitine （DA）. The permeability of aconitum alkaloids extract through a Caco-2 cell monolayer was analyzed in the absence and presence of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, and Pinelliae Rhizoma, respectively. The results showed that Pinelliae Rhizoma could reduce the absorption of the alkaloids and increase the excretion of the alkaloids, which would attenuate the therapeutic effects of Wu-tou decoction. Therefore, Pinelliae Rhizoma is an incompatible herb of Wu-tou decoction because of the inhibition of the absorption of alkaloids in the intestine. And that Fritillariae Cirrhosae Bulbus and Fritillariae rhunbergii Bulbus showed the effects to improve the permeability of the alkaloids in Wu-tou decoction. These effects of these two herbs were similar, but the former was stronger than the latter, which most likely is due to the fact that the compositions of these two traditional Chinese medicines are similar. The in vitro data suggests that the compounds such as fritillary presented in alkaloids in the formula maybe improve the therapeutic function caused by the increased bioavailability of alkaloids in intestine.

关键词： Wu-tou decoction Caco-2 cell Ultra performance liquid chromatographic coupled with tandem mass spectrometry (UPLC-MS/MS~) incompatible herbs

α-Glucosidase immobilization on functionalized Fe_3O_4 magnetic nanoparticles for screening of enzyme inhibitors

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Chinese Chemical Letters 2019年第3期30卷 656-659页

作者： Guorong Cheng Junpeng Xing Zifeng Pi Shu Liu Zhiqiang Liu Fengrui Song National Center of mass spectrometry in Changchun &Jilin Province Key laboratory of Chinese Medicine Chemistry and mass spectrometry Changchun Institute of Applied Chemistry Chinese Academy of Sciences University of Science and Technology of China

Magnetic nanoparticles(MNPs) are widely used for the immobilization of enzyme owing to the unique properties such as good biocompatibility and rapid separation. Herein, we used Fe_3O_4 magnetic nanoparticles(Fe_3O_4 MNPs) as the carrier core with(3-aminopropyl)triethoxysilane(APTES)modification by our approach, in which a-glucosidase was stereoscopically immobilized on the surface of Fe_3O_4 MNPs via covalent binding. The result of immobilization was characterized by scanning electron microscope(SEM) and fourier transform-infrared spectroscopy(FT-IR). Then we optimized some key parameters of the immobilization reaction, including the ratio of MNPs to enzyme, GA concentration,crosslinking time and immobilization time. Moreover, under the optimal conditions, pH tolerance,thermo stability and reusability of the immobilized enzyme were investigated and compared with the free one. In order to evaluate the change of the affinity of the enzyme to its specific substrate after immobilization, the Michaelis-Menten constant(K_m) was also studied. Finally, the immobilized α-glucosidase combining with high performance liquid chromatography-tandem mass spectrometry technique(HPLC-MS/MS) was applied to screen and identify eight inhibitors from Polygonum cuspidatum extract. These results indicated that the established method had the broad prospects for biotechnological applications.

关键词： Magnetic nanoparticles(MNPs) α-Glucosidase Immobilization HPLC-MS/MS Inhibitor screening Polygonum cuspidatum

Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats

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Chinese Journal of Natural Medicines 2018年第6期16卷 418-427页

作者： ZHANG Xue-Ju LIU Shu XING Jun-Peng LIU Zhi-Qiang SONG Feng-Rui National Center of mass spectrometry in Changchun Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass SpectrometryChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Chinese Academy of Sciences Beijing 100039China

Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher Cmax and AUC values(P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats(P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.

关键词： Radix Scutellaria Diabetes mellitus Flavonoid Pharmacokinetics Tissue distribution

Sequential Speciation Analysis of Heavy Metals in Drinking Water Pipe Scales by mass spectrometry

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Chemical Research in Chinese Universities 2022年第3期38卷 774-781页

作者： SONG Lili LI Hui LI Ting XU Jiaquan CHEN Huanwen Jiangxi Key laboratory for mass spectrometry and Instrumentation East China University of TechnologyNanchang330013P.R.China

An electrochemical mass spectrometry technique was developed based on a homemade analytical device for sequential analysis of the heavy metals with various speciations in the *** speciations(e.g.,water-soluble speciation,organic speciation,indissoluble speciation and elemental speciation)of heavy metals are sequentially extracted by H_(2)O,CH_(3)OH,EDTA-2Na and electrolysis for online electrospray ionization mass spectrometry(ESI-MS)*** method takes significant advantages,such as requiring no tedious offline sample pretreatment,high speed of analysis(20 min),high throughput(multi-metals),good sensitivity(0.5µg/L)and rich chemical information(four speciations).As a result,the rapid comprehensive characterization of four speciations of Pb,Ni,Cu,Zn,Fe,Ba,Mn,Cr and Ca in water pipe scales has been qualitatively *** demonstrated that the present method is a powerful tool for the effective assessment of potential hazards in drinking water,which provides a new analytical idea for evaluating water quality.

关键词： Drinking water pipe scale Heavy metal speciation analysis Electrochemical-mass spectrometry Sequential ionization

Therapeutic Effects of Selaginella tamariscina on the Model of Acute Gout with Hyperuricemia in Rats Based on Metabolomics Analysis

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Chinese Journal of Chemistry 2017年第7期35卷 1117-1124页

作者： Weijia Chen Yi Wu Rongbing Bi Shu Liu Zhongying Liu Zhiqiang Liu Fengrui song Yi Shi School of Pharmaceutical Sciences Jilin University Changchun Jilin 130021 China National Center of mass spectrometry in Changchun & Jilin Province Key laboratory of Chinese Medicine Chemistry and mass spectrometry & Chemical Biology laboratory Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China

Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina （ST） is an important traditional Chinese herbal medicine and is used for the treatment of gout and hyperuricemia. In this study, the rat model of acute gout with hyperuricemia was established by intraperitoneal injection of xanthine and oxonic acid potassium salt and articular injection monosodium urate （MSU）. The effect of ST in the treatment of gout was investigated by measuring joint swelling, the expression of IL-1 !3 in serum and histological changes of joint by haematoxylin eosin （H＆E） staining. Subsequently, urine metabolomics analysis for biomarkers discovery in acute gout with hyperuricemia rats was performed by the ultra-performance liquid chromatography-electrospray ionization quadruple time-of-flight mass spectrometry （UPLC-ESI-QTOF/MS） combined with chemometric approach. Principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to detect potential biomarkers. A total of 18 potential biomarkers were identified mainly including tryptophan metabolism; tyrosine metabolism; ly- sine methylation; pyrimidine metabolism; purine metabolism; TCA cycle and fatty acid metabolisms. This study in- dicates that ST could efficiently ameliorate the disease of acute gout with hyperuricemia in rats. The related meta- bolic biomarkers could provide useful information and the metabolic mechanism could be used for further study about the model of acute gout with hyperuricemia in rats.

关键词： Gout Selaginella tamariscina metabonomic UPLC-ESI-QTOF/MS