Zeper Abliz

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (90)292.13 Total impact

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    ABSTRACT: Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides, and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.
    Preview · Article · Sep 2015 · Scientific Reports
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    ABSTRACT: Detection and identification of unknown or low-level drug-related metabolites in complex biological materials is an ongoing challenge. A highly selective and sensitive method could be a possible solution. Here, we proposed a targeted data-independent acquisition and mining (TDIAM) strategy for the rapid identification of trace drug metabolites using ultra high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). In this strategy, raw data is acquired by a novel tm-MS scan, which contains an interleaved full MS scan with a targeted mass range and product ion scan by selecting all ions in the targeted mass range as precursor ions. For efficient discovery of me-tabolites, raw data are analyzed by a new post-acquisition processing method, Molecule- and Fragmentation-driven Mass Defect Filters (MF-MDFs), which was developed based on the fragmentation of parent drug to pick out molecular ions and fragment ions of potential metabolites from the complex matrix. When applying the proposed strategy to paclitaxel metab-olism research, we successfully identified 10 metabolites, among which six were not previously reported. The results demon-strated that TDIAM greatly improved throughput, detective sensitivity and selectivity, and more importantly, yielded almost the same spectrum as traditional HRMS/MS. Therefore, TDIAM provides structure-enriched evidence to confirm the exist-ence and elucidate the structures of metabolites. This strategy is suitable for identification of metabolites present at low con-centrations in a complex matrix, and has the potential to provide an efficient, sensitive, and labor-saving solution for drug metabolite research.
    Full-text · Article · Jul 2015 · Analytical Chemistry
  • Fei Tang · Ying Bi · Jiuming He · Tiegang Li · Zeper Abliz · Xiaohao Wang
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    ABSTRACT: RationaleMass Spectrometry Imaging (MSI) is useful for analyzing biological samples directly, as a spatially resolved, label-free technique. Here we present a method for super-resolution reconstruction of sparse representation to improve resolution of MSI data.Methods Air Flow-Assisted Ionization Mass Spectrometry Imaging (AFAI-MSI) was used to acquire MSI data from ink samples, thyroid tumour samples, rat renal biopsies, and rat brain biopsy samples. Super-resolution reconstruction of sparse representation was adopted for the collected MSI data.ResultsAfter comparison of the reconstructed high-resolution image and the original high-resolution image, it is found that super-resolution reconstruction image is closer to the original high-resolution image than the image obtained with the interpolation method, and the highest Peak Signal-to-Noise Ratio (PSNR) difference value is over 1.4dB. Therefore, the application of the super-resolution reconstruction technique, based on sparse representation MSI, is feasible and effective.Conclusions The method proposed here not only improves the resolution of MSI in post-data processing, but also acquires fewer sampling points at the same resolution, thereby greatly reducing the sampling time, with great application value for large-volume sample MSI, high-resolution MSI, etc. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Jun 2015 · Rapid Communications in Mass Spectrometry
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    ABSTRACT: The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively explored due to their carcinogenic and mutagenic potency; however, little is known about the metabolic responses to chronic environmental PAH exposure among the general population. In the present study, 566 healthy volunteers were dichotomized into exposed and control groups to investigate PAH-induced perturbations in the metabolic profiles. Nine urine PAH metabolites were measured by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level of each individual, and the metabolic profiles were characterized via a LC-MS-based metabolomic approach. PAH exposure was correlated to its metabolic outcomes by linear and logistic regression analysis. Metabolites related to amino acid, purine, lipid, and glucuronic acid metabolism were significantly changed in the exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes, respectively, in general population. These findings generally support the hypothesis that environmental PAH exposure causes oxidative stress related effects in humans. The current study provides new insight into the early molecular events induced by PAH exposure in the actual environment.
    Full-text · Article · May 2015 · Journal of Proteome Research
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    ABSTRACT: Conjugation of a cholesterol moiety to active compounds for cancer treatment or diagnosis is an attractive approach for increasing lipophilicity and improving loading into lipid carriers. We developed a highly sensitive and specific liquid chromatography atmospheric-pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) analytical method to investigate the in vivo plasma and tumor distribution characteristic of a cholesterol-paclitaxel conjugate (CHO-PTX) in nude mice with MDA-MB-231 human breast cancer xenografts. The samples were analyzed in positive ion, multiple reaction monitoring mode. The plasma and tumor tissue samples were processed by liquid-liquid extraction with methyl tert-butyl ether (MTBE). Docetaxel was used as the internal standard (IS) for sample processing and analysis. MS/MS detection was carried out by monitoring the transitions of m/z 1266.7→369.4 and 330.3 for CHO-PTX, and m/z 808.7→226.4 and 509.1 for IS. The calibration curves were linear over 100-25,000 ng/mL in mouse plasma and tumor homogenate samples. The limit of quantitation of CHO-PTX was 100 ng/mL in both matrices. The intra-day and inter-day precisions were less than 15%, and the accuracy was between -8.0% and 8.6% for both matrices. The developed method was successfully applied to measure CHO-PTX levels in plasma and tumor tissues in nude mice. The mean tumor concentrations in mice tumor tissues after intravenous administration of CHO-PTX emulsion at a dose equivalent to 20 mg/kg paclitaxel were 2022 ± 630 ng/mL ng/mL, 2516 ± 982 ng/mL, 3056 ± 1438 ng/mL, and 2367 ± 1029 ng/mL at 0.25, 3, 24, and 120 h, respectively. The accumulation of CHO-PTX in the tumor suggests that cholesteryl drug conjugates are a promising approach for medical treatment of various human cancers.
    No preview · Article · May 2015 · Journal of Pharmaceutical and Biomedical Analysis
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    ABSTRACT: Elucidation of mechanism of action for drug candidates is fundamental to drug development, and is strongly facilitated by metabolomics. Herein, we developed an imaging metabolomics method based on air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) under ambient condition. This method was sub-sequently applied to simultaneously profile a novel anti-insomnia drug candidate, N6-(4-hydroxybenzyl)-adenosine (NHBA), and various endogenous metabolites in rat whole-body tissue sections after administration of NHBA. The principle component analysis (PCA) represented by an intuitive color-coding scheme based on hyperspectral imaging revealed in situ molecular profiling alterations in response to stimulation of NHBA, which are in a very low intensity and hidden in massive interferential peaks. We found that the abundance of six endogenous metabolites changed after drug administration. The spatiotemporal distribution indicated that five altered molecules, including neurotransmitter gamma-aminobutyric acid, neurotransmitter precursors choline and glycerophosphocholine, energy metabolism-related molecules adenosine (an endogenous sleep factor) and creatine, are closely associated with insomnia or other neurological disorders. These findings not only provide insights into deeply understanding on the mechanism of action of NHBA, but also demonstrate that the AFADESI-MSI-based imaging metabolomics is a powerful technique to investigate the molecular mechanism of drug action, especially for drug candidates with multi-target or undefined target in the preclinical study stage.
    Preview · Article · Apr 2015 · Analytical Chemistry
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    ABSTRACT: This paper described the development of a collision energy correlated mass spectrometric (MSE) method combined with data mining tools for the analysis of degradation products from drugs using rapid resolution liquid chromatography. tandem mass spectrometry (RRLC-MS/MS). Based on the high separation ability of RRLC and full scan of MS analysis, MSE was developed to generate product ion spectrum without precursor ion selecting. Mixture of drug degradation products was separated by RRLC, and then the eluate was analyzed by MS with collision energy switching to acquire both of molecule ions and product ions. Mass defect filter (MDF) was used to discover drug degradation products from raw data. Therefore, the relative quantity and structure information of drug degradation products were obtained. The proposed method has been demonstrated as an effective tool for the impurity profiling and drug quality control.
    No preview · Article · Apr 2015 · CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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    ABSTRACT: Usually, insufficient intratumoral concentration of therapeutic drugs is one of the reasons for tumor treatment failure. However, little is known about intratumoral distribution of bromocriptine in non-responding prolactinomas because of extremely low drug concentration and small prolactinoma tissue samples. In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of bromocriptine at trace level in human prolactinoma tissue. As little as 20mg (wet weight) tissue sample was required and total analysis time was 6min in this method. The assay quantifies over a linear range of 50fg/mg to 5pg/mg, and has a 25fg/mg limit of detection at a signal/noise ratio of 3. This validated method was successfully used to quantitatively determine bromocriptine in clinical post-operative bromocriptine-sensitive and -resistant prolactinomas. The results revealed bromocriptine concentration in resistant prolactinomas (0.49-1.25pg/mg) was significantly higher than that in sensitive prolactinomas (0.057-0.47pg/mg). These results provided direct evidence to demonstrate the reseaon for failure of bromocriptine treatment in some patients with prolactinoma was "intrinsic" tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue. Additionaly, this HPLC-MS/MS method has been shown to be suitable for bromocriptine analysis in small amount tissue sample and could be adapted for therapeutic drug monitoring of other clinical medicine. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Mar 2015 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
  • Yang Fen · He Jiu-Ming · Zhang Rui-Ping · Zeper Abliz
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    ABSTRACT: A fast atom bombardment mass spectrometric method to predict and detect the antioxidant ability of phenolic compounds was developed to accelerate the pace of finding the antioxidant with higher effect and low toxicity. The effect of experimental conditions on the relative peak intensity ratio of M+center dot ion to [M+H](+) ion in the FAB mass spectra of the compound was investigated, including matrix, scan time and concentration. The correlation of antioxidant activity with the I(M+center dot)/I([M+H](+)) value of flavonoids obtained in FAB mass spectra was studied. Then the antioxidant activity of 12 phenolic compounds was predicted using the above method and the results were compared with those obtained from thiobarbituric acid (TBA) method. The results show that the I(M+center dot)/I([M+H](+)) value of the phenolic compound obtained from FAB mass spectra could reflect their antioxidant activity, which could help to accelerate the development of the antioxidant drug.
    No preview · Article · Feb 2015 · CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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    ABSTRACT: A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry (IMS) techniques is reported. The strategy divides the whole datacube of the sample into several subsets and analyses them one by one to obtain the results. Instead of analyzing the whole datacube at one time, the strategy makes the analysis easier and decreases the computation time greatly. In this report, the IMS data are produced by the air flow-assisted ionization IMS (AFAI-IMS). The strategy can be used in combination with most multivariate statistical analysis methods. In this paper, the strategy was combined with the principal component analysis (PCA) and partial least square analysis (PLS). It was proven to be effective by analyzing the handwriting sample. By using the strategy, the m/z corresponding to the specific lipids in rat brain tissue were distinguished successfully. Moreover the analysis time grew linearly instead of exponentially as the size of sample increased. The strategy developed in this study has enormous potential for searching for the m/z of potential biomarkers quickly and effectively.
    No preview · Article · Oct 2014 · Chinese Chemical Letters
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    ABSTRACT: The factor analysis method was applied in analysis of IMS data on the basis of air flow-assisted ionization imaging mass spectrometry. In the experiment, the optical image of sample, IMS images of special m/z and score images of different factors were investigated for the factor analysis. Meanwhile, the ion intensity strengths of certain m/z was used as the color values for IMS images and the scores of certain factor were used as the color values to complete the score images of different factors on different sample points.
    Full-text · Article · Aug 2014 · Chinese Journal of Analytical Chemistry
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    ABSTRACT: A water-soluble pillar[10]arene was prepared. Its pH-responsive host–guest complexation with paraquat and application in constructing a supra-amphiphile were investigated.
    No preview · Article · Jul 2014
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    ABSTRACT: RATIONALEImpurity analysis plays an important role to guarantee the quality and safety of pharmaceuticals. However, identification of impurities remains challenging, especially for those unknown or at trace levels. We present an integrated approach to detect and characterize the trace impurities in drugs.METHODS Based on liquid chromatography–tandem mass spectrometry (LC–MS/MS), an approach integrating automatic impurity screening method using multiple mass defect filters (MMDFs) and background subtraction (BS) was developed. This approach was used to acquire the structural and semi-quantitative information in a single sample run, and even to discover the impurity signals submerged by background and drug ions. This approach was illustrated by the comprehensive impurity analysis of levofloxacin.RESULTSThis approach was sensitive to detect impurities at the level of 0.02% with respect to levofloxacin concentration. Nineteen impurities were detected, fourteen of which were structurally characterized and eight impurities were reported for the first time. Impurity profiles of levofloxacin drug substances and degradation samples were obtained reliably. A plausible degradation pathway of levofloxacin was proposed including descarboxyl reaction under acid, piperazinyl ring cleavage degradation under light, and N-oxidation under oxidative condition.CONCLUSIONS The generic approach integrating LC–MS/MS and an automatic impurity screening method was developed for the detection, characterization and monitoring of impurities, especially those unknown or at trace levels. This approach was demonstrated to be rapid, sensitive and automatic for impurity profiling of drugs. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · May 2014 · Rapid Communications in Mass Spectrometry
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    ABSTRACT: The imaging mass spectrometry (IMS) technology has experienced a rapid development in recent years. A new IMS technology which is based on air flow assisted ionization (AFAI) was reported. It allows for the convenient pretreatment of the samples and can image a large area of sample in a single measurement with high sensitivity. The AFAI in DESI mode was used as the ion source in this paper. The new IMS method is named AFADESI-IMS. The adoption of assisted air flow makes the sample pretreatment easy and convenient. An optimization of the distance between the ion transport tube and MS orifice increases the sensitivity of the system. For data processing, a program based on MATLAB with the function of numerical analysis was developed. A theoretical imaging resolution of a few hundred microns can be achieved. The composite AFAI-IMS images of different target analytes were imaged with high sensitivity. A typical AFAI-IMS image of the whole-body section of a rat was obtained in a single analytical measurement. The ability to image a large area for relavent samples in a single measurement with high sensitivity and repeatability is a significant advantage. The method has enormous potentials in the MS imaging of large and complicated samples.
    No preview · Article · May 2014 · Chinese Chemical Letters
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    ABSTRACT: In this article, we present the design and construction of a series of supramolecular poly(benzyl ether) metallodendrimers featuring a well-defined hexagonal metallacycle at their cores via coordination-driven self-assembly. It was found that the second generation metallodendrimer 3c was able to hierarchically self-assemble into the regular vesicle-like structures. These nano-scale vesicles were monodisperse in shape and relatively monodisperse in size as detected in SEM, TEM, AFM, and DLS experiments. Notably, this kind of hierarchically formed vesicle-like nano-structures adopted a discrete metallacycle as the main skeleton, which is obviously different from many previous reports of nano-scale spherical architectures. Moreover, such supramolecular vesicle-like structures could encapsulate some fluorescent molecules like BODIPY and SRB, etc. By taking advantage of the dynamic nature of metal-ligand bonds, the disassembly and reassembly of the hexagonal cavity core could be reversibly controlled by the addition and removal of bromide ions, resulting in the transition from the vesicles to micelles. Thus, the controlled release of fluorescence dye was successfully realized by the halide-induced vesicles-micelles transition. These findings not only enrich the library of supramolecular metallodenrimers but also provide a new avenue to the construction of novel "smart" nano-materials, which have potential application in functional molecules delivery and release.
    No preview · Article · Mar 2014 · Journal of the American Chemical Society
  • Zhengtao Li · Jie Yang · Guocan Yu · Jiuming He · Zeper Abliz · Feihe Huang
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    ABSTRACT: By the introduction of 14 anionic carboxylate groups at its two rims, a water-soluble pillar[7]arene (WP7) was synthesized. Its pH-controlled complexation with paraquat G1 in water was investigated. Host WP7 and guest G1 formed a 1:1 [2]pseudorotaxane with a high association constant of (2.96 ± 0.31) × 10(9) M(-1) in water. Furthermore, we took advantage of this novel molecular recognition motif to fabricate a supra-amphiphile based on WP7 and an amphiphilic paraquat derivative G2. The morphologies and sizes of self-assemblies of G2 and WP7⊃G2 were identified by transmission electron microscopy and dynamic light scattering.
    No preview · Article · Mar 2014 · Organic Letters
  • Zhengtao Li · Jie Yang · Guocan Yu · Jiuming He · Zeper Abliz · Feihe Huang
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    ABSTRACT: A water-soluble pillar[9]arene was synthesized. Its pH-responsive host-guest binding to paraquat in water was studied.
    No preview · Article · Feb 2014 · Chemical Communications
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    Meng-Lan He · Shuai Wu · Jiuming He · Zeper Abliz · Lin Xu
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    ABSTRACT: Through coordination-driven self-assembly, a novel naphthalimide-containing hexagonal metallocycle with well-defined shape and size has been successfully constructed, which was found to maintain the good performance on fluorescence detection of protons.
    Preview · Article · Jan 2014 · RSC Advances

  • No preview · Article · Jan 2014
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    ABSTRACT: A rapid, sensitive and robust method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantitation of S-phenylmercapturic acid (S-PMA), a metabolite of benzene, in human urine. Urine samples to which S-phenylmercapturic acid-d2 (S-PMA-d2) had been added as an internal standard (I.S.) were subjected to liquid-liquid extraction (LLE) with ethyl acetate in an acidic environment. S-PMA and the I.S. were separated on a C18 column and detected in negative ion and multiple reaction monitoring mode within 1.8 min. The assay was fully validated and exhibited good linearity in the concentration range of 0.2-200 ng mL−1, with a lower limit of quantitation of 0.2 ng mL−1. The intra- and inter-day precisions were <8.1%, with a relative error <6.9%. The short run time coupled with the efficient one-step LLE sample preparation procedure makes the proposed method a promising strategy for the high-throughput and cost-effective analysis of urinary S-PMA levels, which is required to evaluate the health risk of exposure to benzene or cigarette smoking.
    Full-text · Article · Nov 2013 · Analytical methods