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Biomedical subjects

Zhen Liu

Publications and source records attributed to Zhen Liu.

At least 37 records · Page 2Linked to original sources

Online coupling of solid-phase microextraction and capillary electrophoresis.

Solid-phase microextraction (SPME) and capillary electrophoresis (CE) are two of the main inventions that shaped 20th Century analytical chemistry. SPME is an effective microscale sampling and sample preparation technique, and CE is a high-efficiency microanalytical method. Online coupling of SPME with CE can be a powerful combination because of the significant advantages of the two techniques. The progress in the development of online SPME-CE coupling is surveyed in this review. Problems encountered and solutions reported are highlighted.

Journal Article↗

Sesamin is one of the major precursors of mammalian lignans in sesame seed (Sesamum indicum) as observed in vitro and in rats.

Plant lignans occur in many foods, with flaxseed presently recognized as the richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesamin, could be metabolized to the mammalian lignans. The total plant lignan concentration in sesame seed (2180 micromol/100 g) was higher than that in flaxseed (820 micromol/100 g). In vitro fermentation with human fecal inoculum showed conversion of sesamin to the mammalian lignans, although at a lower rate (1.1%) compared with that of secoisolariciresinol diglucoside (57.2%). However, when fed to female Sprague-Dawley rats for 10 d, sesamin (15 mg/kg body weight) and a 10% sesame seed diet resulted in greater (P < 0.05) urinary mammalian lignan excretion (3.2 and 11.2 micromol/d, respectively), than the control (< 0.05 micromol/d). We conclude that sesame seed is a rich source of mammalian lignan precursors and sesamin is one of them. From intermediate metabolites of sesamin identified in rat urine by GC-MS, a tentative metabolic pathway of sesamin to mammalian lignans is suggested.

Animals↗

JPEG2000 encoding with perceptual distortion control.

In this paper, a new encoding approach is proposed to control the JPEG2000 encoding in order to reach a desired perceptual quality. The new method is based on a vision model that incorporates various masking effects of human visual perception and a perceptual distortion metric that takes spatial and spectral summation of individual quantization errors into account. Compared with the conventional rate-based distortion minimization JPEG2000 encoding, the new method provides a way to generate consistent quality images at a lower bit rate.

Algorithms↗

Proteomic analysis of rat hippocampal plasma membrane: characterization of potential neuronal-specific plasma membrane proteins.

The hippocampus is a distinct brain structure that is crucial in memory storage and retrieval. To identify comprehensively proteins of hippocampal plasma membrane (PM) and detect the neuronal-specific PM proteins, we performed a proteomic analysis of rat hippocampus PM using the following three technical strategies. First, proteins of the PM were purified by differential and density-gradient centrifugation from hippocampal tissue and separated by one-dimensional electophoresis, digested with trypsin and analyzed by electrospray ionization (ESI) quadrupole time-of-flight (Q-TOF) tandem mass spectrometry (MS/MS). Second, the tryptic peptide mixture from PMs purified from hippocampal tissue using the centrifugation method was analyzed by liquid chromatography ion-trap ESI-MS/MS. Finally, the PM proteins from primary hippocampal neurons purified by a biotin-directed affinity technique were separated by one-dimensional electrophoresis, digested with trypsin and analyzed by ESI-Q-TOF-MS/MS. A total of 345, 452 and 336 non-redundant proteins were identified by each technical procedure respectively. There was a total of 867 non-redundant protein entries, of which 64.9% are integral membrane or membrane-associated proteins. One hundred and eighty-one proteins were detected only in the primary neurons and could be regarded as neuronal PM marker candidates. We also found some hypothetical proteins with no functional annotations that were first found in the hippocampal PM. This work will pave the way for further elucidation of the mechanisms of hippocampal function.

Animals↗

Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan.

Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.

Coumarins↗

Nucleic-acid-based antiviral agents against positive single-stranded RNA viruses.

Positive single-stranded RNA viruses constitute a broad and prevalent group of pathogens that threaten human health and life worldwide. While effective vaccines have been developed for some, such as poliovirus and hepatitis A, others such as coxsackievirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and West Nile virus have no accredited drug treatments. Antisense technologies, which encompass small interfering RNA, antisense oligonucleotides, ribozymes and their chemically modified analogs, involve small sequence-specific nucleic-acid-based molecules that inhibit viral replication at the level of translation. Many antisense oligomers are proven antiviral agents in vitro. In this review, iwe provide an overview of the antiviral antisense field, highlighting specific studies of interest over the past several years, using our experience with coxsackievirus B3 as a reference point. Overall, both the challenges and successes of existing antisense therapies for positive single-stranded RNA viruses can be paralleled to those for other virus groups, and vice versa.

Animals↗

Butyrate sensitizes the release of substance P and calcitonin gene-related peptide evoked by capsaicin from primary cultured rat dorsal root ganglion neurons.

OBJECTIVES: To investigate whether butyrate increases substance P (SP) and calcitonin gene-related peptide (CGRP) release evoked by capsaicin from primary cultured dorsal root ganglion (DRG) neurons. METHODS: DRG was dissected out from embryonic 15-day-old Wistar rat and cultured as dissociate cells for 24 h then exposed to butyrate (0.01 mmol/L, 0.1 mmol/L, 1 mmol/L, 10 mmol/L, respectively) for another 48 h. The neurons cultured continuously in media served as normal control. All above cultured samples were processed for detecting expression of mRNA for SP, CGRP and vanilloid receptor 1 (VR1) of DRG neurons by RT-PCR, and VR1 protein expression by Western blot. SP and CGRP basal release levels were measured by radioimmunoassay (RIA). After that, the DRG cells for RIA were stimulated by capsaicin (300 nmol/L) for 5 min and the culture media were harvested for detecting SP and CGRP release levels by RIA. The neurons exposed to vehicle solution served as vehicle controls. RESULTS: Exposure of butyrate on DRG neurons at higher concentrations (1 mmol/L, 10 mmol/L) for 48 h increased expression mRNA for SP and CGRP than that at lower concentrations (0.01 mmol/L, 0.1 mmol/L) and normal control (P<0.001). VR1 mRNA and VR1 protein expression increased in a dose-dependent manner after exposure of different concentrations of butyrate. Butyrate did not alter the basal release, significantly enhanced neuropeptide release evoked by capsaicin. SP and CGRP release levels in the culture media exposed by butyrate at higher concentrations (1 mmol/L, 10 mmol/L) for 48 h and then stimulated by capsaicin were higher than that at lower concentrations (0.01 mmol/L, 0.1 mmol/L) (P<0.001). The exposure of vehicle solution did not produce any increase of SP and CGRP release from primary cultured DRG neurons. DISCUSSION: Butyrate may promote the expression of mRNA for SP, CGRP and increase sensitivity of capsaicin on SP and CGRP release from primary cultured rat dorsal root ganglion neurons. The promotion of VR1 mRNA and VR1 protein expression by butyrate implicated that VR1 may be involved in the mechanisms of sensory neuropeptide release evoked by capsaicin.

Animals↗

High-performance liquid chromatographic determination of vertilmicin in rat plasma using sensitive fluorometric derivatization.

A sensitive and reliable high-performance liquid chromatographic method was developed for the determination of vertilmicin in rat plasma. Derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) followed by C(18) reversed-phase chromatography allowed the fluorimetric detection of vertilmicin. Optimal conditions for the derivatization of vertilmicin are described. The limit of quantification was 0.02 mg/L. The pharmacokinetics of vertilmicin was studied in 24 rats following intramuscular injection (i.m.) of different doses (4, 8, 16, 32 mg/kg of body weight). The pharmacokinetic parameter values were estimated by use of 3P97 program. In this study, we assessed the dose proportionality of vertilmicin after single intramuscular injection doses and obtained new information on the pharmacokinetics of the compound.

Aminoglycosides↗

Refined phylogenetic profiles method for predicting protein-protein interactions.

MOTIVATION: The increasing availability of complete genome sequences provides excellent opportunity for the further development of tools for functional studies in proteomics. Several experimental approaches and in silico algorithms have been developed to cluster proteins into networks of biological significance that may provide new biological insights, especially into understanding the functions of many uncharacterized proteins. Among these methods, the phylogenetic profiles method has been widely used to predict protein-protein interactions. It involves the selection of reference organisms and identification of homologous proteins. Up to now, no published report has systematically studied the effects of the reference genome selection and the identification of homologous proteins upon the accuracy of this method. RESULTS: In this study, we optimized the phylogenetic profiles method by integrating phylogenetic relationships among reference organisms and sequence homology information to improve prediction accuracy. Our results revealed that the selection of the reference organisms set and the criteria for homology identification significantly are two critical factors for the prediction accuracy of this method. Our refined phylogenetic profiles method shows greater performance and potentially provides more reliable functional linkages compared with previous methods.

Algorithms↗

p-Toluenesulfonyl isocyanate as a novel derivatization reagent to enhance the electrospray ionization and its application in the determination of two stereo isomers of 3-hydroxyl-7-methyl-norethynodrel in plasma.

In this paper, p-toluenesulfonyl isocyanate has been reported as a novel derivatization reagent with strong nuclephilic reactivity for the hydroxyl compounds. The derivatization for the two pharmacologically active 3-hydroxyl metabolites, 3alpha-hydroxyl-7-methyl-norethynodrel and 3beta-hydroxyl-7-methyl-norethynodrel by p-toluenesulfonyl isocyanate can be accomplished in 2 min under room temperature. The offline derivatization procedure introduced an easily ionizable sulfonylcarbamic ester moiety to the metabolites. This greatly improved the analyte's sensitivity in negative electrospray ionization and enabled us to achieve the desired lower limit of quantitation at 100 pg/ml in plasma. Therefore, a sensitive high performance liquid chromatography-mass spectrometry (HPLC-MS) method for the analysis of the two stereo isomers was developed. The method had been validated to be accurate, precise, and sensitive, and can be used for the metabolism pharmacokinetic study of tibolone in human subjects.

Chromatography, High Pressure Liquid↗

Stability indicating reversed-phase ion-pairing liquid chromatographic determination of vertilmicin sulfate as bulk drug and in injections.

A simple reversed-phase high performance liquid chromatographic method was developed for the analysis of vertilmicin sulfate, a novel aminoglycoside (AG). UV detection was used to determine vertilmicin sulfate and its related compounds in drug substance and products without sample derivatization. The method was used to determine the content of vertilmicin and its related compounds and test the stability of vertilmicin sulfate as drug substance and in injections, which was required for registration of new drug.

Aminoglycosides↗

Applications of capillary isoelectric focusing with liquid-core waveguide laser-induced fluorescence whole-column imaging detection.

Capillary isoelectric focusing (CIEF) with liquid-core waveguide (LCW) laser-induced fluorescence (LIF) whole-column imaging detection (WCID) is a recently developed high-resolution, high-sensitivity, and high-speed analytical tool for protein analysis. Several potential applications of this system were demonstrated in this study. First, this system was employed to separate naturally fluorescent phycobiliproteins. Second, denaturing CIEF was suggested to study the conformational and chemical microheterogeneity and to characterize proteins with identical pI values. Third, a modified noncovalent fluorescent labeling procedure was presented, which allows the simple and effective labeling of proteins, antibodies, and viruses with reduced multiple labeling and preserved activity. Finally, extracellular proteins were suggested as signaling biomarkers for evaluation of cell viability. The separation of cyanobacteria and their extracellular phycoerythrins was demonstrated. The effectiveness of CIEF-LCW-LIF-WCID for the analysis of proteins, antibodies, viruses, and cells has been illustrated.

Antibodies↗

Coupling of solid-phase microextraction and capillary isoelectric focusing with laser-induced fluorescence whole column imaging detection for protein analysis.

A coupling method of solid-phase microextraction (SPME) and capillary isoelectric focusing (CIEF) with laser-induced fluorescence (LIF) whole column imaging detection (WCID) was developed for the analysis of proteins. Unlike other liquid-phase separation methods and conventional CIEF, proteins are focused into stationary bands within a pH gradient in CIEF-WCID. Thus, CIEF-WCID is the most compatible liquid-phase separation method for coupling with SPME, which can effectively resolve the problems associated with the slow desorption kinetics of SPME in a liquid phase. By combining SPME and CIEF-WCID, the desorption time can be as long as necessary, allowing complete desorption without any band broadening and analyte carryover. By using this method, R-phycoerythrin in water can be extracted by SPME in 10 min, and subsequently analyzed by CIEF-LIF-WCID within 20 min, providing a limit of detection of 3.5 x 10(-12) M (S/N = 3). The feasibility of the SPME-CIEF-LIF-WCID method was demonstrated by extracting and analyzing extracellular phycoerythrins in cultured cyanobacteria samples. Extracellular phycoerythrins at the nanomolar level were extracted and analyzed in 30 min, while avoiding the interference of the cyanobacteria cells.

Fluorescence↗

Behaviors of the MS2 virus and related antibodies in capillary isoelectric focusing with whole-column imaging detection.

Capillary isoelectric focusing (CIEF) has potential importance for the study of viruses. CIEF with whole-column imaging detection (WCID) is a novel CIEF mode, providing the advantages of high resolution, high speed, and easy method development. To facilitate the application of CIEF-WCID to the immunoassay of viruses, a basic knowledge of related aspects is necessary. In this study, the MS2 bacteriophage was used as a virus model, and the behaviors of MS2 and related antibodies in CIEF were investigated with UV absorbance-WCID and laser-induced fluorescence (LIF)-WCID. The adsorption of the virus and antibodies on the capillary wall was found to be the critical issue in method development. Addition of salt was found to be an effective way to reduce the adsorption and to improve peak shape. The formation of an immunocomplex, which forms the basis of an immunoassay, was monitored with CIEF-WCID. In comparison with UV-WCID, LIF-WCID was advantageous due to its higher detection sensitivity and the elimination of precipitation. Utilization of the noncovalent fluorescent dye, NanoOrange, was demonstrated to be a potential approach for the fluorescent labeling of the virus model and antibody and the associated immunocomplex. The change in microheterogeneity during the immune interactions at different ratios was also observed.

Adsorption↗

Quantitative detection of HIV-1 RNA using NucliSens EasyQ HIV-1 assay.

HIV-1 RNA viral load has become the major biological marker for disease prognosis and outcome of antiretroviral therapy in the treatment of HIV-infected individuals. The aim of this study was to compare the performance of the new CE marked NucliSens EasyQ HIV-1 assay with NucliSens HIV-1 QT assay (reference method). NucliSens EasyQ HIV-1 (EasyQ) couples nucleic acid sequence-based amplification (NASBA) with real-time detection using molecular beacons utilizing the NucliSens EasyQ analyzer. NASBA is a sensitive, isothermal, transcription-based amplification system designed specifically for the detection of RNA targets. There was significant correlation (r = 0.878, P < 0.0001) between the two different assays in the analysis of clinical samples and the frequency of concordant results (log difference <0.5) was 74%. The two assays detected HIV-1 RNA in 81 specimens, and neither detected (below the lower detection limit, 400 copies/ml for NucliSens HIV-1 QT and 500IU/ml for EasyQ) HIV-1 RNA in 12 specimens. Three clinical specimens had detectable HIV-1 RNA using the EasyQ only, and two specimens had detectable HIV-1 RNA using the NucliSens HIV-1 QT only. The EasyQ procedure can analyze 48 clinical samples within 6h. The coefficient of variation of EasyQ ranged from 3.0 to 9.5% (3% at 4.9 log; 5.7% at 3.7 log; 9.5% at 2.7 log). The new assay is shown to be a rapid, convenient, and reliable procedure for HIV-1 RNA viral load monitoring.

HIV Infections↗

Mutual information-based analysis of JPEG2000 contexts.

Context-based arithmetic coding has been widely adopted in image and video compression and is a key component of the new JPEG2000 image compression standard. In this paper, the contexts used in JPEG2000 are analyzed using the mutual information, which is closely related to the compression performance. We first show that, when combining the contexts, the mutual information between the contexts and the encoded data will decrease unless the conditional probability distributions of the combined contexts are the same. Given I, the initial number of contexts, and F, the final desired number of contexts, there are S(I, F) possible context classification schemes where S(I, F) is called the Stirling number of the second kind. The optimal classification scheme is the one that gives the maximum mutual information. Instead of using an exhaustive search, the optimal classification scheme can be obtained through a modified generalized Lloyd algorithm with the relative entropy as the distortion metric. For binary arithmetic coding, the search complexity can be reduced by using dynamic programming. Our experimental results show that the JPEG2000 contexts capture the correlations among the wavelet coefficients very well. At the same time, the number of contexts used as part of the standard can be reduced without loss in the coding performance.

Algorithms↗

Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers.

AIM: To investigate the stereoselectivity in human metabolic 3-reduction of tibolone. METHODS: Twenty healthy Chinese female volunteers were given a single oral dose of tibolone (2.5 mg), and serial blood samples were collected after treatment. The plasma concentrations of the two pharmacologically active 3-hydroxyl metabolites of tibolone, 3alpha-hydroxyl-7-methyl- norethynodrel (3alpha-HMN) and 3beta-hydroxyl-7-methyl- norethynodrel (3beta-HMN) in plasma were determined by using a validated liquid chromatography-mass spectrometry (LC-MS) method. RESULTS: The apparent elimination half-life (T(1/2) of 3alpha-HMN was 1.43+/-0.52 h, and that of 3beta-HMN was 1.53+/-0.60 h. Maximum plasma concentrations (C(max)) were found to be 8.75+/-4.36 microg/L for 3alpha-HMN and 3.59+/-1.81 microg/L for 3beta-HMN. Areas under the plasma concentration versus time curve (AUC(0-t)) were 26.30+/-12.14 microg.h(-1).L(-1) for 3alpha-HMN and 9.89+/-4.93 microg.h(-1).L(-1) for 3beta-HMN. CONCLUSION: Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism in humans.

Administration, Oral↗