Biomedical subjects

Jianguo Sun

Publications and source records attributed to Jianguo Sun.

At least 19 recordsLinked to original sources

PubMed2026

Screening of Fermentative Strains for Reducing the Allergenicity of a Whey Protein-Soy Protein System and Genomic Characterization of the Selected Strain.

Dual-protein systems combining whey protein isolate (WPI) and soy protein isolate (SPI) offer complementary nutritional benefits but are limited by the presence of major allergens. Lactic acid bacteria (LAB) fermentation provides a promising strategy to mitigate this limitation. In this study, Lacticaseibacillus paracasei JM053, selected from 13 LAB strains based on phenotypic screening, significantly reduced the in vitro allergenicity of the dual-protein system, increasing the IgE-binding inhibition rate to 48.75%. Whole-genome sequencing and characterization of JM053 revealed a comprehensive proteolytic system, including the proline-specific peptidase genes pepX and pepQ, which may contribute to the degradation of allergenic peptide sequences. Combined with in silico bioinformatic analysis, potential cleavage sites within the linear epitopes of the dual-protein system were predicted based on the substrate specificity of the identified proteases, offering a testable hypothesis for the strain's mechanism of action. In addition, in vitro safety assessment and genomic analysis supported the safety potential, stress tolerance, and probiotic characteristics of JM053. Collectively, this study provides a valuable candidate strain for the development of hypoallergenic dual-protein products and offers preliminary genomic insights into LAB-mediated allergenicity reduction.

Lacticaseibacillus paracasei↗

PubMed2007

Regression analysis of failure time data with informative interval censoring.

Interval censoring arises when a subject misses prescheduled visits at which the failure is to be assessed. Most existing approaches for analysing interval-censored failure time data assume that the censoring mechanism is independent of the true failure time. However, there are situations where this assumption may not hold. In this paper, we consider such a situation in which the dependence structure between the censoring variables and the failure time can be modelled through some latent variables and a method for regression analysis of failure time data is proposed. The method makes use of the proportional hazards frailty model and an EM algorithm is presented for estimation. Finite sample properties of the proposed estimators of regression parameters are examined through simulation studies and we illustrate the method with data from an AIDS study.

Acquired Immunodeficiency Syndrome↗

PubMed2007

Determination of secnidazole in human plasma by high-performance liquid chromatography with UV detection and its application to the bioequivalence studies.

A simple, accurate, precise and sensitive HPLC-UV method was developed for the determination of secnidazole in human plasma. Secnidazole and tinidazole (IS) were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then separated by HPLC on a Diamond C(18) column and quantified by ultraviolet detection at 319 nm. The mobile phase consisted of acetonitrile-aqueous 5 mm sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0, and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1 microg/mL. The method was linear over the concentration range 0.1-25.0 microg/mL (R(2) = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to 89.1%. Inter- and intra-assay precision ranged from 3.3 to 10.7%. Secnidazole in plasma was stable when stored at ambient temperature for 8 h, at -20 degrees C for 2 weeks and at -20 degrees C for three freeze-thaw cycles. The developed method was successfully applied to the pharmacokinetic and bioequivalence studies between test and reference secnidazole tablets following a single 500 mg oral dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters T(max), C(max), AUC(0-)t, AUC(0-infinity), T(1/2) were determined of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. It was concluded that the two secnidazole preparations are bioequivalence and may be used interchangeably.

Administration, Oral↗

PubMed2007

Testing the proportional odds model for interval-censored data.

This paper discusses the goodness-of-fit test for the proportional odds model for K-sample interval-censored failure time data, which frequently occur in, for example, periodic follow-up survival studies. The proportional odds model has a feature that allows the ratio of two hazard functions to be monotonic and converge to one and provides an important tool for the modeling of survival data. To test the model, a procedure is proposed, which is a generalization of the method given in Dauxois and Kirmani [Dauxois JY, Kirmani SNUA (2003) Biometrika 90:913-922]. The asymptotic distribution of the procedure is established and its properties are evaluated by simulation studies

Biometry↗

PubMed2006

Simultaneous determination of MHD and DMD in dog plasma by high-performance liquid chromatography with fluorescence detection and its application to pharmacokinetic studies.

A rapid, reproducible high-performance liquid chromatographic (HPLC) method with fluorescence detection for the simultaneous determination of 3(or 8)-(1-methoxyethyl)-8(or 3)-(1-hydroxyethyl)-deuteroporphyrin IX (MHD) and 3,8-di-(1-methoxyethyl)-deuteroporphyrin IX (DMD) in dog plasma was described. Fluorescein was used as an internal standard. A simple extraction step with ethyl acetate was performed before chromatography on a Diamonsil C18 column (5 microm, 4.6 mm x 150 mm). The chromatography used 0.02 mol L(-1) sodium acetate/tetrahydrofuran (66:34 v/v). The analytical curve was linear over the concentration range 0.025-2.5 microg mL(-1). For a 100 microL dog plasma sample, the limit of determination for both MHD and DMD was 0.025 microg mL(-1). The recoveries of MHD and DMD were more than 76% and 89%, respectively. The intra-assay (within-run) and interassay (between-run) coefficients of variation (precisions) for MHD and DMD were less than 15%. This method was found to be suitable for the analysis of biosamples and was successfully applied to pharmacokinetic studies of Deuxemether in dogs.

Animals↗

PubMed2006

Simultaneous determination of erythromycin ethylsuccinate and its metabolite erythromycin in human plasma using liquid chromatography-electrospray ionization mass spectrometry for clinical study.

A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.

Adult↗

PubMed2006

Liquid chromatographic/mass spectrometry assay of triptolide in dog plasma and its application to pharmacokinetic study.

A rapid and sensitive method for the determination of triptolide in dog plasma was developed and validated, using high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI/MS). Sample preparation consisted of liquid-liquid extraction with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Detection was performed on a triple quadrupole mass spectrometer using selected-ion monitoring (SIM) mode on the deprotonated ions [M-H]- at m/z 359. Calibration curves were linear over the concentration range of 0.5-200 ng/mL of triptolide with the intra- and inter-day precision (the relative standard deviation values) were being less than 7%. Triptolide was stable under different conditions. The intra-day and inter-day accuracy were 99.3-105.2% and 101.3-107.0%, respectively. The lower limit of quantification was 0.5 ng/mL. The method was successfully applied to a pharmacokinetic study after an intragastric administration (i.g.) of triptolide to dogs with a dose of 0.05 mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of triptolide.

Animals↗

PubMed2006

In vitro assessment of plasma protein binding of 20(R)-ginsenoside Rh2 by equilibrium dialysis and LC-MS analysis: a case of species differences.

20(R)-Ginsenoside Rh2 is isolated from Chinese traditional ginsengs with main antitumor effects. To support its pharmacokinetic study which was essential for the pre-clinical research for new drug development, in this paper, 20(R)-Rh2 plasma protein binding was assessed in vitro at four concentration levels (50, 100, 200, 400 ng/ml) both in rat and human plasma using equilibrium dialysis and followed by LC-MS analysis. The method was optimized against some influencing factors during both experimental procedures. And it was validated to be specific, sensitive, accurate, precise and of satisfactory recovery. The results showed the binding fractions were about 70% for rats and 27% for human within four concentration levels. It exhibited a significant species difference between human and rats for the plasma protein binding of 20(R)-Rh2.

Animals↗

PubMed2005

Sensitive and selective liquid chromatography-electrospray ionisation-mass spectrometry analysis of astragaloside-IV in rat plasma.

Astragaloside-IV (3-O-beta-d-xylopyranosyl-6-O-beta-d-glucopyranosyl-cycloastragenol) is the major active constituent contained in Radix Astragali. This paper describes a rapid, sensitive and specific assay for quantitative determination of astragaloside-IV in rat plasma. After a liquid/liquid extraction (LLE) with n-butanol and high-performance liquid chromatography (HPLC) gradient separation with acetonitrile-NH4Cl solution (0.5 micromol/L) as the mobile phase, the anions adduct [M + Cl]- at m/z 819.4 of astragaloside-IV, and [M + Cl]- at m/z 815.35 of internal standard (IS) digoxin were analyzed by electrospray ionisation-mass spectrometry (LC-ESI-MS) in selected ion monitoring (SIM) mode. Chromatographic separation was achieved in less than 9 min and calibration curve was linear over a concentration range of 2-200 ng/ml. The described assay method was successfully applied to the preclinical pharmacokinetic study of astragaloside-IV. After intragastric administration of astragaloside-IV to rats, Cmax and Tmax of astragaloside-IV were 134.73 +/- 39.86 ng/ml and 1.5 h, respectively, and the elimination half-life (t1/2) was 5.45 +/- 0.39 h.

Animals↗

PubMed2005

Simultaneous determination of loratadine and pseudoephedrine sulfate in human plasma by liquid chromatography-electrospray mass spectrometry for pharmacokinetic studies.

To support the pharmacokinetic and bioavailability study of an extended-release loratadine (LOR)/pseudoephedrine sulfate (PES) tablet, a high performance liquid chromatographic-electrospray ionisation-mass spectrometric method (LC-MS) was developed for the simultaneous determination of LOR and PES in human plasma. Diazepam (DP) and phenylpropanolamine (PPA) were used as internal standards for LOR and PES, respectively. Analytes were extracted from alkalized human plasma by liquid/liquid extraction using ethyl ether. Chromatographic separation was performed on an ODS column at flow rate of 0.2 ml/min. The total chromatographic run time was 10.5 min with the retention time of 7.1 min and 6.2 min for LOR and DP, respectively, and 2.2 min for both of PES and PPA. The LOQ was 10 pg/ml and 50 pg/ml for LOR and PES, respectively. The method is accurate and precise enough for its intended purpose.

Calibration↗

PubMed2005

Statistical analysis of current status data with informative observation times.

Current status data arise when each study subject is observed only once and the survival time of interest is known only to be either less or greater than the observation time. Such data often occur in, for example, cross-sectional studies, demographical investigations and tumorigenicity experiments and several semi-parametric and non-parametric methods for their analysis have been proposed. However, most of these methods deal only with the situation where observation time is independent of the underlying survival time completely or given covariates. This paper discusses regression analysis of current status data when the observation time may be related to the underlying survival time and inference procedures are presented for estimation of regression parameters under the additive hazards regression model. The procedures can be easily implemented and are applied to two motivating examples.

2-Acetylaminofluorene↗

PubMed2005

Simultaneous determination of oxymatrine and its active metabolite matrine in dog plasma by liquid chromatography-mass spectrometry and its application to pharmacokinetic studies.

A simple, rapid and reliable method was developed for the quantification of oxymatrine (OMT) and its metabolite matrine (MT) in beagle dog plasma using a liquid-liquid extraction procedure followed by liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) analysis. Extend-C18 column (2.1 mm i.d. x 50 mm, 5 microm) with a C18 guard column (2.1 mm i.d. x 12.5 mm) was used as the analytical column. Linear detection responses were obtained for OMT concentration ranging from 5 to 4000 ng/ml and for MT concentration ranging from 5 to 2000 ng/ml. The precision and accuracy data, based on intra- and inter-day variations over 5 days, were lower than 5%. The limit of quantitation for OMT and MT were 2 and 1 ng/ml, respectively, and their recoveries were greater than 90%. Pharmacokinetic data of OMT and its active metabolite MT obtained with this method following a single oral dose of 300 mg OMT capsules to six beagle dogs was also reported for the first time.

Alkaloids↗

PubMed2005

Simultaneous rapid quantification of ginsenoside Rg1 and its secondary glycoside Rh1 and aglycone protopanaxatriol in rat plasma by liquid chromatography-mass spectrometry after solid-phase extraction.

Ginseng saponins isolated from ginseng, have been regarded as the principal constituents responsible for the biological activities. The aim of this study was to set up a liquid chromatography-mass spectrometry (LC-MS) method for simultaneously determine the concentration of Ginsenoside Rg1 and its secondary glycoside Rh1 and aglycone protopanaxatriol (PPT) in rat plasma so as to study the pharmacokinetics of Rg(1) after intraveneous (i.v.) and intragastric gavage (i.g.) administration. One hundred microliters or 1.0 ml of rat plasma samples from i.v. or i.g. treated rats were used respectively for analysis. After solid-phase extraction (SPE) and high performance liquid chromatography (HPLC) separation, the chloride adduct anions [M+Cl]- of Rg1, Rh1 and PPT were analyzed by LC-MS in selected ions monitoring (SIM) mode. Rg(1) could be determined by this LC-MS method over the ranges of 1.56-250 ng/ml and 250-20,000 ng/ml with the correlation coefficients of 0.999 and 0.9998, respectively. The detection limits (LOD) of this method was 20 pg (S/N>3) for Rg1, 100 pg for Rh1 and 10 pg for PPT. Chromatographic separation was achieved in less than 8 mins. The method has been used for the pharmacokinetic study of Rg1 in rats.

Animals↗

PubMed2005

Enantioselective pharmacokinetics of ibuprofen and involved mechanisms.

Although dexibuprofen (S-ibuprofen) was marketed in Austria and Switzerland, the racemate at various formulations is still extensively used worldwide, and there are no indications that the racemate will be replaced by the single enantiomer. Thus, elucidation of the characteristics and involved mechanisms of the chiral pharmacokinetics of racemic ibuprofen is of special importance for the understanding of the pharmacological and toxicological consequences, and for prediction of the clinically potential drug interactions and influence of the pathological states. Stereoselective pharmacokinetics and metabolism are common features for chiral nonsteroidal antiinflammatory drugs (NSAIDs) and especially for 2-arylpropionic acid derivatives characterized with a chiral center adjacent to the carboxyl group. Although the enantioselective pharmacokinetic characteristics of different NSAIDs should be treated case by case, they share similar mechanisms underlying the protein binding, metabolism and chiral inversion. Ibuprofen was the most extensively researched drug in terms of chiral characteristics and mechanisms. Therefore, elucidation of the mechanisms derived from research on ibuprofen may provide better understanding and prediction of other chiral drugs. This article attempts to elucidate the chiral pharmacokinetics and involved mechanisms of ibuprofen in comparison with other NSAIDs based on recent developments. Topics on history of ibuprofen, enantioselective analysis method, absorption, protein binding, conventional metabolism, metabolic chiral inversion, gene polymorphism, and biochemical developments were included. It is worth mentioning that some underlying biochemical mechanisms, especially for the metabolic chiral inversion and ethnic differences still remain to be seen. Further research is required to develop human-resourced researching model and to provide more evidence concerning the site of inversion, species variation, CYP450 gene polymorphisms, and biochemical mechanisms.

Animals↗

PubMed2005

Pharmacokinetics of guanfu base I, an active metabolite of guanfu base A, in rats.

A liquid chromatographic-mass spectrometric (LC-MS) method was developed and validated for determination of guanfu base I (GFI), and the pharmacokinetics of GFI in Sprague-Dawley rats was examined. The method was linear in the 0.05-20 mug/ml concentration range (r=0.9994). The recovery of guanfu base I was more than 80%. The intraday and interday precision, expressed as the relative standard deviation (RSD), was generally good (<15%). After i.v. dosing, plasma GFI concentration declined in a bi-phasic manner with a terminal elimination half-life of 2.49 h. The total plasma clearance values was 1.46 l/h/kg. After oral dosing, the plasma GFI concentration reached a maximum within 0.5 h. The absolute bioavailability of GFI was 71.31%.

Animals↗

PubMed2005

Unidirectional inversion of ibuprofen in Caco-2 cells: developing a suitable model for presystemic chiral inversion study.

Intestinal chiral inversion of ibuprofen is still lacking direct evidence. In a preliminary experiment, ibuprofen was found to undergo inversion in Caco-2 cells. This investigation was thus conducted to determine the characteristics and influence of some biochemical factors on the chiral inversion of ibuprofen in Caco-2 cells. The effects of substrate concentration (2.5-40 microg/ml), cell density (0.5-2 x 10(6) cells/well), content of serum (0-20%), coexistence of S ibuprofen (corresponding doses), sodium azide (10 mM), exogenous Coenzyme A (CoA) (0.1-0.4 mM), and palmitic acid (5-25 microM) on inversion were examined. A stereoselective HPLC method based on the Chromasil-CHI-TBB column was developed for quantitative analysis of the drug in cell culture medium. The inversion ratio (F(i)) and elimination rate constant were calculated as the indexes of inversion extent. Inversion of ibuprofen in Caco-2 cells was found to be both dose and cell density dependent, indicating saturable characteristics. Addition of serum significantly inhibited the inversion, to an extent of 2.7 fold decrease at 20% content. Preexistence of S enantiomer exerted a significant inhibitory effect (p<0.01 for all tests). Sodium azide decreased the inversion ratio from 0.43 to 0.32 (p<0.01). Exogenous CoA and palmitic acid significantly promoted the inversion at all tested doses (p<0.01 for all tests). This research provided strong evidence to the capacity and capability of intestinal chiral inversion. Although long incubation times up to 120 h were required, Caco-2 cells should be a suitable model for chiral inversion research of 2-APAs considering the human-resourced and well-defined characteristics from the present study.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Generalized log-rank test for mixed interval-censored failure time data.

This paper considers the problem of non-parametric treatment comparisons when mixed interval-censored failure time data are available, which often occurs in clinical trials and epidemiological studies. By mixed interval-censored data, we mean that the survival time of interest is observed to belong to an interval or to be right-censored. For the problem, we generalize the most commonly used log-rank test for right-censored survival data. Numerical studies are conducted and reported to evaluate and compare the proposed test with the existing method, which indicate that the presented method works well. We apply the method to a data set arising from an AIDS cohort study, that motivated the study.

Cohort Studies↗

PubMed2004

Regression analysis of doubly censored failure time data using the additive hazards model.

Doubly censored failure time data arise when the survival time of interest is the elapsed time between two related events and observations on occurrences of both events could be censored. Regression analysis of doubly censored data has recently attracted considerable attention and for this a few methods have been proposed (Kim et al., 1993, Biometrics 49, 13-22; Sun et al., 1999, Biometrics 55, 909-914; Pan, 2001, Biometrics 57, 1245-1250). However, all of the methods are based on the proportional hazards model and it is well known that the proportional hazards model may not fit failure time data well sometimes. This article investigates regression analysis of such data using the additive hazards model and an estimating equation approach is proposed for inference about regression parameters of interest. The proposed method can be easily implemented and the properties of the proposed estimates of regression parameters are established. The method is applied to a set of doubly censored data from an AIDS cohort study.

Acquired Immunodeficiency Syndrome↗