PubMed Health⌕ Search

Biomedical subjects

Qiang Zhang

Publications and source records attributed to Qiang Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2005

In vitro anti-Helicobacter pylori action of 30 Chinese herbal medicines used to treat ulcer diseases.

Infection by Helicobacter pylori has been ascertained to be an important etiologic impetus leading usually to chronic active gastritis and gastric ulcer with growing incidences worldwide. Utilizing as the test pathogen a standard and five clinic strains of Helicobacter pylori, the antibacterial action was assessed in vitro with ethanol extracts of 30 Chinese herbal medicines which have been frequently prescribed since ancient times for treating gastritis-like disorders. Among the 30 tested materials, the ethanol extracts of Abrus cantoniensis (Fabaceae), Saussurea lappa (Asteraceae) and Eugenia caryophyllata (Myrtaceae) were strongly inhibitory to all test strains (MICs: approximately 40 microg/ml), and Hippophae rhamnoides (Elaeagnaceae), Fritillaria thunbergii (Liliaceae), Magnolia officinalis and Schisandra chinensis (Magnoliaceae), Corydalis yanhusuo (Papaveraceae), Citrus reticulata (Rutaceae), Bupleurum chinense and Ligusticum chuanxiong (Apiaceae) substantially active with MICs close to 60.0 microg/ml. As to antibacterial actions of the aqueous extracts of the same drugs, those derived from Cassia obtusifolia (Fabaceae), Fritillaria thunbergii and Eugenia caryophyllata were remarkably inhibitory against all the six Helicobacter pylori strains (MICs: approximately 60 microg/ml). The work compared almost quantitatively the magnitude of the anti-Helicobacter pylori actions of the 30 most prescribed gastritis-treating Chinese herbal drugs, and located as well some source plants where potent anti-Helicobacter pylori phytochemicals could be characterized.

Anti-Bacterial Agents↗
PubMed2005

Experimental free-space distribution of entangled photon pairs over 13 km: towards satellite-based global quantum communication.

We report free-space distribution of entangled photon pairs over a noisy ground atmosphere of 13 km. It is shown that the desired entanglement can still survive after both entangled photons have passed through the noisy ground atmosphere with a distance beyond the effective thickness of the aerosphere. This is confirmed by observing a spacelike separated violation of Bell inequality of 2.45+/-0.09. On this basis, we exploit the distributed entangled photon source to demonstrate the Bennett-Brassard 1984 quantum cryptography scheme. The distribution distance of entangled photon pairs achieved in the experiment is for the first time well beyond the effective thickness of the aerosphere, hence presenting a significant step towards satellite-based global quantum communication.

Journal Article↗
PubMed2005

3D-QSAR comparative molecular field analysis on opioid receptor antagonists: pooling data from different studies.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) on a series of opioid receptor antagonists. To obtain statistically significant and robust CoMFA models, a sizable data set of naltrindole and naltrexone analogues was assembled by pooling biological and structural data from independent studies. A process of "leave one data set out", similar to the traditional "leave one out" cross-validation procedure employed in partial least squares (PLS) analysis, was utilized to study the feasibility of pooling data in the present case. These studies indicate that our approach yields statistically significant and highly predictive CoMFA models from the pooled data set of delta, mu, and kappa opioid receptor antagonists. All models showed excellent internal predictability and self-consistency: q(2) = 0.69/r(2) = 0.91 (delta), q(2) = 0.67/r(2) = 0.92 (mu), and q(2) = 0.60/r(2) = 0.96 (kappa). The CoMFA models were further validated using two separate test sets: one test set was selected randomly from the pooled data set, while the other test set was retrieved from other published sources. The overall excellent agreement between CoMFA-predicted and experimental binding affinities for a structurally diverse array of ligands across all three opioid receptor subtypes gives testimony to the superb predictive power of these models. CoMFA field analysis demonstrated that the variations in binding affinity of opioid antagonists are dominated by steric rather than electrostatic interactions with the three opioid receptor binding sites. The CoMFA steric-electrostatic contour maps corresponding to the delta, mu, and kappa opioid receptor subtypes reflected the characteristic similarities and differences in the familiar "message-address" concept of opioid receptor ligands. Structural modifications to increase selectivity for the delta over mu and kappa opioid receptors have been predicted on the basis of the CoMFA contour maps. The structure-activity relationships (SARs) together with the CoMFA models should find utility for the rational design of subtype-selective opioid receptor antagonists.

Least-Squares Analysis↗
PubMed2005

Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer.

Transforming growth factor (TGF)-beta is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells may lead to tumor evasion from the host immune surveillance and tumor progression. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. The mouse TRAMP-C2 prostate cancer cells produced large amounts of TGF-beta1 and were used as an experimental model. C57BL/6 mice were primed with irradiated TRAMP-C2 cells. CD8+ T cells were isolated from the spleen of primed animals, were expanded ex vivo, and were rendered TGF-beta insensitive by infecting with a retrovirus containing dominant-negative TGF-beta type II receptor. Results of in vitro cytotoxic assay revealed that these CD8+ T cells showed a specific and robust tumor-killing activity against TRAMP-C2 cells but were ineffective against an irrelevant tumor line, B16-F10. To determine the in vivo antitumor activity, recipient mice were challenged with a single injection of TRAMP-C2 cells for a period up to 21 days before adoptive transfer of CD8+ T cells was done. Pulmonary metastasis was either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. Results of immunofluorescent studies showed that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis in tumor cells. Furthermore, transferred tumor-reactive TGF-beta-insensitive CD8+ T cells were able to persist in tumor-bearing hosts but declined in tumor-free animals. These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for cancer therapy.

Adoptive Transfer↗
PubMed2005

Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function.

The adaptor protein p14 is associated with the cytoplasmic face of late endosomes that is involved in cell-surface receptor endocytosis and it also directly interacts with MP1, a scaffolding protein that binds the MAP kinase ERK1 and its upstream kinase activator MEK1. The interaction of p14 with MP1 recruits the latter to late endosomes and the endosomal localization of p14/MP1-MEK1-ERK1 scaffolding complex is required for signaling via ERK MAP kinase in an efficient and specific manner upon receptor stimulation. Here, we report the three-dimensional solution structure of the adaptor protein p14. The structure reveals a profilin-like fold with a central five-stranded beta-sheet sandwiched between alpha-helices. Unlike profilin, however, p14 exhibits weak interaction with selective phosphoinositides but no affinity towards proline-rich sequences. Structural comparison between profilin and p14 reveals the molecular basis for the differences in these functions. We further mapped the MP1 binding sites on p14 by NMR, and discuss the implications of these important findings on the possible function of p14.

Adaptor Proteins, Vesicular Transport↗
PubMed2005

Restoration of expression of transforming growth factor-beta type II receptor in murine renal cell carcinoma (renca) cells by 5-Aza-2'-deoxycytidine.

The murine renal cell carcinoma (Renca) cells are insensitive to TGF-beta due to a lack of TGF-beta type II receptor (TbetaR-II). The objective of the present study is to determine the mechanism of this loss of sensitivity to TGF-beta in Renca cells. Renca cells were cultured and treated with 5-Aza-2'-Deoxycytidine (5-Aza), a specific inhibitor of methylation. Expression of TGF-beta type I receptor (TbetaRI) and TbetaRII was determined by RT-PCR and Western blot analysis before and after the treatment of Renca cells with 5-Aza. The expression of phosphorylated Smad2 (P-Smad2) was determined by Western blot analysis. TGF-beta levels in the conditioned medium were measured by ELISA. Renca cells did not express TbetaR-II prior to 5-Aza treatment. After 5-Aza treatment, these cells expressed TbetaR-II at both mRNA and protein levels, which corresponded to the restoration of sensitivity to TGF-beta by an increase in P-Smad2. Levels of TGF-beta1 were similar before and after 5-Aza treatment. Results of the present study indicated that, in Renca cells, the loss of sensitivity to TGF-beta is likely due to a promoter hypermethylation in the TbetaR-II gene.

Animals↗
PubMed2005

Intracellular delivery of doxorubicin with RGD-modified sterically stabilized liposomes for an improved antitumor efficacy: in vitro and in vivo.

Passive targeting by sterically stabilized liposomes (SSL), once combined with efficient intracellular delivery, may be a very useful strategy to improve the antitumor efficacy for the anticancer agents. The arginine-glycine-aspartic acid tripeptide (RGD) is known to serve as a recognition motif for several different integrins located on cell surface. In this study, the RGD tripeptide was coupled to the distal end of the poly (ethylene glycol)-coated liposomes (RGD-SSL) aimed to achieve increased tumor accumulation and enhanced intracellular uptake. DOX-loaded RGD-SSL (RGD-SSL-DOX), DOX-loaded SSL (SSL-DOX), and free DOX were compared with respect to their in vitro uptake and cytotoxicity and their in vivo biodistribution and therapeutic efficacy in tumor-bearing mice. Flow cytometry and confocal microscopy studies revealed that RGD-SSL could facilitate the DOX uptake into melanoma cells by integrin-mediated endocytosis. RGD-SSL-DOX displayed higher cytotoxicity on melanoma cells than SSL-DOX. While RGD-SSL-DOX demonstrated prolonged circulation time and increased tumor accumulation as SSL-DOX did, it showed remarkably higher splenic uptake than SSL-DOX. Mice receiving RGD-SSL-DOX (5 mg DOX/kg) showed effective retardation in tumor growth compared with those receiving same dose of SSL-DOX, free DOX solution, or saline. These results suggest that RGD-modified SSL may be a feasible intracellular targeting carrier for efficient delivery of chemotherapeutic agents into tumor cells.

Animals↗
PubMed2005

Artifact and noise suppression in GRAPPA imaging using improved k-space coil calibration and variable density sampling.

A parallel imaging technique, GRAPPA (GeneRalized Auto-calibrating Partially Parallel Acquisitions), has been used to improve temporal or spatial resolution. Coil calibration in GRAPPA is performed in central k-space by fitting a target signal using its adjacent signals. Missing signals in outer k-space are reconstructed. However, coil calibration operates with signals that exhibit large amplitude variation while reconstruction is performed using signals with small amplitude variation. Different signal variations in coil calibration and reconstruction may result in residual image artifact and noise. The purpose of this work was to improve GRAPPA coil calibration and variable density (VD) sampling for suppressing residual artifact and noise. The proposed coil calibration was performed in local k-space along both the phase and frequency encoding directions. Outer k-space was acquired with two different reduction factors. Phantom data were reconstructed by both the conventional GRAPPA and the improved technique for comparison at an acceleration of two. Under the same acceleration, optimal sampling and calibration parameters were determined. An in vivo image was reconstructed in the same way using the predetermined optimal parameters. The performance of GRAPPA was improved by the localized coil calibration and VD sampling scheme.

Algorithms↗
PubMed2005

Contrast-enhanced 4D radial coronary artery imaging at 3.0 T within a single breath-hold.

Coronary magnetic resonance angiography data are usually acquired during mid-diastole of each heartbeat to minimize cardiac motion related artifacts. The proper trigger delay time, which may vary widely among subjects, must be determined individually for each subject before data acquisition to achieve optimal image quality. These complications could be resolved by acquiring contiguous cardiac phase images through the cardiac cycle. In this study, we used a radial sampling technique to acquire 3D cine coronary artery images at 3 T within a single breath-hold. An extravascular, paramagnetic contrast agent was i.v. administered to improve the blood signal intensity. Relatively high temporal resolution and spatial resolution were achieved simultaneously with radial sampling, parallel data acquisition, and interleaved sliding window image reconstruction. Volunteer studies demonstrate the feasibility of this technique in acquiring 4D coronary artery images and the flexibility in postprocessing of 3D image sets.

Contrast Media↗
PubMed2005

4D radial coronary artery imaging within a single breath-hold: cine angiography with phase-sensitive fat suppression (CAPS).

Coronary artery data acquisition with steady-state free precession (SSFP) is typically performed in a single frame in mid-diastole with a spectrally selective pulse to suppress epicardial fat signal. Data are acquired while the signal approaches steady state, which may lead to artifacts from the SSFP transient response. To avoid sensitivity to cardiac motion, an accurate trigger delay and data acquisition window must be determined. Cine data acquisition is an alternative approach for resolving these limitations. However, it is challenging to use conventional fat saturation with cine imaging because it interrupts the steady-state condition. The purpose of this study was to develop a 4D coronary artery imaging technique, termed "cine angiography with phase-sensitive fat suppression" (CAPS), that would result in high temporal and spatial resolution simultaneously. A 3D radial stacked k-space was acquired over the entire cardiac cycle and then interleaved with a sliding window. Sensitivity-encoded (SENSE) reconstruction with rescaling was developed to reduce streak artifact and noise. Phase-sensitive SSFP was employed for fat suppression using phase detection. Experimental studies were performed on volunteers. The proposed technique provides high-resolution coronary artery imaging for all cardiac phases, and allows multiple images at mid-diastole to be averaged, thus enhancing the signal-to-noise ratio (SNR) and vessel delineation.

Adipose Tissue↗
PubMed2005

High-resolution steady-state free precession coronary magnetic resonance angiography within a breath-hold: parallel imaging with extended cardiac data acquisition.

Coronary artery imaging data are conventionally acquired in a single imaging frame during mid-diastole. The data acquisition window must be sufficiently short to avoid cardiac motion artifacts. A short data acquisition window results in decreased imaging efficiency and limited spatial resolution. Parallel imaging may lessen these limitations, but requires highly accurate coil sensitivity. The purpose of this work was to increase the imaging efficiency and spatial resolution in coronary artery imaging using parallel imaging with an extended acquisition window. External coil calibration data were acquired before and after a short mid-diastolic period of accelerated imaging data acquisition. It was assumed that residual cardiac motion in the extended acquisition window would not impede accurate estimation of coil sensitivity since only low spatial frequency signals were acquired for coil calibration. Experimental studies were performed in five healthy volunteers at 3 T using steady-state free precession sequence. Statistical comparison was made between the proposed method and conventional data acquisition for visual quality of image and vessel sharpness. The proposed technique demonstrated higher visual grading and improved vessel sharpness. The proposed method is a new approach to enhance the imaging efficiency and spatial resolution in coronary artery imaging.

Artifacts↗
PubMed2005

Preparation and physicochemical characterization of biodegradable nerve guides containing the nerve growth agent sabeluzole.

The objective of this study was to develop and characterize a biodegradable drug-loaded nerve guide for peripheral nerve regeneration. Sabeluzole, a nerve growth agent, was selected as model compound. Four biodegradable polymers were selected for this study: a copolymer of polylactic acid and polycaprolactone (PCL); a copolymer of polyglycolic acid and polycaprolactone PCL; a copolymer of PCL/polydioxanone (PDO) and PDO. Placebo and drug loaded nerve guides were obtained by melt compression and melt extrusion. It was observed that melt compression and melt extrusion are feasible techniques to prepare the nerve guides. Based on the physicochemical characterization, all samples show absence of crystalline sabeluzole, indicating the formation of an amorphous dispersion. The in vitro release measurements show that the release of sabeluzole is complete, reproducible and can be controlled by the proper selection of the polymer. The release mechanism for all samples follows Fickian release behaviour.

Absorbable Implants↗
PubMed2005

Modulation of P-glycoprotein function and reversal of multidrug resistance by (-)-epigallocatechin gallate in human cancer cells.

Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. In this study, the reversal of P-glycoprotein (P-gp) mediated multidrug resistance by (-)-epigallocatechin gallate (EGCG) and its molecular mechanism were investigated. A three-dimensional model of carboxyl-terminal nucleotide binding domain (NBD2) from P-gp was built by homology modeling. The structural model of the complex indicates that EGCG was tightly bound to the ATP-binding site of NBD2. EGCG modulated the function of P-gp and increased the intracellular accumulation of chemotherapeutic agent doxorubicin (DOX) in drug-resistant KB-A1 cells. When KB-A1 cells were exposed to 10 microg/ml DOX combined with 10, 30, 50 microM EGCG for 4 h, the intracellular concentrations of DOX were increased 1.5, 1.9, 2.3 times, respectively compared with DOX alone treatment. In vitro EGCG potentiated the cytotoxicity of DOX to drug-resistant KB-A1 cells. In KB-A1 cell xenograft model, EGCG could also enhance the efficacy of DOX and increased the DOX concentration in the resistant tumors. Thus, these results suggest that EGCG modulated the function of P-gp and reversed P-gp mediated multidrug resistance in human cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Pharmacodynamics and pharmacokinetics of the insulin-mimetic agent vanadyl acetylacetonate in non-diabetic and diabetic rats.

The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose levels in diabetic rats in all dosing levels, and nearly restored hyperglycemic values to normal values after s.c. injection at a single dose of 2, 4, and 8 mg vanadium (V)/kg, or after i.g. administration at multiple doses of 3 and 6 mg V/kg once daily for seven consecutive days, respectively. The VAC could be rapidly absorbed and T(max) values ranged from 0.9 +/- 0.3 h for s.c. injection to 3.0 +/- 0.9 h for i.g. administration. The average absolute bioavailabilities for i.g. administrations at a single dose of 3, 6, and 10 mg V/kg were 34.7%, 28.1%, and 22.8%, respectively. After i.g. administration at a single dose of 10 mg V/kg, the average elimination half-lives obtained from non-diabetic rats were very long ranging from 144.7 +/- 8.7 h in plasma to 657.3 +/- 34.8 h in femur tissue. In conclusion, VAC widely distributed in various tissues and accumulated more in the femur tissue. The time to reach maximal vanadium level after s.c. injection or i.g. administration was not coincident with the time to reach maximal hypoglycemic effect. The accumulated vanadium in bone, kidney or other tissues may gradually release and exert a longer action. In present dosing levels and administration routes, VAC was effective for lowering plasma glucose levels in diabetic rats and could reverse the higher triglyceride and cholesterol levels to the normal ranges. VAC did not influence the insulin levels in plasma and not cause obvious toxic signs like diarrhea.

Animals↗
PubMed2005

3D-QSAR comparative molecular field analysis on delta opioid receptor agonist SNC80 and its analogs.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) for a series of delta opioid receptor agonists: SNC80 analogs. Quantum chemical calculations on SNC80 show that protonation is preferred at the basic N4 atom over the alternative N1 atom, accordingly N4 protonation may contribute significantly to ligand-receptor interactions under physiologically relevant conditions. Statistically significant and predictive CoMFA models were achieved by pooling biological data from independent published sources, including compounds with both alphaR and alphaS benzylic configurations. Improved CoMFA models were obtained when the compounds were considered as N4-protonated species rather than neutral compounds. The influence of various atomic partial-charge formalisms, alignment schemes and additional molecular descriptors was evaluated in order to produce the highest quality models. In addition, separate CoMFA models were generated for compounds with only the alphaR benzylic configuration. These CoMFA models showed excellent internal predictability and consistency, and external validation using test-set compounds yielded predicted pIC50 values within 1log unit of the corresponding experimentally measured values. Key insights into the structure-activity relationship derived from the CoMFA analysis concur with experimentally observed data, thus the CoMFA models presented here find utility for predicting the binding affinity, and guiding the design, of novel SNC80 analogs and related delta opioid receptor agonists.

Animals↗
PubMed2005

Pharmacodynamics and pharmacokinetics of recombinant hirudin via four non-parenteral routes.

One of recombinant hirudin variants, rHV2, a polypeptide used as an anticoagulant agent in clinic, was administered to anesthetized rats via intratracheal, buccal, nasal and rectal routes. Prolongation in clotting time and thrombin time was measured to calculate pharmacological bioavailability. Plasma concentration of rHV2 was determined using a chromogenic thrombin substrate assay and pharmacokinetic parameters were obtained on the basis of a non-compartmental model. Intravenous administration was also performed as the gold standard by which the other routes were compared. Difference in pharmacological bioavailability (P.A.), bioavailability (F) and absorption rate of rHV2 was found for the four non-parenteral routes. The rank order for both P.A. and F was intratracheal>nasal>buccal>rectal. Absorption was more rapid after both intratracheal and rectal administration (tmax approximately 20-40 min), compared with that after nasal and rectal administration. It is evident that the pulmonary route is preferable to other three routes for successful systemic delivery of rHV2.

Absorption↗