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Biomedical subjects

J X Wang

Publications and source records attributed to J X Wang.

At least 37 records · Page 2Linked to original sources

[Study on brain targeting 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine pharmacosomes].

AIM: To investigate the specific brain drug targeting of 5-fluoro-2'-deoxyuridine (FUdR) by synthesis of 3', 5'-dioctanoyl-5-fluoro-2'-deoxyuridine (DO-FUdR) and incorporation into DO-FUdR pharmacosomes (DO-FUdR-PS). METHODS: DO-FUdR-PS was prepared by thin-layer ultrasonication technique. In vitro drug release was studied in pH 7.4 phosphate-buffered saline containing 0.3% pancreatic enzyme at 37 degrees C using bulk-equilirium reverse dialysis bag technique. The concentration of FUdR in various organs were determined by reversed phase HPLC after i.v. administration of DO-FUdR-PS and FUdR. RESULTS: The mean particle size of DO-FUdR-PS was 76 nm with drug loading of 29.02% and entrapment efficiency of 96.62%. The in vitro drug release kinetics could be characterized by bioexponential equation. Compared with FUdR injection, DO-FUdR-PS showed high concentration in tested organs. The brain AUC ratio of DO-FUdR-PS to FUdR was 10.97. CONCLUSION: DO-FUdR-PS showed a good targeting efficiency in vivo. PS can improve the ability of drug to cross blood-brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.

Animals↗

[Optimization of the preparation of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine pharmacosomes using central composite design].

AIM: To optimize the preparation of 3', 5'-dioctanoyl-5-fluoro-2'-deoxyuridine pharmacosomes (DO-FUdR-PS) by using central composite design. METHODS: DO-FUdR-PS was prepared by a thin-layer ultrasonication technique. The effects of drug phosphatidycholine ratio, pluronic F-68 concentration (%, w/v) and glycerol tristearate (%, w/v) concentration on the mean particle size, entrapment ratio (ER) and drug loading (DL) were investigated. A second-order polynomial equation was fitted to the data and the resulting model was used to predict the response in the optimal region. RESULTS: All the investigated response variables were found to be highly dependent on the formulation variables. Under the optimized conditions, the mean particle size, ER and DL of DO-FUdR-PS were 76 nm, 97.49% and 31.44%, respectively, which highly agreed with the predicted values. CONCLUSION: Central composite design was successfully used to optimize the preparation of DO-FUdR-PS.

Drug Design↗

[Cancer risk assessment among medical X-ray workers in China].

Cancer incidence(1950-1995) among 27,011 medical X-ray workers in comparison with 25,782 non X-ray medical specialists between 1950 and 1980 in China was investigated. The average cumulative dose received by the X-ray workers also reconstructed by retrospective dosimetry methods. Significant cancer risk was seen among medical X-ray workers(RR = 1.2). Significantly elevated risks were found in leukemia, cancer of skin, female breast, lung, liver, bladder and esophagus, the RRs were 2.2, 4.1, 1.3, 1.2, 1.2, 1.8 and 2.7 respectively. The patterns of cancer risk were associated with years since beginning of X-ray work, age and calendar year of initial employment and cumulative dose suggest that the risks of leukemia, skin cancer and female breast cancer, possibly thyroid cancer were related to occupational exposure to X-rays. A significant cancer risk could be induced by prolonged exposure to low dose ionizing radiation when the cumulative dose reached a certain level.

China↗

Development of PCR-based markers linked to the fertility restorer gene for the polima cytoplasmic male sterility in rapeseed (Brassica napus L.).

Bulked segregant analysis was used to identify RAPD markers linked to the Rfp of pol cms in rapeseed (Brassica napus L.) from the fertile and sterile DNA bulks. DNA bands amplified from 1040 random 10-mer primers were screened. Two polymorphic bands S1019(720) and S1036(810) were found linked to the Rfp locus at the same side with a map distance of 5.8 cM and 12.3 cM respectively. These polymorphic fragments were cloned and sequenced. Nucleotide sequence information was used to design 20-24-mer oligo nucleotide primers for PCR amplification. The SCAR markers that generated from the long primers showed the same pattern of segregation as the original RAPD markers in the backcross population. The SCAR markers would facilitate selection on the Pol CMS restorer lines in rapeseed.

Brassica↗

[Simultaneous determination of magnolol and honokiol in serum and urine by high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic method for simultaneous determination of magnolol and honokiol in serum and urine of rat has been established. Two drugs were determined within 15 minutes by the method on the column with spherisorb C18, by using a mobile phase consisted of methanol-water-glacial acetic acid (70:30:1, V/V) at 1 mL/min, monitored at 294 nm and with a sensitivity of 0.005 AUFS. After 0.25, 1 and 8 hour of administration of the drugs, protein in serum and urine of Wistar rat was precipitated by methanol and magnolol and honokiol in acidified body fluid were determined after being extracted by a mixture of ethyl acetate and ether. Good linear relationship between concentration in serum and urine and peak area in the ranges of 0.05-2 mg/L for magnolol and 0.025-1 mg/L for honokiol was obtained. Good precision and reproducibility were found too. The average recoveries of the two drugs were 95.6% (RSD = 3.85%), 93.8% (RSD = 3.95%) in serum and 96.0% (RSD = 3.83%), 94.9% (RSD = 3.54%) for urine respectively. The lower limit of the method was 0.02 mg/L of magnolol and 0.04 mg/L of honokiol respectively. The results showed that this method is suitable for the determination of magnolol and honokiol in body fluids.

Animals↗

[Clinical application of 3D reconstruction in maxillofacial fractures].

OBJECTIVE: To study the value of 3D reconstructive technique in midfacial fractures,especially its significance in preoperative diagnosis and operation planning of complicated,multiple fractures in midface. METHODS: To preoperatively scan and reconstruct 47 fracture patients with spiral CT. RESULTS: 38 cases received operation which confirmed the preoperative diagnosis of 3D CT. The conservationed treatment was applied to other 9 patients. CONCLUSION: The 3D reconstruction can reveal the complicated fractures in midface as approximate model, and benefit the selection of the most suitable plan before operation.

English Abstract↗

High-throughput screening for ligand-induced c-fos mRNA expression by branched DNA assay in Chinese hamster ovary cells.

We have developed a generally useful screening assay for receptor agonists and antagonists in Chinese Hamster Ovary (CHO) cells. Three key features of the assay make it applicable to a broad range of receptors: (1) the use of CHO cells as host cells to overexpress receptors, (2) measurement of endogenous c-fos mRNA, which responds to a wide spectrum of stimuli, and (3) the use of branched chain DNA assay which is highly sensitive, quantifiable, amenable to high-throughput analysis, and easy to execute. The combination of these features provides a powerful means to screen rapidly for peptide and small molecule ligands for a variety of receptors. CHO cells overexpressing insulin receptor were used as a test system to compare conventional signaling assays with the high-throughput c-fos branched DNA assay.

Amino Acid Sequence↗

Semirational design of a potent, artificial agonist of fibroblast growth factor receptors.

Fibroblast growth factors (FGFs) are being investigated in human clinical trials as treatments for angina, claudication, and stroke. We designed a molecule structurally unrelated to all FGFs, which potently mimicked basic FGF activity, by combining domains that (1) bind FGF receptors (2) bind heparin, and (3) mediate dimerization. A 26-residue peptide identified by phage display specifically bound FGF receptor (FGFR) 1c extracellular domain but had no homology with FGFs. When fused with the c-jun leucine zipper domain, which binds heparin and forms homodimers, the polypeptide specifically reproduced the mitogenic and morphogenic activities of basic FGF with similar potency (EC50 = 240 pM). The polypeptide required interaction with heparin for activity, demonstrating the importance of heparin for FGFR activation even with designed ligands structurally unrelated to FGF. Our results demonstrate the feasibility of engineering potent artificial agonists for the receptor tyrosine kinases, and have important implications for the design of nonpeptidic ligands for FGF receptors. Furthermore, artificial FGFR agonists may be useful alternatives to FGF in the treatment of ischemic vascular disease.

3T3 Cells↗

Antianginal effects of ranolazine in various experimental models of angina.

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal drug, on the ST-segment changes induced by coronary ligation, epinephrine, and vasopressin were examined following oral or intraduodenal administration. In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, or 50 mg/kg) or atenolol (10 mg/kg) significantly attenuated the ST-T wave elevation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol was accompanied by more or less maintained decreases in diastolic blood pressure, heart rate, and the maximum first derivative of left ventricular pressure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 mg/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 microgram/kg i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o.) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by vasospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.

Acetanilides↗

High-intensity laser-induced electron acceleration in vacuum.

In this paper, an approximate pulsed-laser-beam solution of Maxwell's equation in vacuum is derived. Then with the numerical simulation method, electron acceleration induced by high-intensity [Q(0)=eE(0)/(m(e)omega c)=3] lasers is discussed in connection with the recent experiment of Malka et al. It is found that the maximum energy gain and the relationship between the final energy and the scattering angle can be well reproduced, but the polarization effect of electron-laser interactions is not very prominent. These results show that the ponderomotive potential model is still applicable, which means that the stimulated Compton scattering is the main fundamental mechanism responsible for the electron acceleration at this laser intensity.

Journal Article↗

Effects of dexamethasone on intracellular Ca2+ in its sensitive cells from neonatal mouse hippocampus and cultured cortical neurogliocytes.

AIM: To investigate the effects of dexamethasone (Dex) on intracellular free calcium ([Ca2+]i) in the single neuron or neurogliocyte. METHODS: Neonatal mouse hippocampal cells (NMHC) and cultured cortical neurogliocytes (CCN) were loaded with Fura 2-AM. The [Ca2+]i was measured with AR-CM-MIC-cation measurement system. RESULTS: Most of freshly isolated NMHC exhibited a rapid and concentration-dependent [Ca2+]i increase after administration of Dex 40-200 mumol.L-1. Only 10% of NMHC showed their [Ca2+]i decreases in total 96 tested cells. Dex-triggered [Ca2+]i rise was prevented by incubating the cells with Mg(2+)-free solution and reduced by adding LaCl3. Suspended NMHC in Ca(2+)-free solution or pretreated cells with mifepristone or tetrodotoxin prevented the initial [Ca2+]i increases caused by Dex 40-90 mumol.L-1, but only diminished the later [Ca2+]i rises by Dex 200 mumol.L-1. About 50% of tested single CCN showed a rapid and concentration-related [Ca2+]i increase due to Dex 90-270 mumol.L-1 exposure. This effect was partially inhibited under extracellular Ca(2+)- or Mg(2+)-free and mifepristone pretreatment conditions. CONCLUSION: Dex produces the rapid [Ca2+]i changes in both neurons and glia cells. Reactions among most cells include a Mg(2+)-dependent and glucocorticoid receptor-related extracellular Ca2+ influx and a high concentration of Dex-mediated intracellular Ca2+ release.

Animals↗

Quercetin decreased heart rate and cardiomyocyte Ca2+ oscillation frequency in rats and prevented cardiac hypertrophy in mice.

AIM: To study the effects of quercetin (Que) on myocardial excitation-contraction coupling and cardiac remodeling. METHODS: Left ventricles and femoral arteries of rats were cannulated for hemodynamic recording. Mouse cardiac hypertrophy was induced by abdominal aortic coarctation (AAC). Cultured myocardial cells in neonatal rats were loaded with Fura 2-AM. The intracellular calcium ([Ca2+]i) and spontaneous [Ca2+]i oscillations ([Ca2+]i-SO) were tested by AR-CM-MIC cation measurement system. RESULTS: Que 3 or 25 mg.kg-1 i.v. in rats decreased heart rate from (420 +/- 19) to (390 +/- 15) and (314 +/- 18) beat.min-1, respectively, companied with very modest changes in both left ventricular pressures (LVP) and its differential dpLV/dtmax. Que 10, 50, 250 mumol.L-1 concentration-dependently slowed the frequency of [Ca2+]i-SO in cultured myocardial cells from (26 +/- 4) to (25 +/- 3), (18 +/- 4), and (12 +/- 3) time.min-1, respectively, but did not change their resting [Ca2+]i or amplitudes of [Ca2+]i-SO. Similarly, the increases in frequency of [Ca2+]i-SO caused by either isoproterenol (Iso) or ouabain (Oua) were prevented by Que 100 mumol.L-1, while the simultaneous increases in amplitude of [Ca2+]i-SO remained. Besides, [Ca2+]i rises excited by angiotensin II (Ang II) but not high [K+]o were prevented by Que 100 mumol.L-1. Daily administration of Que 120 mg.kg-1 i.g. for 5 d markedly prevented the cardiac hypertrophy in AAC mice, without effects on the ventricular mass to body weight ratio (VM/BW) in sham-operated mice. CONCLUSION: Que decreased myocardial [Ca2+]i-oscillation frequency and prevented cardiac remodeling, but had no direct effect on cardiac excitation-contraction coupling.

Animals↗

Gene therapy for human hepatocellular carcinoma with cytosine deaminase gene and prodrug flucytosine.

AIM: To investigate the antitumor effects of cytosine deaminase (CD) gene in combination with prodrug flucytosine (Flu, 5-fluorocytosine) on human hepatocellular carcinoma. METHODS: CD gene was transduced into human hepatocellular carcinoma cell line SMMC7721 with retroviral method and the cytotoxicity of Flu on the tumor cells was assayed in vitro with clonogenic techniques. The xenograft tumor model in nude mice was used to study in vivo therapeutic effects of CD gene/Flu system against human hepatocellular carcinoma. RESULTS: CD gene/Flu system had significant antitumor activities on human hepatocellular carcinoma cells in vitro and in nude mice. The antitumor activities of Flu 500 mg.kg-1 on hepatocellular carcinoma xenografts in nude mice were more potent than those of 5-fluouracil 10 mg.kg-1. CD gene/Flu system possessed bystander killing effects on hepatocellular carcinoma xenografts in nude mice. CONCLUSION: The experiment demonstrates the potential value of the CD gene/Flu system in the treatment of human hepatocellular carcinoma.

Animals↗

Electrochemical immunoassay based on catalytic conversion of substrate by labeled metal ion and polarographic detection of the product generated.

In a new electrochemical immunoassay based on the conversion of a substrate catalyzed by a labeled metal ion and the polarographic detection of the product generated, metal copper ion was used to label model antigen human serum albumin through the bifunctional chelating agent diethylenetriaminepentaacetic acid. After heterogeneous competitive immunoreaction, the labeled copper ion was released or activated by acidification and chemically catalyzed the conversion of the substrate o-phenylenediamine to the electroactive product 2,3-diaminophenazine (DAP). The DAP was quantified using linear-potential scan polarography. The sensitivity of the proposed assay was 100 times higher than that of the previous methods based on direct detection of the metal ion labels. This immunoassay can be used to detect any protein of interest.

Catalysis↗

Naltrexone suppresses the rejection of cardiac tissue transplantation.

The present study demonstrates the following: 1. Transplantation of cardiac tissue induces an inflammatory response that ultimately leads to the rejection of the tissue by the host within 9 days; 2. Treatment with the opiate antagonist, naltrexone, significantly increased the survival of the transplanted cardiac tissue to 13 days, suggesting the involvement of opioid signaling molecules in tissue rejection; 3. In further experiments it was demonstrated that in mixed lymphocyte populations from different mice, the DNA synthesis inhibitor, mitomycin C, reduced the lymphocyte proliferative response as did naltrexone; 4. Mice injected with naltrexone for 10 days and given concanavalin A exhibited a suppressed spleen lymphocyte proliferative response compared to controls. Taken together, these data suggest that endogenous opioid signals not only activate immunocytes, but also stimulate DNA synthesis.

Analysis of Variance↗

Thioredoxin fusion/HIV-1 protease coexpression system for production of soluble human IL6 in E. coli cytoplasm.

In this paper, thioredoxin (TRX) fusion expression system has been modified to produce soluble human IL6 (hIL6) without TRX moiety in E. coli cytoplasm. A novel TRX gene fusion vector was developed that contained at the 3'-end of TRX gene a short DNA sequences encoding a linker peptide '-GSGSGVSQNYPIVQHHHHHH-', serving not only as a specific HIV-1 protease site but also providing six contiguous histidine (His) residues to foreign proteins. The cDNA for hIL6 was cloned into this vector resulting in plasmid pTRX@HISIL6. The cDNA for the HIV-1 protease has been cloned into another compatible plasmid pHMM2, resulting in plasmid pHMM2-PR. Both plasmids were transformed into E. coli strain GI724, and when induced for expression of both proteins, the correct processing of TRX@HISIL6 was obtained, producing hIL6 with His6-tag at the N terminus named HISIL6. A fraction of HISIL6 was found in soluble form and could be purified to homogeneity by Ni-NTA Superflow and ion-exchange chromatography. The biological activity of purified HISIL6 was measured by MTT method in an IL-6-dependent cell line 7TD1 to be 2.1 x 10(8) unit/mg.

Amino Acid Sequence↗