Biomedical subjects

Hai Wang

Publications and source records attributed to Hai Wang.

At least 73 records · Page 4Linked to original sources

PubMed2004

Cardiovascular pharmacological characterization of novel 2,3-dimethyl-2-butylamine derivatives in rats.

The electrophysiological properties and pharmacological effects of newly synthesized 2,3-dimethyl-2-butylamine derivatives on the rat cardiovascular system were evaluated both in vitro and in vivo. In conventional whole-cell recordings, 2,3-dimethyl-2-butylamine derivatives with ethyl, isopropyl, allyl, butyl, 1-methyl-propyl or cyclopropylmethyl substituents on the amine side chain had potent effects on the outward potassium currents in isolated rat tail arterial smooth muscle cell membranes. In contrast, the compounds with hydrogen, methyl, propyl or benzyl substituents displayed very low activities, which were not statistically significant. The effects of compounds with pyridine ring substituents were also investigated and their order of potency was (14)>(12)>(13). In addition, the opening activities of these compounds (5), (6), (8) could be prevented by glibenclamide, a highly specific blocker of ATP-sensitive potassium channels. The influences of the compounds on cardiovascular hemodynamics parameters, including mean blood pressure (MBP), heat rate (HR), myocardial contractility and diastolic force, were examined in normotensive anesthetized rats. The derivatives with branched 2-4 carbon alkyl substituents induced long-duration hypotensive effects with modest inhibition of cardiac function. The hypotensive effects of the compound (5) could also be inhibited by glibenclamide. Collectively, these results indicate that 2,3-dimethyl-2-butylamine derivatives, which differ chemically from previously described potassium channel openers, have potassium channel opening activity, hypotensive and cardiac-modulating properties that depend on their amino group substituents.

Animals↗

PubMed2004

Thermophoretic force and velocity of nanoparticles in the free molecule regime.

We extend our previous gas-kinetic theory analysis of drag force in a uniform temperature field [Li and Wang, Phys. Rev. E. 68, 061206 (2003); 68, 061207 (2003)] to particle transport in fluids with nonuniform temperature. Formulations for drag and thermophoretic forces are proposed for nanoparticle transport in low-density gases. We specifically consider the influence of nonrigid body collision due to van der Waals or other forces between the particle and gas molecules and find that these forces play a notable role for particles a few nanometers in size. It is shown that the present formulations can be easily reduced to the classical result of Waldmann [Z. Naturforsch. A 14a, 589 (1959)] by assuming rigid body collision. From the force formulations we also obtain the equation governing the thermophoretic velocity. This velocity is found to be highly sensitive to the potential energy of interactions between gas molecules and particle, and as such Waldmann's thermophoretic velocity is not expected to be accurate for nanosized particles.

Journal Article↗

PubMed2004

Activities of cAMP-dependent protein kinase and protein kinase C are modulated by desensitized nicotinic receptors in the rat brain.

When rats were treated with different dosages of nicotine, nicotinic acetylcholine receptors (nAChRs) were observed in activated, sub-acute desensitized, acute desensitized, and chronic desensitized states. The activities of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) were assayed in the respective rat brains. The results showed that the activities of PKA and PKC could not be modified when brain nAChRs were in an activated state. However, the activities of PKA and PKC decreased when brain nAChRs were in a sub-acute state, an acute state or a chronic desensitized state induced by repeated administration of nicotine. These results suggest that desensitized nAChRs in the rat brain can inhibit the activities of PKA and PKC, which may be responsible for nicotine dependence.

Animals↗

PubMed2004

Targeting ischemic stroke with a novel opener of ATP-sensitive potassium channels in the brain.

During cerebral ischemia, the opening of neuronal ATP-sensitive potassium channels (K(ATP) channels) affords intrinsic protection by regulating membrane potential. To augment this endogenous mechanism, we have synthesized iptakalim, a K(ATP) opener. Through K(ATP) channel activation, iptakalim affected multiple pathways of the glutamatergic system, limiting glutamate release and receptor actions, which are involved in excitotoxicity during ischemic damage. The molecule readily penetrated the brain and showed low toxicity in animal experiments. In different animal models of stroke as well as in cell cultures, iptakalim provided significant neuroprotection, not only in promoting behavioral recovery but also in protecting neurons against necrosis and apoptosis. This compound thus has promise as a neuroprotective drug for the treatment of stroke and other forms of neuronal damage.

Animals↗

PubMed2004

Increased hepatic expression of nitric oxide synthase type II in cirrhotic rats.

AIM: To determine the role and effect of nitric oxide synthase type II (NOSII) in cirrhotic rats. METHODS: Expression of NOSII mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum levels of NO, systemic and portal hemodynamics and degrees of cirrhosis were measured with high sensitive methods. Chinese traditional medicine tetrandrine was used to treat cirrhotic rats and to evaluate the function of NO. Double-blind method was applied during the experiment. RESULTS: The concentration of NO and the activity of NOS were increased markedly at all stages of cirrhosis, and iNOSmRNA was greatly expressed. Meanwhile the portal-venous-pressure (PVP), and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the quantity of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. CONCLUSION: Increased hepatic expression of NOSII is one of the important causes of hepatic cirrhosis and portal hypertension.

Alkaloids↗

PubMed2004

Discovering selective agonists of endothelial target for acetylcholine (ETA) via diversity-guided pharmacophore simplification and simulation.

Two types of lead structures for selective agonists of ETA, a biological target not yet fully elucidated, has first been discovered via diversity-guided pharmacophore simplification and simulation. And it is first demonstrated that potent selective ETA agonists might be useful for protection of endothelium and for prophylaxis and treatment of cardiovascular diseases with endothelial dysfunction such as atherosclerosis and thrombosis.

Acetylcholine↗

PubMed2004

Correlation of expression of multidrug resistance protein and messenger RNA with 99mTc-methoxyisobutyl isonitrile (MIBI) imaging in patients with hepatocellular carcinoma.

AIM: To explore whether P-glycoprotein (Pgp) and other pumps, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP), could affect tumor accumulation and efflux of 99mTc-MIBI in liver cancer. METHODS: Surgically treated 78 liver cancer patients were included in this study. Before surgery, 99mTc-MIBI SPECT was performed 15 min and 120 min after injection of 20 mCi 99mTc-MIBI, respectively. Early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of 99mTc-MIBI were obtained. Expressions of Pgp, MRP and LRP were investigated with Western blotting and immunohistochemistry. Messenger RNA (mRNA) level of Pgp, MRP and LRP was determined by RT-PCR. RESULTS: No 99mTc-MIBI uptakes in tumor lesions of 68 of 78 (87.2%) patients with hepatocellular carcinoma were found on 99mTc-MIBI SPECT. P-gp expression was observed in tumor tissues of the patients with no uptake of 99mTc-MIBI (P<0.017). No appreciable correlation was found between liver cancer 99mTc-MIBI images and expression of MRP or LRP on the level of protein or mRNA. CONCLUSION: 99mTc-MIBI SPECT is noninvasive, and useful in predicting the presence of MDR1 gene-encoded Pgp in patients with hepatocellular carcinoma.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2004

[Overcoming multi-drug resistance using anti-MDR1 ribozymes].

OBJECTIVE: To reverse multidrug resistance (MDR) of HepG2 by anti-MDR1 hammerhead ribozyme. METHODS: We developed an anti-MDR1 hammerhead ribozyme and delivered it to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase III promoter. We detected the expression of MDR1/Pgp and Rz in HepG2, HepG2 multidrug-resistant cell line and HepG2 Rz-tranduced cells by real-time RT-PCR, semi-quantitative RT-PCR and western blot methods. Moreover, MTT assay was tested to detect sensitivity of these ribozyme-tranduced cells, and Rhodamine123 (Rh123) applied to test the function of Pgp. RESULTS: The Rz-tranduced HepG2 cells became doxorubicin-sensitive, concomitant with the decreases in MDR1 expression, P-gp amounts and efflux pump function. CONCLUSIONS: The approaches using either retrovirus or liposome-mediated transfer of anti-MDR1 ribozyme may be selectively applicable to the treatment of MDR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Molecular cloning of zebrafish and medaka vitellogenin genes and comparison of their expression in response to 17beta-estradiol.

In the present study, both zebrafish and medaka vitellogenin genes have been isolated and used as a biomarker to compare the two small aquarium fish in response to estrogen treatment and thus to evaluate the two fish models in development of a biomonitoring system for environmental estrogens. The isolated zebrafish vitellogenin gene, zvtg1, is the most abundantly expressed vitellogenin gene in zebrafish and its complete protein sequence of 1360 amino acids was deduced from a genomic and a cDNA clone. The isolated medaka vitellogenin (mvtg1) genomic clone covers 1053 amino acids in the N-terminal. Both zebrafish zvtg1 and medaka mvtg1 are specifically expressed in female liver and their expression can be induced by 17beta-estradiol (E2) in male fish both by intramuscular injection and immersion treatment. A real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for quantification of vitellogenin mRNA level in both control fish and E2-treated fish. The lowest-observed-effect concentrations of E2 for the induction of vitellogenin mRNAs were observed at 1 microg/l for zebrafish and 0.1 microg/l for medaka in a 2-day exposure experiment. Further kinetics studies of the two fish models indicated that medaka was able to respond much faster to E2 treatment than zebrafish, while the zebrafish can attain a much higher level of vitellogenin mRNAs than medaka after a long-term E2 treatment. The implication of these observations may be that the medaka system is better in monitoring acute treatment while the zebrafish system is better in monitoring chronic exposure.

Amino Acid Sequence↗

PubMed2004

[Immunotherapy of metastatic renal cell carcinoma: report of 28 cases].

OBJECTIVE: To determine the efficacy of IL-2, IFN and Furtulon in patients with metastatic renal cell carcinoma. METHODS: During the induction phase of the treatment of 28 patients, which lasted 3 months, IL-2 and IFN were administered subcutaneously three times a week at doses of 5 - 20 MU/m(2) and 6 - 9 MU/m(2), Furtulon was administered at doses of 800 - 1,200 mg daily by oral during 28 days a month. RESULTS: The response rate was 46.4%, including 4 complete response (CR), 9 presented with partial response (PR). CONCLUSION: The three-drugs combination described in this study demonstrates activity. Based on the present data, combined biochemotherapy may be a promising new approach to the therapy of the metastatic renal cell carcinoma.

Administration, Oral↗

PubMed2004

Tetrandrine ameliorates cirrhosis and portal hypertension by inhibiting nitric oxide in cirrhotic rats.

To examine the role and effect of nitric oxide synthase type II (NOS II) in cirrhotic rats, expression of NOS II mRNA was detected by real time RT-PCR. The enzymatic activity of nitric oxide synthase and the circulating levels of NO, systemic and portal hemodynamics and quantification of cirrhosis were measured. Chinese traditional medicine was used to treat cirrhotic rats and the effect of NO was evaluated. Double-blind method was used in experiment. Our results showed the concentration of NO and the enzymatic activity of NOS increased markedly at all stages of cirrhosis and iNOSmRNA was strongly expressed. Meanwhile, the portal-venous-pressure (PVP) and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the degree of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. Our results suggested that increased hepatic expression of NOS II is one of the important factors causing cirrhosis and portal hypertension. Tetrandrine can significantly ameliorate cirrhosis and portal hypertension.

Alkaloids↗

PubMed2004

Evidence that muscarinic receptors are involved in nicotine-facilitated spatial memory.

A delayed nonmatching-to-position task (DNMPT) in a water maze (nine trials per day, 10 days) was used to investigate the role of muscarinic acetylcholinergic receptor (mAChR) in nicotine-facilitated spatial memory in Wistar rats. The index of spatial memory was determined by the number of correct choices made in choice swim (CS) and the time taken to complete the swim in the correct CS. Diazepam (6 mg kg(-1) ip, daily) significantly impaired choice accuracy and increased the swim time for correct CS. In contrast, when nicotine (2 mg kg(-1) sc, twice daily) and diazepam were administered simultaneously in the last three sessions of training, the choice accuracies of CS were similar to controls and significantly higher than in the diazepam group. However, the swim times for correct CS were longer in the nicotine+diazepam group than in controls. Atropine (30 mg kg(-1) ip, daily) significantly decreased the choice accuracies of CS. The choice accuracies of CS swim times for correct CS in the atropine group did not differ significantly from those in the nicotine+atropine group, in which nicotine (2 mg kg(-1) sc, twice daily) and atropine were given simultaneously. These results show that nicotine improves memory performance when the functions of mAChRs are normal; when the mAChRs are blocked, nicotine does not enhance spatial memory. Therefore, mAChRs are involved in the spatial memory-enhancing effect of nicotine.

Animals↗

PubMed2004

Sonochemistry of degrading p-chlorophenol in water by high frequency ultrasound.

The degradation process and mechanism of p-chlorophenol in water using high frequency ultrasound (1.7 mHz) was investigated in this paper. The p-chlorophenol was degraded successfully in the high frequency ultrasonic device with low consumption of energy. The degradation effect was improved by increasing the solution concentration. No products or intermediate products were detected in the reaction mixture by the analytic methods of MS and 1H-NMR after ultrasonic irradiation. The dominant degradation mechanism is high temperature pyrolysis in ultrasonic cavities rather than free radical oxidation, and the experimental results can be explained completely according to pyrolysis mechanism.

Chlorophenols↗

PubMed2004

AMCXO and its test system.

In this paper, we introduce a novel temperature compensated crystal oscillator--analog memory compensated crystal oscillator (AMCXO), a microcomputer compensated crystal oscillator (MCXO) based on an analogue approach, and we compare the performance between MCXO and AMCXO, and analyze the necessity of developing AMCXO. Both AMCXO and MCXO, combined with their test systems, use computers to generate the control signals used for the compensated crystal oscillators according to temperature variation. However, the execution devices are much different from each other in the practical temperature compensated crystal oscillators. A MCXO uses a set of digital units, including a microprocessor, to realize the compensation. For it, equations or tables are used to express the relationship between the control signal and temperature. An AMCXO uses an analogue memory, which has the same functions as the digital units of MCXO. For AMCXO, a curve or figure based on the equations or tables is used to express the same relationship. Their test systems have obvious distinctions in temperature experiment, data acquisition, and processing. A better performance will be obtained by using a more complicated AMCXO test system, and the cost can be reduced at the same time.

Journal Article↗

PubMed2004

Protective effects of nicotine against glutamate-induced neurotoxicity in PC12 cells.

This study aimed to assess whether nicotine prevented glutamate neurotoxicity in PC12 cells, and to identify the molecular mechanisms of any effects. The results showed that glutamate neurotoxicity in PC12 cells could be prevented by treatment with nicotine at concentrations of 10 nmol x l(-1) - 1 mmol x l(-1). This effect was in turn found to be inhibited by the application of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Nicotine significantly decreased the basal level of intracellular free Ca(+2) and enhanced the buffering action on Ca(+2) overload induced by high concentrations of glutamate (5 mmol x l(-1)). In addition, nicotine treatment up-regulated the mRNA and protein expression of apoptosis-related factors including bcl-2 mRNA and protein, but down-regulated the expression of bax mRNA and protein. It is concluded that the protective effects of nicotine against the neurotoxicity induced by glutamate are mediated by nAChRs, due to the increased buffering action on Ca(+2)and the modulation of apoptotic processes.

Animals↗

PubMed2004

Proteomic response analysis of endothelial cells of human coronary artery to stimulation with carbachol.

AIM: To identify the molecular basis of the endothelial target for acetylcholine (ETA). METHODS: Proteomic methods were used to monitor changes in protein expression in the first 10 h following the stimulation of human coronary endothelial cells with carbachol 100 micromol/L. Thirty proteins showing the largest changes were identified by mass spectrometry. RESULTS: Based on analysis with Image Master 2-D Elite software, about 623 protein spots were detected in control cells and 825 protein spots in carbachol-treated cells, the matching rate was 68.1 %. Among all the detected spots, 39 were up-regulated and 29 were down-regulated, showing detectable changes varied from 1.7-3.8 folds. Forty one spots in the peptide mass fingerprints were successfully obtained. The most interesting feature was that all the four newly synthesized proteins belonged to the heat shock protein family. CONCLUSION: These identified proteins played key roles in the molecular mechanism of ETA.

Acetylcholine↗

PubMed2004

[Epigallocatechin-3-gallate interferes with EBV-encoding AP-1 signal transduction pathway].

OBJECTIVE: To elucidate the interference effect of Epigallocatechin-3-Gallate (EGCG) on targets of Activator Protein-1 (AP-1) signal transduction pathway activated by EB virus encoded latent membrane protein 1 in nasopharyngeal carcinoma (NPC) cell lines. METHODS: Survival rate of cells was determined by MTT assay. AP-1 and CyclinD1 activation were analyzed by promoter luciferase reporter system. Nuclear translocation of JNK was analyzed by indirect immunofluorescence. Protein expression and phosphorylation were observed by Western blot. RESULTS: EGCG inhibited the survival of CNE1 and CNE-LMP1 cells and the activity of AP-1 caused by LMP1 in CNE-LMP1 cells. EGCG also inhibited the nuclear translocation of JNK and the phosphorylation of c-Jun. It also inhibited cyclinD1 promoter activity and cyclinD1 expression. CONCLUSION: EGCG inhibits AP-1, JNK, c-Jun and cyclinD1 which are key targets on AP-1 signal transduction pathway. The results may explain the molecular mechanism of action of EGCG against nasopharyngeal carcinoma.

Carcinoma, Squamous Cell↗

PubMed2004

[EB virus encoded latent membrane protein 1 mediated expression of transcription factor Ets-1 in nasopharyngeal carcinoma cells].

OBJECTIVE: To elucidate the expression of tanscription factor Ets-1 mediated by EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cells. METHODS: LMP1-expressing NPC HNE2 cells regulated by Tet-on system (pTet-on-LMP1 HNE2) were used. Expression of LMP1 and Ets-1 was observed after induction with Doxycycline (Dox). Expression of Ets-1 mRNA and protein was detected by RT-PCR and Western blot, respectively. The phosphorylation level of Ets-1 protein was examined by co-immunoprecipitation. The DNA binding activity of Ets-1 was detected by electrophoretic-mobility shift assay (EMSA). RESULTS: After induction with Dox in pTet-on-LMP1 HNE2 cells, to some extent, the expression of Ets-1 mRNA and protein, its phosphorylation level and DNA binding activity were increased with enhancement of LMP1 expression. CONCLUSION: LMP1 induces transcriptional activation and expression of Ets-1 which may contribute to the development of NPC.

Carcinoma, Squamous Cell↗