Biomedical subjects

Hai Wang

Publications and source records attributed to Hai Wang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Chiral separation of ketoprofen on an achiral C8 column by HPLC using norvancomycin as chiral mobile phase additives.

A high-performance liquid chromatographic method for chiral separation of ketoprofen racemate was developed. (R)- and (S)-ketoprofen enantiomers were separated on a Hypersil BDS C8 column (150 mm x 4.6 mm i.d., 5 microm) at 25 degrees C, using acetonitrile-triethylamine acetate (TEAA) buffer (pH 5.2, 20 mM) (35:65, v/v) containing 2.0 mM norvancomycin as the mobile phase. Effects of norvancomycin concentration, content of acetonitrile and TEAA buffer pH on the enantioseparation were investigated. The method was validated for linearity, repeatability, limits of detection (LOD) and limits of quantification (LOQ). Calibration curves (r2 = 0.999) were constructed in the range of 2.01-200.8 microg ml(-1) for (S)-ketoprofen and 2.04-152.4 microg ml(-1) for (R)-ketoprofen, respectively. Repeatability (n = 5) showed less than 2% relative standard deviation (R.S.D.). LOD and LOQ for the two enantiomers were found to be 0.20 and 0.78 ng for (S)-ketoprofen, 0.20 and 0.86 ng for (R)-ketoprofen, respectively. Norvancomycin and vancomycin as chiral mobile phase additives (CMPAs) in the chiral separation showed similar abilities of enantioseparation. However, to obtain the optimum enantioseparation, a lower concentration of norvancomycin than that of vancomycin is required.

Calibration↗

PubMed2005

Non-neuronal nicotinic alpha 7 receptor, a new endothelial target for revascularization.

Alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) is widely expressed in the central and peripheral nervous systems, and is also found in several non-neuronal tissues, such as endothelial cells (ECs), bronchial epithelial cells, skin keratinocytes and vascular smooth muscle cells. Recent evidence suggests that alpha7 nAChR is involved in angiogenesis. Here, we investigated the feasibility of alpha7 nAChR for revascularization in ischemic heart disease. RT-PCR and immunohistochemistry were used to examine the expression of alpha7 nAChR in human umbilical vein endothelial cell (HUVECs). The cellular function was examined using MTT, fluorescence confocal microscopy and angiogenesis assay in vitro. The capillary density in the rat model of myocardial infarction (MI) was investigated using immunohistochemistry. The results showed that alpha7 nAChR agonists choline increased the expression of alpha7 nAChR mRNA and protein, the intracellular Ca 2+ concentration, proliferation and tube formation of ECs. Reverse effects were observed by using alpha7 nAChR antagonist alpha-BTX. Furthermore, in the rat model of MI, alpha7 nAChR agonist enhanced the capillary density in ischemic tissues, whereas antagonist mecamylamine and alpha-BTX inhibited the effect. Our results suggest that alpha7 nAChR is involved in the regulation of cellular function in ECs, and capillary formation in MI, which are the important steps of angiogenesis. Therefore, alpha7 nAChR on ECs may be a new endothelium target for revascularization in therapeutic angiogenesis of ischemic heart disease.

Animals↗

PubMed2005

Iptakalim, opener of K(ATP), reverses the enhanced expression of genes encoding K(ATP) subunits in spontaneously hypertensive rats.

ATP-sensitive potassium channels (K(ATP)) are thought to be targets for antihypertensive drugs that are potassium channel openers. In this study, the expression of genes encoding the K(ATP) subunits, SUR2, Kir6.1 and Kir6.2, was detected in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and SHR undergoing long-term treatment with iptakalim, a novel antihypertensive drug that acts via K(ATP). The transcript levels for SUR2, Kir6.1 and Kir6.2 in the heart, aortic smooth muscle, and tail artery smooth muscle were determined by reverse transcription-polymerase chain reaction (RT-PCR). In general, Kir6.2 and SUR2 were more highly represented in all SHR tissues compared with those of WKY, and transcripts of Kir6.2 were significantly higher in tail artery smooth muscle from SHR. Following long-term treatment with iptakalim, mRNA levels of Kir6.2 and SUR2 were reduced significantly in all tissues compared with those of untreated SHR. Kir6.1 expression was not significantly different between SHR and WKY, and was unaffected by iptakalim treatment. These results indicate that the expression of the K(ATP) subunits genes, SUR2 and Kir6.2, are closely associated with hypertensive pathological states, and the effect of iptakalim on K(ATP) mRNA levels may explain, in part, the effects of iptakalim in reversing vascular and cardiac remodeling. Furthermore, changes in Kir6.2 mRNA levels suggest that Kir6.x, as well as SUR, is responsible for drug binding.

ATP-Binding Cassette Transporters↗

PubMed2005

Iptakalim as a human nicotinic acetylcholine receptor antagonist.

Nicotinic acetylcholine receptors (nAChRs) play many critical roles in nervous system function and have been implicated in a variety of diseases. Drugs acting at nAChRs, perhaps in nAChR subtype-selective manners, can be used to dissect receptor function and perhaps as medications. In the present study, we used patch-clamp whole-cell recording and pharmacological manipulations to evaluate effects of iptakalim hydrochloride (Ipt), which is a drug reported to act as an ATP-sensitive potassium (K(ATP)) channel opener, on selected human nAChRs heterologously expressed in the native nAChR-null SH-EP1 human epithelial cell line. Ipt reduced both peak and steady-state whole-cell current amplitudes mediated by human alpha4beta2-nAChRs in response to nicotinic agonists. It also accelerated current decay, caused a decline in apparent efficacy of agonists, and acted in voltage- and use-dependent manners at alpha4beta2-nAChRs. These findings and the inability of Ipt to block radiolabeled epibatidine binding to alpha4beta2-nAChRs suggest a noncompetitive mechanism of antagonism. Other studies discount effects of Ipt on nAChR internalization or involvement of K(ATP) channels in Ipt-induced inhibition of alpha4beta2-nAChR function. By comparison, alpha7-nAChRs were less sensitive than alpha4beta2-nAChRs to Ipt acting as an antagonist. Thus, alpha4beta2-nAChRs are among the molecular targets of Ipt, which has utility as a tool in functional characterization and pharmacological profiling of nAChRs.

Binding, Competitive↗

PubMed2005

[Synergistic effect of bromocriptine combining tumor necrosis factor-alpha on reversing multidrug resistance in a nude mouse model of liver neoplasm].

OBJECTIVE: To investigate synergistic effect of bromocriptine (BCT) combining tumor necrosis factor-alpha (TNF-alpha) on reversing multidrug resistance in a nude mouse model of liver neoplasm. METHODS: Human hepatocarcinoma cell line HepG(2) (HepG(2) group), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (HepG(2)/ADM group) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF (TNF group and BCT group) were injected into the liver of nude mice via orthotopic implantation to establish multidrug resistance model of liver neoplasm in vivo. All the mice were injected with 5-fluouracil + adriamycin + mitomycin in abdominal cavity for 7 d. The mice in BCT group was simultaneously given bromocriptine through gastric canal. Size and weight of the tumor were measured. Furthermore tumor histological character and growth of the nude mice was observed and its chemosensitivity was tested. MDR associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemical staining and reverse transcriptive polymerase chain reaction (RT-PCR), and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS: The nude mouse model of each cell line was all inoculated successfully. The tumor growth rate and weight were significantly different among groups (P < 0.05). After chemotherapy tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups (P < 0.01), and similar to HepG(2) group (54%). MDR1 and LRP mRNA could be detected in all groups, but TNF-alpha was detected only in TNF-alpha and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF-alpha and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups (P < 0.05) with TUNEL assay. CONCLUSIONS: TNF-alpha gene can down-regulate the MDR associated genes and proteins expression for example MDR1, LRP, and lower its tumorgenesis. Moreover, bromocriptine can enhance the susceptibility of HepG(2)/ADM cells to cytotoxic drugs.

Animals↗

PubMed2005

Thermal decomposition of ethylene oxide: potential energy surface, master equation analysis, and detailed kinetic modeling.

The unimolecular decomposition of ethylene oxide (oxirane) and the oxiranyl radial is examined by molecular orbital calculations, Rice-Ramsperger-Kassel-Marcus (RRKM)/Master Equation analysis, and detailed kinetic modeling of ethylene oxide pyrolysis in a single-pulse shock tube. It was found that the largest energy barrier to the decomposition of ethylene oxide lies in its initial isomerization to form acetaldehyde, and in agreement with previous studies, the isomerization was found to proceed through the *CH2CH2O* biradical. Because of the biradical nature of the transition states and intermediate, the energy barriers for the initial C-O rupture in ethylene oxide and the subsequent 1,2-H shift remain highly uncertain. An overall isomerization energy barrier of 59 +/- 2 kcal/mol was found to satisfactorily explain the available single pulse shock tube data. This barrier height is in line with the estimates made from an approximate spin-corrected procedure at the MP4/6-31+G(d) and QCISD(T)/6-31G(d) levels of theory. The dominant channel for the unimolecular decomposition of ethylene oxide was found to form CH3 + HCO at around the ambient pressure. It accounts for >90% of the total rate constant for T > 800 K. The high-pressure limit rate constant for the unimolecular decomposition of ethylene oxide was calculated as k(1,infinity)(s(-1)) = (3.74 x 10(10))T(1.298)e(-29990/T) for 600 < T < 2000 K.

Journal Article↗

PubMed2005

Baculovirus-mediated promoter assay and transcriptional analysis of white spot syndrome virus orf427 gene.

BACKGROUND: White spot syndrome virus (WSSV) is an important pathogen of the penaeid shrimp with high mortalities. In previous reports, Orf427 of WSSV is characterized as one of the three major latency-associated genes of WSSV. Here, we were interested to analyze the promoter of orf427 and its expression during viral pathogenesis. RESULTS: in situ hybridization revealed that orf427 was transcribed in all the infected tissues during viral lytic infection and the translational product can be detected from the infected shrimp. A time-course RT-PCR analysis indicated that transcriptional products of orf427 could only be detected after 6 h post virus inoculation. Furthermore, a baculovirus-mediated promoter analysis indicated that the promoter of orf427 failed to express the EGFP reporter gene in both insect SF9 cells and primary shrimp cells. CONCLUSION: Our data suggested that latency-related orf427 might not play an important role in activating virus replication from latent phase due to its late transcription during the lytic infection.

Journal Article↗

PubMed2005

Hepatic and extrahepatic expression of vitellogenin genes in the zebrafish, Danio rerio.

Vitellogenins (Vtgs) are yolk precursor proteins in oviparous species and are cleaved into three portions-lipovitellin I (LVI), phosvitin (PV), and lipovitellin II (LVII)-in oocytes in vertebrates. In the present study, we found that the zebrafish genome contains at least seven vtg genes (vtg1-7) encoding heterogeneous vitellogenins with three distinct types of Vtgs: type I (Vtg1, 4-7) contains all the three major portions but lacks the C-terminal half of LVII; type II (Vtg2) is the only one including intact three portions; type III (Vtg3) lacks both PV and the LVII C-terminal half. The seven vtgs were located in two different chromosomes: one (vtg3) in LG11 and the rest closely linked in LG22, probably arisen from local gene duplication events. All of the seven vtgs are predominantly expressed in female liver and can be induced in male liver by 17beta-estradiol (E2). The level of vtg1 mRNA was about 100x and 1000x higher than those of vtg2 and vtg3 mRNAs. We also found vtg mRNAs in several non-liver tissues, but the expression level is generally <10% of that in the liver. In situ hybridization experiments confirmed that the extrahepatic expression was actually in adipocytes associated with several organs such as the intestine, ovary, and E2-induced testis.

Adipocytes↗

PubMed2005

A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats.

The effects of iptakalim, a new ATP-sensitive potassium channel opener, were studied in spontaneously hypertensive rats (SHR). Treatment of 12-week-old male SHR (six animals in each group) with iptakalim by gastric lavage at doses of 1, 3, or 9 mg/kg/day for 12 weeks resulted in a lowering of blood pressure. Iptakalim provided significant renoprotection to SHR rats as measured by decreased proteinuria and improved renal function. Histological evidence demonstrated that iptakalim could reverse renal vascular remodeling (of afferent arterioles, arcuate arteries, or interlobular arteries), and improve pathological changes of glomerular, renal interstitial, and glomerular filtration membranes. These effects were accompanied by the decreased circulation and intrarenal concentrations of endothelin 1 and transforming growth factor beta1 (TGF-beta1), and down-regulated overexpression of genes for ET-1, endothelin-converting enzyme 1, TGF-beta1, and the subunits of ATP-sensitive potassium channels (K(ATP)), Kir1.1 and Kir6.1, in the kidney during hypertension. Abnormal expression of matrix components [collagen IV, fibronectin, matrix metalloproteinase 9 (MMP-9) and MMP tissue inhibitor 1 (TIMP-1)] was also significantly reversed by iptakalim. Our results demonstrate that chronic treatment with iptakalim not only reduces blood pressure but also preserves renal structure and function in SHR. In addition to reducing blood pressure, the renoprotective of iptakalim may be involved in inhibiting the circulation and intrarenal concentrations of endothelin 1 and TGF-beta1, regulating the expression of K(ATP) genes and correcting MMP-9/TIMP-1 imbalance in renal tissue, which may result in reducing the accumulation of extracellular matrix molecules.

ATP-Binding Cassette Transporters↗

PubMed2005

Gas-nanoparticle scattering: a molecular view of momentum accommodation function.

We examine the origin of diffuse gas-particle scattering by molecular dynamics simulation and show that diffuse scattering is the consequence of gas molecule trapping on the particle surface. Trapping occurs because of gas-particle interactions and the particle's ability of energy accommodation. These observations explain the transition from specular-to-diffuse scattering as the particle size becomes larger than the molecular size. We discuss the implication of this transition on the transport properties of nanometer-size particles.

Journal Article↗

PubMed2005

Redox-induced synthesis and encapsulation of metal nanoparticles in shell-cross-linked organometallic nanotubes.

A new approach to encapsulate silver nanoparticles inside block copolymer nanotubes is reported and involves an in situ redox reaction between a polyferrocenylsilane (PFS) inner wall and silver ions. Partial preoxidation of the PFS domains was found to be a key step for the efficient formation of one-dimensional arrays of silver nanoparticles confined within the nanotubes.

Ferrous Compounds↗

PubMed2005

Activation of mitochondrial ATP-sensitive potassium channels improves rotenone-related motor and neurochemical alterations in rats.

Our previous studies revealed that activation of mitochondrial ATP-sensitive potassium channels exerted protective effects on rotenone-treated rats and cultured cells. The aim of the present study is to examine the potential therapeutic effects of iptakalim, an ATP-sensitive potassium-channel opener, and diazoxide, a selective mitochondrial ATP-sensitive potassium-channel opener, on Parkinsonian symptoms in rats induced by rotenone. Rats were treated with rotenone (2.5 mg/kg s.c.) daily for 4 wk. This treatment caused a depletion of dopamine in the striatum and substantia nigra. Behaviourally, rotenone-infused rats exhibit Parkinsonian symptoms. Catalepsy was estimated by a 9-cm bar test. Treatment with L-dopa (10 mg/kg.d p.o.), iptakalim (0.75, 1.5, 3.0 mg/kg.d p.o.) and diazoxide (3.0 mg/kg.d p.o.) for 2 wk improved behavioural dysfunction and elevated dopamine contents in the striatum and substantia nigra of rotenone-treated rats. Studies also found that iptakalim and diazoxide could reduce the enzymic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. All neurorestorative effects by both iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium-channel blocker. Collectively, the data suggested that mitochondrial ATP-sensitive potassium channels play a key role in improving both Parkinsonian symptoms and neurochemistry alterations of rotenone model rats, and selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for treatment of early Parkinson's disease.

Animals↗

PubMed2005

Remarkable nanosize effect of zirconia in Au/ZrO2 catalyst for CO oxidation.

Nanosize effect of ZrO2 in Au/ZrO2 catalyst was studied by deposition-precipitation of Au nanoparticles in similar sizes (4-5 nm) on ZrO2 nanoparticles of varying sizes. The catalysts were characterized with XRD, TEM, XPS, and nitrogen adsorption to understand the effect of ZrO2 particle size on the catalytic nanostructures. Nanocomposite Au/ZrO2 catalysts consisting of comparably sized Au-metal (4-5 nm) and ZrO2 (5-15 nm) nanoparticles are found advantageous over those containing similarly sized Au-metal but larger ZrO2 (40-200 nm) particles for CO oxidation. This finding may have important implications on the designed preparation of advanced nanostructured catalysts and other chemical materials.

Journal Article↗

PubMed2005

Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats.

Our previous studies revealed that iptakalim, a novel ATP-sensitive potassium channel opener, has a significant neuroprotective function against ischemia in vivo or rotenone-induced neurotoxicity in vitro. To investigate the potential pharmaceutical benefit of ATP-sensitive potassium channel openers on neurodegenerative diseases, we studied the effects of iptakalim and diazoxide, a selective mitochondrial ATP-sensitive potassium channel opener, on the rotenone-induced nigrostriatal degeneration in rats. Iptakalim (1.5 mg/kg/day, orally) or diazoxide (1.5 mg/kg/day, orally) alone was administered to rats for 3 days, and then for 4 weeks was used daily with an injection of rotenone (2.5 mg/kg/day, subcutaneously) 1 hr later each time. The results showed that rotenone-infused rats exhibited parkinsonian symptoms and had dopamine depletion in the striatum and substantia nigra. Pretreatment with iptakalim or diazoxide prevented rotenone-induced catalepsy and the reduction of striatum dopamine contents. Moreover, iptakalim and diazoxide reduced the enzymatic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. These neuroprotective effects of iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. In conclusion, our data suggested that mitochondrial ATP-sensitive potassium channels might play a key role in preventing both parkinsonian symptoms and neurochemistry alterations induced by rotenone in rats. The selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for prevention and treatment of neurodegenerative disorders such as Parkinson's disease.

ATP-Binding Cassette Transporters↗

PubMed2005

Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells.

ATP-sensitive potassium (K(ATP)) channels of pulmonary arterial smooth muscle cells (SMCs) have been implicated in pulmonary hypertension. Iptakalim, designed and synthesized by ourselves, is a newly selective K(ATP) channel opener. Here, we explored the effects of iptakalim on the rise of cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) induced by endothelin-1 (ET-1) and on the proliferation of cultured rabbit pulmonary arterial SMCs. The results showed that iptakalim inhibited the [Ca(2+)](cyt) increase. The enhanced [(3)H]thymidine incorporation was inhibited and the transition of cells from static phase (G(0)/G(1)) to DNA synthesis (S) and mitotic phase (G(2)/M) was held back by iptakalim in a concentration-dependent manner. Glyburide abolished the inhibitory effect of iptakalim. In conclusion, we have shown that iptakalim had an inhibitory effect on [Ca(2+)](cyt) increase and the proliferation of pulmonary arterial SMCs induced by endothelin-1 through activation of K(ATP) channels. These findings suggest that iptakalim might be a promising candidate for the treatment of pulmonary arterial remodeling in pulmonary hypertension.

ATP-Binding Cassette Transporters↗

PubMed2005

Copper toxicity and bioaccumulation in Chinese cabbage (Brassica pekinensis Rupr.).

Copper is among the major heavy metal contaminants in the environment with various anthropogenic and natural sources. Human health risk from heavy metal bioaccumulation in vegetables has been a subject of growing concern in recent years. To investigate Cu phytotoxic effects and bioaccumulation in the popular vegetable Chinese cabbage (Brassica pekinensis Rupr) as well as the implications for human health due to Cu in the vegetable supply, seed germination and pot culture experiments with this vegetable were carried out. Six levels (0, 0.008, 0.031, 0.125, 0.5, and 2.0 mM/L) and 3 levels (0, 0.2, and 1.0 mM/kg) of Cu treatments were performed for the seed germination and pot culture experiments, respectively. The LC(50) of Cu for seed germination of Chinese cabbage was 0.348 mM/L. In the pot culture experiments, Cu treatments significantly increased electrolyte leakage and peroxidase activity of shoot tissues, demonstrating Cu phytotoxicity to the plants. On the other hand, Cu treatments significantly stimulated, instead of reduced, chlorophyll content. Cu treatments did not show a significant effect on shoot biomass. Compared to the control, Cu treatments significantly elevated the Cu content of the shoots-9.9, 42.5, and 119.0 mg/kg (DW) of Cu were detected in the 0, 0.2, and 1.0 mM/kg treatments, respectively. These results showed that although the plants accumulated an elevated copper content and suffered damage to some extent under Cu treatment, they looked healthy. It was suggested that Chinese cabbage with an elevated Cu content and without showing visible symptoms of damage possibly could cause a risk to human health from the transfer of the metal in food.

Biomass↗

PubMed2005

Reversal of HCC drug resistance by using hammerhead ribozymes against multidrug resistance 1 gene.

To reverse multidrug resistance(MDR) of HepG2 by anti-MDR1 hammerhead ribozyme, an anti-MDR1 hammerhead ribozyme was developed and delivered to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase III promoter. The expression of mdr1/Pgp and Rz was detected in HepG2, HepG2 multidrug-resistant cell line and HepG2 Rz-transfected cells by semi-quantitative RT-PCR and Western blot methods. Moreover, MTT assay was employed to detect the sensitivity of these ribozyme-transfected cells, and Rhodamine123 (Rh123) was used to test the function of Pgp. The Rz- transfected HepG2 cells became doxorubicin-sensitive, which was concomitant with the decreased MDR1 expression. The study showed that the retrovirus vector encoding the anti-MDR1 ribozyme may be applicable to the treatment of MDR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Desensitized nicotinic receptors in brain.

Desensitization is an intriguing characteristic of ligand-gated channels, whereby a decrease or loss of biological response occurs following prolonged or repetitive stimulation. Nicotinic acetylcholine receptors (nAChRs), as a member of transmitter gated ion channels family, also can be desensitized by continuous or repeated exposure to agonist. Desensitization of nicotinic receptors can occur as a result of extended nicotine exposure during smoking or prolonged acetylcholine when treatment of Alzheimer's disease (AD) with cholinesterase inhibitors, or anticholinesterase agent poisoning. Studies from our lab have shown that nAChRs desensitization is not a nonfunctional state and we proposed that desensitized nAChRs could increase sensitivity of brain muscarinic receptor to its agonists. Here, we will review the regulation of nicotinic receptor desensitization and discuss the important biological function of desensitized nicotinic receptors in light of our previous studies. These studies provide the critical information for understanding the importance of nicotinic receptors desensitization in both normal physiological processing and in various disease states.

Animals↗