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Biomedical subjects

Qing Wang

Publications and source records attributed to Qing Wang.

At least 37 records · Page 2Linked to original sources

Effects of high dose of simvastatin on levels of dopamine and its reuptake in prefrontal cortex and striatum among SD rats.

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.

Analysis of Variance↗

TGF-beta2 inhibition augments the effect of tumor vaccine and improves the survival of animals with pre-established brain tumors.

TGF-beta2 secretion by high grade gliomas has been implicated as one of the major factors contributing to tumor growth, alterations in the host immune response to tumor, and failure of gliomas to respond to current immunotherapy strategies. We hypothesized that targeted delivery and inhibition of TGF-beta2 by TGF-beta2 antisense oligonucleotides (AS-ODNs) would overcome tumor-induced immunosuppression and enhance the capacity of tumor vaccines to eradicate established brain tumors. Utilizing the mRNA sequences of TGF-beta2, specific AS-ODNs were constructed and tested for their ability to inhibit TGF-beta2 production in 9L glioma cells. The effect of combining local intracranial administration of antisense ODNs with systemic tumor vaccine was examined. Fisher 344 rats were vaccinated subcutaneously with irradiated 9L tumor cells 3 days after intracranial tumor implantation. Four days after vaccination, ODNs were administered into the tumor mass and survival was followed. ODNs delivered locally distributed widely within the brain tumor mass and inhibited TGF-beta2 expression. Survival of tumor-bearing rats treated with the combination of local antisense and systemic tumor vaccine was significantly enhanced (mean survival time (MST): 48.0 days). In contrast, MST for animals treated with nonsense plus vaccine, vaccine alone, antisense alone or PBS showed no survival advantage and no statistical differences between groups (33.5 days, 29.0 days, 37.5 days, and 31.5 days, respectively). Our data supports the hypothesis that local administration of antisense TGF-beta2 ODNs combined with systemic vaccination can increase efficacy of immunotherapy and is a novel, potentially clinically applicable, strategy for high-grade glioma treatment.

Animals↗

[The clinical forensic medicine identification on pseudoseizures after head trauma].

Two pseudoseizures after head trauma are reported. We summarize the clinical manifestation of pseudoseizures, and identify difference of pseudoseizures and Seizures after head trauma. The forensic identification of pseudoseizures after head trauma should base on the extend and position of cerebral trauma, sequelae focus in cerebral, and the clinical manifestation.

Adult↗

Regular cellular distribution of plasmids by oscillating and filament-forming ParA ATPase of plasmid pB171.

Centromere-like loci from bacteria segregate plasmids to progeny cells before cell division. The ParA ATPase (a MinD homologue) of the par2 locus from plasmid pB171 forms oscillating helical structures over the nucleoid. Here we show that par2 distributes plasmid foci regularly along the length of the cell even in cells with many plasmids. In vitro, ParA binds ATP and ADP and has a cooperative ATPase activity. Moreover, ParA forms ATP-dependent filaments and cables, suggesting that ParA can provide the mechanical force for the observed regular distribution of plasmids. ParA and ParB interact with each other in a bacterial two-hybrid assay but do not interact with FtsZ, eight other essential cell division proteins or MreB actin. Based on these observations, we propose a simple model for how oscillating ParA filaments can mediate regular cellular distribution of plasmids. The model functions without the involvement of partition-specific host cell receptors and is thus consistent with the striking observation that partition loci can function in heterologous host organisms.

Adenosine Triphosphatases↗

Effects of prolonged metoprolol treatment on neural remodeling and inducible ventricular arrhythmias after myocardial infarction in rabbits.

BACKGROUND: Neural remodeling is part of the pathophysiology of ventricular arrhythmias after myocardial infarction (MI). In this study, we developed a rabbit model of MI to investigate the effect of the beta-blocker metoprolol on ventricular neural remodeling and susceptibility to ventricular arrhythmias. METHODS: MI was induced by ligation of the left anterior descending coronary artery in 30 rabbits, and sham operations were performed in 12 control animals. Metoprolol was then administered to 15 of the MI animals. After electrophysiological recordings, the expression of nerve markers was studied at the infarct border and the non-infarct left ventricle free wall (LVFW) by immunostaining or RT-PCR. RESULTS: Eight weeks after MI, the incidence of inducible ventricular arrhythmias was significantly (P<0.01) higher in the MI group than in the sham group. However, metoprolol treatment decreased incidence of post-MI ventricular arrhythmias (8.3%) compared to those without treatment (58.3%, P<0.001). The density of nerve fibers was increased in MI group (3889+/-521 microm(2)/mm(2)) compared to the sham group (1727+/-304 microm(2)/mm(2)). Treatment of MI rabbits with metoprolol resulted in a partial reduction (2725+/-283 microm(2)/mm(2)). However, the shape and imbalance of nerve fibers appeared to be normalized by the metoprolol treatment. The expression levels of TH mRNA were reduced (P<0.01) by metoprolol treatment. CONCLUSION: Metoprolol reduces post-MI ventricular arrhythmias, partly by altering the neural remodeling process.

Adrenergic beta-Antagonists↗

A dielectric polymer with high electric energy density and fast discharge speed.

Dielectric polymers with high dipole density have the potential to achieve very high energy density, which is required in many modern electronics and electric systems. We demonstrate that a very high energy density with fast discharge speed and low loss can be obtained in defect-modified poly(vinylidene fluoride) polymers. This is achieved by combining nonpolar and polar molecular structural changes of the polymer with the proper dielectric constants, to avoid the electric displacement saturation at electric fields well below the breakdown field. The results indicate that a very high dielectric constant may not be desirable to reach a very high energy density.

Journal Article↗

A p21/WAF1 mutation favors the appearance of drug resistance to paclitaxel in human noncancerous epithelial mammary cells.

We investigated the mechanisms responsible for paclitaxel resistance in HME-1 cells (human mammary epithelial cells immortalized with hTERT). These cells were exposed to paclitaxel (10 pM for 7 days) and 20 cellular surviving populations (PSP) were obtained. PSP demonstrated high levels of resistance to paclitaxel cytotoxicity as compared with HME-1 cells. Activation of mdr-1 gene expression was observed in 2 PSP. Protein expression analysis using a C-terminal targeted antibody showed that 13 PSP were negative for p21/WAF1 expression after ionizing radiation (6 Gy) or doxorubicin (100 nM) treatment. Sequencing of the 3 exons of the CDKN1A gene revealed that 13 PSP contained a point mutation in exon 2. This mutation consisted in a T insertion at codon 104 leading to a premature STOP codon appearance. Mismatch amplification mutation assay and RFLP-PCR confirmed the presence of the mutation in 16 PSP. Western blot using an N-terminal targeted antibody demonstrated that the C-terminal-truncated p21/WAF1 protein (14 kDa) was indeed expressed in the 13 PSP. Our data suggest that p21/WAF1 inactivation may confer a strong resistance to paclitaxel in noncancerous breast epithelial cells harboring a p21/WAF1 mutant.

Amino Acid Sequence↗

Ultrasound elastomicroscopy using water jet and osmosis loading: potentials for assessment for articular cartilage.

Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimeters, but this is not sufficient for applications to skin, articular cartilage, or other fine structures. In this paper, we introduced two methods of ultrasound elastomicroscopy using water jet and osmosis loading for imaging the elasticity of biological soft tissues with high resolutions. In the first system, the specimens were compressed using water jet compression. A water jet was used to couple a focused 20 MHz ultrasound beam into the specimen and meanwhile served as a "soft" indenter. Because there was no additional attenuation when propagating from the ultrasound transducer to the specimen, the ultrasound signal with high signal-to-noise ratio could be collected from the specimens simultaneously with compressing process. The compression was achieved by adjusting the water flow. The pressure measured inside the water pipe and that on the specimen surface was calibrated. This system was easily to apply C-scan over sample surfaces. Experiments on the phantoms showed that this water jet indentation method was reliable to map the tissue stiffness distribution. Results of 1D and 2D scanning on phantoms with different stiffness are reported. In the second system, we used osmotic pressure caused by the ion concentration change in the bathing solutions for the articular cartilage to deform them. When bovine articular cartilage specimens were immerged in solutions with different salt concentration, a 50 MHz focused ultrasound beam was used to monitor the dynamic swelling or shrinkage process. Results showed that the system could reliably map the strain distribution induced by the osmotic loading. We extract intrinsic layered material parameters of the articular cartilage using a triphasic model. In addition to biological tissues, these systems have potential applications for the assessment of bioengineered tissues, biomaterials with fine structures, or some engineering materials. Further studies are necessary to fully realize the potentials of these two new methods.

Algorithms↗

A modular approach to ferroelectric polymers with chemically tunable curie temperatures and dielectric constants.

We present a modular approach toward poly(vinylidene fluoride)-based ferroelectric fluoropolymers with high dielectric constants. This strategy is based on a two-step reaction, including the copolymerization of vinylidene fluoride and chlorotrifluoroethylene and a subsequent hydrogenation reaction. The chemical structures and compositions of the resulting polymers can be precisely controlled, leading to tunable Curie temperatures and dielectric constants and a systematical study of structure-property correlations.

Journal Article↗

Electrical switching of DNA monolayers investigated by surface plasmon resonance.

The switching of DNA monolayers between a "lying" and a "standing" state initiated by applying electric field, and the subsequent DNA hybridization at different states were investigated in a contactless, label-free mode by surface plasmon resonance (SPR) technique. The results showed that the strength of the electric field and surface coverage could influence the switching of DNA monolayers. In addition, it was found that DNA hybridization efficiency could be enhanced or decreased when DNA probes stood straight up or lay flat on the gold surface, depending on the potential of the gold substrate. The enhancement of DNA hybridization efficiency reached the maximum when surface coverage reached 5.87 x 10(12) molecules/cm(2) and the potential of gold substrate was more negative than -0.7 V (versus ITO-coated glass). The research may be helpful for the construction of sensitive biosensors, biochips, and nanoscale electronic devices.

Base Sequence↗

Cooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemia.

1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D(3) in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D(-) murine myelomonocytic leukemia cells induced by 1 nM 1,25D(3) or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 microM) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0 + G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 microg Ro25-4020 in Balb/c mice bearing WEHI-3B D(-) tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 microg Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia.

Abietanes↗

Three-channel transmission line impedance model for mesoscopic oxide electrodes functionalized with a conductive coating.

A three-channel transmission line (TL) impedance model is proposed to address the charge transport behavior of molecular functionalized mesoscopic oxide electrodes at different bias conditions. A full general solution of the three-channel TL for the system is provided in this paper. Selected experimental results of impedance spectroscopy of mesoscopic Al2O3 and TiO2 networks, covered with a monolayer of Ru complex cis-RuLL'(NCS)2 (L = 2,2'-bipyridyl-4,4'-dicarboxylic acid, L' = 4,4'-dinonyl-2,2'-bipyridyl) (Z907), are briefly discussed. It shows that the model constitutes a useful tool for characterizing nanoporous electrodes functionalized with organic conducting layers in the surface. The model makes it possible to determine the separate conductivity of substrate oxide and molecular layer, and interfacial charge transfer, in the functionalized nanostructured electrodes.

Journal Article↗

Down-regulation of PTEN by sodium orthovanadate inhibits ASK1 activation via PI3-K/Akt during cerebral ischemia in rat hippocampus.

In this study, we examined the phosphorylation of ASK1, Akt and PTEN and the effects of sodium orthovanadate on these signal proteins during ischemia. Transient (15 min) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. The following results were observed: (1) the decreased tyrosine phosphorylation of PTEN and the decreased serine phosphorylation of Akt induced by ischemia were suppressed by sodium orthovanadate, respectively. (2) The phosphorylation of ASK1 at serine 83 was decreased and the phosphorylation of ASK1 at threonine 845 was increased during ischemia. Sodium orthovanadate could alter the phosphorylation status of ASK1 at serine 83 and threonine 845 induced by ischemia. However, LY294002 could reverse the effect of sodium orthovanadate on the phosphorylation of ASK1 at threonine 845, namely, sodium orthovanadate inhibited ASK1 through the PI3-K/Akt-dependent pathway. Taken together, we concluded that sodium orthovanadate could increase the tyrosine posphorylation of PTEN and further inhibit the activation of ASK1 via activating Akt during cerebral ischemia.

Animals↗

Enhanced surface plasmon resonance with the modified catalytic growth of Au nanoparticles.

The catalytic growth of Au nanoparticles (AuNPs) has been employed in several analytical methods for improving the detection sensitivity, or integrated with the enzyme reactions for the quantitative detection of the respective substrates. However, the catalytic growth of Au nanoparticles do not work in some situations, such as surface plasmon resonance (SPR), electrochemistry, where metal matrices were used, because metal matrices used in these techniques, e.g. Au, are susceptible to metal deposition, which increased the background seriously. In this work, a SiO(2) layer was vapor-deposited on the gold film. The inhibition of metal deposition by this SiO(2) layer was investigated by SPR sensor. The results showed that the SiO(2) layer could avoid the deposition of metal on Au film. With the low background achieved by SiO(2)-coated Au films, sensitive detection of DNA hybridization using the catalytic growth of Au nanoparticles enhanced SPR was demonstrated. The work described here maybe helpful for the development of sensitive bioanalytical methods.

Catalysis↗

Germline mutations of the PTCH gene in families with odontogenic keratocysts and nevoid basal cell carcinoma syndrome.

BACKGROUND/AIMS: Odontogenic keratocysts (OKC) are aggressive lesions in the jaws, which can occur as isolated cases or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations on PTCH gene have been identified in patients with NBCCS. It was hypothesized that PTCH mutations may be causative in isolated OKC. This study aims to investigate germline mutations of PTCH in families with OKC and NBCCS. METHODS: Three Chinese families with OKC and NBCCS were enrolled in the study. The diagnosis was based on examination and medical history. Mutation analysis was performed by amplifying all exons of PTCH and sequencing the products. RESULTS: One family with isolated OKC (family 1) and the other two families with NBCCS were diagnosed. Three novel germline mutations in PTCH were identified, including a missense mutation (p.S1089 > P) in family 1, a nonsense mutation (p.Q160X) in family 2 and a de novo mutation (c.768_777delGACAAACTTC) in family 3. CONCLUSIONS: It is proposed that isolated OKC can be inherited in an autosomal dominant mode. The results suggest that germline mutations on PTCH can cause isolated OKC, and that the PTCH gene responsible for NBCCS plays an important role in the formation of OKCs even when they are not syndrome-related.

Adult↗

Differential responsiveness of dopamine-beta-hydroxylase gene expression to glucoprivation in different catecholamine cell groups.

Hindbrain catecholaminergic neurons are key participants in systemic glucoregulation. However, the specific subpopulations critical for glucoregulatory function have not been fully identified. Here we used in situ hybridization and immunohistochemistry to investigate effects of glucoprivation on expression of the gene for the catecholamine biosynthetic enzyme, dopamine-beta-hydroxylase (DBH), to further localize the critical cell populations. Glucoprivation induced by the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) (250 mg/kg) increased total DBH mRNA expression in caudal ventrolateral medullary cell groups (namely A1, the A1/C1 overlap, and the middle portion of C1) from six to 49 times control levels. In retrofacial C1, no enhancement was observed. In the dorsomedial medulla, hybridization signal was modestly increased (tripled) in A2 but was not increased in the area postrema. Previous microinjection of the retrogradely transported catecholamine immunotoxin (anti-DBH-saporin, or DSAP) into the paraventricular nucleus of the hypothalamus reduced the number of DBH-immunoreactive cells in cell groups known to project to the paraventricular nucleus of the hypothalamus as well as reducing the 2DG-stimulated increases in total DBH mRNA expression in the caudal ventrolateral medulla and A2. The strong enhancement of DBH gene expression by glucoprivation is consistent with the demonstrated importance of catecholaminergic neurons for glucoregulation. The differential sensitivity of these neurons to glucoprivation is evidence of functional specialization within the total population. The pattern of 2DG-induced gene expression indicates that the ventrolateral medulla contains the vast majority of catecholamine neurons responsive to glucoprivation.

Animals↗

Molecular wiring of nanocrystals: NCS-enhanced cross-surface charge transfer in self-assembled Ru-complex monolayer on mesoscopic oxide films.

We report on rapid ambipolar cross-surface charge transfer within self-assembled monolayers (SAM) of the heteroleptic Ru-complexes cis-RuLL'(NCS)(2) (L = 2,2'-bipyridyl-4,4'-dicarboxylic acid, L' = 4,4'-dinonyl-2,2'-bipyridyl) (1) and cis-RuLL' '(NCS)(2) (L = 2,2'-bipyridyl-4,4'-dicarboxylic acid, L' = 4,4'-dimethyl-2,2'-bipyridyl) (2) on the surface of mesoscopic insulating oxide films. The bipyridyl ligands of the Ru-complex transport electrons, while the NCS groups plays a pivotal role in mediating surface confined hole percolation. Molecular dynamics calculations show the NCS ligands of 1 and 2 to orient in a fashion that enhances the overlap of the HOMOs of neighboring ruthenium complexes. Using ab initio Hartree-Fock calculations the electronic coupling matrix element for intermolecular hole exchange at the surface is estimated to be 0.13 eV. Cyclic voltammetry as well as spectroelectrochemical and impedance measurements performed with a series of other Ru-complexes confirmed the control of the cross surface charge transfer by the molecular structure. Complex 2 shows the highest percolation rate, the surface hole diffusion coefficient being 1.1 x 10(-8) cm(2)/s. The effects of the ligand properties, such as denticity, geometry, and size, on the intermolecular charge transport are discussed in detail.

Journal Article↗

Globular adiponectin decreases leptin-induced tumor necrosis factor-alpha expression by murine macrophages: involvement of cAMP-PKA and MAPK pathways.

Several lines of evidence have supported a link between obesity and inflammation. The present study investigated the capacity of leptin and globular adiponectin to affect tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal macrophages. Leptin stimulated TNF-alpha production at mRNA as well as protein levels in a dose- and time-dependent manner. Intracellular cAMP concentration was increased and protein kinase A (PKA) was activated with the treatment of leptin, subsequently downstream MAPK signal proteins, ERK1/2 and p38, were phosphorylated. Specific inhibitors for the signal proteins, Rp cAMPS, H89, PD98059, and U0126, or SB203580, suppressed the signaling pathway and TNF-alpha expression. Although gAd partially increased cAMP concentration and PKA activity, it directly reduced leptin-induced ERK1/2 and p38 MAPK phosphorylation thus inhibiting TNF-alpha production. In conclusion, leptin promotes inflammation by stimulating TNF-alpha production, which is mediated by cAMP-PKA-ERK1/2 and p38 MAPK pathways. gAd inhibited leptin-induced TNF-alpha production through suppressing phosphorylation of ERK1/2 and p38 pathways.

Adiponectin↗