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Biomedical subjects

Ling Wang

Publications and source records attributed to Ling Wang.

At least 37 records · Page 2Linked to original sources
PubMed2006

In situ fabrication of a water-soluble, self-doped polyaniline nanocomposite: the unique role of DNA functionalized single-walled carbon nanotubes.

Dispersion of carbon nanotubes into solvents affects their surface chemistries, electronic structures, and subsequent functionalization. In this Communication, a water-soluble self-doped polyaniline nanocomposite was fabricated by in situ polymerization of the 3-aminophenylboronic acid monomers in the presence of single-stranded DNA dispersed- and functionalized-single-walled carbon nanotubes. For the first time, we found that the carbon nanotubes became novel active stabilizers owing to the DNA functionalization. The nanotubes reduced the polyaniline backbone from the unstable, degradable, fully oxidized pernigraniline state to the stable, conducting emeraldine state because of their reductive ability, which could improve the chemical stability of the self-doped polyaniline. Electrical measurements demonstrate that the conductivity of the nanocomposite was much higher than that of the pure self-doped polyaniline in both acidic and neutral solutions.

4-Aminobenzoic Acid↗
PubMed2006

Low-energy dynamics of the two-dimensional S=1/2 Heisenberg antiferromagnet on percolating clusters.

We investigate the quantum dynamics of site diluted S=1/2 Heisenberg antiferromagnetic clusters at the 2D percolation threshold. We use Lanczos diagonalization to calculate the lowest excitation gap Delta and, to reach larger sizes, use quantum Monte Carlo simulations to study an upper bound for Delta obtained from sum rules involving the staggered structure factor and susceptibility. Scaling the gap distribution with the cluster length L, Delta approximately L(-), we obtain a dynamic exponent z approximately 2D(f), where D(f)=91/48 is the fractal dimensionality of the percolating cluster. This is in contrast with previous expectations of z=D(f). We argue that the low-energy excitations are due to weakly coupled effective moments formed due to local imbalance in sublattice occupation.

Journal Article↗
PubMed2006

DFT study of new bipyrazole derivatives and their potential activity as corrosion inhibitors.

In the present work, a theoretical study of five bipyrazolic-type organic compounds, 4-{bis[(3,5-dimethyl-1H-pyrazolyl-1-yl)methyl]-amino}phenol (1), N1,N1-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl}]-N4,N4-dimethyl-1,4-benzenediamine (2), N,N-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]aniline (3), 4-[bis(3,5-dimethyl pyrazol-1-yl-methyl)-amino]butan-1-ol (4) and ethyl4-[bis(3,5-dimethyl-1H-pyrazol-1-yl-methyl) aminobenzoate] (5), has been performed using density functional theory (DFT) at the B3LYP/6-31G(d) level in order to elucidate the different inhibition efficiencies and reactive sites of these compounds as corrosion inhibitors. The efficiencies of corrosion inhibitors and the global chemical reactivity relate to some parameters, such as EHOMO, ELUMO, gap energy (DeltaE) and other parameters, including electronegativity (chi), global hardness (eta) and the fraction of electrons transferred from the inhibitor molecule to the metallic atom (DeltaN). The calculated results are in agreement with the experimental data on the whole. In addition, the local reactivity has been analyzed through the Fukui function and condensed softness indices.

Binding Sites↗
PubMed2006

AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts.

The growth of solid tumors is dependent on the continued stimulation of endothelial cell proliferation and migration resulting in angiogenesis. The angiogenic process is controlled by a variety of factors of which the vascular endothelial growth factor (VEGF) pathway and its receptors play a pivotal role. Small-molecule inhibitors of VEGF receptors (VEGFR) have been shown to inhibit angiogenesis and tumor growth in preclinical models and in clinical trials. A novel nicotinamide, AMG 706, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4, platelet-derived growth factor receptor, and Kit receptors in preclinical models. AMG 706 inhibited human endothelial cell proliferation induced by VEGF, but not by basic fibroblast growth factor in vitro, as well as vascular permeability induced by VEGF in mice. Oral administration of AMG 706 potently inhibited VEGF-induced angiogenesis in the rat corneal model and induced regression of established A431 xenografts. AMG 706 was well tolerated and had no significant effects on body weight or on the general health of the animals. Histologic analysis of tumor xenografts from AMG 706-treated animals revealed an increase in endothelial apoptosis and a reduction in blood vessel area that preceded an increase in tumor cell apoptosis. In summary, AMG 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies.

Angiogenesis Inhibitors↗
PubMed2006

Direct evidence for endothelial vascular endothelial growth factor receptor-1 function in nitric oxide-mediated angiogenesis.

Vascular endothelial growth factor-A (VEGF) is critical for angiogenesis but fails to induce neovascularization in ischemic tissue lesions in mice lacking endothelial nitric oxide synthase (eNOS). VEGF receptor-2 (VEGFR-2) is critical for angiogenesis, although little is known about the precise role of endothelial VEGFR-1 and its downstream effectors in this process. Here we have used a chimeric receptor approach in which the extracellular domain of the epidermal growth factor receptor was substituted for that of VEGFR-1 (EGLT) or VEGFR-2 (EGDR) and transduced into primary cultures of human umbilical vein endothelial cells (HUVECs) using a retroviral system. Activation of HUVECs expressing EGLT or EGDR induced rapid phosphorylation of eNOS at Ser1177, release of NO, and formation of capillary networks, similar to VEGF. Activation of eNOS by VEGFR-1 was dependent on Tyr794 and was mediated via phosphatidylinositol 3-kinase, whereas VEGFR-2 Tyr951 was involved in eNOS activation via phospholipase Cgamma1. Consistent with these findings, the VEGFR-1-specific ligand placenta growth factor-1 activated phosphatidylinositol 3-kinase and VEGF-E, which is selective for VEGFR-2-activated phospholipase Cgamma1. Both VEGFR-1 and VEGFR-2 signal pathways converged on Akt, as dominant-negative Akt inhibited the NO release and in vitro tube formation induced following activation of EGLT and EGDR. The identification Tyr794 of VEGFR-1 as a key residue in this process provides direct evidence of endothelial VEGFR-1 in NO-driven in vitro angiogenesis. These studies provide new sites of modulation in VEGF-mediated vascular morphogenesis and highlight new therapeutic targets for management of vascular diseases.

Amino Acid Sequence↗
PubMed2006

[Regulative effect of leptin on gastric motility: experiment with conscious rats].

OBJECTIVE: To observe the role of leptin on the regulation of inter-digestive migrating motor complex (MMC) and gastric motility of postprandial period, as well as the serum leptin level and its relationship with motilin during different fast and postprandial periods. METHODS: Strain gauges were implanted on the serosa of corpus, antrum and pylorus in 50 conscious Wistar rats to record the gastric motility activities. Canula was inserted in the external jugular vein for drug perfusion and blood sampling. The rats were randomly divided into 5 groups: (1) Group 1 to observe the relationship between the postprandial fasting MMC and MMC after feeding. MMC on the empty stomach was recorded, soon afterwards test meal was fed, then the gastric motility was recorded for 60 minutes. Blood samples were collected during the phases I, II, III, and IV, 3 minutes after feeding and then every 5 minutes to test the serum leptin and motilin. (2) Leptin group. After the recording of the first MMC, leptin was perfused during the second MMC to observe its effect on the stomach motility. (3) Anti-leptin serum group. During the second MMC, 5 minutes before feeding and 60 minutes after feeding, anti-leptin serum was perfused to observe its effect on the postprandial stomach motility. (4) Leptin + atropine group. During the first MMC perfusion of atropine was followed by perfusion of leptin. and (5) leptin + cholecystokinin (CCK)-A receptor blocker group. Perfusion of CCK-A receptor blocker was followed by perfusion of leptin. Serum leptin and motilin levels were measured by radioimmunoassay. RESULTS: Typical MMC with phase I, II, III, and IV was recorded in the fasting rats. The phase III of antral MMC could migrate to the pylorus. During the postprandial period, the gastric motility patterns were persistent rhythmic peristaltic contractions. When the stomach was empty, the mean concentration of serum leptin was (5.6 +/- 1.0) microg/L, (11.4 +/- 2.1) microg/L, and (2.1 +/- 0.7) microg/L during the phase I, II and III respectively, being the highest in the phase II, significantly higher than those in the phase I and III (both P < 0.01). During digestive period, the serum concentration of leptin began to increase 3 minutes after the meal and reached its peak of (28.1 +/- 4.4) microg/L 10 minutes after the meal. The serum concentration of leptin remained on a high level till 30 minutes later (compared with that in the inter-digestive period, P < 0.01). On the contrary, the serum concentration of motilin was the highest in the phase III of MMC and the lowest in the digestive period. Intravenous infusion of leptin (2.5 microg x kg(-1) x 10 min) turned the inter-digestive pattern of gastric motility to digestive period pattern with corpus distension and contraction of antrum and pylorus. The effects of leptin on gastric motility were blocked by anti-leptin serum, atropine, and CCK-A receptor blocker loxiglumide. CONCLUSION: Leptin is a hormone to promote the inter-digestive MMC phase II and postprandial digestive motility activities of stomach, the concentration fluctuation of which will cause satiety related delay of gastric emptying. The effect of leptin on gastric motility is mediated by cholinergic nerve and CCK-A receptors.

Animals↗
PubMed2006

Muller glia induce retinal progenitor cells to differentiate into retinal ganglion cells.

Retinal progenitor cells could differentiate into various retinal cells that made cell-replacement therapy possible. Here, we investigated the role of cellular microenvironment on their regulation and differentiation and found that the percentage of proliferating cells and the percentage of retinal ganglion cells produced from them increased, when retinal progenitor cells were cocultured with Muller glia. Muller glia conditioned medium had the similar results. It is speculated that rather than traditional supportive roles, Muller glia may have an active regulatory role inducing retinal progenitor cells to proliferate and differentiate into ganglion cells by secreting some diffusible and membrane-associated factors. Identification of Muller glia-derived factors will be made to elucidate the molecular mechanisms of neurogenesis.

Animals↗
PubMed2006

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats.

AIM: To observe the therapeutic effects of liposome-encapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats. METHODS: LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS: Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 +/- 0.523 vs 1.883 +/- 0.708, 1.847 +/- 0.661, P < 0.01), and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM+BL (231.48 vs 74.66, 94.70) (P < 0.05). CONCLUSION: The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

Animals↗
PubMed2006

Identification and fine mapping of AvrPi15, a novel avirulence gene of Magnaporthe grisea.

Avirulence of Magnaporthe grisea isolate CHL346 on rice cultivar GA25 was studied with 242 ascospore progenies derived from the cross CHL346 x CHL42. Segregation analysis of the avirulence in the progeny population was in agreement with the existence of a single avirulence (Avr) gene, designated as AvrPi15. For mapping the Avr gene, we developed a total of 121 microsatellite DNA markers [simple sequence repeat (SSR)], which evenly distributed in the whole-genome of M. grisea through bioinformatics analysis (BIA) using the publicly available sequence. Linkage analysis of the AvrPi15 gene with these SSR markers showed that six markers on chromosome 6, MS6-1, MS6-2, MS6-3, MS6-7, MS6-8 and MS6-10, were linked to the AvrPi15 locus. To further define the chromosomal location of the AvrPi15 locus, two additional markers, MS6-17 and STS6-6, which were developed based on the sequences of telomeric region 11 (TEL11), were subjected to linkage analysis. The results showed that MS6-17 and STS6-6 were associated with the locus by 3.3 and 0.8 cM, respectively. To finely map the Avr gene, two additional candidate avirulence gene (CAG) markers, CAG6-1 and CAG6-2, were developed based on the gene annotation of the sequence of TEL 11. Linkage analysis of the Avr gene with these two markers revealed that both of them completely cosegregated with the AvrPi15 locus. Finally, this locus was physically mapped into approximately 7.2-kb interval of the TEL11 by BIA using these sequence-ready markers. This is the key step toward positional cloning of the AvrPi15 gene.

Chromosome Segregation↗
PubMed2006

Lateral components in the cone terminals of the rabbit retina: horizontal cell origin and glutamate receptor expression.

We examined the identities of horizontal cell (HC) lateral components in cone terminals and the expression of glutamate receptors on the tips of HC dendrites. We injected A-type horizontal cells (AHCs) with neurobiotin and demonstrated that neurobiotin labeled completely all AHCs within a patch of retina. We converted neurobiotin by using diaminobenzidine and considered labeled processes to be from AHCs and unlabeled processes to be from B-type horizontal cells (BHCs). Three possible combinations of HC dendrites could exist in cone pedicles: both lateral components originating from AHCs, both from BHCs, or one from an AHC and the other from a BHC. EM observations revealed that a majority of cone terminals contained about equal numbers of lateral components originating from each of the two types of HCs and that each of the three possible combinations was present in equal numbers. Localization of different types of glutamate receptors on HC dendritic tips showed that 55% of AHC dendritic tips expressed AMPA receptors and 30% expressed kainate receptors, whereas, in the case of BHCs, 22% of dendritic tips expressed AMPA receptors and 33% expressed kainate receptors. This study suggests that cone photoreceptors feed the light signal equally into networks of AHCs and BHCs and that differential expression of AMPA/kainate receptors by different HCs could account for different functions.

Animals↗
PubMed2006

C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis.

Initially, it was thought that there was no intracellular signaling mediated by NRP-1 alone in response to its ligands. However, the emerging data from our group as well as others suggest that the signaling through NRP-1 actually promotes angiogenesis and is mediated through its C-terminal domain and downstream molecules such as phosphoinositide 3-kinase. Hence, understanding the signal transduction pathways mediated by NRP-1 and identification of its downstream molecules are of importance. By using both in vivo zebrafish model and in vitro tissue culture system, we have shown that the C-terminal three amino acids of NRP-1 (SEA-COOH) are required for NRP-1-mediated angiogenesis. Furthermore, knocking down of RGS-GAIP-interacting protein C terminus (GIPC) in zebrafish, which is associated with C-terminal domain of NRP-1, exhibits similar vasculature phenotypes to those from NRP-1 null. Specific and effective silencing of GIPC in vascular endothelium results in inhibition of NRP-1-mediated migration. In both cases as described, PDZ domain of GIPC is responsible for its function. Taken together, our data suggest a novel role of GIPC in angiogenesis and vessel formation and also support our hypothesis that NRP-1 can facilitate downstream signaling to promote angiogenesis through GIPC.

Animals↗
PubMed2006

Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer.

BACKGROUND: Ribosomal proteins are the components of ribosome, which also exhibit various secondary functions in DNA repair, apoptosis, drug resistance and proliferation. In our previous study of microarray, ribosomal protein L15 (RPL15) was identified as an upregulated gene in gastric cancer. METHODS: We investigated the expression of ribosomal protein L15 in gastric cancer and the effect of RPL15 on proliferation of gastric cancer. RESULTS: It was found that the expression of RPL15 was markedly up-regulated in gastric cancer tissues. RPL15 was also highly expressed in gastric cancer cell lines AGS, MKN45, MKN28, SGC7901 and KATOIII. Inhibition of RPL15 expression by siRNA vector transfection suppressed the growth of SGC7901 cells significantly, which was independent of the expression of Cyclin D1 and B1. Down-regulation of RPL15 expression inhibited SGC7901 cell growth in soft agar and its tumorigenicity in nude mice. CONCLUSION: RPL15 promotes cell proliferation and may be a potential target for anticancer therapy of gastric cancer.

Agar↗
PubMed2006

Photoreactions in the gas-phase complexes of Mg(*+)-dioxanes.

Photoreactions in the gas-phase complexes Mg(*+)(1,4-dioxane) (1) and Mg(*+)(1,3-dioxane) (1M) have been examined in the wavelength region of 230-440 nm. Photoproduct assignments are facilitated with the help of deuterium substitution experiments. The main energy relaxation channel for both photoexcited complexes is the evaporation of Mg(*+). Also observed from 1 are rich photoproducts with m/z 28, 41, 54-58, 67, 69, and 88; the most abundant one at m/z 54 is designated to Mg(*+)(O=CH(2)). In marked contrast, the photolysis of 1M yields only Mg(*+)(O=CH(2)) other than Mg(*+). Density functional calculations are performed to obtain optimized geometries and potential energy surfaces of 1 and 1M. Although Mg(*+)(chair-1,4-C(4)H(8)O(2)) (1a) and Mg(*+)(boat-1,4-C(4)H(8)O(2)) (1b) are comparable in energy, the much better agreement of the experimental action spectrum of Mg(*+)(1,4-C(4)H(8)O(2)) with the calculated absorption spectrum of 1a than with that of 1b indicates the predominance of 1a in the source due to the stability of the chair-1,4-dioxane. For photoreactions, the C-O bond is found to be much more prone to rupture than the C-C bond due to the coordination of O to Mg(+) in the parent complexes. Photoreaction mechanisms are discussed in terms of two key insertion complexes, which rationalize all of the observed photoproducts.

Journal Article↗
PubMed2006

Immortalization of primary endothelial cells by the K1 protein of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to three different human cancers: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The Kaposi's sarcoma lesion expresses high levels of angiogenic factors and is comprised of a mixed cell population, including endothelial cells that are infected with KSHV. We find that the KSHV K1 protein is expressed in Kaposi's sarcoma lesions and can immortalize and extend the life span of primary human umbilical vein endothelial cells in culture. Vascular endothelial growth factor (VEGF) is critical for the survival of endothelial cells, and we show that expression of K1 in endothelial cells resulted in increased levels of secreted VEGF and the activation of key signaling pathways, including the VEGF/VEGF receptor and the phosphatidylinositol-3'-OH-kinase (PI3K) pathway. The SH2 binding motifs present in the cytoplasmic tail of K1 were critical for K1's ability to activate these pathways. Activation of PI3K by K1 results in activation of Akt kinase and mammalian target of rapamycin and inactivation of the proapoptotic proteins FKHR, glycogen synthase kinase-3, and Bad, which are events indicative of cell survival. Because activation of the PI3K pathway is critical for transformation of many human cells, we suggest that PI3K activation by K1 is involved in endothelial cell immortalization and contributes to KSHV-associated tumorigenesis. We also report that K1 enhances angiogenesis in vivo and increases tumor vasculature and tumor size.

Animals↗
PubMed2006

2-(1-Hydroxypentyl)-benzoate increases cerebral blood flow and reduces infarct volume in rats model of transient focal cerebral ischemia.

2-(1-Hydroxypentyl)-benzoate (dl-PHPB), a derivate of 3-n-butylphthalide (dl-NBP), is a novel drug candidate used for treatment of cerebral ischemia. The goal of the present study was to investigate the effects of dl-PHPB on infarct volume, neurological function, and cerebral blood flow (CBF) in transient focal cerebral ischemia. Therefore, an animal model of 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion was used. Rats received dl-PHPB (1.3, 3.9, or 12.9 mg/kg) intravenously 10 min after the onset of MCAO. Compared with the vehicle control group (37.4%), infarct volume in dl-PHPB-treated groups was reduced significantly and dose-dependently to 25.4, 17.4, and 13.7%, respectively. The changes in neurological deficient were also observed in neurobehavioral test in a dose-dependent manner, and the neuronal score was improved significantly from the vehicle control of 3.2 to 2.7, 2.1, and 1.8, respectively. At the highest dose, the potency of dl-PHPB was similar to those of dl-NBP. CBF was quantified by using laser-Doppler flowmetry. During the ischemia, the regional CBF values of dl-PHPB groups were significantly higher than that of vehicle group. In addition, our study showed that dl-PHPB converted into dl-NBP very quickly in blood in vitro. Approximately 70% of dl-PHPB converted into dl-NBP in 5 min when dl-PHPB was added into plasma at final concentrations of 6, 30, and 60 mug/ml. This result demonstrated that the neuronal protection effects of dl-PHPB were mainly induced by dl-NBP, an active compound converted from its precursor, dl-PHPB. In conclusion, dl-PHPB can reduce infarct volume and improve neurobehavioral deficits in a rat model of transient MCAO. Those effects may partially be due to an increase in CBF by the active metabolite (dl-NBP) of dl-PHPB. Therefore, our results suggest that dl-PHPB may be useful for treatment of ischemia stroke.

Animals↗
PubMed2006

Using a kinase/phosphatase switch to regulate a supramolecular hydrogel and forming the supramolecular hydrogel in vivo.

We have designed and synthesized a new hydrogelator Nap-FFGEY (1), which forms a supramolecular hydrogel. A kinase/phosphatase switch is used to control the phosphorylation and dephosphorylation of the hydrogelator and to regulate the formation of supramolecular hydrogels. Adding a kinase to the hydrogel induces a gel-sol phase transition in the presence of adenosine triphosphates (ATP) because the tyrosine residue is converted into tyrosine phosphate by the kinase to give a more hydrophilic molecule of Nap-FFGEY-P(O)(OH)(2) (2); treating the resulting solution with a phosphatase transforms 2 back to 1 and restores the hydrogel. Electron micrographs of the hydrogels indicate that 1 self-assembles into nanofibers. Subcutaneous injection of 2 in mice shows that 80.5 +/- 1.2% of 2 turns into 1 and results in the formation of the supramolecular hydrogel of 1 in vivo. This simple biomimetic approach for regulating the states of supramolecular hydrogels promises a new way to design and construct biomaterials.

Adenosine Triphosphate↗
PubMed2006

Cdc42 activation couples spindle positioning to first polar body formation in oocyte maturation.

During vertebrate egg maturation, cytokinesis initiates after one pole of the bipolar metaphase I spindle attaches to the oocyte cortex, resulting in the formation of a polar body and the mature egg. It is not known what signal couples the spindle pole positioning to polar body formation. We approached this question by drawing an analogy to mitotic exit in budding yeast, as asymmetric spindle attachment to the appropriate cortical region is the common regulatory cue. In budding yeast, the small G protein Cdc42 plays an important role in mitotic exit following the spindle pole attachment . We show here that inhibition of Cdc42 activation blocks polar body formation. The oocytes initiate anaphase but fail to properly form and direct a contractile ring. Endogenous Cdc42 is activated at the spindle pole-cortical contact site immediately prior to polar body formation. The cortical Cdc42 activity zone, which directly overlays the spindle pole, is circumscribed by a cortical RhoA activity zone; the latter defines the cytokinetic contractile furrow . As the RhoA ring contracts during cytokinesis, the Cdc42 zone expands, maintaining its complementary relationship with the RhoA ring. Cdc42 signaling may thus be an evolutionarily conserved mechanism that couples spindle positioning to asymmetric cytokinesis.

Animals↗