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Biomedical subjects

Ying Wang

Publications and source records attributed to Ying Wang.

At least 91 records · Page 5Linked to original sources

Reduction of C-reactive protein by a single 80 mg of simvastatin in patients with unstable angina.

BACKGROUND: Increased concentrations of C-reactive protein (CRP) became widely accepted as a risk factor of the higher incidence of coronary events, and rapid lowering CRP by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available, however, with respect to evaluating a potential effect of a single high-dose simvastatin on CRP in patients with unstable angina (UA) within 48 h. We investigated whether a rapid CRP reduction can be achieved by a single 80 mg of simvastatin therapy in patients with UA given immediately on admission. METHODS: Forty-two patients with rest chest pain were randomly assigned to a single placebo or 80 mg of simvastatin given at the time of admission plus standard therapy. Blood samples were also drawn at the time of admission, and 48 h later for measuring serum CRP concentrations. RESULTS: We found that 80 mg of simvastatin induced significant reductions in serum median CRP concentrations and in mean CRP concentrations 48 h later following administration of simvastatin (25.4% and 32.7%, p<0.001, respectively). CONCLUSIONS: A single high-dose simvastatin, given in the early time on admission, is an effective therapy for controlling inflammatory response in patients with UA, and the benefit to the vascular endothelium might occur quickly by reduction of CRP concentrations in this high-risk subgroup.

Angina, Unstable↗

The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity.

Lat(Y136F) knock-in mice harbor a point mutation in Tyr(136) of the linker for activation of T cells and show accumulation of Th2 effector cells and IgG1 and IgE hypergammaglobulinemia. B cell activation is not a direct effect of the mutation on B cells since in the absence of T cells, mutant B cells do not show an activated phenotype. After adoptive transfer of linker for activation of T cell mutant T cells into wild-type, T cell-deficient recipients, recipient B cells become activated. We show in vivo and in vitro that the Lat(Y136F) mutation promotes T cell-dependent B cell activation leading to germinal center, memory, and plasma cell formation even in an MHC class II-independent manner. All the plasma and memory B cell populations found in physiological T cell-dependent B cell responses are found. Characterization of the abundant plasmablasts found in secondary lymphoid organs of Lat(Y136F) mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In Lat(Y136F) mice, B cell activation was polyclonal and not Ag-driven because the increase in serum IgG1 and IgE concentrations involved Abs and autoantibodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in Lat(Y136F) serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in Lat(Y136F) mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease.

Adaptor Proteins, Signal Transducing↗

Pulmonary nodules detected at lung cancer screening: interobserver variability of semiautomated volume measurements.

PURPOSE: To retrospectively determine interobserver variability of semiautomated volume measurements of pulmonary nodules and the potential reasons for variability. MATERIALS AND METHODS: The Dutch-Belgian lung cancer screening trial (NELSON) is a lung cancer screening study that includes men between the ages of 50 and 75 years who are current or former heavy smokers. The NELSON project was approved by the Dutch Ministry of Health and the ethics committee of each participating hospital. Informed consent was obtained from all participants. For this study, the authors evaluated 1200 consecutive low-dose computed tomographic (CT) scans of the chest obtained during the NELSON project and identified subjects who had at least one 50-500-mm(3) nodule. One local and one central observer independently evaluated the scans and measured the volume of any detected nodule by using semiautomated software. Noncalcified solid nodules with volumes of 15-500 mm(3) were included in this study if they were fully surrounded by air (intraparenchymal) and were detected by both observers. The mean volume and the difference between both measurements were calculated for all nodules. Intermeasurement agreement was assessed with the Spearman correlation coefficient. Potential reasons for discrepancies were assessed. RESULTS: There were 232 men (mean age, 60 years; age range, 52-73 years) with 430 eligible nodules (mean volume, 77.8 mm(3); range, 15.3-499.5 mm(3)). Interobserver correlation was high (r = 0.99). No difference in volume was seen for 383 nodules (89.1%). Discrepant results were obtained for 47 nodules (10.9%); in 16 cases (3.7%), the discrepancy was larger than 10%. The most frequent cause of variability was incomplete segmentation due to an irregular shape or irregular margins. CONCLUSION: In a minority (approximately 11%) of small solid intraparenchymal nodules, semiautomated measurements are not completely reproducible and, thus, may cause errors in the assessment of nodule growth. For small or irregularly shaped nodules, an observer should check the segmentation shown by the program.

Aged↗

Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate through increased mitochondrial translocation of protein kinase Calpha in C2C12 myocytes.

Protein kinase C (PKC) agonists including phorbol 12-myristate 13-acetate (PMA) not only induce the redistribution of cytosolic PKC to various subcellular compartments but also activate the kinase domain of the protein. In the present study we have investigated the nature of mitochondrial PKC pool and its effects on mitochondrial function in cells treated with PMA. Treatment of C2C12 myoblasts, C6 glioma and COS7 cells with PMA resulted in a dramatic redistribution of intracellular PKCalpha pool, with large fraction of the protein pool sequestered in the mitochondrial compartment. We also observed mitochondrial PKCdelta accumulation in a cell restricted manner. The intramitochondrial localization was ascertained by using a combination of protection against protease treatment of isolated mitochondria and immunofluorescence microscopy. PMA-induced mitochondrial localization of PKCalpha was accompanied by increased mitochondrial PKC activity, altered cell morphology, disruption of mitochondrial membrane potential, decreased complex I and pyruvate dehydrogenase activities, and increased mitochondrial ROS production. All of these changes could be retarded by treatment with PKC inhibitors. These results show a direct role for PMA-mediated PKCalpha translocation to mitochondria in inducing mitochondrial toxicity.

Animals↗

Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase.

Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine ring were studied for their EGFR tyrosine kinase inhibitory activity. While the oxazepines were in general more potent than thiazepines, the diazepines displayed somewhat different structure-activity relationships. Moreover, the diazepines, in contrast to the oxazepines, showed appreciable inhibitory activity against the KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated significant ability to inhibit autophosphorylation of EGFR in DiFi cells (generally, IC(50) values in the single-digit micromolar to submicromolar range).

Antineoplastic Agents↗

Role of CDK5 in neuroprotection from serum deprivation by mu-opioid receptor agonist.

Cyclin-dependent kinase 5 (CDK5), a unique member of the CDK family of cyclin-dependent kinases, is predominantly expressed in postmitotic neurons with proposed roles in both cell survival and programmed cell death. To understand how CDK5 participates in such disparate cellular outcomes, we investigated whether activation of CDK5 could mediate neuroprotection from serum deprivation by mu-opioid receptor agonist in differentiated SH-SY5Y cells and primary hippocampal neurons. We found that CDK5 kinase activity decreased following serum deprivation in differentiated SH-SY5Y cells coincident with increased cell loss and activation of caspases cascade activation, which was reversed by opioid antagonist. Overexpression of CDK5 in serum-free medium reversed activation of caspase cascade and augmented DAMGO neuroprotection. Blocking CDK5 activity by pharmacologic inhibitor, roscovitine or overexpression of dominant negative CDK5 augmented activation of cell death markers and diminished mu-opioid receptor agonist protection. Reduction in CDK5 activity corresponded to reduction in protein levels of CDK5 activator p35 during serum deprivation which was also reversed by mu-opioid receptor agonist. Phosphorylation of STAT3 at Serine 727 by CDK5 decreased during serum deprivation, and partly recovered by mu-opioid agonist. PI3K signaling pathway was not required for CDK5-mediated mu-opioid neuroprotection against serum deprivation. These findings indicate that neuroprotection by mu-opioid receptor agonist against serum deprivation is mediated by activation of CDK5 through up-regulation of p35 and phosphorylation of STAT3 by CDK5 may contribute to the neuroprotection.

Animals↗

Liver X receptor agonist T0901317 inhibition of glucocorticoid receptor expression in hepatocytes may contribute to the amelioration of diabetic syndrome in db/db mice.

The glucocorticoid receptor (GR) is a crucial target gene for glucocorticoid-induced insulin resistance and hepatic gluconeogenesis linked to the development of type 2 diabetes. The liver X receptors (LXRs) are nuclear receptors that play an important role in the regulation of the metabolic gene linked to carbohydrate homeostasis. To assess the tissue-specific interaction of LXR with GR in the development of type 2 diabetes, we examined the possible effect of LXR agonist T0901317 on GR gene expression in vivo and in vitro in hepatocytes from db/db mice (a model of type 2 diabetes). Chronic ligand activation of LXR by a synthetic LXR T0901317 markedly decreased the expression of both GR mRNA and its protein in liver and improved the phenotype of type 2 diabetes in obese db/db mice. Suppression of hepatic GR expression was correlated with reduced levels of glucose and corresponded to the inhibition of phosphoenolpyruvate carboxykinase mRNA and 11beta-hydroxysteroid dehydrogenase type 1-mediated synthesis of active corticosterone from inactive 11-dehydrocorticosterone in liver. Treatment of db/db mouse primary hepatocytes with T0901317 resulted in dramatic suppression of GR mRNA and required ongoing protein synthesis. Addition of T0901317 to primary hepatocytes also suppressed the expression of both 11beta-hydroxysteroid dehydrogenase type 1 and phosphoenolpyruvate carboxykinase. These findings suggest that some of antidiabetic actions of LXR agonist T0901317 may be mediated, at least in part, through the suppression of hepatic GR gene expression.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Synthesis, crystal structure, and characterization of new tetranuclear Ag(I) complexes with triazole bridges.

The self-assembly of Ag(I) ions with 3,5-dimethyl-4-amino-1,2,4-triazole (L1) and 4-salicylideneamino-1,2,4-triazole (L2) gave two novel complexes, [Ag4(mu2-L1)6][Ag4(mu2-L1)6(CH3CN)2](ClO4)8.2H2O (1) and [Ag4(mu2-L2)6(CH3CN)2](AsF6)4.2H2O (2), both of which contain tetranuclearic clusters constructed via Ag(I) ions and six N1,N2-bridged triazoles with a Ag4N12 core. When 4-(6-amino-2-pyridyl)-1,2,4-triazole (L3) was employed, {[Ag4(mu2-L3)4(mu3-L3)2](CF3SO3)4.H2O}n (3), {[Ag4(mu2-L3)4(mu3-L3)2](ClO4)4}n (4), and {[Ag4(mu2-L3)2(mu3-L3)4](PF6)4.CH3CN.0.75H2O}n (5) were isolated. 3 and 4 are 1D polymers, while 5 is a 2D polymer. 1D and 2D coordination polymers are constructed via the self-assembly of Ag4N12 cores as secondary building units (SBUs). The connection of these SBUs can be represented as a ladderlike structure for 1D polymers and a 4.8(2) net for 2D polymers. Electrospray ionization mass spectrometry measurements and NMR (1H and 13C) studies demonstrate that the tetranuclear SBU retains its integrity and the coordination polymers decompose into the tetranuclear Ag4N12 core in solution. 2 exhibits blue emission in the solid state and green emission in solution at ambient temperature. Strong blue fluorescence for complexes 3-5 in the solid state can be assigned to the intraligand fluorescent emission.

Journal Article↗

Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression.

CD82, also known as KAI1, was recently identified as a prostate cancer metastasis suppressor gene on human chromosome 11p1.2 (ref. 1). The product of CD82 is KAI1, a 40- to 75-kDa tetraspanin cell-surface protein also known as the leukocyte cell-surface marker CD82 (refs. 1,2). Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models. To define the mechanism of action of KAI1, we used a yeast two-hybrid screen and identified an endothelial cell-surface protein, DARC (also known as gp-Fy), as an interacting partner of KAI1. Our results indicate that the cancer cells expressing KAI1 attach to vascular endothelial cells through direct interaction between KAI1 and DARC, and that this interaction leads to inhibition of tumor cell proliferation and induction of senescence by modulating the expression of TBX2 and p21. Furthermore, the metastasis-suppression activity of KAI1 was significantly compromised in DARC knockout mice, whereas KAI1 completely abrogated pulmonary metastasis in wild-type and heterozygous littermates. These results provide direct evidence that DARC is essential for the function of CD82 as a suppressor of metastasis.

Alleles↗

Removal of phenol from aqueous solution by adsorption onto OTMAC-modified attapulgite.

The potential of octodecyl trimethyl ammonium chloride (OTMAC)-modified attapulgite (AT) for phenol adsorption from aqueous solutions was studied. The comparison of natural AT and modified AT showed that it is possible to utilize the sonication-modified OTMAC-AT in the treatment of phenol-contaminated wastewaters. Batch sorption studies were carried out to evaluate the effect of contact time, shaking frequency, temperature and the amount of AT. The results showed that in a lab-scale reactor, at room temperature, with an amount of the modified AT added (2.5 g), and a shaking frequency of 140 rev/min, the adsorption rate of phenol could be 60.4% for a duration of 60 min. The sorption kinetics were described by a pseudo-second-order model, and the values of k and q(e) were 1.367 mg/ig min and 0.7901 ig/mg, respectively. The analysis of equilibrium data showed that the Freundlich isotherms were found to be applicable for the adsorption equilibrium data. K and 1/n were estimated to be 14.53 and 0.8438, respectively.

Adsorption↗

Optical molecular imaging for systems biology: from molecule to organism.

The development of highly efficient analytical methods capable of probing biological systems at system level is an important task that is required in order to meet the requirements of the emerging field of systems biology. Optical molecular imaging (OMI) is a very powerful tool for studying the temporal and spatial dynamics of specific biomolecules and their interactions in real time in vivo. In this article, recent advances in OMI are reviewed extensively, such as the development of molecular probes that make imaging brighter, more stable and more informative (e.g., FPs and semiconductor nanocrystals, also referred to as quantum dots), the development of imaging approaches that provide higher resolution and greater tissue penetration, and applications for measuring biological events from molecule to organism level, including gene expression, protein and subcellular compartment localization, protein activation and interaction, and low-mass molecule dynamics. These advances are of great significance in the field of biological science and could also be applied to disease diagnosis and pharmaceutical screening. Further developments in OMI for systems biology are also proposed.

Animals↗

Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells.

Neural progenitor cells in the subventricular zone (SVZ) of the lateral ventricular wall give rise to new neurons throughout rodent life. Ischemic stroke induces angiogenesis and neurogenesis. Using laser capture microdissection (LCM) in combination with microarrays containing approximately 400 known genes associated with stem cells and angiogenesis, we investigated gene profiles of SVZ cells in the adult mouse subjected to middle cerebral artery occlusion. Our data revealed that nonstroke SVZ cells expressed sets of genes that are important for neural progenitor cell proliferation, differentiation, and migration. In addition, stroke SVZ cells expressed many genes involved in neurogenesis during embryonic development but were not detected in nonstroke SVZ cells. Stroke upregulated genes were verified by real-time reverse transcriptase-polymerase chain reaction and immunostaining. These data indicate that adult SVZ cells recapture embryonic molecular signals after stroke and provide insight into the molecular mechanisms, which regulate the biological function of neural progenitor cells in the SVZ of adult rodent brain under physiological and stroke conditions.

Animals↗

The role of arabinogalactan proteins binding to Yariv reagents in the initiation, cell developmental fate, and maintenance of microspore embryogenesis in Brassica napus L. cv. Topas.

Arabinogalactan proteins (AGPs) are extracellular proteoglycans involved in plant growth and development. The addition of beta-D-glucosyl Yariv reagent (betaGlcY), a synthetic phenylglycoside that specifically reacts with AGPs, to the culture medium notably disturbed microspore embryogenesis in a concentration-dependent manner. The initiation of microspore embryogenesis was clearly inhibited by 30 microM betaGlcY and completely inhibited by 50 microM betaGlcY. The transfer of microspore-derived embryos at different developmental stages into NLN6 medium containing 50 microM betaGlcY prohibited their normal development, as approximately 21.24, 43.99, and 59.73%, respectively, of the treated globular-, heart-, and torpedo-stage embryos exhibited numerous root hair-like structures. Both heart-stage and torpedo-stage embryos showed a rapid growth of roots with a large number of clustered root hairs. Some root hair-like structures were also observed on the apical portions of embryos. Microscopy of the treated embryos revealed that the basic patterns of cells at both the radial and apical-basal axes were greatly altered, such that the cells lost their ability to carry out programmed embryogenesis. These results show that the betaGlcY-AGP interaction modulates the developmental fate of embryonic cells, especially epidermal cells, and thereby strongly affects root generation and development. Immunofluorescence microscopy revealed that both JIM8 and JIM13 binding to AGP co-localize with betaGlcY-binding sites. Thus, AGPs binding to betaGlcY, co-localized with Jim8- and Jim13-binding protein, appear to play a crucial role in the initiation of Brassica microspore embryogenesis and the maintenance of cell differentiation during embryonic development. In addition, these proteins may also be involved in the regulation of root generation.

Antibodies, Monoclonal↗

Heterogeneous reactions of sulfur dioxide on typical mineral particles.

The heterogeneous reaction of SO2 on Al2O3, CaO, TiO2, MgO, FeOOH, Fe2O3, MnO2, and SiO2, as well as authentic aerosol sample, was investigated by using a White Cell coupled with in situ-FTIR and Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). Simultaneous observations of reactants and products were performed to obtain full information on the mechanism and kinetics of the reactions. SO2 was irreversibly adsorbed to form surface sulfite (SO3(2-)), bisulfite (HSO3(-)), and sulfate (SO4(2-)). The reactivity order of these particles is the following: FeOOH >Al2O3 > mixture > MgO > Fe2O3 > SiO2. Field-collected aerosol showed significant activity for the oxidation of SO2. The uptake coefficient of SO2 on Al2O3 with different acidity varied in the order of basic Al2O3 > neutral Al2O3 > acidic Al2O3. The surface-active oxygen and hydroxyl might be the key factors for the conversion of SO2 to SO4(2-). The faster reaction rate could be achieved with greater surface area on particles with the same mass. On the basis of the same surface area Fe2O3 could be most reactive in the reaction with SO2 compared with all other particles. The apparent rate constants were determined to be 1.35 x 10(-2) and 9.4 x 10(-3) for uptake on Al2O3 and MgO, respectively, which are the same as the results of other scientists.

Journal Article↗

Mechanisms for renal blood flow control early in diabetes as revealed by chronic flow measurement and transfer function analysis.

The purpose of this study was to establish the roles of the myogenic response and the TGF mechanism in renal blood flow (RBF) control at the very earliest stages of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18 h/d, in uninephrectomized control and diabetic rats, and transfer function analysis was used to determine the dynamic autoregulatory efficiency of the renal vasculature. During the control period, MAP averaged 91 +/- 0.5 and 89 +/- 0.4 mmHg, and RBF averaged 8.0 +/- 0.1 and 7.8 +/- 0.1 ml/min in the control and diabetic groups, respectively. Induction of diabetes with streptozotocin caused a marked and progressive increase in RBF in the diabetic rats, averaging 10 +/- 6% above control on day 1 of diabetes and 22 +/- 3 and 34 +/- 1% above control by the end of diabetes weeks 1 and 2. MAP increased approximately 9 mmHg during the 2 wk in the diabetic rats, and renal vascular resistance decreased. Transfer function analysis revealed significant increases in gain to positive values over the frequency ranges of both the TGF and myogenic mechanisms, beginning on day 1 of diabetes and continuing through day 14. These very rapid increases in RBF and transfer function gain suggest that autoregulation is impaired at the very onset of hyperglycemia in streptozotocin-induced type 1 diabetes and may play an important role in the increase in RBF and GFR in diabetes. Together with previous reports of decreases in chronically measured cardiac output and hindquarter blood flow, this suggests that there may be differential effects of diabetes on RBF versus nonrenal BF control.

Albuminuria↗

Prolonged Ca2+ and force transients in myosin RLC transgenic mouse fibers expressing malignant and benign FHC mutations.

Clinical studies have revealed that mutations in the ventricular myosin regulatory light chain (RLC) lead to the development of familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disease characterized by left ventricular hypertrophy, myofibrillar disarray and sudden cardiac death. While mutations in other contractile proteins have been studied widely by others, there is no report elucidating the mechanism(s) associated with FHC-linked RLC mutations. In this study, we have assessed the functional consequences of two RLC mutations, R58Q and N47K, in transgenic mice. Clinical phenotypes associated with these mutations included inter-ventricular hypertrophy, abnormal ECG findings and the R58Q mutation caused multiple cases of premature sudden cardiac death. Simultaneous measurements of the ATPase and force in transgenic skinned papillary muscle fibers from mutated versus control mice showed an increase in the Ca(2+) sensitivity of ATPase and steady-state force only in R58Q fibers. The calculated energy cost or rate of dissociation of force generating myosin cross-bridges (ATPase/force ratio) plotted as a function of activation state was the same in all groups of fibers. Both mutations caused prolonged [Ca(2+)] transients in electrically stimulated intact papillary muscles; however, the R58Q mutation also resulted in a significantly prolonged force transient. Our results suggest that the phenotypes of FHC observed in patients harboring these RLC mutations correlate with the extent of physiological changes monitored in transgenic fibers. Cardiac hypertrophy observed in patients is most likely caused by the activation of compensatory mechanisms ensuing from higher workloads due to incomplete relaxation as evidenced by prolonged [Ca(2+)] transients for both N47K and R58Q fibers. Furthermore, the poor prognosis of the R58Q patients may be associated with more severe diastolic dysfunction due to the slower off-rate of Ca(2+) from troponin C leading to longer force and [Ca(2+)] transients and increased Ca(2+) sensitivity of ATPase and force.

Adenosine Triphosphatases↗

The C2H2 zinc-finger protein SYD-9 is a putative posttranscriptional regulator for synaptic transmission.

Communication between neurons is largely achieved through chemical synapses, where neurotransmitters are released from synaptic vesicles at presynaptic terminals to activate postsynaptic cells. Exo- and endocytosis are coordinated to replenish the synaptic vesicle pool for sustained neuronal activity. We identified syd-9 (syd, synapse defective), a gene that encodes multiple C2H2 zinc-finger domain-containing proteins specifically required for synaptic function in Caenorhabditis elegans. syd-9 loss-of-function mutants exhibit locomotory defects, a diffuse distribution of synaptic proteins, and decreased synaptic transmission with unaffected neurodevelopment. syd-9 mutants share phenotypic and ultrastructural characteristics with mutants that lack synaptic proteins that are required for endocytosis. syd-9 mutants also display genetic interactions with these endocytotic mutants, suggesting that SYD-9 regulates endocytosis. SYD-9 proteins are enriched in the nuclei of both neuron and muscle cells, but their neuronal expression plays a major role in locomotion. SYD-9 isoforms display a speckle-like expression pattern that is typical of RNA-binding proteins that regulate premRNA splicing. Furthermore, syd-9 functions in parallel with unc-75 (unc, uncoordinated), the C. elegans homologue of the CELF/BrunoL family protein that regulates mRNA alternative splicing and processing, and is also required specifically for synaptic transmission. We propose that neuronal SYD-9 proteins are previously uncharacterized and specific posttranscriptional regulators of synaptic vesicle endocytosis.

Animals↗