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Biomedical subjects

Yan Zhang

Publications and source records attributed to Yan Zhang.

At least 199 records · Page 11Linked to original sources

Photophysical properties of Ru(II) bipyridyl complexes containing hemilabile phosphine-ether ligands.

Emission and absorbance spectra, along with low-temperature excited-state lifetimes, were obtained for the hemilabile complexes, [Ru(bpy)2L](PF6)2 [L = (2-methoxyphenyl)diphenylphosphine (RuPOMe) (1) and (2-ethoxyphenyl)diphenylphosphine (RuPOEt) (2)] in solid 4:1 ethanol/methanol solution. Spectral data were evaluated with ground-state reduction potentials using Lever parameters. Lifetime data for these complexes were collected from 77 to 160 K, and the rate constant for the combined radiative and nonradiative decay process, k, the thermally activated process prefactor, k'(0), the rate constant for the MLCT --> d-d transition, k', and the activation energy, DeltaE', were calculated from a plot of ln(1/tau) versus 1/T for both (1) and (2). The low-temperature luminescence lifetimes of (1) were observed to decrease with increases in water concentration. The photophysical and kinetic data of (1) and (2) are compared to literature data for [Ru(bpy)3](PF6)2. The emission maxima of (1) and (2) are blue-shifted relative to [Ru(bpy)3](PF6)2 due to the presence of the strong-field phosphine ligand, which enhances pi back-bonding to the bipyridyl ligands. The thermal activation energy, DeltaE', is significantly larger for [Ru(bpy)3](PF6)2 than for (1) and (2) resulting in a faster MLCT --> d-d transition for (1) and (2). These results are discussed in the context of radiationless decay through thermally activated ligand-field states on the metal complex.

2,2'-Dipyridyl↗

Stable inhibition of hepatitis B virus expression and replication by expressed siRNA.

RNA interference might be an efficient antiviral therapy for some obstinate illness. Here, we studied the effects of hepatitis B virus (HBV)-specific 21-nt small interfering RNAs (siRNA) on HBV gene expression and replication in 2.2.15 cells. Seven vectors expressing specific hairpin siRNA driven by the RNA polymerase II-promoter were constructed and transfected into 2.2.15 cells. In the cell strain that can stably express functional siRNA, the HBV surface antigen (HBsAg) and the HBV e antigen (HBeAg) secretion into culture media was inhibited by 86% and 91%, respectively, as shown by an enzyme-linked immunosorbent assay. Immunofluorescence and Western blot indicated similar results. HBV DNA was markedly restrained by 3.28-fold, as assessed by the fluorescent quantitation PCR. Moreover, the HBV mRNA was significantly reduced by 80% based on semiquantitative RT-PCR. In conclusion, the specific siRNA can knock down the HBV gene expression and replication in vitro, and the silence effects have no relationship with interferon response.

Cell Line, Tumor↗

Interaction between the movement protein of barley yellow dwarf virus and the cell nuclear envelope: role of a putative amphiphilic alpha-helix at the N-terminus of the movement protein.

The open reading frame 4 (ORF 4) gene product of barley yellow dwarf virus (BYDV) may act as a movement protein (MP) by assisting the transport of viral genomic RNA across the nuclear envelope (NE) of host plant cells. To investigate interactions between BYDV MP and the NE, wild-type and mutant open reading frame (ORF 4)-green fluorescent protein (GFP) fusion cistrons were expressed in insect cells. A fusion protein expressed by the wild-type ORF 4-GFP cistron associated with the NE and caused protrusions from its surface. The fusion protein expressed by the mutant ORF 4-GFP cistron lacked a putative amphiphilic alpha-helix at its N-terminus and although associating with the NE, showed decreased levels of protrusions. A peptide homologue of this putative alpha-helix induced an increase of 7 degrees C in the phase transition temperature of dimyrystoyl phosphatidylserine (DMPS) membranes, accompanied by a decrease in membrane fluidity, but exhibited no significant interaction with either dimyristoyl phosphatidylcholine (DMPC) or dimyristoyl phosphatidylethanolamine (DMPE) membranes. These results strongly support the view that BYDV MP may interact with the NE to help transport viral genomic RNA into the nuclear compartment. This function of BYDV MP appears to involve protrusions on the surface of the NE and may require the presence of an N-terminal amphiphilic alpha-helix, which is speculated to destabilize membranes, thereby assisting the entry of BYDV-GAV into the nuclear compartment.

Amino Acid Sequence↗

Development of two enzyme-linked immunosorbent assays for detection of endosulfan residues in agricultural products.

Two competitive immunoassays, a laboratory assay based on microwell plates and a field test based on the use of polystyrene tubes, have been developed for the detection of endosulfan in agricultural products. The limit of detection for the microwell plate format was 0.8 +/- 0.1 microg/kg, and the limit of detection for the tube format was 1.6 +/- 0.2 microg/kg. A simple, rapid, and efficient extraction method was employed, and 76-112% recoveries of spiked samples were obtained. Methanol extracts of some agricultural product samples such as grape, carrot, spinach, and tobacco could be analyzed directly by immunoassay after dilution in 0.5% fish skin gelatin-phosphate buffered saline. In contrast, extracts of green tea caused significant interference in the assay, and a number of simple cleanup methods were ineffective in removing interference. However, use of the coagulating reagent polyvinyl pyrrolidone removed the matrix effect effectively. For the validation of the enzyme-linked immunosorbent assay (ELISA) tests, samples were analyzed by ELISA and gas chromatography (GC) after solid phase extraction. The relationship between data obtained using the tube assay and microwell assay was good (the lowest r(2) value was 0.94), and also, the immunoassay assay data correlated well with data obtained from GC analysis (the lowest r(2) value was 0.93). The developed immunoassay methods are the suitable methods for the rapid quantitative and reliable determination of endosulfan residues in agricultural products.

Camellia sinensis↗

In-fiber reflection mode interferometer based on a long-period grating for external refractive-index measurement.

We present two novel schemes for refractometry based on a long-period fiber grating- (LPG-) based Michelson interferometer. These schemes are designed to overcome the measurement dependence of previously demonstrated LPG-based refractometry on the immersion depth. The first utilizes an unshielded LPG and the second, a shielded one. Both schemes were tested over a certain refractive-index range, and the measurement of glucose concentration in water was experimentally demonstrated. In addition, the temperature sensitivity of the two schemes is discussed.

Journal Article↗

Strain rate imaging differentiates transmural from non-transmural myocardial infarction: a validation study using delayed-enhancement magnetic resonance imaging.

OBJECTIVES: The aim of this study was to determine if strain rate imaging (SRI) correlates with the transmural extent of myocardial infarction (MI) measured by contrast-enhanced magnetic resonance imaging (Ce-MRI). BACKGROUND: Identification of the transmural extent of myocardial necrosis and degree of non-viability after acute MI is clinically important. METHODS: Tissue Doppler echocardiography with SRI and Ce-MRI were performed in 47 consecutive patients with a first acute MI between days 2 and 6 and compared to 60 age-matched healthy volunteers. Peak myocardial velocities and peak myocardial deformation strain rates were measured. Location and size of the infarct zone was confirmed by Ce-MRI using the delayed enhancement technique with a 16-segment model. RESULTS: Contrast-enhanced MRI identified transmural infarction in 21 patients, non-transmural infarction in 15 (mean transmurality of infarct 72.3 +/- 10.6%), and another 11 patients with subendocardial infarction (<50% transmural extent of the left ventricular wall). Peak systolic strain rate (SRs) of the transmural infarction segments was significantly lower compared to normal myocardium or with non-transmural infarction segments (both p < 0.0005). A cutoff value of SRs >-0.59 s(-1) detected a transmural infarction with high sensitivity (90.9%) and high specificity (96.4%), and -0.98 s(-1) >SRs >-1.26 s(-1) distinguished subendocardial infarction from normal myocardium with a sensitivity of 81.3% and a specificity of 83.3%. CONCLUSIONS: Peak myocardial deformation by SRI can differentiate transmural from non-transmural MI, and it allows noninvasive determination of transmurality of the scar after MI and thereby the extent of non-viable myocardium.

Acute Disease↗

Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila.

Hunger elicits diverse, yet coordinated, adaptive responses across species, but the underlying signaling mechanism remains poorly understood. Here, we report on the function and mechanism of the Drosophila insulin-like system in the central regulation of different hunger-driven behaviors. We found that overexpression of Drosophila insulin-like peptides (DILPs) in the nervous system of fasted larvae suppressed the hunger-driven increase of ingestion rate and intake of nonpreferred foods (e.g., a less accessible solid food). Moreover, up-regulation of Drosophila p70/S6 kinase activity in DILP neurons led to attenuated hunger response by fasted larvae, whereas its down-regulation triggered fed larvae to display motivated foraging and feeding. Finally, we provide evidence that neural regulation of food preference but not ingestion rate may involve direct signaling by DILPs to neurons expressing neuropeptide F receptor 1, a receptor for neuropeptide Y-like neuropeptide F. Our study reveals a prominent role of neural Drosophila p70/S6 kinase in the modulation of hunger response by insulin-like and neuropeptide Y-like signaling pathways.

Adaptation, Physiological↗

Ion-exchange chromatography of hepatitis B virus surface antigen from a recombinant Chinese hamster ovary cell line.

About 10% of the Chinese population are chronic carriers of hepatitis B virus (HBV). Thus, the development of a highly efficient process for the preparation of a vaccine based on a recombinant hepatitis B surface antigen (HBsAg) is very important to the Chinese national immunization program. To this end, the ion exchange chromatography recovery of CHO-HBsAg from a recombinant Chinese hamster ovary cell line was shown to increase from about 55 to 80% by the addition of 1% poly(ethylene glycol) (PEG 10,000) to the mobile phase. Furthermore, based on analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the intact glycoprotein form of CHO-HBsAg was completely preserved by the addition of PEG. In the absence of PEG the glycoprotein form of CHO-HBsAg was also spread out into the high salt elution fraction. High-performance size-exclusion chromatography with on-line multiangle-laser-light scattering (HPSEC-MALLS) analysis was performed to monitor the status of the CHO-HBsAg aggregate structure assembly, particle size and molecular weight distribution after each purification step, and the results showed further that the presence of PEG facilitated the separation and recovery of intact glycoprotein form of CHO-HBsAg and promoted their assembly to proper virus-like particles, which are both important features and prerequisites of their immunogenicity.

Animals↗

[Clinical characteristics and management of patients with ST segment elevation myocardial infarction in China: survey of 7510 cases].

OBJECTIVE: To analyze the clinical characteristics and management of the patients with ST segment elevation myocardial infarction (STEMI) in China. METHODS: As part of the international multicentre CREATE Study, the clinical data of 7510 patients with STEMI presenting their symptoms within 12 hours of onset who were hospitalized in 274 centers throughout China from July 2001 through July 2004, aged 62.7, were collected to be analyzed. RESULTS: 99.3% of these patients had STEMI, and 0.7% had new left bundle-branch block. 11.5% of them underwent percutaneous coronary intervention (PCI), 52.5% underwent thrombolytic therapy, and 0.1% coronary artery bypass grafting. All types of reperfusion therapy were carried out to 62.4% of the patients during the hospitalization. The medication therapy used was similar to those in the previous Registry report. The composite of all-cause mortality, re-infarction, and stroke within the first 7 days was 10.3% and the all-cause mortality within 30 days was 11.1%. CONCLUSION: The clinical characteristics and management of the STEMI patients in China have been described. The age of onset of STEMI is 62 years on average. The most common complication is hypertension, and diabetes mellitus is relatively rare. rt-PA was used rarely mainly because of the expensive price. A large proportion of patients in China receive reperfusion, which is worth recommendation. Active intervention should be carried out in the early stage after infarction.

Adult↗

Synthesis and structure-activity relationships of pyrazine-pyridine biheteroaryls as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors.

There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, 4-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-ylamino}-butan-1-ol (39) and N-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-yl}-N',N'-dimethyl-ethane-1,2-diamine (41) exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of 39 and 41 were demonstrated in the A375 human melanoma xenograft nude mice model. Molecular modeling (QSAR analysis) was conducted in an attempt to rationalize the observed structure-activity relationship.

Aminopyridines↗

Evolution of selenium utilization traits.

BACKGROUND: The essential trace element selenium is used in a wide variety of biological processes. Selenocysteine (Sec), the 21st amino acid, is co-translationally incorporated into a restricted set of proteins. It is encoded by an UGA codon with the help of tRNASec (SelC), Sec-specific elongation factor (SelB) and a cis-acting mRNA structure (SECIS element). In addition, Sec synthase (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of Sec on the tRNASec. Selenium is also found in the form of 2-selenouridine, a modified base present in the wobble position of certain tRNAs, whose synthesis is catalyzed by YbbB using selenophosphate as a precursor. RESULTS: We analyzed completely sequenced genomes for occurrence of the selA, B, C, D and ybbB genes. We found that selB and selC are gene signatures for the Sec-decoding trait. However, selD is also present in organisms that do not utilize Sec, and shows association with either selA, B, C and/or ybbB. Thus, selD defines the overall selenium utilization. A global species map of Sec-decoding and 2-selenouridine synthesis traits is provided based on the presence/absence pattern of selenium-utilization genes. The phylogenies of these genes were inferred and compared to organismal phylogenies, which identified horizontal gene transfer (HGT) events involving both traits. CONCLUSION: These results provide evidence for the ancient origin of these traits, their independent maintenance, and a highly dynamic evolutionary process that can be explained as the result of speciation, differential gene loss and HGT. The latter demonstrated that the loss of these traits is not irreversible as previously thought.

Evolution, Molecular↗

Synthesis and identification of [1,3,5]triazine-pyridine biheteroaryl as a novel series of potent cyclin-dependent kinase inhibitors.

On the basis of previous studies, we identified pyrazine-pyridine A as a potent vascular endothelial growth factor inhibitor and pyrimidine-pyridine B as a moderately potent cyclin dependent kinase (CDK) inhibitor. A proposed combination of CGP-60474 and compound B led to the discovery of [1,3,5]triazine-pyridine as a new series of potent CDK inhibitors. Palladium-catalyzed C-C bond formation reactions, particularly the Negishi coupling reaction, were used to assemble various triazine-heteroaryl analogues effectively. Among them, compound 20 displayed high inhibitory potency at CDK1 (IC(50) = 0.021 microM), CDK2, and CDK5 and submicromolar potency at CDK4, CDK6, and CDK7. Compound 20 also displayed high potency at GSK-3beta. It demonstrated potent antiproliferative activity on various tumor cell lines, including HeLa, HCT-116, U937, and A375. When 20 was administered intraperitoneally at 150 and 125 mg/kg to nude mice bearing human A375 xenografts, the compound produced a significant survival increase. Molecular docking studies were conducted in an attempt to enhance the understanding of the observed structure-activity relationship.

Aminopyridines↗

Distinct immunosuppressive effect by Isodon serra extracts.

Distinct effect of ent-Kaurene Diterpenoids from Isodon serra on abnormal proliferation of murine lymphocytes was examined with MTT assay and Flow Cytometry Analyses (FCAS). After choosing the most appropriate monomer from these Diterpenoids, we introduced mouse tumescence model to investigate whether it could impact cytokine production in vivo with ELISA assay. The result of MTT assay showed that four ent-Kaurene Diterpenoids could effectively suppress the murine splenic T lymphocytes overproduction stimulated by Concanavalin A, while inhibitive effect was softer on normal sleep lymphocytes than the stimulated ones. Among four ent-Kaurene Diterpenoids, Enmein was the most sensitive one with IC50/EC50 equaling to 1.55. This inhibitive activity was due to interfering DNA replication in G1-S stage and to regulating cell cycle according to flow cytometry analyses (FCAS) result. Xylene-induced mouse tumescence model result further suggested that Enmein depressed the murine ear swelling extent and the level of Interleukin-2 in blood serum in a dose-dependent manner. In conclusion, it demonstrated that four ent-Kaurene Diterpenoids from I. serra had distinct immunosuppressive effect in vitro and in vivo systems, which primarily differentiated Enmein from the others. The experimental results provided insight into a potential immunosuppressive action of Enmein as a promising drug, though profound mechanism remained to be further studied.

Animals↗

A new scheme for determining the intramolecular seven-membered ring N-H...O=C hydrogen-bonding energies of glycine and alanine peptides.

In this paper a new scheme was proposed to calculate the intramolecular hydrogen-bonding energies in peptides and was applied to calculate the intramolecular seven-membered ring N-H...O=C hydrogen-bonding energies of the glycine and alanine peptides. The density-functional theory B3LYP6-31G(d) and B3LYP6-311G(d,p) methods and the second-order Moller-Plesset perturbation theory MP26-31G(d) method were used to calculate the optimal geometries and frequencies of glycine and alanine peptides and related structures. MP26-311++G(d,p), MP26-311++G(3df,2p), and MP2/aug-cc-pVTZ methods were then used to evaluate the single-point energies. It was found that the B3LYP6-31G(d), MP26-31G(d), and B3LYP6-311G(d,p) methods yield almost similar structural parameters for the conformers of the glycine and alanine dipeptides. MP2/aug-cc-pVTZ predicts that the intramolecular seven-membered ring N-H...O=C hydrogen-bonding strength has a value of 5.54 kcal/mol in glycine dipeptide and 5.73 and 5.19 kcal/mol in alanine dipeptides, while the steric repulsive interactions of the seven-membered ring conformers are 4.13 kcal/mol in glycine dipeptide and 6.62 and 3.71 kcal/mol in alanine dipeptides. It was also found that MP26-311++G(3df,2p) gives as accurate intramolecular N-H...O=C hydrogen-bonding energies and steric repulsive interactions as the much more costly MP2/aug-cc-pVTZ does.

Alanine↗

Tagalsins I and J, two novel tetraterpenoids from the mangrove plant, Ceriops tagal.

[reaction: see text] Two novel bisdolabrane backbone tetraditerpenoids, tagalsins I (1) and J (2), were isolated from the mangrove plant, Ceriops tagal, and their structures were elucidated by means of extensive two-dimensional NMR (COSY, HMQC, HMBC, and NOESY), IR, and MS data analysis. The stereochemistry of 1 was further determined by single-crystal X-ray diffraction.

Crystallography, X-Ray↗

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in Xinjiang, China.

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in China. METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls. RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) than in control subjects (24.0%) (P<0.05; OR, 11.13; 95%CI, 5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vs the control group (3.8%) (P<0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P<0.05; OR, 13.42; 95%CI, 6.29-28.3). CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased the susceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.

Aged↗

Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system.

Phosphodiesterases (PDEs) modulate signaling by cyclic nucleotides in diverse processes such as cardiac contractility, platelet aggregation, lipolysis, glycogenolysis, and smooth muscle contraction. Cyclic guanosine monophosphate (cGMP) stimulated human phosphodiesterase 2 (PDE2) is expressed mainly in brain and heart tissues. PDE2A is involved in the regulation of blood pressure and fluid homeostasis by the atrial natriuretic peptide (ANP), making PDE2-type enzymes important targets for drug discovery. The design of more potent and selective inhibitors of PDE2A for the treatment of heart disease would be greatly aided by the identification of active site residues in PDE2A that determine substrate and inhibitor selectivity. The identification of active site residues through traditional mutational studies involves the time-consuming and tedious purification of a large number of mutant proteins from overexpressing cells. Here we report an alternative approach to rapidly produce active site mutants of human PDE2A and identify their enzymatic properties using a wheat germ in vitro translation (IVT, also known as cell-free translation) system. We also present the crystal structure of the catalytic domain of human PDE2A determined at 1.7 A resolution, which provided a framework for the rational design of active site mutants. Using a rapid IVT approach for expression of human PDE2A mutants, we identified the roles of active site residues Asp811, Gln812, Ile826, and Tyr827 in inhibitor and substrate selectivity for PDE2A.

3',5'-Cyclic-AMP Phosphodiesterases↗