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Biomedical subjects

Yu Wang

Publications and source records attributed to Yu Wang.

At least 91 records · Page 5Linked to original sources
PubMed2006

Solution structure of monomeric BsaL, the type III secretion needle protein of Burkholderia pseudomallei.

Many gram-negative bacteria that are important human pathogens possess type III secretion systems as part of their required virulence factor repertoire. During the establishment of infection, these pathogens coordinately assemble greater than 20 different proteins into a macromolecular structure that spans the bacterial inner and outer membranes and, in many respects, resembles and functions like a syringe. This type III secretion apparatus (TTSA) is used to inject proteins into a host cell's membrane and cytoplasm to subvert normal cellular processes. The external portion of the TTSA is a needle that is composed of a single type of protein that is polymerized in a helical fashion to form an elongated tube with a central channel of 2-3 nm in diameter. TTSA needle proteins from a variety of bacterial pathogens share sequence conservation; however, no atomic structure for any TTSA needle protein is yet available. Here, we report the structure of a TTSA needle protein called BsaL from Burkholderia pseudomallei determined by nuclear magnetic resonance (NMR) spectroscopy. The central part of the protein assumes a helix-turn-helix core domain with two well-defined alpha-helices that are joined by an ordered, four-residue linker. This forms a two-helix bundle that is stabilized by interhelix hydrophobic contacts. Residues that flank this presumably exposed core region are not completely disordered, but adopt a partial helical conformation. The atomic structure of BsaL and its sequence homology with other TTSA needle proteins suggest potentially unique structural dynamics that could be linked with a universal mechanism for control of type III secretion in diverse gram-negative bacterial pathogens.

Amino Acid Sequence↗
PubMed2006

Is [N+-H...O] hydrogen bonding the most important noncovalent interaction in macrocycle-dibenzylammonium ion complexes?

We report a new host molecule in which one diethylene glycol chain (i.e., a loop possessing only three oxygen atoms) incorporated along with two phenolic aromatic rings is linked by a xylene spacer into a macroring. The design of the molecular structure of this macrocycle "amplifies" any potential [cation...pi], [N+-H...pi], and [N+C-H...pi] interactions between the dibenzylammonium (DBA+) ion and the phenolic rings of the macrocycle; as such, these species display a very strong binding affinity in CD3NO2 (Ka = 15,000 M(-1)). The macroring also coordinates to bipyridinium ions in a [2]pseudorotaxane fashion, which makes it the smallest macrocycle (i.e., a 25-membered ring) known to complex both DBA+ and bipyridinium ions in solution. To confirm unambiguously that these pseudorotaxanes exist in solution, we synthesized their corresponding interlocked molecules, namely rotaxanes and catenanes.

Benzylammonium Compounds↗
PubMed2006

Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle.

We demonstrated previously that membrane depolarization and excitatory receptor agonists such as noradrenaline induce Ca2+-dependent Rho activation in VSM (vascular smooth muscle), resulting in MP (myosin phosphatase) inhibition through the mechanisms involving Rho kinase-mediated phosphorylation of its regulatory subunit MYPT1. In the present study, we show in de-endothelialized VSM strips that the PI3K (phosphoinositide 3-kinase) inhibitors LY294002 and wortmannin inhibited KCl membrane depolarization- and noradrenaline-induced Rho activation and MYPT1 phosphorylation, with concomitant inhibition of MLC (20-kDa myosin light chain) phosphorylation and contraction. LY294002 also augmented de-phosphorylation of MLC and resultantly relaxation in KCl-contracted VSM, whereas LY294002 was much less effective or ineffective under the conditions in which MP was inhibited by either a phosphatase inhibitor or a phorbol ester in Rho-independent manners. VSM express at least four PI3K isoforms, including the class I enzymes p110alpha and p110beta and the class II enzymes PI3K-C2alpha and -C2beta. The dose-response relationships of PI3K-inhibitor-induced inhibition of Rho, MLC phosphorylation and contraction were similar to that of PI3K-C2alpha inhibition, but not to that of the class I PI3K inhibition. Moreover, KCl and noradrenaline induced stimulation of PI3K-C2alpha in a Ca2+-dependent manner, but not of p110alpha or p110beta. Down-regulation of PI3K-C2alpha expression by siRNA (small interfering RNA) inhibited contraction and phosphorylation of MYPT1 and MLC in VSM cells. Finally, intravenous wortmannin infusion induced sustained hypotension in rats, with inhibition of PI3K-C2alpha activity, GTP-loading of Rho and MYPT1 phosphorylation in the artery. These results indicate the novel role of PI3K-C2alpha in Ca2+-dependent Rho-mediated negative control of MP and thus VSM contraction.

Animals↗
PubMed2006

Selective heterogeneous nucleation and growth of size-controlled metal nanoparticles on carbon nanotubes in solution.

We present a novel approach to the in situ deposition of size-controlled platinum nanoparticles on the exterior walls of carbon nanotubes (CNTs). The reduction of metal ions in ethylene glycol (EG), by the addition of a salt such as sodium dodecyl sulfate (SDS), p-CH3C6H4SO3Na, LiCF3SO3, or LiClO4, results in high dispersions and high loadings of platinum nanoparticles on CNTs without aggregation. We have performed controlled experiments to elucidate the mechanism. By exploiting the salt effect, our method effectively depresses homogeneous nucleation, leading to selective heterogeneous metal nucleation and growth, even on unmodified CNTs. In the 2.3-9.6 nm size range, the size of platinum nanoparticles, at 50% loading, can be controlled by changing the concentration of metal ions, the reaction temperature, the reducing reagent or the means by which reactive solutions are added. Our method provides a flexible route towards the preparation of novel one-dimensional hybrid materials, for which a number of promising applications in a variety of fields can be envisioned.

Crystallization↗
PubMed2006

[Intra-operative stereotactic accuracy of computer-assisted robot orthopaedic trauma surgery planning system].

OBJECTIVE: To investigate the feasibility and accuracy of the software computer-assisted robot orthopaedic trauma surgery planning system (CAOTS). METHODS: The software CAOTS was developed and used on 85 cases of stereotactic operation, 24 model bones, 21 cadaveric extremity bones, and 40 patients. 307 groups of directional targets in these cases were randomly sampled. The distribution of error sources for evaluating system performance was embodied using Monte-Carlo method in order to derive the theoretic guarantees for further optimizing and enhancing the system performance, then the software SPSS 2.0 was used to analyze the errors. RESULTS: The statistical area of deviation number was 0.0408 +/- 0.4578 mm, corresponding to the result by Monte-Carlo method. Punching succeeded at the first run for all 307 cases without wrong locking and other clinical complications. CONCLUSION: Accurate and reliable, CAOTS improves the intra-operative navigation techniques and facilitates the orthopedists to perform operation.

Cadaver↗
PubMed2006

[Effects of medical robot-assisted surgical navigation system in distal locking of femoral intramedullary nails: an experimental study].

OBJECTIVE: To investigate the effects of medical robot-assisted surgical navigation system based on fluoroscopic images in distal locking of femoral intramedullary nails. METHODS: Using a robot-assisted computer-guided system designed based on modularization and minimization that permitted C-arm alignment assistance and real-time navigation control, provided constant feedback without the need for radiologic updates, thus avoiding constant X-ray exposure. The C-arm was used to collect the orthotopic and lateral X-ray images into the computer so as to calculate the locations of the target points. Nails were locked into 5 plastic femurs (Swiss Sybone, 35 holes), 2 dry human femoral specimens (12 holes), and one leg of fresh human cadaver (6 holes). Radiographs were taken to confirm that screws were positioned correctly, and fluoroscopic time associated with the locking procedure was recorded. RESULTS: All distal holes were locked successfully. In 6 (11.1%) of the 53 holes the drill bit touched the canal of the locking hole, albeit with no damage to the nail. The fluoroscopy time of per screw was 1.83 +/- 0.31 seconds. CONCLUSION: The medical robot-assisted surgical navigation system enables the physicians to precisely navigate surgical instruments throughout the procedure using just a few computer-calibrated radiographic images. The total radiation time per procedure can be significantly reduced because additional X-ray exposure is not required for tool navigation. The idea of a robot-assisted surgical navigation system is practicable.

Bone Nails↗
PubMed2006

Vibrational spectra study on quinolones antibiotics.

In order to be able to fully understand and easily identify the quilonoles, we collected IR and Raman spectra of six quinolones, and attempted to assign the attribution of the observed frequencies and their association with specific modes of vibration. According to the structure, the compounds were divided into the groups, and the similarities and differences were further studied by comparing. The result of the study shows that the frequency and intensity are comparable to the corresponding structure. The spectra not only have the commonness but also the individualities.

Anti-Bacterial Agents↗
PubMed2006

Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome.

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is traditionally thought to be a cytosolic fatty acid chaperone expressed in adipocytes. Mice with targeted disruption of the A-FABP gene exhibit a striking phenotype with strong protection from insulin resistance, hyperglycemia, and atherosclerosis. The clinical relevance of these findings remains to be confirmed. METHODS: We used tandem mass spectrometry-based proteomic analysis to identify proteins secreted from adipocytes and present in human serum. We measured serum A-FABP concentrations in 229 persons (121 men and 108 women; age range, 33-72 years), including 100 lean [body mass index (BMI) <25 kg/m2] and 129 overweight/obese individuals (BMI >25 kg/m2) selected from a previous cross-sectional study. RESULTS: A-FABP was released from adipocytes and was abundantly present in human serum. Mean (SD) circulating concentrations of A-FABP were significantly higher in overweight/obese than in lean persons [32.3 (14.8) vs 20.0 (9.8) microg/L; P < 0.001]. Age- and sex-adjusted serum A-FABP concentrations correlated positively (P < 0.005) with waist circumference, blood pressure, dyslipidemia, fasting insulin, and the homeostasis model assessment insulin resistance index. Moreover, we observed a significant increase in A-FABP concentrations corresponding with increases in the number of components of the metabolic syndrome (P < 0.05). CONCLUSIONS: A-FABP is a circulating biomarker closely associated with obesity and components of the metabolic syndrome, and measurement of serum concentrations of A-FABP might be useful for clinical diagnosis of obesity-related metabolic and cardiovascular disorders.

Adipocytes↗
PubMed2006

Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes.

Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF-1alpha), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein (C/EBPalpha), but had no effect on HIF-1alpha, whereas hypoxia stabilized HIF-1alpha and decreased expression of C/EBPalpha, but not PPARgamma. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

3T3-L1 Cells↗
PubMed2006

Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin.

Adiponectin is a fat cell-secreted hormone with antidiabetic and anti-inflammatory activities. The reduced adiponectin levels are associated with obesity-related metabolic syndrome. Replenishment of this hormone into animal models can improve insulin sensitivity, decrease blood glucose and lipid levels, and prevent the development of atherosclerosis and fatty liver injury. Despite these findings, the underlying molecular mechanisms remain largely unknown. Here, we have used affinity chromatography to purify the protein complexes that are associated with adiponectin in human serum. The nature of these adiponectin-binding proteins was analyzed by MS/MS. Eight proteins from the adiponectin-containing protein mixtures have been identified. Many of them, including thrombospondin-1 (TSP-1), histidine-rich glycoprotein, kininogen 1, and alpha 2 macroglobulin (alpha2M), are well-known glycoproteins involved in the regulation of inflammation, angiogenesis, and tissue remodeling. Coimmunoprecipitation and radioligand competitive-binding assays confirmed the direct interactions between adiponectin and alpha2M, or TSP-1. Moreover, these specific bindings were also detected in the serum samples derived from both healthy human subjects and patients with type 2 diabetes. In summary, our study demonstrated that, in the circulation, adiponectin forms protein complexes with other serum proteins. These proteins might serve as the physiological-binding partners of adiponectin and regulate its bioavailability and biological activities.

Adiponectin↗
PubMed2006

Bioassay-guided isolation of antiatherosclerotic phytochemicals from Artocarpus altilis.

The cytoprotective effects of various solvent extracts of Artocarpus altilis (Parkinson) Fosberg were evaluated. The cytoprotective effects were determined in human U937 cells incubated with oxidized LDL (OxLDL) using the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate (WST-1) assay. The results demonstrated that the ethyl acetate extract showed cytoprotective activities. To identify the main cytoprotective components, a bioassay guided isolation of the ethyl acetate extract afforded b-sitosterol (1) and six flavonoids (2-7). Their chemical structures were established on the basis of spectroscopic evidence and comparison with literature data. Of these compounds, compound 6 was obtained from A. altilis for the first time. The cytoprotective effect offers good prospects for the medicinal applications of A. altilis.

Artocarpus↗
PubMed2006

Transfer of siRNA against XIAP induces apoptosis and reduces tumor cells growth potential in human breast cancer in vitro and in vivo.

BACKGROUND: Gene targeting using short interfering RNA(siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. It is proven that the application of siRNA technology to gene therapy is effective. In this study, we constructed a siRNA expression plasmid against gene X-linked inhibitor of apoptosis (XIAP), and then used breast cancer cells MCF-7 to assess its functions. MATERIALS AND METHODS: XIAP siRNA plasmid was constructed using an U6pro vector contained U6 promoter, After the plasmid had been transfected into MCF-7 cells and effected on the cell cycle, the expression change of XIAP was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The apoptosis of the transfected cells was analyzed by flow cytometry, and TUNEL method. The in vitro cellular growth activities were assayed by MTT incorporation. Twenty-four nude mice were randomly divided into 3 equal groups and were inoculated with electroinjection of blank plasmid, scrambled nucleotide control (control siRNA), or siRNA against XIAP subcutaneously respectively, then the appearance and size of tumors were observed. Four weeks later the mice were killed and the volumes of tumor were calculated so as to evaluate the therapeutic effects of siRNA against XIAP. RESULTS: The successful construction of siRNA against XIAP plasmid was identified with sequencing. After the siRNA expression vector was transfected into the MCF-7 cells, the expression of XIAP gene was inhibited significantly (by 90%). The cellular growth activities in the MCF-7 cells transfected with siRNA against XIAP plasmid decreased obviously. The siRNA against XIAP plasmid knocked down XIAP expression in MCF-7 cells obviously, arrested the cell cycle in G1 phase, inhibited cell proliferation significantly, and promoted cell apoptosis in a tendency. TUNEL assay and flow cytometry showed that the classic apoptosis characters of the MCF-7 cells transfected with siRNA against XIAP plasmid manifested an apoptosis rate of 77.2%, significantly higher than those in the control siRNA group and in the blank plasmid group (both p < 0.01). The growth speed and formation rate of xenograft tumor in mice transfected with siRNA against XIAP transfected mice slowed down significantly. By HE staining, a lot of necrotic tissues could be observed in the siRNA against XIAP transfected group, however, there was no similar inhibitive effect in the control siRNA or blank plasmid group. CONCLUSION: This study represents that MCF-7 transfected cells with siRNA against XIAP remarkably suppress tumor growth and induces apoptosis, both in vitro and in vivo. This novel modality may be a promising tool for cancer therapy.

Apoptosis↗
PubMed2006

Sequence analysis for the complete proviral genome of reticuloendotheliosis virus Chinese strain HA9901.

The genomic DNA extracted from chicken embryo fibroblast (CEF) infected with a Chinese field isolate HA9901 of reticuloendotheliosis virus (REV) was used as the template to amplify the REV proviral genomic cDNA by PCR with 6 pairs of primers according to published sequences. Six overlapping fragments were amplified, cloned into the TA vector and sequenced, including a fragment which was amplified from the circular proviral cDNA and covering both 5'- and 3'-ends. The complete sequence of the whole genome was established and analyzed with a DNAstar software. Comparisons of the sequence with two other strains demonstrated that the genomes of REV were relatively conservative, the homogenecity for all genes or LTR fragments of the 3 strains was over 92%, no matter whether they were isolated from different species and regions in different years. But, the homology of Chinese strain HA9901 to a fowl pox virus-associated strain from Chickens was higher than that to strain SNV isolated from ducks.

Animals↗
PubMed2006

A new method to synthesize complicated multi-branched carbon nanotubes with controlled architecture and composition.

Here we develop a simple method by using flow fluctuation to synthesize arrays of multi-branched carbon nanotubes (CNTs) that are far more complex than those previously reported. The architectures and compositions can be well controlled, thus avoiding any template or additive. A branching mechanism of fluctuation-promoted coalescence of catalyst particles is proposed. This finding will provide a hopeful approach to the goal of CNT-based integrated circuits and be valuable for applying branched junctions in nanoelectronics and producing branched junctions of other materials.

Catalysis↗
PubMed2006

Photolysis behavior of herbicide propisochlor in water media and preliminary analysis of photoproducts under different light sources.

Photolysis behavior of a new herbicide propisochlor in water media as well as the effects of light sources, initial concentration of propisochlor, pH value, dissolved oxygen (DO) level, and salinity on the photolysis process was investigated. It was found that the relationship between initial concentration of propisochlor and its photodegradation rate was negatively correlated. The changes in acidity and alkalinity of the reaction medium influenced the photoreaction rate evidently. In the alkaline solution the degradation was accelerated. In the reaction media with different pH values, the photolysis followed the first-order kinetics. The presence of dissolved oxygen may promote the photolysis and there existed an optimum of dissolved oxygen concentrations. Increasing the DO level can weaken the promotion and even have an adverse effect. It was demonstrated that with dissolved oxygen the photodegradation of propisochlor followed the first-order kinetics equation. The addition of salt ions Ca2+ and Mg2+ changed the ionic strength and solvent polarity, resulting in the effect on propisochlor photolysis. The photoproducts were detected by both HPLC and GC-MS methods. It was found that photolysis products varied under different light sources. Conclusions may be reached that in the photodegradation of propisochlor, the benzene ring remained intact under irradiation of both solar light and high-pressure mercury lamp, and the amido link was relatively stable, while dechlorination was liable to take place; moreover, alpha-hydrogen at the substituent of benzene ring was active.

Acetamides↗
PubMed2006

Meta-analysis of inoperable pancreatic cancer: gemcitabine combined with cisplatin versus gemcitabine alone.

OBJECTIVES: To compare the therapeutic effects of gemcitabine (GEM) monotherapy with GEM-cisplatin (DDP) combination chemotherapy in patients with advanced stage pancreatic cancer (APCa) through meta-analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-DDP combination chemotherapy and GEM alone in APCa. A quantitative meta-analysis using updated information based on inclusion criteria from all available RCTs was carried out by two reviewers. The primary meta-analysis involved the overall survival (OS), objective remission rate (ORR) and toxicity. RESULTS: The meta-analysis included six RCTs. There was no significant advantage for the GEM-DDP combination group in 6-month survival rate (P = 0.24) or clinical benefit rate (P = 0.58). There was a marginal significant improvement for the GEM-DDP combination group in ORR (RD = 6%, P = 0.05; RD, risk difference = risk in the GEM-DDP combination group - risk in the GEM alone group). Moreover, there was a significant improvement for the combination group in 6-month TTP/TTF (RD = 9%, P = 0.02). WHO grade 3-4 toxicity was higher for the GEM-DDP combination group in terms of neutropenia (RD = 6%, P = 0.08), thrombocytopenia (RD = 8%, P = 0.17) and vomiting/nausea (RD = 11%, P = 0.07); none reached significant difference. CONCLUSION: GEM-DDP combination should not be recommended and GEM monotherapy remains the standard treatment for patients with APCa.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Motor learning changes GABAergic terminals on spinal motoneurons in normal rats.

The role of spinal cord plasticity in motor learning is largely unknown. This study explored the effects of H-reflex operant conditioning, a simple model of motor learning, on GABAergic input to spinal motoneurons in rats. Soleus motoneurons were labeled by retrograde transport of a fluorescent tracer and GABAergic terminals on them were identified by glutamic acid decarboxylase (GAD)67 immunoreactivity. Three groups were studied: (i) rats in which down-conditioning had reduced the H-reflex (successful HRdown rats); (ii) rats in which down-conditioning had not reduced the H-reflex (unsuccessful HRdown rats) and (iii) unconditioned (naive) rats. The number, size and GAD density of GABAergic terminals, and their coverage of the motoneuron, were significantly greater in successful HRdown rats than in unsuccessful HRdown or naive rats. It is likely that these differences are due to modifications in terminals from spinal interneurons in lamina VI-VII and that the increased terminal number, size, GAD density and coverage in successful HRdown rats reflect and convey a corticospinal tract influence that changes motoneuron firing threshold and thereby decreases the H-reflex. GABAergic terminals in spinal cord change after spinal cord transection. The present results demonstrate that such spinal cord plasticity also occurs in intact rats in the course of motor learning and suggest that this plasticity contributes to skill acquisition.

Analysis of Variance↗