Biomedical subjects

Wei Wang

Publications and source records attributed to Wei Wang.

At least 235 records · Page 13Linked to original sources

PubMed2006

Freeze-drying of liposomes using tertiary butyl alcohol/water cosolvent systems.

The objective of this study was to obtain dehydrated liposomes using a novel procedure that involves freeze-drying (FD) of liposomes with TBA/water cosolvent systems. The effects of TBA on the integrity/stability of vesicles of HSPC (or SPC):Cholesterol (4:1) were investigated. TBA used as a cosolvent was detrimental to SPC liposomes, leading to increased particle size and leakage of trapped calcein. However, this was not the case for HSPC liposomes. The vesicle size and the retention of trapped calcein after lyophilization from cosolvents were similar to those after FD from water alone. Moreover, the addition of TBA can significantly enhance the sublimation of ice resulting in short FD cycles. The resulting lyophilized cake can form a loose powder upon agitation, which flowed well enough to be easily poured from the vial. Thus FD of HSPC liposomes using TBA/water cosolvent systems can provide sterile powder for specialized applications. In addition, in conjunction with a modified injection method, this FD technology might be used to produce dehydrated HSPC liposomes on a large scale.

Calorimetry, Differential Scanning↗

PubMed2006

Automatic atom type and bond type perception in molecular mechanical calculations.

In molecular mechanics (MM) studies, atom types and/or bond types of molecules are needed to determine prior to energy calculations. We present here an automatic algorithm of perceiving atom types that are defined in a description table, and an automatic algorithm of assigning bond types just based on atomic connectivity. The algorithms have been implemented in a new module of the AMBER packages. This auxiliary module, antechamber (roughly meaning "before AMBER"), can be applied to generate necessary inputs of leap-the AMBER program to generate topologies for minimization, molecular dynamics, etc., for most organic molecules. The algorithms behind the manipulations may be useful for other molecular mechanical packages as well as applications that need to designate atom types and bond types.

Algorithms↗

PubMed2006

The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells.

Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-independent mechanism. At concentrations that suppress extracellular signal-regulated kinase (ERK) phosphorylation, BAY 43-9006 dephosphorylates Bad on Ser(75) and Ser(99), activates Bak and Bax, and reduces the mitochondrial transmembrane potential. BAY 43-9006 (sorafenib) down-modulates the levels of Bcl-2 and Bcl-X(L) in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Of the three lines tested, only A375 cells were rescued from BAY 43-9006-induced apoptosis by knocking down Bad. BAY 43-9006 induced poly(ADP-ribose) polymerase cleavage and the mitochondrial release of cytochrome c and SMAC. However, the pan-caspase inhibitor Z-VAD-fmk had only a modest protective effect against the drug, suggesting that BAY 43-9006-induced apoptosis is largely caspase independent. BAY 43-9006 but not the MAP/ERK kinase inhibitors PD98059 or U0126 induced the nuclear translocation of apoptosis-inducing factor (AIF) in A2058 and SKMEL5 cells, and the introduction of a small interfering RNA (siRNA) for AIF partially protected these cells from BAY 43-9006-induced apoptosis. The AIF siRNA had little effect in A375 cells, in which drug-induced AIF release was negligible. These data indicate that in sensitive cell lines, BAY 43-9006-induced apoptosis is independent of Bad dephosphorylation and caspase activation and largely mediated through the nuclear translocation of AIF.

Apoptosis↗

PubMed2006

[Role of urinary basic fibroblast growth factor in differentiating hemangiomas from vascular malformation].

OBJECTIVE: To investigate a novel method to differentiate hemangioma from vascular malformation, to stage hemangiomas and to monitor the efficacy of management for hemangioma. METHODS: The urinary basic fibroblast growth factor (bFGF) concentration of 144 cases (including 69 cases of proliferating hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular malformations and 11 negative controls) was examined using enzyme linked immunosorbent assay (ELISA). RESULTS: The differences of urinary bFGF concentration among proliferating hemangiomas, involuting hemangiomas, vascular malformations and negative control were all significant, while the differences between the latter three groups were not significant. CONCLUSIONS: Our findings suggest that examination of urinary bFGF concentration using ELISA technique is helpful in differentiating hemangioma from vascular malformation, staging hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas. Our results probably shed new light on the potential pathogenesis of hemangiomas and vascular malformation.

Arteriovenous Malformations↗

PubMed2006

Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.

Protein-protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains, such as Src Homology 2 and 3 (SH2 and SH3) domains, which bind to specific sequence and structural motifs. It is important but challenging to determine the binding specificity of these domains accurately and to predict their physiological interacting partners. In this study, the interactions between 35 peptide ligands (15 binders and 20 non-binders) and the Abl SH3 domain were analyzed using molecular dynamics simulation and the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. The calculated binding free energies correlated well with the rank order of the binding peptides and clearly distinguished binders from non-binders. Free energy component analysis revealed that the van der Waals interactions dictate the binding strength of peptides, whereas the binding specificity is determined by the electrostatic interaction and the polar contribution of desolvation. The binding motif of the Abl SH3 domain was then determined by a virtual mutagenesis method, which mutates the residue at each position of the template peptide relative to all other 19 amino acids and calculates the binding free energy difference between the template and the mutated peptides using the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. A single position mutation free energy profile was thus established and used as a scoring matrix to search peptides recognized by the Abl SH3 domain in the human genome. Our approach successfully picked ten out of 13 experimentally determined binding partners of the Abl SH3 domain among the top 600 candidates from the 218,540 decapeptides with the PXXP motif in the SWISS-PROT database. We expect that this physical-principle based method can be applied to other protein domains as well.

Amino Acid Motifs↗

PubMed2006

Identification of polysaccharides from pericarp tissues of litchi (Litchi chinensis Sonn.) fruit in relation to their antioxidant activities.

A large number of polysaccharides are present in the pericarp tissues of harvested litchi fruits. A DEAE Sepharose fast-flow anion-exchange column and a Sephadex G-50 gel-permeation column were used to isolate and purify the major polysaccharides from litchi fruit pericarp tissues. Antioxidant activities of these major polysaccharide components were also evaluated. An aqueous extract of the polysaccharides from litchi fruit pericarp tissues was chromatographed on a DEAE anion-exchange column to yield two fractions. The largest amount of the polysaccharide fraction was subjected to further purification by gel filtration on Sephadex G-50. The purified product was a neutral polysaccharide, with a molecular weight of 14 kDa, comprised mainly of 65.6% mannose, 33.0% galactose and 1.4% arabinose. Analysis by Smith degradation indicated that there were 8.7% of (1-->2)-glycosidic linkages, 83.3% of (1-->3)-glycosidic linkages and 8.0% of (1-->6)-glycosidic linkages in the polysaccharide. Furthermore, different polysaccharide fractions extracted and purified from litchi fruit pericarp tissues exhibited strong antioxidant activities. Among these fractions, the purified polysaccharide had the highest antioxidant activity and should be explored as a novel potential antioxidant.

Antioxidants↗

PubMed2006

Prediction of binding sites of peptide recognition domains: an application on Grb2 and SAP SH2 domains.

Determination of the binding motif and identification of interaction partners of the modular domains such as SH2 domains can enhance our understanding of the regulatory mechanism of protein-protein interactions. We propose here a new computational method to achieve this goal by integrating the orthogonal information obtained from binding free energy estimation and peptide sequence analysis. We performed a proof-of-concept study on the SH2 domains of SAP and Grb2 proteins. The method involves the following steps: (1) estimating the binding free energy of a set of randomly selected peptides along with a sample of known binders; (2) clustering all these peptides using sequence and energy characteristics; (3) extracting a sequence motif, which is represented by a hidden Markov model (HMM), from the cluster of peptides containing the sample of known binders; and (4) scanning the human proteome to identify binding sites of the domain. The binding motifs of the SAP and Grb2 SH2 domains derived by the method agree well with those determined through experimental studies. Using the derived binding motifs, we have predicted new possible interaction partners for the Grb2 and SAP SH2 domains as well as possible interaction sites for interaction partners already known. We also suggested novel roles for the proteins by reviewing their top interaction candidates.

Amino Acid Sequence↗

PubMed2006

Folding and unfolding of chromophoric foldamers show unusual colorful single molecule spectral dynamics.

A series of well-defined linear multichromophoric foldamers with a specific sequence of alternating rigid perylene chromophores and flexible ethylene glycol chains were studied by single molecule fluorescence spectroscopy. Monomer showed minor spectral fluctuations compared to trimer and hexamer, which showed unusual and colorful spectral dynamics attributed to a stochastic photoinduced unfolding/folding phenomenon. The range of spectral shapes observed indicates varying degrees of pi-pi interaction between adjacent chromophores, with vibronically resolved green emission indicating completely unfolded structures and broad red emission indicating highly coupled and extensively folded pi-stacks. The rate of switching between different spectral shapes in the spectral trajectories suggests the existence of multiple pathways between the folded and unfolded states.

Biomimetic Materials↗

PubMed2006

Ultrasonic treatment of biological sludge: Floc disintegration, cell lysis and inactivation.

The aim of this work was to study the effect of ultra sound treatment on the solid content of sludge and biological activity, and the increase in the soluble chemical oxygen demand (SCOD), proteins and nucleic acids concentrations during sonication. The results showed that sonication effectively degraded and inactivated the sludge. The sludge disintegration and cell lysis occurred continuously while sludge inactivation mainly occurred in the second stage (10-30 min) during sonication. The SCOD, supernatant proteins and nucleic acids concentrations, and sludge mass reduction and inactivation degrees increased with the sonication time and power density increases. Higher energy ultrasound was more efficient than lower energy ultrasound for the sludge treatment.

Flocculation↗

PubMed2006

Synchrotron microradiography study on acute lung injury of mouse caused by PM(2.5) aerosols.

In order to investigate FeSO(4), ZnSO(4) (the two of main metal compositions of Shanghai PM(2.5) (particle matter with those aerodynamical diameter <2.5 microm)) effects on acute lung injury, six solutions contained PM(2.5) aerosol particles, FeSO(4), ZnSO(4) and their mixtures were instilled intratracheally into mouse lungs for experiment. By 2 days after instillation, the live mice were checked in vivo by synchrotron refractive index microradiography. In addition after extracted and examined by dissection, the right lobes of lung were fixed by formalin, then imaged by synchrotron microradiography again. Corresponding parts of those lung tissues were embedded in paraffin for histopathologic study. The synchrotron X-ray microradiographs of live mouse lung showed different lung texture changes after instilled with different toxic solutions. Hemorrhage points in lung were observed more from those mice instilled by FeSO(4) contained toxin solutions groups. Bronchial epithelial hyperplasia can be observed in ZnSO(4) contained solution-instilled groups from histopathologic analysis. It was found that the acute lung injury of mice caused by solution of PM(2.5)+FeSO(4)+ZnSO(4) was more serious than other toxin solutions. Results suggested that FeSO(4) mainly induced hemorrhage and ZnSO(4) mainly induced inflammation and bronchiolar epithelial hyperplasia in the early toxicological effects of PM(2.5).

Aerosols↗

PubMed2006

Activation of JNK and xanthine oxidase by TNF-alpha impairs nitric oxide-mediated dilation of coronary arterioles.

Elevated levels of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine, are associated with coronary artery disease. However, it is unclear whether vasodilator function of coronary resistance arterioles is susceptible to TNF. Herein, we examined whether TNF can affect endothelium-dependent nitric oxide (NO)-mediated dilation of coronary arterioles to adenosine and whether inflammatory signaling pathways such as mitogen-activated protein kinases, ceramide sphingolipids, and oxidative stress are involved in the TNF-mediated effect. To eliminate confounding influences associated with in vivo preparations, coronary arterioles from porcine heart were isolated and pressurized without flow for in vitro study. Intraluminal treatment with TNF (1 ng/ml, 90 min) significantly attenuated the NO release and vasodilation to adenosine. This inhibitory effect was not observed in denuded vessels or in the presence of NO synthase inhibitor l-NMMA. Histochemical data showed that superoxide production and JNK phosphorylation in arteriolar endothelial cells was enhanced by TNF. Administration of superoxide scavenger or inhibitors of ceramide-activated protein kinase (dimethylaminopurine), JNK (SP600125 and dicumarol), and xanthine oxidase (allopurinol) reduced superoxide production as well as restored NO release and vasodilation to adenosine. Conversely, the effects of TNF were insensitive to inhibitors of p38 (SB203580), ERK (PD98059), NAD(P)H oxidase (apocynin), or mitochondrial respiratory chain (rotenone). These data indicate that TNF inhibits endothelium-dependent NO-mediated dilation of coronary arterioles by ceramide-induced activation of JNK and subsequent production of superoxide via xanthine oxidase. Because myocardial ischemia augments adenosine production and elevates TNF level, inhibiting adenosine-stimulated endothelial release of NO by TNF could contribute to inadequate regulation of coronary blood flow during the development of ischemic heart disease.

Adenosine↗

PubMed2006

Adenosine regulation of cystic fibrosis transmembrane conductance regulator through prostenoids in airway epithelia.

Cystic fibrosis is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered ion transport, chronic infection, and excessive inflammation. Here we investigated regulation of CFTR in airway cell monolayers by adenosine, adenosine receptors, and arachidonic acid. Our studies demonstrate that the A2B adenosine receptor is expressed at high levels relative to the other adenosine receptor subtypes, with a characteristic low-affinity profile for adenosine-stimulated CFTR Cl- currents in both Calu-3 cells and CFBE41o- airway cell monolayers stably transduced with wild-type CFTR. The levels of adenosine found in sputum from patients with cystic fibrosis with moderate to severe lung disease stimulated apical prostaglandin release in Calu-3 and CFBE41o- cells, implicating adenosine regulation of phospholipase A2 (PLA2) activity. A2B adenosine receptor and arachidonic acid stimulation produced CFTR-dependent currents in airway monolayers and increased cAMP levels that were sensitive to cyclooxygenase inhibition. Arachidonic acid demonstrated dual regulation of CFTR, stimulating CFTR and Cl- currents in intact airway monolayers, and potently inhibiting PKA-activated Cl- currents in excised membrane patches. Cl- currents produced by arachidonic acid were sensitive to inhibition of PKA, cyclooxygenase, and 5-lipoxygenase. Together, the results provide a converging mechanism to link regulation of CFTR and airway cell inflammation through adenosine and adenosine receptors.

Adenosine↗

PubMed2006

Radioactive 26Al from massive stars in the Galaxy.

Gamma-rays from radioactive 26Al (half-life approximately 7.2 x 10(5) years) provide a 'snapshot' view of continuing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along its plane. This led to the conclusion that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show evidence for locally produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/- 0.8) solar masses of 26Al. We use this to determine that the frequency of core collapse (that is, type Ib/c and type II) supernovae is 1.9 (+/- 1.1) events per century.

Journal Article↗

PubMed2006

Propagation of firing rate in a feed-forward neuronal network.

Propagation of the firing rate and synchronous firings in a 10-layer feed-forward neuronal network are studied. When neurons in layer 1 are subject to white noise, synchrony can be built up in deep layers and the firing rate can be propagated. A network with 6 layers is found to be enough for such behavior. A periodic signal with frequencies of 30-80 Hz can be selectively transmitted through the network. These abilities in information processing due to synchrony can be modulated by noise and the operating mode of neurons, and our results are relevant to experimental findings.

Action Potentials↗

PubMed2006

Lignin degradation by a novel peptide, Gt factor, from brown rot fungus Gloeophyllum trabeum.

Gt factor, a pure component isolated from Gloeophyllum trabeum, was used to decompose lignin materials. The radical intermediates, degradation products and structural changes of treated materials were analyzed by infrared spectrum, NMR and electron paramagnetic resonance, etc. The results indicate that Gt factor makes an oxidative attack on lignin via HO., which might be the initial step in lignocellulose degradation by brown rot fungus.

Basidiomycota↗

PubMed2006

Identification and determination of major flavonoids in rat urine by HPLC-UV and HPLC-MS methods following oral administration of Dalbergia odorifera extract.

Flavonoids are the main active constituents of Dalbergia odorifera. The excretion of the major flavonoids in rat urine after oral administration of D. odorifera extract was investigated by HPLC-UV and HPLC-MS methods. Utilizing the HPLC-MS technique, 18 flavonoids, including five isoflavones, four isoflavanones, four neoflavones, two flavanones, two chalcones and one isoflavanonol were identified in free form in a urine sample based on the direct comparison of the corresponding tR, UV maximum absorbance (lambda(max)) values and MS data with the authentic standards. The amounts of the prominent flavonoids, (3R)-4'-methoxy-2',3,7-trihydroxyisoflavanone and vestitone, were determined by HPLC-UV with the internal standard method, and the validation procedure confirmed that it afforded reliable analysis of these two analytes in urine after oral administration of D. odorifera extract.

Administration, Oral↗

PubMed2006

Determination of puerarin in rat cortex by high-performance liquid chromatography after intravenous administration of Puerariae flavonoids.

In the present study, a rapid and simple high-performance liquid chromatographic (HPLC) assay for determination of puerarin in rat cortex was developed. The analysis was carried out on a Zorbax SB-C18 column with mobile phase acetonitrile-0.5% aqueous phosphoric acid (11:89, v/v). The detection was by UV at 252 nm. The calibration curve for puerarin was linear (r=0.9999) over the concentration range 0.516-206.250 microg/mL. The limit of detection was 0.206 microg/mL (signal-to-noise ratio 3) and the limit of quantification (signal-to-noise ratio 10) was 0.516 microg/mL. Stability studies showed that puerarin was stable at temperatures of 4 degrees C in methanol for at least 30 days. The intra- and inter-day assays of puerarin from rat cortex were less than 2.5% at concentration range 0.516-206.250 microg/mL and good overall recoveries (97.4-101.7%) were found at same concentrations. The method was applied to determine the pharmacokinetic parameters and the time course of puerarin in rat cortex, following a single dosage of intravenous administration of flavonoids from Puerariae radix at 32 mg/kg of puerarin to male Wistar rats.

Animals↗

PubMed2006

Pharmacokinetic study of p-coumaric acid in mouse after oral administration of extract of Ananas comosus L. leaves.

Quantification of p-coumaric acid in mouse plasma following oral administration of Ananas comosus L. leaves was achieved by reversed-phase high-performance liquid chromatography using a mobile phase of water-acetonitrile (82:18, v/v) and UV detection at 310 nm. The method was linear (determination coefficient, r2 = 0.9997) within the tested range (0.04-1.28 microg/mL). Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (maximal CV value was 4.06% for intra-day and 4.19% for inter-day) over the entire range. The recoveries were 90.63, 97.98 and 100.01% for concentrations of 0.04, 0.32 and 1.28 microg/mL, respectively. This is a very rapid, sensitive and economical way to determine p-coumaric acid concentration in mouse plasma after oral administration of A. comosus leaves. The concentration-time curve was fitted to the one-compartment model. This is the first time that p-coumaric acid extracted from A. comosus leaves was detected by HPLC-UV method and its pharmacokinetic characteristic was comprehensively studied.

Administration, Oral↗