Biomedical subjects

Feng Wang

Publications and source records attributed to Feng Wang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Oriented assembly of Fe3O4 nanoparticles into monodisperse hollow single-crystal microspheres.

Magnetite nanoparticles of Fe3O4 were found to assemble into monodisperse hollow Fe3O4 microspheres with tunable diameters ranging from 200 to 400 nm and open pores on the shells in ethylene glycol in the presence of dodecylamine (DDA). The oriented assembly of nanoparticles conferred the individual hollow Fe3O4 microspheres a remarkable feature of single crystals. The morphologies of the products could be easily manipulated by varying the synthesis parameters. Increasing the concentration of DDA led to an obvious shape evolution of the products from rhombic nanoparticles to hollow microspheres, solid microspheres, and finally irregular nanoparticles, which were mainly attributed to the special self-assembly phenomenon of Fe3O4 nanoparticles in the solvothermal process.

Ferrosoferric Oxide↗

PubMed2006

Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226.

The androgen receptor (AR) is a ligand-inducible steroid hormone receptor that mediates androgen action, determining male sexual phenotypes and promoting spermatogenesis. As the androgens play a dominant role in male sexual development and function, steroidal androgen agonists have been used clinically for some years. However, there is a risk of potential side effects and most steroidal androgens cannot be dosed orally, which limits the use of these substances. 1,2-Dihydro-6-N,N-bis(2,2,2-trifluoroethyl)amino-4-trifluoromethyl-2-quinolinone (LGD2226) is a synthetic nonsteroidal ligand and a novel selective AR modulator. The crystal structure of the complex of LGD2226 with the androgen receptor ligand-binding domain (AR LBD) at 2.1 A was solved and compared with the structure of the AR LBD-R1881 complex. It is hoped that this will aid in further explaining the selectivity of LGD2226 observed in in vitro and in vivo assays and in developing more selective and effective therapeutic agents.

Binding Sites↗

PubMed2006

Structural and functional analysis of natrin, a venom protein that targets various ion channels.

Cysteine-rich secretory proteins (CRISPs) are secreted single-chain proteins found in different sources. Natrin is a member of the CRISP family purified from the snake venom of Naja naja atra, which has been reported as a BKca channel blocker. In our study, crystals of natrin were obtained in two different crystal forms and the structure of one of them was solved at a resolution of 1.68A. Our electrophysiological experiments indicated that natrin can block the ion channel currents of the voltage-gated potassium channel Kv1.3. Docking analyses of the interaction between natrin and Kv1.3 revealed a novel interaction pattern different from the two previously reported K(+) channel inhibition models termed "functional dyad" and "basic ring". These findings offered new insights into the function of natrin and how the specific interactions between CRISPs and different ion channels can be achieved.

Amino Acid Sequence↗

PubMed2006

LC-MS determination and relative bioavailability of doxazosin mesylate tablets in healthy Chinese male volunteers.

This study aims to develop a standard protocol for the relative bioavailability testing of doxazosin mesylate tablets. For this purpose, a simple rapid and selective LC-MS method using a single quadrupole mass spectrometer was developed and validated to determine the concentration of doxazosin mesylate in human plasma. Using this method, we carried out a study of relative bioavailability. N-Hexylane-tertiary butyl methyl ether (1:1, v/v) was used to extract doxazosin mesylate and terazosin (internal standard, I.S.) from an alkaline plasma sample. LC separation was performed on a Thermo Hypersil-Hypurity C18 (5 microm, 150 mm x 2.1mm) using aqueous solution (20 mmol/l ammonium acetate, pH 4.28), methanol and acetonitrile (55:10:35, v/v/v) as the mobile phase. The retention time of doxazosin and the internal standard was 2.7 and 1.8 min, respectively. Quadrupole MS detection was done by monitoring at m/z 388 (M+1) corresponding to doxazosin mesylate and at m/z 452 (M+1) for I.S. The assay method described above showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of doxazosin mesylate was evaluated in 12 healthy Chinese male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of 4 mg doxazosin. The area under the plasma concentration versus time curve from time 0 to 72 h (AUC(0-72 h)) 743.4+/-149.5 ngh/ml; peak plasma concentration (C(max)) 47.66 ng/ml; time to C(max) (T(max)) 3.0+/-1.0 h; and elimination half-life (t(1/2)) 18-20 h. The method was successfully used to determine the relative bioavailability of doxazosin mesylate.

Adrenergic alpha-Antagonists↗

PubMed2006

Rapid and simultaneous quantification of 4 urinary proteins by piezoelectric quartz crystal microbalance immunosensor array.

BACKGROUND: Urinary proteins are predictive and prognostic markers for diabetes nephropathy. Conventional methods for the quantification of urinary proteins, however, are time-consuming, and most require radioactive labeling. We designed a label-free piezoelectric quartz crystal microbalance (QCM) immunosensor array to simultaneously quantify 4 urinary proteins. METHODS: We constructed a 2 x 5 model piezoelectric immunosensor array fabricated with disposable quartz crystals for quantification of microalbumin, alpha1-microglobulin, beta2-microglobulin, and IgG in urine. We made calibration curves after immobilization of antibodies at an optimal concentration and then evaluated the performance characteristics of the immunosensor with a series of tests. In addition, we measured 124 urine samples with both QCM immunosensor array and immunonephelometry to assess the correlation between the 2 methods. RESULTS: With the QCM immunosensor array, we were able to quantify 4 urinary proteins within 15 min. This method had an analytical interval of 0.01-60 mg/L. The intraassay and interassay imprecisions (CVs) were <10%, and the relative recovery rates were 90.3%-109.1%. Nonspecificity of the immunosensor was insignificant (frequency shifts <20 Hz). ROC analyses indicated sensitivities were > or =95.8% and, specificities were > or =76.3%. Bland-Altman difference plots showed the immunosensor array to be highly comparable to immunonephelometry. CONCLUSIONS: The QCM system we designed has the advantages of being rapid, label free, and highly sensitive and thus can be a useful supplement to commercial assay methods in clinical chemistry.

Alpha-Globulins↗

PubMed2006

[Expression of c-myc protein on rats' brains after brain concussion].

OBJECTIVE: To study the changes of expression of c-myc protein on rats' brains after brain concussion. METHODS: sixty rats were randomly divided into brain concussion groups and control group. The expression of c-myc protein was microscopically observed by immunohistochemical method. RESULTS: No expression of c-myc protein in control group were observed. However, positive expression of c-myc protein in some neurons was seen at 20 min after brain concussion, and reach to the peak at 8h after brain concussion and then decreased gradually. CONCLUSION: These findings suggest that the detection of c-myc protein could be an index of diagnosis of brain concussion.

Animals↗

PubMed2006

Exciton polarizability in semiconductor nanocrystals.

The response of charge to externally applied electric fields is an important basic property of any material system, as well as one critical for many applications. Here, we examine the behaviour and dynamics of charges fully confined on the nanometre length scale. This is accomplished using CdSe nanocrystals of controlled radius (1-2.5 nm) as prototype quantum systems. Individual electron-hole pairs are created at room temperature within these structures by photoexcitation and are probed by terahertz (THz) electromagnetic pulses. The electronic response is found to be instantaneous even for THz frequencies, in contrast to the behaviour reported in related measurements for larger nanocrystals and nanocrystal assemblies. The measured polarizability of an electron-hole pair (exciton) amounts to approximately 10(4) A(3) and scales approximately as the fourth power of the nanocrystal radius. This size dependence and the instantaneous response reflect the presence of well-separated electronic energy levels induced in the system by strong quantum-confinement effects.

Journal Article↗

PubMed2006

[Construction, expression and identification of recombinant bacillus Calmette-Guérin vaccine secreting human interferon alpha-2a].

OBJECTIVE: To construct a recombinant bacillus Calmette-Guérin vaccine (BCG) secreting human interferon alpha-2a (IFNalpha-2a). METHODS: BCG Ag85B signal sequence was amplified from the genome of BCG by using polymerase chain reaction (PCR) and cloned in E.coli-BCG shuttle-vector pMV261 to get pMS. The cDNA fragment encoding human IFNalpha-2a was amplified from the plasmid pBIFNalpha-2a by using PCR and inserted into the shuttle expression vector pMV261. The recombinant plamid pMSIFNalpha-2a was identified by restriction endonuclease digestion, PCR amplification and nucleotide sequencing. pMSIFNalpha-2a was electroporated into BCG to get rBCG. The DNA and protein expressions of IFNalpha-2a gene in rBCG were determined by PCR and Western blotting respectively. IFNalpha-2a in the culture supernatant of rBCG was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The recombinant plamid pMSIFNalpha-2a was constructed successfully and confirmed by restriction endonuclease analysis, PCR detection and nucleotide sequencing analysis. pMSIFNalpha-2a was successfully transformed into BCG by electroporation and were capable of synthesizing and secreting cytokine IFNalpha-2a. Western blotting revealed that the secretive proteins could specially combine with antibody against human IFNalpha-2a. the level of IFNalpha-2a (324.57 pg/ml) in the culture supernatant of rBCG was higher than control group by ELISA assay. CONCLUSION: The constructed recombinant BCG strain produces and secretes human IFNalpha-2a and it will be used in the treatment of superficial bladder cancer.

BCG Vaccine↗

PubMed2006

Crystal structure of human histone lysine-specific demethylase 1 (LSD1).

Lysine-specific demethylase 1 (LSD1) was recently identified as the first histone demethylase that specifically demethylates monomethylated and dimethylated histone H3 at K4. It is a component of the CoREST and other corepressor complexes and plays an important role in silencing neuronal-specific genes in nonneuronal cells, but the molecular mechanisms of its action remain unclear. The 2.8-A-resolution crystal structure of the human LSD1 reveals that LSD1 defines a new subfamily of FAD-dependent oxidases. The active center of LSD1 is characterized by a remarkable 1,245-A3 substrate-binding cavity with a highly negative electrostatic potential. Although the protein core of LSD1 resembles other flavoenzymes, its enzymatic activity and functions require two additional structural modules: an N-terminal SWIRM domain important for protein stability and a large insertion in the catalytic domain indispensable both for the demethylase activity and the interaction with CoREST. These results provide a framework for further probing the catalytic mechanism and the functional roles of LSD1.

Catalytic Domain↗

PubMed2006

Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid.

Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.

Antitubercular Agents↗

PubMed2006

Determination of curcumin by its quenching effect on the fluorescence of Eu3+-tryptophan complex.

Curcumin (C21H20O6, CU) is a natural antioxidant, which is considered to be a very useful compound in health matters, and is employed in the treatment of cardiovascular and arthritic illnesses. It is found that the fluorescence intensity of Eu3+-tryptophan (Trp) can be greatly quenched by curcumin in the buffer of pH 7.7. Under optimum conditions, the quenched intensity of fluorescence is in proportion to the concentration of curcumin in the range of 1.0x10(-8) to 1.2x10(-4) mol L(-1). The detection limit (S/N=3) is 9.0x10(-10) mol L(-1). The synthetic and actual samples are satisfactorily determined. In addition, the interaction mechanism is also investigated.

Algorithms↗

PubMed2006

Base-displaced intercalated structure of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in the recognition sequence of the NarI restriction enzyme, a hotspot for -2 bp deletions.

The solution structure of the oligodeoxynucleotide 5'-d(CTCGGCXCCATC)-3'.5'-d(GATGGCGCCGAG)-3' containing the heterocyclic amine 8-[(3-methyl-3H-imidazo[4,5-f]quinolin-2-yl)amino]-2'-deoxyguanosine adduct (IQ) at the third guanine in the NarI restriction sequence, a hot spot for -2 bp frameshifts, is reported. Molecular dynamics calculations restrained by distances derived from 24 (1)H NOEs between IQ and DNA, and torsion angles derived from (3)J couplings, yielded ensembles of structures in which the adducted guanine was displaced into the major groove with its glycosyl torsion angle in the syn conformation. One proton of its exocyclic amine was approximately 2.8 A from an oxygen of the 5' phosphodiester linkage, suggesting formation of a hydrogen bond. The carcinogen-guanine linkage was defined by torsion angles alpha' [N9-C8-N(IQ)-C2(IQ)] of 159 +/- 7 degrees and beta' [C8-N(IQ)-C2(IQ)-N3(IQ)] of -23 +/- 8 degrees . The complementary cytosine was also displaced into the major groove. This allowed IQ to intercalate between the flanking C.G base pairs. The disruption of Watson-Crick hydrogen bonding was corroborated by chemical-shift perturbations for base aromatic protons in the complementary strand opposite to the modified guanine. Chemical-shift perturbations were also observed for (31)P resonances corresponding to phosphodiester linkages flanking the adduct. The results confirmed that IQ adopted a base-displaced intercalated conformation in this sequence context but did not corroborate the formation of a hydrogen bond between the IQ quinoline nitrogen and the complementary dC [Elmquist, C. E.; Stover, J. S.; Wang, Z.; Rizzo, C. J. J. Am. Chem. Soc. 2004, 126, 11189-11201].

Base Pairing↗

PubMed2006

Formation mechanism of Si3N4 nanowires via carbothermal reduction of carbonaceous silica xerogels.

Si3N4 nanowires prepared from the carbothermal reduction of carbonaceous silica xerogels with metal salt additives usually contain a small amount of nanotubes. This paper is devoted to the investigation of the formation mechanism of the Si3N4 nanowires. As-prepared samples heated at 1300 degrees C for different reaction times (1, 5, 10, and 30 h) were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The results showed that all the samples mainly consisted of nanowires, while their crystalline phases changed with the heating time. Nitrogen-doped silicon oxide nanowires were first produced via the vapor-liquid-solid process and then underwent a stepwise surface nitrogenization to silicon nitride. The suggested mechanism can easily explain the existence of nanotubes in the Si3N4 nanowires.

Journal Article↗

PubMed2006

Investigation of the interaction between curcumin and nucleic acids in the presence of CTAB.

It is found that nucleic acid can enhance the resonance light scattering (RLS) enhancement effect of curcumin (CU) in the presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The investigation indicates that in BR (pH 4.3) buffer, both the positive CTAB and negative yeast RNA (yRNA) combine and form a positive large association, then which is bound on the two carbon atoms of the carbonyls of CU through hydrogen bond and hydrophobic force and form CU-CTAB-yRNA ternary complex, resulting in the RLS enhancement of this system. Based on it, a sensitive method for determination of nucleic acids at ngml(-1) is established.

Cetrimonium↗

PubMed2006

Alternative methods of identifying the oxidation of metallic nanoparticles embedded in a matrix.

We compare methods for valence-state analysis based on energy-loss near-edge structure (ELNES), including the white-line ratio (WLR), pre-edge peak (prepeak) and post-edge peak (postpeak) techniques. Starting from multiple-scattering calculations, we correlate the appearance of a prepeak in the O-K edge and postpeak in the L-edge with oxidation of a transition metal (TM). The ability to use more than one technique is especially advantageous for a nanocomposite of metallic nanoparticles embedded in a matrix, as we show for the case of iron nanoparticles in a silica matrix.

Journal Article↗

PubMed2006

Evaluation of the thermal stability of Gardasil.

The thermostability of GARDASIL (Merck & Co., Inc, Whitehouse Station, NJ, USA), a developmental vaccine against human papillomavirus (HPV), was evaluated using an enzyme immunoassay, referred to as the in vitro relative potency (IVRP) assay and differential scanning calorimetry (DSC). Gardasil samples were stored at temperatures ranging from 4 to 42 degrees C and tested for IVRP at various time points. Extrapolation of the IVRP results indicates GARDASIL is extremely stable. The half-life of the vaccine is estimated to be 130 months or longer at temperatures up to 25 degrees C. At 37 degrees C, the half-life is predicted to be 18 months and at 42 degrees C, the half-life is predicted to be approximately three months. Differential scanning calorimetry (DSC) analysis was used to evaluate the process of protein denaturation during a rapid temperature increase (as opposed to long-term storage at a specific temperature). Differences were seen among the DSC profiles of the four HPV types tested. This indicates that small differences in the amino acid structure can have a significant effect on the intermolecular contacts that stabilize the L1 proteins and the VLP assembly. For the Gardasil samples evaluated here, DSC results demonstrated the relative overall structural stability of the VLPs, but were not predictive of the excellent long-term stability observed with the IVRP assay.

Calorimetry, Differential Scanning↗

PubMed2006

Sodium chloride-catalyzed oxidation of multiwalled carbon nanotubes for environmental benefit.

A sodium chloride (NaCl) catalyst (0.1 w/w %) lowers the oxidation temperature of graphitized multiwalled carbon nanotubes: MWCNT-20 (diameter: 20-70 nm) and MWCNT-80 (diameter: 80-150 nm). The analysis of the reaction kinetics indicates that the oxidation of MWCNT-20 and MWCNT-80 mixed with no NaCl exhibits single reaction processes with activation energies of E(a) = 159 and 152 kJ mol(-1), respectively. The oxidation reaction in the presence of NaCl is shown to consist of two different reaction processes, that is, a first reaction and a second reaction process. The first reaction process is dominant at a low temperature of around 600 degrees C, while the second reaction process becomes more dominant than the first one in a higher temperature region. The activation energies of the first reaction processes (MWCNT-20: E(a1) = 35.7 kJ mol(-1); MWCNT-80: E(a1) = 43.5 kJ mol(-1)) are much smaller than those of the second reaction processes (MWCNT-20: E(a2) = 170 kJ mol(-1); MWCNT-80: E(a2) = 171 kJ mol(-1)). The comparison of the kinetic parameters and the results of the spectroscopic and microscopic analyses imply that the lowering of the oxidation temperature in the presence of NaCl results from the introduction of disorder into the graphitized MWCNTs (during the first reaction process), thus increasing the facility of the oxidation reaction of the disorder-induced nanotubes (in the second reaction process). It is found that the larger nanopits and cracks on the outer graphitic layers are caused by the catalytic effect of NaCl. Therefore, the NaCl-mixed samples showed more rapid and stronger oxidation compared with that of the nonmixed samples at the same residual quantity.

Journal Article↗

PubMed2006

A picomole-scale method for rapid peptide sequencing through convenient and efficient N-terminal phosphorylation and electrospray ionization mass spectrometry.

Free or resin-bound peptides were phosphorylated at their N-termini by reacting with dimethyl phosphite in the presence of tetrachloromethane and triethylamine, and some of them were labeled using partial deuterium-labeled dimethyl phosphites (molar ratio of m + 6 and m = 1:1 or m + 6, m + 3 and m = 1:2:1) as the phosphorylating agents. The monophosphorylation of the lysine-containing peptides selectively occurred on the amino group of the N-terminus, not the side-chain of lysine residue. The resin-bound phosphoramidate peptides were cleaved by TFA before ESI-MS. The modified peptides were determined by electrospray ionization mass spectrometry, the protonated molecules of the unlabeled phosphoramidate peptides showed the singlet peaks, and those of the labeled phosphoramidate peptides displayed the doublet and/or triplet peaks. Tandem mass spectra (MS/MS) of the chosen protonated molecules gave sequential loss of the amino acid residues from the C-termini of the peptides, providing a convenient and rapid method for peptide sequencing.

Amino Acid Sequence↗