Biomedical subjects

Feng He

Publications and source records attributed to Feng He.

At least 19 recordsLinked to original sources

PubMed2006

Synthesis and biological evaluation of 4-aryl-5-cyano-2H-1,2,3-triazoles as inhibitor of HER2 tyrosine kinase.

4-Aryl-5-cyano-2H-1,2,3-triazoles bearing a variety of substituting groups on 4-phenyl were synthesized. The chemicals, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of inhibiting growth of breast cancer MDA-MB-453 cells. The lowest IC(50) value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6microM and the IC(50) value of cell growth inhibition is correspondingly 30.9microM. The lipophilicity of substituting groups on triazoles is the main factor to influence their bioactivities.

Breast Neoplasms↗

PubMed2006

Use of Autostitch for automatic stitching of microscope images.

Image stitching is the process of combining multiple images to produce a panorama or larger image. In many biomedical studies, including those of cancer and infection, the use of this approach is highly desirable in order to acquire large areas of certain structures or whole sections, while retaining microscopic resolution. In this study, we describe the application of Autostitch, viz. software that is normally used for the generation of panoramas in photography, in the seamless stitching of microscope images. First, we tested this software on image sets manually acquired by normal light microscopy and compared the performance with a manual stitching approach performed with Paint Shop Pro. Secondly, this software was applied to an image stack acquired by an automatic microscope. The stitching results were then compared with that generated by a self-programmed rectangular tiling macro integrated in Image J. Thirdly, this program was applied in the image stitching of images from electron microscopy. Thus, the automatic stitching program described here may find applications in convenient image stitching and virtual microscopy in the biomedical research.

Animals↗

PubMed2006

Structural analysis of the regulatory dithiol-containing domain of the chloroplast ATP synthase gamma subunit.

The gamma subunit of the F1 portion of the chloroplast ATP synthase contains a critically placed dithiol that provides a redox switch converting the enzyme from a latent to an active ATPase. The switch prevents depletion of intracellular ATP pools in the dark when photophosphorylation is inactive. The dithiol is located in a special regulatory segment of about 40 amino acids that is absent from the gamma subunits of the eubacterial and mitochondrial enzymes. Site-directed mutagenesis was used to probe the relationship between the structure of the gamma regulatory segment and its function in ATPase regulation via its interaction with the inhibitory epsilon subunit. Mutations were designed using a homology model of the chloroplast gamma subunit based on the analogous structures of the bacterial and mitochondrial homologues. The mutations included (a) substituting both of the disulfide-forming cysteines (Cys199 and Cys205) for alanines, (b) deleting nine residues containing the dithiol, (c) deleting the region distal to the dithiol (residues 224-240), and (d) deleting the entire segment between residues 196 and 241 with the exception of a small spacer element, and (e) deleting pieces from a small loop segment predicted by the model to interact with the dithiol domain. Deletions within the dithiol domain and within parts of the loop segment resulted in loss of redox control of the ATPase activity of the F1 enzyme. Deleting the distal segment, the whole regulatory domain, or parts of the loop segment had the additional effect of reducing the maximum extent of inhibition obtained upon adding the epsilon subunit but did not abolish epsilon binding. The results suggest a mechanism by which the gamma and epsilon subunits interact with each other to induce the latent state of the enzyme.

Alanine↗

PubMed2006

In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist.

BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-argininamide} was recently shown to display relatively high affinities for neuropeptide FF (NPFF) receptors and exhibit antagonist activities towards NPFF receptors in vitro. The present study was undertaken to investigate the antagonistic effects of BIBP3226 on several in vivo pharmacologic profiles induced by exogenous NPFF and NPVF. (1) BIBP3226 (5 nmol) injected into the third ventricle completely antagonized the hypothermic effects of NPFF (30 nmol) and NPVF (30 nmol) after cerebral administration in mice; (2) BIBP3226 (5 nmol, i.c.v.) prevented the anti-morphine actions of NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay; (3) in urethane-anaesthetized rats, both NPFF (200 nmol/kg, i.v.) and NPVF (200 nmol/kg, i.v.) increased the mean arterial blood pressure, which were significantly reduced by pretreatment with BIBP3226 (500 nmol/kg, i.v.). Collectively, these data suggest that BIBP3226, a mixed antagonist of NPY Y1 and NPFF receptors, shows in vivo antagonistic effects on NPFF receptors. In addition, it seems to be clear that the in vivo pharmacological profiles of NPFF are mediated directly by NPFF receptors.

Animals↗

PubMed2006

In search of functional association from time-series microarray data based on the change trend and level of gene expression.

BACKGROUND: The increasing availability of time-series expression data opens up new possibilities to study functional linkages of genes. Present methods used to infer functional linkages between genes from expression data are mainly based on a point-to-point comparison. Change trends between consecutive time points in time-series data have been so far not well explored. RESULTS: In this work we present a new method based on extracting main features of the change trend and level of gene expression between consecutive time points. The method, termed as trend correlation (TC), includes two major steps: 1, calculating a maximal local alignment of change trend score by dynamic programming and a change trend correlation coefficient between the maximal matched change levels of each gene pair; 2, inferring relationships of gene pairs based on two statistical extraction procedures. The new method considers time shifts and inverted relationships in a similar way as the local clustering (LC) method but the latter is merely based on a point-to-point comparison. The TC method is demonstrated with data from yeast cell cycle and compared with the LC method and the widely used Pearson correlation coefficient (PCC) based clustering method. The biological significance of the gene pairs is examined with several large-scale yeast databases. Although the TC method predicts an overall lower number of gene pairs than the other two methods at a same p-value threshold, the additional number of gene pairs inferred by the TC method is considerable: e.g. 20.5% compared with the LC method and 49.6% with the PCC method for a p-value threshold of 2.7E-3. Moreover, the percentage of the inferred gene pairs consistent with databases by our method is generally higher than the LC method and similar to the PCC method. A significant number of the gene pairs only inferred by the TC method are process-identity or function-similarity pairs or have well-documented biological interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study. CONCLUSION: The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data.

Algorithms↗

PubMed2006

Enzymatic synthesis and characterization of novel biodegradable copolymers of 5-benzyloxy-trimethylene carbonate with 1,4-dioxan-2-one.

Enzymatic ring-opening copolymerization of 5-benzyloxy-trimethylene carbonate (BTMC) and 1,4-dioxan-2-one (DON) was investigated for the first time. Immobilized porcine pancreas lipase (IPPL) on silica particles was selected to perform the copolymerization. A series of novel biodegradable copolymers with different compositions were characterized by (1)H NMR, (13)C NMR, and GPC. The influences of reaction conditions such as polymerization time and catalyst concentration on the yield and molecular weight of the copolymers were also studied. The copolymerizations of different monomer feed ratios were carried out in bulk at 150 degrees C with 4.5 wt per thousand IPPL as a catalyst for 24 h. With the increase of the BTMC molar feed ratio from 20% to 79%, the M(n) of the resulting copolymers increased from 5600 to 63400. Water uptake and static contact angle experiments showed that the hydrophilicity of copolymers could be improved with increasing DON content in the copolymers. Moreover, the in vitro drug release rate (ibuprofen as the model drug) of the resulting copolymers also increased along with the DON content in the copolymers.

Analgesics, Non-Narcotic↗

PubMed2006

Clearance of intravitreal moxifloxacin.

PURPOSE: To study the clearance of moxifloxacin after intravitreal injection in rabbits. METHODS: Intravitreal injections of 200 microg/0.1 mL of moxifloxacin were administered to rabbits. Four eyes per time point after injection (1 hour and 6, 12, 24, and 36 hours) and three eyes at 48 hours, respectively, were enucleated and immediately frozen and stored at -80 degrees C. Ocular dissection and isolation of frozen vitreous was performed. Vitreous samples were acquired at the various time intervals after injection. Antibiotic assays were performed with high performance liquid chromatography. RESULTS: The concentration of intravitreal moxifloxacin showed an exponential decay with a half-life of 1.72 hours. The mean vitreous concentration was 120.49 +/- 49.23 microg/mL 1 hour after injection, and declined to 20.23 +/- 5.85 microg/mL at 6 hours and 1.06 +/- 0.81 microg/mL at 12 hours, respectively. CONCLUSIONS: The vitreous concentrations achieved were several orders of magnitude greater than the MIC90 of organisms commonly involved in bacterial endophthalmitis, and therapeutic levels were maintained at 12 hours in uninflamed, phakic rabbit eyes. The pharmacokinetic data suggest that intravitreal moxifloxacin may have a role in the treatment of bacterial endophthalmitis.

Animals↗

PubMed2006

The effect of sleep-disordered breathing on stages of sleep in patients with Alzheimer's disease.

Patients with Alzheimer's disease (AD) commonly have poor sleep and a high reported incidence of sleep-disordered breathing (SDB). This study examined how the presence of SDB affected sleep stages in AD patients. Sixty-six volunteers with mild - moderate AD underwent home polysomnography. Results showed that patients with SDB spent less of the night in REM sleep than those with no SDB, but there were no differences in other sleep stages. The findings suggest that the decreased amount of REM sleep may be due to the presence of AD and SDB. Treating these patients' SDB may increase their amount of REM sleep, which may result in improved daytime functioning. Controlled trials of SDB treatment in AD are needed to answer this question.

Aged↗

PubMed2006

[Comparison of algal removal efficiencies in different ecological treatment systems and their combinations].

The algal removal efficiencies and their trends of 8 experimental ecological treatment systems, which belonged to 5 groups, were studied under different hydraulic loading rates (HLR). The algal removal efficiencies were compared according to the seasonal changes under the optimum HLR. Gravel-bed horizontal-flow wetland, down-flow wetland, up-flow wetland, aerobic ponds or facultative ponds combined these systems. The results show that the best HLR is 0.8m3/(m2 x d) in all the experimental systems. The systems including aerobic pond and down-flow wetland show a stronger resistance to hydraulic shock loading, as well as horizontal-flow wetland. The algal removal rates of all the systems peaked to over 94% in summer and bottomed in winter that varied from 34% to 90%. It was the combined form that determined the removal efficiency of the ecological treatment systems. The combination system of down-flow and up-flow wetland present the highest capacity of algal removal efficiency and lower seasonal fluctuation, while the gravel-bed horizontal-flow wetland system present the lowest efficiency and higher seasonal fluctuation.

Ecosystem↗

PubMed2006

[Responses of different Vicia faba varieties' photosynthetic characteristics to Pb pollution].

In a field experiment of simulated Pb pollution (40 and 250 mg x kg(-1)), this paper investigated the net photosynthetic rate, stomal conductance, transpiration rate, intercellular CO2 concentration, water use efficiency, and chlorophyll content of three Vicia faba varieties K0883, K0502 and K0697. The results showed that under Pb pollution, there was no significant variation in the transpiration rate and stomal conductance of the three varieties, but their chlorophyll content increased in different extents. When the Pb concentration was 250 mg x kg(-1), the net photosynthetic rate and water use efficiency of K0883 were increased by 121.80% and 193.70%, respectively, while its intercellular CO2 concentration was decreased by 42.76%. According to the Perturbation test based on the responses of test photosynthetic characteristics, the Pb-resistance of the three varieties was in the sequence of K0883 > K0697 > K0502. It was concluded that the responses of different photosynthetic indexes and different Vicia faba varieties to small dosage Pb pollution were differed, and the intraspecific difference could only be detected by the integration of all photosynthetic indices.

Lead↗

PubMed2005

In vitro and in vivo studies of dansylated compounds, the putative agonists and antagonists on neuropeptide FF receptors.

To further evaluate the importance of C-terminal modification of neuropeptide FF (NPFF), in the present work, four dansylated NPFF analogues, including two putative agonists (dansyl-PQRFamide and dansyl-GSRFamide) and two putative antagonists (dansyl-PQRamide and dansyl-GSRamide), were synthesized and investigated to address their potencies and efficacies in a series of in vitro and in vivo assays. (1) In the isolated mouse colon bioassay, the four dansylated compounds showed agonistic profiles: both dansyl-GSRFamide (1-10 microM) and dansyl-GSRamide (1-10 microM) dose-dependently caused colonic contractions, which were attenuated by pretreatment with BIBP3226; dansyl-PQRFamide and dansyl-PQRamide evoked modest colonic contractions at a high dose of 50 microM. (2) In urethane-anaesthetized rats, both dansyl-PQRFamide (50-300 nmol/kg, i.v.) and dansyl-GSRFamide (15-50 nmol/kg, i.v.) dose-dependently increased the mean arterial pressure and heart rate in a manner similar to NPFF (50-300 nmol/kg, i.v.); on the contrary, the two putative antagonists (100-800 nmol/kg, i.v.) decreased blood pressure in a dose-dependent manner. All the results suggest that dansyl-PQRFamide and dansyl-GSRFamide are NPFF full agonists; in contrast, dansyl-GSRamide and dansyl-PQRamide behave as agonists in vitro and antagonists in vivo on NPFF receptors. The findings reveal that the C-terminal Phe might be a crucial residue to determine the efficacy. In addition, the novel analogue dansyl-GSRFamide may be developed as a highly potent agonist to investigate the NPFF system.

Animals↗

PubMed2005

Synthesis, structures, and magnetic properties of heteronuclear Cu(II)-Ln(III) (Ln = La, Gd, or Tb) complexes.

Facile one-pot reactions led to the formations of dinuclear [CuLn(hmp)2(NO3)3(H2O)2] (Ln = Tb (1.Tb), Gd (1.Gd), or La (1.La)), and trinuclear [Cu2Ln(mmi)4(NO3)(H2O)2](ClO4)(NO3).2H2O (Ln = Tb (2.Tb) or Gd (2.Gd)) and [Cu2La(mmi)4(NO3)2(H2O)](ClO4).2H2O (2.La) with polydentate ligands 2-(hydroxymethyl)-pyridine and 2-hydroxymethyl-1-methyl-imidazole. In these complexes, each pair of Cu(II) and Ln(III) ions is linked by a double mu-alkoxo bridge. The temperature dependences of the magnetic susceptibilities of 1 and 2 were investigated in the range of 2-300 K. The dinuclear and trinuclear Cu-Gd complexes exhibit ferromagnetic interaction. The coupling constant J values in the heterodinuclear Cu-Gd complexes are correlated to values of the dihedral angles alpha between the two O-Cu-O and O-Gd-O fragments of the bridging CuO2Gd networks, with the largest J value associated with the smallest alpha value. The occurrence of a ferromagnetic interaction between Cu(II) and Gd(III) ions of the trinuclear entity is supported by the field dependence of the magnetization. The field dependence of the magnetization at 2 K of 1.Gd and 2.Gd confirms the nature of the ground state and of the Cu(II)-Gd(III) interaction, while alternating current susceptibility measurements demonstrates out-of-phase ac susceptibility signals of 1.Tb, which is the molecule-based magnetic material of the smallest nuclearity which exhibits frequency-dependent behavior within the 3d-4f mixed-metal systems.

Journal Article↗

PubMed2005

Relative contributions of codon usage, promoter efficiency and leader sequence to the antigen expression and immunogenicity of HIV-1 Env DNA vaccine.

Optimized antigen expression is critical to the immunogenicity of DNA vaccines. A number of approaches have been proposed to enhance the antigen expression and/or immunogenicity of DNA vaccines, but their relative contributions have not been compared in a same antigen system. In the current study, optimization of codon usage, enhancement of viral promoter function and selection of secretary leader sequences were evaluated for their roles in improving the immunogenicity of a same model antigen, the HIV-1 envelope glycoprotein. Our data demonstrated that all these factors can work synergistically to improve the final antigen expression and immunogenicity of HIV-1 Env DNA vaccines, indicating they work through different mechanisms. The best result came from the approach that optimized all three components in a DNA vaccine design. Our study further revealed that the levels of HIV-1 env-specific RNA transcripts in transiently transfected 293T cells were higher from the codon-optimized gene than the wild type counterpart. This finding suggested other mechanism may also contribute to the increased antigen expression and immunogenicity of codon-optimized DNA vaccines in addition to the improved tRNA usage in mammalian cells for codon-optimized viral genes as previously reported.

AIDS Vaccines↗

PubMed2005

Preparation and characterization of a new class of starch-stabilized bimetallic nanoparticles for degradation of chlorinated hydrocarbons in water.

Dechlorination of TCE and PCBs using bimetallic nanoparticles has received increasing interest in recent years. However, due to the extremely high reactivity, nanoparticles prepared using current methods tend to either react with surrounding media or agglomerate, resulting in the formation of much larger flocs and significant loss in reactivity. To overcome these drawbacks, we developed a simple and green approach for synthesizing palladized iron (Fe-Pd) nanoparticles. We modified the conventional methods by applying a water-soluble starch as a stabilizer. The starched nanoparticles displayed much less agglomeration but greater dechlorination power than those prepared without a stabilizer. TEM analyses indicated that the starched nanoparticles were present as discrete particles as opposed to dendritic flocs for nonstarched particles. The mean particle size was estimated to be 14.1 nm with a standard deviation of 11.7 nm, which translated to a surface area of approximately 55 m2 g(-1). While starched nanoparticles remained suspended in water for days, nonstarched particles agglomerated and precipitated within minutes. The starched nanoparticles exhibited markedly greater reactivity when used for dechlorination of TCE or PCBs in water. At a dose of 0.1 g L(-1), the starched particles were able to destroy 98% of TCE (C0 = 25 mg L(-1)) within 1 h. While trace amounts (<25 microg L(-1)) of 1,1-DCE were detected in the initial stage (<20 min) of degradation, no other intermediate byproducts such as vinyl chloride, cis-, or trans-dichloroethene were detected. The starched nanoparticles at approximately 1 g L(-1) were able to transform over 80% of PCBs (C0 = 2.5 mg L(-1)) in less than 100 h, as compared to only 24% with nonstarched Fe-Pd nanoparticles. The application of an innocuous stabilizer may substantially enhance the performances of palladized iron nanoparticles for environmental applications.

Environmental Pollutants↗

PubMed2005

Cloning and heterologous expression of the NADPH cytochrome P450 oxidoreductase genes from an industrial dicarboxylic acid-producing Candida tropicalis.

NADPH cytochrome P450 oxidoreductase (CPR) catalyses the transfer of electrons during P450-mediated oxidation, which plays an important role in the omega-oxidation pathway of Candida tropicalis. Two putative allelic genes, CPR-a and CPR-b, were cloned from the long chain dicarboxylic acid-producing Candida tropicalis 1230, using cassette PCR methods. Both the identified open reading frames predict the gene products of 679 amino acid residues. The deduced amino acid sequences of CPR-a and CPR-b are highly homologous to CPR genes from C. tropicalis ATCC 750 and Candida maltosa. Both genes were individually expressed in a cpr mutant of Saccharomyces cerevisiae with high CPR activities, in which only a small distinction was observed between recombinant CPR-a and CPR-b. Both CPR-a and CPR-b contain one CTG codon, which codes for serine (amino acid 50) in C. tropicalis rather than universal leucine. A mutated cDNA of CPR-a with a TCG codon instead of CTG codon was constructed and expressed, resulting in little increase in CPR activity. This indicates that the alteration of Ser-50 has little effect on functional expression of CPR. Furthermore, high ketoconazole sensitivity for the cpr mutant was complemented by heterologous expression of the cloned CPR-a or CPR-b.

Alleles↗

PubMed2005

Controlled aggregation of heterometallic nanoscale Cu12Ln6 clusters (Ln = Gd(III) or Nd(III)) into 2D coordination polymers.

Discrete dinuclear and polymeric heterometallic copper(II)-lanthanide(III) complexes have been synthesized upon variation of pH and characterized by X-ray diffraction analysis. Reactions of the ligand Htza (tetrazole-1-acetic acid) with copper(II) and lanthanide(III) salts gave dinuclear [CuLn(tza)4(H2O)5Cl] complexes at the low pH of 3.5 and 2D heterometallic coordination polymers with high-nuclearity [{Cu2(OH)2}2{Cu12Ln6(mu3-OH)24(Cl)(1/2)(NO3)(1/2)(tza)12(H2O)18}](NO3)(9).8H2O (Ln = Gd or Nd) at a higher pH of 6.6. The acidity of the reaction solution can cause drastic changes in the structures of the products. In the dinuclear complexes, each pair of adjacent dinuclear molecules is linked through hydrogen bonds and pi-pi stacking interactions, and the whole structure is a hydrogen-bonded three-dimensional cubic net. In the coordination polymers, the connecting nodes are [Cu12Ln6] units, which are interconnected by [Cu2O2] units into two-dimensional structures. Magnetic studies exhibit the existence of weak exchange interactions between the Cu(II) and Ln(III) ions bridged by carboxylate and hydroxy ligands.

Journal Article↗

PubMed2005

Coupling proton movement to ATP synthesis in the chloroplast ATP synthase.

The chloroplast F(0)F(1)-ATP synthase-ATPase is a tiny rotary motor responsible for coupling ATP synthesis and hydrolysis to the light-driven electrochemical proton gradient. Reversible oxidation/reduction of a dithiol, located within a special regulatory domain of the gamma subunit of the chloroplast F(1) enzyme, switches the enzyme between an inactive and an active state. This regulatory mechanism is unique to the ATP synthases of higher plants and its physiological significance lies in preventing nonproductive depletion of essential ATP pools in the dark. The three-dimensional structure of the chloroplast F(1) gamma subunit has not yet been solved. To examine the mechanism of dithiol regulation, a model of the chloroplast gamma subunit was obtained through segmental homology modeling based on the known structures of the mitochondrial and bacterial gamma subunits, together with de novo construction of the unknown regulatory domain. The model has provided considerable insight into how the dithiol might modulate catalytic function. This has, in turn, suggested a mechanism by which rotation of subunits in F(0), the transmembrane proton channel portion of the enzyme, can be coupled, via the epsilon subunit, to rotation of the gamma subunit of F(1) to achieve the 120 degrees (or 90 degrees +30 degrees) stepping action that is characteristic of F(1) gamma subunit rotation.

Adenosine Triphosphate↗

PubMed2005

Purification, reconstitution on lipid vesicles, and assays of PDE6 and its activator G protein, transducin.

PDE6 in rod and cone photoreceptors is the principal effector of phototransduction. It is kept at a very low activity level in the dark, and in the light it is strongly activated by the guanosine 5'-triphosphate-bound form of the alpha-subunit of the G protein, transducin. Both transducin and PDE6 are peripheral proteins, and understanding both their interactions with one another and the roles of lipids in their function requires reconstituting purified proteins on the surfaces of defined lipid bilayers. We describe here methods for purifying the proteins, reconstituting them with vesicles, and assaying catalytic activity and binding.

3',5'-Cyclic-GMP Phosphodiesterases↗