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Biomedical subjects

Wei Li

Publications and source records attributed to Wei Li.

At least 109 records · Page 6Linked to original sources
PubMed2006

Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves gamma-globin activation by CREB1 and ATF-2.

The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate gamma-globin expression via a p38 mitogen-activating protein kinase (MAPK)-dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the CRE in the (G)gamma-globin promoter (G-CRE) in vitro after drug treatments; subsequent chromatin immunoprecipitation assay confirmed ATF-2 and CREB1 binding to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced (G)gamma-promoter trans-activation which was abolished by a 2-base pair mutation in the putative G-CRE. The data presented herein demonstrate that gamma-gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling.

Activating Transcription Factor 2↗
PubMed2006

Janus and ternary particles generated by microfluidic synthesis: design, synthesis, and self-assembly.

This paper reports a microfluidic method for fast continuous synthesis of Janus particles and three-phase particles with narrow size distribution. Synthesis of particles included emulsification of monomer liquids and in-situ photoinitiated polymerization of multiphase droplets. We show the strategy for precise control over the structure of Janus particles and their structure-dependent assembly in clusters. We demonstrate an asymmetric chemical modification of the surface of JPs by conjugating them with protein molecules. The Janus and ternary particles were synthesized from largely immiscible liquids and had a sharp interface between the constituent phases.

Journal Article↗
PubMed2006

Identification of human STAT5-dependent gene regulatory elements based on interspecies homology.

STAT5 is a transcription factor essential for hematopoietic physiology. STAT5 functions to transduce signals from cytokines to the nucleus where it regulates gene expression. Although several important transcriptional targets of STAT5 are known, most remain unidentified. To identify novel STAT5 targets, we searched chromosomes 21 and 22 for clusters of STAT5 binding sites contained within regions of interspecies homology. We identified four such regions, including one with tandem STAT5 binding sites in the first intron of the NCAM2 gene. Unlike known STAT5 binding sites, this site is found within a very large intron and resides approximately 200 kb from the first coding exon of NCAM2. We demonstrate that this region confers STAT5-dependent transcriptional activity. We show that STAT5 binds in vivo to the NCAM2 intron in the NKL natural killer cell line and that this binding is induced by cytokines that activate STAT5. Neither STAT1 nor STAT3 bind to this region, despite sharing a consensus binding sequence with STAT5. Activation of STAT4 and STAT5 causes the accumulation of both of these STATs to the NCAM2 regulatory region. Therefore, using an informatics based approach to identify STAT5 targets, we have identified NCAM2 as both a STAT4- and STAT5-regulated gene, and we show that its expression is regulated by cytokines essential for natural killer cell survival and differentiation. This strategy may be an effective way to identify functional binding regions for transcription factors with known cognate binding sites anywhere in the genome.

Base Sequence↗
PubMed2006

Upregulation of myeloperoxidase in patients with opticospinal multiple sclerosis: positive correlation with disease severity.

To clarify the role of myeloperoxidase (MPO) in multiple sclerosis (MS), we measured serum MPO levels in 86 Japanese patients with relapsing remitting MS, 47 with opticospinal MS (OSMS) and 39 with conventional MS (CMS), and 85 healthy subjects by sandwich enzyme immunoassays and analyzed relationships with clinical features. We found a significant increase in serum MPO in OSMS patients at relapse and remission, and in CMS patients at remission compared with controls. By logistic regression analysis, the clinical variable associated with high level of MPO at remission in OSMS patients (higher than the mean+/-2 S.D. of healthy controls) was only Kurtzke's Expanded Disability Status Scale (EDSS) score in blood sampling (p=0.0245); that is, a greater EDSS scores in the high MPO group, whereas in CMS none were associated. The results of our study suggest that MPO levels in remission are related with severe tissue destruction in OSMS.

Adult↗
PubMed2006

CEAS: cis-regulatory element annotation system.

The recent availability of high-density human genome tiling arrays enables biologists to conduct ChIP-chip experiments to locate the in vivo-binding sites of transcription factors in the human genome and explore the regulatory mechanisms. Once genomic regions enriched by transcription factor ChIP-chip are located, genome-scale downstream analyses are crucial but difficult for biologists without strong bioinformatics support. We designed and implemented the first web server to streamline the ChIP-chip downstream analyses. Given genome-scale ChIP regions, the cis-regulatory element annotation system (CEAS) retrieves repeat-masked genomic sequences, calculates GC content, plots evolutionary conservation, maps nearby genes and identifies enriched transcription factor-binding motifs. Biologists can utilize CEAS to retrieve useful information for ChIP-chip validation, assemble important knowledge to include in their publication and generate novel hypotheses (e.g. transcription factor cooperative partner) for further study. CEAS helps the adoption of ChIP-chip in mammalian systems and provides insights towards a more comprehensive understanding of transcriptional regulatory mechanisms. The URL of the server is http://ceas.cbi.pku.edu.cn.

Binding Sites↗
PubMed2006

p300/Cyclic AMP-responsive element binding-binding protein mediates transcriptional coactivation by the CD28 T cell costimulatory receptor.

During Ag stimulation of T cells, the recognition of B7 molecules by the CD28 costimulatory receptor increases the level of c-Fos, a component of the AP-1 transactivator known to bind the 5' Il2 gene enhancer. In this study, we show that the costimulation of Fos transcription by CD28 is associated with increased binding of p300/CREB-binding protein (CBP) molecules at the Fos promoter, and is blocked by an adenoviral E1A molecular antagonist of p300/CBP. Furthermore, transcriptional activation by a C-terminal domain of CBP is strengthened when CD28 molecules are actively signaling. This increased amount and activity of p300/CBP molecules at the Fos gene correlated with higher histone H4 acetylation and RNA polymerase II association with the promoter. These data suggest a global mechanism whereby CD28 signaling influences the rate and intensity of new gene expression during Ag recognition via direct control over the coactivator function of p300/CBP.

Acetylation↗
PubMed2006

Biodesulfurization of dibenzothiophene by growing cells of Gordonia sp. in batch cultures.

A new isolate, identified as Gordonia sp. ZD-7 by 16S rDNA sequence analysis, grew in n-hexadecane containing dibenzothiophene (DBT) which was degraded from 2.8 mM to 0.2 mM within 48 h. Biodesulfurization could be repeatedly performed for more than 190 h, with average desulfurization rates of 5 mmol DBT kg cells (dry wt)(-1) h(-1).

Biodegradation, Environmental↗
PubMed2006

"Isolated" diastolic dysfunction in left ventricular outflow tract obstruction.

We sought to investigate the prescence of "isolated" diastolic disease, defined as reduced long-axis early diastolic velocity with normal systolic velocity, in 21 young patients with left outflow tract obstruction. Most patients had depressed systolic velocities despite normal ejection fractions. The close relations amond long-axis velocities suggest isolated diastolic disease is unlikely.

Adult↗
PubMed2006

Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth.

Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process that is independent of the cardiac working load. However, the functional significance of this biological event has not been determined, mainly because of the difficulty in creating an experimental condition for testing the growth potential of functioning heart in the absence of hemodynamic load. Recently, we generated a novel transgenic mouse model (alphaMHC-BMP10) in which the cardiac-specific growth factor bone morphogenetic protein 10 (BMP10) is overexpressed in postnatal myocardium. These alphaMHC-BMP10 mice appear to have normal cardiogenesis throughout embryogenesis, but develop to smaller hearts within 6 weeks after birth. alphaMHC-BMP10 hearts are about half the normal size with 100% penetrance. Detailed morphometric analysis of cardiomyocytes clearly indicated that the compromised cardiac growth in alphaMHC-BMP10 mice was solely because of defect in cardiomyocyte postnatal hypertrophic growth. Physiological analysis further demonstrated that the responses of these hearts to both physiological (e.g. exercise-induced hypertrophy) and pathological hypertrophic stimuli remain normal. In addition, the alphaMHC-BMP10 mice develop subaortic narrowing and concentric myocardial thickening without obstruction by four weeks of age. Systematic analysis of potential intracellular pathways further suggested a novel genetic pathway regulating this previously undefined cardiac postnatal hypertrophic growth event. This is the first demonstration that cardiac postnatal hypertrophic growth can be specifically modified genetically and dissected out from physiological and pathological hypertrophies.

Animals↗
PubMed2006

Surface selective deposition of Mo(IV) on Ni/TiO2 particles in aqueous solutions.

The selective depositions of MoS2 and MoO2 over Ni surfaces are demonstrated on Ni/TiO2 particles in a mild electroless deposition process. High-resolution transmission electron microscopy (HRTEM) images show the uniform distribution of 10-30 nm spherical and hemispherical Ni particles on TiO2 surface, and three to six layers of MoS2 on the surface of Ni particles. The as-prepared MoS2-Ni/TiO2 is used as a catalyst for the hydrodesulfurization (HDS) reaction of dibenzothiophene (DBT), and shows a significant increase over commercial catalysts in turnover frequencies as the result of unique distribution of active components in the binary catalyst. The selective material deposition is explained in the context of Ni catalyzed KBH4 decomposition, which produces strong reducing species responsible for the site selective deposition of Mo. The synthetic method can be potentially used to prepare bimetallic materials with similar nanostructures such as those of Mo-Co, Mo-Pd, and Mo-Rh.

Journal Article↗
PubMed2006

Polarization-degree imaging contrast in turbid media: a quantitative study.

Scattering in biological tissue can degrade imaging contrast and reduce the probe depth. Polarization-based measurement has shown its advantages in overcoming such drawbacks. Here, linear and circular polarization degree imaging is applied to a comblike metal target submerged in Intralipid solutions. Contrasts of the metal bars are measured quantitatively as functions of the Intralipid concentration and the submersion depths. Different behaviors in contrast for linear and circular polarizations are compared. Contributions to the background of circular polarization degree images by backscattering, snake, and diffusive photons are examined carefully.

Algorithms↗
PubMed2006

Enhancement of Ca2+ release from limestone by microbial extracellular carbonic anhydrase.

Three experimental systems were set up to investigate whether carbonic anhydrase (CA) from microorganisms actually plays the driving role in limestone dissolution. In one, redistilled water served as negative control. In a second, microbial origin CA enzyme solution supplemented with CA special inhibitor acetazolamide (AZ) served as positive control. A third contained a crude enzyme solution of microbial CA. The results showed that the amount of released Ca2+ from limestone in a CA non-inhibited system increased by 2.4 times compared to a CA inhibited system, and increased by 11.7 times compared to the redistilled water control. These experiments demonstrated that microbial origin CA significantly enhanced Ca2+ release from limestone (P < 0.01), and therefore, proved the significant driving effect of microbial CA on limestone dissolution. The results also suggested that microbially derived CA might exert an important influence on biokarst process.

Calcium↗
PubMed2006

Abnormal ventilatory response to exercise in adults with congenital heart disease relates to cyanosis and predicts survival.

BACKGROUND: Limited data exist with which to stratify risk in adult congenital heart disease (ACHD). An increased ventilatory response to exercise, expressed as ventilation per unit of carbon dioxide production (V(E)/V(CO2) slope), is an established predictor of impaired survival in acquired heart disease. We sought to establish the distribution, relation to cyanosis, and prognostic value of the V(E)/V(CO2) slope across a wide spectrum of ACHD patients. METHODS AND RESULTS: Five hundred sixty ACHD patients of varying diagnoses and 50 healthy controls underwent cardiopulmonary exercise testing at a single laboratory between 2001 and 2004. Patient age was 33.2 +/- 12.9 years (mean +/- SD). Peak oxygen consumption was 23.5 +/- 9.0 mL.kg(-1).min(-1).V(E)/V(CO2) slope for all patients was 36.3 +/-15.3. The slope was raised in all ACHD groups compared with controls and was 73% higher in cyanotic patients. Cyanosis, with or without pulmonary arterial hypertension, was the strongest predictor of abnormal V(E)/V(CO2) slope. The V(E)/V(CO2) slope was the most powerful univariate predictor of mortality in the noncyanotic group and the only independent predictor of mortality among exercise parameters on multivariate analysis. In cyanotic patients, no parameter was predictive of death. CONCLUSIONS: Ventilatory response to exercise is abnormal across the spectrum of ACHD. Cyanosis is a powerful stimulus for such exaggerated ventilatory patterns irrespective of the presence of pulmonary arterial hypertension. Increased V(E)/V(CO2) slope is the strongest exercise predictor of death in noncyanotic ACHD patients.

Adult↗
PubMed2006

Oxysterol mixtures, in atheroma-relevant proportions, display synergistic and proapoptotic effects.

Apoptotic cells in atheroma lesions may contribute to plaque development and instability. Oxysterols constitute the major toxic component in oxLDL and are present in mixed forms in human atheroma lesions. However, the cellular effects of oxysterols have been mostly studied individually. In the present study, we investigated the cytotoxic effects of 7beta-hydroxycholesterol (7betaOH), 7-ketocholesterol (7keto), 25-hydroxycholesterol (25OH), and 27-hydroxycholesterol (27OH) on U937 monocytic cells, both individually and in atheroma-relevant mixtures mimicking the oxysterol composition reported in human atheroma lesions. Apoptosis and necrosis were studied by examining cell morphology, phosphatidylserine exposure, caspase activation, and the terminal dUTP nick end-labeling technique. Cellular reactive oxygen species and total amount of reduced thiols were measured by using fluorescence probes and 5,5'-dithiobis-(2-nitrobenzoic acid), respectively. We found that 7betaOH and 7keto induced caspase activation, ROS production, cellular thiol depletion, permeabilization of lysosomal and mitochondrial membranes, and cell death. 25OH and 27OH did not cause any of the above alterations, whereas 7betaOH and 7keto exerted synergistic toxic effects. Although single 25OH or 27OH exhibited quenching effects on both 7betaOH- and 7keto-induced cell death, the combination of all four oxysterols in atheroma-relevant proportions was proapoptotic. Our findings indicate that the major oxysterols accumulated in human atheroma are proapoptotic and may contribute to atherosclerotic lesion development.

Apoptosis↗
PubMed2006

Separation of hydrophobic solutes by organic-solvent-based micellar electrokinetic chromatography using cation surfactants.

In this study, the separation of 13 homologous stick-like hydrophobic solutes, i.e., biphenyl nitrile derivatives, by organic-solvent-based micellar electrokinetic chromatography (MEKC) was investigated in terms of separation medium composition, species and concentration of surfactant, other additives, separation voltage and temperature. The results showed that the 13 strong hydrophobic compounds were baseline separated in 25 min with a repeatability of less than 1.3% (RSD) for migration time. The separation medium was a mixture of methanol, 2-propanol and water (58.5:10:31.5), containing 150 mM cetyltrimethylammonium bromide (CTAB) and 20 mM sodium borate. Variety of solvent composition, temperature and applied voltage all showed remarkable effect on the separation. The organic-solvent-based MEKC method proved to be superior to the aqueous MEKC and microemulsion electrokinetic chromatography (MEEKC) methods for the separation of strongly hydrophobic compounds.

Cations↗
PubMed2006

Parallel processing in two transmitter microenvironments at the cone photoreceptor synapse.

A cone photoreceptor releases glutamate at ribbons located atop narrow membrane invaginations that empty onto a terminal base. The unique shape of the cone terminal suggests that there are two transmitter microenvironments: within invaginations, where concentrations are high and exposures are brief; and at the base, where concentrations are low and exposure is smoothed by diffusion. Using multicell voltage-clamp recording, we show that different subtypes of Off bipolar cells sample transmitter in two microenvironments. The dendrites of an AMPA receptor-containing cell insert into invaginations and sense rapid fluctuations in glutamate concentration that can lead to transient responses. The dendrites of kainate receptor-containing cells make basal contacts and respond to a smoothed flow of glutamate that produces sustained responses. Signaling at the cone to Off bipolar cell synapse illustrates how transmitter spillover and synapse architecture can combine to produce distinct signals in postsynaptic neurons.

Animals↗
PubMed2006

[Treatment of descending and abdominal aortic pseudoaneurysm with stent-graft: a report of 13 cases].

OBJECTIVE: To explore the effects of stent-graft on treating descending and abdominal aortic pseudoaneurysms. METHODS: Seven cases of descending and 6 cases of abdominal aortic pseudoaneurysms were treated with stent-graft, aging from 28 to 72 years, average 59 years. RESULTS: Eight cases of aortic pseudoaneurysms were completely excluded after the procedure. Slight leakages were found in 5 cases. Leakages disappeared through balloon dilatation in 2 cases, and one more stent-graft cuff implanted in 1 case. Slight leakages were still presented after dilatation in the other 2 cases, however, the leakages disappeared 3 months later. Eleven cases were followed up from 4 to 30 months with a mean of 18.6 months. One case died of massive hemorrhage from upper digestive tract 5 months after operation. The stent-grafts of other cases maintained patent, and no migration occurred. The diameter of the pseudoaneurysm of all cases did not increased. CONCLUSIONS: It is safe, effective and mini-invasive to use stent-graft in the treatment of descending and abdominal aortic pseudoaneurysm, however, the long-term investigation is needed.

Adult↗