Biomedical subjects

Lu Zhang

Publications and source records attributed to Lu Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Inhibition of SHH signaling pathway: molecular treatment strategy of odontogenic keratocyst.

Odontogenic keratocyst (OKC) is a relatively common cystic lesion occurred in the tooth-bearing areas of the jaws. This entity is thought to arise from the dental lamina or its remnant with significant growth capacity and recurrence potential. The Sonic hedgehog (SHH) signaling pathway plays a critical role in tooth development. Patched (PTCH) combines with Smoothened (SMO) to form a receptor complex for SHH ligand. Mutations in the PTCH resulting in aberrant activation of SHH signaling pathway were identified as the underlying genetic event of both sporadic and syndrome-related OKCs. We postulate that any strategy to develop antagonists of active receptor, transcriptional factors of SHH signaling pathway will be an effective treatment for OKC. These strategies include reintroducing a wild-type form of PTCH, inhibition of the SMO molecule by synthetic small antagonists and suppression of the downstream transcription factors of the SHH signaling pathway. It seems that inhibition of SMO by intracystic injection of antagonist protein of SMO is the most potential treatment choice.

Basal Cell Carcinoma↗

PubMed2006

A possible hypoxia-induced endothelial proliferation in the pathogenesis of epithelioid hemangioma.

Epithelioid hemangioma is an uncommon benign vascular lesion with distinct clinicopathological characteristics. Histologically, this entity mainly composed of well-formed but often immature vessels lined by epithelioid endothelial cells with prominent chronic inflammatory component. There is considerable controversy whether epithelioid hemangioma is a reactive lesion or a true neoplasm. We postulated that the local hypoxia may play a role in the pathogenesis of this vascular tumor. This local hypoxic condition may caused by many incidences such as congenital vascular malformation or trauma. The hypoxia will lead to the proliferation of endothelial cells and the formation of this vascular tumor, which may lead by putative stimulators VEGF and HIF-1. Hypoxia may also promote endothelial cell proliferation through the renin-angiotensin-aldosterone system. Additionally, the inflammatory cells including eosinophils and mast cells may contribute to the endothelial cell proliferation in EH. Further study investigating the associated factors of hypoxia may lead to new, potentially important insights into epithelioid hemangioma, and might also contribute to novel strategies for the management of this entity.

Arteriovenous Malformations↗

PubMed2006

Induction of CML28-specific cytotoxic T cell responses using co-transfected dendritic cells with CML28 DNA vaccine and SOCS1 small interfering RNA expression vector.

CML28 is an attractive target for antigen-specific immunotherapy. SOCS1 represents an inhibitory control mechanism for DC antigen presentation and the magnitude of adaptive immunity. In this study, we evaluated the potential for inducing CML28-specific cytotoxic T lymphocytes (CTL) responses by dendritic cells (DCs)-based vaccination. We constructed a CML28 DNA vaccine and a SOCS1 siRNA vector and then cotransfect monocyte-derived DCs. Flow cytometry analysis showed gene silencing of SOCS1 resulted in higher expressions of costimulative moleculars in DCs. Mixed lymphocyte reaction (MLR) indicated downregulation of SOCS1 stronger capability to stimulate proliferation of responder cell in DCs. The CTL assay revealed transfected DCs effectively induced autologous CML28-specific CTL responses and the lytic activities induced by SOCS1-silenced DCs were significantly higher compared with those induced by SOCS1-expressing DCs. These results in our study indicates gene silencing of SOCS1 remarkably enhanced the cytotoxicity efficiency of CML28 DNA vaccine in DCs.

Antigens, Neoplasm↗

PubMed2006

A postulated role for transcriptional regulator LMO2 in the proliferation and involution of hemangioma.

Hemangiomas are common benign vascular tumors distinctive for their perinatal presentation, rapid growth during the first year of life and subsequent slowly involution. Many evidences suggest that hemangiomas are angiogenesis dependent entity. Research also indicated that the endothelium of hemangioma shared molecular phenotype with blood cells. LMO2 is a transcriptional regulator that play an important role in angiogenesis, hematopoiesis and oncogenesis of hematological tumor. It is logical to postulate that LMO2 may play a role in the pathogenesis, proliferating and involution of hemangioma. Therapies directed against LMO2 have potential importance for treatment of hemangioma because of hemangioma's limited localization and the fact that LMO2-associated protein complexes could regulate angiogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays.

BACKGROUND: DNA microarrays are rapidly becoming a fundamental tool in discovery-based genomic and biomedical research. However, the reliability of the microarray results is being challenged due to the existence of different technologies and non-standard methods of data analysis and interpretation. In the absence of a "gold standard"/"reference method" for the gene expression measurements, studies evaluating and comparing the performance of various microarray platforms have often yielded subjective and conflicting conclusions. To address this issue we have conducted a large scale TaqMan Gene Expression Assay based real-time PCR experiment and used this data set as the reference to evaluate the performance of two representative commercial microarray platforms. RESULTS: In this study, we analyzed the gene expression profiles of three human tissues: brain, lung, liver and one universal human reference sample (UHR) using two representative commercial long-oligonucleotide microarray platforms: (1) Applied Biosystems Human Genome Survey Microarrays (based on single-color detection); (2) Agilent Whole Human Genome Oligo Microarrays (based on two-color detection). 1,375 genes represented by both microarray platforms and spanning a wide dynamic range in gene expression levels, were selected for TaqMan Gene Expression Assay based real-time PCR validation. For each platform, four technical replicates were performed on the same total RNA samples according to each manufacturer's standard protocols. For Agilent arrays, comparative hybridization was performed using incorporation of Cy5 for brain/lung/liver RNA and Cy3 for UHR RNA (common reference). Using the TaqMan Gene Expression Assay based real-time PCR data set as the reference set, the performance of the two microarray platforms was evaluated focusing on the following criteria: (1) Sensitivity and accuracy in detection of expression; (2) Fold change correlation with real-time PCR data in pair-wise tissues as well as in gene expression profiles determined across all tissues; (3) Sensitivity and accuracy in detection of differential expression. CONCLUSION: Our study provides one of the largest "reference" data set of gene expression measurements using TaqMan Gene Expression Assay based real-time PCR technology. This data set allowed us to use an alternative gene expression technology to evaluate the performance of different microarray platforms. We conclude that microarrays are indeed invaluable discovery tools with acceptable reliability for genome-wide gene expression screening, though validation of putative changes in gene expression remains advisable. Our study also characterizes the limitations of microarrays; understanding these limitations will enable researchers to more effectively evaluate microarray results in a more cautious and appropriate manner.

Gene Expression Profiling↗

PubMed2006

Conversion of intramolecular singlet electron transfer at room temperature into triplet energy transfer at 77 K: photoisomerization in norbornadiene- and carbazole-labeled poly(aryl ether) dendrimers.

A series of Fréchet-type poly(aryl ether) dendrimers (CZ-Gn-NBD, n = 1-3) with carbazole (CZ) chromophores and a norbornadiene (NBD) group attached to the periphery and the core, respectively, were synthesized, and their photophysical and photochemical properties were investigated. Selective excitation of the carbazole units in CZ-Gn-NBD resulted in a singlet electron transfer from CZ to NBD at room temperature, and an intersystem crossing followed a triplet-triplet energy transfer from CZ to NBD in glassy 2-methyltetrahydrofuran at 77 K. Both singlet electron transfer and triplet energy transfer processes lead to the isomerization of the norbornadiene group into the quadricyclane (CZ-Gn-QC). The efficiencies and the rate constants for singlet electron transfer are approximately 88, 80, and 74% and 1.8 x 10(9), 6.1 x 10(8), and 4.0 x 10(8) s(-1) for generations 1-3, respectively. The quantum yields of the intramolecular photosensitized isomerization are measured to be approximately 0.013, 0.012, and 0.011, and the efficiencies of triplet norbornadiene formation via singlet electron transfer are approximately 0.070, 0.065, and 0.059 for generations 1-3, respectively. The light-harvesting ability of CZ-Gn-NBD increases with the generation due to an increase of the number of peripheral chromophores. In glassy 2-methyltetrahydrofuran at 77 K, the triplet-triplet energy transfer proceeds with efficiencies of approximately 0.86, 0.64, and 0.36 and rate constants of 0.96, 0.25, and 0.08 s(-1) for generations 1-3, respectively. The intramolecular singlet electron transfer and triplet energy transfer in CZ-Gn-NBD proceed mainly via a through-space mechanism involving the proximate donor (folding back conformation) and acceptor groups.

Journal Article↗

PubMed2006

Direct observation of the intramolecular triplet-triplet energy transfer in poly(aryl ether) dendrimers.

A series of benzophenone (BP) and naphthalene (NA) labeled poly(aryl ether) dendrimers (BP-Gn-NA), generations 1-4, were synthesized, and their photophysical properties were examined. Flash photolysis demonstrates that the triplet energy in BP-Gn-NA can be transferred from the peripheral BP chromophores to the core NA group with the efficiencies of ca. 0.97, 0.96, 0.88, and 0.54 and with the rate constants of 1.4x10(8), 1.2x10(8), 9.5x10(7), and 1.3x10(7) s-1 at room temperature for generations 1-4, respectively. The transient absorption spectra of BP-Gn-NA show clearly the formation of the triplet NA absorption along with the decay of the triplet BP one with an isosbestic point at 475 nm, which gives direct evidence of the triplet energy transfer from the periphery BP chromphores to the core NA group. The phosphorescence of the NA group attached to the focal point was observed when the periphery BP chromophores were selectively irradiated in BP-G1-NA at 77 K. The triplet energy transfer occurs at 77 K with the efficiencies of 1.0, 0.16, 0.17, and 0.21 for generations 1-4, respectively. The intramolecular triplet energy transfer is proposed to proceed mainly via a through space mechanism.

Journal Article↗

PubMed2006

Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population.

OBJECTIVE: The aims of the present study were to assess whether the glutathione S-transferase T1 (GSTT1), M1 (GSTM1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) genotypes are associated with type 2 diabetes mellitus (T2 DM) and to ascertain whether the levels of blood lipids given exposure to diabetes are modified by the specific genetic polymorphisms of GSTT1, GSTM1, and NQO1. METHODS: This case-control study was conducted on 200 subjects. The genotypes were determined using a polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. RESULTS: The GSTT1-present genotype conferred a statistically significant 0.49-fold reduction in risk of T2 DM relative to the null genotype. Individuals with GSTT1-null or GSTM1-null genotype had higher levels of low-density-lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a), respectively. There was no association between either GSTM1 or NQO1 polymorphism and risk of T2 DM. CONCLUSION: The present results suggest that the GSTT1 gene may contribute to the development of T2 DM and may be one of the candidate genes of T2 DM in Chinese population.

Adult↗

PubMed2006

Evaluation of DNA microarray results with quantitative gene expression platforms.

We have evaluated the performance characteristics of three quantitative gene expression technologies and correlated their expression measurements to those of five commercial microarray platforms, based on the MicroArray Quality Control (MAQC) data set. The limit of detection, assay range, precision, accuracy and fold-change correlations were assessed for 997 TaqMan Gene Expression Assays, 205 Standardized RT (Sta)RT-PCR assays and 244 QuantiGene assays. TaqMan is a registered trademark of Roche Molecular Systems, Inc. We observed high correlation between quantitative gene expression values and microarray platform results and found few discordant measurements among all platforms. The main cause of variability was differences in probe sequence and thus target location. A second source of variability was the limited and variable sensitivity of the different microarray platforms for detecting weakly expressed genes, which affected interplatform and intersite reproducibility of differentially expressed genes. From this analysis, we conclude that the MAQC microarray data set has been validated by alternative quantitative gene expression platforms thus supporting the use of microarray platforms for the quantitative characterization of gene expression.

Equipment Design↗

PubMed2006

Rat toxicogenomic study reveals analytical consistency across microarray platforms.

To validate and extend the findings of the MicroArray Quality Control (MAQC) project, a biologically relevant toxicogenomics data set was generated using 36 RNA samples from rats treated with three chemicals (aristolochic acid, riddelliine and comfrey) and each sample was hybridized to four microarray platforms. The MAQC project assessed concordance in intersite and cross-platform comparisons and the impact of gene selection methods on the reproducibility of profiling data in terms of differentially expressed genes using distinct reference RNA samples. The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons. Further, gene lists generated by fold-change ranking were more reproducible than those obtained by t-test P value or Significance Analysis of Microarrays. Finally, gene lists generated by fold-change ranking with a nonstringent P-value cutoff showed increased consistency in Gene Ontology terms and pathways, and hence the biological impact of chemical exposure could be reliably deduced from all platforms analyzed.

Animals↗

PubMed2006

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.

Equipment Design↗

PubMed2006

Purification and characterization of Mycobacterium tuberculosis indole-3-glycerol phosphate synthase.

Indole-3-glycerol phosphate synthase (IGPS) plays an important role in the survival of Mycobacterium tuberculosis. The trpC gene, encoding IGPS, is essential for the growth of M. tuberculosis. It was expressed at the transcriptional level in cultured M. tuberculosis. The recombinant IGPS with an added His-tag was purified. The His-tag was found to have a small effect on the biochemical properties of IGPS. IGPS is a monofunctional enzyme in M. tuberculosis. Recombinant IGPS has considerable beta-pleated sheet and is relatively compact. The enzyme activity is significantly inhibited by denaturants and antibiotics, suggesting that IGPS may be a novel potential drug target of M. tuberculosis.

Bacterial Proteins↗

PubMed2006

Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation.

OBJECTIVE: To study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment. METHODS: By using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation. RESULTS: D1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation. CONCLUSION: D1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway.

Animals↗

PubMed2006

[Strategies for antibody immobilization during the fabrication of antibody microarrays].

As one of the proteomic technologies, antibody microarrays can provide a powerful tool for the high-throughput parallel analysis of thousands of proteins in a single experiment. Because antibodies are chemically and structurally complex; immobilizing antibody on solid phase surface of substrates has been a key step during the development of antibody microarrays. This review will focus on the current strategies for antibody immobilization and discuss the advantages and disadvantages of these methods.

Adsorption↗

PubMed2006

[Study on the TLC-fingerprint of Xiatianwu].

OBJECTIVE: To develop a method that can well evaluate the quality of Xiatianwu. METHODS: Methods are researched and discussed to construct the TLC-FP (thin-layer chromatography finger-print) of Xiatianwu to evaluate its quality. RESULTS: The areas of six evident peaks in the thin-layer chromatography of Xiatianwu are compared with the area of dl-tetrahydropalmatine peak companied with them in the same chromatography. The Rr of every peak and its relative area were acquired to evaluate the quality of Xiatianwu and identify it. CONCLUSION: The TLC-fingerprint of Xiatianwu can well evaluate the quality of Xiatianwu.

Berberine Alkaloids↗

PubMed2006

[Space-time dependent variances of ammonia and phosphorus flux on sediment-water interface in Lake Taihu].

Monthly research of ammonia and phosphorus fluxes in water-sediment interface in East Lake Taihu (ELT, macrophyte dominated) and Meiliang Bay (MB, algae dominated) was processed with intact sediment cores' incubation and pore water diffusive model. The ammonia and phosphorus fluxes calculated with intact sediment cores' incubation (F(i)) showed discrepancy in different lake zones with different ecotype. The yearly average fluxes of ammonia and dissolved phosphorus in ELT were (44.9 +/- 21.9) mg x (m2 x d)(-1) (Mean +/- SD) and (2.06 +/- 1.71) mg x (m2 x d)(-1); and (16.2 +/- 12.0) mg x (m2 x d)(-1) and (0.53 +/- 0.52) mg x (m2 x d)(-1) in MB. The molecular diffusive fluxes (F(m)) of the two lake zones showed the same pattern, but the absolute value difference may as high as an order of magnitudes. So this molecular diffusive model cannot be used to evaluate the nutrients fluxes in sediment-water interface in Lake Taihu, a lake vulnerable with wind and wave affection and benthic bio-disturbation. Compared with the two lake zones with different ecotypes, macrophyte dominated one had higher nutrients fluxes than the algae one. ELT had higher bio-disturbation, which was revealed by the F(i)/F(m) ratio. When the dissolved oxygen (DO) remained in high concentration, known as aerobic condition, the nutrients' fluxes were not correlated with the DO. Similarly, the fluxes were not correlated with the nutrients' concentration of the overlying water at the existing condition. The discrepancy between higher nutrients' fluxes and lower nutrients loading in ELT suggested the higher particulate settlement rate and assimilate rate promoted by the macrophyte. This is the important theoretical basis of rebuilding the healthy ecosystems with restoring the water plants.

Ammonia↗

PubMed2006

[Construction of HA-1-DC nucleic-acid vaccine and induction of specific cytotoxic T lymphocytes].

The purpose of this study was to construct a HA-1-DC nucleic acid vaccine and to induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT). The dendritic cells (DCs) were generated from HSCT donors in vitro, and its immunologic activity was studied by using flow cytometry and mix lymphocyte reaction. HA-1 gene was electroporated into the cultured DCs to construct a DC nucleic acid vaccine. After transfecting for 48 hours, the expression of HA-1 protein was detected by Western blot. The DCs were cultured with isogenic lymphocytes to induce specific cytotoxic T lymphocytes (CTLs). The cytotoxicity of the CTLs was detected by LDH assay. The results showed that the DCs derived from peripheral blood monocytes (PBMCs) expressed the DC phenotype, and were effective in stimulating proliferation of the allogenic lymphocytes. After electroporating for 48 hours, HA-1 protein was detected by Western blot. The cytotoxity of inducing CTLs was higher than that in the control group. It is concluded that the minor histocompatibility antigen HA-1 can be considered as a target of immunotherapy against leukemia after HSCT.

Cancer Vaccines↗

PubMed2006

[Mapping of a pedigree with autosomal dominant inherited congenital sutural cataract].

OBJECTIVE: To map the gene responsible for autosomal dominant congenital sutural cataract of a Chinese family. METHODS: Peripheral blood samples were collected from the members in a family with autosomal dominant congenital sutural cataract. The genomic DNA was extracted from the blood samples. A genescan was performed using approximately 400 microsatellite markers (ABI). Linkage analysis was processed by Linkage software package to define the location of mutation gene. High density primers labeled with fluorescent stain for the positive region were adopted for fine targeting, and haplotype analysis was processed using Cyrillic software. RESULTS: The maximum two-point LOD scores was obtained at D3S1279, Z(max) = 2.32 (theta(max) = 0.00). After fine targeting and haplotype analysis, the gene was located within a 38.6 cM region between D3S1267 and D3S1614. CONCLUSION: The gene responsible for congenital sutural cataract in a Chinese pedigree is located at chromosome 3q21.1 - q26.2 within a 38.6 cM region.

Asian People↗