Biomedical subjects

Hua Su

Publications and source records attributed to Hua Su.

At least 19 recordsLinked to original sources

PubMed2006

Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. RESULTS: Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods--using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software--and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified. CONCLUSION: These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

Aged↗

PubMed2006

Biosorption of copper(II) from aqueous solutions by green alga Cladophora fascicularis.

Biosorption is an effective means of removal of heavy metals from wastewater. In this work the biosorption behavior of Cladophora fascicularis was investigated as a function of pH, amount of biosorbent, initial Cu2+ concentration, temperature, and co-existing ions. Adsorption equilibria were well described by Langmuir isotherm models. The enthalpy change for the biosorption process was found to be 6.86 kJ mol(-1) by use of the Langmuir constant b. The biosorption process was found to be rapid in the first 30 min. The presence of co-existing cations such as Na+, K+, Mg2+, and Ca2+ and anions such as chloride, nitrate, sulfate, and acetate did not significantly affect uptake of Cu2+ whereas EDTA substantially affected adsorption of the metal. When experiments were performed with different desorbents the results indicated that EDTA was an efficient desorbent for the recovery of Cu2+ from biomass. IR spectral analysis suggested amido or hydroxy, C=O, and C-O could combine strongly with Cu2+.

Adsorption↗

PubMed2006

Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation.

We recently established that fibroblast growth factor (FGF)-1 promotes adipogenesis of primary human preadipocytes (phPA). In the current report, we have characterized the adipogenic effects of FGF-1 in phPA and also in a human PA strain derived from an individual with Simpson-Golabi-Behmel syndrome (SGBS PA), which exhibit an intrinsic capacity to differentiate with high efficiency. In further studies, we compared these models with the well-characterized murine 3T3-L1 preadipocyte cell line (3T3-L1 PA). FGF-1 up-regulated the adipogenic program in phPA, with increased expression of peroxisome proliferator-activated receptor-gamma in confluent PA prior to induction of differentiation and increased expression of adipocyte markers during differentiation. Moreover, phPA differentiated in the presence of FGF-1 were more insulin responsive and secreted increased levels of adiponectin. FGF-1 treatment of SGBS PA further enhanced differentiation. For the most part, the adipogenic program in phPA paralleled that observed in 3T3-L1 PA; however, we found no evidence of mitotic clonal expansion in the phPA. Finally, we investigated a role for extracellular regulated kinase 1/2 (ERK1/2) in adipogenesis of phPA. FGF-1 induced robust phosphorylation of ERK1/2 in early differentiation and inhibition of ERK1/2 activity significantly reduced phPA differentiation. These data suggest that FGF-1 treated phPA represent a valuable in vitro model for the study of adipogenesis and insulin action and indicate that ERK1/2 activation is necessary for human adipogenesis in the absence of mitotic clonal expansion.

Adipocytes↗

PubMed2006

Sorption and desorption of lead (II) from wastewater by green algae Cladophora fascicularis.

Biosorption is an effective method to remove heavy metals from wastewater. In this work, adsorption features of Cladophora fascicularis were investigated as a function of time, initial pH, initial Pb(II) concentrations, temperature and co-existing ions. Kinetics and equilibria were obtained from batch experiments. The biosorption kinetics followed the pseudo-second order model. Adsorption equilibria were well described by the Langmuir and Freundlich isotherm models. The maximum adsorption capacity was 198.5 mg/g at 298K and pH 5.0. The adsorption processes were endothermic and the biosorption heat was 29.6 kJ/mol. Desorption experiments indicated that 0.01 mol/L Na(2)EDTA was an efficient desorbent for the recovery of Pb(II) from biomass. IR spectrum analysis suggested amido or hydroxy, CO and C-O could combine intensively with Pb(II).

Adsorption↗

PubMed2006

Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain.

Delivery of therapeutic genes represents a fascinating possibility to accelerate injury-repairing process in tissues that are otherwise difficult to treat, such as cerebral ischemia. Current studies indicate that gene transfer-induced focal angiogenesis in the brain may provide an important therapeutic strategy. In the present study, we reported the efficacy of induction of angiogenesis with an adeno-associated virus (AAV) vector expressing the 165 amino acid isoform of vascular endothelial growth factor (VEGF165). We found AAV serotype 1 has more efficiency in transduction of the brain tissue than AAV serotype 2. Quantitative vessel counting showed that microvessels in AAV-VEGF transduced mice significantly increased from 1 week up to 12 weeks compared to the control groups (AAV-VEGF: 316+/-58 vs. AAV-lacZ: 180+/-34 and saline: 152+/-35 vessels/mm2, at 6 weeks, p<0.05). Proliferating cell nuclear antigen (PCNA) staining confirmed these microvessels were actively proliferating. Double-labeled fluorescence staining demonstrated that neurons, astrocytes, and endothelial cells could express VEGF following AAV-VEGF gene transfer. AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage. Our data underline the importance of angiogenesis in the brain tissue and indicate that VEGF gene transfer might present a valuable approach to treat brain ischemic disorders.

Animals↗

PubMed2006

Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury after focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: Exogenous delivery of vascular endothelial growth factor gene (VEGF) may provide a useful approach to the treatment of brain ischemia. We investigated the use of a hypoxia-responsive element to control VEGF expression given for neuroprotection. METHODS: Three groups (n=36) of mice received AAVH9-VEGF, AAVH9-lacZ, or saline injection. Five days after gene transfer, the mice underwent 45 minutes of transient middle cerebral artery occlusion (tMCAO) followed by 1 to 7 days of reperfusion. Infarct volume was determined using cresyl violet staining; neuronal injury was examined using TUNEL, cleaved caspase-3, and fluoro-Jade B staining. RESULTS: Hypoxia-inducible factor-1 (HIF-1) was overexpressed after tMCAO in the ischemic hemisphere in the brain. Expression of lacZ, mediated by AAV-lacZ, was seen before and after tMCAO; however, AAVH9-lacZ-mediated lacZ expression was detected only after tMCAO. Infarct volume was smaller in the AAVH9-VEGF-transduced group compared with AAVH9-lacZ and saline groups (55% reduction, P<0.05) with reduced TUNEL (29+/-5% and 30+/-7% versus 12+/-3%, P<0.05), cleaved caspase-3 (20+/-3% and 21+/-5% versus 13+/-4%, P<0.05) and fluoro-Jade B (23+/-3% and 24+/-5% versus 12+/-5%, P<0.05) -positive neurons, respectively. CONCLUSIONS: Exogenous expression of VEGF through AAVH9-VEGF gene transfer 5 days before the onset of ischemia provides neuroprotection. Hypoxia-responsive element is a viable strategy of restricting VEGF expression to areas of ischemia to minimize adverse effects of therapy on adjacent normal parenchyma.

Animals↗

PubMed2006

Development of a gradient reversed-phase HPLC method for the determination of sodium ferulate in beagle dog plasma.

A gradient reversed-phase HPLC assay has been developed to determine sodium ferulate (SF) in beagle dog plasma with tinidazole as an internal standard. Chromatographic separation was made on a C(18) column using 0.5% acetic acid and acetonitrile (80:20, v/v) as mobile phase. UV detection was performed at 320 nm. The calibration curve for SF was linear in the range of 0.05-10 microg/ml, and the achieved limit of quantification (LOQ) was 51.4 ng/ml. The results of linearity, within- and between-day precision, and accuracy demonstrate that this method is reliable, sensitive and sufficient for in vivo beagle dog pharmacokinetic (PK) studies of SF.

Animals↗

PubMed2006

A framework of integrating gene relations from heterogeneous data sources: an experiment on Arabidopsis thaliana.

One of the most important goals of biological investigation is to uncover gene functional relations. In this study we propose a framework for extraction and integration of gene functional relations from diverse biological data sources, including gene expression data, biological literature and genomic sequence information. We introduce a two-layered Bayesian network approach to integrate relations from multiple sources into a genome-wide functional network. An experimental study was conducted on a test-bed of Arabidopsis thaliana. Evaluation of the integrated network demonstrated that relation integration could improve the reliability of relations by combining evidence from different data sources. Domain expert judgments on the gene functional clusters in the network confirmed the validity of our approach for relation integration and network inference.

Arabidopsis↗

PubMed2006

In vitro controlled release of sodium ferulate from Compritol 888 ATO-based matrix tablets.

A controlled release matrix formulation for freely water-soluble drug of sodium ferulate (SF) was designed and developed to achieve a 24h release profile. Using Compritol 888 ATO as an inert matrix-forming agent to control the release of SF, formulation granules containing the physical mixtures or solid dispersions were investigated. The matrix tablets for these formulations were prepared by direct compression and their in vitro release tests were carried out. The solid dispersion based tablets were found to be more effective than those compressed from physical mixtures in retarding the release of SF. Drug release from the matrix tablets containing physical mixtures nearly completed within 12h, while that from the solid dispersion formulations lasted for over 24h. Images of the tablet surface and cross-section were characterized by scanning electron microscopy to show the formed pores and channels in the matrices. These might provide the release pathway for the inner embedded drugs. Drug released fast from the matrix tablets with the release-enhancer of lactose. The addition of surfactants was also found to increase the release rate of SF effectively. Moreover, the co-mixing of polyethylene glycol 6000 (PEG 6000) in the waxy matrices played a meaningful role in controlling the drug release for 24h. The drug release from the novel formulation might be attributed to the diffusion-controlled mechanism.

Chemistry, Pharmaceutical↗

PubMed2006

Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP.

BACKGROUND: Generation of functional (CD4+)(CD8-)CD25+ regulatory T cells (Treg) in the murine thymus depends on FoxP3. Removal of the thymus from neonatal mice has been shown to result in a multiple organ autoimmune disease phenotype that can be prevented by introducing the FoxP3+ Treg population to the animal. It has therefore, been proposed that functional FoxP3+ Treg cells are not made in the neonatal thymus; however, it remains unclear when and where functional (FoxP3+)(CD4+)(CD8-)CD25+ thymocytes are generated in postnatal thymus. RESULTS: We report that neither FoxP3 mRNA nor protein is expressed in (CD4+)(CD8-)CD25+, or (CD4+)(CD8-)CD25- thymocytes until 3-4 days post birth, despite the presence of mature (CD4+)(CD8-)CD25+/- thymocytes in the thymus by 1-2 days after birth. (FoxP3-)(CD4+)(CD8-)CD25+ thymocytes from day 2 newborn mice show no Treg activity. Interestingly, we are able to detect low numbers of FoxP3+ thymocytes dispersed throughout the medullary region of the thymus as early as 3-4 days post birth. Expression of FoxP3 is induced in embryonic day 17 fetal thymus organ culture (FTOC) after 4-6 days of in vitro culture. Treatment of FTOCs with thymic stromal derived lymphopoietin (TSLP) enhanced expression of FoxP3, and blocking the TSLP receptor reduces FoxP3 expression in FTOC. Furthermore, TSLP stimulates FoxP3 expression in purified (CD4+)CD8- thymocytes, but not in (CD4+)CD8+, (CD4-)CD8+ and (CD4-)CD8- thymocytes. CONCLUSION: Expression of FoxP3 or Treg maturation is ontogenically distinct and kinetically delayed from the generation of (CD4+)(CD8-)CD25+ or (CD4+)(CD8-)CD25- thymocytes in the postnatal thymus. TSLP produced from medullary thymic epithelia cells (mTEC) contributes to the expression of FoxP3 and the maturation of natural regulatory T cells. Overall, these results suggest that the development of Treg cells requires paracrine signaling during late stages of thymocyte maturation that is distinct from signaling during positive or negative selection.

Animals↗

PubMed2006

Aggregating automatically extracted regulatory pathway relations.

Automatic tools to extract information from biomedical texts are needed to help researchers leverage the vast and increasing body of biomedical literature. While several biomedical relation extraction systems have been created and tested, little work has been done to meaningfully organize the extracted relations. Organizational processes should consolidate multiple references to the same objects over various levels of granularity, connect those references to other resources, and capture contextual information. We propose a feature decomposition approach to relation aggregation to support a five-level aggregation framework. Our BioAggregate tagger uses this approach to identify key features in extracted relation name strings. We show encouraging feature assignment accuracy and report substantial consolidation in a network of extracted relations.

Artificial Intelligence↗

PubMed2006

[Cold tolerance and wintering cultivation effect of different Welsh onion varieties].

With Welsh onion Zhangqiu as the contrast, this paper measured the physiological indices including electrolyte leakage, malondialdehyde content, protective enzyme activity, chlorophyll content, photosynthetic rate and root vitality of two introduced Welsh onion varieties Chunwei and Changhao, and identified their cold tolerance and wintering cultivation effect. The results showed that during wintering cultivation, all test Welsh onion varieties suffered low temperature stress, which led the electrolyte leakage and malondialdehyde content arrived at the maximum, while the chlorophyll content and photosynthetic rate dropped to the bottom at 15 January. At this time, the function data of physiological indices were 0. 452, 0. 364, and 0. 226 for Chuowei, Changbao and Zhangqiu, respectively, suggesting that Chunwei had stronger cold tolerance, followed by Changbao, and Zhangqiu. The bolting rate of Chunwei, Changbao and Zhangqiu when harvested was 0, 35.2% and 81.0% , respectively. Although the biological yield of Changbao was 25.67% and 52. 94% higher than that of Chunwei and Zhangqiu, respectively, the economic yield of Chunwei was the highest (5.49 kg m2) , with an increment of 18. 57% than Changbao, and that of Zhangqiu was only 0. 86 kg x m(-2) It could be concluded that Chonwei was fit to cultivate in low tunnel in winter, while Zhangqiu was weaker in cold tolerance and not fit to wintering cultivation.

Allium↗

PubMed2005

Allelotyping of esophageal squamous-cell carcinoma on chromosome 13 defines deletions related to family history.

We previously reported that esophageal squamous-cell cancers (ESCC) from Shanxi Province in China show frequent allelic loss on chromosome 13. Moreover, tumors from patients with a positive family history of upper gastrointestinal tumors exhibit more frequent loss of heterozygosity (LOH) on this chromosome than do those from patients without a family history. These results suggest the possibility of a familial ESCC susceptibility gene. To investigate this phenomenon further, we performed an in-depth analysis of allelic-loss data sets from both patients with and without a family history of upper gastrointestinal tumors. Comparisons between deletion frequency and location were made with respect to family history status, risk factors, and clinical/pathologic characteristics of the tumors. The analysis confirmed that tumor LOH was significantly higher in patients with a positive family history than in those who were family-history-negative, and four common deletion regions in these family-history-positive patients were defined. Statistically significant associations were also observed between allelic loss and tumor grade and location, as well as the presence of lymph node metastases. Taken together, these data indicate that a gene or genes on chromosome 13 play an important role in the etiology and progression of ESCC.

Carcinoma, Squamous Cell↗

PubMed2005

Linking ontological resources using aggregatable substance identifiers to organize extracted relations.

Systems that extract biological regulatory pathway relations from free-text sources are intended to help researchers leverage vast and growing collections of research literature. Several systems to extract such relations have been developed but little work has focused on how those relations can be usefully organized (aggregated) to support visualization systems or analysis algorithms. Ontological resources that enumerate name strings for different types of biomedical objects should play a key role in the organization process. In this paper we delineate five potentially useful levels of relational granularity and propose the use of aggregatable substance identifiers to help reduce lexical ambiguity. An aggregatable substance identifier applies to a gene and its products. We merged 4 extensive lexicons and compared the extracted strings to the text of five million MEDLINE abstracts. We report on the ambiguity within and between name strings and common English words. Our results show an 89% reduction in ambiguity for the extracted human substance name strings when using an aggregatable substance approach.

Algorithms↗

PubMed2004

Adeno-associated viral vector delivers cardiac-specific and hypoxia-inducible VEGF expression in ischemic mouse hearts.

It has been shown that the adeno-associated virus (AAV) vector can deliver the VEGF gene efficiently into the ischemic mouse myocardium. However, the AAV genomes can be found in extracardiac organs after intramyocardial injection. To limit unwanted VEGF expression in organs other than the heart, we tested the use of the cardiac myosin light chain 2v (MLC-2v) promoter and the hypoxia-response element to mediate cardiac-specific and hypoxia-inducible VEGF expression. An AAV vector, MLCVEGF, with 250 bp of the MLC-2v promoter and nine copies of the hypoxia-response element driving VEGF expression, was constructed. Gene expression was studied in vitro by infection of rat cardiomyocytes, rat skeletal myocytes, and mouse fibroblasts with the vector and in vivo by direct injection of the vector into normal and ischemic mouse hearts. With MLCVEGF infection, VEGF expression was higher in cardiomyocytes than the other two cell lines and was hypoxiainducible. VEGF expression was also higher in ischemic hearts than in normal hearts. No VEGF expression was detectable in organs with detectable MLCVEGF vectors other than the heart. MLCVEGF-injected ischemic hearts had more capillaries and small vessels around the injection site, smaller infarct size, and better cardiac function than the negative controls. Hence, MLCVEGF can mediate cardiac-specific and hypoxia-inducible VEGF expression, neoangiogenesis, infarct-size reduction, and cardiac functional improvement.

Animals↗

PubMed2004

Comprehensive characterization of annexin I alterations in esophageal squamous cell carcinoma.

PURPOSE: The purpose is to characterize alterations of the annexin I gene, its mRNA, and protein expression in esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: Fifty-six cases of esophageal squamous cell carcinoma were analyzed using four microsatellite markers flanking the annexin I gene (9q11-q21) to identify loss of heterozygosity. In addition, we performed (a) single-strand conformation polymorphism and DNA sequencing along the entire promoter sequence and coding region to identify mutations, (b) real-time quantitative reverse transcription-PCR of RNA from frozen esophageal squamous cell carcinoma tissue (n = 37) and in situ hybridization (n = 5) on selected cases to assess mRNA expression, and (c) immunohistochemistry (n = 44) to evaluate protein expression. The prevalence of the allelic variants identified in the first 56 patients was refined in 80 additional esophageal squamous cell carcinoma patients and 232 healthy individuals. RESULTS: Forty-six of 56 (82%) esophageal squamous cell carcinoma patients showed loss of an allele at one or more of the four microsatellite markers; however, only one (silent) mutation was seen. Two intragenic variants were identified with high frequency of allelic loss (A58G, 64%; L109L, 69%). Thirty of 37 (81%) esophageal squamous cell carcinoma patients showed reduced annexin I mRNA expression, which was confirmed by in situ hybridization, whereas annexin I protein expression was reduced in 79% of poorly differentiated tumor cell foci but in only 5% of well-differentiated tumor foci, although allelic loss on chromosome 9 was found in both tumor grades. CONCLUSIONS: Allelic loss of annexin I occurs frequently, whereas somatic mutations are rare, suggesting that annexin I is not inactivated in esophageal squamous cell carcinoma via a two-hit mechanism. A decrease in annexin I protein expression was confirmed, consistent with a quantitative decrease in mRNA expression, and appeared to be related to tumor cell differentiation. We conclude that annexin I is not the tumor suppressor gene corresponding to the high levels of loss of heterozygosity observed on chromosome 9 in esophageal squamous cell carcinoma; however, dysregulation of mRNA and protein levels is associated with this tumor type.

Alleles↗

PubMed2004

A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response.

Fifty million new infections with Mycobacterium tuberculosis occur annually, claiming 2-3 million lives from tuberculosis worldwide. Despite the apparent lack of significant genetic heterogeneity between strains of M. tuberculosis, there is mounting evidence that considerable heterogeneity exists in molecules important in disease pathogenesis. These differences may manifest in the ability of some isolates to modify the host cellular immune response, thereby contributing to the observed diversity of clinical outcomes. Here we describe the identification and functional relevance of a highly biologically active lipid species-a polyketide synthase-derived phenolic glycolipid (PGL) produced by a subset of M. tuberculosis isolates belonging to the W-Beijing family that show 'hyperlethality' in murine disease models. Disruption of PGL synthesis results in loss of this hypervirulent phenotype without significantly affecting bacterial load during disease. Loss of PGL was found to correlate with an increase in the release of the pro-inflammatory cytokines tumour-necrosis factor-alpha and interleukins 6 and 12 in vitro. Furthermore, the overproduction of PGL by M. tuberculosis or the addition of purified PGL to monocyte-derived macrophages was found to inhibit the release of these pro-inflammatory mediators in a dose-dependent manner.

Animals↗

PubMed2004

Selection and validation of endogenous reference genes using a high throughput approach.

BACKGROUND: Endogenous reference genes are commonly used to normalize expression levels of other genes with the assumption that the expression of the former is constant in different tissues and in different physiopathological conditions. Whether this assumption is correct it is, however, still matter of debate. In this study, we searched for stably expressed genes in 384 cDNA array hybridization experiments encompassing different tissues and cell lines. RESULTS: Several genes were identified whose expression was highly stable across all samples studied. The usefulness of 8 genes among them was tested by normalizing the relative gene expression against test genes whose expression pattern was known. The range of accuracy of individual endogenous reference genes was wide whereas consistent information could be obtained when information pooled from different endogenous reference genes was used. CONCLUSIONS: This study suggests that even when the most stably expressed genes in array experiments are used as endogenous reference, significant variation in test gene expression estimates may occur and the best normalization is achieved when data from several endogenous reference genes are pooled together to minimize minimal but significant variation among samples. We are presently optimizing strategies for the preparation of endogenous reference gene mixtures that could yield information comparable to that of data pooled from individual endogenous reference gene normalizations.

Carcinoma↗