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Biomedical subjects

H Miao

Publications and source records attributed to H Miao.

At least 19 recordsLinked to original sources
PubMed2006

NOTCH signaling as a novel cancer therapeutic target.

NOTCH-ligand interaction is a highly conserved mechanism that regulates specific cell fate decision during development. In addition to its functions in developmental and cell maturation processes, studies indicate that NOTCH activation plays a role in the onset and progression of many human malignancies. The prevailing new strategy for rationally targeted cancer treatment is aimed at the development of target-selective "smart" drugs on the basis of characterized mechanisms of action. The connection between NOTCH signaling and tumorigenesis suggests that NOTCH may be such a target candidate. Gamma-secretase is a large membrane-integral multisubunit protease complex, which is essential for NOTCH receptor activation. Inhibitors of this enzyme are being developed for Alzheimer's disease, due to its role in cleaving beta-amyloid precursor in the brain. Recently, Gamma-secretase inhibitors (GSIs), as well as various biopharmaceutical or genetic NOTCH signaling inhibitors have been suggested as potential novel cancer therapeutic strategies. This review summarizes the evidence linking NOTCH signaling to several types of cancer, as well as the possible therapeutic indications of NOTCH inhibitors and the challenges facing their clinical development.

Amyloid Precursor Protein Secretases↗
PubMed2005

Optical edge-projection method for three-dimensional profilometry.

A novel optical edge-projection method is proposed for surface contouring of an object with low reflectivity. A structured light edge is projected onto a dark surface, and the image is captured by a CCD camera. The object contour is evaluated with an active triangular projection algorithm, and one obtains a whole-field three-dimensional contour of the object by scanning the optical edge over the entire object surface. The proposed method is applied to a black nonreflective object made from woven carbon fiber and is also applied to measure the profile of a small object (a coin). The results show that an accurate profile of the specimen can be obtained.

Algorithms↗
PubMed2005

Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma.

BACKGROUND AND AIMS: alpha-Fetoprotein (AFP), a tumour marker for hepatocellular carcinoma (HCC), is associated with poor prognosis. Using cDNA microarray analysis, we previously found that ephrin-A1, an angiogenic factor, is the most differentially overexpressed gene in AFP producing hepatoma cell lines. In the present study, we investigated the significance of ephrin-A1 expression in HCC. METHODS: We examined ephrin-A1 expression and its effect on cell proliferation and gene expression in five AFP producing hepatoma cell lines, three AFP negative hepatoma cell lines, and 20 human HCC specimens. RESULTS: Ephrin-A1 expression levels were lowest in normal liver tissue, elevated in cirrhotic tissue, and further elevated in HCC specimens. Ephrin-A1 expression was strongly correlated with AFP expression (r = 0.866). We showed that ephrin-A1 induced expression of AFP. This finding implicates ephrin-A1 in the mechanism of AFP induction in HCC. Ephrin-A1 promoted the proliferation of ephrin-A1 underexpressing HLE cells, and an ephrin-A1 antisense oligonucleotide inhibited the proliferation of ephrin-A1 overexpressing Huh7 cells. Thus ephrin-A1 affects hepatoma cell growth. cDNA microarray analysis showed that ephrin-A1 induced expression of genes related to the cell cycle (p21), angiogenesis (angiopoietin 1 and thrombospondin 1), and cell-cell interactions (Rho, integrin, and matrix metalloproteinases) in cultured hepatoma cells. These ephrin-A1 induced genes are also activated in HCC tissues that overexpress AFP. CONCLUSION: These findings suggest that the poor prognosis of patients with AFP producing HCC is partially caused by ephrin-A1 expression, which induces expression of genes related to tumour cell growth, angiogenesis, invasion, and metastasis.

Carcinoma, Hepatocellular↗
PubMed2001

The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate.

Release of Abeta peptides from beta-amyloid precursor protein (APP) requires sequential cleavage by two endopeptidases, beta- and gamma-secretases. beta-Secretase was recently identified as a novel membrane-bound aspartyl protease, named BACE1, Asp2, or memapsin 2. Employing confocal microscopy and subcellular fractionation, we have found that BACE1 is largely situated in the distal Golgi membrane with a minor presence in the endoplasmic reticulum, endosomes, and plasma membrane in human neuroblastoma SHEP cells and in mouse Neuro-2a cell lines expressing either endogenous mouse BACE1 or additional exogenous human BACE1. The major cellular beta-secretase activity is located in the late Golgi apparatus, consistent with its cellular localization. Furthermore, we demonstrate that the single transmembrane domain of BACE1 alone determines the retention of BACE1 to the Golgi compartments, through examination of recombinant proteins of various BACE1 fragments fused to a reporter green fluorescence protein. In addition, we show that the transmembrane domain of BACE1 is required for the access of BACE1 enzymatic activity to the cellular APP substrate and hence for the optimal generation of the C-terminal fragment of APP (CTF99). The results suggest a molecular and cell biological mechanism for the regulation of beta-secretase activity in vivo.

Alzheimer Disease↗
PubMed2001

Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands.

The aim of this study is to elucidate the role of integrins in transducing fluid shear stress into intracellular signals in vascular endothelial cells, a fundamental process in vascular biology. We demonstrated that shear stress activates specific integrins in endothelial cells plated on substrates containing the cognate extracellular matrix (ECM) ligands. The shear stress-induced mechanotransduction, as manifested by integrin-Shc association, was abolished when new integrin-ECM ligand interactions were prevented by either blocking the integrin-binding sites of ECM ligands or conjugating the integrins to immobilized antibodies. Our results indicate that the dynamic formation of new connections between integrins and their specific ECM ligands is critical in relaying the signals induced by shear stress to intracellular pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells.

A line of evidence has shown that a link between the common pathological features of beta-amyloid peptide (Abeta) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to Abeta can decrease expression of nicotinic acetylcholine receptors (nAChRs), which have been shown to play roles in brain cognitive functions. Here, we report that treatment with Abeta1-40 and Abeta25-35 at nanomolar concentrations significantly decreased the [3H]epibatidine and [125I]alpha-bungarotoxin binding sites, the protein and mRNA levels of nAChR alpha3, alpha7 and beta2 subunits in PC12 cells. Abeta1-40 and Abeta25-35 at the concentrations used in the treatment study neither bound to nAChRs nor induced apoptosis, but significantly inhibited the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by Abeta may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that Abeta can degenerate nAChRs early in the course of AD before the formation of abundant Abeta fibrils.

Acetylcholine↗
PubMed2001

Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway.

Interactions between Eph receptor tyrosine kinases (RTKs) and membrane-anchored ephrin ligands critically regulate axon pathfinding and development of the cardiovascular system, as well as migration of neural cells. Similar to other RTKs, ligand-activated Eph kinases recruit multiple signalling and adaptor proteins, several of which are involved in growth regulation. However, in contrast to other RTKs, activation of Eph receptors fails to promote cell proliferation or to transform rodent fibroblasts, indicating that Eph kinases may initiate signalling pathways that are distinct from those transmitted by other RTKs. Here we show that stimulation of endogenous EphA kinases with ephrin-A1 potently inhibits the Ras/MAPK cascade in a range of cell types, and attenuates activation of mitogen-activated protein kinase (MAPK) by receptors for platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). In prostatic epithelial cells and endothelial cells, but not fibroblasts, treatment with ephrin-A1 inhibits cell proliferation. Our results identify EphA kinases as negative regulators of the Ras/MAPK pathway that exert anti-mitogenic functions in a cell-type-specific manner.

Animals↗
PubMed2001

[Application of DNDC model in estimation of CH4 and N2O emissions in agricultural ecosystems in Yangtze River Delta].

It was paid attention that CH4 and N2O emission from agricultural soil in Yangtze River Delta where there is most advanced agricultural region in China. In this paper, a regional-scale biogeochemical model DNDC was validated on available field measurement. Then it was used to estimate CH4 and N2O emission in Yangtze River Delta to be 1.69 (1.29-2.09) Tg.a-1 and 0.019 (0.014-0.024) Tg.a-1, respectively. They are about 16.7% and 6.1% of the national total CH4 and N2O emissions from agricultural ecosystems, respectively.

Agriculture↗
PubMed2001

MCF-10A-NeoST: a new cell system for studying cell-ECM and cell-cell interactions in breast cancer.

PURPOSE: There is a continuing need for genetically matched cell systems to model cellular behaviors that are frequently observed in aggressive breast cancers. EXPERIMENTAL DESIGN: We report here the isolation and initial characterization of a spontaneously arising variant of MCF-10A cells, NeoST, which provides a new model to study cell adhesion and signal transduction in breast cancer. RESULTS: NeoST cells recapitulate important biological and biochemical features of metastatic breast cancer, including anchorage-independent growth, invasiveness in three-dimensional reconstituted membranes, loss of E-cadherin expression, and increased tyrosine kinase activity. A comprehensive analysis of tyrosine kinase expression revealed overexpression or functional activation of the Axl, FAK, and EphA2 tyrosine kinases in transformed MCF-10A cells. CONCLUSIONS: MCF-10A and these new derivatives provide a genetically matched model to study defects in cell adhesion and signaling that are relevant to cellular behaviors that often typify aggressive breast cancer cells.

Breast Neoplasms↗
PubMed2001

[Multivariate logistic regression analysis on the risk factors of type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between multivariate factors and type 2 diabetes mellitus. METHODS: Polymorphisms of microsatellite markers in uncoupling protein 3 (UCP3) gene, hormone-sensitive lipase (HSL) gene and protein tyrosine phosphatase-1B (PTP-1B) gene were tested in 106 patients with type 2 diabetes and 102 control subjects by performing polymerase chain reaction (PCR), polyacrylamide gel electrophoresis and silver staining. Multivariate logistic regression analysis was performed by all factors. RESULTS: Through univariate analysis, type 2 diabetes had significantly positive associations with age, systolic blood pressure (SBP), fasting insulin (FINS) level, cholesterol, triglyceride, low-density lipoprotein, apolipoprotein B (ApoB), alpha lipoprotein, UCP3 gene allele 6, UCP3 gene allele 7, HSL gene allele 9, and negative associations with UCP3 gene allele 1 and 3, HSL gene allele 5, high-density lipoprotein. The results of multivariate logistic analysis showed that UCP3 gene allele 6, UCP3 gene allele 7, SBP, ApoB, alpha lipoprotein were still positively related to type 2 diabetes, while HSL gene allele 5, high-density lipoprotein were still negatively related to type 2 diabetes. CONCLUSION: Our data showed that UCP3 gene allele 6, UCP3 gene allele 7, SBP, abnormity of plasma ApoB and alpha lipoprotein might play a role in the development of type 2 diabetes. HSL gene allele 5, high-density lipoprotein might play some protective role in the development of type 2 diabetes.

Blood Pressure↗
PubMed2001

[Analysis of group composit of crude oil by on-line coupling of capillary HPLC-HTGC].

The group composition of crude oil was analyzed by on-line coupled capillary HPLC-HTGC. After removal of asphaltenes, the oil sample was separated by capillary HPLC into aliphatics, aromatics and resins. The interface cut and stored each fraction, and transfered them into GC sequentially. The group contents of oil were determined by FID. The error of reproducibility(RSD) was less than 3%. The method is accurate, time saving, and easy for operation. It is very important for quality control and development of new and better products in crude oil.

English Abstract↗
PubMed2001

[Dynamic pre-concentration method of gas sample].

By utilizing the combination of frontal chromatography at ambient temperature, back-flushing and temperature gradient thermal desorption, a prototype of a dynamic pre-concentration system has been designed and evaluated. It realized the enrichment for gas samples of boiling point higher than - 103 degrees C without cryogenic facilities. To reduce the sample volume and enhance enrichment factor, the technique of momentarily non-steady state produced at the beginning of back-flushing, and the negative temperature gradient generated during thermal desorption were utilized, resulting a very sharp desorption band. Standard samples were tested to demonstrate the applicability of the method. At 10 mL sample volume, the enrichment factor was 100.

Absorption↗
PubMed2001

[Effect of NaFeEDTA fortified soy sauce on iron deficiency anemia in students].

NaFeEDTA fortified soy sauce was given to 300 students with iron deficiency anemia (IDA) for 3 months. The subjects were divided into three groups: control group, low iron supplemented group (Fe 5 mg/d) and high iron supplemented group (Fe 20 mg/d). Hemoglobin (Hb), serum iron, serum ferrtin, erythrocyte protoporphyrin, total iron binding capacity and serum transferrin were evaluated before and after the study. The results showed that Hb, serum iron, ferrtin and transferrin of the intervention groups had improved and erythrocyte protoporphyrin, total iron binding capacity decreased. There were no differences between the two intervention groups after the trial. The parameters of both intervention groups were much better than those of the control group. The results suggested that NaFeEDTA fortified soy sauce had positive influence on IDA.

Adolescent↗
PubMed2000

Regiospecific carbonylative annulation of iodophenol acetates and acetylenes to construct the flavones by a new catalyst of palladium-thiourea-dppp complex.

[reaction: see text] Regiospecific carbonylative annulation of o-iodophenol acetates and acetylenes mediated by palladium-thiourea-dppp complex in the presence of base at 40 degrees C under a balloon pressure of CO generates diversified flavones in high yields. This newly developed synthetic technology provides a highly efficient method for potential application to the combinatorial synthesis of those heterocycles on the solid support.

Acetylene↗
PubMed2000

Sonographic guidance of air enema for intussusception reduction in children.

BACKGROUND: Fluoroscopically guided air reduction of intussusception is a well-accepted technique. There are only two previous reports in which US has been used to monitor pneumatic reduction. OBJECTIVE: To assess the ability of US to monitor the success of air reduction of intussusception. MATERIALS AND METHODS: Sonographically guided air-enema reduction of intussusception in 199 children. In phase I (11 children), the success or failure of reduction was confirmed by fluoroscopy. In phase II (188 children), complete reduction was confirmed by clinical improvement of the child and repeat sonography 1 h later showing no persistent intussusception. RESULTS: In phase I, fluoroscopy confirmed the accuracy of US in all 11 children. In phase II, the success rate of initial reduction was 95%. Following successful reduction, US repeated 1 h later showed no recurrence of intussusception in 92%. In ten (5%) of 188, initial reduction was unsuccessful; fluoroscopically guided air reduction successfully reduced only three of these ten failures. CONCLUSIONS: Air enema guided by US is a practical and reliable technique for the reduction of intussusception.

Air↗
PubMed2000

Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation.

Interactions between receptor tyrosine kinases of the Eph family and their ligands, ephrins, are implicated in establishment of organ boundaries and repulsive guidance of cell migration during development, but the mechanisms by which this is achieved are unclear. Here we show that activation of endogenous EphA2 kinase induces an inactive conformation of integrins and inhibits cell spreading, migration and integrin-mediated adhesion. Moreover, EphA2 is constitutively associated with focal-adhesion kinase (FAK) in resting cells. Within one minute after stimulation of EphA2 with its ligand, ephrin-A1, the protein tyrosine phosphatase SHP2 is recruited to EphA2; this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 complex. We conclude that Eph kinases mediate some of their functions by negatively regulating integrins and FAK.

3T3 Cells↗