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Biomedical subjects

Xiaoping Yang

Publications and source records attributed to Xiaoping Yang.

36 records · Page 2Linked to original sources
PubMed2005

Angiotensin II promotes smooth muscle cell proliferation and migration through release of heparin-binding epidermal growth factor and activation of EGF-receptor pathway.

Transactivation of EGF-receptor (EGFR) by G-protein coupled receptors (GPCRs) is emerging as an important pathway in cell proliferation, which plays a crucial role in the development of atherosclerotic lesion. Angiotensin II (Ang II) has been identified to have a major role in the formation of atherosclerotic lesions, although the underlying mechanisms remain largely unclear. We hypothesize that Ang II promotes the proliferation and migration of smooth muscle cells through the release of heparin-binding epidermal growth factor like growth factor (HB-EGF), transactivation of EGFR and activation of Akt and Erk 1/2, with matrix metalloproteases (MMPs) playing a dispensable role. Primary rat aortic smooth muscle cells were used in this study. Smooth muscle cells rendered quiescent by serum deprivation for 12 h were treated with Ang II (100 nM) in the presence of either GM6001 (20 microM), a specific inhibitor of MMPs or AG1478 (10 microM), an inhibitor of EGFR. The levels of phosphorylation of EGFR, Akt and Erk 1/2 were assessed in the cell lysates. Inhibition of MMPs by GM6001 significantly attenuated Ang II-stimulated phosphorylation of EGFR, suggesting that MMPs may be involved in the transactivation of EGFR by Ang II receptor. Furthermore Ang II-stimulated proliferation and migration of smooth muscle cells were significantly blunted by inhibiting MMPs and EGFR and applying HB-EGF neutralization antibody, indicating that MMPs, HB-EGF and EGFR activation is necessary for Ang-II stimulated migration and proliferation of smooth muscle cells. Our results suggest that inhibition of MMPs may represent one of the strategies to counter the mitogenic and motogenic effects of Ang II on smooth muscle cells and thereby prevent the formation and development of atherosclerotic lesions.

Angiotensin II↗
PubMed2005

Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation.

OBJECTIVE: Vascular smooth muscle cell (VSMC) migration, proliferation, and collagen synthesis are key events involved in the pathogenesis of cardiovascular disease. Growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor, released during vascular injury plays a pivotal role in regulating these events. Curcumin (diferuloyl methane), a major component of the spice turmeric (Curcuma longa), has been shown recently to have beneficial effects in chronic conditions, such as inflammation, cancer, cystic fibrosis, and Alzheimer's disease. The objective of this study was to investigate the ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and collagen synthesis in cultured VSMCs and neointima formation after carotid artery injury in rats. METHODS AND RESULTS: Curcumin (1 to 25 microM) produced a concentration-dependent inhibition of PDGF-elicited VSMC migration, proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine incorporation, and [3H]-L-proline incorporation, respectively. Curcumin blocked PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal transduction, and inhibited the binding of PDGF to its receptors. Carotid artery neointima formation was significantly attenuated by perivascular curcumin compared with vehicle controls 14 days after injury, characterized by reduced DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation. CONCLUSIONS: These data suggest that curcumin is a potent inhibitor of key PDGF-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury.

Actin Cytoskeleton↗
PubMed2005

DNA sequence and analysis of human chromosome 18.

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.

Aneuploidy↗
PubMed2005

A newly synthetic chromium complex--chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance.

Low-molecular-weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with D-phenylalanine ligand in aqueous solution. In mouse 3T3-adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 microg/kg/d, for six weeks) in ob/ob+/+ obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less-toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes.

Adipocytes↗
PubMed2005

Holographic glucose sensors.

A novel holographic sensor system capable of detecting dynamic changes in glucose concentration has been developed. The hologram is recorded within a bio-compatible hydrogel matrix containing phenylboronic acid derivatives. On binding glucose, the colour of the hologram red-shifts to longer wavelengths as the hydrogel expands and this colour change is used to quantify glucose concentration. However, phenylboronic acids are non-selective and bind a wide variety of cis-diols. In blood, glucose is the only sugar found free at high concentration, whilst other sugars are typically found as part of glycoproteins and macromolecular structures. Although glycoproteins have been shown to have no effect on the sensor, phenylboronic acids can bind lactate much more readily than glucose. We have designed two polymer hydrogel systems to increase the selectivity of the sensor for glucose over lactate. The first involved the use of high concentrations of 3-acrylamidophenylboronic acid (3-APB) whilst the second system utilised 2-acrylamido-5-fluorophenylboronic acid (5-F-2-MAPB). Both systems displayed an increased selectivity to glucose over lactate at physiological pH and ionic strength and could be deployed as selective holographic sensors for glucose detection in physiological fluids.

Biosensing Techniques↗
PubMed2005

Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification.

Evidence suggests that aging, per se, is a major risk factor for cardiac dysfunction. Oxidative modification of cardiac proteins by non-enzymatic glycation, i.e. advanced glycation endproducts (AGEs), has been implicated as a causal factor in the aging process. This study was designed to examine the role of aging on cardiomyocyte contractile function, cardiac protein oxidation and oxidative modification. Mechanical properties were evaluated in ventricular myocytes from young (2-month) and aged (24-26-month) mice using a MyoCam system. The mechanical indices evaluated were peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt). Oxidative stress and protein damage were evaluated by glutathione and glutathione disulfide (GSH/GSSG) ratio and protein carbonyl content, respectively. Activation of NAD(P)H oxidase was determined by immunoblotting. Aged myocytes displayed a larger cell cross-sectional area, prolonged TR90, and normal PS, +/- dL/dt and TPS compared with young myocytes. Aged myocytes were less tolerant of high stimulus frequency (from 0.1 to 5 Hz) compared with young myocytes. Oxidative stress and protein oxidative damage were both elevated in the aging group associated with significantly enhanced p47phox but not gp91phox expression. In addition, level of cardiac AGEs was approximately 2.5-fold higher in aged hearts than young ones determined by AGEs-ELISA. A group of proteins with a molecular range between 50 and 75 kDa with pI of 4-7 was distinctively modified in aged heart using one- or two-dimension SDS gel electrophoresis analysis. These data demonstrate cardiac diastolic dysfunction and reduced stress tolerance in aged cardiac myocytes, which may be associated with enhanced cardiac oxidative damage, level of AGEs and protein modification by AGEs.

Aging↗
PubMed2005

Views from within and beyond: narratives of cardiac contractile dysfunction under senescence.

Senescence is associated with enhanced risk of cardio-vascular diseases. It is generally considered that decline in growth hormones (such as insulin-like growth factor I), intrinsic myocardial and endothelial functions, as well as accumulation of reactive oxygen species with increased age may contribute to cardiovascular senescence. It is believed that heart function, especially cardiac reserve declines with advanced age. However, most experimental and clinical investigations on ventricular function only included young or adult subjects and failed to address this important age issue in heart pathophysiology. Although senescent but otherwise healthy hearts may possess normal pumping function at the resting or non-stressed state, some aging-associated factors such as accumulation of reactive oxygen species and activation of selective stress signaling path-ways may interact with certain risk factors and compromise overall cardiac function. The precise cause and progression of compromised cardiac function in the elderly remain controversial. This review will focus on senescence-related alterations in cardiac contractile function with a special emphasis on oxidative stress and activation of stress signaling.

Aged↗
PubMed2004

Synthesis and structure of Zn7(mu4-O)2(OAc)10(Pz)2(OAc = acetate; Pz = pyrazine).

Reaction of Zn(OAc)(2).2H(2)O with pyrazine in refluxing ethanol gives the unusual heptanuclear complex Zn7(mu4-O)(2)(OAc)(10)(Pz)(2) (1) (OAc = acetate, Pz = pyrazine) in 46% yield. A single-crystal X-ray diffraction study of revealed a central Zn(7) core in which two pseudo-tetrahedral Zn(4) units are joined at a common vertex. The two pyrazine molecules are bound as terminal (eta1) ligands.

Journal Article↗
PubMed2004

Glucose-sensitive holographic sensors for monitoring bacterial growth.

A glucose sensor comprising a reflection hologram incorporated into a thin, acrylamide hydrogel film bearing the cis-diol binding ligand, 3-acrylamidophenylboronic acid (3-APB), is described. The diffraction wavelength (color) of the hologram changes as the polymer swells upon binding cis-diols. The effect of various concentrations of glucose, a variety of mono- and disaccharides, and the alpha-hydroxy acid, lactate, on the holographic response was investigated. The sensor displayed reversible changes in diffraction wavelength as a function of cis-diol concentration, with the sensitivity of the system being dependent on the cis-diol tested. The effect of varying 3-APB concentration in the hydrogel on the holographic response to glucose was investigated, and maximum sensitivity was observed at a functional monomer concentration of 20 mol %. The potential for using this holographic sensor to detect real-time changes in bacterial cell metabolism was demonstrated by monitoring the germination and subsequent vegetative growth of Bacillus subtilis spores.

Bacillus subtilis↗
PubMed2004

The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions.

Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream target genes, and displaces Cdt1 from its complex with geminin. By establishing competitive regulation, geminin functions as a coordinator of developmental and proliferative control.

Amino Acid Sequence↗
PubMed2004

In vivo gene delivery and visualization of corneal stromal cells using an adenoviral vector and keratocyte-specific promoter.

PURPOSE: This study was conducted to determine whether intrastromal injection of adenoviral construct could be used to transfect corneal stroma cells effectively in vivo and to determine whether a tissue-specific promoter could be used to express exogenous genes in keratocytes. METHODS: An adenoviral construct with a cytomegalovirus (pCMV)-driven enhanced green fluorescent protein (EGFP) reporter gene was injected into the stroma of murine corneas. In vivo expression was quantitated and samples were analyzed by in vivo stereomicroscopy, and ex vivo expression was determined by confocal three dimensional (3-D) reconstruction. The 3.2-kb keratocan promoter was used to drive tissue-specific reporter gene expression in vivo. RESULTS: EGFP expression was first detected in vivo 11 hours after injection of adeno-EGFP in the corneal stroma, with a duration of approximately 3 weeks. Ex vivo wholemount cornea confocal analysis with 3-D reconstruction allowed visualization of EGFP expression in corneal stroma cells, to accurately assess cellular architecture and distribution in the corneal stroma. Naked pCMV-EGFP plasmid DNA did not express the reporter gene to the levels of the adeno-EGFP. The 3.2-kb keratocan promoter was capable of driving EGFP tissue-specific expression in the cornea. CONCLUSIONS: Intrastromal injection of adenovirus packaged DNA constructs is a rapid and efficient way to deliver and express genes in the corneal stroma. Intrastromal injection is also capable of delivering tissue-specific promoter constructs to the corneal stroma for gene expression. Furthermore, 3-D reconstruction provides a powerful tool for enhanced visualization of the corneal stroma environment and cellular biology.

Adenoviridae↗
PubMed2004

[Visualization of the parapharyngeal space of the Chinese visible human].

OBJECTIVE: To build digitized visible model of the parapharyngeal space(PPS) of Chinese visible human. METHOD: Cross-sectional images from the Chinese visible human data set were reviewed and the structures of the parapharyngeal space were confirmed on a section-by-section basis. Three-dimensional computer reconstructions of the parapharyngeal space and surrounding structures were generated from these data using PC and imaging software. RESULT: The three-dimensional reconstructed images displayed perfectly the anatomical relationships of the parapharyngeal space, parotid, muscles, mandible and vessels. All reconstructed structures can be represented individually or jointly, any diameter and angle of the structures reconstructed could be measured conveniently. CONCLUSION: The Chinese visible human data set can provide complete and accurate data. The digitized model of the parapharyngeal space and its surroundings offer unique insights into the complex anatomy, and provide morphological data for image diagnosis and operation of the parapharyngeal space.

Adipose Tissue↗
PubMed2003

Characterization of tetrandrine, a potent inhibitor of P-glycoprotein-mediated multidrug resistance.

Multidrug resistance (MDR) is one of the main obstacles in tumor chemotherapy. A promising approach to solving this problem is to utilize a nontoxic and potent modulator able to reverse MDR, which in combination with anticancer drugs increases the anticancer effect. Experiments were carried out to examine the potential of tetrandrine (Tet) as a MDR-reversing agent. Survival of cells incubated with Tet at 2.5 micromol/l for 72 h was over 90%. Tet at 2.5 micromol/l almost completely reversed resistance to vincristine (VCR) in KBv200 cells. Tet at a concentration as low as 0.625 micromol/l produced a 7.6-fold reversal of MDR, but showed no effect on the sensitivity of drug-sensitive KB cells in vitro. In the KBv200 cell xenograft model in nude mice, neither Tet nor VCR inhibited tumor growth. However, VCR and Tet combined inhibited tumor growth by 45.7%, 61.2% and 55.7% in three independent experimental settings. In the KB cell xenograft model in nude mice, Tet did not inhibit tumor growth, but VCR and the combination of VCR and Tet inhibited tumor growth by 40.6% and 41.6%, respectively. Mechanism studies showed that Tet inhibited [(3)H]azidopine photoaffinity labeling of P-gp and increased accumulation of VCR in MDR KBv200 cells in a concentration-dependent manner. The results suggest that Tet is a potent MDR-reversing agent in vitro and in vivo. Its mechanism of action is via directly binding to P-gp and increasing intracellular VCR accumulation.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2003

Impairments of ERK signal transduction in the brain in a rat model of depression induced by neonatal exposure of clomipramine.

Depression is associated with deficiencies in monoaminergic transmitters and possibly neurotrophins. A common cellular response to these molecules is the activation of extracellular signal-regulated kinase (ERK). A deficiency of ERK signal transduction in depression was therefore hypothesized and was tested in a rat model of depression, produced by neonatal treatment with clomipramine (CLI). We measured sexual behaviors and brain levels of ERK, phosphorylated ERK (pERK), protein phosphatase 1 (PP1), and MAPK phosphatase-2 (MKP-2) during adulthood in control and neonatally CLI-treated rats (CLI rats). As expected, the CLI rats exhibited significantly lower sexual activities and also exhibited (1). significant decreases of pERK1/2 in the frontal cortex and pERK1 in the hippocampus, (2). slight but significant reduction of ERK2 in the frontal cortex and hippocampus, (3). no change of pERK1/2 levels in the temporal cortex, occipital cortex, parietal cortex, midbrain, and medulla, (4). significantly higher levels of PP1 in both the frontal cortex and hippocampus, (5). no change in MKP-2 in any examined region, and (6). all five measures of sexual function were significantly correlated with ERK2 and pERK2 in the frontal cortex. These findings suggest that a deficiency in the ERK signaling pathway is involved in the display of depressive behaviors.

Animals↗
PubMed2003

Reduced hepatocyte proliferation is the basis of retarded liver tumor progression and liver regeneration in mice lacking N-acetylglucosaminyltransferase III.

Mice lacking N-acetylglucosaminyltransferase III (GlcNAc-TIII) exhibit slightly but significantly retarded liver tumor progression after a single injection of 10 micro g/g diethylnitrosamine (DEN) and continued administration of phenobarbital (PB) in drinking water. A key question is whether the absence of GlcNAc-TIII inhibits cell proliferation or induces apoptosis. Because PB aids tumor progression, we tested whether it diminished the difference in tumor progression between Mgat3(+/+) and Mgat3(Delta/Delta) mice. Here, we show that in the absence of PB, control males developed about twice as many liver tumor nodules as males lacking GlcNAc-TIII. Both the size of liver tumors and liver weights were significantly greater in DEN-treated wild-type or heterozygous mice. Apoptosis assays performed monthly after DEN treatment showed no differences between mutant and wild-type. However, there was a marked retardation in liver regeneration after partial (70%) hepatectomy (PH). Wild-type mice incorporated bromodeoxyuridine in approximately 15% of hepatocyte nuclei at 48 h after PH, whereas mice lacking GlcNAc-TIII had only approximately 5% positive nuclei. This was not because of enhanced apoptosis in mutant mice after PH. Expression of the Mgat3 gene remained undetectable in wild-type liver by Northern analysis after tumor induction or after PH. In addition, transgenic overexpression of GlcNAc-TIII in hepatocytes did not enhance tumor progression in Mgat3(Delta/Delta) mice, and there were no differences in tumor progression or liver regeneration after PH between control and transgenic mice overexpressing GlcNAc-TIII in liver. Therefore, the nonhepatic action of GlcNAc-TIII promotes hepatocyte proliferation after PH, as well as the progression of DEN-induced tumors, providing evidence for a functional role of the bisecting GlcNAc on circulating glycoprotein growth factor(s) that stimulate hepatocyte proliferation.

Acetylglucosamine↗