Biomedical subjects

Y Yang

Publications and source records attributed to Y Yang.

At least 19 recordsLinked to original sources

PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗

PubMed2006

NFV, an HIV-1 protease inhibitor, induces growth arrest, reduced Akt signalling, apoptosis and docetaxel sensitisation in NSCLC cell lines.

HIV-1 protease inhibitor (PI), nelfinavir (NFV) induced growth arrest and apoptosis of NCI-H460 and -H520, A549, EBC-1 and ABC-1 non-small-cell lung cancer (NSCLC) cells in association with upregulation of p21waf1, p27kip1 and p53, and downregulation of Bcl-2 and matrix metalloproteinase (MMP)-2 proteins. We found that NFV blocked Akt signalling in these cells as measured by Akt kinase assay with glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) as a substrate. To explore the role of Akt signalling in NFV-mediated growth inhibition of NSCLC cells, we blocked this signal pathway by transfection of Akt small interfering RNA (siRNA) in these cells; transient transfection of Akt siRNA in NCI-H460 cells decreased the level of Bcl-2 protein and slowed their proliferation compared to the nonspecific siRNA-transfected cells. Conversely, forced-expression of Akt partially reversed NFV-mediated growth inhibition of these cells, suggesting that Akt may be a molecular target of NFV in NSCLC cells. Also, we found that inhibition of Akt signalling by NFV enhanced the ability of docetaxel to inhibit the growth of NCI-H460 and -H520 cells, as measured by MTT assay. Importantly, NFV slowed the proliferation and induced apoptosis of NCI-H460 cells present as tumour xenografts in nude mice without adverse systemic effects. Taken together, this family of compounds might be useful for the treatment of individuals with NSCLC.

Adenocarcinoma↗

PubMed2006

Novel DNA variations to characterize low molecular weight glutenin Glu-D3 genes and develop STS markers in common wheat.

Low-molecular-weight glutenin subunits (LMW-GS) play an important role in bread and noodle processing quality by influencing the viscoelasticity and extensibility of dough. The objectives of this study were to characterize Glu-D3 subunit coding genes and to develop molecular markers for identifying Glu-D3 gene haplotypes. Gene specific primer sets were designed to amplify eight wheat cultivars containing Glu-D3a, b, c, d and e alleles, defined traditionally by protein electrophoretic mobility. Three novel Glu-D3 DNA sequences, designated as GluD3-4, GluD3-5 and GluD3-6, were amplified from the eight wheat cultivars. GluD3-4 showed three allelic variants or haplotypes at the DNA level in the eight cultivars, which were designated as GluD3-41, GluD3-42 and GluD3-43. Compared with GluD3-42, a single nucleotide polymorphism (SNP) was detected for GluD3-43 in the coding region, resulting in a pseudo-gene with a nonsense mutation at the 119th position of deduced peptide, and a 3-bp insertion was found in the coding region of GluD3-41, leading to a glutamine insertion at the 249th position of its deduced protein. The coding regions for GluD3-5 and GluD3-6 showed no allelic variation in the eight cultivars tested, indicating that they were relatively conservative in common wheat. Based on the 12 allelic variants of three Glu-D3 genes identified in this study and three detected previously, seven STS markers were established to amplify the corresponding gene sequences in wheat cultivars containing five Glu-D3 alleles (a, b, c, d and e). The seven primer sets M2F12/M2R12, M2F2/M2R2, M2F3/M2R3, M3F1/M3R1, M3F2/M3R2, M4F1/M4R1 and M4F3/M4R3 were specific to the allelic variants GluD3-21/22, GluD3-22, GluD3-23, GluD3-31, GluD3-32, GluD3-41 and GluD3-43, respectively, which were validated by amplifying 20 Chinese wheat cultivars containing alleles a, b, c and f based on protein electrophoretic mobility. These markers will be useful to identify the Glu-D3 gene haplotypes in wheat breeding programs.

Alleles↗

PubMed2006

Ponicidin inhibits cell growth on hepatocellular carcinoma cells by induction of apoptosis.

BACKGROUND AND AIM: Ponicidin is recently reported to have anti-tumour effects on a large variety of cancers. The present study was undertaken to investigate the anti-proliferation effects of ponicidin on hepatocellular carcinoma cells and its mechanism. METHODS: Two hepatocellular carcinoma cell lines, QGY-7701 and HepG-2 cells, were used. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was assessed by flow cytometry and deoxyribonucleic acid fragmentation analysis. Cell morphology was observed by Hoechst 33258 staining. Reverse transcriptase-polymerase chain reaction and Western blot analysis were used to detect Survivin as well as Bax and Bcl-2 expressions. RESULTS: Ponicidin could inhibit the growth of QGY-7701 and HepG-2 cells significantly by induction of apoptosis. Marked morphological changes of apoptosis were observed clearly. Both Survivin and Bcl-2 expressions were down-regulated remarkably while Bax expression up-regulated when apoptosis occurred. CONCLUSIONS: Ponicidin has significant anti-proliferation effects by inducing apoptosis on hepatocellular carcinoma cells in vitro, down regulation of Survivin and Bcl-2 as well as upregualation of Bax expressions may be the important apoptotic inducing mechanisms.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Modulating bone cells response onto starch-based biomaterials by surface plasma treatment and protein adsorption.

The effect of oxygen-based radio frequency glow discharge (rfGD) on the surface of different starch-based biomaterials (SBB) and the influence of proteins adsorption on modulating bone-cells behavior was studied. Bovine serum albumin, fibronectin and vitronectin were used in single and complex protein systems. RfGD-treated surfaces showed to increase in hydrophilicity and surface energy when compared to non-modified SBB. Biodegradable polymeric blends of cornstarch with cellulose acetate (SCA; 50/50wt%), ethylene vinyl alcohol (SEVA-C; 50/50wt%) and polycaprolactone (SPCL; 30/70wt%) were studied. SCA and SCA reinforced with 10% hydroxyapatite (HA) showed the highest degree of modification as result of the rfGD treatment. Protein and control solutions were used to incubate with the characterized SBB and, following this, MG63 osteoblast-like osteosarcoma cells were seeded over the surfaces. Cell adhesion and proliferation onto SCA was found to be enhanced for non-treated surfaces and on SCA+10%HA no alteration was brought up by the plasma modification. Onto SCA surfaces, BSA, FN and VN single solutions improved cell adhesion, and this same effect was found upscaled for ternary systems. In addition, plasma treated SEVA-C directed an increase in both adhesion and proliferation comparing to non-treated surfaces. Even though adhesion onto treated and untreated SPCL was quite similar, plasma modification clearly promoted MG63 cells proliferation. Regarding MG63 cells morphology it was shown that onto SEVA-C surfaces the variation of cell shape was primarily defined by the protein system, while onto SPCL it was mainly affected by the plasma treatment.

Biocompatible Materials↗

PubMed2006

Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene.

In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp alpha1/Hp alpha2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs.

Acute-Phase Proteins↗

PubMed2006

GAL4-NF-kappaB fusion protein augments transgene expression from neuronal promoters in the rat brain.

Targeted gene expression mediated by a mammalian cellular promoter is desirable for gene therapy in the brain, where there are a variety of different neuronal phenotypes, several types of supportive cells, and blood vessels. However, this approach can be hampered by weak activity of some cellular promoters. In view of the potency of the transcription factor NF-kappaB in regulating neuronal gene expression, we have assessed whether it can be used to enhance the strength of neuron-specific promoters. Our approach was to use a neuronal promoter to drive expression of a chimeric transactivator, which consisted of a part of the transcriptional activation domain of the NF-kappaB p65 protein fused to the DNA-binding domain of GAL4 protein from yeast. The second copy of the neuronal promoter was modified by introducing the unique GAL4 binding sequences at its 5' end and used to drive the expression of a transgene. Binding of the chimeric transcriptional activator upstream of the second promoter was expected to potentiate its transcriptional activity. In this study, the approach was applied to the platelet-derived growth factor beta chain and synapsin-1 neuron-specific promoters and tested in vitro and in vivo using plasmid, lentiviral, and baculoviral vectors. We observed up to a 100-fold improvement in reporter gene expression in cultured neurons and 20-fold improvement in the rat brain in vivo. Moreover, the cell-type specificity of the two tested promoters was well preserved and restricted to neurons. Finally, the expression driven by the new lentiviral vectors with the p65-potentiated synapsin-1 promoter showed no signs of decline or cell damage 4 weeks after injection. This approach should be suitable for constructing powerful and stable gene expression systems based on weak cell-specific promoters in neuronal phenotypes.

Animals↗

PubMed2006

Organic carbon and nitrogen stable isotopes in the intertidal sediments from the Yangtze Estuary, China.

The natural isotopic compositions and C/N elemental ratios of sedimentary organic matter were determined in the intertidal flat of the Yangtze Estuary. The results showed that the ratios of carbon and nitrogen stable isotopes were respectively -29.8 per thousand to -26.0 per thousand and 1.6 per thousand-5.5 per thousand in the flood season (July), while they were -27.3 per thousand to -25.6 per thousand and 1.7 per thousand-7.8 per thousand in the dry season (February), respectively. The delta(13)C signatures were remarkably higher in July than in February, and gradually increased from the freshwater areas to the brackish areas. In contrast, there were relatively complex seasonal and spatial changes in stable nitrogen isotopes. It was also reflected that delta(15)N and C/N compositions had been obviously modified by organic matter diagenesis and biological processing, and could not be used to trace the sources of organic matter at the study area. In addition, it was considered that the mixing inputs of terrigenous and marine materials generally dominated sedimentary organic matter in the intertidal flat. The contribution of terrigenous inputs to sedimentary organic matter was roughly estimated according to the mixing balance model of stable carbon isotopes.

Carbon Isotopes↗

PubMed2006

Source apportionment of polycyclic aromatic hydrocarbons in surface soil in Tianjin, China.

Principal component analysis and multiple linear regression were applied to apportion sources of polycyclic aromatic hydrocarbons (PAHs) in surface soils of Tianjin, China based on the measured PAH concentrations of 188 surface soil samples. Four principal components were identified representing coal combustion, petroleum, coke oven plus biomass burning, and chemical industry discharge, respectively. The contributions of major sources were quantified as 41% from coal, 20% from petroleum, and 39% from coking and biomass, which are compatible with PAH emissions estimated based on fuel consumption and emission factors. When the study area was divided into three zones with distinctive differences in soil PAH concentration and profile, different source features were unveiled. For the industrialized Tanggu-Hangu zone, the major contributors were cooking (43%), coal (37%) and vehicle exhaust (20%). In rural area, however, in addition to the three main sources, biomass burning was also important (13%). In urban-suburban zone, incineration accounted for one fourth of the total.

Biomass↗

PubMed2006

Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism.

Apoptosis and epithelial-to-mesenchymal transition (EMT) have been implicated in a variety of biological processes, such as embryonic development, fibrosis and tumor progression. Transforming growth factor-beta (TGF-beta) can induce simultaneously both EMT and apoptotic response of epithelial cells. However, the underlying mechanism of these biological events remains not well understood. In the present study, we show that TGF-beta1 induces apoptosis and EMT in AML-12 cells in a cell cycle-related manner, in which apoptosis and EMT took place at G2/M and G1/S phases, respectively. TGF-beta1-induced apoptosis was correlated with different extent of caspase activation at different cell cycle phases. Interestingly, increased phosphorylation of protein kinase D (PKD) can be observed in G1/S phase in response to TGF-beta1, and inhibition of PKD by inhibitor or by small interference RNA blocked EMT but not apoptosis. Our data suggest a previously unrecognized role of cell cycle state in the regulation of TGF-beta-induced EMT and apoptosis, and demonstrate that PKD is involved in the TGF-beta1-induced EMT.

Apoptosis↗

PubMed2006

Endogenous overproduction of beta-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells.

Although neurofibrillary tangles and senile plaques have been identified as the hallmark pathological changes in the brain of Alzheimer's disease (AD), the relationship between them is still not fully understood. In the present study, we have studied the effect of endogenously overproduced amyloid beta (A beta) on tau by using wild type amyloid precursor protein (APP) transfected (N2a/APP695), or Swedish mutant APP plus Delta 9 deleted presenilin-1 co-transfected (N2a/APPswe.Delta 9) and APP vector transfected (N2a/vector) cell lines. We measured the secreted and intracellular A beta, including A beta(1-40) and A beta(1-42), by Sandwich ELISA assay. It was shown that the levels of A beta were increased time-dependently in N2a/APP695 and N2a/APPswe.Delta 9 but not in N2a/vector upon butyric acid (BA) treatment. Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment. Obvious accumulation of the hyperphosphorylated tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was observed at 48 h after BA treatment. The total level of the extracted tau was reduced in N2a/APP695 and N2a/APPswe.Delta 9 lines compared with N2a/vector cells by Western blot, and this reduction of total tau was also detected by immunofluorescence staining. No obvious alteration of tau mRNA was observed in both N2a/APP695 and N2a/APPswe.Delta 9 cells compared with N2a/vector. This study provides direct evidence demonstrating that endogenously overproduced A beta not only induces tau hyperphosphorylation but also decreases the level and solubility of tau in N2a cell lines.

Amyloid beta-Peptides↗

PubMed2006

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese.

The MPZL1/PZR gene has been mapped to 1q23.3, located in close proximity to a recognized schizophrenia susceptibility locus. Recently, the MPZL1/PZR gene has been found to be significantly upregulated in schizophrenia brain tissue and to play an important role in cell signaling, thus indicating that MPZL1/PZR could be a potential schizophrenia marker. To test this hypothesis, we selected three single nucleotide polymorphisms (SNPs) for genotyping in 523 Han Chinese trios. We found that two individual SNPs were significant at the Bonferroni's corrected significance level P<0.017: rs3767444 (chi2=6.299, P=0.0121) and rs2051656 (chi2=9.856, P=0.0017). Haplotype transmission/disequilibrium tests revealed a significant association with the disease (global P-value=1.064 x 10(-6)), but no specific transmission distortions. Thus, we propose that the MPZL1/PZR gene may be important in the predisposition to schizophrenia among Han Chinese.

Adult↗

PubMed2006

Alternative splicing factor ASF/SF2 is down regulated in inflamed muscle.

BACKGROUND: In our recent studies, alternative splicing has been shown to have a major role in inflammation and autoimmune muscle diseases. AIM: To examine the novel hypothesis that the expression of an essential alternative splicing factor, alternative splicing factor 2 (ASF/SF2), is modulated in muscle inflammation. METHODS: ASF/SF2 expression in muscle biopsy samples from eight patients with inflammatory myopathy and six non-myositic controls was determined by using western blot with anti-ASF/SF2 antibodies. To further elucidate the mechanism of reduced ASF/SF2 expression in inflamed muscle, differentiated C2C12 myotubes were stimulated with proinflammatory cytokine tumour necrosis factor alpha (TNFalpha), followed by western blot analysis of ASF/SF2 expression. RESULTS: ASF/SF2 expression in the muscle biopsy samples from patients with inflammatory myopathy was found to be lower (mean of relative densitometric units 41.1 (2SD 20.7)) than that of the non-myositic controls (mean of relative densitometric units 76.7 (39.6); p<0.05). In addition to this, ASF/SF2 expression was seen to be significantly down regulated (sevenfold) in C2C12 myotubes compared with expression variations in the beta-actin control (0.62-fold; mean 1.22 (0.40); p<0.05). CONCLUSION: Collectively, it is shown, for the first time, that alternative splicing factor ASF/SF2 is down regulated in autoimmune inflammatory myositis-potentially via a TNFalpha-mediated pathway. The development of (1) novel autoantigen isoform microarrays for disease diagnosis and prognosis; (2) novel autoantigen-tolerising treatments for autoimmune diseases; and (3) novel splicing-redirection treatments can be facilitated by the ongoing study of alternative splicing of autoantigen transcripts.

Aged↗

PubMed2006

Spin proximity effect in ultrathin superconducting Be-Au bilayers.

We present a detailed study of the effects of interface spin-orbit coupling on the critical field behavior of ultrathin superconducting Be/Au bilayers. Parallel field measurements were made in bilayers with Be thicknesses in the range of d=2-30 nm and Au coverages of 0.5 nm. Though the Au had little effect on the superconducting gap, it produced profound changes in the spin states of the system. In particular, the parallel critical field exceeded the Clogston limit by an order of magnitude in the thinnest films studied. In addition, the parallel critical field unexpectedly scaled as [FORMULA: SEE TEXT], suggesting that the spin-orbit coupling energy was proportional to Delta0/d2. Tilted field measurements showed that, contrary to recent theory, the interface spin-orbit coupling induces a large in-plane superconducting susceptibility but only a very small transverse susceptibility.

Journal Article↗

PubMed2006

Characterizing the efficacy of calcium channel agonist-release strategies for bone tissue engineering applications.

We have previously reported on the use of Bay K8644-release strategies in combination with perfusion-compression bioreactor systems for up regulating bone formation in three-dimensional PLLA scaffolds. Here we report on the analysis of Bay activity following its release from our PLLA scaffolds over the culture period imposed in our tissue engineering protocol using UV spectroscopy in combination with whole cell patch clamping techniques. Bay was released continually from scaffolds within the physiological range required for agonist activity (1-10 microM). Patch clamping allowed for the effects of Bay released from scaffolds to be monitored directly with respect to osteoblast electrophysiology. A characteristic shift in the current-voltage (I-V) relationship of L-type VOCC currents was observed in rat osteoblast sarcoma (ROS) cells patched in a solution with Bay released from scaffolds following 14 and 28 days incubation, with statistically significant differences observed in peak currents compared to non-Bay controls. An increase in the magnitude of the peak inward currents was also noted. The electrophysiological response of osteoblasts in the presence of Bay released from scaffolds demonstrates that the released Bay is stable and maintains its bioactivity following culture of up to 28 days.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2006

MRI relaxation fluctuations in acute reperfused hemorrhagic infarction.

MRI evaluations of intramyocardial hemorrhage in acute infarction have relied on T(2) and T(2)(*) shortening only. We propose a more comprehensive evaluation of hemorrhagic infarction based on the concept that fluctuations in T(2) and T(1) relaxation in acute reperfused infarction will reflect transient edema and hemoglobin oxidative denaturation to uncompartmentalized methemoglobin. Anteroapical infarction was created via percutaneous balloon in young swine (22-25 kg, N = 12). T(2), T(1), diastolic wall thickness (DWT), and the Gd-DTPA partition coefficient (lambda) were measured on days 0, 2, and 7. DWT was elevated at 1 hr postreperfusion (128% +/- 53%, P = 0.0001), and alleviated on days 2 and 7 (48% +/- 10%, P = 0.008; 53% +/- 24%, P = 0.003). T(2) and T(1) elevations were coincident with early edema (DeltaT(2) = 55% +/- 24%, P < 0.0001; DeltaT(1) = 27% +/- 18%, P < 0.04). T(2) and T(1) were nearly normal on day 2 (DeltaT(2) = 8% +/- 8%, P = 0.27; DeltaT(1) = 0% +/- 1%, P = 0.65). On day 7, T(2) increased while T(1) decreased (DeltaT(2) = 27% +/- 16%, P = 0.005; DeltaT(1) = -14% +/- 10%, P = 0.02). Lambda was elevated by >150% at all time points (P < or = 0.002). Histology verified hemorrhagic injury. T(1) and T(2) fluctuations are consistent with transient edema, as well as hemoglobin oxidative denaturation to decompartmentalized methemoglobin. This methodological development may broaden our understanding of hemorrhagic microvascular injury and improve its detection in clinical populations.

Acute Disease↗

PubMed2006

Toxicity assessment of contaminated sediments after dredging.

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Biological Assay↗

PubMed2006

Characterization of chitosan films and effects on fibroblast cell attachment and proliferation.

Chitosan has been researched for implant and wound healing applications. However, there are inconsistencies in reports on the tissue and fibroblast responses to chitosan materials. These inconsistencies may be due to variations in chitosan material characteristics. The aim of this study was to correlate fibroblast responses with known chitosan material characteristics. To achieve this aim, chitosan was characterized for degree of deacetylation (DDA), molecular weight (MW), residual protein and ash contents, and then solution cast into films and characterized for hydrophilicity by water contact angle. The films were seeded with normal human dermal fibroblasts and the number of attached cells was evaluated for after 30 min. Cell proliferation was evaluated over 5 days. This study found no relationship between DDA, contact angle, cell attachment, and or proliferation. General trends were observed for increasing proliferation with increasing residual ash content and decreasing residual protein. These data indicate that chitosan characteristics other than DDA may be important to their biological performance.

Acetylation↗