PubMed Health⌕ Search

Biomedical subjects

Q Wang

Publications and source records attributed to Q Wang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells in concert with changes in glucose concentration.

AIMS/HYPOTHESIS: The role of gamma-aminobutyric acid (GABA) and A-type GABA receptors (GABA(A)Rs) in modulating islet endocrine function has been actively investigated since the identification of GABA and GABA(A)Rs in the pancreatic islets. However, the reported effects of GABA(A)R activation on insulin secretion from islet beta cells have been controversial. METHODS: This study examined the hypothesis that the effect of GABA on beta cell insulin secretion is dependent on glucose concentration. RESULTS: Perforated patch-clamp recordings in INS-1 cells demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l, induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R antagonist bicuculline. The current-voltage relationship revealed that I(GABA) reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless, the glucose concentration critically controlled the membrane potential (V (M)), i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential. Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose concentration, but hyperpolarisation at a high glucose concentration. Consistent with electrophysiological findings, insulin secretion assays demonstrated that at 2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion (p<0.05, n=7). This enhancement was blocked by bicuculline (p<0.05, n=4). In contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of insulin (p<0.05, n=5). CONCLUSIONS/INTERPRETATION: These findings indicate that activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with changes in glucose levels.

Animals↗
PubMed2006

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines.

AIMS/HYPOTHESIS: Activin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-beta superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis. METHODS: We detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays. RESULTS: Induction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. CONCLUSIONS/INTERPRETATION: These results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.

Activin Receptors, Type I↗
PubMed2006

Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase.

Glycogen-synthase kinase-3 (GSK-3) and extracellular signal-regulated kinase (ERK) are critical downstream signaling proteins for the PI3-kinase/Akt and Ras/Raf/MEK-1 pathway, respectively, and regulate diverse cellular processes including embryonic development, cell differentiation and apoptosis. Here, we show that inhibition of GSK-3 using GSK-3 inhibitors or RNA interference (RNAi) significantly induced the phosphorylation of ERK1/2 in human colon cancer cell lines HT29 and Caco-2. Pretreatment with the PKCdelta-selective inhibitor rottlerin or transfection with PKCdelta siRNA attenuated the phosphorylation of ERK1/2 induced by the GSK-3 inhibitor SB-216763 and, furthermore, treatment with SB-216763 or transfection with GSK-3alpha and GSK-3beta siRNA increased PKCdelta activity, thus identifying a role for PKCdelta in the induction of ERK1/2 phosphorylation by GSK-3 inhibition. Treatment with SB-216763 increased expression of cyclooxygenase-2 (COX-2) and IL-8, which are downstream targets of ERK1/2 activation; this induction was abolished by MEK/ERK inhibition, suggesting GSK-3 inhibition induced COX-2 and IL-8 through ERK1/2 activation. The transcriptional induction of COX-2 and IL-8 by GSK-3 inhibition was further demonstrated by the increased COX-2 and IL-8 promoter activity after SB-216763 treatment or transfection with GSK-3alpha or GSK-3beta siRNA. Importantly, our findings identify GSK-3, acting through PKCdelta, as a negative regulator of ERK1/2, thus revealing a novel crosstalk mechanism between these critical signaling pathways.

Apoptosis↗
PubMed2006

Assessment of hemodynamics properties of a new-type artificial heart valve prosthesis using catheterization and echocardiography.

OBJECTIVE: The objectives of this study were to assess the hemodynamic properties of the newly developed artificial heart valve prosthesis experimentally in laboratory simulation, in an animal model, and clinically in a human model and to compare the results measured by catheterization and echocardiography. METHODS: (1) Laboratory simulation. The prosthesis was tested using a pulsatile flow simulator in the aortic position. Hydrodynamics parameters were automatically analyzed through a custom-designed data processing program. (2) Animal experiment. Six sheep subjected to mitral replacement with 21-mm-valve prosthesis were measured by open cardiac catheterization intraoperatively. Doppler echocardiography and open cardiac catheterization under dobutamine stress were performed in two sheep subjected to implantation 2.5 years ago. (3) Clinical patient observation. Observations were carried out on 14 patients with aortas replacement and 10 patients with bicuspid replacement using both doppler echocardiography and open cardiac catheterization. RESULTS: (1) Laboratory simulation. The results showed that the value of the transvalvular gradient (DeltaP) decreased with the increase of heart rate, and the values were not greater that 10 mm Hg at any given tissue annulus diameter. (2) Animal experiment. The mean DeltaP value of the six sheep was 5.2 +/- 1.7 mm Hg intraoperatively, while the corresponding DeltaP value of the two sheep 2.5 years after implantation was 6.1 +/- 0.3 mm Hg measured by open cardiac catheterization. (3) Clinical patient observation. The mean DeltaP values in the aortic position measured by catheterization and echocardiography were 6.26 approximately 4.10 and 9.42 approximately 7.48 mm Hg, respectively. The gradients in the mitral position were 2.10 approximately 1.9 and 5.28 approximately 4.10 mm Hg, respectively. CONCLUSIONS: The results demonstrate that the new-type bileaflet heart valve prosthesis only generates a relatively low transvalvar gradient and thus has good hemodynamic properties.

Adult↗
PubMed2006

Histamine induces interleukin-6 expression in the human synovial sarcoma cell line (SW982) through the H1 receptor.

METHODS: The effect of histamine on inositol phosphate generation and interleukin-6 (IL-6) release from the synovial sarcoma cell line SW982 was investigated. RESULTS: SW982 cells express functional H1 and H2 receptors. The H1 receptor antagonist [3H]-mepyramine binds to membranes from SW982 cells with high affinity and the binding was potently blocked by H1 antagonists. Histamine potently stimulated phosphoinositide (PI) hydrolysis and Ca2+ mobilization with EC50 of 4.0 +/- 0.8 microM and 1.3 +/- 0.6 microM respectively and these activities were blocked by the H1 selective antagonist mepyramine. Histamine (EC50 = 1.8 +/- 1.1 microM) stimulated the release of IL-6 that was attenuated by selective H1 antagonists. The PKC inhibitor, GF1090203X, blocked the histamine stimulated IL-6 release. The H2 selective antagonist, cimetidine, had no significant effect on histamine-induced PI turnover, Ca2+ mobilization and IL-6 release. CONCLUSION: We conclude that histamine stimulates IL-6 release from SW982 cells by binding to the H1 receptor and this is coupled to the PI/PKC signal transduction pathway. Development of an H1 antagonist that inhibits the release of IL-6 from synoviocytes may be beneficial for the treatment of inflammatory joint disease.

Cell Line, Tumor↗
PubMed2006

RAIDD is required for apoptosis of PC12 cells and sympathetic neurons induced by trophic factor withdrawal.

Caspase 2 has been implicated in trophic deprivation-induced neuronal death. We have shown that overexpression of the caspase 2-binding protein RAIDD induces neuronal apoptosis, acting synergistically with trophic deprivation. Currently, we examine the role of endogenous RAIDD in apoptosis of PC12 cells and sympathetic neurons. Expression of a truncated caspase recruitment domain-only form of caspase 2, which presumably disrupts the RAIDD interaction with endogenous caspase 2, attenuated trophic deprivation-induced apoptosis. Furthermore, downregulation of RAIDD by small interfering RNA led to inhibition of trophic deprivation-induced death, whereas death induced by DNA damage, which is not caspase 2-mediated, was not inhibited. Therefore, RAIDD, likely through interaction with caspase 2, is involved in trophic deprivation-induced neuronal apoptosis. This is the first demonstration of the involvement of RAIDD in apoptosis, and provides further support for the idea that apoptotic pathways in the same system may differ depending on the initiating stimulus.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Application of I(125) brachytherapy combined artificial joint prosthesis in malignant osteo- and soft-tissue sarcoma.

OBJECTIVES: The aim of this study was to evaluate the brachytherapy effectiveness of I(125) seeds combined with artificial prosthesis in malignant sarcoma therapy. METHODS: The combination of I(125) seeds and artificial prosthesis was implanted to replace tumor section for three clinical cases-2 malignant osteosarcoma patients and 1 malignant soft-tissue tumor patient- through the direct operation. RESULTS: Approximately 14-18 months after the operation, the results of our post-operational investigation showed that the tumor tissues of 3 patients had been completely removed. The limb functions recovered well. The brachytherapy of the combination of I(125) seeds and artificial prosthesis in malignant tumor improved the curative effect. No tumor existed, and no infection occurred. CONCLUSIONS: It was demonstrated that this method was safe and easy. No side-effect was observed after the implantation of I(125) seeds. The brachytherapy was proven to be a potential method for patients who were at high risk to recrudesce the malignant osteosarcoma of tumors after the tumor excision.

Adolescent↗
PubMed2006

Tissue expression and association with fatness traits of liver fatty acid-binding protein gene in chicken.

Fatty acid-binding proteins belong to a superfamily of lipid-binding proteins that exhibit a high affinity for long-chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate expression characterization and association with growth and composition traits of the liver fatty acid-binding protein (L-FABP) gene in the chicken. Northern blot analysis indicated that the gene, similar to the mammal L-FABP gene, was expressed only in liver and intestinal tissues. The mRNA levels of the chicken L-FABP gene in liver and intestine had significant differences between the broilers and Baier layers. The China Agricultural University F(2) population was used in the present study. Body weight and body composition traits were measured in the populations. Primers for the coding region and 5' upstream region of the L-FABP gene were designed according to chicken genomic and cDNA sequence. Polymorphisms were detected by DNA sequencing, and the PCR single-strand conformation polymorphisms method was developed to genotype the F(2) population. The results indicated that the L-FABP gene polymorphisms were associated with abdominal fat weight and percentage of abdominal fat, and the L-FABP gene could be a candidate locus or linked to a major gene(s) that affects fatness traits in the chicken. The results of the current study provided basic molecular information for studying the role of the L-FABP gene in the regulation of lipid metabolism in avian species.

Abdominal Fat↗
PubMed2006

Identification of single nucleotide polymorphism of adipocyte fatty acid-binding protein gene and its association with fatness traits in the chicken.

Fatty acid-binding proteins (FABP) belong to a superfamily of lipid binding proteins that exhibit a high affinity for long chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate the effects of the adipocyte (A)-FABP gene on chicken growth and body composition traits. Two F2 resource populations were used in the current study. Body weight and body composition traits were measured in the populations. Primers for the coding region of the A-FABP gene were designed from chicken genomic and cDNA sequences. Polymorphism between parental lines was detected by DNA sequencing, and the PCR-RFLP method was developed to genotype the F2 populations. The results indicated that an A-FABP gene polymorphism was associated with abdominal fat weight and percentage of abdominal fat, and the A-FABP gene could be a candidate locus or linked to a major gene(s) that affects abdominal fat content in the chicken.

Animals↗
PubMed2006

Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B and ESAT-6 antigens of Mycobacterium tuberculosis.

Antigen 85B (Ag85B) and ESAT-6 are important immunodominant antigens of Mycobacterium tuberculosis, and both are very promising vaccine candidate molecules. In this study, we relied on the T-cell epitopes of Ag85B and ESAT-6 to design a chimaeric protein by inserting ESAT-6 into Ag85B from the amino acids 167-182. We found the ratio of IgG2b/IgG1 and the secretion of interferon (IFN)-gamma in the mice vaccinated with the new protein with adjuvant MPL and TDM were higher than the mice immunized with fusion protein Ag85B-ESAT-6, which have been reported and could induce levels of protective immunity similar to BCG in the mouse model of tuberculosis (TB) infection. These results suggest that the chimaeric protein Ag85B(N)-ESAT-6-Ag85B(C) is a strong candidate for further study and the T-cell epitopes of the antigens should be considered when we design the subunit vaccine.

Acyltransferases↗
PubMed2006

Characterization and application of two novel monoclonal antibodies against human OX40: costimulation of T cells and expression on tumor as well as normal gland tissues.

OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response. Here, we newly generated two specific mouse antihuman OX40 monoclonal antibodies (mAbs) (2G2 and 1F7), whose specificities are quite different from the available OX40 mAb (ACT35) by competition assay. It was also found that both mAbs could enhance the proliferation, activation and differentiation of T lymphocytes primed by anti-CD3 mAb. These results evidenced that both were functional antihuman OX40 mAbs. Furthermore, stained by 2G2 and 1F7, FCM and immunohistochemistry detected the constitutive expression of OX40 on tumor cell lines from epithelium, breast cancer and glioma tissues. Meanwhile, the non-tumor tissues (thyroid gland, stomach gland) were also found OX40 expression. These results suggested that OX40 is not only expressed in activated T cells, but also in some tumors as well as normal gland tissues. Such expression pattern indicated that OX40 may be a valuable surface antigen in unveiling its expression and function outside the immune system. Briefly, these novel antibodies may contribute to the evaluation of the mechanism of tumor metastasis and eventually shed light on further study of tumor immunotherapy and autoimmune diseases.

Animals↗
PubMed2006

Fusion of CpG-ODN-stimulating dendritic cells with Lewis lung cancer cells can enhance anti-tumor immune responses.

Immunogenicity of tumor cells is generally weak. Therefore, dendritic cells (DCs) have been used to boost anti-tumor responses of DC-based vaccines. DC function is highly dependent on its subsets and the level of its maturation. Nowadays, DC/tumor cell fusion vaccines are already used in clinical trials, and there are numerous studies discussing the effects of cytidine-phosphate-guanosine-containing oligonucleotides (CpG-ODN) on various cell types including DC. CpG-ODN a powerful immuno-stimulant can drive DCs fully mature, thus improve the efficacy of vaccine therapy. There are two simple ways to help load tumor antigens onto DCs by direct contact with cells themselves: fusion or co-culture of DCs with whole tumor cells. In this study, we combined these two approaches to improve the efficacy of DC/tumor cell-based vaccine. Mature DCs are adept at presenting processed Ag to T cells with loss of its capacity to capture Ag, while immature DCs are on the contrary. Our results emphasize the necessity of considering the stage of DC maturation and corresponding choice of tumor antigen delivery when designing approaches for prophylaxis or therapy of tumors using DC-based immunization protocols. We used CpG-ODN-1826-stimulated mature DCs and non-CpG-ODN-stimulating DCs as sources of tumor antigen carriers to investigate the appropriate Ag-loading ways between fusion and co-culture. Our results displayed that DC/tumor vaccine using CpG-ODN-stimulating mature DCs fused, not co-cultured, with tumor cells can generate a consistent and highly effective anti-tumor immune responses in vivo.

Adjuvants, Immunologic↗
PubMed2006

QT prolongation due to aortic aneurysm rupture and amiodarone in a patient with a H558R polymorphism in the cardiac sodium channel gene SCN5A.

The duration of the QT interval is influenced by many pathologic processes and drugs. We report a 74-year-old man who was admitted after syncope. His electrocardiogram (ECG) showed a QT interval of 0.44 s (QTc 0.53 s). After 10 h a ruptured abdominal aortic aneurysm was diagnosed and the patient underwent implantation of an aorto-bi-iliac Y-prosthesis. After surgery QT interval normalized. Under therapy with amiodarone, given because of atrial fibrillation, QT prolongation occurred again and disappeared after discontinuation of amiodarone. The postoperative course was complicated by critical illness polyneuropathy and plexopathy. Whereas amiodarone is a well recognized cause of QT prolongation, aortic aneurysm rupture has not been described previously. Vegetative mechanisms and sudden decrease of cardiac afterload due to the ruptured aneurysm may have altered myocardial repolarisation and thus prolonged QT interval duration. In conclusion in a patient with syncope and QT prolongation, extracardiac causes like rupture or an aortic aneurysm have to be included into the differential diagnosis.

Aged↗
PubMed2005

Ferromagnetism in Mn-doped GaN nanowires.

Using density functional theory we show that the magnetic coupling of Mn atoms in the nanowires, unlike that in the thin film, is ferromagnetic. This ferromagnetic coupling, brought about due to the confinement of electrons in the radial direction and the curvature of the Mn-doped GaN nanowires' surface, is mediated by N as is evidenced from the overlap between Mn 3d and N 2p states. Calculations of the anisotropic energy further show that the magnetic moment orients preferably along the [1010] direction while the wire axis points along the [0001] direction.

Journal Article↗
PubMed2005

Chinese medicinal herbs for acute bronchitis.

BACKGROUND: Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics, (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have been also used as treatment. OBJECTIVES: This review aims to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), which includes the Cochrane Acute Respiratory Infections Group's specialised register; The Chinese Cochrane Centre's Controlled Trials Register (up to December 2004); MEDLINE (1966 to March Week 1, 2005); EMBASE (1988 to December 2004); and the Chinese Biomedical Database (CBM) (1980 to December 2004). SELECTION CRITERIA: Randomised controlled trials comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two authors extracted data and assessed trial quality. MAIN RESULTS: Four trials reported the time to improvement of cough, fever, and rales associated with bronchitis and showed that patients treated with Chinese herbs had a shorter duration of signs and symptoms. Two trials reported the proportion of patients with improved signs and symptoms at follow up and showed that Chinese herbs were beneficial in terms of relief of signs and symptoms. Thirteen trials analysed the data on physician global assessment of improvement at follow up. Nine of thirteen trials showed that Chinese herbs were superior to routine treatment and the other four trials showed a similar effect to routine treatment. In general, Chinese herbs appeared beneficial. Only one trial reported on adverse effects during treatment. AUTHORS' CONCLUSIONS: There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. The benefit found in this systematic review could be due to publication bias and study-design limitations of the individual studies. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events are rarely reported. Chinese herbs should be used carefully.

Acute Disease↗
PubMed2005

Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture.

Formation of neurofibrillary tangle from hyperphosphorylated tau is one of the hallmark lesions seen in Alzheimer's disease (AD) brain, and neuronal deregulation of glycogen synthase kinase-3 (GSK-3) activity plays key role in tau hyperphosphorylation. In the present study, the role of GSK-3 on tau phosphorylation in hippocampus slice culture was examined by incubating the slice with wortmannin (WT), an inhibitor of phosphatidylinositol 3-kinase (PI3K) and GF-109203X (GFX), an inhibitor of protein kinase C (PKC). It was found that treatment of the slices with GFX or WT separately induced tau hyperphosphorylation both at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1) sites. The phosphorylation rate of tau at PHF-1 and Tau-1 epitopes was further increased when GFX and WT were used in combination, and at this condition, AD-like tau accumulation was observed. GSK-3 activity was significantly increased with a concurrently decreased level of inactivated form of GSK-3. Lithium chloride (LiCl), a GSK-3 inhibitor, prevented tau from WT- and GFX-induced hyperphosphorylation. It suggests that GSK-3 is regulated through PI3K and PKC pathway, and activation of GSK-3 not only induces hyperphosphorylation of tau but also leads to accumulation of tau in cultured rat brain slice.

Alzheimer Disease↗
PubMed2005

Short-length microstructured phosphate glass fiber lasers with large mode areas.

We report fabrication and testing of the first phosphate glass microstructured fiber lasers with large Er-Yb-codoped cores. For an 11-cm-long cladding-pumped fiber laser, more than 3 W of continuous wave output power is demonstrated, and near single-mode beam quality is obtained for an active core area larger than 400 microm2.

Journal Article↗