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Yuan Min Wang,
Jimmy Jianheng Zhou, Ya Wang,
Debbie Watson,
Geoff Yu Zhang,
Min Hu,
Huiling Wu,
Guoping Zheng,
Yiping Wang,
Anne M Durkan,
David Ch Harris,
Stephen I Alexander
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ABSTRACT: Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia and worldwide. DNA vaccination has been used for targeting foreign antigens to induce immune responses and prevent autoimmune disease, viral infection and cancer. However, the use of DNA vaccination has been restricted by a limited ability to induce strong immune responses, especially against self-antigens which are limited by mechanisms of self-tolerance. Furthermore, there have been few studies on the potential of DNA vaccination in chronic inflammatory diseases, including CKD. We have established strategies of DNA vaccination targeting specific self-antigens in the immune system including co-stimulatory pathways, T cell receptors and chemokine molecules, which have been effective in protecting against the development of CKD in a variety of animal models. In particular, we find that the efficacy of DNA vaccination is improved by dendritic cell (DC) targeting and can protect against animal models of autoimmune nephritis mimicking human membranous nephropathy. In this review, we summarize several approaches that have been tested to improve the efficacy of DNA vaccination in CKD models, including enhanced DNA vaccine delivery methods, DNA vaccine modifications and new molecular targets for DNA vaccination. Finally, we discuss the specific application of DNA vaccination for preventing and treating CKD.
International journal of clinical and experimental pathology 01/2013; 6(3):326-33. · 1.89 Impact Factor
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Ya Wang,
Yuan Min Wang,
Yiping Wang,
Guoping Zheng,
Geoff Yu Zhang,
Jimmy Jianheng Zhou,
Thian Kui Tan,
Qi Cao,
Min Hu,
Debbie Watson,
Huiling Wu,
Dong Zheng,
Changqi Wang,
Mireille H Lahoud,
Irina Caminschi,
David C Harris,
Stephen I Alexander
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ABSTRACT: The CD40-CD154 costimulatory pathway has been shown to be critical for both T- and B-cell activation in autoimmune disease. Here, we assessed the effects of blocking this pathway using CD40 DNA vaccine enhanced by dendritic cell targeting on the development of active Heymann nephritis, a rat model of human membranous nephropathy. DNA vaccination delivers plasmid DNA encoding the target antigen, either alone or in combination with enhancing elements, to induce both humoral and cellular immune responses. To determine whether CD40 DNA vaccine targeting the encoded CD40 directly to dendritic cells would improve the efficacy of the vaccination against self-protein CD40, we utilized a plasmid encoding a single-chain Fv antibody specific for the dendritic cell-restricted antigen-uptake receptor DEC205 (scDEC), the target gene CD40, and the adjuvant tetanus sequence p30. This vaccine plasmid was compared to a control plasmid without scDEC. Rats vaccinated with scDEC-CD40 had significantly less proteinuria and renal injury than did rats receiving scControl-CD40 and were protected from developing Heymann nephritis. Thus, CD40 DNA vaccination targeted to dendritic cells limits the development of Heymann nephritis.Kidney International advance online publication, 5 December 2012; doi:10.1038/ki.2012.374.
Kidney International 12/2012; · 6.61 Impact Factor
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ABSTRACT: Quantum correlation quantified by quantum discord has been demonstrated
experimentally as important physical resources in quantum computation and
communication for some cases even without the presence of entanglement.
However, since the interaction between the quantum system and the noisy
environment is inevitable, it is essential to protect quantum correlation from
lost in the environment and to characterize its dynamical behavior in the real
open systems. Here we showed experimentally in the solid-state P:Si system the
existence of a stable interval for the quantum correlation in the beginning
until a critical time $t_c \approx 166$ ns of the transition from classical to
quantum decoherence. To protect the quantum correlation, we achieved the
extension of the critical time by 50 times to $8 \mu$s by applying a two-flip
dynamical decoupling (DD) pulse sequence. Moreover, we observed the phenomenon
of the revival of quantum correlation, as well as classical correlation. The
experimental observation of a non-decay interval for quantum correlation and
the great extension of it in an important solid-state system with genuine noise
makes the use quantum discord as physical resources in quantum information
processing more practicable.
09/2012;
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Tania Polhill,
Geoff Yu Zhang,
Min Hu,
Andrew Sawyer,
Jimmy Jianheng Zhou,
Mitsuru Saito,
Kylie E Webster, Ya Wang,
Yiping Wang,
Shane T Grey,
Jonathan Sprent,
David C H Harris,
Stephen I Alexander,
Yuan Min Wang
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ABSTRACT: Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease.
Journal of the American Society of Nephrology 06/2012; 23(8):1303-8. · 9.66 Impact Factor
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Xiangkun Xu,
Zixiang Wang,
Changkui Duan,
Pu Huang,
Pengfei Wang, Ya Wang,
Nanyang Xu,
Xi Kong,
Fazhan Shi,
Xing Rong,
Jiangfeng Du
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ABSTRACT: To implement reliable quantum information processing, quantum gates have to
be protected together with the qubits from decoherence. Here we demonstrate
experimentally on nitrogen-vacancy system that by using continuous wave
dynamical decoupling method, not only the coherence time is prolonged by about
20 times, but also the quantum gates is protected for the duration of
controlling time. This protocol shares the merits of retaining the superiority
of prolonging the coherence time and at the same time easily combining with
quantum logic tasks. It is expected to be useful in task where duration of
quantum controlling exceeds far beyond the dephasing time.
05/2012;
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Yuan Min Wang,
Geoff Yu Zhang,
Min Hu,
Tania Polhill,
Andrew Sawyer,
Jimmy Jianheng Zhou,
Mitsuru Saito,
Debbie Watson,
Huiling Wu, Ya Wang,
Xin Maggie Wang,
Yiping Wang,
David C H Harris,
Stephen I Alexander
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ABSTRACT: Autoreactive T cells play a pivotal role in the pathogenesis of autoimmune kidney disease. T cell vaccination (TCV) may limit autoimmune disease and induce CD8+ regulatory T cells (Tregs). We used Heymann nephritis (HN), a rat model of human membranous nephritis, to study the effects of TCV on autoimmune kidney disease. We harvested CD4+ T cells from renal tubular antigen (Fx1A) -immunized rats and activated these cells in vitro to express the MHC Class Ib molecule Qa-1. Vaccination of Lewis rats with these autoreactive Fx1A-induced T cells protected against HN, whereas control-primed T cells did not. Rats that underwent TCV had lower levels of proteinuria and serum creatinine and significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates. Furthermore, these rats expressed less IFN-γ and IL-6 in splenocytes, whereas the numbers of Tregs and the expression of Foxp3 were unchanged. In vitro cytotoxicity assays showed CD8+ T cell-mediated elimination of Qa-1-expressing CD4+ T cells. In vivo, TCV abrogated the increase in Qa-1-expressing CXCR5+ TFH cells observed in HN compared with controls. Taken together, these results suggest that TCV protects against autoimmune kidney disease by targeting Qa-1-expressing autoreactive CD4+ cells.
Journal of the American Society of Nephrology 04/2012; 23(6):1058-67. · 9.66 Impact Factor
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ABSTRACT: Quantum systems unfold diversified correlations which have no classical
counterparts. These quantum correlations have various different facets. Quantum
entanglement, as the most well known measure of quantum correlations, plays
essential roles in quantum information processing. However, it has recently
been pointed out that quantum entanglement cannot describe all the
nonclassicality in the correlations. Thus the study of quantum correlations in
separable states attracts widely attentions. Herein, we experimentally
investigate the quantum correlations of separable thermal states in terms of
quantum discord. The sudden change of quantum discord is observed, which
captures ambiguously the critical point associated with the behavior of
Hamiltonian. Our results display the potential applications of quantum
correlations in studying the fundamental properties of quantum system, such as
quantum criticality of non-zero temperature.
03/2012;
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ABSTRACT: A glucose oxidase (GOx)-mediated glucose metabolism was in vitro mimicked and employed to regulate the self-assembly of peptide-based building blocks. In this new stimuli-responsive self-assembly system, two peptide-based building blocks, respectively, having aspartic acid (gelator 1) and lysine (gelator 2) residues were designed and prepared. When adding glucose and GOx to the aqueous solution of gelator 1 or the self-assembled fibrillar hydrogel of gelator 2 to construct glucose metabolism system, the metabolic product (gluconic acid) can trigger the protonation of the peptide molecules and induce the phase transitions of gelators 1 (sol-gel) and 2 (gel-sol). Because this glucose metabolism regulated peptide self-assembly is built on the oxidation of glucose, it can be used as a simple visual biosensor for glucose detection.
Macromolecular Rapid Communications 03/2012; 33(5):426-31. · 4.60 Impact Factor
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ABSTRACT: Human tumor cell death during radiotherapy is caused mainly by ionizing radiation (IR)-induced DNA double-strand breaks (DSB), which are repaired by either homologous recombination repair (HRR) or nonhomologous end-joining (NHEJ). Although siRNA-mediated knockdown of DNA DSB repair genes can sensitize tumor cells to IR, this approach is limited by inefficiencies of gene silencing. In this study, we show that combining an artificial miRNA (amiR) engineered to target 3'-untranslated regions of XRCC2 (an HRR factor) or XRCC4 (an NHEJ factor) along with an siRNA to target the gene coding region can improve silencing efficiencies to achieve more robust radiosensitization than a single approach alone. Mechanistically, the combinatorial knockdown decreased targeted gene expression through both a reduction in mRNA stability and a blockade to mRNA translation. Together, our findings establish a general method of gene silencing that is more efficient and particularly suited for suppressing genes that are difficult to downregulate by amiR- or siRNA-based methods alone.
Cancer Research 03/2012; 72(5):1221-8. · 7.86 Impact Factor
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Dong Zheng,
Qi Cao,
Vincent W S Lee, Ya Wang,
Guoping Zheng,
YuanMin Wang,
Thian Kui Tan,
Changqi Wang,
Stephen I Alexander,
David C H Harris,
Yiping Wang
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ABSTRACT: Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy.
Kidney International 02/2012; 81(9):892-902. · 6.61 Impact Factor
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Psychopathology 01/2012; 45(2):130-2. · 1.82 Impact Factor
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Jimmy Jianheng Zhou,
Yuan Min Wang,
Vincent Ws Lee,
Richard Ks Phoon,
Geoff Yu Zhang, Ya Wang,
Thian Kui Tan,
Min Hu,
Lucy Dongwei Wang,
Mitsuru Saito,
Andrew Sawyer,
David C H Harris,
Stephen I Alexander,
Anne M Durkan
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ABSTRACT: Monocytes utilise a variety of chemokines to traffic to atherosclerotic plaques. CX3C chemokine ligand 1 (CX3CL1 & Fractalkine) and its receptor CX3CR1 and monocyte chemoattractant protein 1 (CCL2) have been identified as chemokines/receptors that have an important role in the migration and recruitment of monocytes during the pathogenesis of several inflammatory diseases including atherosclerosis. DNA vectors containing single chain variable region fragment (scFv) for DC-targeted receptor DEC205 were cloned with mouse CX3CR1 and CCL2 genes respectively, and vaccinated into C57/BL6 mice weekly for 3 weeks. Induced anti-CX3CR1 and anti-CCL2 in vaccinated mice was examined by ELISA and Western Blot analysis, while the cellular response was examined by ELISPOT. The inhibition of chemotaxis of J774 macrophages to Py-4-1 endothelial cells was examined by in vitro transwell migration assay using serum collected from vaccinated mice. All vaccinated mice generated anti-CX3CR1 and anti-CCL2 Ab and cellular response by 8 weeks after DNA vaccination. Macrophage migration towards TNF-α activated endothelial cells was significantly inhibited by serum containing both anti-CX3CR1 or anti-CCL2 Ab from vaccinated mice. These results demonstrate that DC-targeting of DNA vaccines to self-antigens generates functional immune responses which can inhibit specific key chemotactic targets. This suggests a potential therapeutic role for chemokine/receptor DNA vaccination in atherosclerosis, where chemotaxis has a pivotal role in the inflammatory process.
International journal of clinical and experimental medicine 01/2012; 5(1):24-33.
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ABSTRACT: We studied the antibiotic activity and selective cytotoxicity of beta-1,3-1,4-glucanase from endophytic Bacillus subtilis SWB8.
Based on gel permeation chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry methods, protein fragments of beta-1,3-1,4-glucanase from endophytic Bacillus subtilis strain SWB8 were purified and identified. Then, beta-1,3-1,4-glucanase was used to evaluate the antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Salmonella typhi, Salmonella paratyphi A, Shigella dysenteriae, Candida albicans and Cryptococcus neoformans and cytotoxicity against human pulmonary adenocarcinoma cells (A549) and human bone marrow mesenchymal stem cells (MSCs) by using the disc diffusion, methyl thiazolyl tetrazolium and flow cytometry methods, respectively.
Bacterial beta-1,3-1,4-glucanase showed broad antimicrobial spectrum against all nine bacterial and fungal strains. Furthermore, beta-1,3-1,4-glucanase possessed significant anticancer activity against A549 cells that the IC50 and IC90 values were 11.5 and 20.1 microg/mL, respectively. The percentage of apoptotic A549 cells treated with different concentrations of beta-1,3-1,4-glucanase was significantly increased from 4.43% of the control to 43.1% of 19.2 microg/mL glucanase in a dose dependent manner. In contrast, these changes could not be observed in human bone marrow mesenchymal stem cells.
Beta-1,3-1,4-glucanase could be a potential source of desirable antimicrobial agent, or anticancer compounds with higher efficiency and lower toxicity.
ACTA MICROBIOLOGICA SINICA 11/2011; 51(11):1527-37.
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ABSTRACT: Based on repetitive generation of the Aharonov-Anandan geometric phase, a multi-pass quantum metrology protocol is realized via the electron spin state of a single nitrogen-vacancy defect center in diamond. It is then demonstrated that high-order dynamical decoupling pulse sequences can be implemented in our metrology protocol and hence improve its performance in phase estimation.
EPL (Europhysics Letters) 09/2011; 95(6):60005. · 2.17 Impact Factor
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Psychopathology 08/1970; 45(2):130-132. · 1.82 Impact Factor
