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Xie H.,University of Jinan | Zhang H.,Nevada Cancer Institute | Qi H.,University of Jinan | Wang Y.,University of Jinan | And 3 more authors.
Journal of Proteomics and Bioinformatics | Year: 2013

Injured pancreatic tissue extract contains transcription proteins that are considered as specific soluble proteins, which contribute in promoting the trans-differentiation of stem cells into insulin-producing cells (IPCs). In this present study, 60% of the pancreatic tissues of Sprague-Dawley (SD) rats were removed, and newborn and normal pancreatic tissues were removed after 48 h to extract tissue fluid. Two-dimensional gel electrophoresis (2-DE) separation and spot analysis were conducted on differentially expressed proteins, and peptides were obtained after enzymatic digestion. Twenty two-fold or above differentially expressed proteins were identified via matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/MS), among which, five proteins were related to pancreatic development and differentiation. Moreover, the expression patterns of four proteins detected with Western blot analysis were in agreement with those detected via 2-DE. Our results and those of the bioinformatics analysis suggest that these novel proteins from injured rat pancreatic extract can be a potential source for stem cell differentiation into IPCs. © 2013 Xie H, et al.


Xie H.,University of Jinan | Wang Y.,University of Jinan | Zhang H.,Nevada Cancer Institute | Qi H.,University of Jinan | And 3 more authors.
PLoS ONE | Year: 2013

Mesenchymal stem cells (MSCs) can be successfully induced to differentiate into insulin-producing cells (IPCs) by a variety of small molecules and cytokines in vitro. However, problems remain, such as low transdifferentiation efficiency and poor maturity of trans-differentiated cells. The damaged pancreatic cells secreted a large amount of soluble proteins, which were able to promote pancreative islet regeneration and MSCs differentiation. In this study, we utilized the rat injured pancreatic tissue extract to modulate rat bone marrow-derived MSCs differentiation into IPCs by the traditional two-step induction. Our results showed that injured pancreatic tissue extract could effectively promote the trans-differentiation efficiency and maturity of IPCs by the traditional induction. Moreover, IPCs were able to release more insulin in a glucose-dependent manner and ameliorate better the diabetic conditions of streptozotocin (STZ)-treated rats. Our study provides a new strategy to induce an efficient and directional differentiation of MSCs into IPCs. © 2013 Xie et al.


Huang F.-J.,Shenzhen University | Huang F.-J.,Shenzhen Institute of Gerontology | Wu Z.-Z.,Shenzhen University | Wu Z.-Z.,Shenzhen Institute of Gerontology
Medicine Sciences and Bioengineering - Proceedings of the 2014 International Conference on Medicine Sciences and Bioengineering, ICMSB 2014 | Year: 2015

Special regions in protein sequences with biased compositions of amino acids beyond restricted criteria are simply defined as "unusual sequences." The presence of these unusual sequences has shown not rare and of great importance in human diseases. The present work reviewed the distribution, abundance, structure, and functional features of these unusual sequences with an emphasis on polyQ, polyA, Leu-rich, and tryptophan-aspartic acid (WD) repeats and their association with human diseases as well as other relevant medical significance. © 2015 Taylor & Francis Group, London.


Deng C.Y.,University of Jinan | Qi H.,University of Jinan | Wang X.G.,University of Jinan | Zhou H.X.,University of Jinan | And 4 more authors.
Transplantation Proceedings | Year: 2011

Currently lifelong immunosuppression is required for organ transplant recipients. Anti-CD45RB monoclonal antibody (mAb) prolongs graft survival by mechanisms that are not yet clear. Therefore, we investigated the role of T and dendritic cells (DC) in islet allografts treated with anti-CD45RB mAb after transplantation of 200 allogeneic islets (BALB/c mouse) under the kidney capsules of diabetic C57BL/6 mice treated with intraperitoneal injections of 100 μg of anti-CD45RB mAb on days 0, 1, 3, 5, and 7. We observed a tilt of the ratios of Th1/Th2 and Tc1/Tc2 to Th2 and Tc2. The numbers of nave and memory T cells were down-regulated in peripheral blood after transplantation. In addition, the maturation, endocytosis, and interleukin-12 secreted by DC derived from bone marrow cells was suppressed in recipient mice. Therefore, anti-CD45RB mAb alleviated, rejection by suppressive effects on T-lymphocyte subsets and DC. © 2011 Elsevier Inc.


Li F.-R.,University of Jinan | Li F.-R.,Shenzhen Institute of Gerontology | Li Q.,University of Jinan | Zhou H.-X.,Shenzhen University | And 2 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2013

Early detection of circulation tumor cells (CTCs) in breast cancer patients has great clinical relevance. Currently, immunomagnetic microparticles enriched assays require Fe3O4 inner cores, making it difficult to improve sensitivity. In this study, we prepared magnetic nanoparticles with carbon-coated pure iron (Fe@C) acted as the core, Conjugating with EpCAM monoclonal antibody for immunomagnetic nanoparticles(IMPs). IMPs were used in conjunction with immunocytochemistry (ICC) to develop a refined immunomagnetic nanoparticles enriched assay (IMPEA) for detection of circulating tumor cells (CTCs) in breast cancer patients. Compared with nested RT-PCR, this method achieved the same sensitivity, but with a significantly reduced false-positive rate. This method will help find hidden micrometastases, establish clinical stage, and guide individual treatment post-surgery, suggesting potentially significant value in the clinic. From the Clinical Editor: This team of investigators prepared magnetic nanoparticles with carbon-coated pure iron as core and conjugated them with EpCAM monoclonal antibody to form immunomagnetic nanoparticles for circulating tumor cell (CTC) detection. Compared with nested RT-PCR, this method achieved the same sensitivity, but with a significantly reduced false-positive rate, paving the way to the development of a tool that enables enhanced detection of micrometastases and post-surgical treatment monitoring. © 2013 Elsevier Inc.


Guo W.-J.,North University of China | Qi H.,North University of China | Deng C.-Y.,North University of China | Zhou H.-X.,Shenzhen Institute of Gerontology | And 3 more authors.
Immunologic Research | Year: 2015

As a new type of immune tolerance inducer, anti-CD45RB monoclonal antibodies (anti-CD45RBmAb) can prolong the graft survival time of animal organs or cell transplantation as well as induce stable immune tolerance. Both interleukin (IL)-2 and IL-10 have important roles in the induction and maintenance of immunological tolerance. However, whether these cytokines combined with anti-CD45RBmAb can promote immune tolerance is poorly understood. Therefore, we investigated the effect of IL-2 and IL-10 in vitro and in vivo on the tolerance induction by anti-CD45RBmAb. The changes of Treg and Th17 cells and Th1/Th2 cytokines in anti-CD45RBmAb induced prolongation of skin allograft survival in mice. The finding of a role for IL-2 is novel, of interest, IL-2 promoted anti-CD45RBmAb-induced CD4+ T cell differentiation into Treg and Th2 cells and suppressed Th17 and Th1 cells. IL-2 enhanced the induction of immune tolerance by anti-CD45RBmAb and significantly prolonged skin graft survival time in vivo. In contrast, this effect should be demonstrated experimentally by neutralizing IL-2 and inhibition of the effect of anti-CD45RBmAb, and neutralizing IL-10 showed no effect for anti-CD45RBmAb-induced tolerance. These data reveal that IL-2 significantly enhances anti-CD45RBmAb-induced immune tolerance via up-regulated T regulatory (Treg) cells and the balance of Th1/Th2 shifts. Conversely, IL-10 showed no effect on anti-CD45RBmAb-induced tolerance. © 2014, Springer Science+Business Media New York.


Ye J.,University of Jinan | Liao Y.-T.,University of Jinan | Jian Y.-Q.,University of Jinan | Zhang X.-D.,University of Jinan | And 5 more authors.
Immunology Letters | Year: 2013

Islet transplantation offers hope for patients with type 1 diabetes, which is an autoimmune disease. However, islet transplant recipients must overcome two obstacles in both allograft rejection and autoimmune reaction. Alpha-1-antitrypsin (a1-proteinase inhibitor, AAT) possesses anti-inflammatory properties, reduces cytokine-mediated islet damage, and induces specific immune tolerance. In this study, an insulinoma cell line, NIT-1, was transfected with human AAT (hAAT), named NIT-hAAT, and was transplanted to the left renal subcapsular spaces of 7-week-old female non-obese diabetic (NOD) mice (n= 22). Cyclophosphamide(CY) was administered to synchronize and accelerate the development of diabetes. Thus, the immunosuppressive and cytoprotective activity of hAAT in β-cell transplantation was investigated. NIT-hAAT has immunomodulatory properties, which delay the onset of autoimmune diabetes, reduce diabetes incidence, inhibit insulitis and β-cell apoptosis, and dampen transplant site inflammation. We propose that NIT-hAAT has a dual function by improving islet autoimmunity and protecting transplanted β-cells from allograft rejection. However, the low expression of hAAT in vivo results in the inability of NIT-hAAT to induce long-term specific immune tolerance and to completely block allograft rejection. © 2013 Elsevier B.V.


Gu L.-H.,University of Jinan | Zhang T.-T.,University of Jinan | Li Y.,University of Jinan | Li Y.,Shenzhen Institute of Gerontology | And 4 more authors.
Cellular and Molecular Immunology | Year: 2015

Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivo by transplanting MSCs into normal and diabetic rats via the tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting routes and microenvironments can lead to divergent immunogenicity of MSCs. © 2015 CSI and USTC.

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