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Zhang Y.-S.,Center for Reproductive Medicine | Lu Z.-Y.,Center for Reproductive Medicine | Lu Z.-Y.,Union Stem Cell and Gene Engineering Co. | Yu Y.,Peking University | And 4 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2012

Purpose: Retinal pigment epithelium cells derived from human embryonic stem cells (ESCs) could be useful for restoring retinal function in age-related macular degeneration. However the use of non-human feeder cells to support the growth of ESCs for clinical applications raises the concern of possible contamination because of direct contact between animal and human cells. Methods: In this study, we produced human ESCs using human fibroblast feeder layers isolated from foreskin and abdominal tissues. Using this system, human ESCs differentiated into retinal pigment epithelium cells in differentiation medium. Results: Seven human ESC lines were established from 18 blastocysts. These human ESCs showed normal morphology, expressed all expected cell surface markers, had the ability to form embryoid bodies upon culture in vitro and teratomas after injection into SCID mice, and differentiated further into derivatives of all three germ layers. Under conditions of committed differentiation, these human ESCs could differentiate into retinal pigment epithelium cells after 2 months in culture. Conclusions: The results of this study demonstrated that human foreskin/abdominal fibroblasts have the potential to support the derivation and long-term culture of human ESCs, which can then be used to generate retinal pigment epithelium cells with characteristic morphology and molecular markers. This technique avoids the concerns of contamination from animal feeder layers during human ESC derivation, culture and differentiation, and will thus facilitate the development of retinal pigment epithelium cell transplantation therapy. © Springer Science+Business Media, LLC 2012. Source

Li D.,Tianjin Medical University | Lu Z.,Union Stem Cell and Gene Engineering Co. | Lu Z.,Tianjin University of Traditional Chinese Medicine | Jia J.,Tianjin Medical University | And 2 more authors.
Kidney and Blood Pressure Research | Year: 2014

Background/Aims: Curcumin, a kind of plant polyphenolic compound, has been recently discovered to have renoprotective effects on diabetic nephropathy (DN). Podocyte can respond to various injuries including mechanical stress secondary to DN. Our previous study showed that podocyte miR-124 expression was up-regulated accompanied with podocytic adhesive capacity damage in vitro and in vivo. We hypothesized, in the present research that curcumin would ameliorate podocyte adhesion damage under mechanical stress by inhibiting miR-124 expression. Methods: Gene expression of miR-124 was measured by real-time PCR and protein expression of integrin 3 was measured by Western blotting in STZ-induced uninephrectomized diabetic rats and cultured podocytes under mechanical stress treated with curcumin respectively. Western blot and luciferase reporter assays were used to detect the effects of miR-124 overexpression on the Itga3 expression in podocytes. Results: Gene expression of miR-124 was upregulated and 3 was downregulated in renal cortex of diabetic rats and cultured podocytes under mechanical stress which were ameliorated by curcumin treatment significantly. Transient co-transfection of miR-124 mimics with luciferase expression plasmids resulted in a significant repression of luciferase activity in podocytes. Mechanistically, Itga3 may be a regulation target of miR-124. Conclusions: These results provide a novel idea that curcumin prevents against podocytic adhesive capacity damage under mechanical stress by inhibitting miR-124 © 2014 S. Karger AG, Basel. Source

Zou D.,Chinese Academy of Sciences | An G.,Chinese Academy of Sciences | Zhu G.,Chinese Academy of Sciences | Wang J.,Chinese Academy of Sciences | And 7 more authors.
Biology of Blood and Marrow Transplantation | Year: 2014

Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon that occurs during the treatment of multiple myeloma (MM). The incidence, biological characteristics, and prognostic value of secondary MGUS in patients with MM remain undefined. We proceed with a retrospective systematic review of serum immunofixation electrophoresis studies performed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia. Secondary MGUS was more common in patients with myeloma who had undergone stem cell transplantation than in those who had not (17 [29.8%] of 57 versus 5 [1.4%] of 352, P<.001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The complete response rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (P<.01). For the cohort as a whole, secondary MGUS was associated with significantly prolonged progression-free survival (median, 52.0months versus 22.5months; P= .002) and overall survival (median, not reached versus 35.0months; P<.001). The presence of secondary MGUS retained independent prognostic value with a moderate impact on overall survival (hazard ratio .128 [95% confidence interval .018 to .922]; P= .041) in the multivariate Cox regression model. However, when analysis was restricted to patients undergoing stem cell transplantation, no statistical differences in progression-free survival and overall survival were found. In conclusion, we observe that secondary MGUS was frequently observed in MM patients after transplantation and conferred a survival prolongation. The favorable survival in patients with secondary MGUS may be explained by beneficial effect from myeloablative therapy. © 2014 American Society for Blood and Marrow Transplantation. Source

Ke B.,Tianjin Medical University | Song X.-N.,Union Stem Cell and Gene Engineering Co. | Liu N.,Tianjin Medical University | Zhang R.-P.,Tianjin Medical University | And 2 more authors.
PLoS ONE | Year: 2014

Objective: The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer. Methods: A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan-Meier survival curves and log-rank tests were used for the survival analysis. Results: By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson's correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging. Conclusions: The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system. © 2014 Ke et al. Source

Li D.,Tianjin Medical University | Lu Z.,Union Stem Cell and Gene Engineering Co. | Jia J.,Tianjin Medical University | Zheng Z.,Tianjin Medical University | Lin S.,Tianjin Medical University
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2013

Introduction: Podocytes can respond to various injuries, including mechanical stress secondary to diabetic nephropathy (DN), which may cause deleterious adhesive effects on podocytes. Integrin α3β1 is the major podocyte adhesion molecule. In this study, we aim to investigate α3β1 expression and identify differentially expressed microRNAs in podocytes under mechanical stress compared with normal cells and podocytes under mechanical stress treated with spironolactone, respectively. Materials and methods: Serum and glucocorticoid induced kinase 1 (SGK1), mineralocorticoid receptor (MR) and integrin α3β1 were detected by Western blotting. The miRNA analyses were performed by TaqMan MicroRNA Array v2.0. Genes Itga3 and Itgb1 were analyzed for miRNA binding sites within 3'UTRs using TargetScan and PicTar. Results: Protein SGK1 and MR expression were significantly increased under mechanical stress and decreased after spironolactone treatment. Podocyte α3 and β1 expression were significantly decreased under mechanical stress and increased after spironolactone treatment. MiR-124, miR-190, miR-217 and miR-188 were the overlapped miRNAs that were upregulated under mechanical stress and downregulated after spironolactone treatment. MiR-124 was found to be a predicted miRNA target site in both Itga3 and Itgb1 3'UTRs. Conclusion: These results provide a novel idea that miR-124 might play an important role in podocytic adhesion damage under mechanical stress. © The Author(s) 2012. Source

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