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Yang T.,Tongji University | Yang T.,Hebei Medical University | Liu L.-Y.,Shanghai Yangpu District Central Hospital | Ma Y.-Y.,Fudan University | Zhang W.,Hebei Medical University
Cell Transplantation | Year: 2014

Acquisition of highly efficient neural differentiation based on understanding of initial lineage commitment of human embryonic stem (hES) cells remains a challenge. This study describes a simple three-stage protocol to induce hES cells into neural lineage cells using a 2-week coculture with murine bone marrow stromal cell (BMSC) PA6 followed by a 2-week propagation culture in PA6-conditioned medium and an additional 2-week selection culture in chemically defined neurobasal medium. This protocol generated a relatively high yield of neural lineage cells without mesodermal and endodermal lineage cell contamination. Notably, we demonstrated that PA6 coculture can significantly enhance the expression level of Notch signaling components and promote neural lineage entry of hES cell derivatives. Manipulation of Notch signaling can boost or suppress neural differentiation of hES cell derivatives, suggesting that Notch signaling may underlie the PA6-mediated neural induction. In vivo studies demonstrated that derived neural cells could improve the cognitive function of ischemic stroke rats. Intrastriatal human neural cell grafts were noted to migrate to damaged cerebral regions, enhance basic fibroblast growth factor production in the hippocampus, and restore the pyramidal neuron density and morphology in the hippocampal CA1 region, although only a small number of human donor cells were present in the hippocampus, suggesting that donor cells can boost hippocampal reconstruction by promoting the endogenous regeneration process. These findings demonstrate a pivotal role for Notch in hES cell fate determination and that manipulation of Notch signaling is therefore likely to be a key factor in taking command of hES cell lineage choice. This study suggested the potential of utilizing PA6 coculture to imitate the embryonic niche for hES cell neural induction via Notch signaling and a high application potential of BMSCinvolved protocol, which can yield a whole lineage of human neural cells to promote endogenous regeneration in the hippocampus upon transplantation for potential therapy of ischemic stroke. © 2014 Cognizant Comm. Corp.

Liu B.,Tongji University | Che W.,Tongji University | Yan H.,Tongji University | Zhu W.,Tongji University | Wang H.,Shanghai Yangpu District Central Hospital
Internal Medicine | Year: 2013

Objective Statins prevent cardiovascular events in patients with coronary artery disease (CAD). However, there is little information regarding the vascular effects of statins on arterial wall stiffness in CAD patients. Methods A total of 36 patients were randomly assigned to receive rosuvastatin (10 mg per day) or simvastatin/ezetimibe (10/10 mg per day) for eight weeks. The aim of the present study was to determine the effects of rosuvastatin or simvastatin/ezetimibe on arterial wall stiffness measured according to the brachial and ankle pulse wave velocity (baPWV) in CAD patients. Results Both treatments significantly improved the levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) (p<0.05). The ROCK activity and baPWV were significantly improved in the rosuvastatin group compared with that ob-served in the simvastatin/ezetimibe group (p<0.05). The changes in baPWV were significantly correlated with the changes in the ROCK activity (r=0.488, p<0.01), but not with the changes in the lipid profile or the hs-CRP level. Conclusion Compared with simvastatin/ezetimibe (10/10 mg), rosuvastatin (10 mg) appears to more effectively improve arterial wall stiffness that may be mediated by modulation of the ROCK activity. © 2013 The Japanese Society of Internal Medicine.

Wang C.,Fudan University | Chen R.,Fudan University | Kuang X.,Shanghai Yangpu District Central Hospital | Duan X.,Chinese Research Academy of Environmental Sciences | Kan H.,Fudan University
Science of the Total Environment | Year: 2014

The evidence concerning the association between ambient temperature and mortality is limited in developing countries, especially in China. We assessed the effects of temperature on daily mortality between 2005 and 2008 in Suzhou, China. A Poisson regression model combined with a distributed-lag nonlinear model was used to examine the association between temperature and daily mortality. We investigated effect modification by individual characteristics, including gender, age and educational attainment. We found significant non-linear effects of temperature on total and cardiovascular mortality. Heat effects were immediate and lasted for 1-2. days, whereas cold effects persisted for 10. days. The relative risk of total morality associated with extreme cold temperature (1st percentile of temperature, -. 0.3. °C) over lags 0-14. days was 1.75 [95% confidence interval (CI): 1.43, 2.14)], compared with the minimum mortality temperature (26. °C). The relative risk associated with extremely hot temperature (99th percentile of temperature, 32.6. °C) over lags 0-3. days was 1.43 (95% CI: 1.31, 1.56). We did not observe significant modifying effect by gender, age or educational level. This study showed that exposure to both hot and cold temperatures was associated with increased mortality in Suzhou. Our findings may have implications for developing intervention strategies for extreme cold and hot temperatures. © 2013 Elsevier B.V.

Kuang X.,Shanghai Yangpu District Central Hospital | Xu X.,University of Florida | Kan H.,Fudan University
Environmental Pollution | Year: 2014

Few prior cohort studies exist in developing countries examining the association of ambient particulate matter (PM) with mortality. We examined the association of particulate air pollution with mortality in a prospective cohort study of 71,431 middle-aged Chinese men. Baseline data were obtained during 1990-1991. The follow-up evaluation was completed in January, 2006. Annual average PM exposure between 1990 and 2005, including TSP and PM10, were estimated by linking fixed-site monitoring data with residential communities. We found significant associations between PM10 and mortality from cardiopulmonary diseases; each 10 μg/m3 PM 10 was associated with a 1.6% (95%CI: 0.7%, 2.6%), 1.8% (95%CI: 0.8%, 2.9%) and 1.7% (95%CI: 0.3%, 3.2%) increased risk of total, cardiovascular and respiratory mortality, respectively. For TSP, we observed significant associations only for cardiovascular morality. These data contribute to the scientific literature on long-term effects of particulate air pollution for high exposure settings typical in developing countries. © 2013 Elsevier Ltd. All rights reserved.

Yu Q.,Shanghai JiaoTong University | Chen H.,Shanghai Yangpu District Central Hospital | Sheng L.,Shanghai JiaoTong University | Liang Y.,Shanghai JiaoTong University | Li Q.,Shanghai JiaoTong University
International Immunopharmacology | Year: 2014

Acute rejection is a major problem for allograft transplantation in the clinic. Classic immunosuppressive drug therapy is accompanied by a variety of side effects. Therefore, safe and effective immunosuppressive drugs remain in demand. In this study, the effect of sodium tanshinone IIA sulfonate (STS) on prolonging the allogeneic skin graft survival was determined using a rat skin transplantation model. Rat recipients were divided into four groups that received different treatments: physiological saline, STS, CsA, or STS + CsA. The results indicated that the administration of STS alone, CsA alone or combined STS and CsA all significantly promoted skin allograft survival as demonstrated by a longer mean survival time (MST) compared with the control group. This effect was due to the reductions in the infiltration of inflammatory cells into allograft and the percentages of CD4 + T cells and CD8 + T cells in the peripheral blood of rat recipients. The injection of STS could also downregulate the expression of RANTES, IP-10 as well as IL-2, IFN-γ and TNF-α in allograft tissue. STS markedly inhibited the proliferation of mouse spleen T lymphocytes stimulated by mitogen and alloantigen in vitro. Taken together, these results suggest that STS is a widely applicable drug with few complications that may serve as a new therapeutic alternative for allograft rejection or even other Th1 cell-dominated immune diseases. © 2014 Elsevier B.V.

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