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Cheng Y.,Peoples Hospital of Jiangsu Province | Jiang S.,Jinling Hospital | Hu R.,Zhongda Hospital | Lv L.,Peoples Hospital of Jiangsu Province
Annals of Clinical and Laboratory Science | Year: 2013

Mounting evidence suggests that transplanting endothelial progenitor cells (EPCs) into the myocardium improves cardiac function after myocardial infarction (MI). However, the mechanism remains controversial. The aim of this study was to investigate the role played by the VEGF- PI3K/Akt-eNOS pathway in EPC-based cell therapy. Cultured EPCs, which were identified by morphology, function, and cell surface markers, were transplanted into the border zone after left anterior descending coronary artery ligation in mice. Expression levels of VEGF, p-Akt, and eNOS in the border zone were elevated three days after EPC transplantation. EPC therapy enhanced expression of VEGFR-2, increased microvessel density, and reduced interstitial fibrosis in the border zone after MI. The left ventricular fractional shortening was increased and the left ventricular diameter was smaller after EPC treatment. Wortmannin inhibited the expression of p-Akt and was associated with decreased cardiac function. Our study suggests that EPC transplantation improves cardiac function after MI, mediated at least partially by activation of the VEGF -PI3K/ Akt-eNOS pathway. © 2013 by the Association of Clinical Scientists, Inc.

Yao L.-L.,Fudan University | Liu X.-Y.,Tongji University | Jin J.-Y.,Zhongda Hospital | Tao B.-B.,Fudan University | And 6 more authors.
Molecular Biology Reports | Year: 2011

Mint protein family, as adaptor molecules, contains three members, Mint1, Mint2 and Mint3. Although Mint3 is ubiquitously expressed, Mint1 and Mint2 have been reported to express specifically in neuron. Here we demonstrated Mint1 and Mint2 expression pattern in rat spinal cord. The protein level of Mint2 was found to be higher than that of Mint1 in rat spinal by western blot. In an attempt to know Mint2 distribution in the spinal cord of rat, in situ hybridization was carried out, Mint2 mRNA was showed to be ubiquitously distributed in cervical, thoracic and lumbar sections of rat spinal cord, and high intensive signal was detected in motor neurons. These were further confirmed by fluorescent immunohistochemistry, Mint2 was also found to exist throughout gray matter especially motor neurons where Mint2 was mainly located in perikaryon, however, Mint1 was showed to be relatively lower. By electron microscope, Mint2 was found to be mainly located in vesicles in perikaryon in motor neuron of lumbar section, and at the same time Mint2 was located in axons in myelin and presynaptic terminals. These data suggest that Mint2 may play more important role in spinal cord than the other two family members. © 2010 Springer Science+Business Media B.V.

Wang K.-X.,Chinese University of Hong Kong | Xu L.-L.,Chinese University of Hong Kong | Rui Y.-F.,Zhongda Hospital | Huang S.,Chinese University of Hong Kong | And 5 more authors.
PLoS ONE | Year: 2015

Factors synthesized by mesenchymal stem cells (MSCs) contain various growth factors, cytokines, exosomes and microRNAs, which may affect the differentiation abilities of MSCs. In the present study, we investigated the effects of secretion factors of human umbilical cord derived mesenchymal stem cells (hUCMSCs) on osteogenesis of human bone marrow derived MSCs (hBMSCs). The results showed that 20 μg/ml hUCMSCs secretion factors could initiate osteogenic differentiation of hBMSCs without osteogenic induction medium (OIM), and the amount of calcium deposit (stained by Alizarin Red) was significantly increased after the hUCMSCs secretion factors treatment. Real time quantitative reverse transcription-polymerase chain reaction (real time qRT-PCR) demonstrated that the expression of osteogenesis-related genes including ALP, BMP2, OCN, Osterix, Col1α and Runx2 were significantly up-regulated following hUCMSCs secretion factors treatment. In addition, we found that 10 μ g hUCMSCs secretion factors together with 2×105 hBMSCs in the HA/TCP scaffolds promoted ectopic bone formation in nude mice. Local application of 10 μg hUCMSCs secretion factors with 50 μl 2% hyaluronic acid hydrogel and 1×105 rat bone marrow derived MSCs (rBMSCs) also significantly enhanced the bone repair of rat calvarial bone critical defect model at both 4 weeks and 8 weeks. Moreover, the group that received the hUCMSCs secretion factors treatment had more cartilage and bone regeneration in the defect areas than those in the control group. Taken together, these findings suggested that hUCMSCs secretion factors can initiate osteogenesis of bone marrow MSCs and promote bone repair. Our study indicates that hUCMSCs secretion factors may be potential sources for promoting bone regeneration. © 2015 Wang et al.

Fei Y.,Pla Cancer Center | Hu J.,Nanjing University of Science and Technology | Liu S.,Zhongda Hospital | Liu X.,Pla Cancer Center | And 2 more authors.
Cancer Genetics and Cytogenetics | Year: 2010

Recent studies have implicated E-cadherin-160C/A single-nucleotide polymorphism (SNP) in susceptibility to and early onset of some cancers. We investigated the role of E-cadherin-160 C/A SNP in Chinese pancreatic carcinoma patients without dominant family history by genotyping 254 patients and 101 controls. The risk of cancer for CC genotype individuals was less than half that of AA individuals [odds ratio (OR) = 0.41; 95%confidence interval (95%CI) = 0.18-0.96]. Furthermore, patients with the CC and CA genotypes whose tumors were stages III (T4NxM0) and IV (TxNxM1) (OR = 0.38; 95%CI = 0.17-0.83), poorly differentiated (OR = 0.28; 95%CI = 0.09-0.84), and left-sided (OR = 0.45; 95%CI 0.21-0.98) were associated with significantly lower risk than AA patients. Young (60 years old or younger) AA patients had a 5-year lower mean age at onset than CC/CA patients (P = 0.02). Young male AA patients had worse disease-specific survival than CC/CA patients (P = 0.002). Thus, contrary to Canadians and Portuguese, the AA (rather than CC) genotype is associated with increased susceptibility and advanced pancreatic carcinoma in Chinese patients, suggesting a more complex relationship between the SNP and pancreatic carcinoma risk, possibly modulated by population differences. © 2010 Elsevier Inc. All rights reserved.

Su H.,Nanjing University | Mou Y.B.,Nanjing University | An Y.L.,Jiangsu Key Laboratory of Molecular and Function Imaging | Han W.,Nanjing University | And 7 more authors.
International Journal of Nanomedicine | Year: 2013

Background: The successful biotherapy of carcinoma with dendritic cell (DC) vaccines pivotally relies on DCs' migratory capability into lymph tissues and activation of T cells. Accurate imaging and evaluation of DC migration in vivo have great significance during antitumor treatment with DC vaccine. We herein examined the behavior of DCs influenced by synthetic superparamagnetic iron oxide (SPIO) nanoparticle labeling. Methods: γ-Fe2O3 nanoparticles were prepared and DCs, which were induced from bone marrow monocytes of enhanced green fluorescent protein (EGFP) transgenic mice, were labeled. The endocytosis of the SPIO, surface molecules, cell apoptosis and fluorescence intensity of EGFP-DCs were displayed by Prussian blue staining and flow cytometry (FCM), respectively. After EGFP-DCs, labeled with SPIO, were injected into footpads (n = 5) for 24 hours, the mice were examined in vivo by optical imaging (OPI). Meanwhile, confocal imaging and FCM were applied, respectively, to detect the migration of labeled DCs into draining lymph nodes. Results: Nearly 100% of cells were labeled by the SPIO, in which the intracellular blue color gradually deepened and the iron contents rose with the increase of labeling iron concentrations. In addition, cell apoptosis and the surface molecules on DCs were at similar levels after SPIO labeling. After confirming that the fluorescence intensity of EGFP on DCs was not influenced by SPIO, the homing ability of EGFP-DCs labeled with SPIO displayed that the fluorescence intensity and the ratios of EGFP-DCs in draining lymph nodes were gradually decreased with the increase of labeling iron concentrations. Conclusion: The synthetic SPIO nanoparticles possess perfect labeling ability and biocompatibility. Moreover, DCs labeled with a low dose of SPIO showed stronger migratory capability in vivo. © 2013 Su et al.

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