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Dahua, China

Qiu Y.-Y.,Shanghai University of Traditional Chinese Medicine | Hu Q.,Dahua Hospital | Tang Q.-F.,Shanghai University of Traditional Chinese Medicine | Feng W.,Shanghai University of Traditional Chinese Medicine | And 4 more authors.
Tumor Biology

The study aims to investigate the effect of microRNA-497 (miR-497) expression and bufalin treatment in regulating colorectal cancer invasion and metastasis. The expression of miR-497 in colorectal cancer cells with prior treatment with bufalin was determined using real-time quantitative PCR. The nude mouse abdominal aortic ring assay and the human umbilical vein endothelial cell (HUVEC) migration assays were used to measure the angiogenic effect of bufalin. The effect of both bufalin treatment and miR-497 overexpression on colorectal cancer metastasis was measured using an animal tumor model together with in vivo imaging. These results suggested: (1) In the HCT116 cells and HUVECs, proliferation was inhibited in a time-dependent and/or concentration-dependent manner following the administration of bufalin; (2) Bufalin inhibited cell migration in a concentration-dependent manner by cell motility assays; (3) In the aortic ring assay, administration bufalin to the aortic ring significantly promoted micro-angiogenesis of nude mouse abdominal aorta in a concentration-dependent and time-dependent manner; (4) miR-497 was upregulated in human colorectal cancer HCT116 cells treated with different concentrations of bufalin in a concentration-dependent manner; and (5) Combined application of bufalin and miR-497 significantly reduced metastatic lesions and reduced weight loss compared with bufalin alone and control groups in vivo. This study revealed that bufalin inhibited angiogenesis and regulated miR-497 expression and that bufalin and miR-497 acted in synergy to inhibit colorectal cancer metastasis, resulting in improved quality of life in a nude mouse model. © 2013 International Society of Oncology and BioMarkers (ISOBM). Source

Zhang S.,Fudan University | Zhang S.,Tongji University | Zhao L.,Dahua Hospital | Shen L.,Fudan University | And 6 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology

Objective-Comparative studies are lacking that show the effects of different microenvironments on the activity of engrafted stem cells after myocardial infarction (MI). Here, we analyzed the temporal and spatial variations of angiogenesis, collateralization, and the expression of Akt-related signals after MI to test whether the effects of endothelial progenitor cells (EPCs) were different. Methods and Results-After the induction of MI, pigs were selected that did not develop a collateral coronary circulation (R0) or developed a significant collateral coronary circulation (R2). Both sets were allocated randomly to 4 groups: phosphate-buffered saline (intramyocardial injection of phosphate-buffered saline), EPC transplantation, LY294002 (intramyocardial injection of an Akt inhibitor), and EPCs plus LY294002. Infarcted porcine hearts at different time points and under different collateralized conditions exhibited a variety of vascular microenvironments. At 14 days post-MI, angiogenesis and the expression of Akt-mediated angiogenic cytokines predominated in R2 porcine hearts. When grafted into this microenvironment, EPCs induced the greatest effects in impeding the development of heart failure, preserving left ventricular function and dimensions, and inhibiting infarct expansion. LY294002 significantly reduced these effects. Conclusion-These findings suggest that the microenvironment that coexists with collateralization and Akt-mediated angiogenesis appears to be more beneficial to cardiac repair induced by EPC therapy than other niches after MI. © 2012 American Heart Association, Inc. Source

Shi Z.,Shanghai University | Liu J.,Hubei University of Medicine | Yu X.,Shanghai University | Huang J.,Shanghai University | And 5 more authors.
Annals of Surgical Oncology

Background: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. Methods: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. Results: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis. Conclusions: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC. © 2015, Society of Surgical Oncology. Source

Meng X.-Y.,Dahua Hospital | Zhou Y.,Dahua Hospital | Zhang J.,Fudan University | Tang Z.-H.,Tongji University
International Journal of Clinical and Experimental Medicine

Objective: The purpose of this study was to evaluate the extent to which hypertension (HT) interacts with diabetes mellitus (DM) to affect diastolic heart failure (DHF) in a high-risk population. Methods: We conducted a hospital-based case-control study to investigate the relationship between HT or DM and DHF in 251 patients (case: 133 patients with DHF; control: 118 patients without DHF). Echocardiography was used to assess left ventricular (LV) diastolic function. The association between HT or DM and DHF was assessed by multivariate logistic regression (MLR) analysis controlling for confounders. The effect of the interaction between HT and DM on DHF was assessed in MLR models. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). Results: The MLR analyses showed that HT and DM were independent predictors of DHF after adjustment for potential confounders (OR = 2.35-3.14, P<0.05 for all models). DHF was affected by the interaction between HT and DM (ORInt = 3.11-4.31, PInt<0.1, RETI = 2.13-2.69, AP = 0.38-0.49 and S = 4.11-6.80). Conclusion: The findings provide evidence that HT and DM are independent predictors of DHF and that both risk factors act synergistically to influence DHF in a Chinese high-risk population. © 2015 E-Century Publishing Corporation. All rights reserved. Source

He Z.,Shanghai JiaoTong University | Sun Y.,Shanghai JiaoTong University | Wang Q.,Shanghai JiaoTong University | Shen M.,Shanghai JiaoTong University | And 3 more authors.
Journal of Physical Chemistry C

Studies have shown that monomethoxy(polyethylene glycol)-poly(d,l-lactic-co-glycolic acid)-poly(l-lysine) (mPEG-PLGA-PLL)-prepared nanoparticles (NPs) are promising drugs carriers, with good drug loading and delivery performance. To further promote the use of this material in clinical applications, its degradation and biosafety were evaluated. This paper describes degradation studies and biosafety evaluations of different block composition ratios (LA/GA = 60/40, 70/30, and 80/20) of the main material, PLGA, for mPEG-PLGA-PLL (PEAL) NPs. The degradation of PEAL NPs was studied by characterizing the change in molecular weight, the chemical composition, and the degradation rate in addition to the pH value, the particle size, the zeta potential, and the lactic acid and lysine contents in degradation solutions by transmission electron microscopy (TEM), gel permeation chromatography (GPC), and 1H NMR. The results show that with prolonged degradation time, the pH, particle size, zeta potential, and molecular weight were reduced and that the lactic acid and lysine contents and the molecular weight distribution were increased. 1H NMR demonstrated that the hydrolysis rate for glycolic units was faster than those for lactic acid and lysine units. The degradation rate of NPs in pH 7.4 PBS was faster than that in pH 5.0 PBS. The degradation rate of PEAL NPs increased as the LA/GA increased from LA/GA = 60/40 to 80/20. Investigations of intracellular protein synthesis, lactate dehydrogenase (LDH) release, 4′,6-diamidino-2-phenylindole (DAPI) nuclear staining and reactive oxygen species (ROS) content in Huh7, L02, and RAW 264.7 cells showed that the PEAL NPs had no effect on protein synthesis or cell membrane integrity and did not induce chromatin agglutination. Although the ROS content was slightly concentration-dependent and time-dependent, the change in content was minimal and diffusely distributed within the cell. After THP-1 cells were induced to differentiate into macrophages, a subsequent incubation with 5 mM PEAL NPs for 24 h did not significantly induce the macrophage release of IL-1β, TNF-α, and TGF-β1 compared with the negative control. Embryos that had their chorion removed were coincubated with PEAL NPs to determine if there were any effects on embryonic development. It is known that zebrafish embryos at 10-24 h post-fertilization (hpf) are most sensitive to PEAL NPs. Zebrafish embryos treated with different concentrations of PEAL NPs within this sensitive time frame demonstrated that PEAL NPs have a high level of biosafety. Our work demonstrates that PEAL NPs are safe candidates for use as biodegradable carriers for drug and gene delivery. © 2015 American Chemical Society. Source

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