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Yang K.,Zhejiang University | Shen J.,Traditional Chinese Medical Hospital of Zhejiang Province | Chen S.-W.,Zhejiang University | Qin J.,Zhejiang University | And 2 more authors.
Oncology Reports | Year: 2016

RNA activation (RNAa) is a promising discovery whereby expression of a particular gene can be induced by targeting its promoter using small double-stranded RNAs (dsRNAs) also termed small activating RNAs (saRNAs). We previously reported that several small dsRNAs targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can upregulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in prostate cancer cells. Promisingly, we found that upregulation of PAWR by saRNA inhibited the growth of prostate cancer cells by inducing cell apoptosis which was related to inactivation of the NF-?B and Akt pathways. The decreased anti?apoptotic protein Bcl-2 and activation of the caspase cascade and poly(ADP-ribose) polymerase (PARP) also supported the efficacy of the treatment. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for prostate and other types of cancer. Source


Yang K.,Zhejiang University | Shen J.,Traditional Chinese Medical Hospital of Zhejiang Province | Xie Y.-Q.,Zhejiang University | Lin Y.-W.,Zhejiang University | And 4 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2013

RNA activation is a promising discovery that promoter-targeted double-stranded small RNAs, termed small activating RNAs (saRNAs), can induce gene expression, which represents a novel approach to gene over-expression without traditional vector-based systems. PAWR is a tumor suppressing gene essential for apoptosis and a cancer-selective target for cancer therapeutics. Here our study identified synthetic saRNAs that could activate the expression of PAWR in human cancer cells. Functional analysis of PAWR induction revealed that saRNA treatment induced growth inhibition and apoptosis of cancer cells, and predictably modulated the expression of known downstream target gene Bcl-2. New functional saRNAs can also be harvested by one or two-base shifting of the original target sites. Chromatin immunoprecipitation assays indicated that activation of PAWR is accompanied by reduced dimethylation at histone H3K9 and increased dimethylation at histone H3K4. Moreover, the existence of transcripts in PAWR promoter was detected but its relationship with RNA activation needs more lucubration. These data have enlarged the gene pool of RNAa and hold great promise as an alternative for PAWR-targeted therapeutics. © 2013 Elsevier Ltd. Source


Zhang X.,Traditional Chinese Medical Hospital of Zhejiang Province | Lu X.-M.,Wushan Branch | Huang L.-F.,Traditional Chinese Medical Hospital of Zhejiang Province | Li X.,Traditional Chinese Medical Hospital of Zhejiang Province
Peptides | Year: 2013

Leptin has recently been discussed as a novel biomarker for the clinical outcome of critical illness. This study aims to investigate the prognostic value of leptin with regard to long-term clinical outcomes in patients with intracerebral hemorrhage. In 50 healthy controls and 92 patients with acute spontaneous basal ganglia hemorrhage presenting to the emergency department of a large primary care hospital, we measured plasma leptin levels using an enzyme-linked immunosorbent assay in a blinded fashion. Plasma leptin levels on admission were considerably higher in patients than healthy controls. A significant correlation emerged between plasma leptin level and National Institutes of Health Stroke Scale score. A multivariate analysis identified plasma leptin level as an independent predictor for 6-month clinical outcomes including 6-month mortality and unfavorable outcome (Modified Rankin Scale score > 2). Using receiver operating characteristic curves, we calculated areas under the curve for 6-month clinical outcomes. The predictive performance of leptin was similar to, but did not obviously improve that of National Institutes of Health Stroke Scale scores. Thus, leptin may help in the prediction of 6-month mortality and unfavorable outcome after intracerebral hemorrhage. © 2013 Elsevier Inc. All rights reserved. Source


Zhang X.,Traditional Chinese Medical Hospital of Zhejiang Province | Lu X.-M.,Wushan Branch | Huang L.-F.,Traditional Chinese Medical Hospital of Zhejiang Province | Ye H.,Traditional Chinese Medical Hospital of Zhejiang Province
Peptides | Year: 2012

High plasma copeptin levels have been found to be associated with short-term poor outcome after intracerebral hemorrhage (ICH). We furthermore evaluate the relation of plasma copeptin levels to long-term outcome and early neurological deterioration after ICH. Fifty healthy controls and 89 patients with acute spontaneous basal ganglia hemorrhage were recruited in this study. Plasma copeptin concentrations on admission measured by enzyme-linked immunosorbent assay were considerably high in patients than healthy controls. A multivariate analysis identified plasma copeptin level as an independent predictor for 1-year mortality, 1-year unfavorable outcome (modified Rankin Scale score > 2) and early neurological deterioration. A receiver operating characteristic curve showed that the predictive value of plasma copeptin concentration was similar to that of National Institutes of Health Stroke Scale scores for long-term poor outcome and early neurological deterioration. However, copeptin did not obviously improve the predictive values of National Institutes of Health Stroke Scale scores. Thus, increased plasma copeptin level is an independent prognostic marker of 1-year mortality, 1-year unfavorable outcome and early neurological deterioration after ICH. © 2012 Elsevier Inc. All rights reserved. Source


Tong P.J.,Traditional Chinese Medical Hospital of Zhejiang Province | Xu L.,Traditional Chinese Medical Hospital of Zhejiang Province | Hu B.S.,Traditional Chinese Medical Hospital of Zhejiang Province | Jin H.T.,Traditional Chinese Medical Hospital of Zhejiang Province | And 2 more authors.
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2010

OBJECTIVE: On the basis of YouGui drink ([Chinese characters: see text]) to act on the normal rats in vitro osteoblast proliferation and differentiation, further observe YooGui drink ([Chinese characters: see text]) inductive effect for steroid induced necrosis of femoral head rats in vitro on cultivation of osteoblast proliferation and differentiation. METHODS: Prednisolone acetate 49 mg/kg x d were injected into gluteal of 20 male SD rats (body weight in 100-120 g), continuously 6 days for model. After 7 days, under sterile conditions from the model rats bone marrow stromal cells were induced and cultured to osteoblast, and then randomly divided into 4 groups, respectively, add the high, medium and low concentration YouGui drink ([Chinese characters: see text]) containing serum (group R1, R2, R3) and control serum (group R4). After 72 h, osteoblast proliferation, alkaline phosphatase activities (APA) were detected, and expression level of osteoprotegerin (OPG) and osteoclast differentiation factor (RANKL) were detected by real-time fluorescence quantitative PCR. RESULTS: The high and medium concentration YouGui drink ([Chinese characters: see text]) containing serum group compared with the control group (R1, R2 vs. R4), the rate of osteoblast proliferation was significantly high (P < 0.01), APA significantly increased (P < 0.01), relative expression level of osteoblast OPG mRNA significantly increased (P < 0.01), and with the concentration of a certain dose was positively correlated; RANKL mRNA significantly was lower (P < 0.01). The low concentration YouGui drink (t 91 t) containing serum group compared with the control group (R3 vs R4), there was no significantly different in the rate of osteoblast proliferation, ALP and relative expression level of osteoblast OPG mRNA, RANKL mRNA. CONCLUSION: The high concentration of YouGui drink ([Chinese characters: see text]) containing serum can obviously promote the proliferation and differentiation of steroid induced necrosis of femoral head rats in vitro osteoblast, and plays a clear role in promoting and enhance the relative expression of osteoblast OPG mRNA and an inhibitory effect on RANKL mRNA. The effect of YouGui drink ([Chinese characters: see text]) containing serum acting on induced in vitro cultured osteoblasts have relevance with dose, at a certain concentration range it can promote osteoblast differentiation and proliferation. Source

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