ABSTRACT
Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide.Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers.However,the role of miR-449b in NSCLC is still unknown.In the present study,miR-449b was significantly downregulated in NSCLC samples and cell lines.Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b,which was further confirmed by the luciferase assay.Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4.Interestingly,over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro.Furthermore,ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells.Therefore,the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.
ABSTRACT
Non-small-cell lung carcinoma (NSCLC) is one of the most frequently diagnosed malignancies worldwide.Previous studies have shown that microRNA-449b (miR-449b) functions as a tumor suppressor in many cancers.However,the role of miR-449b in NSCLC is still unknown.In the present study,miR-449b was significantly downregulated in NSCLC samples and cell lines.Bioinformatics analysis revealed that 3'-UTR region of leucine rich repeat containing G protein-coupled receptor 4 (LGR4) mRNA had putative complementary sequences to miR-449b,which was further confirmed by the luciferase assay.Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4.Interestingly,over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro.Furthermore,ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells.Therefore,the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.
ABSTRACT
The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out,and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose-and time-response were investigated.Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs,and the effects on STAT3 expression were detected,then the most effective siRNA was selected for the subsequent experiments.The negative controls of siRNA (siRNA-NC) labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles were transfected into KCs,then the optimal parameters of ultrasonic irradiation were determined.The most effective siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and SonoVue microbubbles was transfected into KCs,and the dose-and time-response of RNA interference was determined.The effect of RNA interference by the most effective siRNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group) was compared with that only carried by Lipofectamine 3000 (L group).The results showed that siRNA-3 achieved the highest silencing efficacy.0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation.The siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue mierobubbles could effectively knock down the STAT3 expression at mRNA and protein levels in dose-and time-dependent manners determined at 100 nmol/L with maximum downregulation on mRNA at 48 h,and on protein at 72 h after transfection.The LUS group achieved the highest silencing efficacy.It was concluded that siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs,and the optimized transfection condition and the sequence of siRNA-3 could serve for further research on gene therapy of psoriasis.
ABSTRACT
<p><b>BACKGROUND</b>Although heart transplantation has become a standard therapy for end-stage heart disease, there are few published studies regarding the use of transplant organs from marginal donors. Here we describe the clinical outcome we have obtained using marginal donor hearts.</p><p><b>METHODS</b>We analyzed 21 cases of orthotopic heart transplantation for end-stage heart disease performed in our department between September 2008 and July 2010. Of these patients, six received hearts from marginal donors and the remainder received standard-donor hearts. The two groups were compared in terms of both mortality and the incidence of perioperative complications such as infection, acute rejection, and right heart insufficiency.</p><p><b>RESULTS</b>The 1-year survival rate of both groups was 100%. Only one death was recorded in standard-donor group during follow-up. Patients who received marginal donor hearts (83%) experienced more early complications than did the standard-donor-heart group (13%), but the mortality of the two groups was the same. The duration of post-ICU stay was greater in the marginal donor group than in the standard-donor group, (35.5 ± 17.4) days and (21.7 ± 2.6) days, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>The use of marginal donor hearts increases the number of patients who can receive and benefit from transplants. However, it may introduce an increased risk of early complications, thus care should be taken both in the choice of patients who will receive marginal donor hearts and in the perioperative treatment of those for whom the procedure is performed.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal , Therapeutic Uses , Heart Transplantation , Methods , Immunosuppressive Agents , Therapeutic Uses , Methylprednisolone , Therapeutic Uses , Recombinant Fusion Proteins , Therapeutic Uses , Tissue DonorsABSTRACT
<p><b>BACKGROUND</b>Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium.</p><p><b>METHODS</b>The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation.</p><p><b>RESULTS</b>The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group (146.83 +/- 2.49) than that in the control group (134.26 +/- 6.84) (P < 0.05). The vascular density in the implanted group (13.00 +/- 1.51) was also higher than that in the control (10.68 +/- 1.79) (P < 0.05).</p><p><b>CONCLUSION</b>The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.</p>