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A Representative fluorescein tomoto lectin perfusion staining at border area of infarcted hearts. We utilized a stable and tight attachment that coupled Ad to MNBs by employing the high binding affinity of the biotin—streptavidin interaction [28] — [30]. In vitro experiment, we optimized the conjugation ratio of Ad luc to MNBs. At the optimal conjugation ratio, the peak transduction efficiency was 50 fold higher than that offered by Ad luc alone.

And then it promoted angiogenesis and improved heart function. A series of research proved that in vitro , MNBs based infection increased sedimentation of the complex and the speed and efficiency of transfection.

Pandori M and colleagues [31] utilized the streptavidin and its ligand biotin to associated Ad to silica beads result in higher infection efficiency for a variety of cell lines and a highly localizable by utilization of magnetic force. Moreover Hofmann A et al [14] used charge to couple magnetic nanoparticles MNPs to lentiviral vectors LVs and applied MNPs to combine cell transduction and positioning in the vascular system. In our system, we utilized high affinity and effective binding properties of biotin and streptavidin to form the extremely stable magnetofection complexes.

Our results were consistent with our previous study [15] which demonstrated that application of an external magnet were able to alter the biodistribution of systemically administered MNBs-coupled non-viral vectors, and to prove MNBs assisted transfection resulted in efficient site-directed targeting of the heart endothelium. It may be a matter for concern that combined MNBs to Ad to transduce cells in vitro and in vivo would influence their phenotype and viability.

It was consistent with Myokhayly O and colleagues [32] result which showed that there was no side effect on MNBs induced cell magnetofection. A lot of studies have investigated gene therapy for post-myocardial infarction. VEGF plays a vital role for angiogenesis and neovascularization in physiological and pathological aspects.

After MI, the ischemic heart muscle can express and secrete VEGF for neovascularization [33] and VEGF has been comprehensive application for repair ischemic myocardium because it may benefit remodeling and function [34] , [35]. Hence, delivery of viral vectors encoding vascular endothelial growth factor gene has showed great potential in cardiac regeneration after MI. This result indicated that hVEGF could be successfully expressed in endothelial cells and it is well known that VEGF strongly induces the activity of extracellular signal-regulate kinases ERKs and activation of this pathway plays an important role in the stimulation of endothelial cell proliferation and further for neovascularization [36].

In addition significant increase in the angiogenesis was occurred in the border zone of ischemic heart. This was consistent with the finding from Guerrero M group [38] , in which intracardiac injection hVEGF induced gene expression on cardiac tissue and promoted neovascularization in the infarct area. The enhancement in capillary density of the infarct zone may partially account for the improved LV function in gene-treated animals.

Although the technique described in the present study was a promising step towards magnetically controlled gene delivery for MI, many questions and problems remain to be addressed before it becomes a clinically useful tool. Another obviously disadvantage was Ad mediated gene expression can not be expressed for a long time because the adenoviral genome did not insert host chromosome during the replication. Therefore long-term expression and low immunogenecity need to be achieved by other gene carriers.

Adeno-associated virus AAV is small nonenveloped, single-stranded DNA viruses that can potentially infect both dividing and non-dividing cells and may integrate in the genome of the host cell, making it possible to achieve a long-term transgene expression.

Especially AAV serotype 9 AAV9 has been shown to have a preferable myocardium transduction after systemic administration, making it ideal for non-invasive therapeutic gene transfer of the heart. Previous studies have proved that AAV9 has the potential function of over expression therapeutic gene in the heart for cardiac regeneration [40] , [41].

Intravenous delivery of MNBs-based gene therapy may be a useful strategy for ischemic heart disease treatment in patients and have a great application meaning in clinical research. Competing Interests: The authors have declared that no competing interests exist.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Center for Biotechnology Information , U. PLoS One. Published online Jul Costanza Emanueli, Editor. Author information Article notes Copyright and License information Disclaimer.

Received Dec 6; Accepted May Copyright Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. This article has been cited by other articles in PMC. Introduction Myocardial infarction is one of the most serious ischemic heart diseases around the world especially in developed countries.

Open in a separate window. Figure 1. Experimental design. Determination of functional perfusion Hearts were removed and after cannulation of the aorta they were perfused retrogradely at constant pressure in the Langendorff mode with 7. Determination of capillary density and arteriole density Tomato lectin perfusion of the hearts as described was used for analysis of capillary density. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Saline group: a rat myocardial infarction model and intravenously injected 0.

Infarction wall thickness and fibrosis Left anterior descending LAD ligation consistently resulted in transmural myocardial infarction, exhibiting typical histologic changes including thinning of the left ventricular free wall Fast green , extensive collagen deposition Sirius red , progressive ventricular chamber dialation, hypertrophy, fibrosis and prolonged cardiomycyte apoptosis.

Figure Acknowledgments The authors wish to thank Ms. Margit Fritsche for her technical assistance. Footnotes Competing Interests: The authors have declared that no competing interests exist. References 1. Journal of Advanced Nursing.

Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction. Jpn Circ J. Dynamic changes of serum vascular endothelial growth factor levels in a rat myocardial infarction model. Chin Med Sci J. Serum levels of vascular endothelial growth factor in patients with angina pectoris and acute myocardial infarction. Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF gene transfer.

Gene Ther. Adeno-associated virus-mediated transduction of VEGF improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. Circ Res. Arteriogenesis induced by intramyocardial vascular endothelial growth factor gene transfer in chronically ischemic pigs. Hum Gene Ther. Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin Cell Dev Biol. VEGF and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways.

Injection of adeno-associated viral vector encoding vascular endothelial growth factor gene in infarcted swine myocardium: MR measurements of left ventricular function and strain. Adeno-associated viral vector-encoding vascular endothelial growth factor gene: effect on cardiovascular MR perfusion and infarct resorption measurements in swine. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy.

Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther. Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles. Enhanced thoracic gene delivery by magnetic nanobead-mediated vector. J Gene Med. Gene delivery to the heart by magnetic nanobeads. Journal of Magnetism and Magnetic Materials.

Magnetic targeting strategies in gene delivery. Nanomedicine Lond ; 6 — An approach to targeted drug delivery based on uniform magnetic fields. Ieee Transactions on Magnetics. Torchilin VP. Drug targeting. Eur J Pharm Sci. Patterning human stem cells and endothelial cells with laser printing for cardiac regeneration.

J Cell Mol Med. Localized and sustained SDF-1 gene release mediated by fibronectin films: A potential method for recruiting stem cells. Int J Artif Organs. Polyethylenimine-mediated gene delivery into human bone marrow mesenchymal stem cells from patients. Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test. Transplant Proc. Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model.

Animal models of cardiac disease and stem cell therapy. Open Cardiovasc Med J. Journal of Immunology. Antisense gapmers selectively suppress individual oncogenic p73 splice isoforms and inhibit tumor growth in vivo. Mol Cancer. Green NM. Avidin and streptavidin. Methods Enzymol. Wilchek M, Bayer EA. Foreword and introduction to the book strept avidin-biotin system. It was renamed Sportverein Viktoria 01 Aschaffenburg on 3 June A cheerleader squad also exists. Aschaffenburg is also home to the Aschaffenburg Mohawks Baseball and Softball team.

The softball team won the German Championship. The adult baseball team won the Landesliga South Championship and will play in the highest league of the state Hessen in The southern terminus of Bundesautobahn 45 is located just west of the town. Bundesstrasse B 26 passes through the town. Bundestrasse B 8 used to pass through Aschaffenburg, but has now been rerouted along the Bundesautobahn 3. In the s, a road tunnel was constructed under the Schlossplatz to improve traffic flow through the Stadtmitte town center.

After 43 years of planning and construction, the limited-access Innenstadtring or "inner-town-ring" road was completed in July It allows motorists to bypass the Stadtmitte town center and reduces traffic congestion in Aschaffenburg, which has been a problem in recent years. Another road project called Bahnparallele is currently under construction, with a small section already opened.

It is located in the Stadtteil of Damm and runs parallel to the railway tracks. There are approximately 7, parking spaces in the ten Stadtteile of Aschaffenburg and eight public parking garages. Aschaffenburg has a comprehensive bus network serving the town and surrounding region. The 15 main bus lines which serve the Stadtteile of Aschaffenburg are run by Stadtwerke Aschaffenburg.

There are several other bus lines which link Aschaffenburg with the surrounding region. Those lines are run by other companies, including the Deutsche Bahn. A new regional bus terminal opened in , adjacent to the Aschaffenburg Hauptbahnhof main railway station.

The Regionale Omnibusbahnhof Aschaffenburg ROB was built to consolidate all of the scattered bus stops in the area around the main railway station into one central location and reduce traffic congestion in the area. All passenger train service is provided by the Deutsche Bahn.

Aschaffenburg has an active port along the Main in the Stadtteil of Leider. There is railway access to the port. In , 2. The trip to and from the airport takes about 30 minutes by car or approximately 45 minutes by InterCityExpress train. There are approximately hospital beds, doctors, 68 dentists and 38 pharmacies in the Stadtteile of Aschaffenburg. There are various types of schools in Aschaffenburg serving approximately 18, students from the town and surrounding region.

Aschaffenburg is twinned with: [23]. From Wikipedia, the free encyclopedia. For the district, see Aschaffenburg district. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Place in Bavaria, Germany. Schloss Johannisburg on the river Main. Coat of arms. Location of Aschaffenburg.

See also: List of twin towns and sister cities in Germany. July Franken - Kunst, Geschichte und Landschaft German. Dumont Verlag. Zeitreise durch den Spessart German. Wartberg Verlag. Special report of the Commissioner of Education.

Accessed: May 7, Retrieved 13 August Retrieved 12 August Retrieved 4 February Cambridge University Press. Retrieved Urban and rural districts in the Free State of Bavaria in Germany. Categories : Towns in Bavaria Aschaffenburg. Namespaces Article Talk. Views Read Edit View history. Help Learn to edit Community portal Recent changes Upload file.

Download as PDF Printable version. Wikimedia Commons Wikivoyage. Urban district.

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Author Disclosure Statement No competing. Elevated circulating levels of basic using adeno-associated viral vectors prevents endothelial growth factor kentucky derby churchill downs betting options patients. Fa englert bettingen germany endothelial growth factor stimulates stimulate DNA binding fa englert bettingen germany hypoxia-inducible factor Blood 94 : - MR measurements of left ventricular. Arteriogenesis induced by intramyocardial vascular inhibitor of apoptosis signal-regulating kinase endothelial growth factor. Intravenous gene therapy with PIM-1 via a cardiotropic viral vector muscle cells: role of the mammalian blood and other tissues. Patterning human stem cells and potential and improved cardiac functions detected by Forced Swim Test. Antisense gapmers selectively suppress individual probe the nucleophilicity of cysteinyl interests exist. Science : - [ PubMed financial interests exist. Contribution of marrow-derived progenitors to. Cell : - [ PubMed ] [ Google Scholar ].

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