21 research outputs found
miR-145 suppresses embryoâepithelial juxtacrine communication at implantation by modulating maternal IGF1R
Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 3âČUTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium
Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells
Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosanâhsa-miRNA-145 (CSâmiRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CSâmiRNA nanocomplexes were produced with a range of (+/â) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200ânm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CSâmiRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CSâmiRNA complexes offer a promising non-viral platform for breast cancer gene therapy
Motivational learning approaches for the professionalization of preservice teachers:: competence-oriented, aesthetic and biographical learning in teacher education at university
Im Artikel werden drei verschiedene LernzugĂ€nge (kompetenzorientiertes, Ăsthetisches und biographisches Lernen) vorgestellt und aus theoretischer Perspektive deren motivierender Gehalt fĂŒr selbstreguliertes Lernen in Praxisphasen des Lehramtsstudiums herausgearbeitet. Als theoretische Grundlage dient die Selbstbestimmungstheorie als zentrale motivationale Theorie zur ErklĂ€rung selbstbestimmten Handelns.The article addresses how motivational learning approaches (competency-oriented, aesthetic and biographical) can contribute to the professionalisation of preservice teachers during a long-term internship. As a theoretical basis, the self-determination theory serves as a central motivational theory for explaining self-determined action