Myogenetic Oligodeoxynucleotide Induces Myocardial Differentiation of Murine Pluripotent Stem Cells

An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts as an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect of iSN04 on murine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). In the undifferentiated state, iSN04 inhibited the proliferation of ESCs and iPSCs but did not affect the expression of pluripotent markers. In the differentiating condition, iSN04 treatment of ESCs/iPSCs from day 5 onward dramatically induced differentiation into Nkx2-5+ beating cardiomyocytes with upregulation of Gata4, Isl1, and Nkx2-5, whereas iSN04 treatment from earlier stages completely inhibited cardiomyogenesis. RNA sequencing revealed that iSN04 treatment from day 5 onward contributes to the generation of cardiac progenitors by modulating the Wnt signaling pathway. Immunostaining showed that iSN04 suppressed the cytoplasmic translocation of nucleolin and restricted it to the nucleoli. These results demonstrate that nucleolin inhibition by iSN04 facilitates the terminal differentiation of cardiac mesoderm into cardiomyocytes but interferes with the differentiation of early mesoderm into the cardiac lineage. This is the first report on the generation of cardiomyocytes from pluripotent stem cells using a DNA aptamer. Since iSN04 did not induce hypertrophic responses in primary-cultured cardiomyocytes, iSN04 would be useful and safe for the regenerative therapy of heart failure using stem cell-derived cardiomyocytes.ArticleInternational Journal of Molecular Sciences 24(18) : 14380, (2023)journal articl

Gynaecologic cancer complicating pregnancy: An overview

Cancer complicating pregnancy endangers two lives. Any approach should look at both maternal and foetal safety. Maternal prognosis will not improve by terminating the pregnancy. Imaging for staging purposes is possible, and sonar and magnetic resonance imaging are the preferred examinations. Abdominopelvic computed tomography exposes the foetus to the highest doses radiation and should be avoided. Provided a thorough maternal monitoring to ensure a stable uteroplacental blood flow and foetal oxygenation, surgical techniques that are used in non-pregnant patients are also safe for pregnant patients. Radiotherapy of the upper part of the body is possible during pregnancy, but during the third trimester the close distance may put the foetus at risk. Chemotherapy during the second or third trimester can be administered without increasing the incidence of congenital malformations. A systematic analysis, especially on the long-term outcome of the offspring after cancer treatment during pregnancy is still lacking. Here, we present a summary of issues related to the diagnosis and treatment of gynaecological malignancies during pregnancy. Firstly, we describe general diagnostic and cancer-treatment-related problems. In the second part, organ pathology including breast, cervical, ovarian, endometrial and vulvar cancer is discussed. (C) 2009 Elsevier Ltd. All rights reserved

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes