Successful reprogramming of epiblast stem cells by blocking nuclear localization of β-catenin.

Epiblast stem cells (EpiSCs) in mice and rats are primed pluripotent stem cells (PSCs). They barely contribute to chimeric embryos when injected into blastocysts. Reprogramming of EpiSCs to embryonic stem cell (ESC)-like cells (rESCs) may occur in response to LIF-STAT3 signaling; however, low reprogramming efficiency hampers potential use of rESCs in generating chimeras. Here, we describe dramatic improvement of conversion efficiency from primed to naive-like PSCs through upregulation of E-cadherin in the presence of the cytokine LIF. Analysis revealed that blocking nuclear localization of β-CATENIN with small-molecule inhibitors significantly enhances reprogramming efficiency of mouse EpiSCs. Although activation of Wnt/β-catenin signals has been thought desirable for maintenance of naive PSCs, this study provides the evidence that inhibition of nuclear translocation of β-CATENIN enhances conversion of mouse EpiSCs to naive-like PSCs (rESCs). This affords better understanding of gene regulatory circuits underlying pluripotency and reprogramming of PSCs

Transmembrane proteins of tight junctions

AbstractTight junctions contribute to the paracellular barrier, the fence dividing plasma membranes, and signal transduction, acting as a multifunctional complex in vertebrate epithelial and endothelial cells. The identification and characterization of the transmembrane proteins of tight junctions, claudins, junctional adhesion molecules (JAMs), occludin and tricellulin, have led to insights into the molecular nature of tight junctions. We provide an overview of recent progress in studies on these proteins and highlight their roles and regulation, as well as their functional significance in human diseases

Inclusion of gaming disorder criteria in ICD-11: A clinical perspective in favor

Data from a specialist treatment facility for Internet addiction (IA) in Japan showed that (a) the vast majority of treatment seekers are addicted to online games, (b) their symptoms are often quite severe, and (c) there is a significant demand for IA treatment. In addition, systemic obstacles to the delivery of medical services in Japan exist due to the exclusion of IA criteria from ICD-10. Consequently, the inclusion of GD criteria in ICD-11 will almost certainly increase the capacity and quality of treatment through advances in research and possible changes in national medical systems to meet treatment demand

Comparison of early outcomes after primary stenting in Japanese patients with acute myocardial infarction between clopidogrel and ticlopidine in concomitant use with proton-pump inhibitor

SummaryBackgroundRecent studies have reported that concomitant use of clopidogrel with proton-pump inhibitors (PPIs) might decrease antiplatelet effects and increase the risk of adverse outcomes after coronary stenting. However, little is known about the difference between clopidogrel and ticlopidine in concomitant use with PPIs, especially within the Asian population.MethodsWe retrospectively analyzed 302 consecutive patients (248 males, mean age 66±12 years) undergoing primary stenting for acute myocardial infarction from July 2006 to June 2010. PPIs were administered to 92% (278/302) of the patients. The patients were divided into two groups on the basis of clopidogrel (clopidogrel group, n=187) or ticlopidine (ticlopidine group, n=91) with PPI. Their characteristics, medications, and 30-day clinical outcomes were examined.ResultsThere were no significant differences in 30-day major adverse cardiac events (cardiac death, non-fatal myocardial infarction, and definite stent thrombosis), bleeding events, and stroke between the two groups. The discontinuation of clopidogrel due to side effects was significantly less frequent than that of ticlopidine (1.1% vs 7.7%, p=0.003, respectively).ConclusionOur findings suggest that concomitant use of clopidogrel with PPIs might be safer than ticlopidine with PPIs in patients undergoing primary stenting for acute myocardial infarction