Prescribing a P2Y12 inhibitor for patients with diabetes mellitus (DM) and acute myocardial infarction (AMI) who have undergone percutaneous coronary intervention (PCI) is challenging because of the risk of bleeding and ischemia. We compared the risk of ischemia and bleeding between clopidogrel and ticagrelor in elderly East Asian patients with diabetes using the Korea Acute Myocardial Infarction Registry (KAMIR)-V data. This study included 838 patients enrolled in the KAMIR-V who were ＞75 years, had DM, AMI, and had undergone PCI. The patients were divided into two groups based on the treatment drug. After propensity score matching, 466 patients (ticagrelor: clopidogrel=233:233) were included in the Cox regression analyses to determine the risk of bleeding and ischemia. The baseline characteristics were not different. The type of antiplatelet therapy did not affect the incidence of Bleeding Academic Research Consortium type ≥2 bleeding. There was no significant difference between ticagrelor and clopidogrel treatment outcomes with respect to ischemia risk. This prospective study of a Korean patient cohort (elderly Korean patients with DM) showed no differences in bleeding and ischemia risks based on the use of either ticagrelor or clopidogrel.Large scale randomized controlled trials are warranted to determine the optimal antiplatelet agents for these patients.

Glutathione (GSH) is a major antioxidant in cells, and plays vital roles in the cellular defense against oxidants and in the regulation of redox signals. In a previous report, we demonstrated that stem cell function is critically affected by heterogeneity and dynamic changes in cellular GSH concentration. Here, we present a detailed protocol for the monitoring of GSH concentration in living stem cells using FreSHtracer, a real-time GSH probe. We describe the steps involved in monitoring GSH concentration in single living stem cells using confocal microscopy and flow cytometry. These methods are simple, rapid, and quantitative, and able to demonstrate intracellular GSH concentration changes in real time. We also describe the application of FreSHtracer to the sorting of stem cells according to their GSH content using flow cytometry. Typically, microscopic or flow cytometric analyses of FreSHtracer and MitoFreSHtracer signals in living stem cells take ~2~3 h, and the fractionation of stem cells into subpopulations on the basis of cellular GSH levels takes 3~4.5 h. This method could be applied to almost every kind of mammalian cell with minor modifications to the protocol described here.
Flow Cytometry ; Fluorescent Dyes ; Glutathione ; Methods ; Microscopy, Confocal ; Oxidants ; Oxidation-Reduction ; Population Characteristics ; Stem Cells

Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin-CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (~3-6 microm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells.
Adult* ; Aging ; Antigens, CD15 ; Bone Marrow ; DNA Methylation ; Embryonic Structures ; Genomic Imprinting ; Human Body ; Humans ; Pluripotent Stem Cells ; Regenerative Medicine ; Rejuvenation ; Stem Cells*

BACKGROUND: Graft vessel preservation solution in coronary artery bypass surgery is used to maintain the graft conduit in optimal condition during the perioperative period. Nafamostat mesilate (NM) has anticoagulation and anti-inflammatory properties. Therefore, we investigated NM as a conduit preservative agent and compared it to papaverine. METHODS: Sprague-Dawley (SD) rat thoracic aortas were examined for their contraction-relaxation ability using phenylephrine (PE) and acetylcholine (ACh) following preincubation with papaverine and NM in standard classical organ baths. Human umbilical vein endothelial cells (HUVECs) were cultured to check for the endothelial cell viability. Histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were performed on the thoracic aortas of SD rats. RESULTS: The anti-contraction effects of papaverine were superior to those of NM at PE (p<0.05). The relaxation effect of NM on ACh-induced vasodilatation was not statistically different from that of papaverine. Viability assays using HUVECs showed endothelial cell survival rates of >90% in various concentrations of both NM and papaverine. A histopathological study showed a protective effect against necrosis and apoptosis (p<0.05) in the NM group. CONCLUSION: NM exhibited good vascular relaxation and a reasonable anti-vasocontraction effect with a better cell protecting effect than papaverine; therefore, we concluded that NM is a good potential conduit preserving agent.
Acetylcholine ; Animals ; Anticoagulants ; Aorta, Thoracic ; Apoptosis ; Baths ; Coronary Artery Bypass* ; Coronary Vessels* ; DNA Nucleotidylexotransferase ; Endothelial Cells ; Guanidines ; Human Umbilical Vein Endothelial Cells ; Mesylates* ; Necrosis ; Papaverine ; Perioperative Period ; Phenylephrine ; Rats ; Rats, Sprague-Dawley ; Relaxation ; Survival Rate ; Transplants ; Vasodilation