A5028592309- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Chemotherapy-induced cardiotoxicity and mitigation
- SARS-CoV-2 and COVID-19 Research
- Neuroscience and Neuropharmacology Research
- COVID-19 Clinical Research Studies
- Tissue Engineering and Regenerative Medicine
- Anesthesia and Neurotoxicity Research
- Chronic Myeloid Leukemia Treatments
- Adipose Tissue and Metabolism
- Marine Biology and Environmental Chemistry
- Cardiac pacing and defibrillation studies
- Estrogen and related hormone effects
- Mitochondrial Function and Pathology
- Environmental Toxicology and Ecotoxicology
- Protein Kinase Regulation and GTPase Signaling
- Computational Drug Discovery Methods
- Cancer, Hypoxia, and Metabolism
- Calcium signaling and nucleotide metabolism
- Long-Term Effects of COVID-19
National Institute of Health Sciences
2016-2025
National Institute of Health Sciences
2013-2024
Pharmac
2019-2023
NTL Institute for Applied Behavioral Science
2019-2023
National Institute of Advanced Industrial Science and Technology
2022-2023
Shinshu University
2023
Okayama University
2022
Osaka University
2022
National Institute of Health
2021
Health and Environmental Sciences Institute
2019-2020
To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated concentration dependence and sources variability electrophysiologic responses to 28 drugs linked low, intermediate, high torsades de pointes (TdP) risk categories using two commercial cell lines standardized protocols a blinded multisite study multielectrode array or voltage-sensing optical approaches. Logistical ordinal linear regression models...
In this study, we used high-speed video microscopy with motion vector analysis to investigate the contractile characteristics of hiPS-CM monolayer, in addition further characterizing extracellular field potential (FP), traction force and Ca2+ transient. Results our demonstrated that development hiPS-CMs correlated well cellular deformation detected by analysis. presence verapamil isoproterenol, showed alteration accordance changes fluorescence peak transient, i.e., upstroke, decay, amplitude...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are anticipated to be a useful tool for conducting proarrhythmia risk assessments of drug candidates. However, torsadogenic prediction paradigm using hiPSC-CMs has not yet been fully established.Extracellular field potentials (FPs) were recorded from the multi-electrode array (MEA) system. The effects on FPs evaluated with 60 drugs, including 57 various clinical risks. Actual concentrations in medium measured equilibrium...
Human induced pluripotent stem cells (hiPSCs) possess the capabilities of self-renewal and differentiation into multiple cell types, they are free ethical problems associated with human embryonic (hESCs). These characteristics make hiPSCs a promising choice for future regenerative medicine research. There significant obstacles, however, preventing clinical use hiPSCs. One most obvious safety issues is presence residual undifferentiated that have tumorigenic potential. To locate cells, in...
Multi-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are frequently used to characterize the electrophysiological effects of drug candidates for prediction QT prolongation proarrhythmic potential. However, optimal experimental conditions obtaining reliable data, such as high-pass filter (HPF) frequency cell plating density, remain be determined. Extracellular field potentials (FPs) were recorded from iPS cardiomyocyte sheets by using MED64...
A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product novel structures and biological activities through total combinatorial biosynthesis. Here, we demonstrate advantage of explore activity-related chemical space comprehensive fungal decalin-containing diterpenoid pyrones (DDPs). Genome reveals putative DDP biosynthetic gene clusters distributed in five genera. In...
Abstract The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review the concepts redox biology and its translational strategy. Glutathione (GSH) is body’s primary detoxifier antioxidant, oxidized form (GSSG) been considered as marker oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure male mice by electrophilic modification dynamin-related...
The ability to undergo self-renewal is a defining characteristic of stem cells. Self-replenishing activity sustains tissue homeostasis and regeneration. In addition, cell therapy strategies require heightened understanding the basis process enable researchers clinicians obtain sufficient numbers undifferentiated cells for gene therapy. Here, we used postnatal muscle-derived test basic biological assumption unlimited replication. Muscle-derived (MDSCs) expanded 300 population doublings (PDs)...
The aims of this study were to (1) characterize basic electrophysiological elements human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond clinical properties such as QT-RR relationship, (2) determine the applicability QT correction and analysis methods, (3) if how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects Torsades de pointes (TdP). Field potential recordings obtained from commercially available hiPSC-CMs using...
Cryopreservation is widely used to maintain backups of cells as it enables the semipermanent storage cells. During freezing process, ice crystals that are generated inside and outside can lethally damage All conventional cryopreservation methods use at least one cryoprotective agent (CPA) render water vitreous or nanocrystallized (near-vitrification) without forming damaging crystals. However, CPAs should ideally be avoided due their cytotoxicity potential side effects on cellular state....
The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, resulting subvariants display further evasion antibody escape. An engineered angiotensin-converting enzyme (ACE2) decoy composed of high-affinity ACE2 an IgG1 Fc domain could offer alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum therapeutic potential in rodent models. Here, we...
Abnormal sulfide catabolism, especially the accumulation of hydrogen (H2S) during hypoxic or inflammatory stresses, is a major cause redox imbalance-associated cardiac dysfunction. Polyhydroxynaphtoquinone echinochrome A (Ech-A), natural pigment marine origin found in shells and needles many species sea urchins, potent antioxidant inhibits acute myocardial ferroptosis after ischemia/reperfusion, but chronic effect Ech-A on heart failure unknown. Reactive sulfur (RSS), which include catenated...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 considered to affect the central nervous system (CNS) by interacting blood–brain barrier (BBB), defined tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although infection of BMECs has been...
Abstract Extracellular signal‐regulated kinase (ERK) belongs to the family of mitogen‐activated protein kinases (MAPKs), which are serine‐threonine activated by phosphorylation in response a variety mitogenic signals. We previously reported that 17β‐estradiol rapidly activates ERK rat hippocampus. However, physiological role this rapid activation estrogen vivo has not yet been elucidated. This study investigated whether may participate mediating neuroprotective effects against quinolinic...
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization mathematical simulation showed that low expression of inward-rectifier potassium (IK1) channel is a determinant To understand impact IK1 on pharmacological properties, we tested if...