MDPI AGActa Medica Okayama1873-149X3312026Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models10ENZheyiWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityFor more than a century, pathology has served as a cornerstone of modern medicine, relying primarily on static microscopic assessment of tissue morphology—such as H&E staining—which remains the “gold standard” for disease diagnosis. However, this conventional paradigm provides only a snapshot of disease states and often fails to capture their dynamic evolution and complex functional mechanisms. Moreover, animal models are constrained by marked interspecies differences, creating a persistent gap in translational research. To overcome these limitations, we propose the concept of New Pathophysiology, a research framework that transcends purely morphological descriptions and aims to resolve functional dynamics in real time. This approach integrates Organ-on-a-Chip (OOC) technology, multi-omics analyses, and artificial intelligence to reconstruct the entire course of disease initiation and to enable personalized medicine. In this review, we first outline the foundations and limitations of traditional pathology and animal models. We then systematically summarize more than one hundred existing OOC disease models across multiple organs—including the kidney, liver, and brain. Finally, we elaborate on how OOC technologies are reshaping the study of key pathological processes such as inflammation, metabolic dysregulation, and fibrosis by converting them into dynamic, mechanistic disease models, and we propose future perspectives in the field. This review adopts a relatively uncommon classification strategy based on pathological mechanisms (mechanism-based), rather than organ-based categorization, allowing readers to recognize shared principles underlying different diseases. Moreover, the focus of this work is not on emphasizing iteration or replacement of existing approaches, but on preserving past achievements from a historical perspective, with an emphasis on overcoming current limitations and enabling new advances.No potential conflict of interest relevant to this article was reported.American Institute of Mathematical Sciences (AIMS)Acta Medica Okayama2377-90981232025Biophysical regulation of extracellular matrix in systemic lupus erythematosus412437ENQiweiLiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQiangLiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityZhaoyangXiaoDepartment of Anesthesiology, The Second Affiliated Hospital of Dalian Medical UniversityKeijiNARUSEDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySystemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by immune dysregulation and multi-organ damage. Recent advances have underscored the critical involvement of extracellular matrix (ECM) biophysical properties in shaping immune cell behavior and metabolic states that contribute to disease progression. This review systematically delineates the pathological remodeling of ECM biophysics in SLE, with a focus on their roles in mechanotransduction, immune-metabolic interplay, and organ-specific tissue injury. By integrating current evidence, we highlight how ECM-derived mechanical cues orchestrate aberrant immune responses and propose new perspectives for targeting ECM-immune crosstalk in the development of organ-specific, mechanism-based therapies for SLE.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts30648ENMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarumiIdeiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Nursing, School of Life and Health Sciences, HuZhou CollegeYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeMatsudaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF.No potential conflict of interest relevant to this article was reported.Springer Science and Business Media LLCActa Medica Okayama2045-23221512025Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts30648ENMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHarumiIdeiDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Nursing, School of Life and Health Sciences, HuZhou CollegeYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeMatsudaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiKamiokaDepartment of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the maturation of the cardiomyocytes. This study aimed to improve the differentiation and subsequent maturation of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunocytochemistry, transmission electron microscopy, calcium imaging and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and MYL2) in both groups, with higher protein expression in the stretch group. Additionally, structural maturation of iPS-CMs in the stretch group was notably better than in the control group. A significant increase in the contractility and calcium cycle of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturation of iPS-CMs co-cultured with HGF.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2073-440913162024Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes1373ENHiroshiYamadaDepartment of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHironaOsakaGraduate School of Science, Nagoya UniversityNanamiTatsumiDepartment of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMiuArakiDepartment of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTadashiAbeDepartment of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeikoKaiharaDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityEizoTakashimaDivision of Malaria Research, Proteo-Science Center, Ehime UniversityTakayukiUchihashiGraduate School of Science, Nagoya UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKohjiTakeiDepartment of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySynaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of alpha-actinin and enhanced the alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221412024Human heart-on-a-chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC-derived cardiomyocytes18063ENYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRumaisaKamranDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityXiaoxiaHanDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityQiangLiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDaoyueLaiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIn recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.No potential conflict of interest relevant to this article was reported.ELSEVIERActa Medica Okayama2215-016182021Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2101404ENChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMasakazuMaedaDepartment of Medicine, Okayama UniversityJianChenDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesThe method presented in this article are related to the research article entitled as "Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress" [1]. TRPM4, a non-selective monovalent cation channel, is not only involved in the generation of the action potential in cardiomyocytes, but also thought to be a key molecule in the development of the ischemia-reperfusion injury of the brain and the heart [2-5]. However, existing pharmacological inhibitors for the TRPM4 channel have problems of non-specificity [6]. This article describes methods used for targeted genomic deletion in the rat cardiomyocyte H9c2 using the CRISPR-Cas9 genome editing system in order to suppress TRPM4 protein expression. Confocal microscopy, flow cytometry, Sanger sequencing, and western blotting are performed to confirm vector transfection and the subsequent knockout of the TRPM4 protein. These data provide information on the comprehensive analyses for knocking out the rat TRPM4 channel using CRISPR/Cas9. The analyses include confocal microscopy, flow cytometry, Sanger sequencing, and western blotting. This dataset will benefit biological and medical researchers studying the function of TRPM4-expressing cells including neurons, cardiomyocytes, and vascular endothelial cells. It is also useful to study the involvement of the TRPM4 channel in pathological processes such as cardiac arrhythmia and ischemia-reperfusion injury. The dataset can be used to guide the experiment of knocking out the TRPM4 gene and its subsequent application to the study of disease process caused by the gene. No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2296-634X92021Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells689662ENYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized that it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells (HUVEC) to simulated microgravity (SMG) using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin (PG) transporter gene SLCO2A1 decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of SLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0006-291X5662021Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress190196ENChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityJianChenDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIschemic heart disease is one of the most common causes of death worldwide. Mitochondrial
dysfunction, excessive reactive oxygen species (ROS) generation, and calcium (Ca2þ) overload are three key factors leading to myocardial death during ischemia-reperfusion (I/R) injury. Inhibition of TRPM4, a Ca2þ-activated nonselective cation channel, protects the rat heart from I/R injury, but the specific mechanism underlying this effect is unclear. In this study, we investigated the mechanism of cardioprotection against I/R injury via TRPM4 using hydrogen peroxide (H2O2), a major contributor to oxidative stress, as an I/R injury model. We knocked out the TRPM4 gene in the rat cardiomyocyte cell line H9c2 using CRISPR/Cas9. Upon H2O2 treatment, intracellular Ca2þ level and ROS production increased in wild type (WT) cells but not in TRPM4 knockout (TRPM4KO) cells. With this treatment, two indicators of mitochondrial function, mitochondrial membrane potential (DJm) and intracellular ATP levels, decreased inWT but not in TRPM4KO cells. Taken together, these findings suggest that blockade of the TRPM4 channel might protect the myocardium from oxidative stress by maintaining the mitochondrial membrane potential and intracellular ATP levels, possibly through preventing aberrant increases in intracellular Ca2þ and ROS.No potential conflict of interest relevant to this article was reported.FrontiersActa Medica Okayama2297-055X82021Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions-Diabetes Mellitus, Cardiovascular Diseases, and Ischemia-Reperfusion InjuryENMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityReactive oxygen species (ROS) plays a role in intracellular signal transduction under physiological conditions while also playing an essential role in diseases such as hypertension, ischemic heart disease, and diabetes, as well as in the process of aging. The influence of ROS has some influence on the frequent occurrence of cardiovascular diseases (CVD) in diabetic patients. In this review, we considered the pathophysiological relationship between diabetes and CVD from the perspective of ROS. In addition, considering organ damage due to ROS elevation during ischemia-reperfusion, we discussed heart and lung injuries. Furthermore, we have focused on the transient receptor potential (TRP) channels and L-type calcium channels as molecular targets for ROS in ROS-induced tissue damages and have discussed about the pathophysiological mechanism of the injury.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672242021Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia1729ENYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityA thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia-reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.No potential conflict of interest relevant to this article was reported.NatureActa Medica Okayama2373-806572021Gravity sensing in plant and animal cells2ENKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHideyukiTakahashiGraduate School of Life Sciences, Tohoku UniversityTakuyaFuruichiFaculty of Human Life Sciences, Hagoromo University of International StudiesMasatsuguToyotaDepartment of Biochemistry and Molecular Biology, Saitama UniversityMakotoFurutani-SeikiDepartment of Systems Biochemistry in Regeneration and Pathology, Graduate School of Medicine, Yamaguchi UniversityTakeshiKobayashiDepartment of Integrative Physiology, Graduate School of Medicine, Nagoya UniversityHarukoWatanabe-TakanoDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research InstituteMasahiroShinoharaDepartment of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with DisabilitiesTakuroNumaga-TomitaDepartment of Molecular Pharmacology, Shinshu University School of MedicineAsakoSakaue-SawanoLab for Cell Function and Dynamics, CBS, RIKENAtsushiMiyawakiLab for Cell Function and Dynamics, CBS, RIKENKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityGravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space.No potential conflict of interest relevant to this article was reported.Journal of Visualized ExperimentsActa Medica Okayama1940-087X1592020Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytese61104ENYunLiuDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYinLiangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMengxueWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University HengWeiInstitute of Laboratory Animals, Graduate School of Medicine, Kyoto UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIschemic heart disease is a significant cause of death worldwide. It has therefore been the subject of a tremendous amount of research, often with small-animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart, underscoring the need for clinically relevant models to study heart disease. Here, we present a protocol to model ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs) and to quantify the damage and functional impairment of the ischemic cardiomyocytes. Exposure to 2% oxygen without glucose and serum increases the percentage of injured cells, which is indicated by staining of the nucleus with propidium iodide, and decreases cellular viability. These conditions also decrease the contractility of hiPS-CMs as confirmed by displacement vector field analysis of microscopic video images. This protocol may furthermore provide a convenient method for personalized drug screening by facilitating the use of hiPS cells from individual patients. Therefore, this model of ischemic heart disease, based on iPS-CMs of human origin, can provide a useful platform for drug screening and further research on ischemic heart disease.No potential conflict of interest relevant to this article was reported.Academic PressActa Medica Okayama0006291X52032019Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells600605ENHengWeiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChenWangDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRuiGuoDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKenTakahashiDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeijiNaruseDepartment of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIschemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart. In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/ml glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs. Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0014482738322019Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1111556ENTakashiOhtsukiDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityAkiraShinaokaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKanaeKumagishi-ShinaokaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiAsanoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOmer FarukHatipogluDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityJunkoInagakiDepartment of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenTakahashiDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeiichiroNishidaDepartment of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeijiNaruseDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama University The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.No potential conflict of interest relevant to this article was reported.Medizinische Universitat OkayamaActa Medica Okayama211930Uber den Verschluss der fotalen Augenbecherspalte bei Uroloncha domestica Flower139ENKenTakahashiArticle10.18926/AMO/30610No potential conflict of interest relevant to this article was reported.