担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

DOI： 10.1186/s12576-022-00851-3

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その他リンク： https://link.springer.com/article/10.1186/s12576-022-00851-3/fulltext.html

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1093/eurheartj/ehac544.3027

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1093/eurheartj/ehab724.3190

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fcell.2021.689662

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2021.03.077

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

DOI： 10.1186/s12576-021-00809-x

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その他リンク： https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

DOI： 10.1186/s12576-021-00809-x

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その他リンク： https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

DOI： 10.1186/s12576-021-00809-x

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その他リンク： https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.mex.2021.101404

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms22084108

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fcvm.2021.649785

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijms22041729

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41526-020-00130-8

PubMed

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その他リンク： http://www.nature.com/articles/s41526-020-00130-8

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3791/61104

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.yexcr.2019.111556

PubMed

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2019.09.119

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The application of mechanical stimuli to cells often induce increases in intracellular calcium, affecting the regulation of a variety of cell functions. Although the mechanism of mechanotransduction-induced calcium increases has not been fully resolved, the involvement of mechanosensitive ion channels in the plasma membrane and the endoplasmic reticulum has been reported. Here, we demonstrate that voltage-gated L-type calcium channels play a critical role in the mechanosensitive calcium response in H9c2 rat cardiomyocytes. The intracellular calcium level in H9c2 cells increased in a reproducible dose-dependent manner in response to uniaxial stretching. The stretch-activated calcium response (SICR) completely disappeared in calcium-free medium, whereas thapsigargin and cyclopiazonic acid, inhibitors of sarcoendoplasmic reticulum calcium ATPase, partially reduced the SICR. These findings suggest that both calcium influx across the cell membrane and calcium release from the sarcoendoplasmic reticulum are involved in the SICR. Nifedipine, diltiazem, and verapamil, inhibitors of L-type calcium channels, reduced the SICR in a dose-dependent manner. Furthermore, small interfering RNA against the L-type calcium channel α1c subunit diminished the SICR dramatically. Nifedipine also diminished the mechanosensitivity of Langendorff-perfused rat heart. These results suggest that the SICR in H9c2 cardiomyocytes involves the activation of L-type calcium channels and subsequent calcium release from the sarcoendoplasmic reticulum.

DOI： 10.1016/j.ceca.2019.02.008

PubMed

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2018.07.116

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/cells7060062

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-016-0519-3

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-018-0610-z

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その他リンク： http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

担当区分：最終著者,　責任著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-018-0610-z

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その他リンク： http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-018-0610-z

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その他リンク： http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1093/eurheartj/ehx501.45

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Long-term habitation in space leads to physiological alterations such as bone loss, muscle atrophy, and cardiovascular deconditioning. Two predominant factors-namely space radiation and microgravity-have a crucial impact on oxidative stress in living organisms. Oxidative stress is also involved in the aging process, and plays important roles in the development of cardiovascular diseases including hypertension, left ventricular hypertrophy, and myocardial infarction. Here, we discuss the effects of space radiation, microgravity, and a combination of these two factors on oxidative stress. Future research may facilitate safer living in space by reducing the adverse effects of oxidative stress.

DOI： 10.3390/ijms18071426

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CELL PRESS  

DOI： 10.1016/j.bpj.2016.11.1471

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記述言語：日本語   出版者・発行元：(一社)日本生理学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1007/bf03405812

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その他リンク： http://link.springer.com/article/10.1007/BF03405812/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/bf03405812

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その他リンク： http://link.springer.com/article/10.1007/BF03405812/fulltext.html

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：論文集(書籍)内論文  

DOI： 10.1002/9781118966174.ch11

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：論文集(書籍)内論文  

DOI： 10.1007/978-4-431-54801-0_15

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3934/biophy.2016.1.63

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

All previous reports concerning the effect of stretch on cultured skin cells dealt with experiments on epidermal keratinocytes or dermal fibroblasts alone. The aim of the present study was to develop a system that allows application of stretch stimuli to human skin equivalents (HSEs), prepared by coculturing of these two types of cells. In addition, this study aimed to analyze the effect of a stretch on keratinization of the epidermis and on the basement membrane. HSEs were prepared in a gutter-like structure created with a porous silicone sheet in a silicone chamber. After 5-day stimulation with stretching, HSEs were analyzed histologically and immunohistologically. Stretch-stimulated HSEs had a thicker epidermal layer and expressed significantly greater levels of laminin 5 and collagen IV/VII in the basal layer compared with HSEs not subjected to stretch stimulation. Transmission electron microscopy revealed that the structure of the basement membrane was more developed in HSEs subjected to stretching. Our model may be relevant for extrapolating the effect of a stretch on the skin in a state similar to an in vivo system. This experimental system may be useful for analysis of the effects of stretch stimuli on skin properties and wound healing and is also expected to be applicable to an in vitro model of a hypertrophic scar in the future.

DOI： 10.1371/journal.pone.0141989

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Ischemic heart disease still remains the most common cause of cardiac death. During ischemia-reperfusion (I/R), reactive oxygen species (ROS) are produced in excess in cardiac tissue, where they induce cell death. Our previous study showed that 9-phenanthrol (9-Phe), a specific inhibitor of the TRPM4 channel, preserves cardiac contractile function and protects the heart from I/R injury-related infarction in the excised rat heart. Accordingly, we hypothesized that TRPM4 channels are involved in the 9-Phe-mediated cardioprotection against ROS-induced injury. In rats, intravenous 9-Phe mitigated the development of myocardial infarction caused by the occlusion of the left anterior descending artery. Immunohistochemical analysis indicated that TRPM4 proteins are expressed in ventricular myocytes susceptible to I/R injury. Hydrogen peroxide (H2O2) is among the main ROS overproduced during I/R. In the cardiomyocyte cell line H9c2, pretreatment with 9-Phe prevented cell death induced by conditions mimicking I/R, namely 200 mu M H2O2 and hypoxia-reoxygenation. Gene silencing of TRPM4 preserved the viability of H9c2 cardiomyocytes exposed to 200 mu M H2O2. These results suggest that the cardioprotective effects of 9-Phe are mediated through the inhibition of the TRPM4 channels.

DOI： 10.1371/journal.pone.0121703

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bpj.2014.11.3189

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1007/bf03405845

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その他リンク： http://link.springer.com/article/10.1007/BF03405845/fulltext.html

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Institute of Mathematical Sciences  

Coarse-grained molecular dynamics (CGMD) simulations are increasingly being used to analyze the behaviors of biological systems. When appropriately used, CGMD can simulate the behaviors of molecular systems several hundred times faster than elaborate all-atom molecular dynamics simulations with similar accuracy. CGMD parameters for lipids, proteins, nucleic acids, and some artificial substances such as carbon nanotubes have been suggested. Here we briefly discuss a method for CGMD system configuration and the types of analysis and perturbations that can be performed with CGMD simulations. We also describe specific examples to show how CGMD simulations have been applied to various situations, and then describe experimental results that were used to validate the simulation results. CGMD simulations are applicable to resolving problems for various biological systems.

DOI： 10.3934/biophy.2014.1.1

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担当区分：筆頭著者   記述言語：日本語  

DOI： 10.11392/jsao.43.206

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/BF03405834

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society for Medical and Biological Engineering  

DOI： 10.11239/jsmbe.51.R-14

CiNii Article

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society for Medical and Biological Engineering  

DOI： 10.11239/jsmbe.51.R-149

CiNii Article

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.

DOI： 10.1371/journal.pone.0070587

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Mechanosensitivity is essential for heart function just as for all other cells and organs in the body, and it is involved in both normal physiology and diseases processes of the cardiovascular system. In this review, we have outlined the relationship between mechanosensitivity and heart physiology, including the FrankStarling law of the heart and mechanoelectric feedback. We then focused on molecules involved in mechanotransduction, particularly mechanosensitive ion channels. We have also discussed the involvement of mechanosensitivity in heart diseases, such as arrhythmias, hypertrophy and ischaemic heart disease. Finally, mechanobiology in cardiogenesis is described with regard to regenerative medicine.

DOI： 10.1111/jcmm.12027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER HEIDELBERG  

Manual palpation or pressure stimulation is often used for pain sensitivity assessment. The aim of the current study was to define a method for investigating the relation between pressure pain sensitivity and pressure propagation in soft or harder muscles. Three-dimensional finite-element computer-models were developed to simulate the tissue stress and strain distribution during pressure stimulation on the tibialis anterior and gastrocnemius muscles. Four cases were modelled representing females and males who were trained and untrained. The model geometry was based on MR images of the lower leg during pressure stimulation. Stress and strain were extracted from the models at pressure intensity levels equivalent to the pressure pain threshold. The principal strain peaked in the adipose tissue at 0.30 and 0.14 for stimulation on the gastrocnemius and tibialis anterior muscle, respectively. The principal strain in the muscle was higher for four models of the stimulation on the gastrocnemius muscle (0.22-0.30) compared with the four models of stimulation on the tibialis anterior muscle (0.11-0.14). Average pressure pain thresholds were significantly lower for the tibialis anterior compared with the gastrocnemius muscle (319 vs. 432 kPa) These data show different pressure propagation profiles in soft and hard muscle at the same pressure pain sensation level. This new approach is relevant as the clinical routine assesses all muscles equally. This results in a different exposure to pressure in relation to the muscle evaluated which may affect the outcome of the examination.

DOI： 10.1007/s11517-012-0974-9

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The heart is an organ that is exposed to extreme dynamic mechanical stimuli. From birth till death, the heart indefinitely repeats periodic contraction and dilation, i.e., shortening and elongation of cardiomyocytes. Mechanical stretch elicits a change in heart rate and may cause arrhythmia if it is excessive. Thus, mechanosensitivity is crucial to heart function. The molecule that is substantially involved in mechanosensitivity is a stretch-activated ion channel. Among several ion channels believed to be activated by stretch in the heart, the stretch-activated K-Ca (SAKCA) channel, a member of the group of large conductance (Big Potassium, BK) channels, shows a mechanosensitive (MS) response to membrane stretch. As BK channels respond to voltage and intracellular calcium concentration with large conductance, they are considered to be involved in repolarization after depolarization. Some BK channels are known to be activated by stretch and are expressed in a number of cells, including human osteoblasts and guinea pig intestinal neurons. The SAKCA channel was found to be sensitive to stretch in the chick heart. Given that the cardiomyocyte is unremittingly exposed to contraction and dilation and that it generates action potential and its contractility is modulated by intracellular calcium concentration, the SAKCA channel, which is dependent voltage and calcium, may be involved in action potential generation. It was recently reported that a BK channel is involved in the modulation of heart rate in the mouse. Further studies regarding the role of MS BK channels, including SAKCA, in the modulation of heart rate and contractility are expected. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pbiomolbio.2012.08.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

DOI： 10.1016/j.cardfail.2012.08.116

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1097/01.hjh.0000420766.99570.ae

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain. To test this hypothesis, brain responses were recorded from 13 normal male subjects in response to repeated painful electrical stimulation of the muscle and skin of the left leg, using 3-T magnetic resonance imaging scanner. The common brain regions that responded to painful stimulations of both skin and muscle were the thalamus, anterior cingulate cortex, bilateral insula, contralateral primary and secondary somatosensory cortices, and ipsilateral cerebellum. Brain regions specifically activated by muscle stimulation were the midbrain, bilateral amygdala, caudate, orbitofrontal cortex, hippocampus, parahippocampus and superior temporal pole, most of which are related to emotion. Regions except the midbrain showed contralateral preference. These results suggest that dull sensation, which is characteristic of muscular pain, is related with processing in these brain regions. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2011.04.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC CELL BIOLOGY  

Continued exposure of endothelial cells to mechanical/shear stress elicits the unfolded protein response (UPR), which enhances intracellular homeostasis and protect cells against the accumulation of improperly folded proteins. Cells commit to apoptosis when subjected to continuous and high endoplasmic reticulum (ER) stress unless homeostasis is maintained. It is unknown how endothelial cells differentially regulate the UPR. Here we show that a novel Girdin family protein, Gipie (78 kDa glucose-regulated protein [GRP78]-interacting protein induced by ER stress), is expressed in endothelial cells, where it interacts with GRP78, a master regulator of the UPR. Gipie stabilizes the interaction between GRP78 and the ER stress sensor inositol-requiring protein 1 (IRE1) at the ER, leading to the attenuation of IRE1-induced c-Jun N-terminal kinase (JNK) activation. Gipie expression is induced upon ER stress and suppresses the IRE1-JNK pathway and ER stress-induced apoptosis. Furthermore we found that Gipie expression is up-regulated in the neointima of carotid arteries after balloon injury in a rat model that is known to result in the induction of the UPR. Thus our data indicate that Gipie/GRP78 interaction controls the IRE1-JNK signaling pathway. That interaction appears to protect endothelial cells against ER stress-induced apoptosis in pathological contexts such as atherosclerosis and vascular endothelial dysfunction.

DOI： 10.1091/mbc.E10-08-0724

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.cbpb.2006.10.090

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Transcutaneous pressure with pressure probes of arbitrary diameters have been commonly used for measuring the threshold and magnitude of muscle pain, yet this procedure lacks scientific validation. To examine the valid probe dimensions, we conducted physiological experiments using 34 human subjects. Pin-prick pain, pressure pain threshold (PPT) to pressure probes of various diameters, heat pain threshold, and electrical pain threshold of deep tissues were measured before and after application of surface lidocaine anesthesia to the skin surface over the brachioradial muscle in a double-blinded manner. The anesthesia neither affected PPT with larger probes (diameters: 1.6 and 15 mm) nor increased electric pain threshold of deep structures, whereas it diminished pain count in pin-prick test and PPT with a 1.0 mm diameter probe, suggesting that mechanical pain thresholds measured with 1.6 and 15 mm probes reflect the pain threshold of deep tissues, possibly muscle. Pain thresholds to heat did not change after application of the anesthesia. These results suggest that larger pressure probes can give a better estimation of muscular pain threshold.

DOI： 10.1080/08990220500420475

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

To examine the effects of change in meteorological parameters on pain-related behaviors in a simulated arthritic condition, rats with an injection of complete Freund's adjuvant into the tibio-tarsal joint were exposed to low barometric pressure (20 mmHg below the natural atmospheric pressure) and low ambient temperature (7 degreesC lower than 22 degreesC) in a climate-controlled room. When the arthritic rats were exposed to these environments, the already increased number of hindpaw withdrawals in response to noxious mechanical stimulation (hyperalgesia) was further increased, and a hindpaw withdrawal response to innocuous mechanical stimulation (allodynia) began to occur. Such exposures did not influence any of the pain-related behaviors of the control rats. These results show that lowering barometric pressure and ambient temperature within the range of natural environmental fluctuation intensify pain in arthritic rats. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2003.09.057

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：INT ASSOC STUDY PAIN (IASP) PRESS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Cold allodynia is an annoying symptom in conditions of chronic inflammation such as rheumatoid arthritis. To examine whether primary afferent nerve activities are changed in association with hypersensitivity to cold, we recorded single nerve activities from the sural nerve in persistently inflamed rats in vivo. Inflammation was induced by an injection of complete Freund's adjuvant (CFA) solution into the tibio-tarsal joint. Inflamed rats showed an increased number of paw shakes to paw immersion in 25degreesC water (pre-inflammation: 1.15 +/- 0.58, 2-week inflammation: 4.70 +/- 1.15). We also recorded cutaneous C-fiber activities under pentobarbital anesthesia and studied their responses to thermal and mechanical stimuli. The response of C-low threshold mechanoreceptors to cooling (total discharges between 27 and 23degreesC) increased 1.8-fold (control group: 5.17 +/- 1.04 impulses, inflamed group: 9.38 +/- 1.47 impulses). In addition, the proportion of C-nociceptor units responding to cold down to 2degreesC was significantly greater in the inflamed group (9 out of 18 units; threshold: 10.0 +/- 2.6degreesC) than in the intact group (1 out of 14 units; threshold: 4.0degreesC). These results suggest that the facilitated responses of these primary afferents are associated with cold hypersensitivity in chronically inflamed conditions. (C) 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2003.08.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：名古屋大学  

国立情報学研究所で電子化したコンテンツを使用している。

DOI： 10.18999/envm.46.122

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その他リンク： http://search.jamas.or.jp/link/ui/2003221359

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：名古屋大学  

CiNii Article

CiNii Books

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記述言語：英語 著書種別：学術書

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記述言語：日本語 著書種別：学術書

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記述言語：日本語   掲載種別：書評論文，書評，文献紹介等  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：岡山医学会  

DOI： 10.4044/joma.128.61

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その他リンク： https://jlc.jst.go.jp/DN/JLC/20022537940?from=CiNii

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語  

Web of Science

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.11477/mf.2425100317

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記述言語：日本語   掲載種別：機関テクニカルレポート，技術報告書，プレプリント等   出版者・発行元：名古屋大学  

CiNii Article

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出版者・発行元：日本生理学会  

CiNii Article

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（国際会議プロシーディングズ）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語  

CiNii Article

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

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記述言語：日本語   掲載種別：研究発表ペーパー・要旨（全国大会，その他学術会議）  

CiNii Article

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開催年月日： 2020年10月27日 - 2020年10月30日

会議種別：シンポジウム・ワークショップ パネル（指名）  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：Singapore  

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開催年月日： 2024年6月28日 - 2024年6月29日

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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開催年月日： 2024年5月23日 - 2024年5月25日

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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開催年月日： 2024年1月30日 - 2024年2月2日

記述言語：日本語   会議種別：ポスター発表  

心不全に対する最終的な治療方法である心臓移植のドナー心臓の不足が問題となっている中、iPS（induced Pluripotent Stem）細胞を使った再生医療が代替手段として注目されている。しかしながらiPS細胞の心筋細胞への分化誘導の過程に異種動物由来の材料が使われることで安全性に関する懸念がある。本研究は、iPS細胞由来の心筋細胞（iPS-CM）の安全性向上を目指し、ヒト歯肉線維芽細胞（HGF）をフィーダー細胞として使用し、異種動物由来の材料を排除した上でiPS-CMへの分化誘導が促進されることを実証した。

実験は、iPS細胞とHGFを共培養し心筋細胞への分化誘導を行い、iPS-CMに対して免疫染色やqPCR、また動画撮影を行い収縮の解析・定量化しiPS-CMの成熟について評価を行った。結果はHGFと共培養して分化誘導されたiPS-CMは有意に心筋特異的マーカーの発現が確認された。また収縮能が向上し、心筋組織特有のサルコメア構造も確認され、これらの結果は心筋の成熟を示唆している。

以上より本研究は、異種動物由来因子のリスクを回避し、より安全で収縮能の高い心筋組織を生成するプロトコルを提案している。

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開催年月日： 2023年11月17日 - 2023年11月18日

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：徳島  

背景：血管内皮細胞は、血圧、血管の伸展、および血流による剪断応力などのメカニカルストレスに常に曝されている。メカニカルストレスに応じて血管内皮細胞から放出される一酸化窒素（NO）は、心臓の収縮力を調節し、心筋肥大の進行を防ぐ役割を果たしている。本研究は、メカニカルストレス応答性のNO放出をライブイメージングする実験システムを確立することを目標とした。
方法：マイクロ流体チップの伸縮性のある弾性膜に30万個のヒト臍帯静脈内皮細胞を播種した。流路の送液チューブに接続したペリスタポンプ（図A）の流量を増加させ、細胞に剪断応力を与えた。圧力刺激は静水圧によって与えた。細胞を培養した弾性膜に伸展刺激を与えた（図B）。10 μMの4,5- diaminofluorescein diacetateを細胞に投与し、蛍光ライブNOイメージングを行なった。
結果：細胞間結合のマーカーであるCD31の免疫染色を行ったところ、頑健な細胞間結合の形成が確認された（図C）。デキストラン（分子量3,000）の透過性アッセイを行ったところ、バリア機能の指標であるapparent permeabilityは約3 × 10-6 cm/sの低値を30日間維持した。このことから、マイクロ流体チップ上の血管内皮細胞は頑健なバリア機能を有することが示唆された。血管内皮細胞に60 mmHgの圧力刺激を60秒間加えたところ、圧力刺激の開始から271秒後にNO濃度のピーク値が観察され、その後2分以上にわたってNOの放出が観察された。次に、血管内皮細胞に1％の伸展刺激を60秒間与えたところ、伸展刺激の開始から105秒後に基準値の1.29 ± 0.33倍のピーク値が観察された。0.01 dyn/cm2の剪断応力を血管内皮細胞に与えたところ、NO放出の有意な増加は認められなかった。
結論：臓器チップを使用した、メカニカルストレス応答性の血管内皮細胞のNO放出をライブイメージングするシステムが確立された。この技術を心臓チップに応用することにより、高血圧などの機械的な刺激が、心臓の収縮機能やリモデリングに与える影響を明らかにすることが期待される。

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開催年月日： 2023年10月28日 - 2023年10月29日

記述言語：英語   会議種別：口頭発表（一般）  

開催地：岡山  

Pulmonary fibrosis is a severe lung condition characterized by lung scarring and thickening, resulting in impaired breathing for affected individuals. While animal models have been commonly employed in research, the use of human cell-based models is essential for the development of more effective therapies for pulmonary fibrosis. In our efforts to establish a lung fibrosis model, we utilized human lung epithelial cell line NCI-H441 and human gingival fibroblasts (HGFs). We induced fibrosis-like changes by administering transforming growth factor beta-1 (TGF-β1). Morphological alterations were observed in HGFs under a microscope, although no such changes were seen in NCI-H441. Subsequently, we extracted mRNA and conducted RT-PCR to assess fibrosis marker expression in both cell types. Our analysis confirmed that the α-SMA gene expression increased in a dose-dependent manner in HGFs following TGF-β1 treatment, whereas NCI-H441 exhibited significant upregulation of fibrosis marker genes, including slug and vimentin. To better replicate the lung's physiological structure, we employed transwell culture systems. Human umbilical vein endothelial cells were seeded on the basolateral side. NCI-H441 and HGFs were then seeded on the apical side of the transwell. Upon reaching full confluence, the culture medium was replaced with TGF-β1-containing medium. After two days of treatment, we simultaneously extracted mRNAs from NCI-H441 and HGFs on the apical side and conducted RT-PCR analysis. Our findings revealed that the expression of fibrosis marker genes, including α-SMA, Slug, and Vimentin, tended to increase in response to TGF-β1. Additionally, we endeavored to create an air-liquid interface (ALI) within the lung alveoli by removing the culture medium on the apical side. Even two days later, confocal microscopy confirmed the uptake of intracellular calcium indicators, indicating successful ALI formation. Immunostaining for PECAM-1, an endothelial junction marker, demonstrated robust intercellular junction integrity among endothelial cells. We are committed to further refining this human triculture model to advance our contributions to the development of treatments for pulmonary fibrosis.

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開催年月日： 2023年9月8日 - 2023年9月9日

記述言語：英語   会議種別：ポスター発表  

開催地：熊本  

Vascular endothelial cells play crucial roles in vasoregulation and atherosclerosis pathogenesis. Traditional 2D or static cell culture models limit morphology and functionality of endothelial cells. To mimic the dynamic microenvironment, we seeded human umbilical vein endothelial cells (HUVECs) into microfluidic organ chips. Assessing barrier function with a dextran permeability assay, we evaluated the impact of shear stress on vascular permeability at different flow rates. Optimized flow rate (80 μl/hr) enhanced barrier function, evidenced by minimized apparent permeability. HUVECs aligned parallel to flow on the microfluidic channel. We have established a method to culture highly barrier-functional endothelium with a similar orientation to in vivo blood vessels within microfluidic channels. This method holds promise for application in organ chips.

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開催年月日： 2023年3月14日 - 2023年3月16日

記述言語：英語   会議種別：ポスター発表  

開催地：京都  

Pulmonary fibrosis is a severe lung disease causing scarring and thickening of the lungs, which make breathing difficult. Although animal models are often used to study lung fibrosis, models using human cells are necessary to develop better therapeutic strategies. To develop a human lung fibrosis model, NCI-H441 lung epithelial cells and human gingival fibroblasts (HGF) were first monocultured. The cells were treated with transforming growth factor beta-1 (TGF-β1) to induce fibrosis-like changes. TGF-β1 treatment increased the area of adhesion to the culture plate of fibroblasts, but not the lung epithelial cells. Gene expression analysis of fibrosis markers using quantitative reverse transcribed polymerase chain reaction (qRT-PCR) revealed that alpha smooth muscle actin (α-SMA) expression increased with increasing doses of TGF-β1 in HGF, but not in NCI-H441 cells. In contrast, expression of fibrosis marker genes, including Slug and Vimentin, increased in a dose-dependent manner in NCI-H441 cells. Transwells were used to recapitulate lung structure. Human umbilical vein endothelial cells were seeded on the basolateral side of the transwells, which were coated with Matrigel to facilitate cell adhesion. NCI-H441 cells and fibroblasts were seeded on the apical side of the transwells. After the cells reached 100% confluency, cells were treated with TGF-β1 for 2 days, and NCI-H441 and HGF were collected from the apical side of the transwells. The expression of fibrosis marker genes, including α-SMA, Slug, and Vimentin, were measured using qRT-PCR. These three marker genes tended to increase in response to TGF-β1. To achieve an air–liquid interface (ALI), similar to lung alveoli, the medium was removed from the apical side of the transwells. Uptake of an intracellular calcium indicator was observed under a confocal microscope even two days after removal of the medium, indicating the successful formation of an ALI. Additionally, immunostaining for PECAM-1 indicated high integrity of the intercellular junctions between the endothelial cells. We will further develop this human triculture model to facilitate the development of treatments for pulmonary fibrosis.

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開催年月日： 2023年3月14日 - 2023年3月16日

記述言語：英語   会議種別：ポスター発表  

開催地：京都  

Cardiovascular diseases have always posed a serious threat to mankind. With the advent of pluripotent stem cell technology, the pathophysiology of human heart diseases can now be mimicked using tissue culture methods, including trans-well and microfluidic chip models. In this study, we developed a tri-culture model comprising human gingival fibroblasts (HGFs), human umbilical vein endothelial cells (HUVECs), and induced pluripotent stem cells (iPSCs) using both trans-wells and microfluidic chips. We seeded iPSCs and HGFs onto the top channel of a chip and the apical side of a trans-well, whereas HUVECs were seeded onto the bottom channel of the chip and the basolateral side of the trans-well. After iPSCs were differentiated into cardiomyocytes in each model, their contractility was compared. Interestingly, cardiomyocytes in the chip model exhibited spontaneous contraction as early as on day 16 post-commencement of differentiation whereas those in the trans-well model showed contractions on day 23. Moreover, 33.3% spontaneous contraction was observed in the chip model compared with 11% in the trans-well model. Fluorescence-activated cell sorting revealed that 12.6% of the cells collected from the top channels in the chip model expressed cardiac troponin T, a specific cardiomyocyte marker. Our study suggests that the continuous supply of medium to the cells may be an important factor governing the differentiation of iPSCs into cardiomyocytes.

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開催年月日： 2022年12月8日 - 2022年12月10日

記述言語：英語   会議種別：ポスター発表  

開催地：Los Angeles  

Drug pharmacology and toxicology tests using laboratory animals have limited applicability to humans and pose a considerable ethical dilemma. These problems can be resolved by developing an organ-on-a-chip technology that realistically simulates human organ function. We developed a heart-on-a-chip that contains fibroblasts similar to those of actual hearts and that also includes vascular endothelial layers that respond to pressure, stretch, and shear stress caused by blood flow. The heart chip consists of a myocardial channel that forms a co-culture system of human induced pluripotent stem cell-derived cardiomyocytes, human fibroblasts, and a vascular channel that forms a vascular endothelial cell layer separated by a 100 μm-thick permeable membrane. The cells in the myocardial channel spontaneously contracted without electrical stimulation and exhibited a dose-dependent increase in heart rate in response to noradrenaline administration in the physiological range to the vascular channel. Moreover, fluorescence live imaging of the intracellular calcium revealed synchronous fluorescence propagation at regular intervals in the myocardial channel and rhythmic excitation propagation without arrhythmia. Immunocytochemical analysis, in which the cardiac troponin T that constitutes the myocardial contraction machinery and the HCN4 channel expressed in pacemaker cells were stained, suggested that contracting cardiomyocytes and pacemaker cells constitute independent populations. Furthermore, when a pressure of 60 mmHg or a stretch stimulus of 1%, which simulates hypertension, was applied, nitric oxide release from vascular endothelial cells, which is expected in the actual heart, was confirmed by live imaging. This human heart-on-a-chip better reflects the functional characteristics of the heart and is expected to provide more accurate results in pharmacological and toxicological drug testing compared to laboratory animals.

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開催年月日： 2022年11月5日 - 2022年11月6日

記述言語：英語   会議種別：口頭発表（一般）  

開催地：高知  

Pulmonary fibrosis is a severe lung disease that causes scarring and thickening of the lungs, making it difficult for patients to breathe. Although animal models have often been used, models using human cells are necessary to develop better therapeutic methods for lung fibrosis. We first cultured a lung epithelial cell, NCI-H441, and administered transforming growth factor beta-1 to induce fibrosis-like changes to develop the human fibrosis model. Increased expression of fibrosis marker genes, including slug and vimentin in a dose-dependent manner, were revealed using quantitative reverse transcription polymerase chain reaction. Next, we used transwells to recapitulate the lung structure more faithfully. We seeded human umbilical vein endothelial cells on the basolateral side of the transwell coated with Matrigel, which facilitated cell adhesion. We then seeded cells NCI-H441 and fibroblasts on the apical side of the transwell. We removed the culture medium on the apical side to achieve an air-liquid interface (ALI) in the lung alveoli. The uptake of the intracellular calcium indicator was observed under a confocal microscope even two days later, suggesting successful ALI formation. Additionally, immunostaining of PECAM-1, a marker of the endothelial junction, indicated high integrity of the intercellular junction between endothelial cells. We will further develop this human triculture model to contribute to the development of treatments for pulmonary fibrosis.

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開催年月日： 2022年7月10日 - 2022年7月14日

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：台北（ハイブリッド）  

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開催年月日： 2022年6月28日 - 2022年6月30日

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：新潟  

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開催年月日： 2021年6月15日 - 2021年6月17日

記述言語：英語   会議種別：口頭発表（一般）  

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開催年月日： 2020年5月25日 - 2020年5月27日

記述言語：英語   会議種別：ポスター発表  

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開催年月日： 2016年7月29日 - 2016年7月30日

記述言語：日本語   会議種別：ポスター発表  

開催地：高槻  

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記述言語：英語   会議種別：ポスター発表  

開催地：仙台（ハイブリッド）  

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記述言語：日本語   会議種別：口頭発表（招待・特別）  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：Online  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

薬物の有効性を試験する際、マウスなどを用いた動物実験が行われる。しかしヒトの臓器と実験動物の臓器との間には機能的な相違があり、動物実験で得られたデータをヒトに外挿するのが困難であることが少なくない。また、薬物の試験に動物を利用することには倫理上の問題がある。ヒト細胞を用いた臓器チップの開発により、これらの問題が解決することが期待されている。本発表では、ヒトiPS心筋細胞を用いた心臓チップを中心に、臓器チップを用いた疾患モデルの開発について紹介する。

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：口頭発表（一般）  

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記述言語：英語   会議種別：ポスター発表  

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記述言語：英語   会議種別：口頭発表（基調）  

開催地：台北  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Okinawa  

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記述言語：英語   会議種別：口頭発表（一般）  

開催地：高松  

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記述言語：英語   会議種別：ポスター発表  

開催地：高松  

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記述言語：英語   会議種別：口頭発表（一般）  

開催地：高松  

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：徳島  

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記述言語：英語   会議種別：口頭発表（一般）  

開催地：Barcelona, Spain  

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記述言語：英語   会議種別：ポスター発表  

開催地：浜松  

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記述言語：英語   会議種別：ポスター発表  

開催地：浜松  

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記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：仙台  

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記述言語：英語   会議種別：ポスター発表  

開催地：New Orleans, USA  

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記述言語：英語   会議種別：ポスター発表  

開催地：San Francisco  

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記述言語：英語   会議種別：ポスター発表  

開催地：San Francisco  

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記述言語：英語   会議種別：ポスター発表  

開催地：Singapore  

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：旭川  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Qingdao, China  

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記述言語：英語   会議種別：ポスター発表  

開催地：Milan, Italy  

Cellular scaffold is extremely important for cellular differentiation. To find efficient method to induce cardiac differentiation of stem cells, we tested several scaffold proteins using two dimensional (2D) and three dimensional (3D) cell culture systems. It is suggested that specific proteins such as vitronectin are necessary for 2D adhesion of stem cells and their cardiac differentiation. Also suggested is that fibroblast may play an essential role in forming 3D structure of cardiac tissue.

SaBPoT7.14

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記述言語：英語   会議種別：ポスター発表  

開催地：Okazaki, Japan  

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記述言語：英語   会議種別：ポスター発表  

開催地：Philadelphia, USA  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：岡山  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：岡山  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：岡山  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：鹿児島  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：岡山  

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：岡崎  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Suzhou, China  

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記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：大宮  

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：倉敷  

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記述言語：日本語   会議種別：口頭発表（一般）  

開催地：岡崎  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：松本  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Beijing, China  

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記述言語：英語   会議種別：口頭発表（一般）  

開催地：福岡  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Dalian  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：Seoul  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：Aalborg  

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記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：幕張  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：横浜  

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記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：名古屋  

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記述言語：英語   会議種別：ポスター発表  

開催地：San Diego, USA  

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発表場所：東京  

人体内応力の有限要素解析シミュレーション

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発表場所：岡山  

てんかん・不整脈の創薬スクリーニングに向けた平面パッチクランプ装置の開発

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発表場所：岡山  

小型・安価な平面パッチクランプ装置

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受賞区分：国内学会・会議・シンポジウム等の賞  受賞国：日本国

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受賞区分：出版社・新聞社・財団等の賞  受賞国：日本国

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受賞区分：出版社・新聞社・財団等の賞  受賞国：日本国

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受賞区分：出版社・新聞社・財団等の賞  受賞国：日本国

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受賞区分：国際学会・会議・シンポジウム等の賞  受賞国：台湾

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受賞国：日本国

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