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Ok, Seong Ho,Bae, Sung Il,Kwon, Seong Chun,Park, Jung Chul,Kim, Woo Chan,Park, Kyeong Eon,Shin, Il Woo,Lee, Heon Keun,Chung, Young Kyun,Choi, Mun Jeoung,Sohn, Ju Tae The Korean Pain Society 2014 The Korean Journal of Pain Vol.27 No.3
Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.
Monodisperse Pattern Nanoalloying for Synergistic Intermetallic Catalysis
Mun, Jeong Ho,Chang, Yun Hee,Shin, Dong Ok,Yoon, Jong Moon,Choi, Dong Sung,Lee, Kyung-Min,Kim, Ju Young,Cha, Seung Keun,Lee, Jeong Yong,Jeong, Jong-Ryul,Kim, Yong-Hyun,Kim, Sang Ouk American Chemical Society 2013 Nano letters Vol.13 No.11
<P>Nanoscale alloys attract enormous research attentions in catalysis, magnetics, plasmonics and so on. Along with multicomponent synergy, quantum confinement and extreme large surface area of nanoalloys offer novel material properties, precisely and broadly tunable with chemical composition and nanoscale dimension. Despite substantial progress of nanoalloy synthesis, the randomized positional arrangement and dimensional/compositional inhomogeneity of nanoalloys remain significant technological challenges for advanced applications. Here we present a generalized route to synthesize single-crystalline intermetallic nanoalloy arrays with dimensional and compositional uniformity via self-assembly. Specific electrostatic association of multiple ionic metal complexes within self-assembled nanodomains of block copolymers generated patterned monodisperse bimetallic/trimetallic nanoalloy arrays consisting of various elements, including Au, Co, Fe, Pd, and Pt. The precise controllability of size, composition, and intermetallic crystalline structure of nanoalloys facilitated tailored synergistic properties, such as accelerated catalytic growth of vertical carbon nanotubes from Fe–Co nanoalloy arrays.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/nalefd/2013/nalefd.2013.13.issue-11/nl403542h/production/images/medium/nl-2013-03542h_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nl403542h'>ACS Electronic Supporting Info</A></P>
Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids
Mun, Seon Ju,Ryu, Jae-Sung,Lee, Mi-Ok,Son, Ye Seul,Oh, Soo Jin,Cho, Hyun-Soo,Son, Mi-Young,Kim, Dae-Soo,Kim, Su Jung,Yoo, Hyun Ju,Lee, Ho-Joon,Kim, Janghwan,Jung, Cho-Rok,Chung, Kyung-Sook,Son, Myung Elsevier 2019 Journal of hepatology Vol.71 No.5
<P><B>Background & Aims</B></P> <P>The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids have not been developed.</P> <P><B>Methods</B></P> <P>We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. The organoids were applied to screening platforms for the prediction of toxicity and the evaluation of drugs that target hepatic steatosis through real-time monitoring of cellular bioenergetics and high-content analyses.</P> <P><B>Results</B></P> <P>Our organoids were morphologically indistinguishable from adult liver tissue-derived epithelial organoids and exhibited self-renewal. With further maturation, their molecular features approximated those of liver tissue, although these features were lacking in 2D differentiated hepatocytes. Our organoids preserved mature liver properties, including serum protein production, drug metabolism and detoxifying functions, active mitochondrial bioenergetics, and regenerative and inflammatory responses. The organoids exhibited significant toxic responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis.</P> <P><B>Conclusions</B></P> <P>Our organoids exhibit self-renewal (expandable and further able to differentiate) while maintaining their mature hepatic characteristics over long-term culture. These organoids may provide a versatile and valuable platform for physiologically and pathologically relevant hepatic models in the context of personalized medicine.</P> <P><B>Lay summary</B></P> <P>A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Pluripotent stem cell (PSC)-derived expandable human hepatocyte-like liver organoids were generated. </LI> <LI> PSC-derived human hepatic organoids are capable of long-term expansion with competent liver functionality. </LI> <LI> PSC-derived human hepatic organoids provide a robust hepatic model for toxicity prediction and drug screening. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>