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Suvarna H. Pagire Haushabhau S. Pagire Kun-Young Park Eun Jung Bae Kwang-eun Kim Minhee Kim Jihyeon Yoon Saravanan Parameswaran Jun-Ho Choi Sungmi Park Jae-Han Jeon Jin Sook Song Myung Ae Bae In-Kyu Lee Hail Kim Jae Myoung Suh Jin Hee Ahn 《Molecules (Basel, Switzerland)》2022,27(11)
Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation. 相似文献
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Ye Seul Kim Jung Won Yoon Dasol Kim Seunghak Choi Hyoung Kyu Kim Jae Boum Youm Jin Han Soon Chul Heo Sung-Ae Hyun Jung-Wook Seo Deok-Ho Kim Jae Ho Kim 《Experimental & molecular medicine》2022,54(4):493
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.Subject terms: Heart failure, Embryonic stem cells, Stem-cell differentiation 相似文献
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We fabricated high quality epitaxial Bi0.9Ho0.1FeO3 thin films which exhibited the tetragonally stained structure with a c/a ratio of about 1.04. The Bi0.9Ho0.1FeO3 thin film showed a good ferroelectric property with the high remanent polarization (Pr) of about 80 μC/cm2. The ferromagnetic hysteresis loop with a clear remanent magnetization was shown. The coercive field and the remanent magnetization of the Bi0.9Ho0.1FeO3 film are 6200 Oe and 1.7 emu/g, respectively. The abrupt conduction due to space charge limited (SCL) was revealed in leakage current density versus electric field. 相似文献
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Dr. Chi Kyung Kim Taeho Kim In‐Young Choi Min Soh Dr. Dohoung Kim Young‐Ju Kim Dr. Hyunduk Jang Hye‐Sung Yang Dr. Jun Yup Kim Dr. Hong‐Kyun Park Dr. Seung Pyo Park Sangseung Park Dr. Taekyung Yu Prof. Byung‐Woo Yoon Prof. Seung‐Hoon Lee Prof. Taeghwan Hyeon 《Angewandte Chemie (International ed. in English)》2012,51(44):11172-11172
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Keng Yoon Yeong Mohamed Ashraf Ali Chee Wei Ang Soo Choon Tan Hasnah Osman 《Tetrahedron letters》2014
A facile method to synthesize various 1,2-disubstituted benzimidazoles is developed. It is suggested that formation of a Meisenheimer adduct between the substrate, amine, and solvent aids the N-arylation process. The generality of the protocol is demonstrated by the efficient reactions involving numerous substituents ranging from electron-withdrawing groups to electron-donating groups. 相似文献
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In this study, a phase-change memory device was fabricated and the origin of device failure mode was examined using transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). Ge2Sb2Te5 (GST) was used as the active phase-change material in the memory device and the active pore size was designed to be 0.5 m. After the programming signals of more than 2×106 cycles were repeatedly applied to the device, the high-resistance memory state (reset) could not be rewritten and the cell resistance was fixed at the low-resistance state (set). Based on TEM and EDS studies, Sb excess and Ge deficiency in the device operating region had a strong effect on device reliability, especially under endurance-demanding conditions. An abnormal segregation and oxidation of Ge also was observed in the region between the device operating and inactive peripheral regions. To guarantee an data endurability of more than 1×1010 cycles of PRAM, it is very important to develop phase-change materials with more stable compositions and to reduce the current required for programming. 相似文献
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Wi SG Chung BY Kim JS Kim JH Baek MH Lee JW Kim YS 《Micron (Oxford, England : 1993)》2007,38(6):553-564
This review discusses the morphological changes and biological responses of plants irradiated with gamma rays. Seedlings exposed to relatively low doses of gamma rays (1-5 Gy) developed normally, while the growth of plants irradiated with a high dose gamma ray (50 Gy) was significantly inhibited. Based on TEM observations, chloroplasts were extremely sensitive to gamma irradiation compared to other cell organelles, particularly thylakoids being heavily swollen. In addition, some portions of the mitochondria and endoplasmic reticulum were structurally altered, for example, distortion and swelling. The cerium perhydroxide deposition, as a maker for H(2)O(2) deposition, was typically manifest on the plasma membranes and cell walls of the tissues from both the control and irradiated plants. However, the intensities of cerium perhydroxide deposits (CPDs) were remarkably increased in the plasma membranes and cell walls of pumpkin tissues such as petiole, cotyledon, hypocotyl and especially leaf after gamma irradiation. These observations are in good agreement with the results of H(2)O(2) content in all tissues. The immuno-localization analysis for peroxidase (POD) on the tissues from pumpkin plant showed the same pattern between the control and irradiated plants, but the density of gold particles as indication of POD localization was significantly increased on the cell corner middle lamellae of parenchyma cells, especially in the petiole after gamma irradiation. However, accumulation and localization of H(2)O(2) and POD in vessels were not significantly different between both plants. The accumulation and localization of both H(2)O(2) and POD were differentially affected by gamma irradiation depending on the different tissue types. The deposition of both H(2)O(2) and POD in parenchyma cells appeared much higher than in vessels, suggesting that the former is more sensitive than the latter against gamma rays. 相似文献