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Kim, Dong Eon,Jang, Mi-Jin,Kim, Young Ran,Lee, Joo-Young,Cho, Eun Byul,Kim, Eunha,Kim, Yeji,Kim, Mi Young,Jeong, Won-il,Kim, Seyun,Han, Yong-Mahn,Lee, Seung-Hyo Elsevier 2017 Toxicology Vol.387 No.-
<P><B>Abstract</B></P> <P>Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an <I>in vitro</I> model system for assessment of drug-induced as well as immune-mediated hepatotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Generation and characterization of hES-HLCs for evaluation of drug-induced immune cell-mediated hepatotoxicity. </LI> <LI> The secretion of inflammatory cytokines is highly enhanced from APAP-treated hES-HLCs. </LI> <LI> Immune cells are activated and produce pro-inflammatory cytokines by conditioned medium from hES-HLCs cultured with APAP. </LI> <LI> Hepatotoxic results in hES-HLCs are consistent with those of primary human hepatocytes. </LI> <LI> Hepatotoxic drugs such as TZD, and non-hepatotoxic drugs such as aspirin and metformin, are also validated with our drug screening system. </LI> </UL> </P>
The Expanding Significance of Inositol Polyphosphate Multikinase as a Signaling Hub
Kim, Eunha,Ahn, Hyoungjoon,Kim, Min Gyu,Lee, Haein,Kim, Seyun Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.5
The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates ($IP_4$ and $IP_5$), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity. Through its PI3-kinase activity, IPMK activates Akt/PKB and its downstream signaling pathways. IPMK also regulates several protein targets non-catalytically via protein-protein interactions. These non-catalytic targets include cytosolic signaling factors and transcription factors in the nucleus. In this review, we highlight the many known functions of mammalian IPMK in controlling cellular signaling networks and discuss future challenges related to clarifying the unknown roles IPMK plays in physiology and disease.
Kim, Jinbum,Choi, Seongheum,Park, Taejin,Kim, Jinyong,Kim, Chulsung,Cha, Taeho,Lee, Hyangsook,Lee, Eunha,Won, Jung Yeon,Lee, Hyung-Ik,Hyun, Sangjin,Kim, Sunjung,Shin, Dongsuk,Kim, Yihwan,Kwon, Keewon American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.1
<P>To synthesize a thermally robust Ni1-xPtxSi film suitable for ultrashallow junctions in advanced metal-oxide-semiconductor field-effect transistors, we used a continuous laser beam to carry out millisecond annealing (MSA) on a preformed Ni-rich silicide film at a-local surface temperature above 1000 degrees C while heating the substrate to initiate a phase transition. The melting and quenching process by this unique high-temperature MSA process formed a Ni1-xPtxSi film with homogeneous Pt distribution across the entire film thickness. After additional substantial thermal treatment up to 800 degrees C, the noble Ni1-xPtxSi film maintained a low-resistive phase without agglomeration and even exhibited interface flattening with the underlying Si substrate.</P>
Kim, Eunha,Tyagi, Richa,Lee, Joo-Young,Park, Jina,Kim, Young-ran,Beon, Jiyoon,Chen, Po Yu,Cha, Jiyoung Y.,Snyder, Solomon H.,Kim, Seyun National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.49
<P>Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes.</P>
Kim, Hoijoon,Park, Taejin,Park, Seongjae,Leem, Mirine,Ahn, Wonsik,Lee, Hyangsook,Lee, Changmin,Lee, Eunha,Jeong, Seong-Jun,Park, Seongjun,Kim, Yunseok,Kim, Hyoungsub Elsevier 2019 THIN SOLID FILMS - Vol.673 No.-
<P><B>Abstract</B></P> <P>For the fabrication of high-performance top-gated MoS<SUB>2</SUB> transistors, a uniform atomic layer deposition (ALD) of an ultrathin high-<I>k</I> gate dielectric film without abnormal leakage paths on a MoS<SUB>2</SUB> channel is required. In this study, we fabricated a ~5.2 nm-thick monolithic HfO<SUB>2</SUB> gate dielectric film by utilizing an e-beam-evaporated Hf seed layer (target thickness of 3 nm) prior to the ALD of a HfO<SUB>2</SUB> film (~2 nm). The Hf seed layer was fully converted to HfO<SUB>2</SUB> without metallic residues during the following ALD process, without damages to the Raman and photoluminescence characteristics of the underlying MoS<SUB>2</SUB>. The conformal and pinhole-free ALD of the subsequent HfO<SUB>2</SUB> film was verified using conductive atomic force microscopy. In addition, operation of a top-gated MoS<SUB>2</SUB> transistor was demonstrated by integrating the Hf-seeded HfO<SUB>2</SUB> gate dielectric film.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Conformal and monolithic Hf-seeded ALD-HfO<SUB>2</SUB> film is formed on MoS<SUB>2</SUB>. </LI> <LI> Hf seed layer formation does not impose significant damages on MoS<SUB>2</SUB>. </LI> <LI> Hf-seeded HfO<SUB>2</SUB> gate dielectric film can be integrated in top-gated MoS<SUB>2</SUB> transistor. </LI> </UL> </P>