• Title/Summary/Keyword: HscA

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Inhibitory Effect of Salvia Miltiorrhiza on Fibrogenesis in Rat Hepatic Stellate Cells (단삼(丹蔘)이 간성상세포의 섬유화 억제에 미치는 영향)

  • Choi, Eun-Kyung;Lee, Jang-Hoon;Kim, Young-Chul;Woo, Hong-Jung
    • The Journal of Internal Korean Medicine
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    • v.29 no.2
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    • pp.299-310
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    • 2008
  • Objectives : This study was performed to investigate the anti-fibrogenic effect of Salvia miltiorrhiza on rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Salvia miltiorrhiza extract for 24 hours. It was extracted either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured Results : The viability and proliferation of the hepatic stellate cells were decreased as concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water. This indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Salvia miltiorrhiza, but increased by a high concentration. It seemed that the cells were responding to Salvia miltiorrhiza in low- concentration, thus producing smaller amounts of collagen. When the drug was administered in high enough concentration to give direct toxicity to cells, an overproduction of collagen was observed. Conclusion : These results suggest that Salvia miltiorrhiza is a possible candidate for the treatment of cirrhotic patients as well as for patients with chronic hepatitis when extracted with water in the proper concentrations.

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Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

  • Kim, Mi-Sun;Bae, Kil-Soo;Kim, Hye-Jin;Yoon, Suk-Ran;Oh, Doo-Byung;Hwang, Kwang-Woo;Jun, Woo-Jin;Shim, Sang-In;Kim, Kwang-Dong;Jung, Yong-Woo;Park, So-Young;Kwon, Ki-Sun;Choi, In-Pyo;Chung, Jin-Woong
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.206-210
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    • 2011
  • Natural Killer (NK) cells are the lymphocytes that are derived from hematopoietic stem cells, developed in the bone marrow from hematopoietic stem cells (HSC) by sequential acquisition of functional surface receptors, and express the repertoire of inhibitory and activating receptors. Recently, Osteopontin (OPN) has been identified as a critical factor for differentiation of natural killer cells. However, the detailed mechanism of OPN-induced NK differentiation has been still to be elucidated. Here, we determined the signaling pathway and possible receptor for OPN in NK differentiation. OPN induced expression of Bcl-2 and activation of Erk kinase. Inhibition of Erk pathway decreased the effect of OPN on NK differentiation. In addition, the expression of integrin ${\alpha}9$ was significantly increased by OPN during NK differentiation, suggesting the possible role of a major signaling molecule for OPN- induced NK differentiation.

Insights into Systems for Iron-Sulfur Cluster Biosynthesis in Acidophilic Microorganisms

  • Myriam, Perez;Braulio, Paillavil;Javiera, Rivera-Araya;Claudia, Munoz-Villagran;Omar, Orellana;Renato, Chavez;Gloria, Levican
    • Journal of Microbiology and Biotechnology
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    • v.32 no.9
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    • pp.1110-1119
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    • 2022
  • Fe-S clusters are versatile and essential cofactors that participate in multiple and fundamental biological processes. In Escherichia coli, the biogenesis of these cofactors requires either the housekeeping Isc pathway, or the stress-induced Suf pathway which plays a general role under conditions of oxidative stress or iron limitation. In the present work, the Fe-S cluster assembly Isc and Suf systems of acidophilic Bacteria and Archaea, which thrive in highly oxidative environments, were studied. This analysis revealed that acidophilic microorganisms have a complete set of genes encoding for a single system (either Suf or Isc). In acidophilic Proteobacteria and Nitrospirae, a complete set of isc genes (iscRSUAX-hscBA-fdx), but not genes coding for the Suf system, was detected. The activity of the Isc system was studied in Leptospirillum sp. CF-1 (Nitrospirae). RT-PCR experiments showed that eight candidate genes were co-transcribed and conform the isc operon in this strain. Additionally, RT-qPCR assays showed that the expression of the iscS gene was significantly up-regulated in cells exposed to oxidative stress imposed by 260 mM Fe2(SO4)3 for 1 h or iron starvation for 3 h. The activity of cysteine desulfurase (IscS) in CF-1 cell extracts was also upregulated under such conditions. Thus, the Isc system from Leptospirillum sp. CF-1 seems to play an active role in stressful environments. These results contribute to a better understanding of the distribution and role of Fe-S cluster protein biogenesis systems in organisms that thrive in extreme environmental conditions.

Selonsertib Inhibits Liver Fibrosis via Downregulation of ASK1/MAPK Pathway of Hepatic Stellate Cells

  • Yoon, Young-Chan;Fang, Zhenghuan;Lee, Ji Eun;Park, Jung Hee;Ryu, Ji-Kan;Jung, Kyung Hee;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • v.28 no.6
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    • pp.527-536
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    • 2020
  • Liver fibrosis constitutes a significant health problem worldwide due to its rapidly increasing prevalence and the absence of specific and effective treatments. Growing evidence suggests that apoptosis-signal regulating kinase 1 (ASK1) is activated in oxidative stress, which causes hepatic inflammation and apoptosis, leading to liver fibrogenesis through a mitogen-activated protein kinase (MAPK) downstream signals. In this study, we investigated whether selonsertib, a selective inhibitor of ASK1, shows therapeutic efficacy for liver fibrosis, and elucidated its mechanism of action in vivo and in vitro. As a result, selonsertib strongly suppressed the growth and proliferation of hepatic stellate cells (HSCs) and induced apoptosis by increasing Annexin V and TUNEL-positive cells. We also observed that selonsertib inhibited the ASK1/MAPK pathway, including p38 and c-Jun N-terminal kinase (JNK) in HSCs. Interestingly, dimethylnitrosamine (DMN)-induced liver fibrosis was significantly alleviated by selonsertib treatment in rats. Furthermore, selonsertib reduced collagen deposition and the expression of extracellular components such as α-smooth muscle actin (α-SMA), fibronectin, and collagen type I in vitro and in vivo. Taken together, selonsertib suppressed fibrotic response such as HSC proliferation and extracellular matrix components by blocking the ASK1/MAPK pathway. Therefore, we suggest that selonsertib may be an effective therapeutic drug for ameliorating liver fibrosis.

A Hyper Suprime-Cam View of the Interacting Galaxies of the M81 Group - Structures and Stellar Populations

  • Arimoto, Nobuo;Okamoto, Sakurako
    • The Bulletin of The Korean Astronomical Society
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    • v.42 no.2
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    • pp.39.2-39.2
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    • 2017
  • Over the last decade, deep studies of nearby galaxies have led to the discovery of vast stellar envelopes that are often rich in substructure. These components are naturally predicted in models of hierarchical galaxy assembly, and their observed properties place important constraints on the amount, nature, and history of satellite accretion. One of the most effective ways of mapping the peripheral regions of galaxies is through resolved star studies. Using wide-field cameras equipped to 8 m class telescopes, it has recently become possible to extend these studies to systems beyond the Local Group. Located at a distance of 3.6 Mpc, M81 is a prime target for wide-field mapping of its resolved stellar content. In this talk, we present the detailed results from our deep wide-field imaging survey of the M81 group with the Hyper Suprime-Cam (HSC), on the Subaru Telescope. We report on the analysis of the structures, stellar populations, and metallicities of old dwarf galaxies such as NGC3077, IKN, KDG061, as well as young stellar systems such as Arp's Loop and Holmberg IX. Several candidates for yet-undiscovered faint dwarf galaxies and young stellar clumps in the M81 group will also be introduced. The peculiar galaxy NGC3077 has been classified as the irregular galaxy. Okamoto et al. (2015, ApJ 809, L1) discovered an extended halo structure with S-shape elongated tails, obvious feature of tidal interaction. With a help of numerical simulation by Penarrubia et al. (2009, ApJ 698, 222), we will demonstrate that this tidal feature was formed during the latest close encounters between M81, M82, and NGC 3077, which induced star formation in tidally stripped gas far from the main bodies of galaxies. It is not clear whether the latest tidal interaction was the first close encounters of three galaxies. If NGC3077 is still surrounded by the dark matter halo, it implies that NGC3077 has undergone the first tidal stripping by larger companions. Kinematic studies of inter galactic globular clusters and planetary nebulae would tell us the past history of tidal interaction in this group of galaxies.

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Alloy Design and Properties of Ni based Superalloy LESS 1: I. Alloy Design and Phase Stability at High Temperature (Ni기 초내열 합금 LESS 1의 합금설계 및 평가: I. 합금 설계 및 고온 상 안정성 평가)

  • Youn, Jeong Il;Kang, Byung Il;Choi, Bong Jae;Kim, Young Jig
    • Journal of Korea Foundry Society
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    • v.33 no.5
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    • pp.215-225
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    • 2013
  • The alloys required for fossil power plants are altered from stainless steel that has been used below $600^{\circ}C$ to Ni-based alloys that can operate at $700^{\circ}C$ for Hyper Super Critical (HSC) steam turbine. The IN740 alloy (Special Metals Co. USA) is proposed for improved rupture strength and corrosion resistance at high temperature. However, previous studies with experiments and simulations on stable phases at about $700^{\circ}C$ indicated the formation of the eta phase with the wasting of a gamma prime phase, which is the most important reinforced phase in precipitation hardened Ni alloys, and this resulted in the formation of precipitation free zones to decrease the strength. On the basis of thermodynamic calculation, the new Ni-based superalloy named LESS 1 (Low Eta Sigma Superalloy) was designed in this study to improve the strengthening effect and structure stability by depressing the formation of topologically close packed phases, especially sigma and eta phases at high temperature. A thermal exposure test was carried out to determine the microstructure stability of LESS 1 in comparison with IN740 at $800^{\circ}C$ for 300 hrs. The experimental results show that a needle-shaped eta phase was formed in the grin boundary and it grew to intragrain, and a precipitation free zone was also observed in IN740, but these defects were entirely controlled in LESS 1.

ANTICANCER EFFECT OF TAMOXIFEN IN ORAL CANCER CELL (구강암세포주에서의 Tamoxifen의 항암효과)

  • Jung, Jae-Hwa;Yun, Pil-Young;Myoung, Hoon;Shin, Jae-Il;Lee, Jong-Ho;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.29 no.6
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    • pp.365-373
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    • 2003
  • Tamoxifen is an selective estrogen receptor antagonist widely used in the management of patients with breast cancer for more than 30 years. It was thought to act primarily through occupying the estrogen receptor sites in ER positive breast cancer cells and directly on cancer cell proper. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanism of therapeutic action of tamoxifen. The purposes of this study were to identify ER in oral carcinoma cell lines and to evaluate ER independent cytotoxic effect of tamoxifen. KB(SCC), HSC-3(SCC) and A253(ACC) cell line were used and capacity of cell proliferation, apoptosis, in vitro invasion and gelatin zymography were tested. ER expression of each cell line were detected by RT-PCR and immunocytochemistry. Dose dependent inhibition of cell proliferation and inhibition of gelatinolytic activity were observed in all oral carcinoma cell lines and significant difference of apoptotic index were observed in A253 and KB. Tamoxifen inhibited in vitro invasion in all experimental groups. ER expression was detected in KB and A253. These data suggest that tamoxifen may play a role in management of oral carcinoma by independent cytotoxic effect and more advanced research must processed confirming ER-dependent cytotoxicity.

The increasing hematopoietic effect of the combined treatment of Korean Red Ginseng and Colla corii asini on cyclophosphamide-induced immunosuppression in mice

  • Lee, Yuan Yee;Irfan, Muhammad;Quah, Yixian;Saba, Evelyn;Kim, Sung-Dae;Park, Seung-Chun;Jeong, Myung-Gyun;Kwak, Yi-Seong;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.591-598
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    • 2021
  • Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8+ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

Novel Inhibitors of Prolyl 4-Hydroxylase; Solid-phase Synthesis of 2,2-Dimethyl-3,4-Dialkoxy-Substituted 6-Aminobenzopyran Derivatives

  • Seo, Jin-soo;Joo, Yang-Hee;Yi, Jung-Bum;Lee, Eun-Ju;Lee, Nam-Kyu;Cho, Yong-Balk;Kwak, Wie-Jong;Hwang, Jong-Yeon;Jeon, Yong-Seog;Jeon, Hyun-Suk;Yoo, Sung-eun;Yoon, Cheol-Min;Dong, Mi-Sook;Gong, Young-Dae
    • Bulletin of the Korean Chemical Society
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    • v.27 no.6
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    • pp.909-917
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    • 2006
  • 2,2-Dimethyl-3,4-dialkoxy-substituted 6-aminobenzopyran analogues (eg., 7 and 8) were identified as prolyl 4-hydroxylase inhibitors via a screening process using HSC-T6 and LI 90 cells that express an immortalized rat hepatic stellate cell line and as part of a test of the type I collagen contents employing the ELISA method. A subsequent lead optimization effort based on solid-phase parallel synthesis led to the identification of 2,2-dimethyl-3,4-dialkoxy-substituted 6-aminobenzopyrans as potent inhibitors of prolyl 4-hydroxylase.

Microstructure Observation of the Grain Boundary Phases in ATF UO2 Pellet with Fission Gas Capture-ability (핵분열 기체 포획 기능을 갖는 사고저항성 UO2 펠렛에서 형성되는 입계상의 미세구조 관찰)

  • Jeon, Sang-Chae;Kim, Dong-Joo;Kim, Dong Seok;Kim, Keon Sik;Kim, Jong Hun
    • Journal of Powder Materials
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    • v.27 no.2
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    • pp.119-125
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    • 2020
  • One of the promising candidates for accident-tolerant fuel (ATF), a ceramic microcell fuel, which can be distinguished by an unusual cell-like microstructure (UO2 grain cell surrounded by a doped oxide cell wall), is being developed. This study deals with the microstructural observation of the constituent phases and the wetting behaviors of the cell wall materials in three kinds of ceramic microcell UO2 pellets: Si-Ti-O (STO), Si-Cr-O (SCO), and Al-Si-Ti-O (ASTO). The chemical and physical states of the cell wall materials are estimated by HSC Chemistry and confirmed by experiment to be mixtures of Si-O and Ti-O for the STO; Si-O and Cr-O for SCO; and Si-O, Ti-O, and Al-Si-O for the ASTO. From their morphology at triple junctions, UO2 grains appear to be wet by the Si-O or Al-Si-O rather than other oxides, providing a benefit on the capture-ability of the ceramic microcell cell wall. The wetting behavior can be explained by the relationships between the interface energy and the contact angle.