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Ahnak depletion accelerates liver regeneration by modulating the TGF-β/Smad signaling pathway

  • Yang, Insook;Son, Yeri;Shin, Jae Hoon;Kim, Il Yong;Seong, Je Kyung
    • BMB Reports
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    • v.55 no.8
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    • pp.401-406
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    • 2022
  • Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

HPV-18 E7 Interacts with Elk-1 Leading to Elevation of the Transcriptional Activity of Elk-1 in Cervical Cancer

  • Go, Sung-Ho;Rho, Seung Bae;Yang, Dong-Wha;Kim, Boh-Ram;Lee, Chang Hoon;Lee, Seung-Hoon
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.593-602
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    • 2022
  • The human papillomavirus (HPV)-18 E7 (E7) oncoprotein is a major transforming protein that is thought to be involved in the development of cervical cancer. It is well-known that E7 stimulates tumour development by inactivating pRb. However, this alone cannot explain the various characteristics acquired by HPV infection. Therefore, we examined other molecules that could help explain the acquired cancer properties during E7-induced cancer development. Using the yeast two-hybrid (Y2H) method, we found that the Elk-1 factor, which is crucial for cell proliferation, invasion, cell survival, anti-apoptotic activity, and cancer development, binds to the E7. By determining which part of E7 binds to which domain of Elk-1 using the Y2H method, it was found that CR2 and CR3 of the E7 and parts 1-206, including the ETS-DNA domain of Elk-1, interact with each other. As a result of their interaction, the transcriptional activity of Elk-1 was increased, thereby increasing the expression of target genes EGR-1, c-fos, and E2F. Additionally, the colony forming assay revealed that overexpression of Elk-1 and E7 promotes C33A cell proliferation. We expect that the discovery of a novel E7 function as an Elk-1 activator could help explain whether the E7 has novel oncogenic activities in addition to p53 inactivation. We also expect that it will offer new methods for developing improved strategies for cervical cancer treatment.

Houttuynia cordata Thunberg exhibits anti-tumorigenic activity in human gastric cancer cells

  • Hong, Se Chul;Eo, Hyun-Ji;Song, Hoon-Min;Woo, So-Hee;Kim, Mi-Kyeong;Lee, Jin-Wook;Seo, Jeong-Min;Park, Su-Bin;Eom, Jung-Hye;Koo, JinSuk;Jeong, JinBoo
    • The Korea Journal of Herbology
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    • v.28 no.6
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    • pp.155-160
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    • 2013
  • Objectives : Gastric cancer is a leading cause of cancer-related deaths, worldwide. Houttuynia cordata Thunberg (H. cordata) has been used as a medicinal plants and it has an anti-cancer activity in human colorectal cancer and leukemic cancer. However, the potential anti-cancer activity and mechanisms of H. cordata for human gastric cancer cells have not been tested so far. Thus, this study examined the biological effects of H. cordata on the human gastric cancer cell line SNU-1 and AGS. Methods : Inhibition of cell proliferation and cell cycle by H. cordata was carried out by MTT assay and Muse cell cycle analysis and the expressions of protein associated with apoptosis and cell cycle regulation were investigated with Western blot analysis. Results : In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by H. cordata in a time and dose dependent manner, Inhibition of cell proliferation by H. cordata was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bax to Bcl-2 by H. cordata. Also, H. cordata regulated the expression of cell cycle regulatory proteins such as pRb, cyclin D1, cyclin E, CDK4, CDK2, p21 and p15. Conclusion : The antiproliferative effect of H. cordata on SNU-1 and AGS gastric cancer cells revealed in this study suggests that H. cordata has intriguing potential as a chemopreventive or chemotherapeutic agent.

DK-MGAR101, an extract of adventitious roots of mountain ginseng, improves blood circulation by inhibiting endothelial cell injury, platelet aggregation, and thrombus formation

  • Seong, Hye Rim;Wang, Cuicui;Irfan, Muhammad;Kim, Young Eun;Jung, Gooyoung;Park, Sung Kyeong;Kim, Tae Myoung;Choi, Ehn-Kyoung;Rhee, Man Hee;Kim, Yun-Bae
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.683-689
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    • 2022
  • Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl3 (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H2O2) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B2 production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H2O2 cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B2 production, and granule release, but also in delaying blood coagulation, FeCl3-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.

Atomic Fountain towards a single atom trap (단원자 포획을 위한 원자분수)

  • H. S. Rawat;S. H. Kwon;Kim, J. B.;K. An
    • Proceedings of the Optical Society of Korea Conference
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    • 2000.08a
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    • pp.74-75
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    • 2000
  • The past few decades have witnessed the development of very robust technique, known as magneto-optical trap(MOT), for cooling and trapping of neutral atoms using lasers and magnetic fields. This technique can easily produce cooled atoms to a temperature range of nano-kelvin $s^{(1)}$ . These laser cooled and trapped atoms have found applications in various fields, such as ultrahigh resolution spectroscopy, precision atomic clocks, very cold atomic collision physics, Bose-Einstein Condensation, the Atom laser, etc. Particularly, a few isolated atoms of very low temperature are needed in the cavity QED studies in the optical regime. One can obtain such atoms from a MOT using the atomic fountain technique. The widely used technique for atomic fountain is, first to cool and trap the neutral atoms in MOT. And then launch them in the vertical (1, 1, 1) direction with respect to cooling beams, using moving molasses technique. Recently, this technique combined with the cavity-QED has opened an active area of basic research. This way atoms can be strongly coupled to the optical radiation in the cavity and leads to various new effects. Trapping of single atom after separating it from MOT in the high Q-optical cavity is actively initiated presentl $y^{(2.3)}$. This will help to sharpen our understanding of atom-photon interaction at quantum level and may lead to the development of single-atom laser. Our efforts to develop an $^{85}$ Rb-atomic fountain is in progress. (omitted)

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Geochemistry and Petrogenesis of Pan-african Granitoids in Kaiama, North Central, Nigeria

  • Aliyu Ohiani Umaru;Olugbenga Okunlola;Umaru Adamu Danbatta;Olusegun G. Olisa
    • Economic and Environmental Geology
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    • v.56 no.3
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    • pp.259-275
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    • 2023
  • Pan African granitoids of Kaiama is comprised of K-feldspar rich granites, porphyritic granites, and granitic gneiss that are intruded by quartz veins and aplitic veins and dykes which trend NE-SW. In order to establish the geochemical signatures, petrogenesis, and tectonic settings of the lithological units, petrological, petrographical, and geochemical studies was carried out. Petrographic analysis reveals that the granitoids are dominantly composed of quartz, plagioclase feldspar, biotite, and k-feldspar with occasional muscovites, sericite, and opaque minerals that constitute very low proportion. Major, trace, and rare earth elements geochemical data reveal that the rocks have moderate to high silica (SiO2=63-79.7%) and alumina (Al2O3=11.85-16.15) contents that correlate with the abundance of quartz, feldspars, and biotite. The rocks are calc-alkaline, peraluminous (ASI=1.0-<1.2), and S-type granitoids sourced by melting of pre-existing metasedimentary or sedimentary rocks containing Al, Na, and K oxides. They plot dominantly in the WPG and VAG fields suggesting emplacement in a post-collisional tectonic setting. On a multi-element variation diagram, the granitoids show depletion in Ba, K, P, Rb, and Ti while enrichment was observed for Th, U, Nd, Pb and Sm. Their rare-earth elements pattern is characterized by moderate fractionation ((La/Yb)N=0.52-38.24) and pronounced negative Eu-anomaly (Eu/Eu*=0.02-1.22) that points to the preservation of plagioclase from the source magma. Generally, the geochemical features of the granitoids show that they were derived by the partial melting of crustal rocks with some input from greywacke and pelitic materials in a typical post-collisional tectonic setting.

A Development of Integrated Prototype Model for Risk Management of Construction Projects (건설공사의 리스크관리를 위한 통합전산모형 구축)

  • Kim, Chang-Hak;Park, Seo-Young;Kang, In-Seok
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.26 no.3D
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    • pp.469-480
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    • 2006
  • The results of the study include a computerized system and a systematic process model for risk management and analysis. This study analyzes the present status of risk management in the construction industry, and then suggests reasonable methods for improved risk management plans. This study defines risk management procedures as preparation, identification, analysis, response and management to manage potential risks in the construction project. The modules for computerizing in this system consist of planning, construction, application of WBS (Work Breakdown Structure) and RBS (Risk Breakdown Structure), and risk analysis. The methodology for analyzing construction risk uses fuzzy theory, and the scope of developed system is focused to the contractors. The risk management system suggested in this study operates on the Internet, for providing contractors with a useful risk management tool by online system, with web-based menus that is helpful for practical application.

Development of a Risk Management Procedure Model for the Construction Project Using Construction Risk Management System (CRMS를 활용한 건설공사의 리스크관리 절차모형 개발)

  • Kim, Chang Hak;Kang, Leen Seok;Park, Hong Tae
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.30 no.4D
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    • pp.423-432
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    • 2010
  • This study suggested CRMS (construction risk management system) which is a new risk analysis model after analyzing existing risk management process for to guarantee a successful performance at the construction planning and work phase. CRMS is risk management procedures in order that the contractor identify, analyze and administrate the risk during performing construction project. This model may give much help to quantify and be ready the right managing methods about identified risk by the contractor. Especially, the most important and difficult things of all risk management may be to identify risk in the project. This study make more focusing on the developing a procedure that can identify risk more easily in the construction project. The risk is divided into global risk and local risk of a project. Also, this study suggests methods which are using the RBS (risk breakdown structure) related with WBS. This result will be useful as basic materials for developing computerizing system for risk management.

Ginseng root-derived exosome-like nanoparticles protect skin from UV irradiation and oxidative stress by suppressing activator protein-1 signaling and limiting the generation of reactive oxygen species

  • Wooram Choi;Jeong Hun Cho;Sang Hee Park;Dong Seon Kim;Hwa Pyoung Lee;Donghyun Kim;Hyun Soo Kim;Ji Hye Kim;Jae Youl Cho
    • Journal of Ginseng Research
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    • v.48 no.2
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    • pp.211-219
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    • 2024
  • Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry

  • Yoon Young Cho;Jeong Hill Park;Jung Hee Lee;Sungkwon Chung
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.301-308
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    • 2024
  • Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca2+ entry (CCE), a refilling mechanism of intracellular Ca2+, resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydiphenyl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.