• Biomolecules & Therapeutics
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• 제29권2호
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• pp.205-210
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• 2021

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

• Nutrition Research and Practice
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• 제15권1호
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• pp.12-25
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• 2021

BACKGROUND/OBJECTIVES: The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. MATERIALS/METHODS: Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. RESULTS: At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. CONCLUSIONS: We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

• 보존과학회지
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• 제38권1호
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• pp.33-44
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• 2022

The study, iron-making process was examined through the scientific analysis of six by-products that were obtained during iron making at the Songdu-ri site in Jincheon. The total Fe content of the slags excavated from the Songdu-ri site was 36.29-54.61 wt%, whereas the deoxidation agent was 26.48-49.08 wt%. The compound analysis result indicated that fayalite and wüstite are the main compounds in slag. Furthermore, the microstructure analysis result confirmed the presence of fayalite and wüstite in the slag. It can be inferred from the flat shape in a bright matrix structure of the hammer scales that forging was performed in the latter stage. The Raman micro-spectroscopy results confirmed that the surface was hematite (Fe₂O₄), middle layer was magnetite (Fe₃O₄), and inner layer was wüstite (FeO). The presence of smelting and smithing slags, spheroid hammer scales, and flake hammer scales suggests that at the Songdu-ri site, iron-making process is carried out by division of labor into producing iron bloom through direct smelting, refining and forge welding, and ingot production.

• International Journal of Stem Cells
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• 제15권1호
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• pp.104-111
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• 2022

Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InS^exp) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs). We did functional chararcterization of InS^exp derived from 3D HIOs, differentiated from human pluripotent stem cells, and optimization culture methods. Our results indicate that InS^exp can be rapidly expanded and easily passaged, and show enhanced growth rates via WNT pathway activation. InS^exp are capable of exponential cell expansion and cryopreservation. Furthermore, in vitro-matured HIO-derived InS^exp proliferate faster than immature HIO-derived InS^exp with preservation of the parental HIO characteristics. These findings may facilitate the development of scalable culture systems for the long-term maintenance of human ISCs and provide an alternative platform for studying ISC biology.

• KSBB Journal
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• 제16권1호
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• pp.24-29
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• 2001

급성 간부전 환자나 간이식 대기 상태의 환자의 생명을 간이 재생되거나 간 이식때 까지 연장시키기 위하여 생인공간이 많이 연구되고 있다. 본 연구에서는 적당한 cell opening을 가지는 폴리우레탄 폼을 15% NCO-prepolymer를 이용하여 직접 제조하였으며 이를 직경 3~4 mm 크기의 정육면체로 절단하여 충진형 반응기를 제조하였다. 분리된 일차간세포를 원심분리 방법을 이용하여 PUF 1 $cm^3$ 당 5.5$\pm$1.1$\times$$10^6$개의 세포를 접종하였으며 일주일간 관류 배양하면서 생인공간으로서의 성능을 측정하였다. 접종된 간세포는 구상체를 형성하였고 안정된 암모니아 제거능력과 요소 분비율을 나타내었다. 알부민 분비율은 배양 4일 이후 감소하는 경향을 보였다. 이상의 결과를 볼 때 PUF 충진형 간세포 반응기는 생인공간으로 개발되기에 충분한 가능성을 가진 것으로 판단된다.

• 터널과지하공간
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• 제26권2호
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• pp.100-109
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• 2016

이 연구에서는 횡등방성 암석파괴함수의 개발에 활용할 수 있는 3가지 강도정수 공간분포함수를 제안하였다. 제안된 분포함수는 편구(oblate spheroid)분포함수, 지수분포함수, 강도정수텐서 방향투영함수이며 모두 2개의 모델파라미터로 정의된다. 제안된 분포함수들을 점착력과 마찰각의 공간분포함수로 활용하여 횡등방성 Mohr-Coulomb 파괴함수를 유도한 후 이를 활용하여 수치삼축시험을 모사하였다. 연약면의 경사각과 구속압의 변화에 따른 파괴축응력 변화 및 파괴면 방향 변화를 계산한 결과 3개의 분포함수을 적용한 경우 모두 실제 실험에서 관찰되는 이방성 파괴특성을 재현하고 있음을 확인하였다. 3개의 분포함수 중 강도정수텐서 방향투영함수를 채용한 경우가 가장 큰 파괴축강도를 계산하였으며 지수분포함수, 편구분포함수 순으로 낮은 파괴축강도 값을 예측하였다.

• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1830-1840
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• 2019

Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a three-dimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of β-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/β-catenin signaling pathway.

• BMB Reports
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• 제51권10호
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• pp.514-519
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• 2018

Ovarian cancer is the most fatal gynecological malignancy in women and identification of new therapeutic targets is essential for the continued development of therapy for ovarian cancer. TRRAP (transformation/transcription domain-associated protein) is an adaptor protein and a component of histone acetyltransferase complex. The present study was undertaken to investigate the roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer stem cells. TRRAP expression was found to be up-regulated in the sphere cultures of A2780 ovarian cancer cells. Knockdown of TRRAP significantly decreased cell proliferation and the number of A2780 spheroids. In addition, TRRAP knockdown induced cell cycle arrest and increased apoptotic percentages of A2780 sphere cells. Notably, the mRNA levels of stemness-associated markers, that is, OCT4, SOX2, and NANOG, were suppressed in TRRAP-silenced A2780 sphere cells. In addition, TRRAP overexpression increased the mRNA level of NANOG and the transcriptional activity of NANOG promoter in these cells. Furthermore, TRRAP knockdown significantly reduced tumor growth in a murine xenograft transplantation model. Taken together, the findings of the present study suggest that TRRAP plays an important role in the regulation of the proliferation and stemness of ovarian cancer stem cells.

• 천문학회보
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• 제36권2호
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• pp.115.1-115.1
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• 2011

We analyzed the line profiles of the planetary nebula (PN) NGC 7009 secured with the Keck I HIES and BOES's spectral data. The 5 positions were taken over the nebular image, 4 points on the bright rim plus 1 point at the central position. The covered spectral wavelength range was $3250{\AA}-8725{\AA}$ in these observations. We decomposed the lines of HI, HeI, HeII, CII, NIII, [ClIII], [NII], [OII], [OIII], [SII], [SIII], [ClIII], and [ArIII] using the IRAF and StarLink/Dipso. After correcting the Earth's movement and the PN's radial velocities, -48.6 & -48.9 km/s, respectively, for the Keck & BOES, we produced the line profiles in a velocity scale. The zero velocity at each line profile clearly indicates which part of the components is approaching or receding, giving a general information of the kinematical structure. Almost all of the low-to-medium excitation lines, such as [NII], [SII], [O III], and [ArIII], secured at the central position and four positions along the major & minor axes, showed 3 components, double peak + a wide wing component, suggesting the fast outflow structures are present. The overall geometry is a prolate shell which also has a fainter outer shell in the halo zone, but there appears to be some peculiar sub-structures inside the main shell. The high excitation He I, HeII, NIII lines which might be formed close to the inner boundary of the shell show unusual features, completely different from the other lines. The HeII and these high excitation lines may be indicative of a relative recent fast outflow from the central star and the permitted lines such as NIII might be affected by the innermost structure. We discuss a possible presence of a jet-like fast outflow structure in an out-flow axis different from the main axis of the spheroid shell.

• 천문학회보
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• 제37권2호
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• pp.211.1-211.1
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• 2012

The on-orbit test simulation for predicting the instrument directional responsivity was conducted by the Monte Carlo based integrated ray tracing (IRT) computation technique and analytic flux-to-signal conversion algorithms. For the on-orbit test simulation, the Sun model consists of the Lambertian scattering sphere and emitting spheroid rays, the Amon-Ra instrument is a two-channel including a broadband scanning radiometer (energy channel) and an imager with ${\pm}2^{\circ}$ FOV (visible channel). The solar radiation produced by the Sun model is directed to the instrument viewing port and traced through the dual channel optical train. The instrument model is rotated on its rotation axis and this gives a slow scan of the Sun model over the full field of view. The direction of the incident lights are fed with scanned images obtained from the visible channel instrument. The instrument responsivity was computed by the ratio of the incident radiation input to the instrument output. In the radiometric simulation, especially, measured BRDF of the 3D CPC was used for scattering effects on radiometry. With diamond turned 3D CPC inner surface, the anisotropic surface scattering model from the measured data was applied to ray tracing computation. The technical details of the on-orbit test simulation are presented together with field-of-view calibration plan.