• 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.

• Journal of Conservation Science
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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.

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

Recently hepatocyte-based bioartificial liver (BAL) and hepatocyte transplantation have been actively investigated to treat acute hepatic failure. The BAL acts as a bridge to provide patients with more time until a donor organ becomes available for transplantation or until their own liver can be regenerated. In this study, we manufactured a polyurethane foam (PUF) using 15% NCO-prepolymer with a pore opening that allows it to be used as a hepatocyte immobilizing material. Cubes of PUF (3 mm dim.) were seeded with rat primary hepatocytes at a density of 5.5$\pm$1.1$\times$ $10^6$ cells/$cm^3$ PUF by centrifuging them together. The cell laden PUF cubes were packed into a prototype reactor and perfused with a hormonally defined medium for a week. Hepatocytes in the pores of the PUF formed spheroids that showed stable ammonia removal and urea synthesis activities. The albumin production level was comparable to other BAL systems. The PUF packed hepatocyte bioreactor has the potential to be used as a BAL.

• Tunnel and Underground Space
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• 제26권2호
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• pp.100-109
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• 2016

This study suggests three spatial distribution functions of strength parameters, which can be adopted in the derivation of failure conditions for transversely isotropic rocks. All three proposed functions, which are the oblate spheroidal function, the exponential function, and the function based on the directional projection of the strength parameter tensor, consist of two model parameters. With assumption that the cohesion and friction angle can be described by the proposed distribution functions, the transversely isotropic Mohr-Coulomb criterion is formulated and used as a failure condition in the simulation of the conventional triaxial tests. The simulation results confirm that the failure criteria incorporating the proposed distribution functions could reproduce the general trend in the variations of the axial stress at failure and the directions of failure planes with varying inclination of the weankness planes and confining pressure. Among three distribution functions, the function based on the directional projection of the strength parameter tensor yields the highest axial strength, while the axial strength estimated by the oblate spheroidal distribution function is the lowest.

• 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.

• The Bulletin of The Korean Astronomical Society
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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.

• The Bulletin of The Korean Astronomical Society
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.493-502
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• 2020

Apigenin, a naturally occurring flavonoid, is known to exhibit significant anticancer activity. This study was designed to determine the effects of apigenin on two malignant mesothelioma cell lines, MSTO-211H and H2452, and to explore the underlying mechanism(s). Apigenin significantly inhibited cell viability with a concomitant increase in intracellular reactive oxygen species (ROS) and caused the loss of mitochondrial membrane potential (ΔΨm), and ATP depletion, resulting in apoptosis and necroptosis in monolayer cell culture. Apigenin upregulated DNA damage response proteins, including the DNA double strand break marker phospho (p)-histone H2A.X. and caused a transition delay at the G₂/M phase of cell cycle. Western blot analysis showed that apigenin treatment upregulated protein levels of cleaved caspase-3, cleaved PARP, p-MLKL, and p-RIP3 along with an increased Bax/Bcl-2 ratio. ATP supplementation restored cell viability and levels of DNA damage-, apoptosisand necroptosis-related proteins that apigenin caused. In addition, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin. In a 3D spheroid culture model, ROS-dependent necroptosis was found to be a mechanism involved in the anti-cancer activity of apigenin against malignant mesothelioma cells. Taken together, our findings suggest that apigenin can induce ROS-dependent necroptotic cell death due to ATP depletion through mitochondrial dysfunction. This study provides us a possible mechanism underlying why apigenin could be used as a therapeutic candidate for treating malignant mesothelioma.

• Journal of Veterinary Science
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• 제22권3호
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• pp.25.1-25.16
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• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.