• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.441-452
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• 2020

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

• Journal of Veterinary Science
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• v.22 no.3
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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.

• Journal of Microbiology and Biotechnology
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• v.32 no.5
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• pp.645-656
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• 2022

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.449-462
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• 2023

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.94-103
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• 2024

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

• The Bulletin of The Korean Astronomical Society
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• v.42 no.1
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• pp.30.2-31
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• 2017

Compact elliptical (cE) galaxies are in a rare class of stellar systems characterized by high stellar densities, small sizes, high velocity dispersion, and high metallicity corresponding to elliptical galaxies. cE galaxies have been observed around massive galaxies, so they could be formed under strong influences of tidal stripping and truncation. However, the recent discovery of isolated cE galaxies requires the need of new formation scenarios. We aim at finding cE galaxies in various environments using SDSS DR12, and studying stellar population of cEs as function of environments. Based on the typical properties of cE galaxies, we selected cE candidates by restricting that low-luminosity Mg > 19.5 mag, small sizes Re < 700 pc, and high velocity dispersions ${\sigma}$ > $60kms^{-1}$. Since effect radii of cE candidates are mostly smaller than the seeing size of SDSS photometry, we calculated the effective radius by fitting a Sersic profile. In addition, we assumed that host galaxies have brightness with Mr < -21 mag, and an environmental parameter is computed as distances between cE galaxies and host-galaxies. We found 112 cE galaxies at z < 0.05, which have high sersic indices (mean value is 5.2) similar to the typical massive elliptical galaxies. Mgb values of cE galaxies increase as the distances from the host galaxies decrease. Especially, for cEs close to the host galaxies (NcE; $D_{host}$ < 300 pc), the Mgb values are similar to those of massive elliptical galaxies, which is consistent with the previous studies. On the other hand, cE galaxies distant from the host galaxies (DcE; Dhost >300 pc) have lower Mgb values than the conventional cE. The Mgb values follow the ${\sigma}$-Mgb relation of elliptical galaxies, and are connected to its faint end. This can be explained as a result of different merger histories for differing environments. For example, NcE galaxies are formed by tidal stripping by massive galaxies as suggested by previous studies, but DcE galaxies could be linked with high-redshift spheroids (e.g. red nuggets) which have not evolved into present-day elliptical galaxies because of the environmental influences.

• Journal of the Mineralogical Society of Korea
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• v.21 no.1
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• pp.27-35
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• 2008

Characterization of mineralogy and nanocrystals of ingredient materials of $Lumilite^{(R)}$ used for water treatment was made using optical microscopy, XRD, SEM, FTIR, and XRF analyses. Constituent minerals identified by XRD and microscope are clinoptilolite, illite, quartz, and albite, characterized by dense and fine texture. The cross section of nanocrystals with the size $70{$\sim}100\;nm$ is generally round or subround. Numerous spheroids with few nanometers in diameter are extensively formed on the surface of nanocrystals. Bulk chemistry is $SiO_2$ $74.22{\sim}75.65\;wt.%$, $Al_2O_3$ $13.25{\sim}13.72\;wt.%$, CaO $4.23{\sim}5.15\;wt.%$, with other major elements being minimal. When heated to $700^{\circ}C$, the crystal structure was mostly destroyed, though it persisted to $500^{\circ}C$. It is likely that high capacity and applications of $Lumilite^{(R)}$ for water treatment are originated from its structural properties such as development of nanocrystals and various tiny pores.

• Journal of the Society of Naval Architects of Korea
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• v.33 no.3
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• pp.35-47
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• 1996

A surface panel method treating a boundary-value problem of the Dirichlet type is presented to design a three dimensional body with free surface corresponding to a prescribed pressure distribution. An integral equation is derived from Green's theorem, giving a relation between total potential of known strength and the unknown local flux. Upon discretization, a system of linear simultaneous equations is formed including free surface boundary condition and is solved for an assumed geometry. The pseudo local flux, present due to the incorrect positioning of the assumed geometry, plays a role f the geometry corrector, with which the new geometry is computed for the next iteration. Sample designs for submerged spheroids and Wigley hull and carried out to demonstrate the stable convergence, the effectiveness and the robustness of the method. For the calculation of the wave resistance, normal dipoles and Rankine sources are distributed on the body surface and Rankine sources on the free surface. The free surface boundary condition is linearized with respect to the oncoming flow. Four-points upwind finite difference scheme is used to compute the free surface boundary condition. A hyperboloidal panel is adopted to represent the hull surface, which can compensate the defects of the low-order panel method. The design of a 5500TEU container carrier is performed with respect to reduction of the wave resistance. To reduce the wave resistance, calculated pressure on the hull surface is modified to have the lower fluctuation, and is applied as a Dirichlet type dynamic boundary condition on the hull surface. The designed hull form is verified to have the lower wave resistance than the initial one not only by computation but by experiment.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.933-941
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• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• Journal of Radiation Protection and Research
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• v.39 no.1
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• pp.7-13
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• 2014

Phosphate rock, phosphogypsum, and products in phosphate processing facility contain naturally occurring radioactive materials (NORM). Therefore, they may give rise to enhanced radiation dose to workers due to inhalation of airborne particulates. Internal dose due to particle inhalation varies depending on particle properties. The objective of the present study was to characterize particle properties at the largest phosphate processing facility in Korea. A cascade impactor was employed to sample airborne particulates at various processing areas in the plant. The collected samples were used for characterization of particle size distribution, particle concentration in the air, and shape analysis. Aerodynamic diameters of airborne particulates ranged 0.03-100 ${\mu}m$ with the highest concentration at the particle size range of 4.7-5.8 ${\mu}m$ (geometric mean = 5.22 ${\mu}m$) or 5.8-9.0 ${\mu}m$ (geometric mean = 7.22 ${\mu}m$). Particle concentrations in the air varied widely by sampling area up to more than two orders of magnitude. The large variation resulted from the variability of mechanical operations and building ventilations. The airborne particulates appeared as spheroids or rough spherical fragments across all sampling areas and sampled size intervals. Average mass densities of phosphate rocks, phosphogypsums, and fertilizers were 3.1-3.4, 2.1-2.6, and 1.7 $gcm^{-3}$, respectively. Radioactivity concentration of uranium series in phosphate rocks varied with country of origin, ranging 94-866 $Bqkg^{-1}$. Among the uranium series, uranium was mostly concentrated on products, including phosphoric acid or fertilizers whereas radium was concentrated on byproducts or phosphogypsum. No significant radioactivity of $^{226}Ra$ and $^{228}Ra$ were found in fertilizer. However, $^{40}K$ concentration in fertilizer was up to 5,000 Bq $g^{-1}$. The database established in this study can be used for the accurate risk assessment of workers due to inhalation of airborne particles containing NORM. In addition, the findings can be used as a basic data for development of safety standard and guide and for practical radiation safety management at the facility.