• Journal of Life Science
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• v.30 no.7
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• pp.651-659
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• 2020

Cardiovascular disease is one of the leading causes of death across the world, and gold-standard treatments such as percutaneous coronary intervention and artery bypass grafting have various limitations including myocardial damage and subsequent maladaptive cardiac remodeling. To overcome this, stem-cell therapies are emerging as a promising strategy for cardiovascular regeneration. Endothelial progenitor cells (EPCs) have high potential to proliferate and differentiate into endothelial cells for vascularization and tissue regeneration, and several clinical trials have explored EPC function in tissue repair in relation to clinical safety and improving cardiac function. Consequently, EPC has been suggested as a feasible stem-cell therapy. However, autologous EPC transplantation in cardiovascular disease patients is restricted by risk factors such as age, smoking status, and hypertension that lead to reduced bioactivity in the EPCs. New approaches for improving EPC function and stem-cell efficacy have therefore been suggested, including cell priming, organoid culture systems, and enhancing transplantation efficiency through 3D bioprinting methods. In this review, we provide a comprehensive understanding of EPC characteristics, therapeutic approaches, and the current state of clinical research into EPCs as stem-cell therapy for cardiovascular disease.

• Journal of fish pathology
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• v.11 no.2
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• pp.89-96
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• 1998

Marine birnavirus (MABV) has wide host range in marine organisms. To clarify various infection properties of MABV in different host species, in vitro study was performed by subculture for 10 passages in several fish cell lines. In CHSE-214, RTG-2 and RSBK-2 cells, the virus produced high yield of virus. Typical CPE with high protein expression was observed in these cells. On the contrary, the virus grown in EPC, FHM and BF-2 cells exhibited no CPE appearance although virus protein was detected. In EPC and FHM cells, the virus titer increased in later passages. The plaque size was distinctly bigger in CHSE-214, RTG-2 and RSBK-2 cells than in other cell lines. The nucleotide sequence of VP2/NS junction region on genome segment A exhibited one specific nucleotide change at 195. The different infection properties in several cell types performed in the present work might reflect in vivo MABV infection in various host species occurring in natural conditions.

• The Korean Journal of Pesticide Science
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• v.18 no.1
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• pp.8-13
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• 2014

This study evaluated in vitro cytotoxicity of 5 pesticides, including 2 herbicides, 2 germicides, and an insecticide, as an alternative to the fish acute toxicity test. The in vitro cytotoxicity was tested using a neutral red uptake (NRU) assay with epithelioma papulosum cyprini (EPC) cells that originated from the epidermal tissue of Cyprinus carpio (common carp). An in vivo fish acute toxicity test was conducted according to OECD Test Guideline No. 203 using Aphyocypris chinensis (Chinese bleak), Oryzias latipes (Japanese medaka), and C. carpio. The results showed that the sensitivity of the cell viability assay for the pesticides was similar to the fish acute test in ranking order despite having approximately 10 times less absolute sensitivity. The $r^2$ correlation values were calculated as 0.38 (p = 0.26), 0.76 (p = 0.05) and 0.90 (p = 0.01) for A. chinensis, O. latipes, and C. carpio, respectively. These results suggested that the potential of EPC cell viability assay as an alternative to the fish acute toxicity test due to their good correlation and NRU assay is expected to serve as a useful tool for predicting acute fish lethality for pesticides if further studies with a large set of pesticides are conducted.

• Journal of fish pathology
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• v.11 no.2
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• pp.129-136
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• 1998

In March 1997, a new rhabdovirus was isolated from moribund cultured Japanese flounder Paralichthys olivaceus in sea water tank and cage culture systems in Kyung-Nam and Chun-Nam province, Korea. At temperature $15^{\circ}C$ the virus replicated and induced cytopathic effects (CPE), which progressed to eventual cytolysis, in susceptible cell lines, including RTG-2 and EPC. The CHES-214 cell line was refractory. Virus particles were bullet-shaped and measured $70nm{\times}100$ to 150 nm in size. The isolate was sensitive to pH 3, to diethyl ether, and to heat ($50^{\circ}C$ 5 min, $60^{\circ}C$ 1 min). Viral replication was not inhibited by $10^{-4}$ M 5-iododeoxyuridine. Virus infectivity was reduced by anti-HRV (8401-H) rabbit serum, but can not reduced by antisera against infectious hematopoietic necrosis virus (IHNV), chum salmon reovirus (CSV), retrovirus of salmonid (RVS) and infectious pancreatic necrosis virus (IPNV). HRV virus antigen was detected by fluorescent antibody test (FAT) in the cytoplasm of infected EPC cell. Purified isolates virions were composed of: polymerase (L), glycoprotein (G), nucleoprotein (N) and 2 matrix proteins (M1 and M2). Based upon their relative mobilities, the estimated molecular weights of the proteins were: L, 160 kDa; G, 55 kDa; N, 45 kDa; M1, 26 kDa; and M2, 22 kDa.

• Journal of fish pathology
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• v.12 no.1
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• pp.56-62
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• 1999

Since 1998, mass mortality of the Japanese flounder has widely occurred in the south and west coastal area of Korea. A new serotype birnavirus was isolated during the investigation of the cause of the disease. By the electromicroscopic examination, the isolated virus particles appeared hexagonal and unenveloped with an average diameter 52 to 56 nm. Birnavirus specific fragment was amplified by RT-PCR. High yield of virus (10.3 to 10.8 log $TCID_{50}/ml$) was produced in CHSE-214. RTG-2 and RTE-2 cells. Typical birnavirus CPE was observed in these cells. On the contrary, the virus CPE was not shown in the FHM and EPC cells. By a cross-neutralization test with IPNV Ab, IPNV Sp, IPNV VR-299 and MBV Y6, the isolated virus was closely related to marine birnavirus (MBV).

• Polymer(Korea)
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• v.33 no.6
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• pp.602-607
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• 2009

A polyurethane (PU) surface enabling in vivo endothelialization via endothelial progenitor cell (EPC) capture was prepared for cardiovascular applications. To introduce CD34 monoclonal antibody (mAb) inducing EPC adhesion onto a surface, poly (poly (ethylene glycol) acrylate-co-butyl methacrylate) and poly (PEGA-co-BMA) were synthesized and then coated on a surface of PU, followed by immobilizing CD34 mAb. $^1H$-NMR analysis demonstrated that poly(PEGA-co-BMA) copolymers with a desired composition were synthesized. Poly(PEGA-co-BMA)-coated PU was much more effective for the immobilization of CD34 mAb, comparing with PEG-grafted PU prepared in our previous study, as demonstrated by that surface density and activity of CD34 mAb increased over 32 times. Physico-chemical properties of modified PU surfaces were characterized by X-ray photoelectron spectroscopy (XPS), water contact angle, and atomic force microscopy (AFM). The results demonstrated that the poly(PEGA-co-BMA) coating was effective for CD34 mAb immobilization and feasible for applying to cardiovascular biomaterials.

• Journal of fish pathology
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• v.15 no.1
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• pp.9-16
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• 2002

The objective of the study was to clarify the mechanism of persistent infection of marine birnavirus (MABV) in various nonpermissive cell lines. It was observed in CHSE-214, RTG-2 and RSBK-2 that the virus produced at high yield with typical cytopathic effect (CPE). On the contrary, the CPE was not produced in EPC, FHM and BF-2 cells. However amount of virus protein in both permissive and nonpermissive cell lines detected by ELISA was almost the same. Electron microscopy showed virions in permissive cells but not in nonpermissive cells. From the results, it is clear that virus protein and RNA were produced in nonpermissive cells as observed in permissive cells; however, assembly of the virus particles did not occur in nonpermissive cells.

• Molecules and Cells
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• v.41 no.6
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• pp.582-590
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• 2018

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of $CD34^+$ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against $H_2O_2$-induced oxidative stress via the augmented expression of Bcl-2, a pro-survival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

• Journal of fish pathology
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• v.11 no.2
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• pp.97-104
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• 1998

Since 1989, mass mortality has repeatly occurred in cage-cultured sevenband grouper, Epinephelus septemfasciatus along the southern coast of Korea in the summer season and usually reached over 80% within a few months. Diseased fish showed the clinical signs of anorexia, dark coloration, loss of eqilibrium, spinal swimming behaviour, vertebral deformity and inflation of swim bladder. Histopathologically, necrosis and/or vacuolation of the nerve cells in the brain and retina were observed. We previously reported that the causative agent was filtrable. The causative agent was not culturable in various fish cells; RTG-2, CHSE-214, BF-2, EPC and FHM. However, electron microscopic observation revealed unenveloped icosahedral viral particles with about 30 nm in diameter in the cytoplasm of nerve cells of the brain. The characteristics of the virus was tested by an artificial infection with the filtrate of the homogenate of diseased fish. The pathogenicity of the virus was retained after treatment with ether or heat ($50^{\circ}C$, 30 min) but partly lost by pH 3 or 11 treatment. These results suggest that the causative agent are similar to the fish nodavirus. In order to compare the causative agent with a fish nodavirus, Striped Jack Nervous Necrosis Virus (SJNNV), a polymerase chain reaction (PCR) was performed with primers specific to SJNNV. As a result, about 430 by PCR products were detected from the brain and the eye of both naturally and artificially infected sevenband grouper. All these results represent that the mass mortality in the cultured sevenband grouper is caused by the infection of a nodavirus similar to SJNNV and this is the first report of a fish nodavirus from the cultured sevenband grouper in Korea.

• Molecules and Cells
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• v.37 no.6
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• pp.487-496
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• 2014

Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout ($AGT^{+/-}$) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of $AGT^{+/-}$ EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in $AGT^{+/-}$ EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-$1{\alpha}$and $-2{\alpha}$ were downregulated in $AGT^{+/-}$ early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-$1{\alpha}$ were suppressed in $AGT^{+/-}$ EPCs. In $AGT^{+/-}$ mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.