• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.17-36
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• 1998

This experimental study was carried out to evaluate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism. In order to investigate the effects of Hwallakhyoreungdan on angiogenic inhibition mechanism, MTT assay, cell adhesive inhibition effect, DNA fragmantaion analysis, Nuclear condensation assay, FACScan analysis, Angiogenic lumen formation assay, Immunocytochemistry analysis, RT-PCR for mRNA expression, Western blot analysis and Confocal analysis for $Ca^{2+}$ change were performed. The results were summarized as follows: 1. The cell adhesive inhibition ability was strong from $5{\mu}g/ml$. 2. The $G_0/G_1$ arrest peak was existed on ECV304 cell-line. 3. The cells on Collagen plate were inhibition of proliferation and inducement of apoptosis by HR water extract. 4. Angiogenic lumen formation was inhibited by HR water extract. 5. LFA-1 and ELAM-1's expression were inhibited by HR water extract. They are commenly participation on inflammation and tumor regeneration. 6. The expression of MMP-9 and uPA were inhibited by HR water extract. 7. The expression of integrin ${\alpha}_v{\beta}_3$ was inhibited by HR water extract. 8. The expression of intracellular molecule were successively inhibited by HR water extract therefore the proliferation of ECV304 cell line was stopped and apoptosis was induced. 9. The change of $Ca^{2+}$ was decreased by HR water extract it cause confusion of signal transduction pathway therefore it was take part in apoptosis. According to the results, Hwallakhyoreungdan showed to be a key antaonist of integrin ${\alpha}_v{\beta}_3$, and to be induction of apoptosis by p53 through flow cytometry. This report also demonstrated that expressions of MMP-9 and uPA was blocked under the angiogenesis model. Thus, we suggests that Hwallakhyoreungdan blocks angiogenesis by inducing apoptosis of ECV304 and ECVPAR cell lines and another oriental herbal medicine that treats blood-stasis type also has angiogenic inhibition effects.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.108-112
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• 2016

Molecular imaging with the radiolabeled RGD peptides for ${\alpha}_v{\beta}_3$ integrin has been an increasing interest for tumor diagnosis and the treatment monitoring. Recently, $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ was developed for quantification of ${\alpha}_v{\beta}_3$ integrin and its biological properties was elucidated. To better understand the molecular process in vivo, we performed the kinetic analysis for the $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$. After preparation of a radiotracer, dynamic PET images were obtained in the U87MG xenograft mice for 60 min (n = 6). Binding potential values were estimated from the 3-tissue compartment model, reference Logan and simplified reference tissue model. In the early time frame (0-20 min), the liver, kidney, intestine, urinary bladder and tumor were visualized but these uptakes were diminished as time went by. The tumors showed a good contrast at 40 min after administration. $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ showed the 2-fold uptake in the tumor compared with that in the muscle. The parametric maps for binding values also provide the higher tumor-to-background contrast than the static images. A binding value obtained from the 3-tissue compartment model was comparable to other modeling methods. From these results, we conclude that $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ may be a promising PET radiotracer for the evaluation of angiogenesis.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.118-122
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• 2016

Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.45 no.4
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• pp.415-422
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• 2019

Human epidermal stem cells(ESCs) residing in the basement membrane of the skin have an important role in maintenance of skin homeostasis of epidermal layer. Although, ESCs provide new cells to repair damaged tissue in response to tissue injury, subsets of stem cells remain in the quiescent state protected from differentiation and senescence for prolonged survivals. In this perspective, the stem cell niche, which is specific microenvironment composed of niche cells and an extracellular matrix(ECM), supplies the relevant signal to save stem cells from microenvironmental damages. The expression of stemness marker on the surface of ESCs contributes to the attachment on their ECM of the basement membrane, which lead to growth potential and apoptotic resistance against environmental stimuli. In this study, we observed that UV irradiation, a major factor of environmental stimuli, reduced the expression of α2, β1 and α6 integrin in ESCs. Rhus Semialata M extract(RSE) showed inhibitory effect on the UVB-induced reduction of integrin expression. Furthermore, RSE could upregulate the expression of Col-IV and Laminin, which contribute to the attachment of ESCs. These results indicated that RSE could be a potent ingredient for the protection of ESCs from UV irradiation by increasing the expression of integrin and substrate ECM components at their niche.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.118-125
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• 2018

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), but the genes associated with the host immune system can be attributed to the development of TB. The ITGB2 gene encodes the integrin beta 2 chain CD18 protein and is present on chromosome 21. The integrin beta 2 chain is an integrin expressed in leukocytes and plays a very important role in leukocyte maturation and attachment. ITGB2 plays an important role in the phagocytosis of MTB and the aggregation of leukocytes in MTB infections. This study examined the genetic polymorphisms of the ITGB2 gene between the TB case and normal control using Korean genomic and epidemiologic data. As a result, a statistically significant correlation was confirmed in 10 SNPs. The most significant SNP was rs113421921 (OR=0.69, CI: 0.53~0.90, $P=5.8{\times}10^{-3}$). In addition, rs173098, one of the significant 10 SNPs, is possibly located in a binding motif with the transcription factor cofactor p300, and can affect ITGB2 gene expression. These findings suggest that the pathogenesis of TB may be influenced by a range of genetic factors related to the immune function of the host, e.g., the reactions associated with the recruitment and attachment of leukocytes. The results of this study could be used to predict the infection control for tuberculosis in a patient-tailored manner.

• Journal of Embryo Transfer
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• v.18 no.3
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• pp.243-248
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• 2003

Sperrnatogenesis, the process by which the male germ-line stem cells(GSCs; type A spermatogonia) divide and differentiate to produce the mature spermatozoa, occurs in the seminiferous tubules of the testis. The GSCs proliferate actively to produce two types of cells: other GSCs and differentiating spermatogonia. GSCs have unipotentcy, devoted solely to the generation of sperm. The function of GSCs has broad implications for development, disease, and evolution. Spermatogenesis is fundamental for propagation of species and the defects of this system can result in infertility or disease. The ability to identify, isolate, culture, and alter GSCs will allow powerful new approaches in animal transgenesis and human gene therapy relating to infertility. Until recently, research on stem cells in the testis has been limited because of technical difficulties in isolating and identifying these cell populations. Here, we were trying to find out optimal conditions for in vitro culture of GSCs for identifying and isolating GSCs. We collected mouse GSCs from 3-days old mouse by two-step enzyme digestion method. GSCs were plated and grown on mouse embryonic fibroblasts in Dulbecco's modified Eagle's medium (DMEM) containing 15％ fatal bovine serum, 10 mM 2-mercaptoethanol, 1％ non-essential amino acids, 1 ng/$m\ell$ bFGF, 10 $\mu$M forskolin, 1500 U/$m\ell$ human recombinant leukemia inhibitory factor (LIF). Over a period 3∼5 days, GSCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells. After 5th passages, cells within the colonies continued to be alkaline phosphatase and Oct-4 positive and tested positive against a panel of two immunological markers(Integrin $\alpha$ 6 and Integrin $\beta$ 1) that have been recognized generally to characterize GSCs. SSEA-1, SSEA-3, and SSEA-4 also showed positive signals. Based on our data, these GSCs-derived cultures meet the criteria for GSCs itself and even other pluripotent stem cells. We reported here the establishment of in vitro cultures from mouse male GSCs.

• Molecules and Cells
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• v.40 no.2
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• pp.109-116
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• 2017

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

• Anatomy & Biological Anthropology
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• v.31 no.4
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• pp.143-149
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• 2018

Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates ${\beta}1$ integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased ${\beta}1$-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.236-243
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• 2023

Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A₂ production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A₂, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Proceedings of the Zoological Society Korea Conference
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• 1997.10b
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• pp.198.1-198
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• 1997

No Abstract, See Full Text