• Food Science and Biotechnology
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• v.18 no.6
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• pp.1423-1429
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• 2009

Rhizopus oryzae KSD-815 was isolated from nuruk that has been used to make Korean traditional wines. This study was performed to investigate the effect of cultures of R. oryzae KSD-815 on cardiovascular disorders and cancer metastasis. Firstly, these cultures were sequentially fractionationed with n-hexane (TAHe), ethylacetate (TAE), n-butanol (TAB), and $H_2O$ (TAW). The TAE inhibited the activity of angiotensin-converting enzyme (ACE) and TAB suppressed platelet aggregation in vitro. TAE and TAB inhibited cell motility of human breast cancer cells. Furthermore, TAW interrupted the formation of neovasculature and tube-like structure, and down-regulated the expression of angiogenic factors, basic fibroblast growth factor (bFGF), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in breast cancer cells. These results indicated that cultures of R. oryzae KSD-815 display the inhibitory activities on hypertension, platelet aggregation, and metastasis, and suggest that these cultures might be further probed for the purposes as therapeutic agents or dietary supplements.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.31-31
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• 1999

Characterization of mutant mice has been utilized as an animal model for the study of human inherited diseases. In addition to the pathogenesis stduy using the mutant mice, the mice have been used for the identification of the genes causing the phenotypes. Functional cloning and positional cloning are two approaches, depending on the phenotypes of the mutant mice. Though it takes a long time positional cloning has been well used to identify the gene of which function can not be presumed from the mouse phenotype. Recently by the advance of the molecular tools and the human genome project close to 10,000 genetic markers are developed to make the procedure faster. We obtained a new mutant mouse, sims, spontaneously arose and the affected mouse has a mild tremor and seizure was observed. Homozygote in either sex is sterile since uterus growth in female and seminal vesicle in male are not induced for the growth in puberty, implying the abnormal hormonal regulation during puberty. Supporting this, there is no detectable testosterone in the serum of the mutant male and the brain of the mutant is 30% heavier than littermate. To identify the location of the mutated gene, intraspecies cross to CAST/Ei was carried out and the 37 affected mice was analyzed for the linkage. The gene was mapped on chromosome 18, 20 cM from the centromere. More than 500 F2 progenies have been analyzed for the linkage and the locus becomes narrow within 3cM between Egrl and Fgf gene.f gene.

• Journal of Microbiology and Biotechnology
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• v.32 no.3
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• Medical Lasers
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• v.10 no.3
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• pp.161-169
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• 2021

Background and Objectives Fractional microneedle radiofrequency systems are popular options to increase elasticity in aging skin. Laser-assisted drug delivery is a promising method for the epidermal injection of topically applied drugs and cosmetic ingredients. This study assesses the safety and efficacy of topical delivery of L-ascorbic acid, vitamin E, and ferulic acid after fractional microneedle radiofrequency treatment for reducing photodamage. Materials and Methods In this prospective, single-center, split-face, controlled pilot study, six women (mean age, 48.0 years; range, 35-57 years; Fitzpatrick skin types III and IV) exhibiting mild to moderate photodamage, underwent a single session of fractional microneedle radiofrequency treatment. The patients were instructed to apply the antioxidant formulation to only one side of the face. Patients were evaluated 3 days, 7 days, and 4 weeks thereafter, using three-dimensional imaging and ultrasound. Ex vivo, the full-thickness human skin was used for molecular and histological evaluation. Statistical analysis was achieved by applying t-tests, Mann-Whitney U tests, and one-way analyses of variance. Results Compared to the untreated side, the antioxidant-treated side exhibited a significant increase in dermal thickness (10.32% vs. 17.54%, p < 0.05), but not in skin elasticity (4.76% vs. 4.69%, p > 0.05). The difference in erythema between the sides was statistically not significant (p > 0.05). In the ex vivo model, expression of FGF2 in the skin was significantly increased after application of the antioxidant formulation, as compared to results obtained subsequent to fractional microneedle radiofrequency treatment only (p < 0.01). Conclusion This study demonstrates that for the treatment of photodamaged skin, laser-assisted delivery of the antioxidant formulation is a safe and effective adjuvant modality following fractional microneedle radiofrequency.

• The Korea Journal of Herbology
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• v.32 no.6
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• pp.55-62
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• 2017

Objectives : This study aims to evaluate the effects of natural herb mixutre (NHM) on atopic dermatitis and skin regeneration using in vivo test. Methods : NHM was prepared with DW. 25% of NHM was applied to skin lesion, where atopic dermatitis was induced by DNCB in NC/Nga mice. The levels of cytokines (IL-4, IL-5, IL-6, IL-13, TNF-a, and $IFN-{\gamma}$), and IgE in serum were measured by Luminex. Immune cells (WBC, eosinophil, lymphocyte, and monocyte) in blood were counted by coulter counter. The gross investigation of atopic dermatitis index score test were performed during the NHM treatment period. Also, the histopathological change of dorsal skin was observed by H&E and M&T staining. Results : NHM showed the levels of IL-4, IL-5, IL-6, IL-13, IgE, WBC, eosinophil, lymphocyte, and monocyte in serum or blood were significantly decreased. On the contrary, the productions of FGF, and VEGF were increased in the serum. Also, atopic dermatitis index score in NHM-treated mice were observed in the similar levels to those of normal group. Histological examination demonstrated that NHM suppressed immune cell infiltration and thickening of epidermis, meanwhile the extraction induced collagen production in the dorsal skin. Conclusion : This study demonstrated that NHM is appeared to be effective on atopic dermatitis and skin regeneration efficacy based on the observations with hematologic, gross, and histologic examinations. Therefore, we suggest that NHM could be effectively used as an external therapeutics against atopic dermatitis and a consequence skin damage.

• Korean Journal of Poultry Science
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• v.40 no.4
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• pp.299-304
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• 2013

Tracheal epithelial cells (TECs) are an important tool for studies of viral respiratory diseases. Primary TECs have been cultured from human, mouse and hamster. It is also necessary to diagnose viral respiratory disease and reveal infection mechanisms in chicken. In this study, we isolated tracheal epithelial layers from tracheal of 20-day-old chicks and cultured primary TECs from the isolated layers. Ciliated cells which were a typical morphology of TECs were observed in cultured primary TECs and maintained until cell passage 5 (15 to 20 days). When we analyzed expression patterns of epithelial marker genes (retinoic acid responder, FGF-binding protein, virus activating protease (VAP) in TECs compared to immortalized chicken embryonic fibroblast cell line (DF-1), all the marker genes are highly expressed in TECs than in DF-1. When TECs were cultured with 0.1 and 1 MOI of ND virus (rNDV-GFP strain) to test the susceptibility of TECs for ND virus, 12.6% and 48.2% of the incubated TECs were infected respectively. In addition, when DF-1 was incubated with 1 MOI of ND virus, the virus infection rate of DF-1 was three times lower than the virus infection rate of TECs. These data could contribute to study infection mechanisms of viral respiratory diseases and control them in chicken.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.1-14
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• 2003

Objective : Ikiyangeumhaedoc-tang(IYHT) has an effect of nourishing Yin(陰) and Jin(津), and has been used to cancer patient effectively. In order to prove the anticancer's and antimetastic effect of IYHT experimentally, studies were done. Methods : We evaluated the cytotoxic activity on HT-1080 cells as well as inhibitory effect on activity of DNA topoisomerase Ⅰ, cell adhesion, cell invasion and proliferation of HUVEC cells induced by bFGF and measured the expression of mRNA(uPA, MMP2, TIMP2), p-ERK protein, recovery effect of gap junctional intercellular communication by $H_{2}O_2$ and survival time of ICR mice bearing sacoma-180. Results : IYHT showed the inhibitory effect on DNA topoisomerase Ⅰ in the concentration of $100{\mu}g/ml,\;500{\mu}g/ml$ and the dosage-dependent inhibitory effect on the adhesion of HT-1080. The concentration of 1mg/ml of IYHT inhibited 15% of adhesion compared with control. IYHT decreased the expression of uPA, but not in MMP2, TIMP2 by RT-PCR and inhibited the expression of p-ERK effectively in the concentration of more than $500{\mu}g/ml.$ IYHT recovered the inhibited gap junctional intercellular communication by $H_{2}O_2$ to the level of 60% of normal control in the concentration of $400{\mu}g/ml$ but, did not extended the mean survival time of sarcoma 180-bearing mouse. Conclusions : It was concluded that IYHT could be applied usefully for prevention and treatment of human cancer, And also experimental study for the evaluation of molecular biological study and antimetastatic research would be recommended in the near future.

• Animal Bioscience
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• v.36 no.7
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• pp.991-1002
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• 2023

Objective: This study aimed to elucidate the underlying gene regions responsible for productive, phenotypic or adaptive traits in different ecological types of Tibetan sheep and the discovery of important genes encoding valuable traits. Methods: We used whole-genome resequencing to explore the genetic relationships, phylogenetic tree, and population genetic structure analysis. In addition, we identified 28 representative Tibetan sheep single-nucleotide polymorphisms (SNPs) and genomic selective sweep regions with different traits in Tibetan sheep by fixation index (Fst) and the nucleotide diversity (θπ) ratio. Results: The genetic relationships analysis showed that each breed partitioned into its own clades and had close genetic relationships. We also identified many potential breed-specific selective sweep regions, including genes associated with hypoxic adaptability (MTOR, TRHDE, PDK1, PTPN9, TMTC2, SOX9, EPAS1, PDGFD, SOCS3, TGFBR3), coat color (MITF, MC1R, ERCC2, TCF25, ITCH, TYR, RALY, KIT), wool traits (COL4A2, ERC2, NOTCH2, ROCK1, FGF5, SOX9), and horn phenotypes (RXFP2). In particular, a horn-related gene, RXFP2, showed the four most significantly associated SNP loci (g. 29481646 A>G, g. 29469024 T>C, g. 29462010 C>T, g. 29461968 C>T) and haplotypes. Conclusion: This finding demonstrates the potential for genetic markers in future molecular breeding programs to improve selection for horn phenotypes. The results will facilitate the understanding of the genetic basis of production and adaptive unique traits in Chinese indigenous Tibetan sheep taxa and offer a reference for the molecular breeding of Tibetan sheep.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.452-457
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• 2002

Galla Rhois is a gallnut of Rhus javanica Linne used for treatment of diarrhea, hemorrhage, cough, leukorrhea and toxic tumor etc in oriental medicine. For the evaluation of antitumor effect of Galla Rhois, activity based fractionation was done. We isolated an effective compound and identified 1,2,3,4,6-penta-O-galloyl-β-D-glucose(PGG) by photometric analysis such as NMR and MASS. Then, we studied the angiogenic activity of PGG. It showed a cytotoxicity against SK-OV-3, SK-OV-3, HT1080 with IC/sub 50/ of 50 ug/ml approximately. It also effectively inhibited proliferation of HUVEC cells treated by bFGF to 30% of control at 20 ug/ml and cell migration to 80% at 10 ug in a dose dependent fashion. Tube formation of HUVEC cells on matrigel was effectively suppressed from 2.5 ug/ml of concentration by PGG. Moreover, it effectively recovered the dysfunction of gap junctional intercellular communication in WB-F344 rat liver epithelial cells caused by hydrogen peroxide at 4 ug/ml suggesting it potently can inhibit tumor promotion. Taken together, it indicates 1,2,3,4,6-penta-O-galloyl- β -D-glucose has antiangiogenic activity.