• 한국임상수의학회지
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• 제18권4호
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• pp.324-328
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• 2001

This study was performed to evaluate the effects of $AS_2O_3$ upon antiangiogenesis in rat cornea, to examine it\`s possible application as an anticancer drug and to provide basic data for further studies of antiangiogenetic mechanism of $AS_2O_3$ . Angiogenesis was induced by cornea micropocket assay, as previously described. Sixteen of forty-eight eyes of Sprague-Dawley rats were randomly assigned to one of three groups, namely, only a bFGF group(control group), and a group treated by $AS_2O_3$ ($AS_2O_3$ group). After pellet implantation, we measured the number of new vessels, vessel length and clock hour of neovascularization, and area of neovascularization was determined using a mathematical formula. New vessels growing began at day 3, number of vessels in $AS_2O_3$ group were significantly more less than those in control group (p<0.05). The length of vessels of $AS_2O_3$ group was significantly shorter than that of control group after day 3(p<0.05). The clock hours of all group were slowly increased at all days but $AS_2O_3$ group was inhibited more than control group. Neovascularization areas of $AS_2O_3$ group were more significantly inhibited than those of control group (p<0.05). This study showed that $AS_2O_3$ had powerful antiangiogenetic effects and it would be useful in the choice of anticancer drug.

• Molecules and Cells
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• 제40권8호
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• pp.550-557
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• 2017

The periodontal ligament (PDL) is the connective tissue between tooth root and alveolar bone containing mesenchymal stem cells (MSC). It has been suggested that human periodontal ligament stem cells (hPDLSCs) differentiate into osteo/cementoblast and ligament progenitor cells. The periodontitis is a representative oral disease where the PDL tissue is collapsed, and regeneration of this tissue is important in periodontitis therapy. Fibroblast growth factor-2 (FGF-2) stimulates proliferation and differentiation of fibroblastic MSCs into various cell lineages. We evaluated the dose efficacy of FGF-2 for cytodifferentiation of hPDLSCs into ligament progenitor. The fibrous morphology was highly stimulated even at low FGF-2 concentrations, and the expression of teno/ligamentogenic markers, scleraxis and tenomodulin in hPDLSCs increased in a dose dependent manner of FGF-2. In contrast, expression of the osteo/cementogenic markers decreased, suggesting that FGF-2 might induce and maintain the ligamentogenic potential of hPDLSCs. Although the stimulation of tenocytic maturation by $TGF-{\beta}1$ was diminished by FGF-2, the inhibition of the expression of early ligamentogenic marker by $TGF-{\beta}1$ was redeemed by FGF-2 treatment. The stimulating effect of BMPs on osteo/cementogenesis was apparently suppressed by FGF-2. These results indicate that FGF-2 predominantly differentiates the hPDLSCs into teno/ligamentogenesis, and has an antagonistic effect on the hard tissue differentiation induced by BMP-2 and BMP-4.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권5호
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• pp.424-430
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• 2005

The oral cavity is humid environment mainly due to the continuous salivary flow. The reaction of oral mucosa to fluid flow is important for homeostasis and pathogenesis. The objective of this study is the screening the change of gene expression after the application of fluid induced shear stress (FISS) on the gingival fibroblast using cDNA microarray assay. The immortalized human gingival fibroblasts were grown and FISS was applied using a cone viscometer at a rotational velocity of 40 rpm, respectively for periods of 2 and 4 hours. The synthesis of cDNA was done from the extracted total RNA and cDNA microarray assay was done subsequently. The genes that showed over 1.6 in the Cy3/Cy5 or the Cy5/Cy3 value were regarded as genes influenced significantly by the FISS application ion (/M/>0.7). The " RUNX-1" was increased its expression in 2 hours group and " RUN and SH3 domain containing 1" was increased its expression in 4 hours group. The "CC020415", "cyclin L1", "interferon regulatory factor1", "early growth response 1", "immediate early response 2", and "immediate early response 3" genes were increased their expression in 2 and 4 hours after FISS application. In conclusion, we could find many genes that were probably related to the FISS application. Interestingly, most of them were placed in similar molecular pathways and these findings improve the reliability of chip data and usefulness in overall screening. From this experiment, we could find many items for further study and it will make improvement in the understanding of intracellular events in response to FISS.

• 한국발생생물학회지:발생과생식
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• 제10권1호
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• pp.63-73
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• 2006

간질환 환자의 대부분은 간 조직 손상으로 인해 간세포의 재생 능력이 감소한다. 간세포 이식은 이러한 간질환을 치료하는데 있어 혁신적인 방법으로 대두되고 있으나, 여전히 많은 의문과 문제점이 제기되고 있다. 사람의 양막으로부터 얻은 줄기 세포를 이용하여 간세포 분화를 위한 최적의 조건을 알아 보고자 하였다. 세포내 알부민에 대한 면역 화학적 방법, 세포내 글리코겐의 특이 염색법, 세포의 형태적 변화 연구 방법 등을 이용하여 여러가지 배양 조건을 조사한 결과, 배양 접시를 fibronectin으로 coating하고 배양액내에 insulin/transferrin/selenium(ITS)을 첨가하는 것이 양막 줄기세포의 간세포로의 분화에 효과적이었다. 또한 배양액내에 fibroblast growth factor(FGF)-1과 FGF-2를 함께 첨가하는 것이 둘 중 하나만 첨가하거나 첨가하지 않는 것보다 효과적이었다. 한편 분화 배양은 한가지 배양액을 사용한 지속적인 배양법(continuous culture method)보다 배양 조건을 달리하여 두 단계로 배양하는 2단계 배양법(two-step culture method)가 훨씬 효과적이었다. 마지막으로, 기본 배양액에 FGF-2와 FGF-4를 첨가한 조건과 FGF-4와 $TGF-{\alpha}$를 첨가한 조건이 다른 조건 보다 알부민 분비를 많이 하는 것으로 보아 FGF-4가 간세포 분화 과정에 중요한 역할을 하는 것으로 여겨지며 FGF-2 및 $TGF-{\alpha}$ 첨가는 더욱 효과적인 배양 조건으로 관찰되었다. 따라서, 양막에서 유래한 성체 줄기 세포는 적절한 배양 조건이 주어질 때, 간세포로 분화가 가능하며, 분화 과정에서 FGF-4가 주도적인 역할을 하며 FGF-2와 $TGF-{\alpha}$는 상승 효과를 갖는 것으로 사료된다.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.533-547
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• 2022

This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.

• 한국산학기술학회논문지
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• 제22권2호
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• pp.326-335
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• 2021

본 연구는 대두 단백질을 효소(pepsin) 분해 및 미생물(Lactobacillus Rhamnosus) 발효를 통해 생성된 저분자 생리활성 펩티드로 제조하여 인간 유래 피부세포에서 세포활성에 미치는 효과를 확인하고, 천연유래 기능성 미용소재로서의 이용 가능성을 확인하고자 하였다. 연구를 수행하기 위해 대두발효물을 제조하였고, 대두발효물에 대해 LC-MS 분석을 하였으며, WST-1 assay의 방법을 통해 cell viability를 측정하였다. 세포독성을 측정한 결과, 0~2,000 ㎍/mL의 모든 농도 구간에서 세포독성이 나타나지 않았다. 특히 800 ㎍/mL의 농도에서는 대조군에 비해 160~180 %, 양성대조군으로 사용한 EGF(epidermal growth factor)에 비해 120 %에서는 세포증식 효과가 나타나 피부노화 억제 및 피부세포 재생 소재로서의 뛰어난 가능성을 보여주었다. 또한 대두발효물과 그 분획물의 상처 치유 능력을 확인하기 위해 세포이동 실험을 수행한 결과, 대두발효물과 분핵물 중 F4와 F5가 대조군에 비해 우수한 세포이동능을 보여주었고, EGF와는 유사하거나 그 이상의 효과를 보여주었다. 결론적으로 대두발효물과 분핵물(F4 and F5)의 피부개선효과가 유사하게 나타나 피부미용 소재 및 피부 질환 치료의 소재로의 활용이 기대된다.

• 대한한방부인과학회지
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• 제30권2호
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• pp.49-70
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• 2017

목 적: 본 연구는 한의학에서 면포질환에 빈번히 사용하는 대표적인 복합처방인 청상방풍탕의 열수 추출물 동결건조물의 피부 노화 개선 효과 평가를 위하여 피부재생, 주름개선, 미백 및 보습 효과를 각각 평가하였고, 기본적인 독성 평가의 일환으로 세포독성 또한 in vitro 방법으로 평가하였다. 방 법: 본 연구에서는 human normal fibroblast(CRL-2076) 세포 및 B16/F10 murine melanoma(CRL-6475) 세포에 대한 청상방풍탕 열수 추출 동결건조물(수율 18.71%)의 세포독성을 MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium Bromide) 방법을 통해 평가하였고, B16/F10 melanoma cells의 melanin 생성 억제 정도 및 melanin 합성 필수 효소인 tyrosinase 활성 억제와 arbutin을 비교 평가하여 미백효과를 평가하였다. 또한 피부 재생 및 주름 개선 효과를 transforming growth factor(TGF)-${\beta}1$와 fibroblast의 collagen type I 합성능을 비교, phosphoramidon disodium salt(PP)와 세포외 기질의 분해에 관여하는 elastase활성 억제를 비교, oleanolic acid(OA)와 hyaluronidase, collagenase 및 matrix metalloproteinase(MMP)-1 활성 억제를 비교하여 각각 평가하였고, 마우스 피부 수분함량 변화를 관찰하여 보습효과를 평가하였다. 결 과: 본 실험의 결과, 청상방풍탕은 human normal fibroblast 세포 및 B16/F10 murine melanoma 세포에서 최고 농도인 500 mg/ml까지 유의한 세포독성이 나타나지 않았고, fibroblast의 collagen type I 합성을 증가시켰다. 또한 세포외기질 파괴와 연관된 것으로 알려진 hyaluronidase, elastase, collagenase 및 MMP-1 활성을 각각 억제하였고 melanin의 생성에 관여하는 tyrosinase의 활성 및 B16/F10 melanoma 세포의 melanin 생성을 농도 의존적으로 차단함이 관찰되었다. 이와 더불어 정상매체 대조군에 비해 청상방풍탕 경구 투여군이 투여 용량 의존적으로 마우스 피부 수분 함량을 유의성 있게 증가시켰다. 결 론: 이상의 결과에서, 청상방풍탕은 세포 독성 없이 피부재생, 주름개선, 미백 및 보습 효과를 나타남이 관찰되어 차후 피부 개선 소재로서 그 가치가 높을 것으로 판단되나 금후 개별 구성 약재 각각에 대한 효능 및 생리활성을 나타내는 화학성분의 검색과 더불어 다양한 방면으로 기전적인 연구와 피부 보호 효과에 대한 in vivo평가를 체계적으로 수행해야 할 것으로 판단된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.359.2-359.2
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• 2002

In the previous study, we reported that 2'-hydroxy-4'-methxoychalcone, synthetic chalcone inhibited PGE2 production in TPA- stimulated rat peritoneal macrophages by inhibiting the induction of COX-2 protein. The present study was carried out to clarify whether 2'-hydroxy-4'-methoxychalcone inhibit angiogenesis by the experimental methods in vitro and in vivo. 2'-Hydroxy-4'-methoxychalcone decreased angiogenesis of both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation inthe mouse Martigel plug assay. (omitted)

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권1호
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• pp.11-19
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• 2007

This study was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in tumor and stromal cells of tougue squamous cell carcinoma (SCC). We also wanted to characterize the differences, from the angiogenic aspect, between cancer-associated stromal cells and non-malignant stromal cells. Paraffin-embedded tumor specimens from eleven patients with tongue SCCs were studied. Immunohistochemical staining for VEGFR-1,-2, and -3 was performed on the tumor cells, stromal fibroblasts and tumor-associated macrophages of the specimens. The expression of all 3 receptors was detected in the tumor cells themselves of the biopsy specimens. All 3 receptors were also expressed on stromal cells, except that VEGFR-2 was not expressed in stromal fibroblasts. In radical excision specimens, the staining intensity for VEGFR-1, -2 in the tumor cells and VEGFR-1,-3 in the tumor-associated macrophages was significantly lower than that in the biopsy specimens (P < 0.05). By using the general marker of fibroblast and macrophage, 5B5 and CD68, respectively, we performed double immunofluorescence staining for 5B5 and each VEGFR in the stromal fibroblasts and for CD68 and each VEGFR in the tumor-associated macrophages of the radical excision specimens. We used 4 cases of fibroma and 4 cases of chronic inflammation tissue as the controls. It was found that only each marker was expressed in the control group, however, 5B5/VEGFR-1 and 5B5/VEGFR-3 in the stromal fibroblasts, and CD68/VEGFR-1 and CD68/VEGFR-3 in the tumor-associated macrophages were double stained in the radical excision specimens. Although our study used small number of specimens, the results of our study showed that in tongue SCC, in association with the angiogenesis, the stromal cells showed the activated phenotype and this was different from the nonmalignant stromal cells.

• 대한한방내과학회지
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• 제26권4호
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• pp.753-760
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• 2005

목적 : 본 연구는 100명의 암환자를 대상으로 항암단의 항혈관형성 효과를 측정하기 위하여 고안되었다. 방법 : 100명의 암환자 전체의 치료전후의 VEGF, bFGF 및 혈소판 수치의 변화량을 측정하였고, 병기, 삶의 질 및 암종별로 환자를 나누어 각각의 치료전후의 VEGF, bFGF 및 혈소판 수치의 변화량을 측정하여 통계적 유의성을 살펴보았다. 결과 : 항암단으로 치료한 암환자의 bFGF 수치는 치료전 후 통계적으로 유의성 있게 감소하였다. 특히 유방암 환자에서 bFGF 수치의 감소가 눈에 띄었다. 비록 통계적으로 유의하지는 않았지만 VEGF수치도 항암단으로 치료 후 다소 감소하는 경향을 보였다. 결론 : 따라서 항암단이 암환자 치료에 있어 항혈관형성 약물로써 작용한다고 추론할 수 있다.