• 대한기관식도과학회지
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• 제8권1호
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• pp.29-34
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• 2002

Background and Objectives : Sulfur dioxide gas is one of the major airborne Pollutants noxious to human in industrialized countries. The most vulnerable areas in the human respiratory system were the trachea and main bronchi and a gradient of decreasing damage was observed in the peripheral tracheobronchial tree. Induced functional alteration was increased mucosal permeability, and morphological changes were epithelial sloughing, intracellular edema, mitochondrial swelling, widened intercellular spaces, and ciliary cytoplamic extrusions. The laminins are a family of extracellular matrix glycoproteins localized in the basement membrane. Their primary role is cell-matrix attachment, but many additional biologic activities, including Promoting cell growth and migration, tumor growth and metastasis, wound repair, and graft survival, have been demonstrated. Materials and Methods : Histologic changes and expression of laminin in tracheal mucosa sacrificed at 1 day, 2 day, 3 day, 1 week, 2 weeks, and 3 weeks after continued SO2 exposure of 250 ppm for 30 minutes a day(to 7week) were studied in rats. In this study, mild immune reaction for laminin was noted at the apical cytoplasm of epithelial cells and basement membrane one day after a 7 week $SO_2$ exposure. The cilia and nucleoi of epithelial cells were normal and no immune reaction was noted in Goblet cells. The lamina propria of the tracheal tissue was infiltrated by monocytes and lymphocytes. Results : At 24 hours after exposure, all tracheal cells except Goblet cells revealed a mild immune reaction for laminin. No immune reactions were noted in the basement membrane. At 72 hours after exposure, mild or moderate immune reactions for laminin was seen in the tracheal cell cytoplasm. Irregular faint immune reaction for laminin was noted in the basement membrane. At 1 week after exposure, strong immune reaction for laminin was detected over all tracheal cells, and the basement membrane was seen clearly. At 2~3 weeks after exposure, strong immune reaction for laminin was seen in all tracheal epithelial cells except Goblet cells and a mild immune reaction was partly revealed in the basement membrane. Conclusion : Our study suggests that 502 produces histologic damage on the tracheal mucosa. Longer duration after exposure of $SO_2$ makes more progressive healing on the tracheal mucosa and increased immunoreactivity for laminin.

• Archives of Plastic Surgery
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• 제37권4호
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• pp.340-345
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• 2010

Purpose: Recently, bioceramics have become popular as a substitute graft material for reconstruction of bony defect after trauma or tumor surgery. Among the bioceramic materials, hydroxyapatite (HA) is favored due to its biocompatibility. HA scaffold is composed of the interconnected reticular framework, macropores and micropores. Macropores play an important role in cell migration, nutrients supply and vascular ingrowth. On the other hand, a number of micropores less than $10{\mu}m$ form an irregular surface on HA scaffolds, which prevents the osteoblast from adhering and proliferating on the surface of HA scaffold. Methods: In this study, three different groups were designed for comparison. In the first group (group A), conventional method was used, in which HA pellet was applied without surface pretreatment. The second group (group B) was given a HA pellet that has been coated with crystalline HA solution prior to application. In the third group (group C), the same method was used as the second group, where the pretreated HA pellet was heated ($1250^{\circ}C$, 1 hour) before application. Osteoblast-like cells ($2{\times}10^4$/mL) were scattered onto every pellet, then they were incubated in 5% $CO_2$ incubator at $37^{\circ}C$ for twelve days. During the first three days, osteoblast cells were counted using the hemocytometer daily. ALP activity was measured on the 3, 6, 9 and 12 culture days using the spectrophotometer. Results: Under SEM, group A showed a surface with numerous micropores, and group B revealed more rough crystal surface. Group C revealed a fused crystal appearance and flattened smooth surface. In proliferation and ALP activity of osteoblast cells, group C showed better results compared to group B. Group A which lacks pretreatment of the surface showed less osteoblast proliferation and ALP activity than group C, but showed better results than group B. Conclusion: We found that crystallized HA with heat treatment method enhances the osteoblasts proliferation and differentiation on the surface of HA pellets.

• 융합정보논문지
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• 제11권4호
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• pp.194-202
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• 2021

부처손 잎은 전통한방에서 탈항, 혈뇨, 부정출혈, 월경불순, 자궁출혈 및 만성간염을 치료 목적으로 사용되어 왔다. 본 연구에서는 부처손을 이용하여 얻은 열수추출물(STW)과 80%에탄올추출물(STE)의 항산화, 항염 및 세포 재생활성을 평가하였다. 그 결과 열수추출물과 에탄올추출물의 폴리페놀 화합물 함량은 각각 38.108±0.766 mg/g, 17.927±1.064 mg/g이었다. DPPH와 ABTS radical 소거능 IC50은 열수추출물이 에탄올추출물에 비해 2배 이상 낮았다. MTT 결과, RAW264.7 세포 생존율은 두 추출물 모두 1 mg/mL에서 6% 감소한 반면, HaCaT 세포의 생존율은 50 ㎍/mL에서 18%로 증가하였다. 열수추출물과 에탄올추출물은 LPS로 자극한 RAW264.7 세포의 NO, TNF-�� 그리고 COX-2, PGE2 등의 염증 매개물질의 생성을 억제하였다. 또한 TNF-a에 의한 각질형성 세포의 손상을 저해시켰다. 이상의 결과로 부처손 열수추출물과 에탄올추출물은 피부건강과 미용 식품을 위한 기능성 원료로 가능성이 높다고 사료된다.

• BMB Reports
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• 제55권2호
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• pp.98-103
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• 2022

Increased mRNA levels of cancer upregulated gene (CUG)2 have been detected in many different tumor tissues using Affymetrix microarray. Oncogenic capability of the CUG2 gene has been further reported. However, the mechanism by which CUG2 overexpression promotes cancer stem cell (CSC)-like phenotypes remains unknown. With recent studies showing that pyruvate kinase muscle 2 (PKM2) is overexpressed in clinical tissues from gastric, lung, and cervical cancer patients, we hypothesized that PKM2 might play an important role in CSC-like phenotypes caused by CUG2 overexpression. The present study revealed that PKM2 protein levels and translocation of PKM2 into the nucleus were enhanced in CUG2-overexpressing lung carcinoma A549 and immortalized bronchial BEAS-2B cells than in control cells. Expression levels of c-Myc, CyclinD1, and PKM2 were increased in CUG2-overexpressing cells than in control cells. Furthermore, EGFR and ERK inhibitors as well as suppression of Yap1 and NEK2 expression reduced PKM2 protein levels. Interestingly, knockdown of β-catenin expression failed to reduce PKM2 protein levels. Furthermore, reduction of PKM2 expression with its siRNA hindered CSC-like phenotypes such as faster wound healing, aggressive transwell migration, and increased size/number of sphere formation. The introduction of mutant S37A PKM2-green fluorescence protein (GFP) into cells without ability to move to the nucleus did not confer CSC-like phenotypes, whereas forced expression of wild-type PKM2 promoted such phenotypes. Overall, CUG2-induced increase in the expression of nuclear PKM2 contributes to CSC-like phenotypes by upregulating c-Myc and CyclinD1 as a co-activator.

• 대한본초학회지
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• 제24권3호
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• pp.161-167
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• 2009

Objectives : Maekmoondong-tang (MMDT), a Korean herbal medicine, has been used to treat severe dry cough in patients with bronchitis and pharyngitis. MMDT has been reported to have anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating, and metabolic regulatory actions. However, there are no evidence in regard to the effects of MMDT on carcinogenesis and metastasis. Here, we investigated the effects of 70% ethanol extract of MMDT on cell viability, apoptosis, and motility in human hepatocarcinoma HepG2 cells. Methods : Cell viability was measured using the CCK-8 assay, and the apoptosis induction was evaluated by caspase-3 activity. To detect apoptotic features, the cells treated with MMDT were stained with 4'-6-diamidino-2-phenylindole (DAPI). Cell motility was examined by Boyden chamber assay and Real-time Cell Index of Migration assay. Gelatin zymography also performed to measure matrix metalloproteinase (MMP)-2/9 activity. Results : We found that MMDT significantly inhibited cell proliferation and increased caspase-3 activity in a dose-dependent manner in HepG2 cells. Apoptotic features such as chromatin condensation and apoptotic bodies were observed in MMDT-treated cells by DAPI staining. MMDT also suppressed PMA-induced cell motility and activities of MMP-2/9. Conclusions : Our results exhibited that MMDT possess the anti-carcinogenetic and anti-metastatic activities via caspase-3 activation and down-regulation of cell motility and invasion in HepG2 cells. Therefore, these findings suggest that MMDT could be potentially applied to the prevention and treatment of cancer.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.368-378
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• 2024

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44^highCD133^high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

• 생명과학회지
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• 제32권4호
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• pp.271-278
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• 2022

신규 종양 유전자 Cancer Upregulated Gene (CUG) 2가 어떻게 유사-종양줄기세포 표현형을 유도하는지 잘 알려져 있지 않다. Cyclin E, c-Myc, Notch, 그리고 Yap1와 같은 종양단백질를 분해하여 그 발현을 조절하는 FBXW7 E3 ligase의 발현이 대장암, 자궁경부암, 그리고 위암 등 여러 암조직에서 낮아져 있음이 보고되고 있다. 그래서 우리는 이 FBXW7 단백질이 CUG2에 의한 종양형성에 관여할 수 있다는 가설을 세웠다. 이 연구에서 우리는 각 대조구 세포주보다 CUG2가 과발현된 A549 폐암 세포주와 BEAS-2B 기관지 세포주에서 FBXW7 단백질 발현이 낮게 나왔다. 여기서 MG132를 처리하게 되면 감소된 FBXW7과 FBXW7 기질로 알려진 Yap1 단백질 발현이 증가되는 결과를 관찰하였다. 종양줄기세포 현상에서 FBXW7의 역할을 규명하기 위하여, FBXW7 siRNA를 처리하였다. 대조구 세포주에서 감소된 FBXW7의 조건은 세포 이동 침습, 그리고 구형 형성이 증가되는 종양줄기세포 현상이 촉진되는 것을 관찰하였고, CUG2가 과발현된 두 세포주에서 FBXW7 발현 벡타 도입으로 FBXW7 발현 증가는 종양줄기세포 현상이 억제됨을 알 수 있었다. 또한 FBXW7의 감소는 EGFR-Akt-ERK1/2와 β-catenin-Yap1-NEK2 신호 경로를 활성화시키고, 반대로 FBXW7 발현 증가는 이 두 경로의 활성이 억제됨을 알 수 있었다. 이들 결과를 종합해 보면, CUG2 과발현은 FBXW7의 발현 감소로 이어지고, 이는 EGFR-Akt-ERK1/2와 β-catenin-Yap1-NEK2 신호경로를 활성화시켜 유사-종양줄기세포 현상을 촉진하는 것으로 생각된다.

• Radiation Oncology Journal
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• 제19권2호
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• pp.181-189
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• 2001

목적 : 피부나 폐, 간, 신장 등의 섬유화가 방사선 조사 후 주요한 부작용 중의 하나이나 아직까지 이 과정에서 $TGF-\beta$가 주요한 역할을 하는 것 이외에는 밝혀진 것이 거의 없는 상태이다. 또 matrix metalloproteinase (MMP) 및 tissue inhibitor of metalloproteinase (TIMP) 유전자 활성 및 발현이 조직의 재구성과 손상, 암세포의 침윤과 전이에 관여하고 있고, 방사선이 종양의 치료에 널리 이용되고 있음에도 방사선에 의한 MMP와 TIMP 유전자의 발현에 대한 연구는 거의 없는 상태이다. 이에 저자들은 방사선 조사가 TIMP-1, TIMP-2의 발현에 어떤 영향을 끼치는지 알아보고자 본 연구를 시작하였다. 대상 및 방법 : C57BL/6 생쥐를 Varian CL4/100을 사용하여 각각 0, 2, 10 Gy의 조사량으로 전신조사를 하였다. 방사선 조사 후 24, 48 시간에 생쥐를 희생하여 폐, 간, 신장을 얻어 paraffin 포매 조직 절편을 만들어 Avidin-Biotin Complex 방법으로 면역 염색을 한 후 광학 현미경으로 관찰하여 염색의 강도와 면적에 따라 점수화 하였다. 결과 : TIMP-1은 대조군에 비해 방사선 조사 후 폐조직에서는 변화가 없는 것으로 나타났다. 간조직에서는 간세포와 Kupffer 세포에서 발현이 증가하였고, 신장조직에서는 주로 세뇨관 세포에서 발현이 증가하였고 방사선 조사 후 경과 시간에 따른 변화는 거의 없었다. 방사선량에 따른 발현의 정도는 신장을 제외하고는 변화가 거의 없었다. TIMP-2는 폐조직에서는 2 Gy 조사 후 발현이 증가되었고, 간조직에서도 2 Gy 24 시간에는 활성이 증가했으나 10 Gy에서는 대조군 수준이었다. 신장조직에서는 10 Gy에서는 발현의 정도의 변화는 없었고 2 Gy에서는 발현이 감소하였다. 결론 : 각 장기에서 TIMP-1과 TIMP-2의 발현의 정도는 차이가 있었으며, 각 장기의 특정한 세포에서만 발현이 되었다. TIMP-1의 경우 간과 신장에서는 방사선에 의해 발현이 증가되었으나 폐에서는 발현이 증가되지 않았다. TIMP-2의 경우 폐에서는 방사선에 의해 발현이 증가하였으나 간과 폐에서는 방사선에 의한 발현의 변화는 불규칙적이었다. 방사선 조사 후 경과 시간과 방사선량에 따른 발현의 변화도 일정하지 않았다.

• Journal of Acupuncture Research
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• 제24권6호
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• pp.1-14
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• 2007

Backgrounds : Rheumatoid Arthritis(RA) is known as the chronic inflammatory diseasethat induces persistent inflammation in the joint cavity. The destruction of cartilage occurs as the result of bones destoyed by pannus, several influential cytokines induced by the synovial capsulitis, varieties of proteinases, $O_2$ radicals, and the secondary degenerative changes of articular cartilage. The type 2 collagen-induced arthritis model is used in recent experimental research on rheumatoid arthritis. Cervus elaphus sibiricus (Nockyong) has the effect of relieving pain by nourishing the muscles, joints, and bones. It is also known to be efficacious in promoting and enhancing the immune system. The objective of this study was to investigate the effect of Cervus elaphus sibiricus herbal acupuncture to inhibit the generation of proinflammatory enzyme on type 2 collagen-induced arthritis. I investigated the inhibition of mRNA transcription of MIF(macrophage migration inhibitory factor), $TNF-{\alpha}$(Tumor necrosis $factor-{\alpha}$) and MMP-9 (matrix metalloproteinase-9) of Cervus elaphus sibiricus herbal acupuncture using an in vitro test. Also investigated was the inhibition of differentiation of Th 1 cells and activation of cytokines(MIF, $TNF-{\alpha}$, IL-6, MMP-9), which are known to cause initial RA ,and are also related to the morphology of the synovial membranes of the joint capsule, by an in vivo test, using CIA(collagen induced arthritis) model mice. Materials & methods : The laboratory animals used in this experiment were 4 week-old DBA female mice, weighing approximately 20 grams, and adjusted to the laboratory environment. The experiment was divided into the normal group(NOR)-no treated group, control group(CON)-CIA induced group, and sample group(SAM)-Cervus elaphus sibiricus herbal acupuncture treated group. RA was induced in the mice via injection of $50{\mu}{\ell}$ C II mixed CFA. The Cervus elaphus sibiricus herbal acupuncture solution was applied on $GB_{35}$(陽陵泉) for 26 days from the 3rd day of RA inducement. The concentration of the solution was determined via a MTT assay. To research the effect on the expression of MIF, $TNF-{\alpha}$ and MMP-9 mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. C II induced RA knee joint's histo-chemical synovial membrane was observed using a specimen model via the Hematoxilin and Eosin dying technique. Results : The expression of mRNA of RA-related cytokines such as MIF, $TNF-{\alpha}$, and MMP-9 dosedependently decreased in the cell from the synovial membranes of the joint, which is treated with Cervus elaphus sibiricus herbal acupuncture solution. In mice treated with Cervus elaphus sibiricusherbal acupuncture, the damage of synovial membranes of the joint was lessened, and differentiation of Th 1 cells was suppressed. The activation of RA-related cytokines such as MIF was suppressed, and the generation of $TNF-{\alpha}$ and MMP-9 showed a statistically significant decreas. Conclusions : It is speculated that Cervus elaphus sibiricus herbal acupuncture has the therapeutic effect of palliating the damage of the tissue impaired by RA by inhibition of the initial RA progression and by regulating excessive differentiation of Th 1 cell as it suppresses the generation of RA-related cytokines during the highest stage of RA by acting on pro-inflammatory enzymes.

• Journal of Gastric Cancer
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• 제8권2호
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• pp.70-78
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• 2008

목적: VEGF-C와 VEGF-D는 맥관형성성 인자이고, E-cadherin의 비정상 발현은 위암의 진행에 중요한 역할을 한다. 이 연구의 목적은 조기위암에서 E-cadherin, VEGF-C, -D 그리고 cytokeratin 18번을 이용하여 정확하게 측정된 림프절 전이와의 연관성을 연구하는데 있다. 대상 및 방법: 1997년 3월부터 2002년 12월까지 49명의 조기 위암환자들을 대상으로 E-cadherin, VEGF-C와 VEGF-D 면역화학염색을 시행하였다. 림프절 전이를 정확하게 측정하기 위하여 49명 환자들의 1,562개의 림프절을 cytokertin 18을 사용하여 재검사 하였다. 결과: 11 (0.7%)개의 림프절이 12.2% (n=6)의 환자들로부터 새롭게 발견되었다. 정확한 림프절 전이는 점막암에서 3.6%였고, 점막하암에서 38.1%였다. 병기 이동은 3명(6.1%)의 환자에서 관찰되었다. E-cadherin의 비정상 발현은 36.7%에서 발견되었고, VEGF-C와 VEGF-D의 발현은 각각 16.3%와 36.7%에서 관찰되었다. E-cadherin의 비정상 발현은 종양의 분화도(P<0.0103)와 Lauren 분류(P<0.0001)와 뚜렷한 연관성이 있었다. VEGF-C와 VEGF-D는 조기위암에서 림프절 전이를 포함한 임상병리학적 연관성이 없었다. 그러나 E-cadheirn이 비정상 발현되고 VEGF-C 또는 VEGF-D의 발현이 동반되는 환자들에서 림프절 전이의 빈도가 높았다(P=0.0031). 결론: 본 연구에서 조기위암에서 림프절 전이와 VEGF-C, VEGF-D의 발현과의 관계를 증명할 수 없었다. 하지만 E-cadherin이 비정상 발현을 하면서 VEGF-C 또는 VEGF-D의 발현을 동반할 경우 림프절 전이와 연관성이 있었다.