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      • KCI등재

        A Methanol Fraction from Chaenomeles sinensis Inhibits Hepatocellular Carcinoma Growth in vitro and in vivo

        Jin Mi Chun,Kyoung Jin Nho,이아영,문병철,박준언,Ho Kyoung Kim 한국응용생명화학회 2012 Applied Biological Chemistry (Appl Biol Chem) Vol.55 No.3

        The fruits of Chaenomeles sinensis have numerous therapeutic properties, including anticancer and antiinflammatory activities; however, its antitumor activity and underlying molecular mechanism are poorly understood. The present study evaluated the in vitro and in vivo antitumor activities of a fraction of C. sinensis extract purified on amberlite resin and eluted in 30%methanol (CSAM 30). In vitro, cell viability was assessed using the CCK-8 assay, cell cycle was analyzed by flow cytometry, and apoptosis was measured by Hoechst DNA staining, caspase activity assays and Western blotting. In vivo antitumor efficacy of CSAM 30 was evaluated by oral administration on the human HepG2 hepatocellular carcinoma preclinical xenograft model. In vitro, CSAM 30 inhibited HepG2 cell proliferation and induced apoptosis via activation of caspases, cleavage of poly ADP-ribose polymerase, up-regulation of Bad, and down-regulation of Xlinked inhibitor of apoptosis protein XIAP and bcl-2. In vivo,CSAM 30 inhibited HepG2 tumor growth in a dose-dependent manner without inducing body weight loss. These results demonstrate that CSAM 30 induces apoptosis and has antitumor activity in vivo and in vitro.

      • Ethanol Extract of <i>Dianthus chinensis</i> L. Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells <i>In Vitro</i>

        Nho, Kyoung Jin,Chun, Jin Mi,Kim, Ho Kyoung Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

        <P><I>Dianthus chinensis</I> L. is used to treat various diseases including cancer; however, the molecular mechanism by which the ethanol extract of <I>Dianthus chinensis</I> L. (EDCL) induces apoptosis is unknown. In this study, the apoptotic effects of EDCL were investigated in human HepG2 hepatocellular carcinoma cells. Treatment with EDCL significantly inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis. This induction was associated with chromatin condensation, activation of caspases, and cleavage of poly (ADP-ribose) polymerase protein. However, apoptosis induced by EDCL was attenuated by caspase inhibitor, indicating an important role for caspases in EDCL responses. Furthermore, EDCL did not alter the expression of bax in HepG2 cells but did selectively downregulate the expression of bcl-2 and bcl-xl, resulting in an increase in the ratio of bax:bcl-2 and bax:bcl-xl. These results support a mechanism whereby EDCL induces apoptosis through the mitochondrial pathway and caspase activation in HepG2 cells.</P>

      • Ampelopsis japonica ethanol extract suppresses migration and invasion in human MDA?MB?231 breast cancer cells.

        Nho, Kyoung Jin,Chun, Jin Mi,Kim, Dong-Seon,Kim, Ho Kyoung SPANDIDOS PUBLICATIONS 2015 MOLECULAR MEDICINE REPORTS Vol.11 No.5

        <P>Ampelopsis japonica (AJ) is a well?known traditional oriental herb with anti?inflammatory and anticancer activities. However, the molecular mechanisms by which AJ inhibits metastasis in breast cancer cells remain to be elucidated. The aim of the present study was to investigate the effects of AJ ethanol extract (EAJ) on highly metastatic human MDA?MB?231 breast cancer cells in vitro. AJ was extracted and chemically characterized. Cell proliferation was determined using a CCK?8 assay and migration was detected using a wound healing motility assay. A Transwell assay was used to evaluate the invasion and metastatic capabilities of the MDA?MB?231 cells. In addition, the mRNA expression levels of metalloproteinase (MMP)?2 and MMP?9 and tissue inhibitors of metalloproteinases (TIMP)?1 and TIMP?2 were evaluated using reverse transcription quantitative polymerase chain reaction in vitro. The results of the present study characterized the signaling cascades that mediated the antimetastatic activity of AJ in the human MDA?MB?231 breast cancer cell line. EAJ significantly suppressed the migration and invasion of MDA?MB?231 cells in vitro and inhibited the expression of metalloproteinase (MMP)?2 and MMP?9. These findings identified the biological activity of EAJ in an in vitro model of cancer metastasis and provided a rationale for further investigation.</P>

      • SCOPUSKCI등재

        A Methanol Fraction from Chaenomeles sinensis Inhibits Hepatocellular Carcinoma Growth in vitro and in vivo

        Chun, Jin-Mi,Nho, Kyoung-Jin,Lee, A-Yeong,Moon, Byeong-Cheol,Park, Jun-Yeon,Kim, Ho-Kyoung The Korean Society for Applied Biological Chemisty 2012 Journal of Applied Biological Chemistry (J. Appl. Vol.58 No.3

        The fruits of Chaenomeles sinensis have numerous therapeutic properties, including anticancer and antiinflammatory activities; however, its antitumor activity and underlying molecular mechanism are poorly understood. The present study evaluated the in vitro and in vivo antitumor activities of a fraction of C. sinensis extract purified on amberlite resin and eluted in 30% methanol (CSAM 30). In vitro, cell viability was assessed using the CCK-8 assay, cell cycle was analyzed by flow cytometry, and apoptosis was measured by Hoechst DNA staining, caspase activity assays and Western blotting. In vivo antitumor efficacy of CSAM 30 was evaluated by oral administration on the human HepG2 hepatocellular carcinoma preclinical xenograft model. In vitro, CSAM 30 inhibited HepG2 cell proliferation and induced apoptosis via activation of caspases, cleavage of poly ADP-ribose polymerase, up-regulation of Bad, and down-regulation of X-linked inhibitor of apoptosis protein XIAP and bcl-2. In vivo, CSAM 30 inhibited HepG2 tumor growth in a dose-dependent manner without inducing body weight loss. These results demonstrate that CSAM 30 induces apoptosis and has antitumor activity in vivo and in vitro.

      • KCI등재

        마우스 유방암 모델에서 5-Aza-2'-deoxycytidine의 암줄기세포 유지 억제 효과

        노경진(Kyoung-Jin Nho),양인숙(In-Sook Yang),김란주(Ran-Ju Kim),김수림(Soo-Rim Kim),박정란(Jeong-Ran Park),정지윤(Ji-Youn Jung),조성대(Sung-Dae Cho),남정석(Jeong-Seok Nam) 한국생명과학회 2009 생명과학회지 Vol.19 No.8

        비정상적 DNA메칠화는 암 발생에 있어 중요한 역할을 한다. 최근 연구에 의하면 암줄기세포 유지에 있어 DNA과메칠화가 연관되어 있다고 보고하고 있다. 따라서 본 연구는 4T1 유방암 실험모델에서 demethylating agent인 AZA 처리에 따른 후성유전적 변화가 암줄기세포의 유지 및 증식에 있어 어떠한 영향을 미치는지 조사 하였다. 4T1 세포에서 AZA 처리에 따른 tumorsphere 형성이 감소 하는 것을 in vitro 실험을 통해 관찰 하였고, in vivo 실험에서는 줄기세포 조절 유전자들(Oct-4, Nanog. Sox2)의 발현이 감소 되는 것을 확인 하였다. 본 연구 결과로 볼 때 4T1 유방암 실험모델에서 AZA에 의한 후성유전적 변화는 줄기세포 조절 유전자(SRG)들의 발현을 조절하면서 암줄기세포 특성을 변화시켜 암줄기세포의 증식 및 유지를 억제 할 것으로 사료된다. 향후 이러한 DNA 메칠화억제를 항암치료에 응용하면, 암줄기세포를 파괴함으로써 암의 재발 및 악성화를 효과적으로 제어 할 수 있을 것으로 사료된다. Aberrant DNA methylation plays an important role in the development of cancer. It has been reported recently that DNA hypermethylation is involved in the maintenance of cancer stem cells. The present study was designed to test the hypothesis that the demethylating agent, 5-aza-2‘-deoxycytidine (AZA), can inhibit the potential for maintenance of cancer stem cells. To validate this hypothesis, we used 4T1 syngeneic mouse models of breast cancer. The AZA pre-treated 4T1 cells showed a dramatic inhibition of tumorsphere formation, compared to their counterparts in vitro. In addition, the AZA treatment significantly suppressed the expression of stem regulator genes, such as oct-4, nanog and sox2, compared to counterparts in vivo. Therefore, selective inhibition of DNA methylation may be useful for stem-specific cancer therapy.

      • KCI등재
      • KCI등재

        방사선 가교에 의해 제조된 하이드로겔의 제조 및 특성

        이진현 ( Jin Hyun Lee ),박경란 ( Kyoung Ran Park ),노영창 ( Young Chang Nho ),손태일 ( Tae Il Son ) 한국키틴키토산학회 2003 한국키틴키토산학회지 Vol.8 No.1

        본 실험에서는 상처 치료용 드레싱으로 고분자 용액에 Cobalt-60 감마선을 조사시켜 하이드로겔을 제조하였다. 대체로 겔화율이 높은 하이드로겔의 경우에는 함수율이 낮았다. 이것은 팽윤정도가 낮은 하이드로겔은 가교밀도가 높아 물을 함유할 수 있는 고분자의 망상 공간의 크기가 작아서 함수율이 낮기 때문이다. 상처치료용 하이드로겔의 중요한 요소 중의 하나인 기계적 물성, 즉 겔 강도는 조사선량과 고분자의 농도에 의해 영향을 받는다. 고분자의 농도가 증가할수록 겔 강도는 비례적으로 증가했다. 분자량이 증가할수록 겔 강도가 농도에 따른 영향을 받아 대체로 증가하는 경향을 보였다. 하이드로겔의 치료 효능을 보강하기 위해 첨가되는 천연고분자인 알긴산나트륨은 첨가된 하이드로겔의 함수율을 증가시켰다. 키토산을 직접 조사시키면 분자량이 작아지고 산 용액에 녹인 경우, 그 용액의 점도가 낮으므로 공정상 이점을 제공할 수 있다. 조사된 키토산과 조사되지 않은 키토산을 섞어 만든 다양한 종류의 PVP-키토산 하이드로겔의 겔 강도 차이는 거의 없었다. PVP 접착성을 약간 감소시키기 위해 제조된 PVP-PEC 하이드로겔은 겔 강도가 고분자 농도와 조사선량에 크게 의존하는 경향은 PVP 하이드로겔의 결과와 비슷하며 수분 증발 속도가 좀 더 빠르고, 겔 강도는 건조시 초기에는 일정하다가 급격히 증가하는 특이한 양상을 보였다. 동물 실험결과, 14일 전후에서 상처는 거의 아물었으나 하이드로겔을 붙인 상처의 치료 속도가 더 빠르게 나타났다. 바셀린 거즈의 경우 건조속도가 상대적으로 매우 빨랐고 상처에 달라 붙었다. 하이드로겔은 상처에 잘 부착이 되면서도 제거시에는 상처로부터 용이하게 제거할 수 있었으며, 전반적으로 치료 효과는 거즈 보다 훨씬 우수하였다. 한편 키토산이 첨가된 하이드로겔이 빠른 시간 안에 피를 응고시켜 출혈을 방지하였고 치료 효과가 우수했으나 치료말기에 상처에 약간 달라붙는 아쉬운 점이 있었다. In this study, hydrogels from mixtures of poly (N-vinylpyrrolidone)(PVP), chitosan, sodium alginate and poly(ethy1ene oxide)(PEO) were prepared by y-ray irradiation, and the physical properties such as gelation, water absorptivity, and gel strength were examined to evaluate the applicability of the hydrogels for wound dressing. Gamma ray of 10-50 k㏉ was exposed to an aqueous mixture of PVP, chitosan, sodium alginate and PEO to evaluate the effect of irradiation dose. Gel content and gel strength increased as concentration of polymers in the solution increased, and as irradiation dose increased. Swelling degree increased as concentration of polymers in the solution decreased, and as irradiation dose decreased. These hydrogel dressings had better curing effect than vaseline gauge.

      • Effects of <i>Viola mandshurica</i> on Atherosclerosis and Hepatic Steatosis in ApoE <tex> $ ^{-\slash -}$</tex> via the AMPK Pathway

        Park, Sun Haeng,Sung, Yoon-Young,Nho, Kyoung jin,Kim, Dong Sun,Kim, Ho Kyoung World Scientific Publishing Company 2017 The American journal of Chinese medicine Vol.45 No.4

        <P>Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of <I>Viola mandshurica</I> W. Becker (<I>V. mandshurica</I>) water extract on atherosclerosis in apolipoprotein E deficient (ApoE<TEX>$ ^{-\slash -}$</TEX>) mice. The administration of <I>V. mandshurica</I> to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that <I>V. mandshurica</I> attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. <I>V. mandshurica</I> also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). <I>V. mandshurica</I> reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of <I>V. mandshurica</I> by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of <I>V. mandshurica</I> may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by <I>V. mandshurica</I> may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.</P>

      • KCI등재

        Low Positive Predictive Value of Bone Scan to Predict Impending Complete Fracture among Incomplete Atypical Femoral Fracture

        Lee, Young-Kyun,Lee, You Jin,Lee, Na Kyoung,Nho, Jae-Hwi,Koo, Kyung-Hoi KOREAN ACADEMY OF MEDICAL SCIENCE 2018 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.33 No.22

        <P><B>Background</B></P><P>Although bone scan might be useful to detect incomplete atypical femoral fractures (AFFs) earlier than radiographs, there is no study on predicting further progression to a complete fracture among incomplete AFFs. Our purposes are to determine whether bone scan detects impending complete fracture among incomplete AFFs.</P><P><B>Methods</B></P><P>We reviewed 18 patients (20 AFFs) who underwent bone scan at the diagnosis of incomplete AFF and were not treated with prophylactic fixation. A diagnosis of impending complete fracture was made, when the femur completely fractured within 6 months after the scan. We correlated radioisotope uptake with the impending complete fracture to calculate sensitivity, specificity, positive predictive value and negative predictive value of bone scan.</P><P><B>Results</B></P><P>Thirteen AFFs (65%, 13/20) showed a positive uptake in bone scan. Among the 13, only one femur was completely fractured within 6 months. None of the 7 femurs without uptake in bone scan fractured. In diagnosing impending complete fracture, the sensitivity of bone scan was 100% and negative predictive value was 100%. However, the specificity (36.8%) and positive predictive value (7.7%) were quite low.</P><P><B>Conclusion</B></P><P>Bone scan has no significant role in detecting the impending complete fracture, and a positive uptake does not mean the necessity of prophylactic fixation of incomplete AFF.</P>

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