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      • SCOPUSKCI등재

        Articles : Anti-hyperlipidemic Effect of Insamsansa-eum in Mice

        ( Sang Hyun Jung ),( Chang Nam Ko ),( Hyung Sup Bae ),( Young Suk Kim ),( Ki Ho Cho1 ),( Sung Won Min ),( Dong Hyun Kim ) 한국생약학회 2008 Natural Product Sciences Vol.14 No.4

        Hypolipidemic effect of Insamsansa-eum (ISE, Ren-Shen-Shan-Zah-Yin in Chinese) consisted of Red ginseng (RG; the steamed root of Panax ginseng C.A. Meyer) and Crataegii fructus (CF, the fruit of Crataegus pinnatifida BGE) is used frequently in China and Korea as a herbal medicine to treat arteriosclerosis, was investigated. Treatment of ISE significantly reduced blood triglyceride (TG) and total cholesterol (TC) levels in Triton WR-1339-induced hyperlipidemic mice and serum TG levels in corn oil-induced hypertriglyceridemic mice. ISE significantly lowered the high blood TG and TC levels as well as body and epididymal mass weights in hyperlipidemic mice induced by long-term feeding of a high-fat diet and increased blood HDL cholesterol level. ISE and its ingredients, RG and CF, inhibited pancreatic lipase and HMG-CoA reductase activities. Of its ingredients, RG reduced the blood TC level and HMG-CoA reductase activity more than CF. CF reduced blood TG level and pancreatic lipase activity more than RG. These finding suggest that the antihyperlipidemic effect of ISE may be due to synergistic inhibition of HMG-CoA reductase and pancreatic lipase by RG and CF, and that ISE may be effective hypolipidemic agents.

      • LC, Acute : O-061 ; Mode of cirrhosis related complication in Korean patients with liver cirrhosis -A prospective multicenter cohort study

        ( Hyun Young Woo ),( Jeong Won Jang ),( Sang Gyune Kim ),( Chang Hyeong Lee ),( Tae Yeob Kim ),( Won Young Tak ),( Sung Kyu Choi ),( Mong Cho1 ),( Jong Young Choi ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

        Background: Cirrhosis-related complications are indications for transplantation. However, the mode of complication has not been evaluated so far. To better address this issue, we investigated the mode of cirrhosis related complication and impact of these complications on survival in prospective, multicenter, inception cohort study of subjects with liver cirrhosis presenting with the first onset of decompensated complication. Methods: In this observational study, 1515 patients with the confirmed onset time of the first decompensated complication were enrolled. The mortality risk of cirrhosis-related complications, including ascites, portal hypertensive gastrointestinal bleeding (PHGB), spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), hepatorenal syndrome (HRS), was analyzed in these cirrhotic patients. Result: As the first complication, ascites was the most frequent (53.8%), followed PHGB (36.2%), HE (7.6%), SBP (1.7%) and HRS (0.7%). During follow-up (mean 32±47 months), 484 (31.9%) experienced subsequent decompensations and the proportion of subsequent complication was consistently changed; the proportion of HE, SBP, HRS increased as time progressed. The interval between subsequent decompensative events was progressively shortened. The mortality rate according to the first complication was as follows; Ascites =PHGB> HE=SBP>HRS. The mortality rate of patients experienceing subsequent complication was significantly higher than those without subsequent complication. According to the kinds of subsequent complication, survival of HE was also higher than HRS but lower than ascites or PHGB and similar to that of SBP and this difference of survival disappeared after repeated complication. Conclusion: The mortality risk correlated with initial complication and the risk increases as the number of complication episodes is repeated. Patient`s mean age was 56±11.50 years and 72.1% was male. The cause of liver cirrhosis is hepatitis B virus (38.6%), alcohol (35.5%) and hepatitis C virus (8.9%).

      • KCI등재

        법률회피

        조승현(Cho Sung Hyun) 한국재산법학회 2011 재산법연구 Vol.28 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

        법률회피란 하나의 행위에 대해 적용할 수 있는 법규가 있음에도 그 행위를 법적용으로부터 부당하게 배제시키려는 시도를 말한다. 일반 사법영역에서 법률회피현상은 원칙적으로 대부분 법률과 법률행위의 해석에 의해서 해결될 수밖에 없을 것이다. 다만, 법률과 법률행위의 해석은 모든 법 영역에서 동일한 방법론으로 일관되게 관철될 수 없다. 왜냐하면 유추해석이 충분히 허용되는 영역에서는 해석에 의하여 만족한 결과를 얻을 수 있겠지만 그렇지 않은 영역에서는 해석의 한계와 동시에 법률의 흠결이라는 문제점에 직면할 수밖에 없기 때문이다. 법률은 시간과 공간의 제약을 받을 수밖에 없으며 이러한 제약을 입법자의 입법의도나 목적을 고려하고 법률회피가 발생한 시점의 객관적 법의 취지를 살려 최대한 현실을 법에 포섭시키더라도 타당한 결론을 얻을 수 없는 상황이 존재하는 것이다. 이러한 문제점들을 반영한 현상이 법률회피에 대한 새로운 인식과 함께 여기서 얻어진 요건들을 입법에 반영하는 흐름이라고 할 것이다. Gesetzesumgehung ist der Versuch, einen Tatbestand von der Anwendung eines auf ihn anwendbaren Rechtssatzes unstatthafterweise auszuschließen. Seit der Erlörterung dieser Frage können drei Ansichten über den Charakter der Gesetzesumgehung, d.ß das Verständnis der Gesetzesumgehung als Scheingeschäft, als ein Problem der Gesetesauslegung, als selfständiges Rechtsinstitut unterschieden werden. Das Reichgericht hatte Rechtsgeschäft, die unter dem Gesichtspunkt der Umgehung hätten geprüft werden müssen, als simulierte Geschäfte behandelt. Aber diese Ansicht hat es auf Kritik aufgegeben, die darauf hinwiesen, daß man das geschäft so, wie man es abschließe, tatsächlich wolle und auch die unbequemen Flogen um des wirtschaftllichen Erfolges in Kauf nehme. Denn nur auf diese Weise könne man den verbotennen Erfolg errechein. Nach der Lösung, Umgehungsgeschäft als Scheingschäft zu behandeln, wurde schlagen die Ansicht, eine Art ausdehnender Anwendung von Vervotsgesetzen auf solche Handlungen vor, die zwar direct dem Verbote nicht widerstreiten, die aber zu dessen Umgehung dienen. Aber die Ansicht dachte nicht an die extensive Interpretation, sondern befürwortete ein slbständiges Rechtsinstitut Gesetzesumgehung, mit dessen Hilfe die beschriebenen Rechtsgeschäfte für nichtig erklärt werden sollten. Bei den Versuchen, die Umgehung des Gesetzes von den zulässigen Rechtsgeschäften ahzugrenzen, stand von Anfang an der sogensnnte Umgehungsvorsatz im Vordergrund der Erörterungen. Wenn dieses Merkmal vorliegt, dann sollen die Rechtsnachfolgen der Umgehung(Nichtigkeit oder Einordnung des Geschäfts unter die gesetzlichen Folgen kraft des Satzes von der Gleichstellung) eintreten, wärend das gleiche Rechtsgeschäft bei unvorsätzlich handelnden Parteien zulässig sein soll. Aber die Begründung für die Ablehung dieses Merkmales ird häufig in den Schwierigkeiten gesehen, den Vorsatz der Parteien nachzuweisen. Ihr Verhältnis zum Rechtsmißbrauch wird stärk erörtert. Der Begriff des Mißbrauchs worden besonders durch die Formulierung des §5 der Reichsabgaben-ordnung(1919) hervorgehoben. Im Steuerrecht lassen sich in drei Merkmal über das Verständnis des Mißbrauches im Zusammenhang mit der Gesetzesumgehung unterschneiden. Das ist Ungewönlichkeit, Umgehungszweck, wirtschaftliche Unzulässigkeit. Jedoch kann die Ungewönlichleit, Umgehungszweck, wirtschaftliche Unzulässigkeit nicht das entscheidende Kriterium für das Verliegen einer Umgehung sein. Denn diese Merkmals sind wenig faßbar und ein Problem der Auslegung des Rechtsgeschäfts und haben die Schwierigkeit des Beweis. Der Schwerpunkt der auseinandersetzung lag auf der Frage, ob Gesetzesumgehung als selbständiges Rechtsinstitut anzusehen sei oder ob es sich lediglich um eine Frage der Auslegung oder Analogie handele. Bis 1960er Jare waren die Meinungen zu dieser Frage geteilt, die wohl noch überwiegende Meinung gig von einem selbständigen Rechtsinstitut der Gestzesumgehung aus. Aber den Anstoß zu einer Wandlung des Meinungsstandes gab die 1962 erschienene Dissertation „ Die Gesetzesumgeung„ von Teichmann. Teichmann legte anhand mehrerer Beispiele dar, wie bisher unter dem Aspekt der Gestzesumgehung diskutierte Fragen mit dem Mittel der Gestzesanalogie gelöst werden könnten. Manche Umgehungsfälle können mit Auslegung oder analoger Anwendung des umgangenen Gestzes werden gelösten. Umgehungsfälle sind Ausnamefälle, die sich weder mit Auslegung noch mit anderen Rechtsinstituten befriegend lösen lassen. In Umgeungsfälle gibt es keine einheitliche Lösung. Dnnoch ist Gesetzesumgehung als Rechtsbegriff nicht überflüssig. Gesetzesumgehung im materiellen Sachreht u

      • SCIESCOPUSKCI등재

        Three-Dimensional Porous Collagen/Chitosan Complex Sponge for Tissue Engineering

        Kim, Sung Eun,Cho, Yong Woo,Kang, Eun Jung,Kwon, Ick Chan,Lee, Eunhee Bae,Kim, Jung Hyun,Chung, Hesson,Jeong, Seo Young The Korean Fiber Society 2001 Fibers and polymers Vol.2 No.2

        A three-dimensional, porous collagen/chitosan complex sponge was prepared to closely simulate basic extracellular matrix (ECM) constitutes, collagen and glycosaminoglycan. The complex sponge was prepared by a lyophilization method and had the regular network with highly porous structure, suitable for cell adhesion and growth. The pores were well interconnected, and their distribution was fairly homogeneous. The complex sponge was crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to increase its boilogical stability and enhance its mechanical properties. The crosslinking medium has a great effect on the inner structure of the sponge. The homogeneous, porous structure of the sponge was remarkably collapsed in an aqueous crosslinking medium. However, the morphology of the sponge remained almost intact in a water/ethanol mixture crosslinking milieu. Mechanical properties of the collagen/chitosan sponge were significantly enhanced by EDC-mediated crosslinking. The potential of the sponge as a scaffold for tissue engineering was investigated using a Chinese hamster ovary cell (CHO-K1) line.

      • KCI등재

        연구논문 : 1분과 ; 종 분포 모형을 이용한 구상나무림의 지속 및 쇠퇴에 관한 연구 - 전라남도 광양시 백운산을 중심으로 -

        조선희 ( Seon Hee Cho ),박종영 ( Jong Young Park ),박정호 ( Jeong Ho Park ),이양근 ( Yang Geun Lee ),문이만 ( Lee Man Mun ),강상호 ( Sang Ho Kang ),김광현 ( Gwang Hyun Kim ),윤종국 ( Jong Guk Yun ) 한국임학회 2015 한국산림과학회지 Vol.104 No.3

        본 연구에서는 백운산 내 구상나무 서식지를 조사하여 현존 분포도를 작성하고 분포에 영향을 미치는 생물학적 환경인자와 비 생물학적 환경인자의 기여도를 정량화하여 서식지 또는 대체서식지로써 잠재성을 가지고 있는 지역을 도출하고 보호구역 설정 안을 제시하였으며, RCP 8.5 기후변화 시나리오를 적용하여 기후변화가 향후 구상나무의 분포에 미치는 영향을 분석한 미래 잠재 서식지를 예측 하였다. 연구 결과 백운산 내 구상나무는 3,325개체(DBH >= 2.5 cm)가 서식하고 있었고 분포 면적은 150 ha 정도였다. 해발 900 m에서 구상나무의 개체가 확인되어 1,200 m까지 분포하고 있었으며, 잠재 분포도를 기반으로 현재 구상나무가 서식하기에 적합한 지역은 상봉, 억불봉, 따리봉, 도솔봉을 중심으로 현존 분포 면적의 3배인 450 ha로 분석되었다. 주봉인 상봉 인근이 구상나무의 서식에 가장 적합한 잠재력을 가진 임분으로 평가 되었으며, 남사면보다는 북사면을 선호하는 경향을 보이고 있었다. 기후변화 시나리오 RCP 8.5를 적용하여 미래의 잠재적 분포를 분석한 결과 2050년에는 상봉 주변을 중심으로 20 ha까지 서식지 면적이 감소될 것으로 나타나며, 2080년에는 서식에 적합한 지역이 존재하지 않을 것으로 예측된다. 이러한 결과로 볼 때 지구온난화가 가속화될수록 구상나무는 저지대에서 고지대로 서식지의 이동 양상이 뚜렷해질 것으로 판단된다. The present study investigated the habitats of Korean fir trees (Abies koreana E. H. Wilson) on Mt. Baekwun (Baekwun-san), determined the current distribution, quantified the contribution of biological and nonbiological environmental factors affecting the distribution, derived actual and potential habitats, presented a plan for the establishment of protected areas, applied RCP 8.5 climate change scenario to analyze the effects of climate change on the future distribution of Korean fir trees, and predicted future potential habitats. According to the results of the study, 3,325 Korean fir trees (DBH >= 2.5 cm) inhabited Mt. Baekwun, and their distribution area was approximately 150 ha. Populations of Korean fir trees were confirmed to exist at an altitude of 900 m above sea level and were distributed up to 1,200 m. Based on potential distribution, areas appropriate for habitation by Korean fir trees were analyzed to be 450 ha, three times the current distribution area, with a focus on Sang Peak (Sang-bong), Eokbul Peak (Eokbul-bong), Ddari Peak (Ddari-bong), and Dosol Peak (Dosol-bong). The forest stands near Sang Peak, the main peak, were evaluated as those with the most appropriate potential for the habitation of Korean fir trees, and populations of the trees tended to prefer the northern slope rather than the southern slope. When climate change scenario RCP 8.5 was applied and future potential distribution was analyzed, the habitats were expected to decrease in area to 20 ha by 2050, with a focus on Sang Peak, and areas appropriate for habitation were predicted not to exist by 2080. Judging from such results, as global warming accelerates, the habitats of Korean fir trees are clearly expected to move from lowlands to highlands.

      • KCI등재

        3T Multi Voxel Spectroscopy에서 SENSE와 NEX 변화에 따른 정상인 뇌 대사물질 변화 분석

        성열훈,임재동,이재현,조성봉,우동철,최보영,Seong, Yeol-Hun,Rhim, Jae-Dong,Lee, Jae-Hyun,Cho, Sung-Bong,Woo, Dong-Chul,Choe, Bo-Young 한국의학물리학회 2008 의학물리 Vol.19 No.4

        자기공명분광법(magnetic resonance spectroscopy: MRS)은 인체내 대사물질을 정량분석하여 병변의 조기진단 및 정밀진단에 도움을 주고 있으며, 최근 임상에 이용되고 있는 자기공명분광법은 single voxel spectroscopy (SVS) 기법과 multi voxel spectroscopy (MVS) 기법이 있다. 본 연구에서는 SENSE와 NEX를 변화시킨 multi voxel spectroscopy (MVS)의 데이터와 기존 single voxel spectroscopy (SVS)의 데이터를 비교 분석하여, 각각의 데이터의 유의성 차이를 평가하고자 하였다. 정상 성인 지원자 13명(남자: 5명, 여자: 8명, 평균 41세, 표준편차 11.65세)을 대상으로 chemical shift image (CSI)를 이용한 MVS검사를 시행하였다. 장비는 3.0T Achieva Release Version 2.1 (Philips Medical System, Netherland)을 이용하였고, 8 channel head coil을 사용하여 brain thalamus 부위에서 CSI spectrum을 1 slice 획득하였다. Scan parameter로는 FOV (field of view): $230{\times}184mm^2$, TR (time to repetition): 2000 msec, TE (time to echo): 288 msec, matrix: $15{\times}12$, VOI(view of interest): $110{\times}110mm^2$, voxel size: $15{\times}15{\times}15mm^3$로 하였다. SENSE factor (S)와 NEX (N)는 S1*N1, S2*N1, S2*N2, S3*N2로 변화하여 스펙트럼을 획득하였고, 각 scan time은 5분 54초, 3분 32초, 6분 20초, 4분 20초였다. 얻은 모든 MRS 데이터는 jMRUI 3.0 Version 프로그램에서 분석하였고, SENSE factor와 NEX를 변화시켜 얻은 MVS data 그룹들이 정상 성인 뇌 대사물질의 변화에 영향을 주는지 검증하기 위해 그룹 간에 ANOVA분석을 실행하여 P 값이 0.05보다 크게 나오면 그룹들 사이에 유의한 차이가 없다고 분석하였다. NAA/Cr과 Cho/Cr의 상대적 비율은 MV와 SVS사이에서는 유의한 차이가 없었다. 즉, SENSE factor와 NEX를 변화시켜 얻은 MVS data에서 정상 성인 뇌조직의 대사물질의 변화를 관찰한 결과, S1*N1의 NAA/Cr은 $1.45{\pm}0.03$, Cho/Cr은 $0.88{\pm}0.03$이고, S2*N1의 NAA/Cr은 $1.44{\pm}0.03$, Cho/Cr은 $0.87{\pm}0.05$, S2*N2의 NAA/Cr은 $1.43{\pm}0.02$, Cho/Cr은 $0.87{\pm}0.04$이며, S3*N2의 NAA/Cr은 $1.45{\pm}0.03$, Cho/Cr은 $0.87{\pm}0.03$으로 나타났다(F-value : 1.37, D.F : 3, P-value : 0.262). 그러나 데이터의 질을 측정하기 위한 MVS 데이터의 NAA Peak line-width는 SVS 데이터의 NAA Peak line-width 보다 약 3배 정도 넓었다. 본 연구에서는 MVS에서 SENSE factor와 NEX 값을 다양하게 변화시킨 MVS의 데이터와 SVS의 데이터가 큰 차이가 없음을 확인하였다. 즉, 어는 특정 부위의 뇌 조직의 대사물질은 MVS와 SVS 기법 모두 큰 차이가 없음을 확인할 수 있었다. 그러므로 MVS는 SVS보다 광범한 부위를 짧은 시간 안에 검사할 수 있으므로 매우 유용한 방법이라고 사료된다. To evaluate the metabolic changes in normal adult brains due to alterations SENSE and NEX (number of excitation) by multi voxel MR Spectroscopy at 3.0 Tesla. The study group was composed of normal volunteers (5 men and 8 women) with a mean ($\pm$ standard deviation) age of 41 (${\pm}11.65$). Their ages ranged from 28 to 61 years. MR Spectroscopy was performed with a 3.0T Achieva Release Version 2.0 (Philips Medical System-Netherlands). The 8 channel head coil was employed for MRS acquisition. The 13 volunteers underwent multi voxel spectroscopy (MVS) and single voxel spectroscopy (SVS) on the thalamus area with normally gray matter. Spectral parameters were as follows: 15 mm of thickness; 230 mm of FOV (field of view); 2000 msecs of repetition time (TR); 288 msecs of echo time (TE); $110{\times}110$ mm of VOI (view of interest); $15{\times}15{\times}15$ mm of voxel size. Multi voxel spectral parameters were made using specially in alteration of SENSE factor (1~3) and 1~2 of NEX. All MRS data were processed by the jMRUI 3.0 Version. There was no significant difference in NAA/Cr and Cho/Cr ratio between MVS and SVS likewise the previous results by Ross and coworkers in 1994. In addition, despite the alterations of SENSE factor and NEX in MVS, the metabolite ratios were not changed (F-value : 1.37, D.F : 3, P-value : 0.262). However, line-width of NAA peak in MVS was 3 times bigger than that in SVS. In the present study, we demonstrated that the alterations of SENSE factor and NEX were not critically affective to the result of metabolic ratios in the normal brain tissue.

      • Construction of Stably Transformed Bm 5 Cells by Using Autographa californica Nuclear Polyhedrosis Virus IE 0 Gene

        Cho, Eun Sook,Jin, Byung Rae,Sohn, Hung Dae,Choi, Kwang Ho,Kim, Soung Ryul,Kang, Seok Woo,Yun, Eun Young,Kim, Sang Hyun,Kim, Keun Young,Je, Yeon Ho,Kang, Seok Kwon 한국잠사학회 1998 한국잠사곤충학회지 Vol.40 No.2

        To construct transfurmed Bm5 cells, Autographa californica nuclear polyhedrosis virus(AcNPV) IE1 gene, an immediate early viral gene was firstly used in this study. AcNPV IE1 gene, which shares on 95.3% nucleotide sequence homology with Bombyx mori nuclear polyhedrosis virus (BmNPV) IE1 gene, was isolated and cloned into pBluescript. Neomycin gene from pKO-neo was inserted under the control of the IE1 promoter to yield pAcIE1-neo. The plasmid pAcIE1-neo was transfected into Bm5 or Sf9 cells, and neomycin-resistant cells were selected in TC100 medium containing 10% fetal bovine serum (FBS) and 1 mg/ml G4l8 for two weeks. Individual clones were picked and each was amplified for further characterization. The genomic DNA from neomycin-resistant cells was isolated and characterized by PCR using AcNPV IEI gene-specific primers and by Southern blot analysis using neomycin gene probe. We concluded that AcNPV IE1 gene was functional in B. mori-derived Bm5 cells as well as Spodoptera fugjprrda-derived Sf9 cells to produce stably-transformed insect cells

      • KCI등재

        Effects of Ca Doping on Nodule Formation of on ITO Target during DC Magnetron Sputtering

        Sang-Hyun Cho,강용민,이정락,류봉기,이진호,최준호,송풍근 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.3

        Indium tin oxide (ITO) and Ca-doped ITO films were deposited on non-alkali glass substrates by DC magnetron sputtering without substrate heating using three different ITO targets (10 wt% SnO2) containing 0, 0.025 and 0.05 wt% CaCO3. In the case of the Ca-doped ITO films, relatively stable electrical properties were obtained at increasing erosion ratios of the target (0, 15, 30, 45, 65, 75 %) and sputtering times (0, 6, 12, 18, 24, 30 h), which was attributed to decreases in both micro- arcing and the plasma impedance. On the other hand, the resistivity of the ITO films deposited using a commercial ITO target increased remarkably with increasing levels of micro-arcing and erosion of the target surface.

      • SCISCIESCOPUS

        Oral siRNA delivery using dual transporting systems to efficiently treat colorectal liver metastasis

        Hyun, Eun-Ju,Hasan, Mohammad Nazmul,Kang, Sung Hun,Cho, Sungpil,Lee, Yong-Kyu Elsevier 2019 International journal of pharmaceutics Vol.555 No.-

        <P><B>Abstract</B></P> <P>Oral siRNA delivery is an ideal way to translate siRNA therapeutic effects in the clinic due to its ability to be administered in convenient and multiple dosages. However, an effective oral delivery system requires overcoming both a hostile gastrointestinal (GI) environment and non-specific targeting. Here, an HTsRP-NC system is a new oral siRNA delivery system consisting of a siRNA/protamine (sRP) nano-complex protected by a multi-functional hyaluronic acid-taurocholic acid (HA-TCA) conjugate. The HTsRP-NC promotes cell penetration and enhances endosomal escape in cancer cells. Moreover, protection of the sRP by HA-TCA from the hostile GI environment helps the AKT siRNA complex to reach the liver through the utilization of a TCA-mediated enterohepatic bile acid recycling system. AKT siRNA was released by 90% in presence of hyaluronidase in the tumor cells which indicate the potential use of HTsRP-NCs for siRNA delivery to treat tumor. After HA receptor (CD44)-mediated cellular uptake of the HTsRP-NC by the liver cancer cells, functional expression of AKT siRNA leads to the suppression of metastatic liver cancer growth in a colorectal liver metastasis (CLM) murine model. Tumor nodules were reduced by more than 1 mm size compared to control group and tumor cells were suppressed by 50% after HTsRP-NCs treatment with AKT siRNA. Overall, oral administration of the HTsRP-NC supports its potential in therapeutic applications for the effective treatment of CLM.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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