Signal transducer and activator of transcription 3‐mediated CD133 up‐regulation contributes to promotion of hepatocellular carcinoma

Won, Cheolhee,Kim, Byung‐,Hak,Yi, Eun Hee,Choi, Kyung‐,Ju,Kim, Eun‐,Kyung,Jeong, Jong‐,Min,Lee, Jae‐,Ho,Jang, Ja‐,June,Yoon, Jung‐,Hwan,Jeong, Won‐,Il,P John Wiley and Sons Inc. 2015 Hepatology Vol.62 No.4

<P>Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed <I>in vivo</I> tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. <I>Conclusion</I>: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (H<SMALL>EPATOLOGY</SMALL> 2015;62:1160‐1173)</P>

Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene

Chang-Min Lee(이창민),Jeong Hyun Chang(장정현),In Duk Jung(정인덕),Young-Il Jeong(정영일),Noh Kyung Tae(노경태),Hee-ju Park(박희주),Jong-Suk Kim(김종석),Yong Kyoo Shin(신용규),Sung Nam Park(박성남),Yeong-Min Park(박영민) 한국생명과학회 2009 생명과학회지 Vol.19 No.6

Naringin은 레몬, 오렌지에서 발견되는 flavonoid계열에 속하는 물질로 여러 식물과 과일에 다량 함유되어 있다. 항암, 항산화 작용을 하는 것으로 알려져 있는 Naringin을 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델을 이용하여 치료효과를 알아 보았다. 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 또한, 최근에 Th1/Th2 전사인자로서 GATA-3가 밝혀졌는데 이번 실험에서 Naringin이 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1, Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 Naringin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 Naringin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 Naringin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

一部 美容業 從事者들의 織責別 腰痛 有病率과 關聯要因

김춘일,박종,류소연,김석산,김기순,하상호,변주남 조선대학교 부설 의학연구소 1999 The Medical Journal of Chosun University Vol.24 No.1

To find the prevalence and related factors of low back pain experienced by some beauticians. a survey was made toward 252 beauticians in Kwangju City from March 1st to April 1st, 1998. The results were as follows; 1. The prevalence rate of low back pain among the respondents for the last week was 59.5%. 2. The aid group and staff group with low back Pain had significantly longer duration of work than those without low back pain. Managers who had bad posture with twisted or too much extended back showed a significantly higher prevalence of low back pain than those with good posture during work(P<05). 3. Aid group with low back pain showed significantly higher points at total stress score, depression score, general health score and vitality score than those without low back Pain. The staff group with low back pain showed significantly higher points for total stress score, sleep disorder and anxiety score, depression score, general well-being and vitality score than those without low back pain. Managers with low back Pain showed significantly higher points of stress at social performance and self confidence (P<05) than those without low back pain. The above results suggest that low back pain is related to different jobs and work environments for beauticians. So effective measures and further studies against risk factors must be made considering their jobs. To prevent or reduce low back pain, appropriate management of stress for beauticians is necessary.

電子商去來와 著作權 : 라이센스계약과 知的財産法의 충돌 A Conflict of License Contract and the Intellectual Property Law

조성종,전일주 진주산업대학교 2001 論文集 Vol.40 No.-

The relationship between contract and intellectual property about the future of copyright in the information industries on the electronic commerce(for example a software transaction on the Internet), it often appears as if some believe that we are facing an impending big bang as the fields of copyright and contract(for example a "shrink-wrap" contract) head toward some unclearly defined, but inevitably cataclysmic conflict. The fields of contract and intellectual property law have always co-existed, not only peacefully, but in an aggressive interaction between ordinarily consistent and mutually supportive fields. Modern efforts to tailor contract themes to fit the digital information era and the commerce it yields follow that great tradition. This study aims at understanding the scope of protection for intellectual property and effectiveness of unilateral form license contract. The Contents are as follow : Ⅰ. Introduction Ⅱ. Scope of protection for intellectual property Ⅲ. Effectiveness of unilateral form license contract Ⅳ. Conclusion

저작권보호에 관한 연구 : 인터넷상의 저작권을 중심으로

조성종,전일주 진주산업대학교 2002 論文集 Vol.41 No.-

By now, most everyone is familiar with the Internet and the World Wide Web and has at least sent a few e­mails or reviewed a number of web site. The Internet makes it extraordinarily easy to copy data. Copying or distributing of materials on the Internet, without the owner's consent, could result in copyright infringement. This study aims at understanding the protection of copyright, desiring to remove the distortions and impediments in the Internet, and taking into account the needs to promote effective and adequate protection of copyright.

흰쥐 악하선 세포에서 gap junction 봉쇄제인 octanol이 타액분비 및 세포내 Ca²+ 농도 조절에 미치는 영향

이승일,서정택,이종갑,이주석,손흥규 大韓小兒齒科學會 1999 大韓小兒齒科學會誌 Vol.26 No.2

세포내 유리칼슘(free calcium. Ca²+)은 세균에서 고등동물에 이르기까지 거의 모든 세포에서 세포 고유작용을 조절하는 중요한 세포내 신호전달체계(signal transduction system)의 매개체이다. 타액선 세포에서 부교감 신경 자극으로 타액분비가 증가될 때에도 세포내 Ca²+ 농도 증가가 가장 중요한 역할을 한다. 그러나 췌장(pancreas)의 경우 세포내 Ca²+ 이외에도 인접세포를 전기적, 화학적으로 연결해주는 gap junction이 외분비 기능을 직접적으로 조절할 가능설이 제시되었다. 타액선 세포에서도 세포막에 고농도의 gap junction이 존재하고 있으며, gap junction을 통해 인접세포들이 전기적, 화학적으로 연계되어 있어 gap junction이 타액선 세포의 기능을 직접적으로 조절할 가능성을 내포하고 있다. 따라서 gap junction이 타액선의 타액분비 작용에도 중요한 역할을 하며 이러한 작용이 세포내Ca²+ 농도를 조절하여 이루어질 것이라는 가정하에 이를 확인하는 실험을 시행하였다. 흰쥐 악하선에서 유리되는 타액양을 측정하기 위해서 악하선으로 혈액을 공급하는 동맥에 가는 관을 삽입하여 생리 식염수를 관류하면서 타액선관을 통해 타액을 채취하였다. 세포내Ca²+ 농도는 분리한 악하선 acini 내에Ca²+ 농도 변화에 민감하게 반응하는 형광물질인 fura-2를 축적시키고 형광 분석기를 사용하여 형광강도를 측정하여 다음과 같은 결과를 얻었다. 1. CCh 투여로 타액 분비가 증가하였을 때 gap junction을 봉쇄하는 약물인 octanol(1 mM)을 투여하면 타액분비가 봉쇄되었으며 이는 가역적 반응이었다. 2. CCh 투여로 세포내 Ca²+ 농도가 증가하였을 때 1mM octanol을 투여하면 세포내 Ca²+농 도가 CCh 투여전의 상태로 감소되었다. 3. Octanol은 CCh에 의하여 유발된 초기Ca²+ 증가를 억제하지는 못한 반면에 후기 vvvvv 농도를 감소시켰다. 4. 세포막 Ca²+ 통로를 열어주는 약물인 thapsigarain(1μM)을 투여하여 세포내Ca²+ 농도를 증가시킨 후 1mM octanol을 투여하면 세포내 Ca²+ 농도가 thapsigarain 투여 전의 상태로 감소하였다. 5. 2,5-di-tert-butyl-1, 4-benzohydroquinone (TBQ)의 투여로 세포막을 통한 Ca²+농도의 주기적 변동인Ca²+ 의 oscillation이 유발되었는데, 이때 1mM octanol을 투여한 경우에 Ca²+ 농도의 oscillation이 정지하여 역시 gap juncion을 봉쇄하면 TBQ에 의해서 유발된 세포내 Ca²+ 농도의 주기적 변동이 사라지고 Ca²+ 농도의 감소가 나타남을 확인하였다. 6. Gap junction을 봉쇄하는 또 다른 약물인 glycyrrhetinic acid(100μM)도 CCh 자극으로 인한 타액분비를 억제하였다. 이상의 결과로 미루어 gap junction은 흰쥐 악하선 세포로부터의 타액분비 조절에 중요한 역할을 하는 이는 gap junction이 세포막 Ca²+ 통로를 조절함으로써 수용체 자극으로 유발된 세포내 농도 변화에 영향을 미친 결과인 것으로 추측된다. From bacteria to mammalian cells, one of the most important mediators of intracellular signal transduction mechanisms which regulate a variety of intracellular processes is free calcium. In salivary acinar cells, elevation of intracellular calcium concentration ( 〔Ca²+〕 ) is essential for the salivary secretion induced by parasympathetic stimulation. However, in addition to〔Ca²+〕, gap junctions which couple individual cells electrically and chemically have also been reported to regulate enzyme secretion in pancreatic acinar cells. Since the plasma membrane of salivary acinar cells has a high density of gap junctions, and these cells are electrically and chemically coupled with each other, gap junctions may modulate the secretory function of salivary glands. In this reapect, I planned to investigate the role of gap junctions in the modulation of salivary secretion and 〔Ca²+〕 using mandibular salivary glands of rats. In order to measure the salivary flow rate, fluid was collected from the cannulated duct of the isolated perfused rat mandibular glands at 2 min intervals.〔Ca²+〕 was measured form the cells loaded with fura-2 by spectrofluorometry. The results obtained were as follows : 1. CCh-induced salivary secretion was reversibly inhibited by 1 mM octanol, a gap junction blocker. 2. CCh-induced increase in 〔Ca²+ 〕was also reversed by the applocation of 1 mM octanol. 3. Octanol did not block the initial increase in 〔Ca²+〕 caused by CCh, which suggested that the reduction of〔Ca²+〕 caused by gap junction blockade was not resulted from the inhibition of Ca²+ release from intracellular Ca²+ stores. 4. Addition of octanol during stimulation with 1μM thapsigargin, a potent microsomal ATPase inhibitor, reduced 〔Ca²+ 〕to the basal level. This suggested that inhibition of gap junction permeability closed plasma membrane Ca²+ channels. 5. 2,5-di-tert-butyl-1, 4-benzohydroquinone (TBQ) generated 〔Ca²+ 〕oscillations resulting from periodic influx of Ca²+ via plasma membrane. The TBQ-induced〔Ca²+ 〕 oscillations were stopped by the application of 1mM octanol which implicated that gap junctions modulate the permeability of plasma membrane Ca²+ channels. 6. Glycyrrhetinic acid, another well known gap junction blocker, also inhibited CCh-induced salivary secretion from rat mandibular glands. These results suggested that gap junctions play an important role in the modulation of fluid secretion from the fat mandibular glands and this was probably due to the inhibition ofCa²+ influx through the plasma membrane Ca²+ channels.

미역 폐기물의 중금속 흡탈착 특성

조주식,박일남,허종수,이영석 한국환경농학회 2004 한국환경농학회지 Vol.23 No.2

본 연구에서는 생물흡착제인 미역을 사용하여 인공폐액 내의 중금속의 흡착 특성을 조사하였으며, 다음과 같은 결론을 얻었다. 미역 폐기물을 이용하여 제조된 생물흡착제의 단일 중금속 흡착효율은 각 중금속 100 mg/L인 용액에 biosorbent 3 g을 처리했을 때 Pb는 거의 100%였고 Cu와 Cd가 약 85~86% Zn과 Cr은 약 60~64%, Co와 Ni은 약 57%, Mn은 약 48%였다. 복합중금속 흡착효율은 단일중금속 흡착효율에 비하여 Pb를 제외한 다른 중금속들은 크게 감소되었으나 biosorbent g당 전체 중금속 흡착량은 더 증가되었다. 온도, pH에 따른 중금속 흡착효율은 별 차이가 없었으며 전반적으로 pH는 pH 5~6 범위, 온도는 20~30℃ 범위의 실온이 적당한 것으로 나타났다. 생물흡착제의 흡착평형은 모든 중금속이 1시간 이내에 이루어졌다. Freundlich와 Langmuir 등온흡착식을 구하여 실제 폐수처리에 적용여부를 검토한 결과 Pb, Cu, Cr, Cd, Co 순으로 비교적 친화도가 큰 것으로 나타났다. Freundlich 등온흡착식에 가장 잘 일치하였다. 모든 중금속의 Freondlich 지수 1/n값이 0.1~0.5 범위에 포함되어 흡착이 용이하고, Pb, Cr, Cu, Cd 순으로 비교적 평형 흡착량이 큰 것으로 나타났으며, 이 결과는 Langmuir 흡착등온식의 결과와 거의 유사하였다. 따라서, 중금속 농도범위에 따른 한계범위를 설정하여 등온흡착식을 적용시키면 매우 높은 중금속 처리효율을 나타낼 것으로 판단된다. 생물흡착제가 중금속 흡착 후의 구조적인 특성을 조사하기 위하여 FT-IR 분석 결과, 중금속 이온과 치환될 것으로 생각되는 functional group을 확인할 수 있었으며, 3,400/cm에서의 -OH group, 1,648/cm에서의 C=O bond, 1,426/cm에서의 C-O bond 그리고 850/cm에서의 S=O등이 전반적으로 중금속 흡착 후에 peak가 커지는 것이 관찰되었다. 생물흡착제의 재사용 가능성을 검토하기 위하여 최적의 중금속 탈착조건 검토하였는데, 탈착제 종류에 따른 중금속 탈착효율은 탈착제 종류와 중금속 종류에 따라 차이가 있었고, 전반적으로 NTA>H₂SO₄>HCl>EDTA 순으로 우수하였으며, 전체적으로 특정 중금속의 탈착효율이 떨어지지 않는 NTA가 탈착제로 가장 적합하였다. NTA농도에 따른 중금속 탈착효율은 NTA 0.1~0.3% 농도범위에서는 농도 증가에 따라 탈착효율도 약간 증가되었으나 그 이상의 농도에서는 별 차이 없었다. 온도와 pH 변화에 따른 중금속 탈착효율은 Cr을 제외한 다른 중금속들은 크게 영향을 받지 않는 것으로 나타났으며 전반적으로 온도는 30℃, pH는 2에서 높았다. 탈착제 접촉 반응시간에 따른 탈착효율은 10분 이내에 전체 탈착량의 80%이상이 탈착 되었으며 1시간 이후에는 거의 변화가 없었다. The adsorption and desorption of Pb, Cd, Co, Zn, Cr, Co, Ni, and Mo on the waste Undaria sp. were studied. Except for Pb, the mono adsorption rate for all heavy metals were lower than that of the heavy metals mixed. However, the adsorption capacity of the heavy metals by 1 g of biosorbent in mixed heavy metals increased. According to FT-IR analysis of the biosorbent after heavy metal biosorption, the replacement of the functional group by the heavy metals ions could be confirmed and the inverted peaks became larger after heavy metals adsorption. The adsorption equilibrium of heavy metals was reached in about 1 hour. The equilibrium parameters were determined based on Langmuir and Freundlich isotherms. The affinity of metals on the biosorbent decreased in the following order: Pb>Cu>Cr>Cd>Co. The desorption rate decreased in the following sequence: NTA>H₂SO₄>HCl>EDTA. The desorption rate of heavy metals by NTA increased with increase in the concentration from 0.1 to 0.3% but the desorption rate became constant beyond 0.3%. Therefore, it represented that desorption rate of heavy metals was suitable under optimized condition (30℃, pH 2 and 0.3% NTA solution) and was fast with 80% or more the uptake occurring within 10 min of contact time.

Capsaicin과 Paradol이 구강내 유해자극에 의한 개구반사와 신경흥분 전달에 미치는 영향

최동주,신일영,김중수,이종흔 대한구강생물학회 1988 International Journal of Oral Biology Vol.12 No.2

This study was performed to elucidate the analgesic mechanism of paradol and to compare effects of paradol with those of dihidrocapscaicin(DHC). Rabbits(2-2.5kg both sexes) were anesthetized with pentobarbital sodium(30mg/kg I.V.), and cannulated in trachea and external jugular vein. To observe effects on jaw opening reflex, inferior alveolar nerve(IAN) of both sides were exposed for drug application, and wire electrodes were inserted in anterior belly of digastric muscle for recording of EMGs of anterior belly of digastric muscle(dEMG) and in oral mucosa covering mental foramen for applying noxious stimulation. dEMGs evoked by noxious stimulation with double intensity of threshold for digastric EMG were recorded in magnetic tape recorder. To observe effects on action potential, saphenous nerve were exposed, and three tissue pools were made from surrounding tissue. The most distal pool was used for applying stimulation, the most proximal one for recording of action potentials, and the other on for drug application. Action potentials evoked by 200 folds intensity of threshold for most sensitive fiber were recorded in magnetic tape recorder. One side of IAN and saphenous nerves were used for DHC or paradol applications, the other side of nerves for control experiments(only vehicle application). Vehicle consisted of 10% Tween 80, 10% ethanol and 80% physiological saline(v/v), and drugs were solubilized in vehicle for 1.5% concentration(w/v). dEMGs and action potentials were recorded before drug application, immediate after 30 minutes drug application, at 30 and 60 minutes after drug had been washed out. DHC application on IAN could not influence on dEMG, but paradol application decreased the amplitude of dEMG. In action potential experiments, DHC decreased amplitude and conduction velocity of only C fiber, while paradol did those of C-fiber and Aδ-fiber.

주정중독 환자에서 Marchiafava-Bignami Disease로 판명된 환자 2례

이종일,조연규,양병환,김주한 大韓神經精神醫學會 1993 신경정신의학 Vol.32 No.6

Among the many neuropsychiatric complications in chronic alcoholics, the Marchiafava-Bignami disease is a rare clinical condition, which is pathologically characterized by selective degeneration of the corpus callosum as well as the anterior and posterior commissural fibers. It can share many of the common symptoms of chronic alcoholism, but frontal lobe signs(motor and mental slowness, apathy, and frontal releasing signs) are the most consistent findings. We report two cases of Marchiafava-Bignami disease that showed abnormal signal density in the corpus callosum on MRI or CT, and that presented with initial symptoms of psychiatric problems such as personality and behavioral changes.

商標權의 侵害와 그 保護에 관한 硏究

조성종,전일주 진주산업대학교 1998 論文集 Vol.37 No.-

The owner of a registered trademark shall have the exclusive right to prevent all third parties not having his consent from using in the course of trade identical or similar signs for goods or services which are identical or similar to those in respect of which the trademark is registered where such use would result in a likelihood of confusion. But the trademark is prevented by thrid parties excessively so often. Many international treates were prescribed for the protectiuon of trademark. This study aims at understanding the treaties for protection of the trademark, desiring to remove the distortions and impediments to international trade, and taking into account the needs to promot effective and adepuate protection of trademark, and to ensure that the measures and procedures to enforce trademark do not themselves become barriers to the legitimate trade, and examining the problems of the Paris Convention for the Protection of Industrial Property and korean trademark law.