• Title/Summary/Keyword: growth regulation

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Apoptosis Induction of Human Breast Carcinoma Cells by Ethyl Alcohol Extract of Hizikia fusiforme (Apoptosis 유도에 의한 톳 ethyl alcohol 추출물의 인체 유방암세포 증식 억제)

  • Jung, Sun-Hwa;Hwang, Won-Deuk;Nam, Taek-Jeong;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.11
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    • pp.1581-1590
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    • 2009
  • Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest pacific, including Korea, Japan and China, and has been widely used as a health food for hundreds of years. Recently, H. fusiforme has been known to exert pharmacological activities including antioxidant, antimutagenic and anticoagulant activities. However, the molecular mechanisms of H. fusiforme in malignant cells have not been clearly elucidated yet. In this study, the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells were investigated. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells, which could be proved by MTT assay, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF treatment correlated with up-regulation of pro-apoptotic Bax expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase, $\beta$-catenin, phospholipase-${\gamma}1$ protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme.

Pro-apoptotic Effects of Platycodin D Isolated from Platycodon grandiflorum in Human Leukemia Cells (도라지 유래 사포닌 platycodin D에 의한 인체 백혈병세포의 apoptosis 유도)

  • Park, Sang Eun;Lee, Su Young;Shin, Dong Yeok;Jeong, Jin-Woo;Jin, Myung Ho;Park, Seon Young;Chung, Yoon Ho;Hwang, Hye Jin;Hong, Sang Hoon;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.3
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    • pp.389-398
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    • 2013
  • Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

Induction of Apoptosis by Piceatannol in YD-15 Human Oral Cancer Cells (피세아타놀에 의한 YD-15 구강암세포의 세포자가사멸 유도 효과)

  • Lee, Hae-Nim;Jang, Hye-Yeon;Kim, Hyeong-Jin;Shin, Seong-Ah;Choo, Gang-Sik;Park, Byung-Kwon;Kim, Byeong-Soo;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.975-982
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    • 2015
  • Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

A Study on the Working Environment Recognition and the Caracter Disposition of Nurse Aides (간호조무사의 근무환경인식과 성격성향에 관한 연구)

  • Lee Sun Yi
    • Journal of Korean Public Health Nursing
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    • v.4 no.1
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    • pp.57-74
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    • 1990
  • As the whole world took on the tendency to be highly industrialized, it became necessary for each field of occupation to require professional man power. Especially, since the World War n, the participation of woman power in economic activities has been continually increasing. In our country also, because of the rapid economic growth, change in the way of thinking of women as well as their participation in economic activities are increasing. Thus, woman power is being utilized in various occupational fields from simple physical labor to those that require high-professional skill. Also, continued economic development policies, by setting the establishment of welfare society as the ideology to be fulfilled, brought expansion of medical facilities in the field of public health and increase in man power in that field. As for the nursing specialists, more than 6000 have been being produced per year and as of the end of 1988, the total number of nursing specialists, reached 123, 115. Therefore, this study is done to recognize the professional knowledge and ability of nursing specialists, who take up $40\%$ of the total public-health related man power in our country, through evaluating their working environment and their disposition of character. This study, which was done from September 18th to September 30th 1989, took on the method of using formed questionnaires that had been amended and supplemented during two preparatory investigations, 322 of such questionnaires were used as an analytical material. In the formation of questionnaires, 12 questions were related to the working environment, and 26 in fortotal were related to the disposition of character, 5 for wise-disposition, 11 for activedisposition and 10 for open-disposition. The measuring method, which used 5-point-standard, allowed 5 points for affirmative recognition of the working environment, also 5 points for showing wise, active and open disposition of character and only point in opposite cases. Collected materials were analyzed, through an electronic calculation, into the average value, the standard deflection percentage, pearson corelative number and stepwise multiple regression. Summarizing the results from this study is as follows: 1. It was shown that the nursing specialists with the average of 3.07 have affirmative recognition of their working environment. The questions which drew most affirmative reaction were those concerning finance-management system such as hand, the questions that received negative reaction were those concerning communication method with the average of 2.49. Such reaction seems to have resulted from the cramming regulation by the superior authorities. Concerning the recognition of working environment in relation to employment conditions, more affirmative recognition is shown with the average of 3.14. at hospitals where injection job is not performed. The nursing specialists working at regular hospitals show more affirmative recognition than those at general hospitals, the averages being respectiely 3.16 and 3.03. 2. As for the disposition of character of the nursing specialists, active-disposition was highest with the average of 3.38, next was wise-disposition with 3.20 and the lowest was open-diposition with 2.98. Variable-wise disposition of character shows that wise-disposition and academic background are beneficially correlated by 0.12. Ative-disposition and open-disposition show correlation to the office term by respectively 0.16 and 0.21. In other words. better academic background leads to higher wise-disposition and more - experience results in higher active and open disposition. Also, the class that performs the injection job, in relation to the working environment, might cause change in the self-conceit that identify those in that class with the nurses; however, as far as professional judgment and action, in dealing with nursing job, being wise, active and open is concerned, not much effect is made. 3. The relation between the recognition of the working environment and the disposition of character is that more afirmative recognition- a nursing specialist has about her working environment, the higher the active-disposition becomes by 0.13. The degrees of the relation between recongnition of environment and wise and open dispositions show respectively 0.06 and -0.06 and -0.06. That is to say that when having more affirmative recognition of the working environment, a nursing specialist shows wise but closed disposition of character. This, howerver, didn't mean much statistically. When observing the results mentioned above, it is conspicuous that the nursing specialists, working as substitutes for the nurse at medical institutions of various sizes, get the feeling of being somewhat equal to the nurses and to some extent, fulfill their desire to accomplish their ego; however, as far as professional ability expansion if concerned. they lack wise and open dispositions. Therefore, considiering upon the results of this study, in medical institutions where the work of nursing specialists is regaded equal to that of the nurses, as a medical member who deals with human lives, it is desirable to make the nursing specialists work under the supervision of the nurses and to offer them continuous education to strengthen and improve their natural dispositions.

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Ethanol Extract from Cnidium monnieri (L.) Cusson Induces G1 Cell Cycle Arrest by Regulating Akt/GSK-3β/p53 Signaling Pathways in AGS Gastric Cancer Cells (AGS 위암세포에서 Akt/GSK-3β/p53 신호경로 조절을 통한 벌사상자 에탄올 추출물의 G1 Cell Cycle Arrest 유도 효과)

  • Lim, Eun Gyeong;Kim, Eun Ji;Kim, Bo Min;Kim, Sang-Yong;Ha, Sung Ho;Kim, Young Min
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.417-425
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    • 2017
  • Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

Expression Pattern of KLF4 in Korean Gastric Cancers (한국인 위암에서 KLF4 단백 발현 양상)

  • Song, Jae-Hwi;Cho, Yong-Gu;Kim, Chang-Jae;Park, Cho-Hyun;Kim, Su-Young;Nam, Suk-Woo;Lee, Sug-Hyung;Yoo, Nam-Jin;Lee, Jung-Young;Park, Won-Sang
    • Journal of Gastric Cancer
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    • v.5 no.3 s.19
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    • pp.200-205
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    • 2005
  • Purpose: KLF4, a member of the KLF family, is a zinc finger tumor suppressor protein that is critical for gastric epithelial homeostasis. Our aim was to determine whether the altered expression of KLF4 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 84 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF4 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF4 protein was expressed in cytoplasm and nucleus of superficial and foveolar epithelial cells in the normal gastric mucosa. We found markedly reduced or loss of KLF4 expression in 43 (51.2%) of the 84 gastric cancer tissues. There was no significant correlation between KLF4 expression and pathologic parameters, including histologic type, depth of invasion, lymph node metastasis and peritoneal dissemination. Conclusion: Our findings suggest that altered expression of KLF4 may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development of Korean gastric cancer, as an early event.

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Space Development and Law in Asia (아시아의 우주개발과 우주법)

  • Cho, Hong-Je
    • The Korean Journal of Air & Space Law and Policy
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    • v.28 no.2
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    • pp.349-384
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    • 2013
  • The Sputnik 1 launching in 1957 made the world recognize the necessity of international regulations on space development and activities in outer space. The United Nations established COPUOS the very next year, and adopted the mandate to examine legal issues concerning the peaceful uses of outer space. At the time, the military sector of the U.S.A. and the Soviet Union were in charge of the space development and they were not welcomed to discuss the prohibition of the military uses of outer space at the legal section in the COPUOS. Although both countries had common interests in securing the freedom of military uses in outer space. As the social and economic benefits derived from space activities have become more apparent, civil expenditures on space activities have continued to increase in several countries. Virtually all new spacefaring states explicitly place a priority on space-based applications to support social and economic development. Such space applications as satellite navigation and Earth imaging are core elements of almost every existing civil space program. Likewise, Moon exploration continues to be a priority for such established spacefaring states as China, Russia, India, and Japan. Recently, Companies that manufacture satellites and ground equipment have also seen significant growth. On 25 February 2012 China successfully launched the eleventh satellite for its indigenous global navigation and positioning satellite system, Beidou. Civil space activities began to grow in China when they were allocated to the China Great Wall Industry Corporation in 1986. China Aerospace Corporation was established in 1993, followed by the development of the China National Space Administration. In Japan civil space was initially coordinated by the National Space Activities Council formed in 1960. Most of the work was performed by the Institute of Space and Aeronautical Science of the University of Tokyo, the National Aerospace Laboratory, and, most importantly, the National Space Development Agency. In 2003 all this work was assumed by the Japanese Aerospace Exploration Agency(JAXA). Japan eases restrictions on military space development. On 20 June 2012 Japan passed the Partial Revision of the Cabinet Establishment Act, which restructured the authority to regulate Japanese space policy and budget, including the governance of the JAXA. Under this legislation, the Space Activities Commission of the Ministry of Education, Culture, Sports, Science, and Technology, which was responsible for the development of Japanese space program, will be abolished. Regulation of space policy and budget will be handed over to the Space Strategy Headquarter formed under the Prime Minister's Cabinet. Space Strategy will be supported by a Consultative Policy Commission as an academics and independent observers. By revoking Article 4 (Objectives of the Agency) of a law that previously governed JAXA and mandated the development of space programs for "peaceful purposes only," the new legislation demonstrates consistency with Article 2 of the 2008 Basic Space Law. In conformity with the principles laid down in the 1967 Outer Space Treaty JAXA is now free to pursue the non-aggressive military use of space. New legislation is the culmination of a decade-long process that sought ways to "leverage Japan's space development programs and technologies for security purposes, to bolster the nation's defenses in the face of increased tensions in East Asia." In this connection it would also be very important and necessary to create an Asian Space Agency(ASA) for strengthening cooperation within the Asian space community towards joint undertakings.

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Prognostic Significance of Cyclin D1 Overexpression in Non-Small Cell Lung Cancer (Cyclin D1의 발현이 비소세포폐암의 예후에 미치는 영향)

  • Yang, Seok-Chul;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Keum, Joo-Seob;Kong, Gu;Lee, Jung-Dal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.776-784
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    • 1998
  • Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

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Silica induced Expression of IL-1$\beta$, IL-6, TNF-$\beta$, TGF-$\alpha$, in the Experimental Murine Lung Fibrosis (유리규산에 의한 폐장내 IL-1$\beta$, IL-6, TNF-$\alpha$, TGF-$\beta$의 발현)

  • Ki, Shin-Young;Park, Sung-Woo;Lee, Myung-Ran;Kim, Eun-Young;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.835-845
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    • 1998
  • Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.

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Effects of Ginseng and Its Saponins on Experimental Amnesia in Mice and on Cell Cultures of Neurons (인삼 및 인삼 사포닌이 쥐의 건망증 및 신경세포배양에 미치는 영향)

  • Saito Hiroshi;Nishiyama Nobuyoshi;Iwai Akihiko;Kawajiri Shinichi;Himi Toshiyuki;Sakai Toshimi;Fukunaka Chizu
    • Proceedings of the Ginseng society Conference
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    • 1988.08a
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    • pp.92-98
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    • 1988
  • The present study was performed to find the effects of ginseng and its saponins. which is written in Chung Yao Ta Tsu Tien as anti-amnesia in its chief indication. on experimental amnesia in mice. In the step through test. ginsenoside $Rb_1\;(GRb_1)\;and\;GRg_1$ facilitated the registration of memory and antagonized the electroconvulsive shock (ECS)-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory. In the step down test. $GRb_1\;GRb_2\;and\;GRg_1$ antagonized the ECS-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory and facilitated the acquisition of short term memory. In the shuttle hox and lever press tests. they have no effects on acquisition and retrieval of memory. except $GRb_1\;GRb_1$ depressed the retrieval of conditioned avoidance response in the shuttle box test. After the end of four tests. the effects of these orally administered drugs on sedative. analgesic. antipyretic and anticonvulsant actions. and on spontaneous and exploratory movements were tested in doses of less than 500mg/kg. but they had none of these effects. Present study may indicate that $GRg_1$ had effects on the retrieval of memory and on the acquisition process of learning response. The recent research on the role of NGF for the survival. regeneration and regulation of brain in adult animals. indicated the importance of NGF on dementia and amnesia. During our research on the specificity of the neurite out growth induced by NGF. we found that the effect of NGF was potentiated by $GRb_1$ in organ cultures of chick embryonic dorsal root ganglia. Then. the effect of $GRb_1$ on neuronal cell survivalin cell culture system was studied. $GRb_1$ potentiated the NGF-mediated increase of neurofilaments in cell cultures of chick embryonic sensory and sympathetic neurons. NGF with $GRb_1$ also showed a tendency to increase the number of surviving neurons of rat embryonic cerebral cortex. NGF increased choline acetyl transferase activity in cell cultures of rat embryonic septum area neurons. but $GRb_1$ did not potentiate NGF activity in cell cultures of rat embryonic septum area neurons. Present study may indicate that $GRb_1$ plays an important role for the survival or regeneration of neurons in the brain.

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