• Title/Summary/Keyword: repressing

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Early Growth Response 1 Induces Epithelial-to-mesenchymal Transition via Snail (Egr-1-Snail 작용에 의한 epithelial-to-mesenchymal transition 유도)

  • Jeon, Hyun Min;Lee, Su Yeon;Ju, Min Kyung;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.23 no.8
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    • pp.970-977
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    • 2013
  • The epithelial-to-mesenchymal transition (EMT) plays an essential role in embryogenesis and is involved in tumor metastasis and invasion; it significantly contributes to tumor progression and aggressiveness. The EMT is characterized by a loss of epithelial cell polarity as a result of the reduced expression of epithelial E-cadherin, a hallmark of the EMT, and the acquisition of mesenchymal-like cell morphology. Reactive oxygen species (ROS) such as $O_2{^-}$, $H_2O_2$, and $OH^-$ have been demonstrated to induce the EMT; although Snail is involved in ROS-induced EMT by transcriptionally repressing E-cadherin, its mechanism is not fully understood. In this study, we examined the effects of early growth response 1 (Egr-1) overexpression in noninvasive breast tumor cell line MCF-7 cells. Upon Egr-1 overexpression, MCF-7 cells lost epithelial cell polarity and became more spindle-shaped, indicating that Egr-1 may induce EMT. We found that Snail is implicated in Egr-1 induced EMT. We further demonstrate that the Egr-1-Snail axis is activated by ROS and plays a critical role(s) in ROS-induced EMT.

Effect of Hydropsyche kozhantschikovi Extracts on Oxidative Stress (줄날도래 추출물이 산화적 스트레스에 미치는 영향)

  • Park, Young Mi;Lim, Jae Hwan;Lee, Jong Eun;Seo, Eul Won
    • Journal of Life Science
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    • v.23 no.1
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    • pp.31-37
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    • 2013
  • The present study aimed to investigate effects of ethanol extracts from Hydropsyche kozhantschikovi on cell and DNA damage caused by oxidative stress. In a radical scavenging assay, compared with ascorbic acid used as a control, the level of DPPH (1,1-diphenyl-2-picrylhydrazyl) and that of hydroxyl radicals in H. kozhantschikovi extracts were 60.0% and 43.7%, respectively. The ferrous iron chelating level was 37.5% compared to the chelating value of EDTA (ethylenediaminetetraacetic acid) as a positive control at the same concentration. To verify inhibitory effects of oxidative cell damage induced by reactive oxygen species (ROS), the relative level of lipid peroxidation and the expression level of the p21 protein were compared in extracts-treated and untreated groups. Lipid peroxidation was completely inhibited in the extracts-treated group compared with the radical-only treated group. The level of p21 protein expression was restored to 92.2% of p21 protein expression in the control sample. In addition, DNA cleavage inhibition in the H. kozhantschikovi extracts was 74.1% compared with that of the control group, suggesting that H. kozhantschikovi extracts repress DNA cleavage induced by ROS. Moreover, the phosphorylation ratio of the H2AX protein was 16.7% in the radical-treated group, indicating that the ethanol extracts inhibited 83.3% of DNA damage. Our findings suggest that ethanol extracts from H. kozhantschikovi are effective not only in repressing the oxidation of free radicals and highly toxic hydroxyl radicals, but also in decreasing cell and DNA damage caused by oxidative stress.

Inhibitory Role of TRIP-Br1/XIAP in Necroptosis under Nutrient/Serum Starvation

  • Sandag, Zolzaya;Jung, Samil;Quynh, Nguyen Thi Ngoc;Myagmarjav, Davaajargal;Anh, Nguyen Hai;Le, Dan-Diem Thi;Lee, Beom Suk;Mongre, Raj Kumar;Jo, Taeyeon;Lee, MyeongSok
    • Molecules and Cells
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    • v.43 no.3
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    • pp.236-250
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    • 2020
  • Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

The Effect of Haptoglobin on Expression of Inflammatory Cytokines in 3T3-L1 Preadipocytes. (3T3-L1 지방전구세포에서 합토글로빈에 의한 염증성 cytokine 발현 조절)

  • Cho, Jin-Kyung;Kim, Nam-Hoon;Oh, Mi-Kyung;Park, Seon-Joo;Kim, In-Sook
    • Journal of Life Science
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    • v.18 no.4
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    • pp.537-541
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    • 2008
  • White adipose tissue is now recognized as an important endocrine organ which secretes various signal factors and proteins termed 'adipokine'. Haptoglobin (Hp), which has been known as an acute phase protein, belongs to the adipokine. However, the function of Hp in adipose tissue remains unclear. To verify the role of Hp in preadipocytes, in this study, 3T3-L1 preadipocyte cells were stably transfected with human Hp gene and Hp-overexpressing cells were made. The Hp had no effect on cell growth of preadipocytes. By RT-PCR and Western blot analysis, the Hp inhibited gene expression of IL-6 and COX-2 and enhanced HO-1 synthesis in preadipocytes. Moreover, invasion assay showed the Hp suppressed migration of monocytes to preadipocytes. These findings suggest that the Hp may inhibit an inflammatory reaction in adipose tissue by regulating the expressions of pro-inflammatory and anti-inflammatory mediators, and by repressing monocytes/macrophages infiltration.

Curcumin represses lipid accumulation through inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis in porcine subcutaneous preadipocytes

  • Pan, Shifeng;Chen, Yongfang;Zhang, Lin;Liu, Zhuang;Xu, Xingyu;Xing, Hua
    • Animal Bioscience
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    • v.35 no.5
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    • pp.763-777
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    • 2022
  • Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL-2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

The number of primitive endoderm cells in the inner cell mass is regulated by platelet-derived growth factor signaling in porcine preimplantation embryos

  • Jong-Nam Oh;Mingyun Lee;Gyung Cheol Choe;Dong-Kyung Lee;Kwang-Hwan Choi;Seung-Hun Kim;Jinsol Jeong;Chang-Kyu Lee
    • Animal Bioscience
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    • v.36 no.8
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    • pp.1180-1189
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    • 2023
  • Objective: Discovering the mechanism of cell specification is important to manipulate cellular lineages. To obtain lineage-specific cell lines, the target lineage needs to be promoted, and counterpart lineages should be suppressed. Embryos in the early blastocyst stage possess two different cell populations, the inner cell mass (ICM) and trophectoderm. Then, cells in the ICM segregate into epiblasts (Epi) and primitive endoderm (PrE). PrE cells in embryos show specific expression of platelet-derived growth factor (PDGF) and its receptor, PDGF receptor A (PDGFRA). In this study, we suppressed PDGF signaling using two methods (CRISPR/Cas9 injection and inhibitor treatment) to provide insight into the segregation of embryonic lineages. Methods: CRISPR/Cas9 RNAs were injected into parthenogenetically activated and in vitro fertilized embryos. The PDGF receptor inhibitor AG1296 was treated at 0, 5, 10, and 20 µM concentration. The developmental competence of the embryos and the number of cells expressing marker proteins (SOX2 for ICM and SOX17 for PrE) were measured after the treatments. The expression levels of the marker genes with the inhibitor were examined during embryo development. Results: Microinjection targeting the PDGF receptor (PDGFR) A reduced the number of SOX17-positive cell populations in a subset of day 7 blastocysts (n = 9/12). However, microinjection accompanied diminution of Epi cells in the blastocyst. The PDGF receptor inhibitor AG1296 (5 µM) suppressed SOX17-positive cells without reducing SOX2-positive cells in both parthenogenetic activated and in vitro fertilized embryos. Within the transcriptional target of PDGF signaling, the inhibitor significantly upregulated the Txnip gene in embryos. Conclusion: We identified that PDGF signaling is important to sustain the PrE population in porcine blastocysts. Additionally, treatment with inhibitors was a better method to suppress PrE cells than CRISPR/Cas9 microinjection of anti-PDGF receptor α gene, because microinjection suppressed number of Epi cells. The PDGF receptor might control the number of PrE cells by repressing the proapoptotic gene Txnip. Our results can help to isolate Epi-specific cell lines from blastocysts.

An Experimental Study on the Properties of Concrete Using the Waste Gypsum (폐석고를 시멘트 대체재로 활용한 콘크리트의 특성에 관한 실험적 연구)

  • Kim, Nam Wook;Song, In;Park, Rae Seon;Bae, Ju Seong
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.11 no.2
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    • pp.69-76
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    • 2007
  • As amount of waste matter rapidly increases with fast growth of cities and industry, how to dispose them has arisen as an important problem. Current policy of the government on disposal of waste is repressing generation of waste itself and in case of already generated waste, resource cycle waste management system that recycles waste after proper environmental process is getting established. Therefore recycling of waste and industrial by-products is rising hugely. One of largely wasted matters is waste gypsum, which was categorized as designated waste but changed to general since 1994. Due to disposal cost and lack of impurities removal technology, recycling of it was quite low. However, as impurities removal technology using semi-dried desulfurization process is developed lately, study on recycling of waste gypsum is going on lively. This study examines possibility of utilizing waste gypsum as alternative for concrete cement and analyzed attributes of waste gypsum before and after ball mill process to find out proper alternation ratio, and conducted strength and property tests on concrete subject whose percentage of cement use is substituted with 0, 5.0, 7.5, 10.0 and 12.5% of waste gypsum.

A Study on the Resilience Process of Persons with Disabilities (중도장애인의 레질리언스(Resilience) 과정에 관한 연구)

  • Kim, Mi-Ok
    • Korean Journal of Social Welfare
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    • v.60 no.2
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    • pp.99-129
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    • 2008
  • This study analyzed the resilience process of persons with disabilities using the grounded theory approach. To conduct this study, the researcher conducted in-depth interviews with 8 persons with disabilities. In data analysis, this study identified 393 concepts on the resilience process of persons with disabilities and the concepts were categorized into 45 sub-categories and 18 primary categories. In the paradigm model on the resilience process of persons with disabilities, it was identified that casual conditions included 'unawareness of disability before being disability', 'extreme pain', 'repressing psychological pain', and the contingent conditions were 'dis-empowerment by staying in home', 'isolation by himself with difficulty in accepting the disability', 'experience of frustration from social barriers with prejudice against persons with disabilities'. Also, it was identified that the resilience process could be dependent on the type and the degree of the disability, the gender, and the length of time being disability. In spite of the casual and contingent conditions, the central way in which persons with disabilities could acquire resilience was identified as 'enhancement of the power of positive thinking'. The control conditions which accelerate or retard central phenomenon were 'the awareness of not being alone through family, friends, neighborhood and the social system' externally and 'finding purpose in life through religion and help from other persons with disabilities', internally. The action/interactional sequences enhanced the efforts, self searching and active acting, and as a result, persons with disabilities could find comfort in life, participate in society and change the perspective of disability in society. The core categories of resilience process in persons with disabilities were a belief in affirmation and choice of life by initiative. In the process analysis, stages developed in the following: 'pain', 'strangeness', 'reflection', 'daily life'. This stage was more continuous and causal than discrete and complete. In this process, the types of resilience of persons with disabilities are divided into 'existence reflection', 'course development', 'implicit endeavor', and 'active execution'. This study showed the details of the paradigm models, the process and types with an in-depth understanding of the resilience process of persons with disabilities using grounded theory as well as theory construction and policy and clinical involvement on the study of persons with disabilities.

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A Study on Seok-kok Lee, Kyu-jun's Pu-yang-non (석곡 이규준의 부양론(扶陽論)에 관한 연구(硏究))

  • Hwang, In-Deok
    • Journal of Korean Medical classics
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    • v.12 no.2
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    • pp.16-53
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    • 1999
  • On the viewpoint of Nae-Kyung and Ju-Yeok, the Seok-Kok's Pu-Yang-Non and other oriental medical doctor's Po-Eum-Eok-Yang, Pu-Yang-Eok-Eum theory which are on the basis of the Kun-Shin-Sang-Wha theory of Nae-Kyung and Myung-Mun theory of Nan-Kyung were compared and studied. The results were as follows : 1. Ju-Yeok and Nae-Kyung said the South is Fire. And explained it as the chief object of life activity by likening to king or saint. And said the North is Water. but didn't mentioned that there exists Fire. The activity of Kun-Wha is regarded as the the chief object of life activity and the Shin-Su can be vatalized by receiving the Shim-Kun-Wha. Therefore, the Seok-Kok's opinion that Shang-Wha is the Fire received by Shin-Su matchs the theory of Nae-Kyung and Nan-Kyung. 2. The Kidney(Shin) in Nae-Kyung means Puk-Bang- Han-Su(The North Cold Water) which has two characters, charging and discharging, ascending and descending. The paragrap "Kam-Ga-Seub(坎加習)" in Ju-Yeok means Puk-Bang-Su(The North Water) which also has two characters, charging and discharging, ascending and descending. The beginning and the end. And One Eum and Two Yang of Ri Sign of divination(離卦) cannot be divided into Su-Jang and Wha-Jang, the same as that, One Yang and Two Eum of Kam Sign of divination(坎卦) is Puk-Bang-Han-Su which cannot be divided into Shin and Myung-Mun. The theory of Choa-Shin-Woo-Myung-Mun of Nan-Kyung is the result that the Shin which has two characters is regarded as two organs. Therefore, from the viewpoint of Nae-Kyung and Ju-Yeok, the Seok-Kok's opinion that the Shin is the Puk-Bang-Han-Su which charges from the right and discharges to the left is more proper. 3. For the first time, the right kidney(Woo-Shin) defined as Myung-Mun in the Nan-Kyung and it is trailblazing theory which dosen't exist in the Nae-Kyung. But from the viewpoint of Nae-Kyung, Myung-Mun-Shang-Wha which some oriental medical doctors thought importantly is considered as Shim-Po which is in charge of the order of Shim(心命). 4. The rush of heat to the upper part(上熱) is raised by blind acting of Shang-Wha which exists in the lower part. This theory is on the basis of the Myung-Mun-Shang-Wha theory of Nan-Kyung. The theory that Wha is in the Shin(Kidney) doesn't exist and only the theory exists that the fever happens by the Kun-Wha not going down but ascending in the Nae-Kyung. Therefore the Shang-Wha blind acting theory of the lower part is not coincided with the theory of Nae-Kyung. 5. When the Vital power(陽氣) is blocked by bad tendencies(邪氣) like uncontrolled joy and anger or too much cold and heat etc, the trapped heat(鬱熱) or Ascending Shang-Wha apper, so Vital power itself cannot have blind activity or excess. Therefore, the theory of oriental medical doctors that the remaining vital power is the fire(氣有餘便是火) cannot be materialized. 6. On the basis of the Woo-Shin-Myung-Mun theroy, oriental medical doctors attached importance to Shin-Eum and Shin-Yang. So they emphasized on Ja-Eum-Gang-Wha or On-Bo-Shin-Yang for curing the Fire. Contrarily, On the viewpoint of siding with the vital power which is the Good and repressing the bad tendency which is the Bad, and another viewpoint that when the vital power which is Shim-Kun-Wha moves through the body consistently and fills up the body, then the enery and blood can be made, the Seok-Kok's theory is coincided with the theory of Nae-Kyung.

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Appraisal of the Special Production Area Development Project in Rural Area and Countermeasures for Off-farm Income Increase (The Case of Chungnam Province) (농어촌(農漁村) 특산단지개발사업(特産團地開發事業)의 평가(評價)와 농외소득증대방안(農外所得增大方案) (충청남도(忠淸南道)를 중심(中心)으로))

  • Lim, Jae Hwan
    • Korean Journal of Agricultural Science
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    • v.18 no.2
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    • pp.164-179
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    • 1991
  • Korean agriculture has encountered two problems. One is internal income disparity between rural and urbarn area and the other is external Uruguay Round trade problems as an abolition of direct and indirect import barriers, reduction in export subsidies and to reduce internal price supports. These problems will be brought severe farm problems such as decreasing farm household income and repressing agricultural growth in the near future. Considering the above inevitable facts Korean government has implemented several development projects such as rural industrial area development project, rural special production area development project, leisuresight seeing farm development project, traditional food development project, unskilled labor training project for off-farm employment and so on, to increase farm household income through off-farm income increase. This study was mainly concentrated on the identification of operational problems and post evaluation of the rural special production area development projects which aimed at increasing non-farm incomes and giving employment opportunity for rural farmers in small factories processing regional special farm products and mine products. The main findings and problems to be solved for the successful project implementation are as followed ; 1. Total number of the special production area development projects as of the end of 1991 was amount to 138, and total number of farm household participated were estimated at 2,079, and total amount of off-farm income per farm household was reached to 3,011 thousand won. 2. The total number of processed special products have increased from 21 items in 1981 to 56 items in 1991. On the other hand the total number of farm household participated in the projects have decreased from 2,518 to 2,079 during same period. 3. Total amount of investment for the projects has increased from 1,429 million won in 1981 to 24,760 million won in 1991 but the rate of G'T loan of the total investment has reduced from 24.5% to 5.2% during same period. 4. 138 special production area development project are classified into 6 kinds of commodity groups such as 19 of general industrial good production areas, 52 of folks-industrial art objects production areas, 39 of food processing areas, 9 of fiber and texstile processing areas, 18 of agricultural and fishery inputs processing areas and 1 of stone processing area. 5. The total production value in 1990 was estimated 20,169 million won of which export was amount to 2,627 million won. 6. The finacial rate of return of the UNGOK KUGIJA Tea processing Project operated by UNGOK coops and BAKSAN ginseng tea processing project were estimated at 45.4% (B/C Ratio=1.17, NPV=152.5 million won) and 17.7% (B/C Ratio=1.12, NPV=120.2 million won) respectively. 7. More favorite terms and condition of the loan including collateral problems have to be given to farmers participated. Heavy investment and G'T subsidy policies should be started for the successful project implementation anf farm household income increase. 8. To expand market demand of the rural special goods G'T have to provide special program of TV or other mass media for commodity propaganda and the total cost concerned must be supported by G'T subsidy. 9. The special farm products as GUGUJA,MOSI'Ramie', Ginseng. SOGOKJU,HEMP,Mushroom.DUGYUNJU and Chesnut processing projects have to be propelled and expanded for off-farm income increase in Chung Nam Province. 10. Direct operational pattern of the special production area by coops is more favorable to farmers and recommendable considering with off-farm income increase and market demand creation throughout Korea. 11. In rural area, special organizations for project appraisal are not exist. Accordingly special training program, project appraisal, formulation and preparation for civil servants concerned have to be prepared for project selection and sound implementation under limited budget and financial support.

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