• Title/Summary/Keyword: 억제인자

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THE EFFECT OF BMP REGULATED SMAD PROTEIN ON ALKALINE PHOSPHATASE GENE EXPRESSION (Smad에 의한 alkaline phosphatase 유전자의 발현 조절기전)

  • Kim, Nan-Jin;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.2
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    • pp.238-246
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    • 2001
  • Bone morphogenetic proteins(BMPs), members of the transforming growth factor $\beta$(TGF-$\beta$) superfamily were first identified as the factors that induce ectopic bone formation in vivo, when implanted into muscular tissue. Especially BMP-2 inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells. In the molecular mechanism of the signal transduction of TGF-$\beta$ and related factors, intracellular signaling proteins were identified as Smad. In previous study, it has been reported that Smad 1 and Smad 5, which belong to the R-Smad family mediate BMP signaling, were involved in the induction of osteoblast differentiation in C2C12 cells. To understnad the role of Smads involved in osteogenic transdifferentiation in C2C12 cell, in present study, after we stably transfected C2C12 cells with each. Smad(Smad 1,Smad 5) expression vector, cultured for 3 days and stained for alkaline phophatase activity. ALP activity positive cells appeared in the Smad 1, Smad 5 stably transfected cell even in the abscence of BMP. After transiently co-transfected C2C12 cells with each Smad expression vector and ALP promoter, it was examined that Smad 1 and Smad 5 expression vector had increased about 2 fold ALP promoter activity in the abscence of BMP. These result suggested that both Smad 1 and Smad 5 were involved in the intracellular BMP signals which induce osteoblast differentiation in C2C12 cells. The effect of BMP on C2C12 cells with Smad 1, Smad 5 transfected were studied by using northern blot analysis. the treatment of BMP upregulated ALP mRNA level in three groups, especially upregulation of ALP was larger in Smad 1, Smad 5 transfected cell than control group. Pretreatment with cycloheximide($10{\mu}g/ml$), a protein synthesis inhibitor resulted in blocking the ALP gene expression even in BMP(100ng/ml) treated cell. These results suggested that Smad increased the level of ALP mRNA via the synthesis of a certain transcriptional regulatory protein.

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Clinical Characteristics and Abnormal p53 Expression of Lung Cancer Associated with Multiple Primary Cancer (다발성 악성종양에 동반된 폐암의 임상 특징과 변이형 p53 발현)

  • Shin, Chang-Jin;Park, Hye-Jung;Shin, Kyeong-Cheol;Shim, Young-Ran;Chung, Jin-Hong;Lee, Kwan-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.331-338
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    • 1999
  • Background: Nearly 10% of cancer patients will develop a second primary cancer within ten years after surgical removal of the primary tumor. The detection of risk factors for developing multiple primary tumors would be important This study was conducted to evaluate the clinical characteristics and abnormal p53 expression of lung cancer associated with multiple primary cancer(MPC). Method: Clinical characteristics and abnormal p53 expression were compared between 20 cases of lung cancer(NSCLC ; 16 cases, SCLC ; 4 cases) associated with MPC and 26 cases of primary non-small cell lung cancer. Result: MPC associated with lung cancer was gastric cancer(8), lung cancer(2), esophageal cancer(2), colon cancer(2), laryngeal cancer(1), bladder cancer(1), small bowel cancer(l), adrenal cancer(1), hepatocellular carcinoma(1), and breast cancer (1) in order. The clinical stage of primary NSCLC was relatively advanced, but NSCLC associated with MPC was even distribution at each stage. The detected incidences of abnormal p53 expressions were 62.5% in NSCLC associated with MPC and 76.9% in primary NSCLC(p>0.05). Conclusion: There was no difference in abnormal p53 expression between non-small cell carcinoma associated with multiple primary cancer and primary non-small cell carcinoma.

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Effect of Hog Millet Supplementation on Hepatic Steatosis and Insulin Resistance in Mice Fed a High-fat Diet (고지방식이로 유도한 지방간 마우스에서 기장 첨가식이가 지방간 및 인슐린 저항성에 미치는 영향)

  • Park, Mi-Young;Jang, Hwan-Hee;Lee, Jin-Young;Lee, Young-Min;Kim, Jae-Hyun;Park, Jae-Hak;Park, Dong-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.4
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    • pp.501-509
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    • 2012
  • The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In our previous study, hog millet (HM, $Panicum$ $miliaceum$ L.) water extract showed the highest anti-lipogenic activity among nine cereal types in 3T3-L1 cells. In this study, the effect of hog millet water extract on hepatic steatosis and lipid metabolism in mice fed a high fat diet was investigated. Mice were fed a normal-fat diet (ND), high-fat diet (HFD) or HFD containing 1% or 2% (w/w) HM for 7 weeks. Body weight and food intake were monitored during the study period. Insulin resistance by homeostasis model assessment (HOMA-IR), fasting lipid profile, hepatic fatty acid metabolism-related gene expression determined, and intraperitoneal glucose tolerance test (IGTT) were performed at the study's end. The results indicated that 1% and 2% HM diets effectively decreased liver weights, blood TG and T-cholesterol levels (p<0.05), while the HDL-cholesterol level was increased (p<0.05) compared to HFD-induced steatotsis mice. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, and SCD1) expressions decreased, whereas lipolysis- related gene (CPT1) expression increased in animals fed the 2% PME diet (p<0.05). In addition, mice fed 1% or 2% HM diet had markedly decreased IGTT and HOMA-IR, compared to the those of the HFD-induced hepatic steatosis control group (p<0.05). These results indicated that HM inhibited hepatic lipid accumulation by regulating fatty acid metabolism, and suggested that HM is useful in the chemoprevention or treatment of high fat-induced hepatic steatosis and hepatic steatosis-related disorders including hyperlipidemia, glucose sensitivity, and insulin resistance.

Quality and shelf life of sliced root of Platycodon grandiflorum treated by ozon-microbubble-heat shock (오존-마이크로버블-열수 처리한 세절 도라지의 품질 및 저장성)

  • Park, Kyung Min;Lee, Ji Young;Min, So-Ra;Jeong, Moon-Cheol;Koo, Minseon
    • Food Science and Preservation
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    • v.23 no.5
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    • pp.605-613
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    • 2016
  • The quality and shelf life of sliced root of Platycodon grandiflorum (Doraji) treated by ozon-microbubble-heat shock (OMH) were investigated by combining modified-atmosphere packaging [MAP, ($50%O_2+15%CO_2+35%N_2$)]. The study was based on microbiological (total viable bacteria, fungi, Enterobacteriaceae and coliforms numbers), physicochemical and sensory changes. OMH treatment was effective in reducing microbial populations of the sliced Doraji, especially Enterobacteriaceae and coliforms reduced by 2 log CFU/g. However OMH-MAP treatment remained the aerobe and fungi numbers. Regarding the color, OMH-MAP delayed the change of Hunter $b^*$ and the sliced Doraji by OMH-MAP treatment exhibited lower decrease of flavor and overall acceptability compared to those by polypropylene packaging after tap water treatment (Control). The OMH and $50%O_2+15%CO_2$ MAP treatment gave better sensory quality and extended shelf-life for sliced Doraji (~3 days longer shelf-life than Control). Flavor was significantly related to overall acceptability at both Control and OMH-MAP, whereas total coliforms prevalence was associated with overall acceptability at only OMH-MAP. Therefore microbubble-heat shock treatment may improve microbial safety and sliced Doraji by OMH treatment can stored under $50%O_2+15%CO_2$ treatment for up to 7 days. Thus, OMH and MAP treatment may be used in maintaining the storage quality and marketability of sliced Doraji.

Clinical Significance of Plasma TGF-${\beta}_1$ in Coal Workers' Pneumoconiosis (탄광부 진폐증에서 혈장 Transforming Growth Factor-${\beta}_1$의 의의)

  • Kim, Chong-Ju;Lee, Won-Yeon;Hong, Ae-Ra;Shin, Pyo-Jin;Yong, Suk-Joong;Shin, Kye-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.76-83
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    • 2001
  • Background : Coal workers' pneumoconiosis is a fibrotic lung disease resulting from chronic inhalation of coal dust. The precise mechanism of lung fibrosis in coal workers' pneumoconiosis is uncertain. However, a relationship between the stimulation of fibroblast proliferation and collagen production by mediators released from in flammatory and resident lung cells is thought to be a major factor. The transforming growth factor-$\beta$(TGF-$\beta$), a multifunctional cytokine and growth factor, plays a key role in the scarring and fibrotic processes due to its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. To determine the involvement of TGF-$\beta$ in the development of lung fibrosis in coal workers' pneumoconiosis, the TGF-${\beta}_1$ level in plasma was measured in patients with coal workers' pneumoconiosis. Methods : Plasma was collected from 40 patients with coal workers' pneumoconiosis (20 with simple coal workers' pneumoconiosis and 20 with complicated coal workers' pneumoconiosis) and from 10 normal controls. The ELISA method was used to measure the plasma TGF-${\beta}_1$ concentration. Results : Compared to the control group ($0.63{\pm}01.8$ ng/mL), there was no significant difference in the plasma TGF-${\beta}_1$ level in patients with simple coal workers' pneumoconiosis ($0.64{\pm}0.17$ ng/mL) (p>0.05). However, in patients with complicated coal workers' pneumoconiosis the plasma TGF-${\beta}_1$ level ($0.79{\pm}0.18$ ng/mL) was significantly higher than in patients with simple coal workers' pneumoconiosis and the control group (p<0.05). Conclusion : The data suggests that TGF-${\beta}_1$ has some influence in the development of lung fibrosis in coal workers' pneumoconiosis.

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Loss of FHIT Expression in Non-Small Cell Lung Cancer; The Clinical Significance and Effects on Apoptosis and Cell Proliferation Cycle (비소세포 폐암에서 FHIT 유전자의 발현소실의 임상적의의 및 세포고사 및 세포분열주기에 미치는 영향)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.6
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    • pp.610-620
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    • 2003
  • Background : 3p deletion has been shown to be the most frequently occurring change in lung cancers, suggesting the presence of a tumor suppressor gene in this region. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT. Therefore, the association of the expression of FHIT, with apoptosis, cell proliferation cycle and the clinicopathological features, including survival, were investigated Materials and Methods : 83 patients with non-small cell lung cancer, who underwent curative operation, between Jan. 1996 and Aug. 2000, at the Wonkwang university hospital, were analyzed. The expression of the FHIT was identified by immunohistochemical staining, and rate of apoptosis and cell proliferation cycle by flow cytometry. Results : 43% (36/83) of patients exhibited no FHIT expression. The rates of FHIT loss were 52% (28/54), 22% (5/23), 50% (3/6); 30% (11/37), 48% (16/33), 69% (9/13); 54% (30/56) and 22% (6/27), in squamous cell cancers, adenocarcinomas, large cell cancers, TNM stages I, II and III, smokers and non-smokers, respectively. All the differences in FHIT loss rates, according to the histopathology, TNM stages and smoking habits, were statistically significant. The median survival time and 2-year survival rate of the FHIT(-) group were 24 months and 44%, and those of the FHIT(+) group were 25 months and 51% (p>0.05), respectively. The apoptotic rate of the FHIT(-) and FHIT(+) groups were 50.72 (${\pm}13.93$) and 59.38 (${\pm}14.33$)%, respectively (p=0.01). The S- and G1-phase fractions of the FHIT(-) and FHIT(+) groups were 13.93 (${\pm}7.35$) and $51.50({\pm}23.15$)% and 15.65(${\pm}6.59$) and 54.16 (${\pm}20.25$)%, respectively (p>0.05). Conclusion : The loss of FHIT expression was increased to a greater extent with advancing TNM stage, smoking habits and squamous cell cancer compared to the adenocarcinomas. However, no survival differences were found according to the expression of FHIT. The apoptotic rate of the FHIT(+) group was greater than in the FHIT(-) group, but differences in the S- and G1-phase fractions, according to the expression of the FHIT, were not found.

Screening of the Antimicrobial Activity against Helicobacter pylori and Antioxidant by Extracts from Mulberry Fruits (Morus albba L.) (품종이 다른 오디추출물의 Helicobacter pylori에 대한 항균활성 탐색과 항산화 효과)

  • Cho, Young-Je;Chun, Sung-Sook;Lee, Kyoung-Hwan;Kim, Jeung-Hoan;Kwon, Hyo-Jung;An, Bong-Jeun;Kim, Myung-Uk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.1
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    • pp.15-20
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    • 2006
  • The water and $40\%$ ethanol extracts from mulberry fruits were tested for their antimicrobial activities against Helicobacter pylori and antioxidant. Kangwon III (Morus albba L.) was higher phenolic content (2.90 mg/g) than other water extracts. The phenolic contents of $40\%$ ethanol extracts from Kangwon III and Hihak were 3.02 mg/g and 2.46 mg/g, respectively . The ABTS [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfornic acid)] radical decolorization, electron donating ability (EDA), thiobarbituric acid reactive substance (TBARS) and antioxidant protection factor (PF) were determined for water extracts and $40\%$ ethanol extracts from mulberry fruits. EDA was higher in water extracts than ethanol extract. EDA of water extract from Kangwon III was determined as $99.54\%$ while the activity of ethanol extracts was $89.61\%$ in Daechoukmyeun. The water extracts from Cheongilppong showed higher antioxidative activity than another mulberry fruits extract when evaluated by ABTS [2,2'-azinobis(3-ethylbenzothiaznoline-6-sulfornic acid)] radical decolorization, TBARS and antioxidant PF by water extracts. Kangwon III was higher phenolic content (2.90 mg/g) than other that of water extracts. $40\%$ ethanol extracts were determined that phenolic contents of Kangwon III, Hihak were 3.02 mg/g, 2.46 mg/g for each other. Antimicrobial activity showed the high value in water extracts of Cheongilppong, Kuksang 20. The result will be useful nature microbial medicine for mulberry fruits.

Onion Beverages Improve Amyloid β Peptide-Induced Cognitive Defects via Up-Regulation of Cholinergic Activity and Neuroprotection (양파(Allium cepa L.) 음료의 콜린성 활성 증가 및 뇌신경세포 보호로 인한 Amyloid β Peptide 유도에 대한 인지장애 개선 효과)

  • Park, Seon Kyeong;Kim, Jong Min;Kang, Jin Yong;Ha, Jeong Su;Lee, Du Sang;Kim, Ah-Na;Choi, Sung-Gil;Lee, Uk;Heo, Ho Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1552-1563
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    • 2016
  • To examine the cognitive function of onion (Allium cepa L.) beverages (odourless and fortified), we analyzed in vitro neuronal cell protection against $H_2O_2$-induced cytotoxicity and performed in vivo tests on amyloid beta ($A{\beta}$)-induced cognitive dysfunction. Cellular oxidative stress and cell viability were evaluated by DCF-DA assay and MTT assay. These results show that fortified beverage resulted in better neuronal cell protection than odourless beverage at lower concentration ($0{\sim}100{\mu}g/mL$). Fortified beverage also showed more excellent acetylcholinesterase (AChE) inhibitory activity ($IC_{50}$: 4.20 mg/mL) than odourless beverage. The cognitive functions of odourless beverage and fortified beverage in $A{\beta}$-induced neurotoxicity were assessed by Y-maze, passive avoidance, and Morris water maze tests. The results show improved cognitive function in both groups treated with beverages. After in vivo tests, cholinergic activities were determined based on AChE inhibition and acetylcholine levels, and antioxidant activities were measured as SOD, oxidized glutathione (GSH)/total GSH ratio, and MDA levels in mouse brain tissue. In a Q-TOF UPLC/MS system, main compounds were analyzed as follows: odourless beverage (five types of sugars and three types of phenolics) and fortified beverages (six types of phenolics and two types of steroidal saponins).

DNA Methylation of Multiple Genes in Gastric Cancer: Association with CpG Island Methylator Phenotype and Helicobocter pylori Infection (위암에서 유전자 메틸화와 CpG Island Methylator Phenotype 및 Helicobacter pylori균 감염과의 연관성)

  • Jun, Kyong-Hwa;Won, Yong-Sung;Shin, Eun-Young;Cho, Hyun-Min;Im, Myoung-Goo;Chin, Hyung-Min;Park, Woo-Bae
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.227-236
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    • 2006
  • Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

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Anti-Oxidative and Anti-Inflammatory Activities of Euptelea Pleiosperma Ethanol Extract (Euptelea pleiosperma 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Park, Jung Ae;Lee, Ji Young;Kang, Ji Sook;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.42 no.2
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    • pp.170-176
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    • 2014
  • In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.