• Title/Summary/Keyword: human liver

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STUDY ON MUTATION OF P53 AND EXPRESSION OF MDM-2 IN DMBA INDUCED CARCINOMA OF HAMSTER BUCCAL POUCH (DMBA로 유도된 햄스터 협낭암종에서 p53 유전자 변이와 mdm-2 단백의 발현에 관한 연구)

  • Park, Yong-Sun;Kim, Kyung-Wook;Lee, Jae-Hoon;Kim, Chang-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.5
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    • pp.373-384
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    • 2001
  • Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

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Administration of Triticum aestivum Sprout Water Extracts Reduce the Level of Blood Glucose and Cholesterol in Leptin Deficient ob/ob Mice (Leptin 결핍 ob/ob 마우스에서 소맥엽 추출물의 혈당 강하 및 혈중 콜레스테롤에 미치는 효과)

  • Lee, Sun-Hee;Lim, Sung-Won;Mihn, Nguyen Van;Hur, Jung-Mu;Song, Bong-Joon;Lee, Young-Mi;Lee, Hoi-Seon;Kim, Dae-Ki
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.3
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    • pp.401-408
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    • 2011
  • Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

Protective Effects of Enzymatic Oyster Hydrolysate on Acetaminophen-induced HepG-2 Cell Damage (아세트아미노펜 유도 HepG-2 세포주 손상에 대한 굴 효소 가수분해물의 보호 효과)

  • Park, Si-Hyang;Moon, Sung-Sil;Xie, Cheng-Liang;Choung, Se-Young;Choi, Yeung-Joon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.8
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    • pp.1166-1173
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    • 2014
  • This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.

Apoptotic Cell Death by Pectenotoxin-2 in p53-Deficient Human Hepatocellular Carcinoma Cells (종양억제유전자 p53 결손 인체간암세포에서 Pectenotoxin-2에 의한 Apoptosis 유도)

  • Shin, Dong-Yeok;Kim, Gi-Young;Choi, Byung-Tae;Kang, Ho-Sung;Jung, Jee-H.;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.10
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    • pp.1447-1451
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    • 2007
  • Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

Beneficial Effect of an Agar Mask against Skin Damage Induced by UV Exposure in SKH-1 Hairless Mice (UV조사에 의해 유발된 SKH-1 hairless 마우스의 피부노화에 미치는 한천마스크의 개선효과)

  • Song, Bo Ram;Kim, Ji Eun;Yun, Woo Bin;Lee, Mi Rim;Choi, Jun Young;Park, Jin Ju;Kim, Dong Seob;Lee, Chung Yeoul;Lee, Hee Seob;Lim, Yong;Jung, Min Wook;Kim, Bae Hwan;Hwang, Dae Youn
    • Journal of Life Science
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    • v.27 no.9
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    • pp.975-985
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    • 2017
  • To investigate the beneficial effects of an agar gel mask (AGM) on UV-induced photoaging, SKH-1 hairless mice were treated with a topical application of AGM and an AGM dipped in essence (AGMdE). The mice were divided into an no radiation group, UV + AGM, UV + AGMdE, and UV + vehicle (PBS) treatment groups. Alterations in skin wrinkles, skin phenotype, histological structures, oxidative status, and toxicity were then evaluated during 4 weeks of exposure. The topical application of AGM and AGMdE inhibited wrinkle formation, suppressed the erythema index, prevented transepidermal water loss, and enhanced skin hydration. In addition, epidermal thickness recovered to a similar level as that in the no irradiation group in the UV + AGM and UV + AGMdE treatment groups compared with the UV + vehicle (distilled water) group. Furthermore, the expression levels of matrix metalloproteinase-1 (MMP-1) and tyrosinase were reduced in the UV + AGM and UV + AGMdE treatment groups, although the highest level varied. Moreover, superoxide dismutase (SOD) activity was significantly lower in the UV + AGM and UV + AGMdE treatment groups as compared with the UV + vehicle group. No significant alterations induced by most toxic compounds were measured in serum biochemical markers and liver and kidney histological features of the UV + AGM and UV + AGMdE treatment groups. These results suggest that AGM may protect against skin aging by regulating skin morphology, histopathological structures, and oxidative conditions.

Effect of Hot Water Extracts of Roasted Rhus vemiciflua Stokes on Antioxidant Activity and Cytotoxicity (볶음 처리한 옻나무 열수추출물의 항산화성 및 암세포 성장억제효과)

  • Kwak, Eun-Jung;Jo, Il-Jin;Sung, Ki-Seung;Ha, Tae-Youl
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.6
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    • pp.784-789
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    • 2005
  • The inhibitory effects of hot water extracts of Rhus verniciflua Stokes pith and peel roasted at 170, 200 and $220^{\circ}C$ on lipid peroxidation, formation of DPPH free radicals and growth of four human cancer cells such as HepG2 (liver cancer), SNU-1 (stomach cancer), MCF-7 (breast cancer) and Widr (colon cancer) were examined. The antioxidant activities and growth inhibitory effects on cancer cells of hot water extracts of peel were higher than those of pith, and the activities were dose-dependent. The roasting temperature showing the highest antioxidant activities and growth inhibitory effects on cancer cells was in the range of $170\~200^{\circ}C$ The lipid peroxidation and formation of DPPH free radicals of hot water extracts of roasted pith and peel were inhibited to 50.9, $56.5\%\;and\;79.0,\;78.4\%$ at the concentration of $500\mu g/mL$, respectively. The growth inhibitory effects of roasted pith and peel on cancer cells were in the order of Widr (41.5, $36.0\%$) > HepG2 (61.5, $44.0\%$) > MCF-7 (92.0, $69.2\%$)> SNU-1 (100, $100\%$) cells at the concentration of $1,000\mu g/mL$ as compared with the control, respectively. These results suggest that roasted Rhus verniciflua Stokes could be an useful natural medicinal plant for colon cancer.

Effect of Dandelion Juice Supplementation on Alcohol-Induced Oxidative Stress and Hangover in Healthy Male College Students (건강한 남자 대학생에서 민들레즙 보충이 알코올에 의한 산화적 스트레스 및 숙취에 미치는 효과)

  • Noh, Kyung-Hee;Jang, Ji-Hyun;Kim, Jin-Ju;Shin, Jin-Hyuk;Kim, Dong-Kyoo;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.6
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    • pp.683-693
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    • 2009
  • This study was designed to investigate the effect of dandelion juice supplementation on attenuation of oxidative stress and hangover after drinking alcohol in healthy college male students. This human trial was conducted by two phase cross over design with two weeks wash out period. The subjects (age $24{\sim}28$ years) were volunteers who had more than 72 g of ethanol drinking capacity. Dandelion group was given dandelion juice 220 mL daily for 7 days. Biochemical markers were determined in blood samples taken at 0 and 150 minutes after administration 72 g of alcohol. The levels of plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase and bilirubin, the indicators of liver cell damage, were not significantly different between groups. No significant differences in lymphocyte DNA damage level between groups was observed. However, plasma acetaldehyde dehydrogenase (ALDH) and high density lipoprotein cholesterol levels were significantly (p<0.01) increased in dandelion supplemented group compared to that of control group. Furthermore, activities and protein expressions of glutathione-reductase and catalase of erythrocytes were significantly elevated in dandelion supplemented group compared to that of control group. From the above results, it is concluded that dandelion juice supplementation can reduce oxidative stress and hangover syndrome through the elevation of ALDH and antioxidative enzyme system in healthy male adults.

The Effect of LDL on Vibrio vulnificus Septicemia (비브리오 패혈증에 미치는 LDL의 영향)

  • Kim, Jong-Hyeon;Kim, Jong-Suk;Yoo, Wan-Hee;Hur, Hyeon
    • Journal of Food Hygiene and Safety
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    • v.21 no.4
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    • pp.213-217
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    • 2006
  • The halophilic bacterium Vibrio vulnificus is known to be a foodborne pathogen that causes septicemia in human. V. vulnificus infection is characterized by the high fatality rates and the primary attack against a person who have underlying diseases such as liver cirrhosis. However, there is no effective treatment for V. vulnificus septicemia except for classical treatments such as antibiotics. Recently, it has been known that lipoprotein (LDL) plays a major role in the protection against infection and inflammation. Consequently in this paper we analyzed the effects of LDL on V. vulnificus septicemia. We purified V. vulnificus cytolysin, a major virulent factor of V. vulnificus infection and measured inhibitory effects of mouse serum, cholesterol, and LDL on its hemolytic activity. Next experiments were performed to investigate whether LDL has a protective role against septicemia induced by V. vulnificus in mice. Intraperitoneal injection of LDL (1mg as protein) into mice 3hr before V. vulnificus $(1\times10^6\;CFU)$ injection, and V. vulnificus -induced lethality was determined. For the determination the relationship between LDL or cholesterol and prognosis, we determined serum levels of cholesterol and lipoprotein from V. vulnificus septicemia patients (n=15) who had visited the Chonbuk National University Hospital in Chonju. V. vulnificus cytolysin -induced hemolysis of mice erythrocytes was completely inhibited by serum, cholesterol, and low-density lipoprotein. V. vulnificus- induced lethality of mice injected with LDL showed only 40% compared to 100% of control. In survival groups (n=4) of V. vulnificus septicemia patients (n=15), their serum LDL and cholesterol revealed normal levels ($153.3{\pm}40.7,\;LDL;\;190.8{\pm}16.3$, Total cholesterol). However, in death groups (n=11) showed very low levels ($35.6{\pm}13.9,\;LDL;\;59.2{\pm}15.1$, Total cholesterol). Our study indicates that cholesterol and LDL are a prognosis indicator of V. vulnificus septicemia as well as an inhibitor of virulent action of V. vulnificus cytolysin. We suggested that the serum levels of cholesterol or LDL would be major index in the treatment and prevention of V. vulnificus septicemia.

Analysis of the Effect of Entry-Level 3D Printer Materials on CT Images (보급형 3D프린터 재료가 CT 영상에 미치는 영향 분석)

  • Se-Hwan, Park;Hyun-Jung, Jo;Sung-Jun, Lee;Song-Bin, Lee;Sang-Hyub, Park;Dae-Yeon, Ryu;Yeong-Cheol, Heo
    • Journal of the Korean Society of Radiology
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    • v.16 no.6
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    • pp.673-680
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    • 2022
  • In this study, based on PLA, we analyzed the Hounsfield Unit (HU) of materials containing 20% each of aluminum, wood, copper, carbon, and marble, and tried to analyze how they affect the image. A cylindrical phantom of 5×30×30 ㎣ (thickness×diameter×height) was fabricated using a entry-level 3D printer. The kV was changed to 80, 100 and 120, and the mAs was changed to 100 and 200 mAs, and the phantom in the center of the table was cross-scanned under a total of six conditions. A circular ROI was set using image J program and the quantification value of the material part HU and the quantification value of the peripheral part CNR were obtained. The HU average of the material part increased in the order of [PLA - wood 20%], [PLA - marble 20%], [PLA - carbon 20%], [PLA 100%], [PLA - aluminum 20%], [PLA - copper 20%] (p<0.05) a negative correlation was confirmed with the HU by increasing kV. It was confirmed that the CNR value in the peripheral area increased in the order of [PLA - marble 20%], [PLA - copper 20%], [PLA - carbon 20%], [PLA - wood 20%], [PLA - aluminum 20%], and [PLA - 100%] (p<0.05). Human organs with similar HU values for each material are [PLA - copper 20%] compact bone, [PLA - aluminum 20%] cancellous bone, [PLA 100%] coagulated blood, [PLA - carbon 20%] and [PLA - marble 20%] liver, muscle, spleen and [PLA - wood 20%] had similar values to fat. In addition, we confirmed the blur phenomenon that blurs the image around the filament with all materials, and confirmed that [PLA 100%] especially has the most blur around the filament. Therefore, it is considered desirable to reflect the HU value of the target organ and consider cloudiness around the phantom when selecting materials for medical phantom fabrication, and this research can provide basic data.

Microcystins Concentration in Fishes Collected from the Weirs of Four Rivers in Korea and Risk Assessment (국내 4대강 보에서 채집된 어류 조직에서 microcystins 농도 분석 및 위해도 평가)

  • Do-Hwan Kim;Yuna Shin;Min Jeong Park;Young-Cheol Cho
    • Korean Journal of Ecology and Environment
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    • v.55 no.2
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    • pp.120-131
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    • 2022
  • Microcystins (MCs) are cyano-toxins mainly produced by cyanobacteria in the genera of Microcystis, Anabaena, and Oscillatoria. The concentrations of MCs in the water bodies and fish tissues taken from the four weirs (Ipo, Gangjeong-goryeong, Baekje, and Juksan) in the four main rivers in Korea, and the health risk of human due to consumption of toxin-detected fish was examined. The maximum values of MCs concentration in the water samples were as follows: Juksan (3.261 ㎍ L-1), Gangjeong-goryeong (1.014 ㎍ L-1), Baekje (0.759 ㎍ L-1), and Ipo (0.266 ㎍ L-1) weirs. The MC-RR concentration was the highest among the MCs, and MC-YR was not detected. MCs of 0.222~9.808 ㎍ g-1 dry weight were detected in the liver of 3 out of 215 fishes of 16 species, and below the detection limit in muscle. As a result of comparing the feeding characteristics of the collected fishes and toxin concentrations in water and fish tissue, it was concluded that the biomagnification of MCs through the food chain did not occur. It was judged that there was no health risk due to the consumption of the fish detected the toxin, based on the amount of the fish intake of the Korean people and the allowable daily intake of MCs. However, in order to reduce the health risk due to MCs, further studies should be conducted to analyze the concentration of MCs contained in fish tissues collected at various times in the area dominated by harmful cyanobacteria to obtain data on the exposure of MCs due to fish consumption. In addition, it is necessary to establish the management guidelines for MCs in fish tissues.