• Toxicological Research
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• 제21권4호
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• pp.339-345
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• 2005

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

• 생명과학회지
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• 제20권2호
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• pp.153-160
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• 2010

면역조직 화학법 및 단백질체 변화 분석을 통한 한우에서 발생한 브루셀라증의 특성 본 연구는 브루셀라증 감염 소 혈청으로부터 분리한 항 브루셀라 면역글로블린 항체를 이용하여 조직 면역 염색을 통한 브루셀라증 진단의 활용 가능성을 조사하고 병의 발생과 관련한 기능적 진단 마커를 개발하고자 하였다. Rose-Bengal test에 대해 양성 반응을 나타내어 브루셀라증으로 진단된 17개의 케이스와 음성 반응을 나타낸 19개의 대조군 케이스에 대해 조사를 실시하였다. 본 실험실에서 분리한 항 브루셀라 항체를 이용한 면역조직화학적 반응에서 간의 중심 소엽에 위치한 간세포의 세포질, 신장의 사구체 및 관 상피에서 강한 양성 반응을 나타내었다. 감염된 소의 간과 비감염 대조군의 간의 2차원 전기 영동법에 의한 단백질체를 비교 분석한 결과, 발현량이 대조군에 비해 유의적으로 증가한 5개의 단백질 스팟과 반대로 대조군에 비해 발현량이 현저히 감소한 5개의 단백질 스팟을 선별 하였다. 이 중 카탈라아제와 3-hydroxyacyl-CoA dehydrogenase의 발현 증가는 브루셀라증에 의한 장독 쇼크에 의한 산화적 스트레스 증가에 대한 방어적 반응으로 사료 되었다. 결론적으로, 항 브루셀라 면역글로불린 항체는 감염 조직의 감별 진단을 위한 좋은 진단 재료 임과, 더 나아가 단백질체학 분석을 통해 브루셀라증 진단 및 병리 연구를 위한 새로운 마커 단백질을 제시하였다.

• 생명과학회지
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• 제27권3호
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• pp.289-294
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• 2017

삼채(Allium species)는 전통적인 약재나 건강 증진 식품으로 사용되어 왔다. 특히, Allium hookeri (A. hookeri)는 제 2형 당뇨병 모델 마우스에서 혈당 감소 효과가 보고되었다. 본 연구에서는 A. hookeri 추출물이 3T3-L1 세포에서 인슐린 민감성을 증진시키는지 시험하였다. 3T3-L1 지방세포분화가 불완전하게 유도되는 저농도의 인슐린 조건에서, A. hookeri 추출물은 세포 내 지방 함량을 증가시키고, 분화 유도 전사인자인 $PPAR{\gamma}$의 발현을 상승시켰다. 또한, A. hookeri 추출물은 포도당 수송체 4(GLUT4)의 발현을 증가시킴으로써 세포 내 포도당 흡수(glucose uptake)를 향상시켰다. 이러한 결과들은 A. hookeri 추출물이 인슐린 민감성을 증진시켜 $PPAR{\gamma}$와 GLUT4를 활성화하고, 세포 내 포도당 흡수를 촉진한다는 사실을 보여준다. 따라서, A. hookeri 추출물은 당뇨병의 예방 및 치료에 임상적으로 응용될 수 있을 것으로 생각된다.

• 한국식품영양학회지
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• 제29권4호
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• pp.547-556
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• 2016

The purpose of this study was to investigate the relationship between frequency of coffee consumption, metabolic biomarkers, and nutrition intake in adult participants in the combined 2007~2009 Korean National Health and Nutrition Examination Survey (KNHANES). Subjects (2,095 males and 3,297 females) were classified according to sex and frequency of coffee consumption (${\leq}1$ time/month, ${\geq}2$ times/month and ${\leq}6$ times/week, 1 time/day, 2 times/day, 3 times/day) using food frequency questionnaires. Nutrition intake was analyzed using 24 h recall data. The 3 times/day coffee consumption group had a significantly higher age, and frequency of smokers and drinkers compared to the ${\leq}1$ time/month coffee consumption group in both male and female participants. Males in the 3 times/day coffee consumption group had a significantly lower HDL-cholesterol level, but females had a higher waist circumference compared with the ${\leq}1$ time/month coffee consumption group. Males in the 3 times/day coffee consumption group had a significantly lower nutrient density of fiber, vitamin B2, vitamin C, calcium and phosphorus compared with the ${\leq}1$ time/month coffee intake group. Females in the 3 times/day coffee consumption group had a significantly higher nutrient density of fat and niacin, but lower nutrient density of carbohydrate, calcium, phosphorus, and iron compared with the ${\leq}1$ time/month coffee intake group. In males, the frequency of coffee consumption was not associated with the levels of metabolic biomarkers. In females, the frequency of coffee consumption was positively associated with diastolic blood pressure after adjustments for multiple confounding factors, including age, BMI, smoking status, alcohol consumption, physical activity and energy intake. Coffee consumption was associated with decreased diastolic blood pressure in females. These findings suggest the importance of an awareness of the association between coffee consumption and metabolic risk.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6599-6603
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• 2015

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6391-6395
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• 2012

Background: Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia, it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer but its diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumor marker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposed for the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4 quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this study was to determine reference intervals for HE4 in an Asian population presenting in University Malaya Medical Centre, a tertiary reference hospital. Materials and Methods: 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. Results: The upper limits of the $95^{th}$ percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups. Conclusions: More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination.

• 생태와환경
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• 제53권2호
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• pp.165-172
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• 2020

중금속은 다양한 경로를 통해 환경 중 배출되어 서식 생물에 노출되며 체내 다양한 생리학적 불균형을 유도한다. 본 연구에서는 수서생물지표종으로 이용되는 깔따구(Chironomus riparius)를 이용하여 야외 중금속(Al, Aluminum; Cr, Chromium; Cu, copper; Mn, Manganese; Zn, Zinc) 농도 노출에 따른 다양한 분자발현 반응과 상관성을 분석하였다. 생물 체내 분자 반응을 관찰하기 위해 heat shock protein 40, 70, 90 (HSP40, 70, 90), cytochrome 450(CYP450), Glutathione S-transferase (GST) and Serine-type endopeptidase (SP)를 이용하였다. 그 결과, 스트레스 분자마커로 이용되는 HSPs 유전자들은 중금속 노출된 개체들에서 대조군보다 높은 경향을 보였으며 Cu 노출 시 가장 높은 발현을 나타냈다. 해독에 관여하는 CYP450과 GST 유전자 발현 결과, Cr과 Cu에서는 다른 노출군에 비해 높은 발현 경향을 나타냈다. SP 유전자 발현 결과 Al을 제외한 모든 노출군이 대조군과 유사한 발현 패턴을 보였다. 이와 같은 연구 결과는 실내에서 환경 중 존재하는 실제 농도를 반영한 독성실험을 통해 노출물질과 농도에 따라 특이적으로 발현하는 분자마커 패턴을 보고하였다. 또한, 수생태계로 유입되는 중금속이 하천에 서식하는 생물에 주는 유해 영향에 대한 정보와 분자 지표 유전자들의 현장 적용 가능성을 보여준다.

• 환경영향평가
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• 제22권6호
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• pp.591-607
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• 2013

본 연구에서는 생물학적 바이오마커, 물리적 서식지 지표 및 화학적 수질지표를 종합하여 12-메트릭 생태평가 모형을 확립하였고, 도심하천에 적용하여 수생태계 평가를 실시하였다. 생태모형 적용을 위해 도심하천의 상류역의 대조군 지역($C_Z$), 중류의 전이대($T_Z$) 및 하류역의 오염지역(IZ)을 선정한 후, 모델값에 대한 계절별 변이특성을 분석하였다. DNA 손상도 분석은 혈액을 이용한 단세포 전기영동법(Single-cell gel electrophoresis, SCGE)인 Comet assay 지표에 의거한 생지표 메트릭으로 이용되었고, Tail moment, Tail DNA(%) 및 Tail length(${\mu}m$)값이 분석되었다. DNA의 손상은 하류역의 오염지역($I_Z$)에서 분명하게 나타났지만, 대조군($C_Z$) 지역에서는 그렇지 않았다. 개체군 지표로서 비만도 지수인 $C_F$ 값 분석, 체장빈도 분포 지표 및 개체 이상도(Abnormality) 지표가 생물지표로서 이용되었다. 물리적 서식지 지표는 QHEI 모델을 이용하였고, 4개 메트릭이 분석되었다. 화학적 수질지표는 부영양화 지표인 인(P)/질소(N), 화학적 산소요구량 및 전기전도도 지표가 이용되었다. 본 연구를 종합해보면, 12-메트릭 생태모형의 생지표 속성은 대조군($C_Z$)지역에 비해 오염지역($I_Z$)에서 화학적 스트레스 지표(부영양화 지표)에 아주 민감하게 반응 하는 것으로 나타났으며, 또한 이들은 부분적으로 서식지 평가지표에 의해 영향 받는 것으로 분석되었다.

• Archives of Plastic Surgery
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• 제33권4호
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• pp.433-439
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• 2006

Purpose: DNA in most cell is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage resulted in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in an reduced DNA repair capacity. These polymorphisms are highly prevalent in the population, and therefore the attributable risks for cancer could be high. Several studies have documented that polymorphisms of XRCC1, XPD and XRCC3 are associated with skin cancer, especially, XRCC1 among of them has been reported frequently. So, this study involves the relationship between mutation of XRCC1 of squamous cell and basal cell cancer of the skin and risk of cancer development in Korean population. Methods: In case control study, study population (n=100, each cancer) is patients who were pathologically diagnosed as skin cancer(squamous cell carcinoma and basal cell carcinoma) in Yonsei Wonju Christian Hospital and Bundang CHA General Hospital between 1998 and 2004. The samples of DNA from whom no history of premalignant skin lesion and other malignant diseases were reported belonged to the control group(n=210). Blood and tissue samples were analyzed for presence of XRCC1 Arg399Glu, Arg280His, Arg194Trp using PCR/ RFLP method. Results: For Korean, there was a significant correlation between XRCC1 Arg399Gln gene mutation and risk of basal cell carcinoma development(Arg 399Gln(GA), p=0.012, OR=2.016, 95% CI; 1.230-3.305) /Arg399Gln (AA), p=0.011, OR=1.864, 95% CI; 1.149-3.026)). And, there was also significant correlation between XRCC1 Arg194Trp and risk of skin squamous cell carcinoma development (Arg194Trp (CT+TT), p=0.041, OR=0.537, 95% CI; 0.301-0.960)). In contrast, there was no significant correlation between XRCC1 Arg280His and risk of either basal cell carcinoma or squamous cell carcinoma development. Conclusions: Our result present that XRCC1 Arg399 Gln in basal cell carcinoma and XRCC1 Arg194Trp in squamous cell carcinoma have possibility of cancer risk and biomarker in Korean population. But XRCC1 Arg280 His known having cancer risk on other studies is not associated with cancer risk to squamous cell carcinoma and basal cell carcinoma in Korean population.

• 동의생리병리학회지
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• 제20권2호
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• pp.365-371
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• 2006

Bee Venom aqua-acupuncture (BVA) simultaneously exerts pharmacological effects of biologically active compounds, existed in the whole bee venom, and medicinal effect of the stimulation of acupuncture points. BVA has been considered as a promising therapeutic method for treating various chronic diseases, mainly accompanying severe pain and inflammation. As a painless injection device, jet injectors have been commercially marketed for various clinical applications including insulin injection and vaccination. Among them, a pressure-driven jet injector system could be used for intradermal delivery of a variety of drugs. The aim of this study was to investigate the analgesic effects of the BVA using a needle-free injector (Biojector $2000^{\circledR}$, Bioject Inc., OR, USA), compared to the conventional BV aqua-acupuncture using a typical syringe. Adult Sprague-Dawley rats were injected with bee venom $(0.08mg/kg,\;50{\mu}l)$ using Biojector $2000^{\circledR}$ (BVA-B) or a syringe (BVA-5) into the Zusanli (ST36) acupoint, 30 minutes before plantar injection of 2% formalin. It was found that BVA-B-, or BVA-5-treated rats, compared to controls, exhibited significantly less licking behavior during the late phase in the rat formalin test, when compared to controls. During early phase, however, those effects were not significant but substantial. The analgesic effect of BVA-B was also compatible with that of the conventional BVA-5. In the immunohistochemical studies, BVA-B significantly suppressed the expression of formalin-evoked c-fos, a biomarker of neuronal activity, in the lumbar dorsal horn of the spinal cord. These results indicated that BVA-B waseffective in the modulation of pain in the rat formalin test, compared to BVA-5. Taken together, the needle-free jet injector system could be substituted for the conventional aqua- acupuncture with the advantage of little pain.