한국인에서 5,10-Methylenetetrahydrofolate Reductase 유전자 다형성 분석 및 임신의 결과에 미치는 영향

김아리 ( Ari Kim ),강은지 ( Eun Ji Kang ),이경아 ( Kyung A Lee ),박세나 ( Se Na Park ),박종순 ( Jong Soon Park ),박보현 ( Bo Hyun Park ),박혜숙 ( Hyesook Park ),박미혜 ( Mi Hye Park ),전선희 ( Sun Hee Chun ),안정자 ( Jung Ja Ahn ) 대한주산의학회 2006 大韓周産醫學會雜誌 Vol.17 No.3

목적: 본 연구는 한국인 임신 여성에서 MTHFR 유전자형 변이와 혈청내 호모시스테인 및 엽산의 농도와 이들이 임신에 미치는 영향을 알아보고자 하였다. 방법: 임신부 600명에게서 혈액을 채취하여 얻어진 DNA로 MTHFR C677T와 A1298C 유전자의 다형성을 PCR-RELP로 분석하였고 혈청내 호모시스테인은 HPLC 방법으로, 엽산은 RIA 방법으로 측정하였다. 결과: 혈청내 호모시스테인은 MTHFR C677T 유전자형이 C/C형이나 C/T인 군에 비해 T/T인 군에서 유의하게 높았으며 MTHFR A1298C 유전자형이 A/C형이나 C/C인 군에 비해 A/A인 군에서 역시 유의하게 높았다( p<0.05). 혈청 호모시스테인은 모든 MTHFR 유전자형에서 혈청 엽산농도와 역상관관계를 보였으나, 변이형 유전자형(T/T와 A/A유전자형)에서 더 큰 역 상관관계를 보였다. 15?mol/L 이상의 고호모시스테인혈증의 임신부에서 임신 주수와 출생체중이 36.1주, 3053.8 g으로 15 ?mol/L미만인 군의 38.3 주, 3215.3 g 보다 유의하게 낮았다( p<0.05). 결론: 혈청 호모시스테인의 농도는 MTHFR C677T와 A1298T 유전자의 다형성에 의해 영향을 받으며, MTHFR C677T와 A1298T 유전자의 다형성과 혈청 호모시스테인은 모두 임신주수와 신생아의 체중에 영향을 미친다. Objective: The purpose of this study was to analyze MTHFR polymorphism among the Korean population and to evaluate the relationship between serum levels of homocysteine and MTHFR polymorphism and also to investigate the effect on pregnancy outcomes. Methods: DNA was extracted from whole blood of 600 pregnant women. All samples were genotyped for the C677T and A1298C polymorphisms in MTHFR gene by PCR-RELP assay. Serum levels of homocysteine and folate were measured by high performance liquid chromatography for homocysteine and radioassay for folate. Pregnancy outcomes were estimated by gestational weeks and birth weights of newborns. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR C677T polymorphism (p<0.05). And also serum homocysteine was higher in women with the A/A genotype than those with the A/C or C/C genotype of the MTHFR A1298C polymorphism (p<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes, especially prominent in T/T genotype of MTHFR C677T polymorphism and A/A genotype of MTHFR A1298C polymorphism. Gestational age and the birth weight of infant from hyperhomocysteinemic mothers whose homocysteine levels higher than 15 μmol/L were 36.1 weeks, 3053.8 g, respectively, which were significant lower than those from normohomocysteinemic mothers (38.3 weeks, 3,215.3 g) (p<0.05). Conclusion: Serum homocysteine was influenced significantly by MTHFR C677T polymorphism and MTHFR A1298C polymorphism. MTHFR C677T and A1298C polymorphism and serum homocysteine levels affect pregnancy outcomes, although not mainly by serum folate level.

청가시덩굴 추출물의 기능성 원료 표준화를 위한 지표성분 Resveratrol, trans-Scirpusin A의 분석법 개발 및 검증

권진관(Jin Gwan Kwon),정연우(Yeon Woo Jung),최윤혁(Yun-Hyeok Choi),이지은(Ji Eun Lee),정원식(Wonsik Jeong),이정아(Jung A Lee),최춘환(Chun Whan Choi),안은경(Eun-Kyung Ahn),최용문(Yongmun Choi),홍성수(Seong Su Hong) 한국식품영양과학회 2022 한국식품영양과학회지 Vol.51 No.11

본 연구는 HPLC를 이용하여 청가시덩굴 추출물을 개별인정형 건강기능식품의 기능성 원료로 개발하기 위한 원료 표준화의 일환으로, 청가시덩굴 추출물의 지표성분을 resveratrol과 trans-scirpusin A로 설정하고 이에 대한 HPLC 분석법을 확립하여 유효성의 검증을 실시하였다. 분석법 유효성 검증은 특이성, 직선성, 정확도, 정밀도, 검출한계 및 정량한계 등을 통해 분석법의 신뢰성을 검증하였으며, 그 결과 표준용액과 청가시덩굴 추출물 간의 HPLC 크로마토그램 및 UV spectrum의 일치 여부 등의 비교를 통해 다른 물질과 간섭 없이 피크가 분리된 것으로 특이성을 확인하였다. 또한 표준용액 검량선의 상관계수(R²)는 0.9999로 매우 우수한 직선성으로 관찰되어 분석에 적합한 것으로 확인되었으며, 검량선의 기울기 및 표준편차를 이용한 검출한계는 resveratrol이 0.98 μg/mL, trans-scirpusin A는 0.49 μg/mL였고 정량한계는 resveratrol이 2.98 μg/mL, trans-scirpusin A는 1.48 μg/mL로 각각 확인되었다. 청가시덩굴 추출물에 표준물질을 3개 농도 첨가하고 분석한 회수율은 resveratrol이 98.77~99.24%, trans-scirpusin A는 98.45~99.45%로 나타나 정확성이 있는 것을 확인할 수 있었다. 청가시덩굴 추출물의 조제 농도 2.2, 4.4 및 6.6 mg/mL에서 반복성은 resveratrol이 0.99~1.22%, trans-scirpusin A는 1.12~1.32%를, 실험실 내 정밀성에서는 일내 정밀성은 resveratrol이 0.67~0.87%, trans-scirpusin A는 1.18~1.33%로 나타났고 일간 정밀성은 resveratrol이 0.93~1.22%, trans-scirpusin A는 1.33~2.27%로 확인되어 본 분석법은 정밀성이 있음을 확인할 수 있었다. 이상의 분석결과를 통해 확립된 청가시덩굴 추출물의 지표성분인 resveratrol과 trans-scirpusin A의 HPLC 분석법은 적합한 시험법으로 검증되었으며, 본 시험법은 향후 청가시덩굴 추출물의 건강기능식품 기능성 원료 개발과 표준화를 위한 기초자료로 활용될 것으로 사료된다. This study was undertaken to establish an analytical method using high-performance liquid chromatography (HPLC). HPLC for the standard determination of resveratrol and trans-scirpusin A as functional ingredients in Smilax sieboldii extract. We evaluated the specificity, linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) of various analytical methods for detecting resveratrol and trans-scirpusin A using HPLC. The specificity was confirmed by the chromatogram obtained using the HPLC analytical method. Also, the results of UV and the coefficient of correlation (R²) obtained was 0.999, which confirmed that this was a suitable analysis with high linearity. The LOD was 0.98, 0.49 μg/mL, and LOQ was 2.98, 1.48 μg/mL, which was confirmed as a suitable limit level for the analysis of resveratrol and trans-scirpusin A content in the S. sieboldii extract. The recovery of resveratrol and trans-scirpusin A content was determined to be 98.77±0.73∼99.24±1.47% and 98.45±1.18∼99.45±1.66%, respectively, indicating high accuracy. The intra-day repeatability and the intra-laboratory precision of the daily repetition were confirmed to be 0.67∼0.87%, 1.18∼1.33% and 0.93∼1.22%, 1.33∼2.27%, respectively, for trans-scirpusin A, for the relative standard deviation. These results indicate that the reported HPLC method is simple, reliable, and reproducible for the detection of resveratrol and trans-scirpusin A in S. sieboldii extract.

Base-pair opening dynamics of the microRNA precursor pri-miR156a affect temperature-responsive flowering in Arabidopsis

Kim, Hee-Eun,Kim, Wanhui,Lee, Ae-Ree,Jin, Suhyun,Jun, A.Rim,Kim, Nak-Kyoon,Lee, Joon-Hwa,Ahn, Ji Hoon Academic Press 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Internal and environmental cues, including ambient temperature changes, regulate the timing of flowering in plants. Arabidopsis miR156 represses flowering and plays an important role in the regulation of temperature-responsive flowering. However, the molecular basis of miR156 processing at lower temperatures remains largely unknown. Here, we performed nuclear magnetic resonance studies to investigate the base-pair opening dynamics of model RNAs at 16 °C and investigated the <I>in vivo</I> effects of the mutant RNAs on temperature-responsive flowering. The A9C and A10CG mutations in the B5 bulge of the lower stem of pri-miR156a stabilized the C15∙G98 and U16∙A97 base-pairs at the cleavage site of pri-miR156a at 16 °C. Consistent with this, production of mature miR156 was severely affected in plants overexpressing the A9C and A10CG constructs and these plants exhibited almost no delay in flowering at 16 °C. The A10G and A9AC mutations did not strongly affect C15∙G98 and U16∙A97 base-pairs at 16 °C, and plants overexpressing A10G and A9AC mutants of miR156 produced more mature miR156 than plants overexpressing the A9C and A10CG mutants and showed a strong delay in flowering at 16 °C. Interestingly, the A9AC mutation had distinct effects on the opening dynamics of the C15∙G98 and U16∙A97 base-pairs between 16 °C and 23 °C, and plants expressing the A9AC mutant miR156 showed only a moderate delay in flowering at 16 °C. Based on these results, we propose that fine-tuning of the base-pair stability at the cleavage site is essential for efficient processing of pri-miR156a at a low temperature and for reduced flowering sensitivity to ambient temperature changes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A mutation in pri-miR156a B5 affected base-pairing stability at the cleavage site. </LI> <LI> Mutations in the B5 bulge increased base-pair stabilities and decreased miR156. </LI> <LI> The A9AC mutation affected opening dynamics between 16 and 23 °C. </LI> <LI> Cleavage site base-pair stabilities reflected miR156 levels and flowering time. </LI> </UL> </P>

A Driving Method of Pixel Circuit Using a-IGZO TFT for Suppression of Threshold Voltage Shift in AMLED Displays

Woo-Sul Shin,Hyun-A Ahn,Jun-Seok Na,Seong-Kwan Hong,Oh-Kyong Kwon,Ji-Hun Lee,Jae-Gwang Um,Jin Jang,Sung-Hwan Kim,Jeong-Soo Lee IEEE 2017 IEEE electron device letters Vol.38 No.6

<P>A driving method of pixel circuit using amorphous indium gallium zinc oxide (a-IGZO) thin-film transistor (TFT) is proposed to improve the image quality of active matrix light-emitting diode displays. The proposed pixel circuit employs a diode-connected structure to compensate for variation in threshold voltage (V-th) of the a-IGZO TFT. In addition, the proposed driving method adopts negative bias annealing to suppress the V-th shift. The annealing time is optimized based on the experimental observation of the minimum V-th shift. After a stress time of 30 000 s, the measurement results showthat the (Vth) shift is reducedby 29.6%, using an optimized annealing time of 5% of one frame time. In addition, the maximum deviation in the emission current using the proposed driving method wasmeasured to be less than 4.32% after a stress time of 30 000 s.</P>

Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry

Kyung-A Kim,Ji-Won Lee,Jeong-Ho Park,Byoung-Ho Kim,Hyo-Won Ahn,Su-Jung Kim 대한치과교정학회 2017 대한치과교정학회지 Vol.47 No.3

Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries.

Base-pair opening dynamics of primary miR156a using NMR elucidates structural determinants important for its processing level and leaf number phenotype in <i>Arabidopsis</i>

Kim, Wanhui,Kim, Hee-Eun,Lee, Ae-Ree,Jun, A Rim,Jung, Myeong Gyo,Ahn, Ji Hoon,Lee, Joon-Hwa Oxford University Press 2017 Nucleic acids research Vol.45 No.2

<P>MicroRNAs originate from primary transcripts containing hairpin structures. The levels of mature miR156 influence the leaf number prior to flowering in the life cycle of plants. To understand the molecular mechanism of biogenesis of primary miR156a (pri-miR156a) to mature miR156, a base-pair opening dynamics study was performed using model RNAs mimicking the cleavage site of wild type and B5 bulge-stabilizing mutant pri-miR156a constructs. We also determined the mature miR156 levels and measured leaf numbers at flowering of plants overexpressing the wild type and mutant constructs. Our results suggest that the stabilities and/or opening dynamics of the C15·G98 and U16·A97 base-pairs at the cleavage site are essential for formation of the active conformation and for efficient processing of pri-miR156a, and that mutations of the B5 bulge can modulate mature miR156 levels as well as miR156-driven leaf number phenotypes via changes in the base-pair stability of the cleavage site.</P>

Bioassay-guided isolation and identification of anti-obesity phytochemicals from fruits of Amomum tsao-ko

Hong Seong Su,Choi Chun Whan,Lee Ji Eun,Jung Yeon Woo,Lee Jung A,Jeong Wonsik,Choi Yun-Hyeok,Cha Hanna,Ahn Eun-Kyung,Oh Joa Sub 한국응용생명화학회 2021 Applied Biological Chemistry (Appl Biol Chem) Vol.64 No.1

Amomum tsao-ko (Zingiberaceae), an important traditional medicinal herb, possesses many biological activities, including anti-inflammatory effects. Though the anti-obesity properties of the crude ethanol extract of A. tsao-ko fruits have been reported, the anti-adipogenic properties of its phytochemical constituents have not been reported. Therefore, in the present study, we isolated the active constituents of A. tsao-ko and investigated their anti-adipogenic effects. The bioassay-guided isolation of the phytochemicals from the ethanol extract of A. tsao-ko fruits identified four bioactive compounds, comprising one fatty acid (1), one sesquiterpene alcohol (2), and two phenolic compounds (3 and 4). Their structures were elucidated by a combination of 1D and/or 2D nuclear magnetic resonance and mass spectrometry. The anti-adipogenic activities of the four compounds evaluated by Oil Red O staining in 3T3-L1 cells revealed that the treatment with the isolated compounds 1 and 3 reduced the lipid accumulation in 3T3-L1 adipocytes more strongly than the compounds 2 and 4, in a dose-dependent manner.

β-Lactam 유도체의 N(1)-C(4) 위치에 한 개의 탄소를 도입한 입체 선택적 고리확장에 관한 연구

하진렬,오선주,김지아,신동수,안철진 昌原大學校 基礎科學硏究所 2003 基礎科學硏究所論文集 Vol.15 No.-

The base induced ring opening of β -1actam derivatives with LDA gave γ-lactam derivatives stereoselectively. The γ -1actam derivatives were formed stereoselectively depending on β-3 substituent of B-lactam derivatives.

락탐화합물의 고리 확장 연구 : 입체 선택성과 Mechanism에 관한 연구 Study of Stereoselectivity and Mechanism

하진렬,최경민,김지아,원태진,신동수,이민주,안철진 昌原大學校 基礎科學硏究所 2002 基礎科學硏究所論文集 Vol.14 No.-

The ring expansion chemistry is one of the most important methods to prepare five-and six-membered heterocylic compounds. We have studied about γ-lactam ring expansion with stereoselectivity from β-lactam derivative. To do this chemistry, proton of N-benzyl group in β-lactam derivatives is eliminated by LDA and make carbanion.This anion make unstable 4-membered lactam intermediate, and then the ring is opened by homo clevage or hetero cleavage for releasing ring strain, followed by recyclization to one carbon to make γ-lactam ring with stereoselectivity in β-, γ- positions.

Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/beta-catenin signal via ISGylation of beta-catenin.

Lee, Ji Hee,Bae, Jeong A,Lee, Jae Hyuk,Seo, Young-Woo,Kho, Dhong Hyo,Sun, Eun Gene,Lee, Song Eun,Cho, Sang Hee,Joo, Young Eun,Ahn, Kyu Youn,Chung, Ik Joo,Kim, Kyung Keun British Medical Association 2010 Gut Vol.59 No.7

<P>BACKGROUND AND AIMS: 90K, a tumour-associated glycoprotein, interacts with galectins and has roles in host defence by augmenting the immune response, but the serum 90K level was suggested to indicate poor prognosis in several cancers. The cellular mechanisms of 90K action on colorectal cancer (CRC) cell motility and its effect on CRC progression were investigated. METHODS: The impact of 90K was analysed by combining cell cultures, in vitro assays, and immunohistochemistry. RESULTS: Secreted 90K suppresses CRC cell invasion, but this action of 90K is masked through binding with extracellular galectins. A novel pathway is identified comprising a secretory 90K and a CD9/CD82 tetraspanin web; in this pathway, 90K interacts with CD9/CD82, suppresses the Wnt/beta-catenin signal via a novel proteasomal-ubiquitination mechanism of beta-catenin that is dependent on ISG15 (interferon-stimulated gene-15) modification (ISGylation) but not on glycogen synthase kinase 3beta (GSK-3beta) and Siah/Adenomatous polyposis coli (APC). In a syngeneic mouse colon tumour model, tumour growth and lung metastasis were increased with 90K knockdown. In colon tissues from stage IV human CRC and invading cancer cells of corresponding metastatic liver tissues, in which beta-catenin and galectin expression was higher, immunostained 90K and CD9/CD82 were lower than in adjacent hepatic tissues or colon tissues from stage I. CONCLUSIONS: 90K itself has antitumour activity in CRC cells via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of beta-catenin when it interacts with CD9/CD82, but is downregulated in advanced CRC tissues. The data suggest a strategy of strengthening this novel pathway with concomitant knockdown of galectins as a potential therapeutic approach to CRC progression.</P>