• Mass Spectrometry Letters
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• 제13권1호
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• pp.11-19
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• 2022

Although translational research is referred to clinical chemistry measures, correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm have not been carefully considered in bioanalytical assays yet. The objective of this study was to identify steroidogenic roles in preeclampsia and verify accuracy of quantitative results by comparing two different linear regression models with weighting factor of 1 and 1/x². A liquid chromatography-mass spectrometry (LC-MS)-based adrenal steroid assay was conducted to reveal metabolic signatures of preeclampsia in both serum and placenta samples obtained 15 preeclamptic patients and 17 age-matched control pregnant women (33.9 ± 4.2 vs. 32.8 ± 5.6 yr, respectively) at 34~36 gestational weeks. Percent biases in the unweighted model (w_i = 1) were inversely proportional to concentrations (-739.4 ~ 852.9%) while those of weighted regression (w_i = 1/x²) were < 18% for all variables. The optimized LC-MS combined with the weighted linear regression resulted in significantly increased maternal serum levels of pregnenolone, 21-deoxycortisol, and tetrahydrocortisone (P < 0.05 for all) in preeclampsia. Serum metabolic ratio of (tetrahydrocortisol + allo-tetrahydrocortisol) / tetrahydrocortisone indicating 11β-hydroxysteroid dehydrogenase type 2 was decreased (P < 0.005) in patients. In placenta, local concentrations of androstenedione were changed while its metabolic ratio to 17α-hydroxyprogesterone responsible for 17,20-lyase activity was significantly decreased in patients (P = 0.002). The current bioanalytical LC-MS assay with corrected weighting factor of 1/x² may provide reliable and accurate quantitative outcomes, suggesting altered steroidogenesis in preeclampsia patients at late gestational weeks in the third trimester.

• 한국정보통신학회논문지
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• 제25권12호
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• pp.1797-1808
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• 2021

4차 산업혁명을 주도하는 기술 중 가장 핵심적인 기술로 꼽히고 있는 인공지능은 다양한 분야에 접목되면서 우리 사회 전반에 걸쳐 패러다임의 전환을 가져오고 있다. 바이오 분야 역시 예외는 아니어서 컴퓨터, 전기·전자, 기계 등 타 학문과 융합되면서 방대한 데이터 기반의 AI 기술을 도입하고 있다. 신약개발에서 AI 기술 도입은 신약개발의 효율성을 개선하고 효능 및 품질 향상을 가져올 수 있다. 신약개발은 다학제 분야가 접목된 융합 분야이고 개발 과정 단계별로 결과의 불확실성이 존재하고 있어 실용적 수준의 신약 개발을 위해서는 화학, 생물학, 독성학, 약동학 등 전문지식의 융합을 기반으로 하는 AI 기술 개발이 필요하다. 신약개발은 크게 주어진 질병에 대한 타겟 물질 발굴 및 검증, 히트 및 선도물질 발굴, 도출된 화합물에 대한 합성 가능성 및 효능 등에 대한 평가(Scoring)를 거쳐 최적의 신약 후보 물질을 발굴하고 마지막으로 전임상과 임상 과정의 단계를 거친다. 이때 AI 기술은 모든 단계에서 적용될 수 있고 단계마다 특화되어 적용될 수 있다. 본 논문에서는 신약개발을 위해 적용되고 있는 AI 기술 현황과 현재 기술의 한계를 살펴보고 향후 신약개발에서 AI 기술의 발전 방향을 고찰해 보고자 한다.

• Journal of Electrochemical Science and Technology
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• 제14권3호
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• pp.252-261
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• 2023

Glucose detection is particularly important for clinical diagnosis and personal prevention and control. Herein, the smartphone-based amperometric glucose sensors were constructed using the NiS/CuS nanorods (NRs) as sensing electrodes. The NiS/CuS NRs were prepared through a facile hydrothermal process accompanied by the subsequent vulcanization treatment. The morphological and structural properties of NiS/CuS NRs were characterized with SEM, EDS, XRD, and XPS. Electrochemical measurements including cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy display that NiS/CuS NRs can act as highly efficient electrocatalyst for glucose detection. The NiS/CuS NRs electrodes present a wide detection range of 1-8000 µM for glucose sensing with the sensitivity of 956.38 µA·mM^-1·cm^-2. The detection limit was 0.35 µM (S/N=3). When employed in smartphone-based glucose sensing device, they also display a high sensitivity of 738.09 µA·mM^-1·cm^-2 and low detection limit of 1.67 µM. Moreover, the smartphone-based glucose sensing device also presents favorable feasibility in determination of glucose in serum samples with the recoveries ranging between 99.5 and 105.8%. The results may provide a promising viewpoint to design other new portable glucose sensors.

• Toxicological Research
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• 제14권4호
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• pp.547-555
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• 1998

The subchronic toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) mixed in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance at a dose of 52 mg/kg, 156 mg/kg, or 467 mg/kg intragastrically for 30 consecutive days. Control rats were treated with vehicle only. Each group consisted of 10 rats. No death or abnormal clinical signs were observed throughout the administration period. A transient decrease in body weight gain and food intake was observed in the rats treated with the high dose (467 mg/kg), which was recovered to normal in a week. There were no drug-related differences in urinalysis and hematological results. A significant increase in serum total cholesterol and total protein was observed in both sexes of the rats treated with a dose of 467 mg/kg daily, but all the other values obtained in serum chemistry appeared to be within normal range. A dose dependent increase in liver weight was observed in both male and female rats. Relative kidney weight was also increased in the high dose groups. There was no gross pathological finding at terminal sacrifice. Microscopic histopathological examination did not show any lesion in terms of correlation with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be 52 mg/kg/day.

• Toxicological Research
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• 제16권4호
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• pp.293-301
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• 2000

Toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance intragastrically at a dose of 0 mg/kg, 17 mg/kg, 52 mg/kg or 156 mg/kg for 91 consecutive days. No death or abnormal clinical sign was observed throughout the administration period. There was no difference in body weight gain, food intake or water consumption among different dose groups. Test sub-stance-related differences were not observed in urinalysis. In hematological results mean corpuscular hemoglobin (MCH) of low and high dose male group was increased. Prothrombin time of medium and high dose female group was decreased. A significant increase in serum total cholesterol was observed in both sexes of rats treated with a daily dose of 156 mg/kg, but all the other values obtained in serum chemistry appeared to be within normal ranges. A dose dependent increase in the relative liver and kidney weights was observed in both male and female rats. There were no gross pathological findings at terminal sacrifice. Microscopic histopathological examination did not show any lesion associated with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be greater than 17 mg/kg/day, but less than 52 mg/kg/day.

• 디지털융복합연구
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• 제20권2호
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• pp.311-316
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• 2022

Tertomotide는 hTert의 일부분이며 항암 백신으로 개발된 펩타이드이나 임상시험과 동물실험에서 염증성 질환을 개선하는 활성이 다수 보고된 바 있다. 다양한 연구에서 발견된 항염활성에도 불구하고 약물성이 높지 않아 일반적인 항염약물로의 개발이 어렵다. 다양한 부위에서 일어나는 염증성 증상에 활용하기 위해서는 항염활성과 약물성이 동반되어야 하므로 구조의 개선이 필요하다. 본 연구에서는 tertomotide의 구조를 기반으로 12 종의 옥타펩타이드를 설계하고 항염증 활성을 측정하여 약물성이 개선된 tertomotide 유래의 항염 펩타이드를 도출하고자 하였다. 이를 위해 활성화된 단핵구에서 염증성 cytokine인 TNF-α의 분비에 미치는 영향을 측정하여 각 펩타이드의 항염 활성을 평가하였고 양성대조군으로 비교한 estradiol이나 tertomotide 이상의 항염활성을 가진 펩타이드를 도출하였다. 본 연구의 결과는 tertotmotide 유래 펩타이드들을 활용한 신규 항염증 소재 개발 연구에 도움이 될 것으로 예상되며, 항염증 활성 등의 생리활성이 있으나 약물성이 낮은 펩타이드에 대해 계산화학적 접근으로 구조를 변경하여 기능적 잠재력 있는 신규활성물질을 도출하는 융합연구의 좋은 예가 될 것으로 사료된다.

• Korean Journal of Radiology
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• 제1권3호
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• pp.121-126
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• 2000

Objective: To evaluate the therapeutic efficacy of a new liquid embolic material, Embol, in embolization of the renal artery. Materials and Methods: Embol is a new embolic material obtained by partial hydrolysis of polyvinyl acetate mixed in absolute ethanol and Iopromide 370 and manufactured by Schering Korea, Kyonggido, Korea. Six patients who underwent embolization of the renal artery using Embol were evaluated. Four were male and two were female and their ages ranged from 11 to 70 (mean, 53) years. Clinical and radiologic diagnoses referred for renal artery embolization were renal cell carcinoma (n = 3), renal angiomyolipoma (n = 2) and pseudoaneurysm of the renal artery (n = 1). After selective renal angiography, Embol was injected through various catheters, either with or without a balloon occlusion catheter. Changes in symptoms and blood chemistry which may have been related to renal artery embolization with Embol were analyzed. Results: The six patients showed immediate total occlusion of their renal vascular lesions. One of the three in whom renal cell carcinoma was embolized with Embol underwent radical nephrectomy, and the specimen thus obtained revealed 40% tumor necrosis. In the two patients with angiomyolipomas, the tumors decreased in size and abdominal pain subsided. Bleeding from pseudoaneurysm of the renal artery was successfully controlled. Four patients showed symptoms of post-embolization syndrome, and one of these also showed increased levels of blood urea nitrogen and creatinine. One patient experienced transient hypertension. Conclusion: Embol is easy to use, its radiopacity is adequate and it is a safe and effective embolic material which provides immediate and total occlusion of renal vascular lesions.

• Clinical Endoscopy
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• 제55권1호
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• pp.113-121
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• 2022

Background/Aims: We have been developing artificial intelligence based polyp histology prediction (AIPHP) method to classify Narrow Band Imaging (NBI) magnifying colonoscopy images to predict the hyperplastic or neoplastic histology of polyps. Our aim was to analyze the accuracy of AIPHP and narrow-band imaging international colorectal endoscopic (NICE) classification based histology predictions and also to compare the results of the two methods. Methods: We studied 373 colorectal polyp samples taken by polypectomy from 279 patients. The documented NBI still images were analyzed by the AIPHP method and by the NICE classification parallel. The AIPHP software was created by machine learning method. The software measures five geometrical and color features on the endoscopic image. Results: The accuracy of AIPHP was 86.6% (323/373) in total of polyps. We compared the AIPHP accuracy results for diminutive and non-diminutive polyps (82.1% vs. 92.2%; p=0.0032). The accuracy of the hyperplastic histology prediction was significantly better by NICE compared to AIPHP method both in the diminutive polyps (n=207) (95.2% vs. 82.1%) (p<0.001) and also in all evaluated polyps (n=373) (97.1% vs. 86.6%) (p<0.001) Conclusions: Our artificial intelligence based polyp histology prediction software could predict histology with high accuracy only in the large size polyp subgroup.

• Clinical Endoscopy
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• 제55권1호
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• pp.122-127
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• 2022

Background/Aims: Endoscopic ultrasonography (EUS) is warranted when cross-sectional imaging demonstrates common bile duct (CBD) dilatation without identifiable causes. This study aimed to assess the diagnostic performance of EUS in CBD dilatation of unknown etiology. Methods: Retrospective review of patients with dilated CBD without definite causes undergoing EUS between 2012 and 2017. Results: A total of 131 patients were recruited. The mean age was 63.2±14.1 years. The most common manifestation was abnormal liver chemistry (85.5%). The mean CBD diameter was 12.2±4.1 mm. The area under the receiver operating characteristic curve (AUROC) of EUS-identified pathologies, including malignancy, choledocholithiasis, and benign biliary stricture (BBS), was 0.98 (95% confidence interval [CI], 0.95-1.00). The AUROC of EUS for detecting malignancy, choledocholithiasis, and BBS was 0.91 (95% CI, 0.85-0.97), 1.00 (95% CI, 1.00-1.00), and 0.93 (95% CI, 0.87-0.99), respectively. Male sex, alanine aminotransferase ≥3× the upper limit of normal (ULN), alkaline phosphatase ≥3× the ULN, and intrahepatic duct dilatation were predictors for pathological obstruction, with odds ratios of 5.46 (95%CI, 1.74-17.1), 5.02 (95% CI, 1.48-17.0), 4.63 (95% CI, 1.1-19.6), and 4.03 (95% CI, 1.37-11.8), respectively. Conclusions: EUS provides excellent diagnostic value in identifying the etiology of CBD dilatation detected by cross-sectional imaging.

• 대한핵의학회지
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• 제33권3호
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• pp.298-305
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• 1999

목적: PET을 이용하여 도파민운반체를 영상화하는데 유용한 [$^{18}F$]FP-CIT는 그 동안 여러 연구팀들에 의하여 합성이 시도되어졌으나 합성의 난이성 때문에 문제가 되어왔다. 이 연구에서는 새로운 방법에 의하여 유효비방사능이 높은 [$^{18}F$]FP-CIT를 높은 수율로 합성하고자 하였다. 대상 및 방법: [$^{18}F$]Fluoropropyl기를 도입하기 위하여 사용된 3-bromo-1-[$^{18}F$]Fluoropropane은 THF 용매 하에서 3-bromo-propyl-1-triflate $5{\mu}L$와 $nBu_4N^{18}F$를 $80^{\circ}C$에서 2분 동안 가열하여 얻어졌으며 정제하지 않고 직접 알킬화반응에 사용하였다. 이렇게 생성된 3-bromo-1-[$^{18}F$]fluoropropane에 nor-${\beta}$-CIT를 넣고 DMF $5{\sim}6$방울이 함유된 아세토니트릴을 반응용매, $Et_3N$을 생성된 산의 중화제로 사용하여 140f에서 20분동안가열하였다. 생성된 [$^{18}F$]FP-CIT는 HPLC에 의해 정제되고 13% 에탄올이 함유된 생리식염수를 사용하여 제제화하였다. 정도관리는 HPLC 및 방사능 박층크로마토그라피에 의한 분석, pH, 발열성 검사로 이루어졌다. 결과· 3-Bromo-1-[$^{18}F$]Fluoropropane은 3-bromopropyl-1-triflate의 triflate기를 $^{18}F$으로 치환하여 $77{\sim}80%$의 높은 방사화학적 수율로 얻어졌으며 같은 반응용기에 nor-${\beta}$-CIT를 넣고 $140^{\circ}C$의 반응온도에서 아세토니트릴과 최소량의 DMF를 사용하여 알킬화반응을 실행하였다. 이때 DMF의 높은 극성과 비점 때문에 HPLC로 정제할 때 문제가 되었으므로 초기에 0.8% $Et_3N$을 포함한 물만을 사용하는 정제방법을 개발하였다. [$^{18}F$]FP-CIT의 동정은 비방사성 동일물질인 FP-CIT와 동시에 HPLC에 주입하여 확인되었다. [$^{18}F$]FP-CIT의 정도관리를 실행한 결과, 방사화학적 순도는 99% 이상, 유효비방사능은 $37GBq/{\mu}mol$ 이상으로 우수하였으며 총 감쇠보정된 방사화학적 수율도 $5{\sim}10%$로 높았다. 최종생성물의 pH는 약 7.0이었으며 발열물질은 없었다. 결론: 이 연구에서는 [$^{18}F$]fluorination 반응의 전구물질로서 3-bromopropyl-1-triflate를 사용하였고 HPLC 정제 조건을 새롭게 개발함으로써 유효비방사능이 높고 비교적 수율도 높은 [$^{18}F$]FP-CIT를 합성하는 새로운 방법을 확립하였다. 이 [$^{18}F$]FP-CIT는 뇌 도파민운반체의 체내 연구에 유용하게 사용될 것으로 사료된다.