• Title/Summary/Keyword: drug discovery process

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A pilot application study of densitometric image analysis as a potential comparative evaluation method for visualized fingerprints

  • Kim, Eun-Ji;Kim, Soo-Kyung;Seo, Kyung-Suk;Choi, Sung-Woon
    • Analytical Science and Technology
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    • v.33 no.4
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    • pp.197-207
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    • 2020
  • The current comparison methods with scoring systems that are used to compare visualized latent fingerprints (LF) have disadvantages. Evaluators using these methods are prone to make errors and fail to discriminate LFs correctly to notice the differences among those LFs. Therefore, a comparative and quantitative evaluation method that is capable of obtaining more objective and quantitative results is needed. Densitometric image analysis (DIA) is used in other fields as a reliable semi-quantitative comparison method. To apply DIA to LFs, the potential variables that can occur during the DIA process were tested. The visualized ridges of LFs can be compared using the concentration of dots against the background to make it possible to analyze the ridges with DIA. The variables that can be present during the DIA process include the thickness of the analysis line, the number of ridges to be taken, the number of divided zones within each of the fingerprints, and the angles of the analysis line against the ridge lines that were selected. From the analysis of the inked fingerprints and circular lines that are similar to fingerprints, the angle of the analysis lines with the ridge line was the most significant variable. The preliminary test result was applied to the comparison of LFs that were developed with the powder method and then compared with the AFIS analysis. A similar trend was found, and a more detailed and semi-quantitative comparison of the visualized LFs was possible. In the future, it is necessary to check the evaluative ability of the DIA method by analyzing the visualized LFs with other various development methods. However, DIA is currently an option that can be used as an objective comparative evaluation method during fingerprint studies with supplementary role.

Bayesian Model for the Classification of GPCR Agonists and Antagonists

  • Choi, In-Hee;Kim, Han-Jo;Jung, Ji-Hoon;Nam, Ky-Youb;Yoo, Sung-Eun;Kang, Nam-Sook;No, Kyoung-Tai
    • Bulletin of the Korean Chemical Society
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    • v.31 no.8
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    • pp.2163-2169
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    • 2010
  • G-protein coupled receptors (GPCRs) are involved in a wide variety of physiological processes and are known to be targets for nearly 50% of drugs. The various functions of GPCRs are affected by their cognate ligands which are mainly classified as agonists and antagonists. The purpose of this study is to develop a Bayesian classification model, that can predict a compound as either human GPCR agonist or antagonist. Total 6627 compounds experimentally determined as either GPCR agonists or antagonists covering all the classes of GPCRs were gathered to comprise the dataset. This model distinguishes GPCR agonists from GPCR antagonists by using chemical fingerprint, FCFP_6. The model revealed distinctive structural characteristics between agonistic and antagonistic compounds: in general, 1) GPCR agonists were flexible and had aliphatic amines, and 2) GPCR antagonists had planar groups and aromatic amines. This model showed very good discriminative ability in general, with pretty good discriminant statistics for the training set (accuracy: 90.1%) and a good predictive ability for the test set (accuracy: 89.2%). Also, receiver operating characteristic (ROC) plot showed the area under the curve (AUC) to be 0.957, and Matthew's Correlation Coefficient (MCC) value was 0.803. The quality of our model suggests that it could aid to classify the compounds as either GPCR agonists or antagonists, especially in the early stages of the drug discovery process.

A Study on a past pregnancy experiences of maternity with handicaped children (장애아를 가진 일부 모성의 임신기왕력에 대한 연구)

  • 김초강
    • Korean Journal of Health Education and Promotion
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    • v.3 no.1
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    • pp.63-73
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    • 1985
  • Ratio of physically and mentally handicapped people among the total population is about 3∼4%. Regardless of the extent of seriousness of handicaps, they have to sustain various difficulties in their life time and pose challenging problems to their homes, community and nation. In the spectrum of their problems, measures such as treatment, rehabilitation and welfare work all occupied important part but most significant measure is the prevention. Such handicaps items from health care of maternal and child, mostly causes throughout the process of pregnancy, delivery and upbringing. And then this study is focused on the pregnant history of the mothers with handicapped children. The objective of this study is to identify the basic factors which can create a handicapped child during pregnancy and is to prevent the birth of such a child. For this study, 301 mothers who have handicapped children were selected, now receiving various training at 5 rehabilitation and educational facilities. And questionnaires distributed to them during the period of Oct, 1983 to Dec, 14. The collected responses have been analized in terms of significant numbers, percentage and metic average. Their related results are as follows: 1. The sexual ratio between the male and female was 58.5% compare 41.5%. The average age of the handicapped children was 10.1 years old and that of mothers at the time of the children's birth was 28.9 old years. They were born as 2.14th in their family, the ratio of antenatal care for pregnant mothers was 36.2% and 22.9% were abnormally delivered. 37.9% out of the total were born from mothers with ages above 35 years and as their first baby. 2. The time of confirming the handicapped nature of children was during babyhood by 97.1% and discovery of these misfortunes were made by chance. As for causes of those-handicapped status 20.9% disease from complication, 15.3% from difficulties experience at the time of delivery, 11.3% from heredity and 10% were results of drug abuse during pregnancy, and 49.8% of the handicapped children were mentally retarded.

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Development of Atopic Dermatitis Mouse Model with Spleen Deficiency (비허형 아토피 동물모델 개발)

  • Yang, Won Kyung;Lyu, Yee Ran;Kim, Ho Kyoung;Kim, Seung Hyeong;Park, Yang Chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.4
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    • pp.213-219
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    • 2017
  • Atopic dermatitis (AD) is a common skin disease characterized by chronic and relapsing inflammatory dermatitis with immunological disturbances. Spleen deficiency (脾虛) is one of the major causes of AD, so development of animal model is required for AD research that reflects the pattern identification. The groups that we have used in this study included Senna folium extracts (SFE), 2,4-dinitrochlorobenzene (DNCB), and normal mice. Therefore, the present study was developed to atopic dermatitis mouse model with spleen deficiency in 2,4-dinitrochlorobenzene (DNCB) and senna leaves extracts induced AD in NC/Nga mice. The results demonstrated that senna leaves extract treatment significantly increased the dermatitis clinical score and epidermal thickness in AD-like skin lesions. We also proved beyond doubt that there was occurrence of erythema and skin moisture indices in the senna leaves extract groups. Further, we also found that the level of serum immunoglobulin E (IgE) in the senna leaves extract-treated group was increased. The amount of IL-4, IL-13, $TNF-{\alpha}$ and $TGF-{\beta}$ mRNA determined by real-time PCR was increased remarkably when senna leaves extract groups were treated on dorsal skin. Senna leaves extract groups significantly promoted the number of CD11B+/Gr-1 cell in skin, as well as the number of CD4+/CD8+ cell in dorsal skin compared with control. The review summarizes recent process in our understanding of the immunopathophysiology of spleen deficiency AD and the implications for spleen deficiency mouse models of AD on drug discovery from medical plants.

Screening, Diagnosis, and Treatment of Familial Hypercholesterolemia: Symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis (가족성 고콜레스테롤혈증의 스크린, 진단, 치료: 한국지질동맥경화학회 교육위원회 심포지엄)

  • Lee, Chan Joo;Lee, Ji Hyun;Choi, Seonghoon;Kim, Shin-Hye;Kang, Hyun-Jae;Lee, Sang-Hak;Park, Kyong Soo
    • Journal of Lipid and Atherosclerosis
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    • v.7 no.2
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    • pp.122-154
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    • 2018
  • Familial hypercholesterolemia (FH) is typically associated with single gene mutation that is inherited by autosomal dominant manner. Due to high cardiovascular risk, aggressive discovery, diagnosis, and treatment of FH are critical. Although FH is being increasingly spotlighted, we do not have sufficient data on Korean patients with FH. Here, we present the content of symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis held in May 2018: 1) epidemiology, clinical diagnosis, Korean FH data, and regulation in Korea; 2) genes associated with FH, sequencing process in suspicious proband, cascade screening, and difficulty in genetic diagnosis in FH; 3) the importance of lipid-lowering therapy in FH, conventional and novel therapeutics for FH; 4) diagnosis of FH in children and adolescence, screening, and treatment of FH in children and adolescence; 5) history of FH studies in Korea, the structure and current status of FH registry of Korean Society of Lipid and Atherosclerosis; and 6) difficulty in diagnosis of heterozygous and homozygous FH, drug intolerance and achievement of treatment target. Discussion between speakers and panels were also added. We hope that this article is helpful for understanding FH and future studies performed in Korea.

Evaluation for Long-term Stability of EGCG Rich Green Tea Extract (EGTE) (신규 건강기능식품소재 'EGCG 고함유 녹차추출물(EGTE)'의 장기안정성 평가)

  • Cheon, Se In;Heo, Eun Ji;Yoon, Min Ji;Choi, Sang Un;Ryu, Geon-Seek;Ryu, Shi Yong
    • Korean Journal of Pharmacognosy
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    • v.49 no.4
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    • pp.328-335
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    • 2018
  • 'EGCG(epigallocatechin gallate) rich Green Tea extract(EGTE)' was prepared by a convenient chromatographical manner using water and alcohol which was regarded as the most suitable and appropriate process for food manufacturing. The EGCG content in EGTE was estimated above 97%. Analysis of polyphenol components in green tea, i.e., catechin(C), epigallocatechin(EGC), epicatechin(EC), epigallocatechin gallate(EGCG), epicatechin gallate(ECG) and caffeine was performed by HPLC. The optimized HPLC method exhibited a good linearity of calibration curve, accuracy and precision. The long-term stability evaluation of EGTE was carried out with a powdered formulation and solution formulation by estimating the color change and measuring the EGCG content by HPLC analysis for one year. The EGCG content of the powdered EGTE stored in a transparent bottle at room temperature was retained over 97% at the end of the experimental period. The EGCG content of 0.1% water solution of EGTE stored in a transparent bottle at RT were observed to decrease below 30%, whereas that stored at $2^{\circ}C$ retained over 70%, respectively. These results suggested that a powdered formulation could be recommended for the commercialized nutraceutical product of EGTE rather than a solution formulation.

1H-NMR-Based Metabolic Profiling of Cordyceps militaris to Correlate the Development Process and Anti-Cancer Effect

  • Oh, Junsang;Choi, Eunhyun;Yoon, Deok-Hyo;Park, Tae-Yong;Shrestha, Bhushan;Choi, Hyung-Kyoon;Sung, Gi-Ho
    • Journal of Microbiology and Biotechnology
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    • v.29 no.8
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    • pp.1212-1220
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    • 2019
  • The study of metabolomics in natural products using the diverse analytical instruments including GC-MS, LC-MS, and NMR is useful for the exploration of physiological and biological effects and the investigation of drug discovery and health functional foods. Cordyceps militaris has been very attractive to natural medicine as a traditional Chinese medicine, due to its various bioactive properties including anti-cancer and anti-oxidant effects. In this study, we analyzed the metabolite profile in 50% ethanol extracts of C. militaris fruit bodies from three development periods (growth period, matured period, and aging period) using $^1H-NMR$, and identified 44 metabolites, which are classified as 16 amino acids, 10 organic acids, 5 carbohydrates, 3 nucleotide derivatives, and 10 other compounds. Among the three development periods of the C. militaris fruit body, the aging period showed significantly higher levels of metabolites including cordycepin, mannitol (cordycepic acid), and ${\beta}-glucan$. Interestingly, these bioactive metabolites are positively correlated with antitumor growth effect; the extract of the aging period showed significant inhibition of HepG2 hepatic cancer cell proliferation. These results showed that the aging period during the development of C. militaris fruit bodies was more highly enriched with bioactive metabolites that are associated with cancer cell growth inhibition.

The Primary Process and Key Concepts of Economic Evaluation in Healthcare

  • Kim, Younhee;Kim, Yunjung;Lee, Hyeon-Jeong;Lee, Seulki;Park, Sun-Young;Oh, Sung-Hee;Jang, Suhyun;Lee, Taejin;Ahn, Jeonghoon;Shin, Sangjin
    • Journal of Preventive Medicine and Public Health
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    • v.55 no.5
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    • pp.415-423
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    • 2022
  • Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

  • Yu, Yeon Hee;Kim, Seong-Wook;Kang, Juhyeon;Song, Yejin;Im, yHyuna;Kim, Seo Jeong;Yoo, Dae Young;Lee, Man-Ryul;Park, Dae-Kyoon;Oh, Jae Sang;Kim, Duk-Soo
    • Journal of Korean Neurosurgical Society
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    • v.65 no.5
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    • pp.665-679
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    • 2022
  • Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

2D-QSAR analysis for hERG ion channel inhibitors (hERG 이온채널 저해제에 대한 2D-QSAR 분석)

  • Jeon, Eul-Hye;Park, Ji-Hyeon;Jeong, Jin-Hee;Lee, Sung-Kwang
    • Analytical Science and Technology
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    • v.24 no.6
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    • pp.533-543
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    • 2011
  • The hERG (human ether-a-go-go related gene) ion channel is a main factor for cardiac repolarization, and the blockade of this channel could induce arrhythmia and sudden death. Therefore, potential hERG ion channel inhibitors are now a primary concern in the drug discovery process, and lots of efforts are focused on the minimizing the cardiotoxic side effect. In this study, $IC_{50}$ data of 202 organic compounds in HEK (human embryonic kidney) cell from literatures were used to develop predictive 2D-QSAR model. Multiple linear regression (MLR), Support Vector Machine (SVM), and artificial neural network (ANN) were utilized to predict inhibition concentration of hERG ion channel as machine learning methods. Population based-forward selection method with cross-validation procedure was combined with each learning method and used to select best subset descriptors for each learning algorithm. The best model was ANN model based on 14 descriptors ($R^2_{CV}$=0.617, RMSECV=0.762, MAECV=0.583) and the MLR model could describe the structural characteristics of inhibitors and interaction with hERG receptors. The validation of QSAR models was evaluated through the 5-fold cross-validation and Y-scrambling test.