• 통합자연과학논문집
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• 제17권1호
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• pp.21-30
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• 2024

Several anti-inflammatory small molecules have been found in the process of the inflammatory response, and these small molecules have been used to treat some inflammatory and autoimmune diseases. Numerous tools for predicting anti-inflammatory peptides (AIPs) have emerged in recent years. However, conducting experimental validations in the lab is both resource-intensive and time-consuming. Current therapies for inflammatory and autoimmune disorders often involve nonspecific anti-inflammatory drugs and immunosuppressants, often with potential side effects. AIPs have been used in treating inflammatory illnesses like Alzheimer's disease and can limit the expression of inflammatory promoters. Recent advances in adverse incident predictions (AIPs) have been made, but it is crucial to acknowledge limitations and imperfections in existing methodologies.

• 생약학회지
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• 제50권3호
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• pp.198-204
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• 2019

A facile and convenient method was developed for the mass production of epigallocatechin gallate (EGCG) rich green tea extract (Er-GTE). The Er-GTE was successfully obtained from the crude water extract of green tea by the combination of two step purification, i.e., a simple adsorption process on the cation exchange resins (Trilite SCR-B) followed by the chromatography with Diaion HP-20 resins. The green tea extract produced by water extraction under $45^{\circ}C$ was subjected to adsorb on the strongly acidic cation exchange resin, Trilite SCR-B. The eluate passed through the resin was reabsorbed on Diaion HP-20 resin, which was subjected to elute with a mixture of water and alcohol by conventional chromatographical manner. The EGCG content in Er-GTE was estimated above 97% by HP-LC analysis and the newly developed method was regarded as the most suitable and appropriate process for the mass production of epigallocatechin gallate rich green tea extract (Er-GTE).

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.65-74
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• 2006

Modem drug discovery requires rapid pharmacokinetic evaluation of chemically diverse compounds for early candidate selection. This demands the development of analytical methods that offer high-throughput of samples. Naturally, liquid chromatography / tandem mass spectrometry (LC-MS/MS) is choice of the analytical method because of its superior sensitivity and selectivity. As a result of the short analysis time(typically 3-5min) by LC-MS/MS, sample preparation has become the rate- determining step in the whole analytical cycle. Consequently tremendous efforts are being made to speed up and automate this step. In a typical automated 96-well SPE(solid-phase extraction) procedure, plasma samples are transferred to the 96-well SPE plate, internal standard and aqueous buffer solutions are added and then vacuum is applied using the robotic liquid handling system. It takes only 20-90 min to process 96 samples by automated SPE and the analyst is physically occupied for only approximately 10 min. Recently, the ultra-high flow rate liquid chromatography (turbulent-flow chromatography)has sparked a huge interest for rapid and direct quantitation of drugs in plasma. There is no sample preparation except for sample aliquotting, internal standard addition and centrifugation. This type of analysis is achieved by using a small diameter column with a large particle size(30-5O ${\mu}$m) and a high flow rate, typically between 3-5 ml/min. Silica-based monolithic HPLC columns contain a novel chromatographic support in which the traditional particulate packing has been replaced with a single, continuous network (monolith) of pcrous silica. The main advantage of such a network is decreased backpressure due to macropores (2 ${\mu}$m) throughout the network. This allows high flow rates, and hence fast analyses that are unattainable with traditional particulate columns. The reduction of particle diameter in HPLC results in increased column efficiency. use of small particles (<2 urn), however, requires p.essu.es beyond the traditional 6,000 psi of conventional pumping devices. Instrumental development in recent years has resulted in pumping devices capable of handling the requirements of columns packed with small particles. The staggered parallel HPLC system consists of four fully independent binary HPLC pumps, a modified auto sampler, and a series of switching and selector valves all controlled by a single computer program. The system improves sample throughput without sacrificing chromatographic separation or data quality. Sample throughput can be increased nearly four-fold without requiring significant changes in current analytical procedures. The process of Bioanalytical Method Validation is required by the FDA to assess and verify the performance of a chronlatographic method prior to its application in sample analysis. The validation should address the selectivity, linearity, accuracy, precision and stability of the method. This presentation will provide all overview of the work required to accomplish a full validation and show how a chromatographic method is suitable for toxirokinetic sample analysis. A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method developed to quantitate drug levels in dog plasma will be used as an example of tile process.

• 대한안전경영과학회지
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• 제15권1호
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• pp.293-301
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• 2013

The purpose of this study is to introduce the limit of previously used six sigma quality process evaluation metrics, $Z_{st}$ and $P_{pk}$, and a solution to overcome this drawback by using a metric based on performance evaluation of Z-factor quality innovation. Case analysis on projects from national six sigma contest from 2011 to 2012 is performed and literature review on new drug development HTS (High Throughput Screening) is used to propose innovative performance evaluation metrics. This research shows that experimental study on six sigma evaluation metric, $Z_{st}$ and $P_{pk}$, have no significance difference between industrial type (Manufacturing, Semi-Public Institute, Public Institute) and CTQ type (Product Technology Type CTQ, Process Technology Type CTQ). Following discovery characterize this quality improvement as fixed target type project. As newly developed moving target type of quality innovation performance metric Z-Factor is used for evaluating experimental study, hypothetical analysis suggests that $Z_{st}$ and $P_{pk}$ share different relationship or even show reciprocal relationship. Constraints of the study are relatively small sample size of only 37 projects from past 2 years and conflict on having interview and communication with six sigma quality practitioner for qualitative experimental study. Both moving target type six sigma innovation project and fixed target type improvement project or quality circle enables efficient ways for a better understanding and quality practitioner use by applying quality innovation performance metric. Downside of fixed target type quality performance evaluation metric, $Z_{st}$ and $P_{pk}$, is presented through experimental study. In contrast, advantage of this study is that high throughput requiring product technology, process technology and quantum leap typed innovation effect is evaluated based on precision and accuracy and Z-Factor that enables relative comparison between enterprises is proposed and implemented.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.573-580
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• 2016

Caspases, a family of cysteine proteases, cleave substrates and play significant roles in apoptosis, autophagy, and development. Recently, our group identified 72 genes that interact with Death Caspase-1 (DCP-1) proteins in Drosophila by genetic screening of 15,000 EP lines. However, the cellular functions and molecular mechanisms of the screened genes, such as their involvement in apoptosis and autophagy, are poorly understood in mammalian cells. In order to study the functional characterizations of the genes in human cells, we investigated 16 full-length human genes in mammalian expression vectors and tested their effects on apoptosis and autophagy in human cell lines. Our studies revealed that ALFY, BIRC4, and TAK1 induced autophagy, while SEC61A2, N-PAC, BIRC4, WIPI1, and FALZ increased apoptotic cell death. BIRC4 was involved in both autophagy and apoptosis. Western blot analysis and luciferase reporter activity indicated that ALFY, BIRC4, PDGFA, and TAK1 act in a p53-dependent manner, whereas CPSF1, SEC61A2, N-PAC, and WIPI1 appear to be p53-independent. Overexpression of BIRC4 and TAK1 caused upregulation of p53 and accumulation of its target proteins as well as an increase in p53 mRNA levels, suggesting that these genes are involved in p53 transcription and expression of its target genes followed by p53 protein accumulation. In conclusion, apoptosis and/or autophagy mediated by BIRC4 and TAK1 may be regulated by p53 and caspase activity. These novel findings may provide valuable information that will aid in a better understanding of the roles of caspase-related genes in human cell lines and be useful for the process of drug discovery.

• Fisheries and Aquatic Sciences
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• 제21권8호
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• pp.22.1-22.7
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• 2018

Background: Apoptosis is a process of programmed cell death, and apoptosis defect results in serious diseases such as cancer. Apoptosis induction is one of the key mechanisms of anti-cancer agents. This study was aimed to find anti-prostate cancer compounds from marine-derived fungus Microsporum sp. Results: We found that physcion isolated from the fermentation broth extract of the marine fungus Microsporum sp. strain MFS-YL decreases the cell proliferation of PC3 human prostate cancer cells. Physcion induced cell apoptosis as determined by Annexin V/propidium iodide double staining. Physcion downregulated the anti-apopotoic proteins such as Ras, Bcl-xL, and Bcl-2, whereas upregulated the pro-apoptotic Bax. Physcion also activated caspase-3, caspase-8, and caspase-9. Conclusion: These results suggest that physcion from Microsporum sp. inhibits the proliferation of PC3 human prostate cancer cells via the pathway leading to apoptotic cell death. Physcion may be a potential candidate in the field of anticancer drug discovery against human prostate cancer.

• Natural Product Sciences
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• 제20권3호
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• pp.170-175
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• 2014

Twenty five methanolic plant extracts were investigated to determine the anticancer activity against sonic hedgehog (shh)/Gli signaling pathway dependent cancer, PANC-1 human pancreatic cancer cells, through three screening programs. All extracts were inspected their inhibitory properties on sonic hedgehog-conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity in C3H10T1/2 mouse mesenchymal stem cells to examine whether the plant extracts affect the shh/Gli signaling pathway. Next, plant extracts were screened the ability to suppress the cell proliferation of PANC-1 human pancreatic cancer cells. Finally, active plant extracts from the two screening systems were evaluated for the suppressive effect on Gli-mediated transcriptional activity in PANC-1 cells. Among active plants, Cinnamomum cassia suppressed Gli-mediated transcriptional activity leading to the down-regulated expression of Gli-target genes such as Gli-1 and Patched-1 (Ptch-1). This study provides the consideration for the important role of natural products in drug discovery process as well as the basis for the further analysis of active plant and potential identification of novel bioactive compounds as inhibitors of Gli and therapeutic candidates against shh/Gli signaling pathway dependent cancers.

• Bulletin of the Korean Chemical Society
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• 제29권5호
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• pp.1013-1017
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• 2008

Syndecan-3 is a cell-surface heparan sulfate proteoglycan, which performs a variety of functions during cell adhension process. It is also a coreceptor for growth factor, mediating cell-cell and cell-matrix interaction. Syndecan-3 contains a cytoplasmic domain potentially associated with the cytoskeleton. Syndecan-3 is specifically expressed in neuron cell and has related to neuron cell differentiation and development of actin filament in cell migration. Syndecans each have a unique, central, and variable (V) region in their cytoplasmic domains. And that region of syndecan-3 may modulate the interactions of the conserved C1 regions of the cytoplasmic domains by tyrosine phosphorylation. Cytoplasmic domain of syndecan-3 has been synthesized for NMR structural studies. The solution structure of syndecan-3 cytoplasmic domain has been determined by two-dimensional NMR spectroscopy and simulated-annealing calculation. The cytoplasmic domain of the syndecan proteins has a tendency to form a dimmer conformation with a central cavity, however, that of syndecan-3 demonstrated a monomer conformation with a flexible region near C-terminus. The structural information might add knowledge about the structure-function relationships among syndecan proteins.

• Asian Journal of Innovation and Policy
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• 제12권1호
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• pp.054-074
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• 2023

With the advent of the '4th Industrial Revolution', digitalization using AI (Artificial Intelligence), big data, IoT (Internet of Things), cloud computing and mobile is accelerating across all industries and global companies have fundamentally reorganized customer experiences, business models, and operations centering on digital transformation. Business innovation drives productivity improvement, process simplification, price, competitiveness and sustainable expansion. Whether digital transformation will be necessary for the current industrial environment is no longer important, and how quickly companies achieve digitalization has emerged as the utmost crucial element in industrial continuity. As non-face-to-face and remote technologies have begun in earnest, and accelerated in the pharmaceutical industry. They are looking for ways to provide value, generate profits, improve efficiency, and sustain the future. Compared to other industries, the pharmaceutical-related sectors have shown high interest in digital transformation especially to reduce costs and meet the challenge of delivering products during the pandemic environment.

• 한국산학기술학회논문지
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• 제16권2호
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• pp.1200-1206
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• 2015

신약 개발의 주요 표적이 되는 G-protein coupled receptor (GPCR)은 대부분의 생리적 활동에 관여하며 다양한 질병과 질환들에 관련되어 있다. GPCR을 타겟으로 하는 의약개발 연구에서 필수적인 실험방법으로 많이 활용되고 있는 세포기반 스크리닝 기술들은 사용되는 세포의 상태에 따라 데이터의 질이 좌우되는데 최근, 실험에 사용할 세포를 매번 배양하면서 소모되는 비용과 데이터의 변동을 줄이기 위해 냉동보관 세포를 적용하는 추세이다. 이에 본 연구에서는 단일 세포를 많은 양으로 배양하고 냉동 보관한 다음 사용되는 세포의 반응을 최적화하기 위하여 칼슘 검출을 위한 광 단백질이 포함된 세포주에 calcium sensing receptor와 urotensin II receptor가 안정적으로 발현되는 안정화 세포를 제작하고 $-80^{\circ}C$에서 보관한 다음 7 일 간격으로 실험했을 때 효능제와 길항제 반응을 비교하였다. 실험결과 보관기간이 증가함에 따라 세포 신호 값이 감소하였지만 $EC_{50}$와 $IC_{50}$ 값의 변화는 나타나지 않았다($EC_{50}:3.46{\pm}1.36mM$, $IC_{50}:0.49{\pm}0.15{\mu}M$). 그러나 액체질소에서 보관한 세포의 경우에서는 비냉동 세포와 비교하여 세포 신호 값이 감소했지만 보존기간에 따른 변화가 나타나지 않았으며 기간에 따른 $IC_{50}:0.49{\pm}0.15{\mu}M$와 $IC_{50}$의 변화도 없었다. 보관기간이 경과 될수록 세포의 신호 값이 감소하는 것은 세포 손상도 증가가 원인인 것으로 판단되며, 이러한 결과들로부터 장기간 냉동 보관을 위해서는 액체질소를 이용하는 것이 가장 효과적이고 한 달 이내 단기간 사용의 목적으로는 $-80^{\circ}C$ 보관조건도 가능할 것으로 판단된다. 이와 같이 냉동세포의 적극적인 활용을 통하여 초기 스크리닝 과정에서 나타나는 실험 유동성을 감소시킬 수 있을 것으로 예상된다.