• Journal of Plant Biotechnology
• /
• 제46권3호
• /
• pp.236-245
• /
• 2019

열매가 성숙하는 과정은 유전학적으로 프로그램화 되어 있는 과정으로 다른 여러 유전자 발현과 효소의 작용에 의한 생화학적, 생리적 조절의 결과물이다. 이런 일련의 과정에서 과실과 채소에 화학적 조성과 활성 물질에 변화가 나타나는 것을 당연한 결과일 것이다. 해당화의 열매가 성숙하는 과정에서 이들 활성 물질의 변화를 측정하기 위해 우리는 성숙단계 별로 채집 된 열매 시료 추출물에서의 항산화 활성의 차이, 항 elastase 활성 및 polyphenol 화합물의 함량을 분석하였다. 결과적으로 미성숙 단계의 열매 추출물에서 높은 phenolic 화합물과 플라보노이드 함량이 검출되었으며, 그에 따라 높은 radical 소거능, 환원력 및 ORAC 활성을 나타냈다. 또한 elastase 저해 활성에서도 다른 성숙 단계의 추출물에 비해 미성숙 단계의 열매 추출물에서 높은 활성을 나타내는 것으로 조사되었다. 더불어 성숙과정에서 플라보노이드 생합성 과정에 관련된 유전자의 발현이 감소하는 것을 확인하였으며, 이를 통해 플라보노이드의 함량이 감소하는 것을 설명할 수 있었다. HPLC분석을 통해 다른 성숙 단계의 추출물과 비교하여 미성숙 열매 추출물에서 높은 함량의 myricetin, caffeic acid, chlorogenic acid, syringic acid, р-coumaric acid 등이 검출되었다. 구조 기반의 molecular doking을 사용하며 이들 화합물과 elastase의 결합부위와 패턴을 분석하였으며 이를 통해 chlorogenic acid와 elastase가 강하게 결합하는 것을 확인하였다. 따라서, 본 연구를 통해서 해당화 열매의 성숙 정도가 이 식물의 약리학적 가치에 영향을 미치는 것을 규명하였고, 미성숙한 해당화 열매는 향후 활성산소 생성에 의해 유발되는 피부 노화 억제 효과뿐 아니라 피부의 탄력성 강화를 위한 기능성 천연소재로서의 가능성을 입증하였다.

• 우주기술과 응용
• /
• 제3권2호
• /
• pp.101-117
• /
• 2023

우주상에 존재하는 우주물체에 접근하여 궤도상에서 제거하는 능동 제거 기술(active debris removal, ADR)과 연료 충전, 배터리 교환 등의 위성의 수명연장을 위한 기술인 궤도상 서비싱(on-orbit servicing)은 우주물체의 증가와 함께 그 관심이 커지고 있다. 인공위성연구소에서는 국내에서 발사되었던 국가 자산 중 임무가 종료된 후 궤도상에서 여전히 우주를 돌고 있는 국가 우주자산을 포획 및 제거하는 목적의 위성을 개발하기 위한 연구를 수행 중에 있다. ADR 소형위성은 지금껏 국내에서 개발되었던 지구 및 우주환경 관측 위성과 다르게 랑데부/도킹 기술 등을 포함한 우주 탐사 임무 등 미래 임무에 요구되는 기술을 구현 및 실증하는 것을 주요 임무로 가지고 있다. 본 논문에서는 여러 국가 우주자산들 중 1990년대에 발사된 우리별 위성의 포획 및 제거 임무를 갖고 있는 ADR 소형위성의 궤도 전이 방법에 대해서 소개한다. 소형 위성은 무게가 약 200 kg 이하가 되도록 개발을 수행할 예정이고, 2027년 한국형 발사체를 통해 궤도상에 투입되는 상황을 가정하여 임무를 설계했다. 특히, 지구의 J2 섭동력을 이용해서 목표물과 다른 RAAN 일변화를 만들어 줌으로써, 목표물로의 궤도면 변경을 직접 천이 방식과 비교하여 더 적은 연료를 이용하는 전략을 구성하였다. 이 방법을 이용하여 소형위성급 무게의 위성으로 우주쓰레기 제거 임무를 가능하게 하며, 뉴스페이스 시대에 새로운 형태의 우주탐사를 수행하는 기술 검증 플랫폼이 될 것으로 기대한다.

• Bulletin of the Korean Chemical Society
• /
• 제32권3호
• /
• pp.1000-1006
• /
• 2011

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

• Journal of Ginseng Research
• /
• 제47권3호
• /
• pp.376-384
• /
• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Ginseng Research
• /
• 제44권2호
• /
• pp.247-257
• /
• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Genomics & Informatics
• /
• 제13권1호
• /
• pp.15-24
• /
• 2015

Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and ${\beta}$-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and ${\beta}$-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.

• Molecules and Cells
• /
• 제27권6호
• /
• pp.651-656
• /
• 2009

The formation of ${\beta}$-amyloid peptide ($A{\beta}$) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, ${\alpha}$-, ${\beta}$-, and ${\gamma}$-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the ${\beta}$-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the ${\beta}$-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of ${\beta}$-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of ${\beta}$-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of ${\beta}$-secretase (P5-P3'), and the side chain of P2- Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by ${\beta}$-secretase than Sub W. The two substrate peptides showed different tendency to bind to ${\beta}$-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

• 한국해양공학회지
• /
• 제21권2호
• /
• pp.67-74
• /
• 2007

Maritime and Ocean Engineering Research Institute (MOERI), a branch of KORDI, has designed and manufactured a model of an autonomous underwater vehicle (AUV) named ISiMI (Integrated Submergible for Intelligent Mission Implementation). ISiMI is an AUV platform to satisfy the various needs of experimental test required for development of challenging technologies newly investigated in the field of underwater robot; control and navigational algorithms and software architectures. The main design goal of ISiMI AUV is downsizing which will reduce substantially the operating cost compared to other vehicles previously developed in KORDI such as VORAM or DUSAUV. As a result of design and manufacturing process, ISiMI is implemented to be 1.2 m in length, 0.17 m in diameter and weigh 20 kg in air. A series of tank test is conducted to verify the basic functions of ISiMI in the Ocean Engineering Basin of MOERI, which includes manual control with R/F link, auto depth, auto heading control and a final approach control for underwater docking. This paper describes the implementation of ISiMI system and the experimental results to verify the function of ISiMI as a test-bed AUV platform.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10345-10350
• /
• 2015

Background: Punica granatum (family: Lythraceae) is mainly found in Iran, which is considered to be its primary centre of origin. Studies on pomegranate peel have revealed antioxidant, anti-inflammatory, anti-angiogenesis activities, with prevention of premature aging and reducing inflammation. In addition to this it is also useful in treating various diseases like diabetes, maintaining blood pressure and treatment of neoplasms such as prostate and breast cancer. Objectives: In this study we identified anti-cancer targets of active compounds like corilagin (tannins), quercetin (flavonoids) and pseudopelletierine (alkaloids) present in pomegranate peel by employing dual reverse screening and binding analysis. Materials and Methods: The potent targets of the pomegranate peel were annotated by the PharmMapper and ReverseScreen 3D, then compared with targets identified from different Bioassay databases (NPACT and HIT's). Docking was then further employed using AutoDock pyrx and validated through discovery studio for studying molecular interactions. Results: A number of potent anti-cancerous targets were attained from the PharmMapper server according to their fit score and from ReverseScreen 3D server according to decreasing 3D scores. Conclusion: The identified targets now need to be further validated through in vitro and in vivo studies.

• Journal of Advanced Marine Engineering and Technology
• /
• 제39권4호
• /
• pp.399-404
• /
• 2015

최근 국제 원유가의 폭등으로 선박의 연료비 부담이 상대적으로 가중되고 있으며, 또한 연료의 연소과정에서 발생하는 온실가스에 대한 국제적 규제 움직임도 가속되고 있다. 이에 따라 에너지 효율 개선을 위해서 선체의 설계변경, 마찰저항을 줄이기 위한 도료개발, 엔진의 열효율을 개선하기 위한 첨가제 개발, 연료를 절감하기 위하여 저속운전 등 다양한 방법들이 적용되고 있다. 따라서 최근 고유가 시대에 선박의 고속화와 대형화 및 에너지 절감형 선형의 개발이 필수요건이 되고 있다. 또한 선체 표면의 국부 영역에서 저항 값들의 정성 및 정량적인 변화와 보다 세밀한 분석은 불가피하다고 판단되어진다. 따라서 본 연구는 에너지 효율 개선을 위한 기초연구로서 현재 운항중인 선박의 선체에서 자생하는 해양생물로 인한 마찰저항을 확인하기 위하여 도크 전 후의 엔진성능을 분석하고 그 결과를 도크와 도크사이 2.5년의 데이터와 비교함으로서 주기관의 성능, 마찰저항과 부하변화 및 연료소비량과 선속에 미치는 연구 결과 등을 보고한다.