• BMB Reports
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• 제49권12호
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• pp.681-686
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• 2016

Fructose 1,6-bisphosphate aldolase (FBA) is important for both glycolysis and gluconeogenesis in life. Class II (zinc dependent) FBA is an attractive target for the development of antibiotics against protozoa, bacteria, and fungi, and is also widely used to produce various high-value stereoisomers in the chemical and pharmaceutical industry. In this study, the crystal structures of class II Escherichia coli FBA (EcFBA) were determined from four different crystals, with resolutions between $1.8{\AA}$ and $2.0{\AA}$. Native EcFBA structures showed two separate sites of Zn1 (interior position) and Zn2 (active site surface position) for $Zn^{2+}$ ion. Citrate and TRIS bound EcFBA structures showed $Zn^{2+}$ position exclusively at Zn2. Crystallographic snapshots of EcFBA structures with and without ligand binding proposed the rationale of metal shift at the active site, which might be a hidden mechanism to keep the trace metal cofactor $Zn^{2+}$ within EcFBA without losing it.

• 약학회지
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• 제36권6호
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• pp.518-528
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• 1992

To determine the optimal conformation of sulfonylureas, the correlation between conformation and hypoglycemic activity of the two sulfonylureas of tolbutamide and chlorpropamide as hypoglycemic agent was studied using an empirical potential function (ECEPP/2) and the hydration shell model in the unhydrated and hydrated states. The conformational energy was minimized from several starting conformations with possible torsion angles in each molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecules in aqueous solution, the contribution of water-accessible volume of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of two sulfonylureas, it could be suggested that the hydration of sulfonylurea moiety is related to increase the hypoglycemic activity. From the calculation results, it was known that the conformational entropy is the major contribution to stabilize the low-free-energy conformations of two sulfonylureas in unhydrated state. Whereas, in hydrated state, the hydration free energy largely contributes to the total free energies of low-free-energy conformations of tolbutamide and conformational entropy contributes to stabilize the low-free-energy conformations of chlorpropamide. The torsion angles from phenyl ring to urea moiety of the low-free-energy conformations of the two sulfonylureas were shown the nearly regular trend. On the basis of these results, the conformation exhibiting the optimal hypoglycemic activity of sulfonylureas and the binding direction to pancreatic receptor site A could be predicted. Also, according to the side chain lengthening of urea moiety, tolbutamide showed various conformational change. Therefore, steric effect may be important factor in the interaction between sulfonylureas and the putative pancreatic receptor.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권4호
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• pp.319-324
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• 2006

Although the sera used in animal cell culture media provide the macromolecules, nutrients, hormones, and growth factors necessary to support cell growth, it could also be an obstacle to the production of recombinant proteins in animal cell culture systems used in many sectors of the biotechnology industry. For this reason, many research groups, including our laboratory, have been trying to develop serum-free media (SFM) or serum-supplemented media (SSM) for special or multi-purpose cell lines. The Chinese hamster ovary (CHO) cell, for example, is frequently used to produce proteins and is especially valuable in the large-scale production of pharmaceutically important proteins, yet information about its genome is lacking. Also, SFMs have only been evaluated by comparing growth patterns for cells grown in SFMs with those grown in SSM or by measuring the titer of the target protein obtained from cells grown in each type of medium. These are not reliable methods of obtaining the type of information needed to determine whether an SFM should be replaced with an SSM. We carried out a cDNA microarray analysis to evaluate MED-3, an SFM developed in our laboratory, as a CHO culture medium When CHO cells were cultured in MED-3 instead of an SSM, several genes associated with cell growth were down-regulated, although this change diminished over time. We found that the insulin-like growth factor (IGF) gene was representative of the proteins that were down-regulated in cells cultured in MED-3. When several key supplements - including insulin, transferrin, ethanolamine, and selenium - were removed from MED-3, the IGF expression was consistently down- regulated and cell growth decreased proportionately. Based on these results, we concluded that when an SFM is used as a culture medium, it is important to supplement it with substances that can help the cells maintain a high level of IGF expression. The data presented in this study, therefore, might provide useful information for the design and development of SFM or SSM, as well as for the design of genome-based studies of CHO cells to determine how they can be used optimally for protein production in pharmaceutical and biomedical research.

• 센서학회지
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• 제21권4호
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• pp.241-248
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• 2012

Recently healthcare industry such as pharmaceutical, medical device and healthcare service technology is growing significantly. Mobile healthcare has attracted big attention due to IT convergence technology. Paradigm of healthcare has been changed from the 1st generation(communicable disease prevention) and the 2nd generation(treatment of disease due to extended life expectancy) to the 3rd generation(extended life expectancy due to prevention and control). In our study, we suggest the 3rd generation mobile healthcare system using Bluetooth based wearable ECG monitoring system and smart phone technology. The mobile healthcare system consists of wearable shirts with Bluetooth communication module, ECG sensor, battery, and mobile phone. The ECG data is obtained by a miniaturized sensor and the data is transferred to a mobile phone using Bluetooth communication. Then, user can monitor his/her own ECG signal on an application using Android in mobile phone. The Bluetooth communication device is used due to highly reliable data transmission property and the Bluetooth chip is embedded in every mobile phone. The wearable shirts with chest belt of Bluetooth ECG module is designed with a focus on convenience in the daily life of a wearer. The ECG signal evaluation software in Android based mobile phone is developed for the health check and the ECG signal variation is tested according to the activities of the wearer such as walking, climbing stairs, stand up and sit down, and so on.

• 한국의사학회지
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• 제27권2호
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• pp.11-37
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• 2014

Objectives : The purpose of this study was to analyze and identify the problems of the changes in regulations that are relevant to approval, notification, and review of herbal medicinal preparations and crude drug preparations. Methods : I collected the regulations of approval, notification, and review of medicinal products mostly from official gazettes, analyzed enactment and amendments regarding herbal medicinal preparations and crude drug preparations, and studied it from the view point of Korean medicine field. Results : Regulations in regards to approval, notification, and review of herbal medicinal preparations and crude drug preparations were first established in 1978. Herbal drugs started to be categorized as crude drug preparations in 1981 and the regulatory outlines were completed in 1999. From 2008 to 2012, the regulatory standards that let crude drug preparations be new drugs from natural products were established. Through those procedures, the followings became crude drug preparations: 1) wholly new prescriptions that are not recorded in Korean Medical Classics, 2) prescriptions that are recorded in Korean Medical classics but prepared with new standard, composition and efficacy, 3) prescriptions that are recorded in Korean Medical classics but prepared with new formulation, and 4) herbal drugs. In case of herbal medicinal preparations, however, only regulations that are related to 1) drugs prepared with new compositions that are not recorded in Korean Medical Classics, 2) drugs with same prescription and same formulation, and 3) drugs with new formulation were arranged. Conclusions : Actual circumstances on crude drug-oriented regulations regarding approval, notification and review and future forms of prescription and drug administration in Korean Medical Institutions can be expected due to expansion in range of herbal medicinal preparations and shrink in that of on-site preparations. Reasonable improvement in efficient usage of modernized herbal medicinal preparations in Korean medical institutions and prospective cooperation from related pharmaceutical industry are needed.

• 한국근적외분광분석학회:학술대회논문집
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• 한국근적외분광분석학회 2001년도 NIR-2001
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• pp.1242-1242
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• 2001

The use of fibre optic probes for NIR quality control in the industry is becoming very important, as it provides a powerful tool to reduce sample analysis time and it facilitates the implementation of on-line analyses. However, most of the applications of fibre optics and probes have been done on suspensions, clear liquids and films, chemical and pharmaceutical products and also on fruits and animal products. Traditional applications of near infrared spectroscopy in agriculture have been developed in reflectance mode and calibration transfer could be an interesting way to reduce efforts. Classical methods for calibration transfer between different instruments involve the use of sealed reference cups, but, as fibre optic analysis does not use cups, it is necessary to develop new methods for calibration transfer without standards (Blank et al., 1996). In this paper, we have studied how the most used mathematical pretreatments (three methods of Multiplicative Scatter Correction, Standard Normal Variate, Detrending and derivatives) and their combinations applied to calibration development can contribute to reduce spectral differences between instruments. Calibration equations were obtained for three sets of cereals (barley, wheat and maize) scanned in reflectance mode and then they were validated with samples analysed in reflectance and interactance-reflectance mode (fibre optic). Preliminary results show how some combination of pretreatments reduce the differences in the predicted values, measured as standard error of differences, facilitating the use of calibrations obtained in reflectance for samples analysed by interactance-reflectance. However, the application of pretreatments is not enough to satisfy the control limits for calibration transfer suggested by Shenk et al. (1992), and it should be necessary to combine them with a specific algorithm for instruments standardization.

• Journal of Plant Biotechnology
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• 제37권3호
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• pp.275-282
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• 2010

고등식물의 엽록체 형질전환은 핵 형질전환에서 기대 할 수 없는 여러 가지 이점을 가진다. 외래 단백질의 발현율을 획기적으로 높일 수 있고, 여러 유전자를 동시에 발현시킬 수 있으며, 상동재조합에 의한 부위-특이적 유전자 삽입으로 인해 유전자 침묵 및 위치효과가 없다. 더욱이, 대부분 작물은 화분을 통한 도입된 유전자의 전이가 불가능한 모계 유전을 하기 때문에 엽록체 형질전환은 환경 친화적이다. 엽록체 형질전환 시스템은 핵 형질 전환과 달리 작물에서의 성공에 제한적이었으나 지난 10년 동안 이런 한계가 극복되어 콩, 당근, 상추 및 유채 등의 작물에서도 성공하게 되었다. 그러므로 이제 작물의 엽록체 형질전환은 농업적 형질의 개선뿐 만 아니라, 고부가가치 백신과 의료용 단백질 생산을 통한 의약품 산업의 성장에 활용될 수 있을 것이다.

• 한국식품위생안전성학회지
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• 제30권1호
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• pp.98-102
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• 2015

Oleanolic acid는 다수의 식물 종에서 분리 되어 왔고 주로 유해한 영향이 없는 과일과 약초에 존재하기 때문에 전세계적으로 많은 나라에서 안전하게 소비되고 있으며, 현재는 화장품이나 약품에 사용되고 있다. Oleanolic acid는 peptidoglycan을 표적으로 하기 때문에 petidoglycan이 세균외막에 덮여있는 그람음성세균인 E. coli, Y. enterocolitica, S. flexneri, S. sonnei와 같은 세균에는 뚜렷한 oleanolic acid 항균활성이 관찰되지 않았다. 하지만 oleanolic acid의 유도체를 사용할 경우 그람음성세균에 대한 항균활성도 증가하였다. 반면 S. aureus와 L. monocytogenes와 같은 그람양성세균의 경우 peptidoglycan층이 세균외막에 덮여 있지 않기 때문에 oleanolic acid에 매우 민감하였다. 또한 oleanolic acid는 사람에 대한 세포독성 실험에서도 그 독성이 낮은 것으로 판단되었기 때문에 식중독 세균제어를 목적으로 연구를 진행할 필요가 있으며, 이 결과들은 식품에 적용되거나 항생제 대체를 위한 치료목적으로도 사용될 수 있을 것으로 사료된다.

• Nutrition Research and Practice
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• 제9권2호
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• pp.111-116
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• 2015

BACKGROUND/OBJECTIVES: Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS: To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were cultured in the presence of $2.5-10{\mu}g/mL$ of EEIO, and analyzed the cell cycle arrest by flow cytometry and the cell cycle controlling protein expression by Western blotting. RESULTS: Treatment cells with $2.5-10{\mu}g/mL$ of EEIO reduced viable HT-29 cell numbers and DNA synthesis, increased the percentage of cells in $G_1$ phase, decreased protein expression of CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions, fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as EEIO treatment on cell proliferation and cell cycle-related protein levels. CONCLUSIONS: These results demonstrate that fraction 2 is the major fraction that induces $G_1$ arrest and inhibits cell proliferation, suggesting I. obliquus could be used as a natural anti-cancer ingredient in the food and/or pharmaceutical industry.

• Nutrition Research and Practice
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• 제7권2호
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• pp.103-108
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• 2013

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ${\beta}$-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.