• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.579-588
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• 2015

Fungi of the genus Pestalotiopsis have drawn attention for their capability to produce an array of bioactive secondary metabolites that have potential for drug development. Here, we report the determination of a polyketide derivative compound, pestalotiollide B, in the culture of the saprophytic fungus Pestalotiopsis microspora NK17. Structural information acquired by analyses with a set of spectroscopic and chromatographic techniques suggests that pestalotiollide B has the same skeleton as the penicillide derivatives, dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein (CETP), and as purpactins A and C', inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Strain NK17 can make a fairly high yield of pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid culture. Moreover, we found that a putative histone deacetylase gene, designated as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90 mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia production of the fungus. These results suggest that hid1 is a modulator, concerting secondary metabolism and development such as conidiation in P. microspora. Our work may help with the investigation into the biosynthesis of pestalotiollide B and the development for new CETP and ACAT inhibitors.

• Journal of Dairy Science and Biotechnology
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• v.23 no.1
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• pp.9-17
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• 2005

Nanotechnology has penetrated into the various branches of research and development and it is particularly of benefit to the particle size engineering. It has been widely known that the particle size of an active pharmaceutical ingredient (API) is critical in determining the bioavailability and processability of pharmaceutical formulation. However, the window of appropriate particle size has been limited mainly due to related processing difficulties. The windows have been widened by the recent development of nanotechnologies, resulting in diversified drug delivery systems. The impact of this development is far more fundamental than what can be expected from conventional particle size engineering. It is the case that the preparation and use of nanoparticles will soon be a common task in the particle engineering step of pharmaceutical unit operations. In this chapter, the basic principles of variouspreparation techniques will be discussed in detail. Regardless of processing details, the preparation methods of pharmaceutical nanoparticles mainly concern how to deal with the extra energy related with particle size. Depending on the ways of treating the e103 energy, preparation methods can be classified into two major classes, i.e.. thermodynamic and kinetic approaches. The recent progresses have shown the possibilities of much more complex combinations of different approaches and the use of new types of energy and nanostructures.

• 한국균학회소식:학술대회논문집
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• 2016.05a
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• pp.39-39
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• 2016

There is a growing consumer preference for self-medication, which has resulted in the growth of the Korean functional food market to \1.5 trillion in 2014. Functional foods that can modulate immune responses and enhance liver health are in the top 2 product-specific health functional food categories. The aim of this project was to develop and commercialize new health functional foods incorporated with Cordyceps militaris. Cordyceps genus includes about 400 species, many of which have been used as traditional medicines for many years in Asian countries. C. militaris belongs to the class Ascomycetes and has been used extensively as a crude drug and tonic food in East Asia. Owing to the various physiological activities of its main active constituent, cordyceptin, C. militaris is currently being used for multiple medicinal purposes. Recently, many studies have tried to elucidate the pharmacological mechanisms underlying the activities of Cordyceps spp., which include immune activation, anti-inflammatory, anticancer, and antiviral effects. After continuous attempts and research toward industrialization, C. militaris cultivated using brown rice was developed into a product by a standardized process and mass-cultivating system. It was successfully introduced into the market and was approved as a functional food ingredient for the first time in Korea. Based on this information, C. militaris containing functional food product for strengthening the immune system was released in August 2014 under the brand name "Dongchoong Ilgi." Dongchoong Ilgi is potentially beneficial for improving immune and liver functions and may enhance both the convenience and effectiveness of health functional foods taken by healthy people and patients with minor illness. In addition, the results of our study may be applicable for the development of health functional foods that could lower the risk of diseases such as the common cold and cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.349-354
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• 2006

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. The application of recombinant reporter plasmid such as the firefly luciferase gene has proven to be a very effective method to detect these chemicals. The bioassay system, CALUX, is sensitive in directly detecting AhR-agonists from a variety of environmental and biologic materials. However, responses of the AhR-dependent bioassays are dependent on the cell types used. Thus, we developed a sensitive bioassay using the recombinant mouse hepatoma cell (Hepa1c1c7) for the determination of dioxins. The recombinant cell line was stably transfected with firefly luciferase reporter gene (pGudLuc1.1). The transfected cells showed the highest induction of luciferase activity at 4.5 hr and a decrease beyond this time point. The system showed the highest sensitivity of detection ever reported. Upon TCDD exposure cells showed 2 fold increase at 10 pM and 7 fold increase at 100 pM, respectively. The passage number after the transfection played an important role in the sensitivity. The increase of passage number tended to increase the sensitivity of the cells up to 15. The media without phenol red showed a higher induction rate than with phenol red, suggesting the preferable use of phenol red-free media for the bioassay. Since each of the assays has unique characteristics that make them suitable for some screening applications and not others, development of sensitive bioanalytical methods based on a variety of cellular systems in a key to the successful determination of dioxins. The bioassay system developed in this study will contribute to further development of successful screening the AhR agonists among the environmental mixture. In addition, the rapid and sensitive nature of this cellular system can be applied as a valuable tool to screen the dioxin-like moieties among the prodrugs at the initial stage, thereby expediting the new drug discovery.

• Mass Spectrometry Letters
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• v.12 no.3
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• pp.66-75
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• 2021

Interleukin-4 (IL-4) and IL-13 are cytokines secreted by immune cells. Cytokines induce the proliferation of macrophages or promote the differentiation of secretory cells. The initiation and progression of allergic inflammatory diseases, such as asthma, are dependent on cytokines acting through related receptor complexes. IL-4 and IL-13 are N-glycoproteins. Glycan structures in glycoproteins play important roles in protein folding, protein stability, enzymatic function, inflammation, and cancer development. Therefore, the glycan structure of IL-4 and IL-13 needs to be elucidated in detail for the development of effective therapies. We report the first attempt to characterize the site-specific N-glycosylation of recombinant IL-4 and IL-13 via liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The tandem mass spectra of intact N-glycopeptides were identified using the Integrated GlycoProteome Analyzer (I-GPA) platform, which can automatically and rapidly analyze multiple N-glycopeptides, including their glycan composition and amino acid sequences. The recombinant IL-4 and IL-13 were identified with amino acid sequence coverages of 84% and 96%, respectively. For IL-4, 52 glycoforms on one N-glycosylation site were identified and quantified. In IL-13, 232 N-glycopeptides from three N-glycosylation sites were characterized, with the site Asn52 being the most extensively glycosylated (~80%). The complex glycans were the most abundant glycan on IL-4 and IL-13 (~96% and 91%, respectively), and the biantennary glycans were the most abundant in both recombinant IL-4 and IL-13 proteins.

• Journal of Food Hygiene and Safety
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• v.26 no.1
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• pp.57-63
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• 2011

This survey was conducted to develop an appropriate management for safety of children snacks. In this study, monitorings of food additives such as nine kinds of tar colors (tartrazine, sunset yellow FCF, brilliant blue FCF, indigo carmine, new coccine, amaranth, erythrosine, allura red and fast green FCF) which are sold at stationary store around the school, were performed. Eighty two samples (3 snacks, 71 candies, 4 chocolates and 4 beverages) were analyzed for tar colors. Results of risk assessment for tar colors were expressed as EDI (Estimated Daily Intake) comparing with ADI (Acceptable Daily Intake). The ratio of high risk group for tar color intake (95th) were 0-3.56%. The consumptions of tar colors from domestic and imported products for nine kinds of tar colors in candies were not significantly different. The results of this study indicated that each ED! of nine kinds of tar colors sold at stationary store around the school is much lower than each ADI in general. Consequently, the children snacks are thought to be safe for consumption.

• Analytical Science and Technology
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• v.26 no.2
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• pp.142-153
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• 2013

A new, rapid, and simple analytical method was developed and validated using high performance liquid chromatograph-photodiode array detector (HPLC-PAD) for the determination of lepimectin residues in agricultural commodities. The lepimectin residues in samples were extracted with methanol, partitioned with dichloromethane, and then purified with glass column filled with subsequently to aminopropyl ($NH_2$) solid phase extraction (SPE) cartridge. The purified samples were detected using HPLC-PAD. Correlation coefficient ($R^2$) of both lepimectin $A_3$ and $A_4$ solutions were 0.9999. The method was validated using cucumber spiked with lepimectin at 0.02 and 0.2 mg/kg and pepper, mandarin, hulled rice, potato, soybean at 0.02 and 0.5 mg/kg. Average recoveries were 76.0~114.8% with relative standard deviation less than 10%, and limit of detection (LOD) and limit of quantification (LOQ) were 0.005 and 0.01 mg/kg, respectively. The result of recoveries and overall coefficient of variation of a laboratory results in Gwangju regional KFDA and Daejeon regional KFDA was followed with Codex guideline (CAC/GL 40). Therefore, developed method in this study is accurate, rapid, and appropriate for lepimectin determination and will be used to keep safety of lepimectin residues in agricultural products.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.3-3
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• 2018

For centuries, Panax ginseng Meyer (Korean ginseng) has been widely used as a medicinal herb in Korea, China, and Japan. Ginsenosides are a class of triterpene saponins and recognized as the bioactive components in Korean ginseng. Ginsenosides, which can be classified broadly as protopanaxadiols (PPD), protopanaxatriols (PPT), and oleanolic acids, have been shown to flaunt a vast array of pharmacological activities such as immune-modulatory, anti-inflammatory, anti-tumor, anti-diabetic, and antioxidant effects. In recent years, a number of ginseng and ginsenoside researches have increasingly gained wide attention owing to its unique pharmacological properties. Although good efficacies of ginsenosides have been reported, lack of target specific delivery into tumor sites, low solubility, and low bioavailability due to modifications in gastro-intestinal environments limit their biomedical application in clinical trials. As a result to this major challenge, nanotechnology and drug delivery techniques play a significant role to solve this problematic issue. Thus, we reported the preparation of poly-ethylene glycol (PEG) and glycol chitosan (GC) functionalized to ginsenoside (Compound K and PPD) conjugates via hydrolysable ester bonds with improved aqueous solubility and pH-dependent drug release. In vitro cytotoxicity assays revealed that PEG-CK, and PPD-CK conjugates exhibited lower cytotoxicity compared to bare CK and PPD in HT29 cells. However, GC-CK conjugates exhibited higher and similar cytotoxicity in HT29 and HepG2 cells. Furthermore, GC-CK-treated RAW264.7 cells did not exhibit significant cell death at higher concentration of treatment which supports the biocompatibility of the polymer conjugates. They also inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW64.7 cells. In addition to polymer-ginsenoside conjugates, silver (AgNps) and gold nanoparticles (AuNps) have been successfully synthesized by green chemistry using different m. The biosynthesized nanoparticles demonstrated antimicrobial efficacy, anticancer, anti-inflammatory, antioxidant activity, biofilm inhibition, and anticoagulant effect. Special interest on the effective delivery methods of ginsenoside to treatment sites is the focus of metal nanoparticle research.In short, nano-sizing of ginsenoside results in an increased water solubility and bioavailability. The use of nano-sized ginsenoside and P. ginseng mediated metallic nanoparticles is expected to be effective on medical platform against various diseases in the future.

• Genomics & Informatics
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• v.15 no.4
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• pp.147-155
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• 2017

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

• Interdisciplinary Bio Central
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• v.3 no.1
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• pp.5.1-5.5
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• 2011

Introduction: Many signal transduction pathways mediate cell's behavior by regulating expression level of involved genes. Abnormal behavior indicates loss of regulatory potential of pathways, and this can be attributed to loss of expression regulation of downstream genes. Therefore, function of pathways should be assessed by activity of a pathway itself and relative activity between a pathway and downstream genes, simultaneously. Results and Discussion: In this study, we suggested a new method to assess pathway's function by introducing concept of 'responsiveness'. The responsiveness was defined as a relative activity between a pathway itself and its downstream genes. The expression level of a downstream gene as a function of an upstream pathway activation characterizes disease status. In this aspect, by using the responsiveness we predicted potential progress in cancer development. We applied our method to predict primary and metastatic status of melanoma cancer. The result shows that the responsiveness-based approach achieves better performance than using gene or pathway information alone. The mean of ROC scores in the responsiveness-based approach was 0.90 for GSE7553 data set, increased more than 40% compared to a gene-based method. Moreover, identifying the abnormal regulatory patterns between pathway and its downstream genes provided more biologically interpretable information compared to gene or pathway based approaches.