• YAKHAK HOEJI
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• v.52 no.5
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• Clinical and Experimental Pediatrics
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• v.62 no.6
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• pp.224-234
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• 2019

Purpose: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. Methods: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. Results: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. Conclusion: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

• Journal of Korean Medicine for Obesity Research
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• v.18 no.2
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• pp.83-95
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• 2018

Objectives: The aim of this study was optimized mixing ratio of mulberry leaf, mulberry fruit, and silkworm for amelioration of the metabolic syndrome by using response surface method (RSM). Methods: Antioxidant, antidiabetic and antihypertensive activities of fifteen mixed powder of mulberry leaf, mulberry fruit, and silkworm by RSM were measured as indicators of metabolic syndrome. Results: The optimal mixing ratio of mulberry leaves, mulberry fruits, and silkworm with the greatest antioxidant, antidiabetic and antihypertensive activities was as follows: 2.5890 of mulberry leaf (A), 0.1222 of mulberry fruit (B), 2.9999 of silkworm (C). At this time, it was predicted that the total polyphenol content was estimated to be 185.51 tannic acid equivalent mg/g, 1, 1-diphenyl-2-picrylhy drazyl radical scavenging activity 84.77%, 1-deoxynojirimycin content 415.66 mg/100 g, ${\alpha}-glucosidase$ inhibitory activity 64.31%, ${\gamma}-aminobutyric$ acid content 267.77 mg/100 g, potassium content 1,899.11 mg/100 g, and angiotensin-converting-enzyme inhibitory activity was estimated to be 73.78%. Conclusions: It was concluded that the significant effect of the mulberry leaf, mulberry fruit, and silkworm on the metabolic syndrome-related biological activity indices (antioxidant activity, antidiabetic activity and antihypertensive activity) was as follows: 2.5890 of mulberry leaf (A), 0.1222 of mulberry fruit (B), 2.9999 of silkworm (C).

• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.147-151
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• 2019

This study was performed to investigate the physiological activity of Hongsan garlic and Hansan garlic, which were registered in the plant breeders' right in 2016. The content of mineral components, except sodium and sulfur ingredients, was found to be high in Hansan garlic. In addition, organic sulfur components were high in Hansan garlic. Moreover, the total soluble solid content, reducing sugar content, and alpha glucosidase inhibitory activity were high in Hansan garlic. Acidity, pH, total phenol, and flavonoid content were high in Hongsan garlic. Both varieties showed higher inhibitory activity to gram-positive bacteria than to gram-negative bacteria. The antimicrobial activity of Hongsan garlic was slightly higher than that of Hansan garlic. These results are expected to provide useful information to farmers who grow the above garlic varieties.

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.163-170
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• 2021

Enzyme replacement therapy for lysosomal storage diseases usually requires recombinant enzymes containing mannose-6-phosphate (M6P) glycans for cellular uptake and lysosomal targeting. For the first time, a strategy is established here for the in vitro mannosyl-phosphorylation of high-mannose type N-glycans that utilizes a recombinant Mnn14 protein derived from Saccharomyces cerevisiae. Among a series of N-terminal- or C-terminal-deleted recombinant Mnn14 proteins expressed in Pichia pastoris, rMnn1477-935 with deletion of N-terminal 76 amino acids spanning the transmembrane domain (46 amino acids) and part of the stem region (30 amino acids), showed the highest level of mannosyl-phosphorylation activity. The optimum reaction conditions for rMnn1477-935 were determined through enzyme assays with a high-mannose type N-glycan (Man8GlcNAc2) as a substrate. In addition, rMnn1477-935 was shown to mannosyl-phosphorylate high-mannose type N-glycans (Man7-9GlcNAc2) on recombinant human lysosomal alpha-glucosidase (rhGAA) with remarkably high efficiency. Moreover, the majority of the resulting mannosyl-phosphorylated glycans were bis-form which can be converted to bis-phosphorylated M6P glycans having a superior lysosomal targeting capability. An in vitro N-glycan mannosyl-phosphorylation reaction using rMnn1477-935 will provide a flexible and straightforward method to increase the M6P glycan content for the generation of "Biobetter" therapeutic enzymes.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.12a
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• pp.68-68
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• 2020

최근 기후온난화 및 다문화 가정 증가에 따라 아열대작물 재배 및 수요가 증가하고 있다. 차요테(Sechium edule (Jacq.) Sw.)는 멕시코 남부와 중앙아메리카가 원산인 아열대 채소로 박과에 속하는 다년생 덩굴식물이다. 차요테는 아삭아삭한 식감에 가벼운 단맛을 가지고 있으며, 그 맛이 오이, 무와 비슷하다. 라틴아메리카에서는 튀김, 샐러드, 수플레로 필리핀에서는 수프과 볶음의 재료로 활용한다. 국내에서는 식감이 좋아 열매를 장아찌 용으로 이용하거나 어린순과 잎을 무침용으로 이용하기도 한다. 차요테는 매우 낮은 칼로리를 지녔으며 포화지방이나 콜레스테롤을 함유하지 않아 다이어트 식품으로 알맞은 채소이다. 또한 비타민 C와 E, K가 풍부하여 피로 해소, 면역력 개선, 피부 미용, 감기 예방, 골다공증이나 암 예방, 동맥경화 방지는 물론 신경전달물질인 세로토닌과 멜라토닌 형성에도 도움을 준다. 그밖에 칼륨, 마그네슘, 망간, 구리, 아연 등의 미네랄이 함유되어 있어 세포의 성장과 분열, 면역체계의 활성화, 심장과 근육 기능 유지 등에 기본적인 도움을 준다. 따라서, 본 연구는 차요테의 가공식품 소재화를 위해 부위별 유용성분 함량 분석을 통한 차요테 이용 확대를 위해 수행하였다. 차요테는 잎에서 열매와 어린순에 비해 지방, 단백질, 탄수화물, 식이섬유 등이 높게 나타났으며, 비타민 C, E 및 칼슘과 철분도 높은 함량을 나타내었다. 또한 장에 존재하여 다당류를 단당류로 분해하는 효소인 Alpha-Glucosidase의 활성을 억제하여 탄수화물 흡수를 지연시켜 체내 혈당을 낮추는 효과를 나타내는 AGI 활성은 열매 부위에 가장 높게 나타났다.

• The Korean Journal of Food And Nutrition
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• v.28 no.3
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• pp.369-375
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• 2015

This study was performed to investigate the physiological activities of Ginkgo biloba sarcotesta extracts before and after heat treatment. G. biloba sarcotesta was heated at $130^{\circ}C$ for 2 h and extracted with water, 70% ethanol and 80% methanol. ABTS and DPPH radical scavenging activities increased after heating in the water (14.95 mg AAE/g and 7.36 mg TE/g) and ethanol extracts (12.20 mg AAE/g and 6.23 mg TE/g). ${\alpha}$-Glucosidase inhibitory activity decreased after heating in all but the water extract. Angiotensin converting enzyme I inhibitory activities decreased after heating in all extracts. Nitric oxide production inhibitory activity increased from 12.40~44.55% of the raw sample to 40.76~72.39% of the heated sample at a concentration of $200{\mu}g/mL$. Lipid accumulation inhibitory activities were similar before and after heat treatment. The highest antiproliferative effects on MCF-7 human breast cancer cell lines were observed in 80% methanol extract in the heated sample. Cell viability at concentrations of 25, 50, 100, and $200{\mu}g/mL$ measured 34.88, 17.58, 8.44 and 10.48%, respectively. From the results, the antioxidant and antiproliferative activities of G. biloba sarcotesta extracts increased with heat treatment, and research on the identification of the structure for the active compounds are needed in further studies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.1
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• pp.68-75
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• 2013

The physiological properties of water extracts from Jerusalem artichoke (Helianthus tuberosus L.) leaves (JAL) with different extraction processes (stirrer extraction, SE; reflux extraction, RE; autoclave extraction, AE; low temperature high pressure extraction, LTPE) were investigated. The freeze-dried powder yields of SE, RE, AE, and LTPE were 22.33%, 29.88%, 31.65, and 15.74%, respectively. AE showed the highest value of extract yield. The $a^*$ and $b^*$ values were higher in AE compared to other extracts. Total polyphenolics and flavonoids contents in AE was significantly higher than in other extracts. The amount of proanthocyanidin related substances were highest in LTPE (29.36 mg/g), followed by RE (21.57 mg/g), SE (20.35 mg/g), and AE (13.02 mg/g). The electron donating abilities of SE, RE, AE, and LTPE at a concentration of $500{\mu}g/mL$ (w/v) were 76.16%, 39.55%, 25.50%, and 12.59%, respectively. Reducing power for the four different processes was 1.79, 1.60, 1.51, and 1.17, respectively. Additionally the same tendency was observed with electron donating ability and reducing power for ABTS radical and nitrite scavenging abilities. AE and LTPE showed relatively high antioxidant activities. Alpha-glucosidase, xanthine oxidase, and angiotensin I-converting enzyme inhibitory activities of LTPE at a concentration of $500{\mu}g/mL$ (w/v) were somewhat higher than other extracts. Additionally, there was significantly higher or little lower inhibitory activity compared to the control group. In conclusion, we provided experimental evidence that extracts of JAL have potential as functional materials, and component analysis of JAL could be used as new cosmeceuticals. Also, LTPE is the superior method for the enhancement of biological activity.

• Journal of Applied Biological Chemistry
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• v.58 no.4
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• pp.317-323
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• 2015

The extracted phenolic compounds from Cornus kousa fruit for biological activities as functional resources were examined. The phenolic compounds which were extracted with water and 40% ethanol from Cornus kousa fruit were $7.04{\pm}0.27$ and $4.47{\pm}0.18mg/g$, respectively. The 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity of water and ethanol extracts were 84% and 86% at $50{\mu}g/mL$phenolics, respectively. The 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical decolorization activity of water and ethanol extracts were 84 and 95% at $100{\mu}g/mL$ phenolics, respectively. Antioxidant protection factor in water and ethanol extracts at $50{\mu}g/mL$ phenolics were 1.93 and 1.82 PF, respectively. Thiobarbituric acid reactive substance were 69% in water extracts and 89% in ethanol extracts at $150{\mu}g/mL$ phenolics. The inhibition activity on xanthine oxidase in water and ethanol extracts was 34 and 60%, respectively. The inhibition activity on ${\alpha}$-glucosidase was 29% in water extracts and 87% in ethanol extracts. The tyrosinase inhibitory activity was 19% in ethanol extracts. The collagenase inhibition activity of anti-wrinkle effect showed an excellent wrinkle improvement effect as 53% in water extracts and 77% in ethanol extracts at $200{\mu}g/mL$ phenolics. The hyaluronidase inhibition activity as antiinflammation effect of water extracts was confirmed to 34% of inhibition at $200{\mu}g/mL$ phenolic. The results can be expected extracts from Cornus kousa fruit to use as functional resource for antioxidant, antigout, inhibitor of carbohydrate degradation, antiwrinkle activity and antiinflammation activity.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.668-675
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• 2017

To assess the physiological effects of Aruncus dioicus var. kamtschaticus extract on cytoxicity of a neuronal cell line, antioxidant activity, and neuroprotection against intensive glucose-induced oxidative stress were quantitated. Compared to the other fractions, the ethyl acetate fraction of Aruncus dioicus var. kamtschaticus (EFAD) showed the highest total phenolics and flavonoids. The 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay and malondialdehyde inhibitory effect test confirmed the superior antioxidant activity of EFAD. Moreover, EFAD also decreased the intracellular ROS level and suppressed neuronal cell death against intensive glucose- or $H_2O_2$-induced oxidative stress. Additionally, assessment of ${\alpha}$-glucosidase and acetylcholinesterase inhibitory activities revealed that EFAD was an effective inhibitor of ${\alpha}$-glucosidase and acetylcholinesterase. Finally, high-performance liquid chromatography analysis identified caffeic acid as the main ingredient of EFAD. Overall, these results suggest that the EFAD is a good natural source of biological compounds that counteract hyperglycemic neuronal defects.