• Journal of Radiation Industry
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• v.17 no.2
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• pp.127-134
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• 2023

Pharmacokinetic (PK) data provide pivotal information in drug development, and they are usually first studied in the preclinical stage using various animals. However, quite often, animal PK data may not match with human PK, especially in metabolites. Thus, most regulatory agencies in the world make it mandatory to obtain metabolite information using ¹⁴C radiolabeled drug in human for small molecule drug candidates. However, such studies are expensive and time consuming and they are usually done at the end of Phase II trials using ~3.7 MBq of ¹⁴C labeled drug in a limited number of human subjects. Introduction of accelerator mass spectrometry (AMS) in this kind of study has revolutionized it. Since AMS can measure ¹⁴C level as close as natural abundance, it can quantify the amounts of ¹⁴C labeled drugs and their metabolites produced in human body that consumes less than the amount of 0.0037 MBq of ¹⁴C labeled drug, a very safe level of radioactive dose in human. Therefore, it is now possible to conduct human ¹⁴C studies safely in early clinical trials without spending hefty amount of money and time. Korea Radioisotope Center for Pharmaceuticals(KRICP) at Korea Institute of Biological and Medical Sciences(KIRAMS) has established an AMS facility in 2018, housing a 0.5MV AMS manufactured at the US National Electrostatics Corps (NEC). The AMS instrument has been validated using various standard samples that have been prepared at Lawrence Livermore National Laboratory in the US, a worldly reputable provider of AMS standards. In this paper, we present a mass balance study for acetaminophen in rats using AMS and prove that the study results are equivalent with those of literature, which shows the AMS facilities at KRICP has successfully installed and be ready to be used in the various PK studies using ¹⁴C labelled compounds for new drug development.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.200-207
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• 2015

Various natural products or their derivatives, mostly originating from plants, fungi, and bacteria, have been exploited as therapeutic drugs to treat various human diseases. In addition to previously explored organisms, research on natural compounds has now expanded into unexamined living organisms in order to identify novel bioactive substances. Here, we determined whether or not the larval form of the mealworm beetle Tenebrio molitor, a species of darkling beetle, contains cytotoxic substances that exclusively affect cancer cell viability. Ethanol extract and its solvent partitioned fractions, hexane and ethyl acetate fractions, showed anticancer effects against various human cancer cells derived from the prostate (PC3 and 22Rv1), cervix (HeLa), liver (PLC/PRF5, HepG2, Hep3B, and SK-HEP-1), colon (HCT116), lung (NCI-H460), breast (MDA-MB231), and ovary (SKOV3). Cell death induced by the fractions was a mix of apoptosis, necrosis, and autophagy. The hexane fraction was administered intraperitoneally to nude mice bearing a hepatocellular carcinoma SK-HEP-1 and showed inhibition of tumor growth in vivo. Therefore, we concluded that worm extracts contain cytotoxic substances, which can be enriched by proper fractionation protocols, and further separation and purification could lead to the identification of novel molecules to treat human cancers.

• Food Science and Preservation
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• v.22 no.2
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• pp.275-280
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• 2015

Among the naturally occurring antioxidants, polyphenols are widely distributed in various fruits, vegetables, wines, juices, and plant-based dietary sources and divided into several subclasses that included phenolic acid, flavonoids, stilbenes, and lignans. As part of our continuing search for bioactive food ingredients, the antioxidant and ${\alpha}$-glucosidase inhibitory activities of the aqueous ethanolic extract from the aerial parts of Ainsliaea acerifolia were investigated in vitro. The antioxidant properties were evaluated via radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) ($ABTS^+$) radicals. In addition, the anti-diabetic effect of A. acerifolia extracts was tested via ${\alpha}$-glucosidase inhibitory assay. Furthermore, the total phenolic contents were determined using a spectrophotometric method. All the tested samples showed dose-dependent radical scavenging and ${\alpha}$-glucosidase inhibitory activities. In particularly, the ${\alpha}$-glucosidase inhibitory and radical scavenging properties of the ethyl acetate (EtOAc)-soluble portion from the aerial parts of the A. acerifolia were higher than those of the other solvent-soluble portions. These results suggest that A. acerifolia could be considered a new potential source of natural antioxidants and antidiabetic ingredients. More systematic investigation of the aerial parts of A. acerifolia will be performed for the further development of anti-oxidative and antidiabetic drugs.

• Journal of Korean Medical classics
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• v.5
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• pp.200-251
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• 1992

As concerned the life and the medical idea of Choo, Tan-Kye(朱丹溪), which it can be summarized as follows by studying. 1. Tan-Kye(丹溪) lived in the end of the won dynasty(元代末期), When the people starved and suffered from a flood-disaster and drought. etc, also the social conditions were in disorder on account of the corrupt ion of politics. And Cheol Kang seong(浙江省), located in the south region of China, has sterile soil and the climate condition humid and heatful. So the south district peoples have very weak constitution. So We can found that his medical idea reflected the phases of the periods and the regional enviornmental situations. 2. For that reason, Tan-Kye(丹溪) rejected the prescription of the "WHa Che Gook Bang(和劑局方)" which was prevalent at that time, in which the the pungent-dried herbs were widly used ; So he persisted in the "Sang Wha Lon(相火論)" and the "Positivity is usually excedeed while the negativity deficient(陽有餘陰不足論)". Then he treated with the drugs to nourish the negativity for the prime object to be applied in the clinic. 3. Tan-Kye(丹溪) refined the follows from the natural law; Heaven is to the positivity(陽) and the Earth is defined the negativity(陰), so the heaven is to the Macro(大) and the earth, micro(小):So the Sun is to the Positivity(陽), the Moon, the Negativity(陰): as to the Sun is always full while the moon always defected too. Therefore the "positivity is always excedeed for that the negativity is deficientalways(陽有餘陰不足)". In Human body, "the negativity energy (陰精) "is hard formed-easily defected(難成易虧)". And the heat(相火) in the body can be moved easily and let the negative energy to leak out. Therefore the more the positivity excedeed, the more the negativity deficient"(陽當有餘陰常不足). 4. He made it expanded the contents of the "Heat(相火)" in the Chapter Woon Chi of the Nae Kyeong(內徑) and discribed, the Life-string of the human body is originated from the movement of the "Heat with unique energy(相火一氣)". And more in human body, it is specifically regulated by the two visceras, Liver and Kidney, and is distributed in the 'Pericardium(心包絡)' 'Tripie Warmer(三焦)' 'Gallbladder(膽)' etc. In the point of his assertion of heat(相火), it is concluded both the physiological and the pathological heat of all. 5. Tan-Kye(丹溪) grew up in the family or the Confucianism. He was instructed the Confucianism(性理學) from Heo-Kyeom(許謙), the fourth diciple of Chu-Ja(朱子), and was received the Yoo Chang Ri(劉 張 李)'s triple doctrine from the La Tae Moo(羅太無), the second disciple of Yoo Wan So(劉完素). So there are much of content of Confucianism(性理學) in his medical thedry, and his theory has succeeded the achievements of the triple study. 6. About the theory of the "positivity is usually excedeed while the negativity deficient"(陽常有餘陰常不足論) of Tan-Kye, it was asserted that the positivity is never sufficient for the vital mainspring, by Chang, Kye-Pin(張介賓) and Lee, Kyoo-Zoon(李奎晙) etc. And for the Heat theory(相火論), eventhough the scholars of postorior generations criicized all of that, there are defect of the content and unification between them. 7. The father of the "Cha Eum Pa(滋陰派), Tan-Kye(丹溪) contributed considerably to the development of the oriental medicine and to the general therapy for the various diseases(一般雜病施治). 8. there are handed down and remained twenty or more of volumes of list of his writings. Among them, except "Kyeok Chi Yeo Ron"(格致餘論), "Kuk Pang Pal Hyeu"(局方發揮), they are reorganized by posteriority. There are Cho, Do-Chin(趙道震). Cho, Ee-Teok(趙以德), Tae, Sa-Gong(戴思恭), Wang Ri(王履) and Yoo, Suk-Yeon(劉淑淵) etc as disciples of his. And Wang Ryoon(王論) and Woo Pak(虞搏) as the admirer of him.

• Journal of Korean Medical classics
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• v.12 no.2
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• pp.56-71
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• 1999

1. In the recohnition of cosmos true form, It is compared to the Boundless(無極) the Great Absolute(太極),Yin and Yang(兩儀) throungh the fertilazation process of spermatozoon and ovum. 2. It is explained that principle of unchange through the Form and Action(體 用) relation of the outer appearances and Number (象數) with matching the number of nine and ten to HaDoo(河圖) and RakSye(洛書). 3. Eigth divinations(八卦) being compared to the human body, Care presevation of pregnancy(養胎) is explained that head forms firstly(Gun-I 1乾一), secondly lung(Tae-E 兌二), heart(E-Sam 離三), liver(Jin-Sa 震四), gall bladder(Son-Oo 巽五), kidney(Gam-Yuk 坎六), intestines and stomach(Gan-Chill 艮七), lastly flesh forms(Gon-Pal 坤八). 4. It is explained that process of physiological change of $\ll$Nei Ching The Natural Truth in Ancient Times$\gg$(內經 上古天眞論) by matching boy at the age of 8 to Gan-divination(艮卦), and girl at the age of 7 to Tae-divination(兌卦). 5. The theory of six sons from Gun-Gon(乾坤六子論) is explained by relation of Apriority Eight-divination(先天八卦) obedience and disobedience-left and right. 6. It is explained that form of the human-body and the relationship of the Heart - the Kidney through the Gam(坎) Li(離) - divination 7. The effort of interpretating time and space of the Twelve Horary signs is explanined by season, direction, Five elements(五行), rise and decline, the Three Sum(三合), the Six Sum (六合), the six crash(六衡)'s relation. 8. the process of change from apriority(先天) to postery(後天) in the book of Changes(周易) is explanined by comparing to the phenomenum of nature and the human body. 9. The Energy Satus(氣位) are different from the direction of Eight-divination(八卦) and the properties of the good or bad of herb-drugs are differnt from the place of production. 10. The rightness of realizating the Overlapping-divinations(重卦) are compared to the phenomenum of nature through the Divination Virture(卦德). 11. The dependence-relations of The Twelve Meridians(十二經脈) are explained by-matching January with liver meridian, February with gall bladder meridian, march with heart pericardium meridiam, April with small intestine meridkan, August with lung spleen meridian, jury with stomach meridian, August with lung meridian, September with large intestine meridian, October with urinary bladder meridianm November with kidney meridian. December with triple energizer meridian throng The Twelve Byuk-divination. 12. The process of menstration cycle is explained by The Month symbolizing-divination(月候卦). 13. Through The Trade(交易) prove the reason of feverish sympotoms to use feverish Drug, mill sympotoms to use mill drug of prescription and Heart-Kidneys Consensus(心賢相交) and through The Change(變易), prove the chill and feverish consensus of forechill after feverish, fore feverish after chill and through. The Non-Change(不易) explain the reason of chill sympotoms to use feverish drug, feverish sympotoms to use chill drug of prscription. 14. Ho-divination(互卦) applicate Jxa Sa(佐使) herb drug match of Kun Sin Jwa Sa() theory. 15. According to the Hyo-position(爻位) match the ages, body form and drug by matching Ehight-divination(八卦) to the human body form and function in medicine and the book of Changes(周易) application emphasize the human body Ehight-divination(人身八卦). 16. Throgh the Order-divination(序卦) explain the rightness of Divination Image(卦象) arrangement and all things take shape by cosmo-energy conseusus(宇宙氣交). 17. Throgh the Mixing-divination(難卦) supply the vacancy of medicine and the book of Changes(周易) relationship in the foreword explian the human energy movements, sleep, vomitting, the energy arrival(逮氣), heart pericardium(心包), lung membrane(肺膜) etc.... Like the above sentence medicine and the book of Changes(周易) theory of scholar Tang on the viewpoint of easten-the way Western appliance(東道西器) researching abyss of medicine impart to descendants, so I think that the achievement of medicine and the book of Changes(周易) study is very excellant and I expect that the study Korean Oriental Medicine(韓醫學) theory by means of medicine the book of Changes(周易) reference, will be accelarated.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.365-375
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• 1995

The anemia-inducing strain of Friend virus (FVA) is a murine retrovirus which stimulates the proliferation of erythroid progenitor cells. The progenitor cells synthesized by FVA-stimulation are unable to proceed with differentiation and accumulate in the spleen resulting in splenomegaly in infected mice. Using FVA-inoculated mice as a model, we have investigated the antiretroviral effects of 2',3'-dideoxycytidine (ddC) and recombinant $interferon-{\alpha}-A\;(rIFN-{\alpha}-A)$ on FVA infection. The extent of the infection was determined by measuring the weights of the spleens. Daily intraperitoneal injection of ddC (100 mg/kg body weight), $rIFN-{\alpha}-A$ (10 KU/mose) and the combination of both drugs to FVA inoculated mice for 18 days resulted in suppression of the growth of spleens by 15.1%, 52.7% and 61.6%, respectively. When ddC was dissolved in drinking water (0.1 mg/ml) and administered to a group of FVA inoculated mice ad libitum, and $rIFN-{\alpha}-A$ (10 KU/mouse) was intraperitoneally injected daily to another group of ddC (0.1 mg/ml) drinking mice for 18days, the growth of spleens was suppressed by 38.4% and 83.2%, respectively. These results indicate that administration of ddC via drinking water is more effective in suppressing FVA infection than the daily injection of ddC, and that the combined effects ddC and $rIFN-{\alpha}-A$ are not synergistic but additive. In order to determine whether ddC treatment alters the characteristic of the progenitor cells with respect to $Ca^{++}$ uptake, $Ca^{++}$ uptake in erythroid cells and the effect of cyclohexyladenosine (CHA) on the $Ca^{++}$ uptake were studied. $Ca^{++}$ uptake in the erythroid progenitor cells was about 20-fold greater than in mouse erythrocytes and the inhibition of $Ca^{++}$ uptake by CHA was the greatest in the progenitor cells from FVA infected mice which were treated with ddC. The inhibition was obviated by theophylline. Results of CHA binding studies showed that the erythroid progenitor cells contain both high and low affinity CHA binding sites, whereas mose erythrocytes contain only the low affinity CHA binding sites.

• KSBB Journal
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• v.22 no.5
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• pp.356-361
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• 2007

Cyanobacteria are a very old group of prokaryotic organisms that produce very diverse secondary metabolites, especially non-ribosomal peptide and polyketide structures. Although some cyanobacteria produce lethal toxins such as microcystins and anatoxins, some may be useful either for development into commercial drugs or as biochemical tools. Detection of unknown secondary metabolites was carried in the present study by a screening of 98 cyanobacterial strains from Cyanobiotech GmbH in order to establish a screening process, isolate pure substances and determine their bioactivities. A degenerated polymerase chain reaction technique as molecular approaches has been used for general screening of NRPS gene and PKS gene in cyanobacteria. A putative PKS gene was detected by DKF/DKR primer in 38 strains (38.8%) and PCR amplicons resulted from a presence of NRPS gene were showed by MTF2/MTR2 primer in 30 strains (30.6%), respectively. A screening of interesting strains was performed by comparing PCR screening results with HPLC analyses of extracts. HPLC analysis for a detection of natural products was performed in extracts from biomass. 5 strains were screened for further scale-up processing. 7 pure substances were isolated from the scale-up cultures and tested for bioactivities under consideration to purity, amount and molecular weight of substances. One substance isolated from CBT 635 showed cytotoxic activity. This substance may be regarded as Microcystin LR.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.285-289
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• 2006

Background : North Korea's economic and public health problems began in the early 1990s as a result of the gradual loss of economic support from its communist allies, combined with an inordinate number of natural disasters. The decline in public health has increased the incidence of tuberculosis in North Koreans and refugees. This study investigated tuberculosis situation in North Korean refugees in order to prepare for the future impact of tuberculosis control in Korea. Material and Methods : From 2001 to 2005, tuberculosis patients among North Korean refugees who were diagnosed before or after arriving in South Korea, based on the official records of OO hospital, were enrolled in this study. The demographic and clinical data of the cases were evaluated retrospectively. Results : A total of 42 TB cases were reviewed during the study period. Of these, 37 (88.1%) cases were pulmonary TB. based on the cases identified among the number of North Korean refugees' arriving each year, the annual incidence of pulmonary TB were 900 per 100,000 in 2004, 700 in 2003, The number of smear-positive patients was 20 (47.6%) and the number of culture-positive patients was 18 (42.9%). Of the M. tuberculosis isolates, 2 cases were found to be susceptible to all anti-TB drugs available, 4 were resistant to isoniazid, and 3 were multi-drug resistant. Conclusion : The prevalence of pulmonary TB in North Korean Refugees is high. In addition, North Korean refugees suffer from more severe tuberculosis in bacteriological and radiological aspects.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.196-204
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• 2009

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

• Natural Product Sciences
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• v.8 no.1
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.