• BMB Reports
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• v.40 no.3
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• pp.439-443
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• 2007

Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

• Bulletin of the Korean Chemical Society
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• v.17 no.1
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• pp.24-28
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• 1996

A procedure is described for the synthesis of the title compound via phosphotriester intermediates. The preparation of $R_p$ and $S_p$ diastereomeric dinucleotide of d[Cp(S)T] was performed by the condensation of the protected deoxycytidine, the protected thymidine, 2,5-dichlorophenylphosphorodichloridothioate and 1-hydroxybenzotriazole in THF. Their designation of configuration at phosphorus as $R_p$ and $S_p$ follows from anaylsis of ${31}^P$ NMR spectroscopy and reverse-phase HPLC and the stereospecificity in the hydrolysis catalyzed by Nuclease S1 and snake venom phosphodiesterase. Diastereomerically pure $R_p$ and $S_p$ d[Cp(S)T] were utilized to synthesize oligonucleotides containing the XhoI recognition sequence with a phosphorothioate group at the cleavage site.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.8
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• pp.1262-1267
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• 2004

An anticoagulant was purified from corn silk which has been used in Oriental Medicine. The anticoagulant from corn silk has a molecular mass of 135 kDa, and purified by 24 folds with a recovery of 11%. It was not sensitive to heat and protease treatment. However, periodate oxidation of the anticoagulant resulted in loss of activity significantly, implying that a carbohydrate was responsible for an anticoagulant activity. Galactose, glucose, mannose, fucose, glucosamine, and galactosamine were detected after acid hydrolysis by thin layer chromatography (TLC) and Bio-LC. It was confirmed that anticoagulant had OH and NH bonds by IR, supporting that the anticoagulant is composed of neutrosugar and aminosugar. Its anticoagulating activity was measured by delay in thrombin time (TT) and prothrombin time (PT) without affecting clotting by snake venom and delay in activated partial thromboplastin time (APTT). TT was more sensitive than PT, and was delayed two and three times at the concentration of 60 and 88 nM, respectively. The anticoagulating activity was reduced in the thrombin-induced clotting assay using purified fibrinogen according to the increase of fibrinogen concentration with the apparent Ki value of 23 nM.

• Journal of the korean academy of Pediatric Dentistry
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• v.28 no.1
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• pp.72-81
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• 2001

Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38-amino acid peptide containing a 17-amino acid disulfide ring structure similar to that of the natriuretic peptide family. The natriuretic peptide family was known to induce histamine release from human and rat mast cells, but there are no published data concerning the effects of DNP on histamine release from mast cells. The purpose of this study is to investigate whether DNP induces the histamine release from rat peritoneal mast cells (RMPCs) and to determine the mechanism of DNP-induced histamine release from RPMCs. After treatment of the various doses of DNP in RPMCs, the mast cell degranulation was observed with inverted microscopy and the histamine release was measured by radio-enzymatic assay. Calcium uptake and intracellular cyclic GMP level were measured by radioimmunoassays. DNP induced the mast cell degranulation. DNP released the histamine and increased the calcium uptake and the level of intracellular cyclic GMP of RPMCs, in a dose-dependent manner. The results indicate that DNP is capable of inducing histamine release from RPMCs by increasing of calcium uptake and intracellular cyclic GMP level.

• Journal of The Korean Society of Clinical Toxicology
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• v.20 no.2
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• pp.45-50
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• 2022

Purpose: This study utilizes the NEDIS (National Emergency Department Information System) database to suggest a predictive model for snakebite and envenomation in Korea by analyzing the geographical distribution and seasonal variation of snakebite patients visiting the ER. Methods: This was a retrospective study on snakebite patients visiting the ER using the NEDIS database from January 2014 to December 2019. The subjects include patients with the KCD (Korea Standard Classification of Disease) disease code T63.0 (Toxic effect of contact with snake venom). Geographical location, patient gender, patient age, date of ER visit, treatment during the ER stay, and disposition were recorded to analyze the geographical distribution and seasonal variation of snakebite patients in Korea. Results: A total of 12,521 patients were evaluated in this study (7,170 males, 54.9%; 5,351 females, 40.9%). The average age was 58.5±17.5 years. In all, 7,644 patients were admitted with an average admission time of 5.04±4.7 days, and 2 patients expired while admitted. The geographical distribution was Gyeongsang 3,370 (26.9%), Cheonra 2,692 (21.5%), Chungcheong 2,667 (21.3%), Seoul Capital area 1,999 (16.0%), Kangwon 1,457 (11.6%), and Jeju 336 (2.7%). The seasonal variation showed insignificant incidences in winter and higher severity in spring and summer than in fall: winter 27 (0.2%), spring 2,268 (18.1%), summer 6,847 (54.7%), and fall 3,380 (27.0%). Conclusion: Patients presenting with snakebites and envenomation in the emergency room were most common in the Gyeongsang area and during summer. The simple seasonal model predicted that 436 snakebites and 438 envenomation cases occurred in July and August. The results of this study can be applied to suitably distribute and stock antivenom. Appropriate policies can be formed to care for snakebite patients in Korea.

• Korean Journal of Environment and Ecology
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• v.12 no.1
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• pp.58-77
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• 1998

Four species(25%) of Viperidae(Agkistrodon brevicaudus, Agkistrodon ussuriensis, Agkistrodon saxatilis) and Cloubridae(Rhabdophis tigrenus tigrenus) were Korean poisonous snake. Copulation season of these species was from July to August. Reproduction mode of genus Agkistrodon species was ovoviviparous but Rhabdophis tigrinus tigrinus was the other pattern of oviparous. Optimal movement temperature range was from 20$\circ $C to 29$\circ $C(March~September). Wjen atmosphere temperature was below 10$\circ $C, at that time they hibernate at the ground, rock bottom, stone wall and embankment around the end of a field. The venom of these snakes consist mainly Hematoxin, Cytolysin, Neurotoxin and Cardiotoxin of poisonous liquids. These material injection to animal cause systemic syndrome such as Dizziness(25.7%), Vomitting(23.1%), Fever(22%), Visual trouble(18%), Headace(17.7%), Dyspnoea(17.6%) and bring about other local syndrome such as Discoloration(54.2%), Bleeding(20.2%), Bullae(10.7%) and Skin ulcer(!0.8%). The annual distribution was appeared to decrease 1972 after 1992 and average snakebiting patients was 25.6 per year, but practically total estimated snakebiting was 2,700 per year. The seasonal distribution was most frequent in August(25%), and mortality was 1.8%(26 per 1,430). The sex ratio was 2:1 and according to age distribution, it was most prevalent at one's fifties(19%). The most frequent place where the accident happened was the field(48.2%) and most predilection site of the body for victim were hand(47.8%) and foot(39.5%), Commonly bite snake were Agkistrodon ussuriensis(27.1%), Agkistrodon brevicaudus(22.6%) and Agkistrodon saxatilis(9.6%) but 40.7% of species could not be identified. Treatment of antivenin patient was 75.9% (1,068/1,407).

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.25-35
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• 2012

목적 : 이 연구는 $Vipera$ $lebetina$ $turanica$ 사독(蛇毒)이 인간 대장암 세포주인 HCT116 세포에서 세포주기진행, death receptor 의존적 세포자멸사 경로 관련단백질 발현 및 NK-${\kappa}B$와 STAT3 활성에 미치는 영향을 규명함으로써 대장암 세포 성장에 대한 억제와 그 기전에 대하여 살펴보고자 하였다. 방법 : 사독을 처리한 후 HCT116의 세포주기를 분석하기 위해서 FACS analysis를 시행하였고, apoptosis 평가에는 TUNEL assay를 시행하였으며 death receptor 의존적 세포자멸사 경로 관련단백질 및 NF-${\kappa}B$와 STAT3 활성 변동 관찰에는 RT-PCR 및 western blot analysis를 시행하였다. 결과 : 1. 0.1, 0.5 및 $1{\mu}g/m{\ell}$ 등의 사독을 처리한 결과 농도 의존적으로 HCT116 대장암 세포활성의 억제가 나타났다. 2. 0.1, 0.5 및 $1{\mu}g/m{\ell}$ 등의 사독을 처리한 결과 농도의존적으로 세포자멸사 활성세포의 증가가 나타났고, SVT $1{\mu}g/m{\ell}$에서는 60-70%의 대장암세포 억제 효과가 나타났다. 3. 0.1, 0.5 및 $1{\mu}g/m{\ell}$ 등의 사독을 처리한 결과 약한 G1 arrest와 강한 G2/M arrest가 나타났고, G0/G1 또는 G2/M 관련 cyclin D, E 및 B1의 증가가 나타났다. 4. 0.1, 0.5 및 $1{\mu}g/m{\ell}$ 등의 사독을 처리한 결과 death receptor4, 5의 발현증가와 그에 따른 세포자멸사 촉진 Bax, PARP, caspase-3, -8, -9 발현 증가 및 세포자멸사 억제의 Bcl-2의 발현 감소 등이 나타났다. 6. 0.1, 0.5 및 $1{\mu}g/m{\ell}$ 등의 사독을 처리한 결과 NF-${\kappa}B$와 STAT3의 활성변동은 관찰되지 않았다. 결론 : 이상의 연구에서 사독은 death receptor 의존적인 세포자멸사를 촉진하여 대장암의 화학치료 내성을 극복할 수 있는 하나의 대안이 될 것으로 생각되지만 보다 심화된 연구가 필요할 것으로 사료된다.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.37-45
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• 2012

목적 : 최근 NF-${\kappa}B$와 STAT3의 활성억제와 관련된 항암제 연구가 주목받고 있으며, 본 연구는 사독(蛇毒)이 세포자멸사 관련 단백질의 발현 조절을 통하여 세포자멸사를 유도하고, NF-${\kappa}B$와 STAT3의 활성억제를 유도하여 난소암 PA-1 세포의 성장을 억제하는지를 확인하고, 해당 기전을 살펴보고자 하였다. 방법 : 사독을 처리한 후 난소암 PA-1 세포의 세포자멸사의 관찰에는 DAPI, TUNEL staining assay를 시행하였고, 세포자멸사 조절단백질 및 NF-${\kappa}B$, STAT3의 활성 변동 관찰에는 western blot analysis를 시행하였다. 결과 : 1. 사독을 처리한 후 난소암 PA-1 세포에서 세포자멸사가 유도되어 암세포성장이 억제되었다. 2. 사독을 처리한 후 세포자멸사 관련 단백질 중 세포자멸사 촉진 단백질인 cleaved caspase-3, Bax의 발현은 증가되었고, 세포자멸사 억제 단백질인 Bcl-2의 발현은 감소되었다. 3. 사독을 처리한 후 난소암 PA-1 세포의 NF-${\kappa}B$와 STAT3 발현은 감소되었고, 각각의 길항제인 salicylic acid와 stattic 처리 후 NF-${\kappa}B$와 STAT3 발현은 더욱 감소되었다. 결론 : 사독은 난소암 세포의 세포자멸사 유발과, NF-${\kappa}B$와 STAT3의 활성억제를 통해 치료 효율이 높고, 내성이 적은 난소암 치료제의 개발에 도움이 될 것으로 기대된다.

• Tuberculosis and Respiratory Diseases
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• v.83 no.3
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• pp.201-210
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• 2020

Background: North Korea is one of the 30 countries with the highest tuberculosis (TB) and drug-resistant TB burdened. To understand the medical issues and research trends associated with TB in North Korea, we performed a comprehensive review of articles related to clinical and laboratory research on TB published in North Korean medical journals. Methods: We reviewed all types of TB-related articles published in nine North Korean medical journals (Yebang ŭihak: Preventive medicine; Koryo ŭihak: Korea Medicine; Chosŏn ŭihak: Chosun Medicine; Naekwa: Internal Medicine; Soa, sanbuinkwa: Pediatrics, Obstetrics, and Gynecology, Surgery; Ŭihak: Medicine; Kich'o ŭihak: Basic Medicine; and Chosŏn yakhak: Chosun Pharmacy). We classified the articles according to the type and field of study and analyzed the data qualitatively to gain insights. Results: We reviewed 106 articles (one- or two-page length) written in Korean, including reviews (n=43), original articles (n=52), and case reports (n=8). They were classified as follows: articles on diagnosis (n=52, 49%) and treatment (n=39, 37%). None of the studies investigated the commercialized molecular diagnosis systems such as Xpert MTB/RIF. Directly Observed Treatment, Short-course was reported as the basic treatment approach. Furthermore, six studies used Korean traditional medicines for treating TB, with one of them containing snake venom. Conclusion: The articles were not sufficiently detailed. Original articles on the treatment of multi-drug resistant TB were not found, and those on latent tuberculosis infection and nontuberculous mycobacteria were limited. To understand the current medical issues associated with TB in North Korea, articles from these nine journals were not sufficient.

• Microbiology and Biotechnology Letters
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• v.7 no.2
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• pp.75-89
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• 1979

One strain of Penicillium sp. (175-66-B), isolated from soil, was able to produce a substance that has a strong inibition activity against the Agkistrodon and Trimeresurus venoms. In this experiment, the chemical and biological properties of the sample were investigated. As an inhibitory substance, it was effective to the proteinase, hemorrhagic and lethal factors of Agkistrodon and Trimeresurus venoms, and also effective to several fractions of the proteinases and hemorrhagic factors of Agkistrodon halys blomhoffi venom. Moreover, in the addition of prednisotone, it was more effective for the cure of the mouse envenomated with the venom amount of two fold of MLD$_{100}$. This substance was very stable to the acid, alkali and heat. Its melting point was high enough to sublime at 222$^{\circ}C$ without any decomposition. This sample was easily dissolved only in hot water, but not in several organic solvents except for a little dissolution in elate. It did not have the chelating activity. It had very strong specificity to the snake venoms. but its activity was depressed by the addition of zinc or cupric salts. This sample had no acute toxicity to the mouse. Its chemical formula was $C_{16}$ $H_{12}$$N_2$ $O_{10}$ with the molecular weight of about 392. It has two epoxy groups and four carboxyl radicals, but amino, nitrite and nitrate radicals, unsaturated bonds and aromatic ring were not detected. Theuchemical configuration of this sample was suggested to be;