• Biomolecules & Therapeutics
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• 제22권4호
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• pp.347-354
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• 2014

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

• 생명과학회지
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• 제28권1호
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• pp.37-42
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• 2018

NAG-1 단백질은 TGF-${\beta}$ superfamily 유전자로서 암세포의 apoptosis를 유도하고 항암 활성과 관련이 있는 것으로 알려져 있다. 본 연구에서는 프로폴리스 유래의 파이토케미칼 CAPE (caffeic acid phenethyl ester)에 의한 항암유전자 NAG-1의 발현과 발현조절에 대해 연구하였다. 인간 대장암 세포주 HCT116에서 CAPE의 처리에 의해 농도의존적, 시간의존적으로 NAG-1의 발현이 증가됨을 확인하였다. 게다가, 다른 대장암 세포주인 LOVO 세포주에서도 농도의존적으로 NAG-1의 발현이 증가됨을 확인하였다. p53-null HCT116세포주를 이용한 실험에서 CAPE에 의한 NAG-1의 발현은 전사조절인자인 p53에 의존하지 않음을 증명하였다. 또한, 3가지 종류의 NAG-1 프로모터 construct를 이용한 실험에서, cis-element 후보가 -474와 -1,086사이에 있음을 증명하였다. CAPE에 의해 전사조절인자인 ATF3와 CREB의 발현이 변화되는 지를 확인한 결과, CREB은 전혀 발현이 증가되지 않는 반면 ATF3는 CAPE 처리에 의해 농도의존적으로 발현이 증가함을 확인하였다. 그리고, pCG-ATF3와 pCREB의 cotransfection 실험에서 CREB은 NAG-1의 발현에 영향을 못 미치는 반면, ATF3의 과대발현에 의해 NAG-1의 발현이 증가됨을 확인하였다. 결론적으로, CAPE에 의한 NAG-1의 발현은 주로 전사조절인자인 ATF3를 경유하여 일어남을 시사한다.

• Journal of Preventive Medicine and Public Health
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• 제24권3호
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• Journal of Preventive Medicine and Public Health
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• 제34권2호
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• pp.109-118
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• 2001

우리는 이 글에서 대기오염의 건강영향, 특히 사망에 대한 역학 연구 결과를 해석하는데 논란이 되고 있는 쟁점들을 고찰하였다. 과거 런던스모그 때와 같은 극심한 대기오염 사건 때는 그로 인한 건강영향도 매우 자명하여 별다른 논란의 소지가 없었다. 그러나 오늘날 우리가 경험하는 수준의 대기오염은 눈에 바로 띨 정도의 건강영향을 초래하지는 않기 때문에 많은 연구에서 관찰되는 통계적 유의성이 인과적 관련성을 의미하는지에 대한 많은 논란이 있다. Hill의 인과성기준에 비추어 대기오염에 관한 역학 연구 결과들을 평가해보면 각 기준 별로 부합되는 소견과 그렇지 않은 소견이 같이 존재하지만 전체적으로는 인과적인 관련성을 지지하는 증거들이 많은 편이다. 특히 세계 여러 지역에서 수행된 연구들에서 공통된 결과들이 나오는 것이 인과성을 지지해주는 강력한 근거라고 할 수 있다. 대기오염이 사망을 증가시킨다고 가정할때 구체적으로 어떤 병태 생리적인 기전을 통해서 증가시키는지는 아직 충분히 밝혀져 있지 않다. 현재까지의 역학연구 결과들과 동물실험 결과들을 종합해보면 대기오염 물질이 일차적으로 폐포에 염증을 유발하고 이에 따라 이차적으로 혈장의 응고성이 증가하거나, 심장에 대한 자율신경조절에 이상이 생겨서 사망위험이 증가한다는 가설이 가장 폭넓은 지지를 받고 있다. 시계열분석에서 나타나는 대기오염에 의한 초과사망자들이 어떤 특성을 가지고 있는지에 대한 논란도 많다. 대기오염이 아니더라도 곧 사망할 사람들이 대기오염 때문에 몇 일 앞당겨 사망한다는, 즉 추수효과에 의한 것이라는 것이 상식적인 판단이지만 최근의 연구들은 추수효과 외에도 대기오염에 의해 실질적인 수명의 감소가 있다는 증거들을 제시하고 있다. 대기오염 물질과 사망의 양-반응 관계가 어떤 모양일지, 그리고 문턱값이 존재하는지의 여부도 중요한 관심사이다. 특히 문턱값의 존재 여부는 대기오염 관리 대책과도 밀접한 관계가 있다. 대기환경 기준을 정해서 대기오염 수준을 관리하는 현재의 대책은 문턱간의 존재를 전제하고 있기 때문이다. 그러나 현재까지의 증거를 종합해보면 대기오염과 사망의 관련성은 문턱값이 없는 선형적 관계일 가능성이 높다. 따라서 향후 대기오염 관리대책에서는 대기오염 물질의 평균농도를 낮추려는 노력을 병행하여야 할 것을 생각한다.

• 생명과학회지
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• 제11권2호
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• 생명과학회지
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• 제25권11호
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• pp.1255-1264
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• 2015

천궁(C. officinale)은 예로부터 민간처방 약재로 사용되었으며, 항염증, 항산화, 항암 및 신생혈관억제 등의 효능을 가지는 것으로 알려져 있다. 하지만 혈구암세포에서 apoptosis 유발과 관련된 분자생물학적 기전에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 혈구암세포인 U937 세포에서 천궁의 열수, 에탄올 및 메탄올 추출물(WECO, EECO 및 MECO)이 유발하는 항암효과 및 항암기전을 조사하였다. 먼저 WECO, EECO 및 MECO가 유발하는 증식억제 정도를 조사한 결과 EECO가 가장 뛰어난 효능을 가진다는 것을 알 수 있었으며, 이러한 현상이 apoptosis 유발에 의한 것임을 annexin-V 염색, apoptotic body 형성, DNA 단편화 및 MMP 소실 등을 통하여 확인하였다. EECO 처리에 의한 apoptosis 유발에는 DR4의 발현 증가와 함께 cIAP-1, Bcl-2 및 total Bid의 발현감소가 관여하였으며, caspases-3, -8 및 -9의 활성화와 함께 caspases-3의 기질 단백질인 PARP, β-catenin 및 PLC γ1의 단편화도 관찰되었다. 또한 EECO는 AMPK signaling pathway를 활성화시키는 것으로 나타났으며, AMPK 억제제인 compound C를 이용하여 AMPK의 활성을 억제하였을 경우 EECO에 의하여 유발되었던 apoptosis가 현저하게 감소되는 것으로 나타났다. 이상의 결과를 살펴볼 때 인체 혈구암세포인 U937 세포에서 EECO에 의하여 유발되는 apoptosis는 AMPK가 중요한 조절자로서 작용하는 것으로 생각된다.

• 한국축산식품학회지
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• 제36권4호
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• pp.494-498
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• 2016

Cold plasma has been developed to reduce microbial contamination and to improve safety of food and medical products. In addition, the technology can be used in the manufacture of sausages without addition of nitrite. To be applied in food industry commercially, the new technology should be safe and efficient. However, toxicological test of plasma-treated food is limited. Therefore, the purpose of this study was to determine the mutagenicity and immune toxicity of the meat products cured with plasma-treated water (PTW) as a nitrite source. Emulsion sausages were prepared with no nitrite (control), sodium nitrite (SCS), and PTW (SCP). For a mutagenicity test, the Ames test was performed with the sausage samples. For immune toxicity test, 8-wk-old female Balb/c mice were given free access to the sausages in order to evaluate the tumor necrosis factor (TNF)-α level. As a result, no mutagenicity was detected in the sausages by the Ames test. The serum TNF-α values were less than 10 pg/mL in mice after feeding control and treated samples for 32 d, indicating that no inflammatory response was occurred by feeding the sausages made by PTW. Therefore, the present study opens the possibility of using plasma-treated water as a nitrite source without any toxicity.

• 한국패류학회지
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• 제28권4호
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• pp.377-384
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• 2012

The importance of biological resources has been gradually increasing, and mollusks have been utilized as main fishery resources in terrestrial ecosystems. But little is known about genomic and transcriptional analysis in mollusks. This is the first report on the transcriptomic profile of Meretrix lusoria. In this study, we constructed cDNA library and determined 542 of distinct EST sequences composed of 284 singletons and 95 contigs. At first, we identified 180 of EST sequences that have significant hits on protein sequences of the exclusive Mollusks database through BLASTX program and 343 of EST sequences that have significant hits on NCBI NR database. We also found that 211 of putative sequences through local BLAST (blastx, E < e-10) search against KOG database were classified into 16 functional categories. Some kinds of immune response related genes encoding allograft inflammatory factor 1 (AIF-1), B-cell translocation gene 1 (BTG1), C-type lectin A, thioester-containing protein and 26S proteasome regulatory complex were identified. To determine phylogenetic relationship, we identified partial sequences of four genes (COX1, COX2, 12S rRNA and NADH dehydrogenase) that significantly matched with the mitochondrial genomes of 3 species-Ml (Meretrix lusoria), Mp (Meretrix petechialis) and Mm (Meretrix meretrix). As a result, we found that there was a little bit of a difference between sequences of Korean isolates and other known isolates. This study will be useful to develop breeding technology and might also be helpful to establish a classification system.

• Journal of Trauma and Injury
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• 제19권1호
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• pp.67-73
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• 2006

Purpose: The arterial base deficit (BD) has proven to be useful in the evaluation and management of trauma patients. Indicators such as the Triage-Revised Trauma Score (t-RTS) and the systemic inflammatory response syndrome (SIRS) score have been used as triage tools for emergency trauma patients in Korea. The purpose of this study was to assess the usefulness of the initial BD in predicting injury severity and outcome in the trauma population. Methods: The medical records of 308 consecutive trauma patients admitted to the Emergency Center of Masan Samsung Hospital from January 2004 to December 2004 were carefully examined prospectively and retrospectively, and 291 patients were selected as subjects for this research. The SIRS score and the t-RTS were calculated based on the records from the emergency department, and the BD was calculated based on the arterial blood gas analysis obtained within 30 minutes of admission. The efficiency of the three indicators as triage tools was evaluated by using cross tabulations in two - by - two matrices and by using a receiver operating characteristic (ROC) curve analysis. Results: When the mortality was used as the outcome parameter, the sensitivity and the accuracy of the initial BD were higher than those of the SIRS score (p<0.05) and were same as those of the t-RTS. The areas under the ROC curves of the initial BD, the SIRS score, and the t-RTS were $0.740{\pm}0.087$, $0.696{\pm}0.082$, and $0.871{\pm}0.072$, respectively (95% confidence interval). When emergency operation and blood transfusion requirements were used as outcome parameters, the comparisons of the sensitivities and the accuracies of the initial BD and the other two indicators showed the same pattern as mentioned above. The areas under the ROC curves of the initial BD were 0.7~0.8 and were larger than those of the SIRS score (p<0.05). Conclusion: The ability of the initial BD to predict injury severity and outcome was similar to those of the t-RTS and the SIRS score. Therefore, the authors suggest that the initial BD may be used as an alternative to previous triage tools for trauma patients.

• Tuberculosis and Respiratory Diseases
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• 제50권3호
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• pp.300-309
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• 2001

배 경 : 패혈증의 병태생리에는 많은 인자들이 관여를 한다. 이중 ET-1은 혈관수축 및 다장기 부전 등을 초래하고 IL-8은 호중구 매개성 염증반응을 유도하는 역할을 하며, 임상적 지표로서도 유용성이 알려지고 있다. 본 연구는 패혈증 환자에서 ET-1과 IL-8의 혈중농도를 연속적으로 측정하여 변화 양상과 상호 관련성을 평가하고 임상적인 의의를 조사하고자 한다. 방 법 : 패혈증 환자 19예에서 1일, 3일, 7일, 14일에 연속적으로 채혈을 하였고 APACHE III 점수를 측정하였다. 혈청 검체에서 ET-1과 IL-8의 농도를 immunoassay 법으로 측정하였다. 결 과 : 패혈증 환자에서 정상 대조군에 비하여 혈청 ET-1이 유의하게 높았다. 패혈증 환자에 있어서 1일 및 7일 ET-1은 생존군보다 사망군에서 더 높았다. 패혈성 쇼크를 동반한 군에서 1일 ET-1이 높았으며, 혈청 ET-1은 혈청 creatinine과 1일, 7일, 14일에 유의한 상관성이 있었다. 혈청 ET-1과 IL-8 농도는 14일에 서로 유의한 상관성이 나타났다. 결 론 : 패혈증에 있어서 혈청 ET-1은 예후, 패혈성 쇼크, 신부전 등과 관련성이 있었고 IL-8과도 상관성을 보여 임상적인 평가 및 예후 인자로서 유의성을 보였다.