• Reproductive and Developmental Biology
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• 제28권3호
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• pp.203-207
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• 2004

형질전환 동물의 유선에서 특이적으로 발현되도록 고안된 pBIL-10 발현 벡터를 이용하여 인간 IL-10 유전자가 삽입되어 한 계통으로 확립된 형질전환 생쥐에서 이 유전자가 장기 세대까지 안정적으로 전이되고, 또한 발현 수준도 지속적으로 유지되는지를 조사하였다. 이를 위해 제 8 세대의 수컷 hIL-10 형질전환 생쥐를 실험에 공시하였고, 제 15 세대까지의 전이율과 hIL-10 유전자의 발현 수준을 분석하였다, 제 8 세대 생쥐의 계대 번식에 의한 자손 중 50.9±5.8％가 형질전환 생쥐로 판명되었다. 또한 제 9 세대에서 외래 유전자의 전이율은 66.0±20.1％이렀고, 제 10 세대에서 외래 유전자의 전이율은 61.5±16.7％이었고, 제 11 세대에서 외래 유전자의 전이율은 41.1±8.4％이었고, 제 12 세대에서 외래 유전자의 전이율은 40.7±20.3％이었고, 제 13 세대에서 외래 유전자의 전이율은 61.3±10.8％이었고, 제 14 세대에서 외래 유전자의 전이율은 49.2±18.8％이었고, 제 15 세대에서 외래 유전자의 전이율은 43.8±25.9％이었다. 이러한 결과로 hIL-10 형질전환 생쥐는 그 외래유전자의 유전적 손상이 없이 장기 세대까지 안정적으로 전이되는 것으로 판다된다. 제 9 세대의 암컷 형질전환 생쥐로부터 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 3.6± 1.2 mg/ml의 수준에서 측정되었다. 제 10세대에서는 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 4.2±0.9 mg/ml의 수준에서 측정되었고, 제 11세대에서는 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 5.7± 1.5 mg/ml의 수준에서 측정되었고, 제 12세대에서는 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 6.3±3.5 mg/ml의 수준으로 측정되었고, 제 13세대에서는 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 6.8±4.5 mg/ml의 수준으로 측정되었고, 제 14세대에서는 유즙내 인간 hIL-10의 발현 수준을 분석하였을 때, 그 농도는 평균 6.8±3.1 mg/ml의 수준으로 측정되었다. 이러한 수준은 제 1 세대의 것보다 높은 결과로 형질전환 생쥐에서 인간 IL-10 유전자의 발현은 최소한 15 세대까지 지속적으로 유지된다는 것을 알 수 있었으며, 장기 세대까지도 발현수준이 유지될 것으로 판단된다. 이러한 연구결과는 계통으로 확립된 형질전환 동물에 부여된 새로운 유전형질은 지속적으로 후대로 유전될 수 있음을 제시한다.

• IMMUNE NETWORK
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• 제20권3호
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• pp.27.1-27.11
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• 2020

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.213-220
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• 2023

본 연구는 비자나무(Torreya nucifera (L.) Siebold & Zucc, TN)와 생물전환 된 비자나무 추출물(TNB)의 항염증 효과를 평가하기 위해 수행되었으며 이를 위해 C. acnes에 의해 유도된 RAW264.7 염증 모델에서 염증인자의 발현을 조사하였다. 실험 결과, TNB는 50, 100, 200 ㎍/mL 농도에서 TN의 높은 세포독성을 개선하였으며 nitric oxide (NO)와 NO 합성 효소인 inducible NO synthase (iNOS) 및 prostaglandin의 합성 효소인 cyclooxygenase-2 (COX-2)의 발현을 유의하게 억제하였다. 또한 TNB는 염증성 사이토카인인 tumor necrosis factor-α (TNF-α) 및 interleukin (IL)-1β, IL-6, IL-8의 발현을 유의하게 억제하였으며 특히 IL-6, IL-8의 경우 가장 고 농도인 200 ㎍/mL에서 정상세포 수준으로 감소하였다. 이후 진행된 western blot에서 인산화 된 IκB-α 및 NF-κB의 발현이 농도의존적으로 억제됨을 확인하였으며 인산화가 억제되면서 degradation이 감소하여 TNB처리 농도가 높아짐에 따라 IκB-α의 농도가 증가하는 경향을 보였다. 결론적으로, TNB는 NF-κB신호 전달 경로를 차단함으로써 다양한 염증 매개 인자의 발현을 효과적으로 하향 조절할 수 있으며 이를 통해 항 염증 활성을 유도하는 것으로 확인된다. 이러한 결과를 근거로 TNB가 C. acnes에 의해 유발된 염증성질환의 치료에 효과적인 천연물 소재로 적용될 수 있음을 제안한다.

• BMB Reports
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• 제33권6호
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• pp.463-468
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• 2000

Anthrax lethal toxin, which consists of two separate protein, protective antigen (83 KDa) and lethal factor (85 KDa) is responsible for major symptoms and death from systemic infection of Bacillus anthracis. High concentrations of this toxin are cytolytic to macrophages, whereas sublytic concentrations of lethal toxin induce these cells to produce interleukin $1{\beta}$ ($IL-1{\beta}$). It is proposed that melatonin and dehydroepiandrosterone (DHEA) may play an important role in modifying immune dysfunction. In this study, we investigated whether or not melatonin and DHEA could prevent $IL-1{\beta}$ production that is induced by anthrax lethal toxin in mouse peritoneal macrophages. Treatment of melatonin or DHEA alone, as well as together, prevented the production of $IL-1{\beta}$ caused by anthrax lethal toxin. We found that melatonin at a concentration of $10^{-6}-10^{-7}$ M inhibits $IL-1{\beta}$ production induced by anthrax lethal toxin. As expect, treatment of DHEA at a concentration $10^{-6}-10^{-7}$ M also suppressed production of $IL-1{\beta}$ by lethal toxin stimulated macrophages. The results of these studies suggest that melatonin and DHEA, immunomodulators, may have an important role in reducing the increase of cytokine production in anthrax lethal toxin-treated macrophages.

• Parasites, Hosts and Diseases
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• 제34권3호
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• pp.185-190
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• 1996

폐흡층(Paragonimus westermani) 감염시 일어나는 TH cytokin 반응을 알아보고자 마우스에 폐흡충 피낭유충을 감염시킨 후 비장세포를 Con A로 자극하여 TH1-specific cytokine인 $IFN-{\gamma}$와 TH2-specific cytokin인 IL-4의 생산량을 감염시기별로 효소표식 면역검사법으로 측정하였다. 폐흡충 감염 마우스의 비장세포에서 생산되는 IL-4는 감염 후 3일($410{\;}{\pm}{\;}60.9{\;}pg/ml$)에 최고치에 도달한 후 2주($343{\;}{\pm}{\;}59.0{\;}pg/ml$)까지 대조군에 비해 높게 유지되었으나 감염 후 4주에는 감소되기 시작하여 6주에는 대조군의 생산량과 비슷하였다. 한편 폐흡충 감염 마우스의 비장세포에서 생산되는 $IFN-{\gamma}$는 감염 후 1주($151{\;}{\pm}{\;}32.2{\;}pg/ml$)에만 대조군에 비해 높게 증가되었을 뿐 2주부터 감소되기 시작하여 감염 후 6주에는 전혀 측정되지 않아 오히려 대조군의 생산량보다도 적었다. 또한 폐흡충 감염 마우스의 혈청 내 IL-4의 양은 감염 후 4주부터 6주에 대조군에 비해 높게 증가되었으며 혈청내 $IFN-{\gamma}$의 양은 전 실험기간을 통해 측정되지 않았다. 이상의 결과를 종합할때 폐흡층 감염마우스에서는 $IFN-{\gamma}$보다는 IL-4가 증가되는 TH2 cytokine 반응이 주로 일어남을 알 수 있었다.

• 대한한의학회지
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• 제26권4호
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• pp.1-11
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• 2005

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from Cerebral infarction(CI) patients. Methods: We examined how the inhibition rate of tumor necrosis factor (TNF)-$\alpha$, interleukin(IL)-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or desferrioxamine(DFX)treated cells compared to unstimulated cells. Results: DCWGG inhibited the productions of TNF-$\alpha$, IL-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 induced by LPS in a dose-dependent manner. Conclusions: DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• 동의생리병리학회지
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• 제20권4호
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• pp.929-935
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• 2006

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral mononuclear cells (PBMCS) from Cerebral infarction(CI) patients. Methods: We examined that the inhibition rate of tumor necrosis factor $(TNF)-{\alpha},\;interleukin(IL)-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or Oesferrioxamine(DFX)-treated cells compared to unstimulated cells. DCWGG inhibited the productions of $TNF-{\alpha},\;IL-1{\alpha},\;IL-1{\beta}$, IL-6, and IL-8 induced by LPS in a dose-dependent manner DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• 대한의생명과학회지
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• 제23권3호
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• pp.272-276
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• 2017

HOX genes are transcription factors that play important roles in body patterning and cell fate specification during normal development. In previous study, we found aberrant overexpression of HOXB5 in breast cancer tissues and cell lines, and demonstrated that HOXB5 is important in regulation of cell proliferation, tamoxifen resistance, and invasiveness through the epithelial-mesenchymal transition (EMT). Although the relationship between HOXB5 and phenotypic changes in MCF7 breast cancer cells has been studied, the molecular function of HOXB5 as a transcription factor remains unclear. IL-6 has been reported to be involved in not only inflammation but also cancer progression, which is characterized by the increase of growth speed and invasiveness of tumor cells. In this study, we selected Interleukin-6 (IL-6) as HOXB5 putative downstream target gene and discovered that HOXB5 transcriptionally up-regulated the expression of IL-6 in HOXB5 overexpressing MCF7 cells. The upstream region (~1.2 kb) of IL-6 promoter turned out to contain several putative HOX consensus binding sites. Chromatin immunoprecipitation assay confirmed that HOXB5 directly binds to the promoter region of IL-6 and positively regulated the expression of IL-6. These data all together, indicate that HOXB5 promotes IL-6 transcription by actively binding to the putative binding sites located in the upstream region of IL-6, which enable to increase its promoter activity in MCF7 breast cancer cells.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2022년도 추계학술대회
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• pp.312-312
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• 2022

Peanut hull as by-product has been discarded during peanut processing. However, peanut hull contains plenty of polyphenols that shows various physiological activities. The objectives of this study were to investigate anti-inflammatory and enzyme inhibitory activities of polyphenols from 'Sinpalkwang' peanut (Arachis hypogaea L.) hull. Compounds were isolated from methanol extracts of peanut hull by preparative-high performance liquid chromatography after identifying and quantifying polyphenols using Ultra performance liquid chromatography (UPLC) and UPLC-Quadrupole time-of-flight-mass spectrometry profiling. The structures of compounds were elucidated by one-dimensional [¹H, ¹³C] nuclear magnetic resonance (NMR) and two-dimensional NMR (correlated spectroscopy, heteronuclear single quantum coherence and heteronuclear multiple bond correlation). Three compounds were identified as 5,7-dihydroxy-4H-chromen-4-one (peak 2), luteolin (peak 4) and eriodictyol (peak 5). Significant differences in inflammatory mediator such as nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-lβ) in lipopolysaccharide stimulated Raw 264.7 macrophages and in enzyme (xanthine oxidase [XO] and α-glucosidase [AG]) inhibitory activities were observed between three compounds (p < 0.05). Peak 5 treated Raw 264.7 macrophages showed lower content of NO (16.4 uM), IL-6 (7.0 ng/mL), and IL-1β (60.6 pg/mL) than peak 2 (NO: 28.3 uM, IL-6: 11.3 ng/mL, IL-1β: 66.9 pg/mL) and peak 4 (NO: 24.7 uM, IL-6: 9.3 ng/mL, IL-1β: 62.6 pg/mL). Peak 5 showed higher XO inhibitory activity (84.7%) and higher AG inhibitory activity (52.4%) than peak 2 (XO inhibitory activity: 45.4%, AG inhibitory activity: 21.6%) and peak 4 (XO inhibitory activity: 37.9%, AG inhibitory activity: 37.5%) at concentration of 0.5mg/mL. This study suggests that peanut hull could be a potential source of anti-inflammatory and physiological materials while creating new use of discarded peanut hull as by-products concomitantly.

• 대한의생명과학회지
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• 제24권3호
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• pp.168-174
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• 2018

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, rectal bleeding and diarrhea. Gastrodia elata Blume (GE) has been used for the treatment of various diseases including neurodegenerative diseases and inflammatory disease. However, there has been no information on whether GE regulates intestinal inflammation. The aim of this study is to elucidate whether GE can protect against dextran sulfate sodium (DSS)-induced colitis in a mouse model. The colitis mice were induced by drinking water containing 5% DSS for 7 days. Body weight, colon length and clinical score were assessed to determine the effects on colitis. The levels of inflammatory cytokines, tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in colitis tissue were also measured. The results showed that mice administrated with DSS showed clinical signs including weight loss and reduced colon length. GE inhibited the DSS-induced loss of body weight and shortening of colon and increased Disease activity index score. Additionally, we observed that GE suppressed the levels of $TNF-{\alpha}$ and IL-6 in DSS-treated colon tissues. Collectively, these findings provide experimental evidence that GE might be a useful therapeutic agent for patients with UC.