• Gut and Liver
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• 제12권6호
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• pp.682-693
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• 2018

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

• 생명과학회지
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• 제31권4호
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• pp.430-441
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• 2021

세스퀴테르펜 락톤(Sesquiterpene lactones; STL) 화합물은 테르페노이드의 일종으로 주로 국화과에서 발견이 되고 강한 세포 독성을 나타내는 생리학적 특성을 지니고 있다. 이러한 세스퀴테르펜 락톤은 강한 세포 독성으로 인해 연구가 미미하였으나, 최근 화학적 변형을 통해 독성이 적은 형태로 합성하여 새로운 의약품 개발로서의 연구가 활발히 진행되고 있다. 세스퀴테르펜 락톤 화합물인 artemisinin 및 mipsagargin 화합물은 현재 말라리아 및 종양성장에 대한 약물로 사용되고 있다. 또한 항산화, 간보호, 항바이러스, 항균, 항종양 및 항노화 등의 생리활성 효능이 보고되어 있으며, 종양세포에서 자멸사를 유도하여 항암제로서의 연구가 진행되고 있다. 본 연구에서는 세스퀴테르펜 락톤 화합물인 artemisinin, costunolide, thapsigargin, arglabin, parthenolide, alantolactone, cynaropicrin, helenalin, 및 santonin의 생리활성 효능에 대한 연구 동향을 검토하고자 한다.

• 생명과학회지
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• 제29권4호
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• pp.499-508
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• 2019

암줄기세포는 전이와 재발의 주요한 요인이 되는 자가재생능력, 분화할 수 있는 능력, 치료에 대한 저항성 및 암 형성 능력의 특성을 가진다. WNT/${\beta}$-catenin, Hedgehog, Notch, BMI1, BMP 및 TGF-${\beta}$와 같은 암줄기세포의 특성을 획득 및 유지할 수 있는 신호기전의 연구 결과가 존재하지만, 현재까지 선택적으로 암줄기세포를 표적할 수 있는 치료 전략은 미미하다. 최근, 면역관문억제제인 CTLA-4, PD-1/PD-L1 단일클론항체는 흑색종, 폐암, 췌장암 및 혈액암에 괄목할만한 임상 시험 결과를 나타냈으며, 긴 항암지속효과와 적은 부작용은 기존 항암제보다 개선 된 모습을 보였다. 또한 두경부편평상피암, 흑색종, 유방암 줄기세포를 선택적으로 제거 하였다. 위의 결과를 종합하면, 면역관문억제제는 이전 항암제에 비해 효과적인 항암전략이며, 동시에 암줄기세포를 선택적으로 제거할 수 있는 가능성을 시사한다. 따라서 본 리뷰에서는 암줄기세포와 면역관문억제제의 이해를 통해, 면역관문억제제의 암줄기세포 표적 가능성에 대해 고찰하고자 한다.

• 대한임상검사과학회지
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• 제50권4호
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• pp.391-398
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• 2018

중간엽줄기세포는 항염증능, 면역조절능 뿐만 아니라 다계통으로의 분화능 때문에 난치성 환자 치료를 위한 매력적인 대안적 치료방법으로 알려져 왔다. 지금까지 중간엽줄기세포의 이식 치료법은 면역질환, 심혈관질환, 암, 간질환 및 뇌졸중을 비롯한 다양한 질병의 전임상 및 임상적용에 긍정적인 결과를 가져왔다. 여러 연구들에 의하면, 중간엽줄기세포를 이용한 치료는 손상된 세포나 조직에 중간엽줄기세포가 이동하여 직접 세포를 대체하거나 분화시키는 작용이 아니라 중간엽줄기세포에서 분비하는 여러 인자들 즉, 주변분비 효과(paracrine effect)에 의한 것으로 확인되고 있다. 최근에 중간엽줄기세포 유래 엑소좀은 핵산, 단백질, 지질 등을 손상된 세포나 조직의 국소 미세환경으로 전달함으로써 세포간 상호작용을 통해 조직재생을 중재할 수 있는 중요한 역할을 하는 것으로 알려졌다. 엑소좀의 이용은 세포이식으로부터 발생할 수 있는 종양형성과 같은 다양한 위험성을 피할 수 있으므로 줄기세포 기반 치료 적용에 유용성이 매우 높다. 이러한 이유에서 중간엽줄기세포 유래 엑소좀은 재생의학 및 조직공학에서 안전하고 효율적인 치료적 도구(tool)가 될 수 있다. 여기에서 우리는 치료제로서의 중간엽줄기세포 유래 엑소좀의 정의와 역할에 대한 최신 지견과 함께 포괄적인 이해를 제공하고자 한다.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1089-1098
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• 2018

Objective: To investigate the diagnostic yield of contrast-enhanced computed tomography (CT) in Crohn's disease (CD) patients presenting with acute severe lower gastrointestinal bleeding (LGIB), and the role of CT in predicting the risk of rebleeding. Materials and Methods: A consecutive series of 110 CD patients presenting with acute severe LGIB between 2005 and 2016 were analyzed. Among them, 86 patients who had undergone contrast-enhanced CT constituted the study cohort. The diagnostic yield of CT for detecting contrast extravasation was obtained for the entire cohort and compared between different CT techniques. In a subgroup of 62 patients who had undergone CT enterography (CTE) and showed a negative result for extravasation on CTE, the association between various clinical and CTE parameters and the risk of rebleeding during subsequent follow-up was investigated using Cox regression analysis. Results: The diagnostic yield of CT was 10.5% (9 of 86 patients). The yield did not significantly differ between single-phase and multiphase examinations (p > 0.999), or between non-enterographic CT and CTE (p = 0.388). Extensive CD (adjusted hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.09-9.80; p = 0.034) and bowel wall-to-artery enhancement ratio (adjusted HR, 2.81; 95% CI, 1.21-6.54; p = 0.016) were significantly independently associated with increased rebleeding risks, whereas anti-tumor necrosis factor-${\alpha}$ therapy after the bleeding independently decreased the risk of rebleeding (adjusted HR, 0.26; 95% CI, 0.07-0.95; p = 0.041). Conclusion: The diagnostic yield of contrast-enhanced CT was not high in CD patients presenting with acute severe LGIB. Nevertheless, even a negative CTE may be beneficial as it can help predict the risk of later rebleeding.

• 생명과학회지
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• 제28권11호
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• pp.1316-1320
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• 2018

녹차(GT) 추출물의 효과를 인간 유방암 유래 세포인 MCF-7 세포를 사용하여 조사 하였다. GT추출물의 세포 독성 효과를 MTT 방법을 사용하여 관찰한 결과, MCF-7 세포는 현저한 세포 독성 효과를 보였고, 이 독성 효과는 GT추출물 농도 의존적으로 증가하였다. p53과 관련 단백질인 p21/cip1과 CDK2의 연관성을 조사하기 위해 GT추출물 처리 후 웨스턴 분석법을 통해 이들 단백질의 발현을 조사하였다. GT추출물 처리 후, MCF-7 세포에서 p53 단백질의 양은 농도에 따라 현저하게 증가 하였다. p21/cip1 단백질의 발현은 낮은 농도의 GT추출물에서 증가되며, 고농도에서도 감소하지 않았다. 그러나 CDK2의 단백질의 양은 높은 농도의 GT추출물에서 CDK2 발현의 급격한 감소가 관찰되었다. 이 결과는 GT추출물의 처리는 MCF-7 세포에서 p53와 p21/cip1를 증가시켜, 그 결과로 활성화 된 p21/cip1는 CDK2의 발현을 억제 함을 나타내고 있다. GT추출물이 MCF-7 세포의 세포주기에 어떤 영향을 미치는지 확인하기 위하여 FACS 분석으로 관찰한 결과, MCF-7 세포에서 세포주기의 G1 단계가 점차 증가하는 결과를 보였다. 이 결과는 GT추출물의 유방암 세포에서의 항암 효과는 세포주기의 G1 단계에서 MCF-7 세포를 정지시키는 p53에 의해 조절된다는 사실을 명확하게 보여 주고 있다.

• 대한영양사협회학술지
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• 제25권3호
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• pp.217-228
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• 2019

There have been no published studies concerning the anti-inflammatory effects of corn silk on colon cancer cells. Thus, this study was conducted to investigate the effect of corn silk extract containing high levels of maysin on inflammation and its mechanism of action in colon cancer cells. SW 480 human colon cancer cells were treated with $1{\mu}g/mL$ of lipopolysaccharide (LPS) to induce inflammation, and next they were treated with different concentrations of corn silk extract (0, 5, 10 and $15{\mu}g/mL$). The concentrations of nitric oxide (NO) were determined. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6), were determined. Western blot analysis was performed to determine the protein expressions of nuclear factor-kappa B ($NF-{\kappa}B$) and mitogen-activated protein kinases, and the latter consists of extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 MAP kinase (p38). The concentration of NO and the mRNA expression of iNOS were significantly and dose-dependently decreased in the corn silk-treated groups (P<0.05). The mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were significantly increased in the LPS-treated group (P<0.05), but these expressions were significantly and dose-dependently decreased in the corn silk treated groups (P<0.05). The protein expressions of $NF-{\kappa}B$ (in a dose-dependent fashion), ERK (at 10 and $15{\mu}g/mL$), JNK (at $15{\mu}g/mL$) and p38 (at 10 and $15{\mu}g/mL$) were significantly decreased with corn silk treatments (P<0.05). In conclusion, corn silk extract containing high levels of maysin seems to inhibit the LPS-induced inflammatory responses in SW480 colon cancer cells via the $NF-{\kappa}B$ pathway.

• Journal of Dental Anesthesia and Pain Medicine
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• 제22권4호
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• pp.277-287
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• 2022

Background: Inflammatory dental diseases that occur during pregnancy can cause preterm labor and/or intrauterine growth restriction. Therefore, proactive treatment of dental diseases is necessary during pregnancy. Dexmedetomidine (DEX) is a widely used sedative in the dental field, but research on the effect of DEX on pregnancy is currently insufficient. In this study, we investigated the effects of co-treatment with DEX and lipopolysaccharide (LPS) on inflammatory responses in human amnion-derived WISH cells. Methods: Human amnion-derived WISH cells were treated with 0.001, 0.01, 0.1, and 1 ㎍/mL DEX with 1 ㎍/mL LPS for 24 h. Cytotoxicity of WISH cells was evaluated by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂), p38, and nuclear factor kappa B (NF-𝜅B) was examined by western blot analysis. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-1𝛽 and tumor necrosis factor (TNF)-𝛼 was analyzed by real-time quantitative polymerase chain reaction. Results: Co-treatment with DEX and LPS showed no cytotoxicity in the WISH cells. The mRNA expression of IL-1𝛽 and TNF-𝛼 decreased after co-treatment with DEX and LPS. DEX and LPS co-treatment decreased the protein expression of COX-2, PGE₂, phospho-p38, and phospho-NF-𝛋B in WISH cells. Conclusion: Co-treatment with DEX and LPS suppressed the expression of COX-2 and PGE₂, as well as pro-inflammatory cytokines such as IL-1𝛽 and TNF-𝛼 in WISH cells. In addition, the anti-inflammatory effect of DEX and LPS co-treatment was mediated by the inhibition of p38/NF-𝜅B activation.

• 대한본초학회지
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• 제37권3호
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• pp.9-19
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• 2022

Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

• 대한본초학회지
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• 제28권6호
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• pp.119-127
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• 2013

Objectives : ${\beta}$-Asarone (BAS) is an active ingredient in Acori Rhizoma. This study investigated anti-neuroinflammatory and memory ameliorating effects of BAS in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : BAS was administered orally at doses of 7.5, 15, and 30 mg/kg for 3 days prior to LPS (3 mg/kg, intraperitoneal) injection. Pro-inflammatory cytokine mRNA, including tumor necrosis factor-${\alpha}$ (TNF-ㅍ), interleukin (IL)-$1{\beta}$ and IL-6, was measured in hippocampus tissue using real-time polymerase chain reaction at 4 h after the LPS injection. An ameliorating effect of 30 mg/kg BAS on learning and memory impairment in the LPS-treated mice was verified using the Morris water maze test. Results : BAS significantly attenuated up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA in hippocampus tissue of the LPS-treated mice. In acquisition training test, BAS improved learning performance of the LPS-treated mice with a significant decrease of escape latency to the platform. In memory retention test, BAS also ameliorated memory impairment of the LPS-treated mice with a significant increase of swimming time in zones neighboring to the platform, number of target heading, and memory score. Conclusion : The results suggest that inhibition of pro-inflammatory cytokines and neuroinflammation in the hippocampus by BAS could be one of the mechanisms for BAS-mediated ameliorating effect on learning and memory impairment in LPS-treated mice.