• Biomolecules & Therapeutics
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• 제31권3호
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• pp.330-339
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• 2023

Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• Biomolecules & Therapeutics
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• 제29권6호
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• pp.650-657
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• 2021

Metformin is an anti-diabetic drug and has anticancer effects on various cancers. Several studies have suggested that metformin reduces cell proliferation and stimulates cell-cycle arrest and apoptosis. However, the definitive molecular mechanism of metformin in the pathophysiological signaling in endometrial tumorigenesis and metastasis is not clearly understood. In this study, we examined the effects of metformin on the cell viability and apoptosis of human cervical HeLa and endometrial HEC-1-A and KLE cancer cells. Metformin suppressed cell growth in a dose-dependent manner and dramatically evoked apoptosis in HeLa cervical cancer cells, while apoptotic cell death and growth inhibition were not observed in endometrial (HEC-1-A, KLE) cell lines. Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphate-activated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. To determine why the anti-proliferative effects are observed only in HeLa cells, we examined the expression level of liver kinase B1 (LKB1) since metformin and LKB1 share the same signalling system, and we found that the LKB1 gene is not expressed only in HeLa cancer cells. Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.

• Nutrition Research and Practice
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• 제14권4호
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• pp.309-321
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to evaluate the effects of folic acid supplementation in high-fructose-induced hepatic steatosis and clarify the underlying mechanism of folic acid supplementation. MATERIALS/METHODS: Male SD rats were fed control, 64% high-fructose diet, or 64% high-fructose diet with folic acid for eight weeks. Plasma glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lipid profiles, hepatic lipid content, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: The HF diet significantly increased hepatic total lipid and triglyceride (TG) and decreased hepatic SAM, SAH, and SAM:SAH ratio. In rats fed a high fructose diet, folic acid supplementation significantly reduced hepatic TG, increased hepatic SAM, and alleviated hepatic steatosis. Moreover, folic acid supplementation in rats fed high fructose enhanced the levels of phosphorylated AMP-activated protein kinase (AMPK) and liver kinase B (LKB1) and inhibited phosphorylation of acetyl coenzyme A carboxylase (ACC) in the liver. CONCLUSIONS: These results suggest that the protective effect of folic acid supplementation in rats fed high fructose may include the activation of LKB1/AMPK/ACC and increased SAM in the liver, which inhibit hepatic lipogenesis, thus ameliorating hepatic steatosis. The present study may provide evidence for the beneficial effects of folic acid supplementation in the treatment of non-alcoholic fatty liver disease.

• 대한한의학방제학회지
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• 제29권4호
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• pp.277-283
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• 2021

Objectives : We investigated the effects of Bojungikgi-tang (BJIGT) on P450 cytochrome enzyme and oxidative stress in the cells. Methods : We enrolled the HepG2 hepatocyte cell line to assess MTT assay, flow cytometer, and immunoblotting analysis. Expression of CYP450 was confirmed by immunoblotting analysis in the Huh7 cell line. Results : We determined that BJIKT markdely changed the expression of the CYP2C19, CYP2D6, and CYP2E1. Moreover, BJIKT inhibited the cell toxicity induced by arachidonic acid + iron treatment, as assessed by FACS analysis. BJIKT induced AMPK activation, which increased the phophorylation of ACC. Conclusions : This study verified the effects of BJIKT, on P450, ROS production, mitochondrial damage and AMPK signaling pathway, which might give us the scientific information about the traditional herbal prescription.

• Journal of Ginseng Research
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• 제41권3호
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• pp.392-402
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• 2017

Background: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. Methods: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides. $H_2O_2$ productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and small interfering RNA (siRNA) transfection. Results and conclusion: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-$\text\tiny L$-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S-PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1-AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.

• 대한치과의사협회지
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• 제20권7호통권158호
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• pp.625-630
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• 1982

The author observed the behavior of inflammatory cells in the primary intension of incisional wound on the Albino rat palate. The superficial wounds (0.5mm depth) were made anteroposterior lineally by surgical knife. They were sacrified on 4, 8, 12, 16, 24, 48, 72 and 120 hr after wounding. The specimens were fixed in 2.5% glutaraldehyde in 0.1 M cacodylate buffer and 1% osmic acid in 0.1M cacodylate buffer, and embeddd in Epon 812. Ultrathin sections were obtained by LKB 8800, and stained with uranyl acetate/lead citrate, and observed with Corynth 500 EM.

• 대한한의학방제학회지
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• 제30권1호
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• pp.1-9
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• 2022

Objectives : This study investigated the protective effect of Ojeok-san (OJS) on cellular damage induced by oxidative stress and whether it induces changes in CYP450 expression. Methods : To investigate the protective effect, we used cells stimulated by oxidative stress caused by the combination treatment of AA+iron. Changes in CYP450 expression were detected by immunoblotting analysis using Huh7 cells. Results : We observed that OJS altered the expression of CYP1A2, CYP3A4, CYP2C19, CYP2D6, and CYP2E1. OJS increased cell viability against AA+iron-induced oxidative stress and inhibited mitochondrial dysfunction. OJS increased phosphorylation of LKB1, phosphorylation of AMPK, and phosphorylation of ACC, which are related to the LKB1-AMPK pathway. In addition, phosphorylation of LATS1 and phosphorylation of YAP, which are related to the Hippo-YAP pathway, were increased. Conclusions : Our results show that OJS has 1) the ability to protect hepatocytes against oxidative stress, and 2) the potential to induce changes in CYP450.

• 한국식품영양과학회지
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• 제26권4호
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• pp.697-703
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• 1997

본 연구는 급원이 다른 n-3 지방산 섭취가 휜쥐에서 면역반응과 PGE$_2$ 및 LTB$_4$ 생성에 미치는 영항을 알아보기 위해 시도되었다. 실험동물은 생후 4주 정도의 Sp-rague-Dawley종 수컷을 사용하였으며 실험식 이를 4 주간 섭취 시 킨 후 희생하여 면역 실험을 행하였다. 실험 군간의 식이 섭취량, 체중 증가량, 식이 효율, 비장무게는 유의적인 차이가 없었다. 비장세포의 ConA와 PWM에 대한 증식능력 실험 결과는 ConA의 경우, 대조군과 FO군의 증식비율은 비슷하였고 PO군이 약간 높게 나타났으나 유의적인 차이는 없었다. PW의 경우는 대조군 보다 FO군과 PO군이 높게 나타나 n-3 지방산을 섭취한 군들이 증식 능력이 높은 유의적인 차이를 보였다. 그리고 PGE$_2$의 농도는 대조군이 FO군과 PO군에 비해 유의적으로 높았으며, LTB$_4$의 농도는 실험군간의 차이가 나타나지 않았다. 그러므로 비장세포의 PWM에 대한 증식능력이 n-3 지방산을 섭취한 경우에 대조군보다 높았던 것이 PGE$_2$ 농도와 관련이 있는 것으로 보이며 들기름과 어유는 같은 정도의 효과를 가지는 것으로 나타났다.

• 감성과학
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• 제12권4호
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• pp.433-442
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• 2009

요즈음 인터넷을 통해 물건을 구매하는 경향이 증가하고 있다. 또한 물건을 구매한 소비자는 리뷰, 댓글, 비평 또는 블로그 등의 형식으로 온라인에 그들의 사용 후기를 작성한다. 또한 작성된 사용 후기부터 많은 구매자들은 물건을 구매하기 전에 자신이 구입하고자 하는 물건에 대한 정보를 얻는다. 따라서 회사나 공공기관은 대중이 다른 사람의 의견에 관심을 기울인다는 점 때문에 대중의 의견을 수집하고 분석할 필요성에 직면하였다. 그러나 온라인상에 댓글이 너무 많고, 중복적이면서 짧은 경향이 있다. 이러한 환경 속에서 텍스트 문서의 감성을 인식하는 시스템의 필요성이 대두되었다. 텍스트로부터 작성자의 의견이나 주관적인 생각을 추출할 수 있게 영어에서는 단어에 속성이 주어진 GI와 LKB가 있으나 한글은 아직 속성이 주어진 사전이 존재하지 않는다. 이 논문에서는 한글 품사 중 4개의 품사(명사, 동사, 형용사, 부사)에 속성을 주었다. 그리고 학습 군을 만들어서 감성 단어의 패턴을 구성하고, 문장에서 단어 사이의 공기관계를 구성하여 학습 시켰다. 이 학습을 바탕으로, SO-PMI을 이용하여 문서를 긍정과 부정 2가지 극성을 분류하고, 4개의 품사(명사, 동사, 형용사, 부사)를 각각 조합하여 최상의 조건을 구하였다. 마지막으로 사용자 인터페이스를 통해 새로운 감성 표현, 구성형식, 단어 연관성을 반자동적으로 삽입하고 교정할 수 있는 시스템을 설계하였다.