• Biomolecules & Therapeutics
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• 제29권3호
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• The Plant Pathology Journal
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• 제38권6호
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• pp.603-615
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• 2022

Soybean (Glycine max (L) Merr.) provides plant-derived proteins, soy vegetable oils, and various beneficial metabolites to humans and livestock. The importance of soybean is highly underlined, especially when carbon-negative sustainable agriculture is noticeable. However, many diseases by pests and pathogens threaten sustainable soybean production. Therefore, understanding molecular interaction between diverse cultivated varieties and pathogens is essential to developing disease-resistant soybean plants. Here, we established a pathosystem of the Korean domestic cultivar Kwangan against Pseudomonas syringae pv. syringae B728a. This bacterial strain caused apparent disease symptoms and grew well in trifoliate leaves of soybean plants. To examine the disease susceptibility of the cultivar, we analyzed transcriptional changes in soybean leaves on day 5 after P. syringae pv. syringae B728a infection. About 8,900 and 7,780 differentially expressed genes (DEGs) were identified in this study, and significant proportions of DEGs were engaged in various primary and secondary metabolisms. On the other hand, soybean orthologs to well-known plant immune-related genes, especially in plant hormone signal transduction, mitogen-activated protein kinase signaling, and plant-pathogen interaction, were mainly reduced in transcript levels at 5 days post inoculation. These findings present the feature of the compatible interaction between cultivar Kwangan and P. syringae pv. syringae B728a, as a hemibiotroph, at the late infection phase. Collectively, we propose that P. syringae pv. syringae B728a successfully inhibits plant immune response in susceptible plants and deregulates host metabolic processes for their colonization and proliferation, whereas host plants employ diverse metabolites to protect themselves against infection with the hemibiotrophic pathogen at the late infection phase.

• Journal of Veterinary Science
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• 제21권3호
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• pp.39.1-39.15
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• 2020

Background: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. Objectives: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. Methods: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. Results: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. Conclusions: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.39-48
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• 2024

Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.

• 한국식품영양학회지
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• 제37권2호
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• pp.110-122
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• 2024

This study investigated major constituents and anti-inflammatory effects of an ethanol extract of Platycodon grandiflorum leaves. Through HPLC analysis, chlorogenic acid and luteolin-7-O-glucoside were identified as predominant constituents in the ethanol extract. Their anti-inflammatory effects were evaluated using murine macrophage (RAW 264.7 cells) and human lung carcinoma cells (NCI-H292 & A549). The ethanol extract significantly (p<0.01) inhibited the production of nitrite, interleukin-6 (IL-6), and prostaglandin E2 (PGE2) induced by lipopolysaccharide (LPS) in RAW 264.7 cells. Furthermore, the ethanol extract suppressed the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) proteins in RAW 264.7 cells stimulated with LPS. In NCI-H292 and A549 cells, treatment with the ethanol extract significantly (p<0.05) decreased levels of pro-inflammatory cytokines IL-6 and IL-8 induced by IL-1β. The phosphorylation of ERK rather than JNK in the mitogen-activated protein kinase signaling pathway was observed to be a more important mediator in the down-regulation of pro-inflammatory cytokines in NCI-H292 cells. These findings suggest that the ethanol extract of Platycodon grandiflorum leaves containing luteolin-7-O-glucoside exhibits promising anti-inflammatory properties.

• 생명과학회지
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• 제30권1호
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• pp.106-112
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• 2020

아미노아실-트랜스퍼 리보핵산 합성효소-상호작용 다기능 단백질 2(AIMP2)는 여러 tRNA 합성효소들과의 결합체를 이루게 하는 기능을 하며, DNA 손상에 대한 반응으로 세포사멸 활성을 나타낼 수 있다. DNA에 손상이 발생하면 AIMP2는 MDM2 공격으로부터 p53을 보호하기 위해 MDM2에 결합한다. TGF-β 신호에서 AIMP2는 세포 핵으로 들어가 FUSE 결합 단백질(FBP)과 결합하여 c-myc을 억제한다. TNF 수용체 관련 인자 2(TRAF2)는 c-Jun N-말단 키나아제(JNK), NF-κB 및 p38 미토겐 활성화 단백질 키나아제(MAPKs)의 신호에서 실행되는 두 수용체, TNF 수용체 1과 2 사이의 중요한 중재자이다. TARF2는 TNF-α 신호에서 JNK와 NF-κB의 활성화에 필요하며, 세포사멸 신호를 막는 중재자 역할을 수행한다. 또한 TNF-α 신호에서 AIMP2는 세포사멸을 향상시킨다. 이 신호에서, AIMP2는 TRAF2를 분해하는 것으로 잘 알려진 E3 유비키틴 효소인 c-IAP1과의 결합을 향상시킨다. AIMP2, TRAF2 및 c-IAP1을 포함한 복합체의 형성은 proteasome을 매개로 하여 TRAF2의 분해를 초래한다. 이러한 연구 결과는 AIMP2가 TNF-α 신호에서 직접적인 상호작용을 통해 TRAF2를 하향 조절시켜 세포사멸을 유도할 수 있음을 시사한다.

• 한국식품저장유통학회지
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• 제24권8호
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• pp.1149-1157
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• 2017

본 연구에서는 넓패 에탄올 추출물의 항염증 효과를 알아보기 위해 RAW 264.7 세포에 LPS로 유도된 염증 반응 in vitro 및 in vivo 실험을 실시하였다. RAW 264.7 세포에 LPS와 함께 세포를 배양하였다. 먼저 MTT assay 실험을 통해 넓패 에탄올 추출물이 모든 농도(0.1, 1, 10, 50, $100{\mu}g/mL$)에서 세포독성을 나타내지 않는 것을 학인 하였다. 또한 모든 농도에서 염증억제 효과를 살펴 본 결과, LPS 처리구는 iNOS, COX-2, NF-${\kappa}B$ 그리고 MAPKs의 발현양을 증가 시켰으나, 넓패 에탄올 추출물의 경우 염증 반응에 관여하는 전사인자인 NF-${\kappa}B$와 MAPKs의 활성을 억제함으로써 항염증 효과를 나타내었다. 마지막으로 넓패 에탄올 추출물의 mast cell의 피부 조직학적 변화를 알아본 결과, control의 경우 진피와 경피의 면적이 확장 되어있고, mast cell의 침윤이 정상 군에 비하여 현저하게 증가함을 알 수 있었다. 반면에 넓패 에탄올 추출물의 경우 대조군에 비해 진피와 경피의 두께가 줄었으며 mast cell의 침윤감소에 효과가 있는 것을 확인하였다. 따라서 모든 결과를 종합하였을 때 넓패 에탄올 추출물이 항염증 치료제 뿐만 아니라 더 나아가 항염증에 유용한 기능성 식품소재로써 가치가 높다고 사료된다.

• 생명과학회지
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• 제21권2호
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• pp.183-193
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• 2011

중간엽 줄기세포의 이동과 분화는 손상된 조직의 재생을 위해 필수적이다. Sphingosine-1-phosphate (S1P)는 세포성장, 생존, 분화, 이동성 등 여러 가지 생명현상에 중요한 역할을 하는 생리활성 지질이다. 본 연구에서는 인체 골수유래 중간엽 줄기세포의 이동과 세포분화에 대한 S1P의 영향을 조사하였다. S1P는 중간엽 줄기세포의 이동을 증가시켰으며 pertussis toxin의 전처리는 S1P에 의한 세포이동을 억제하였다. 본 결과는 S1P에 의한 세포 이동과정에 Gi에 연결된 수용체가 관여함을 제시한다. $S1P_1$과 $S1P_3$ 수용체에 대한 길항제인 VPC23019의 전처리나 siRNA를 이용한 $S1P_1$ 수용체의 발현억제는 S1P에 의한 세포 내 칼슘 증가와 중간엽 줄기세포의 이동을 저해 하였다. 또한, S1P의 처리는 중간엽 줄기세포에서 평활근세포의 표지유전자인 $\alpha$-smooth muscle actin ($\alpha$-SMA)의 발현을 증가시켰으며 VPC23019의 전처리는 S1P에 의한 $\alpha$-SMA의 발현증가를 저해하였다. S1P는 중간엽 줄기세포에서 p38 mitogen-activated protein kinase (p38 MAPK)의 인산화를 촉진하였으며 p38 MAPK의 저해제인 SB202190의 전처리 또는 p38 MAPK의 dominant negative mutant의 과발현은 S1P에 의한 중간엽 줄기세포의 이동 $\alpha$-SMA 발현증가를 억제하였다. 본 연구결과는 S1P가 $S1P_1$-p38 MAPK 신호전달기전을 통해 중간엽 줄기세포의 이동과 평활근세포로의 분화를 촉진함으로써 중간엽 줄기세포를 이용한 조직재생에의 활용 가능성을 제시한다.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.209-215
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• 2005

Recently, a large number of clinical experiments have shown that exposure of organic pollutants lead to various cancers through the abnormal cell growth. Environmental pollutants, such as 2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs), are carcinogen and are known to cause the cognitive disability and motor dysfunction in the developing of brain. The effects of these pollutants on neurodevelopmental disorder is well established, but the underlying mechanism(s) and similarity of gene expression profiles in human brain tumors with organic pollutants still remain unclear. In this study, we first examined the gene expression profiles in glioblastomas compared with meningioma that are kinds of primary human brain tumor by using human cDNA microarray. The results of cDNA microarray analysis revealed that 26 genes were upregulated (Z-ratio>2.0) and 14 genes were downregulated (Z-ratio<-2.0) in glioblastoma compared with meningioma. From the altered gene patterns, mitogen-activated protein kinase (MAPK) signaling related genes, such as MAP2K3, MAP3K11 and jun activated domain binding protein, and transcription factors, such as UTF2 and TF12, were upregulated in glioblastoma. Also, we tried to investigate the relation between important genes up- and down-regulated in giloblastoma and various organic pollutants. Therefore, the identification of changes in the patterns of gene expression may provide a better understanding of the molecular mechanisms involved in human primary brain tumors and of the relation between gene expression profiles and organic pollutants in brain tissue.

• 대한본초학회지
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• 제38권1호
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• pp.11-19
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• 2023

Objectives : Neuroinflammation is a common pathological mechanism of neurodegenerative diseases, and the development of therapeutic agents is urgently needed. Red ginseng has been known to be good for the immune stimulation in Eastern Asia. Although the immuno-stimulatory activity of red ginseng are already known, the neuro-protective effects of cultivated red ginseng with fermented complex mushroom-cereal mycelium (RGFM) have not been conducted. Thus, in this study, we tried to investigate the anti-neuroinflammatory effect of RGFM water extract on lipopolysaccharide (LPS) stimulated BV2 cells. Methods : BV2 cells were pretreated with RGFM 1 h prior to LPS exposure. To determine the neuro-protective effects of RGFM water extract, we measured the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6 and tumor necrosis factor (TNF)-𝛼 in LPS-stimulated BV2 cells. In addition, to find out the regulatory mechanism of RGFM water extract, we assessed the protein levels of mitogen-activated protein kinases (MAPKs) and inhibitory 𝜅B𝛼 (I𝜅B𝛼) by western blotting. Results : In our study, treatment of RGFM reduced the mRNA expression of iNOS and COX-2 and suppressed NO production in LPS-stimulated BV2 cells. Additionally, the secretion of IL-1𝛽 and TNF-𝛼 but not IL-6 was significantly inhibited by RGFM. Furthermore, RGFM water extract inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). Conclusions : Taken together, these findings suggest that RGFM water extract has a protective effect on neuroinflammation through inhibition of JNK.