• BMB Reports
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• 제51권10호
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• pp.486-492
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• 2018

The CCN protein family is composed of six matricellular proteins, which serve regulatory roles rather than structural roles in the extracellular matrix. First identified as secreted proteins which are induced by oncogenes, the acronym CCN came from the names of the first three members: CYR61, CTGF, and NOV. All six members of the CCN family consist of four cysteine-rich modular domains. CCN proteins are known to regulate cell adhesion, proliferation, differentiation, and apoptosis. In addition, CCN proteins are associated with cardiovascular and skeletal development, injury repair, inflammation, and cancer. They function either through binding to integrin receptors or by regulating the expression and activity of growth factors and cytokines. Given their diverse roles related to the pathology of certain diseases such as fibrosis, arthritis, atherosclerosis, diabetic nephropathy, retinopathy, and cancer, there are many emerging studies targeting CCN protein signaling pathways in attempts to elucidate their potentials as therapeutic targets.

• The Korean Journal of Pain
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• 제33권4호
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• pp.335-343
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• 2020

Background: Zhongyi paste is a traditional Chinese medicine herbal paste that is externally applied to reduce inflammation and relieve pain. Methods: An acute foot swelling inflammation model in C57BL/6J mice was established by carrageenan-induced pathogenesis. Zhongyi paste raised the pain threshold and also reduced the degree of swelling in mice with carrageenan-induced foot swelling. Results: Analysis indicated that serum tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E₂ (PGE₂) cytokine levels and PGE₂ levels in the paw tissue of the mice were decreased by Zhongyi paste treatment. The quantitative polymerase chain reaction and western blot results showed that Zhongyi paste downregulated the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), and also downregulated the mRNA expression of PGE₂. At the same time, the Zhongyi paste exerted a stronger effect as an external drug than that of indomethacin, which is an oral drug, and voltaren, which is an externally applied drug. Conclusions: Our results indicated that Zhongyi paste is a very effective drug to reduce inflammatory swelling of the foot, and its mechanism of action is related to regulation of the ERK1/2-COX-2-PGE₂ pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권5호
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• pp.243-250
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• 2016

Objectives: Many studies have examined histopathological factors and various prognostic scores related to inflammation to predict outcomes. Here, we examined the prognostic value of the C-reactive protein/albumin (CRP/alb) ratio in oral squamous cell carcinoma (OSCC). Materials and Methods: This retrospective study included 40 patients with OSCC. Using univariate and multivariate analyses, we focused on the correlation of the CRP/alb ratio with clinicopathological characteristics and with overall survival. We then compared five inflammation-based prognostic scores, CRP/alb ratio, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), based on receiver operating characteristic (ROC) curves. Results: The optimal cut-off value for the CRP/alb ratio was 0.085. The group with a high CRP/alb ratio had a high TNM clinical stage (P=0.002) and larger primary tumors (P=0.029), with statistically significant differences in lymph node metastasis and distant metastasis. In addition, when the CRP/alb ratio was high, multivariate analysis showed a lower survival rate (P=0.002; hazard ratio=6.078), and the ROC curve showed more outstanding discriminatory ability regarding overall survival compared to other inflammation-based prognostic scores. Conclusion: The CRP/alb ratio can be an independent prognostic factor when predicting prognosis in OSCC and has good prognostic ability.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Clinical and Experimental Pediatrics
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• 제56권12호
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• pp.519-522
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• 2013

Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) $1{\beta}$ and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. Serum sodium levels in hyponatremia are inversely correlated with the percentage of neutrophils, C-reactive protein, and N-terminal-pro brain type natriuretic peptide. Additionally, elevated levels of serum IL-6 and IL-$1{\beta}$ are found in inflammatory diseases, and their levels are higher in patients with hyponatremia. Because it is significantly correlated with the degree of inflammation in children, hyponatremia could be used as a diagnostic marker of pediatric inflammatory diseases. Based on available evidence, we hypothesize that hyponatremia may be associated with inflammatory diseases in general. Understanding the mechanisms responsible for augmented ADH secretion during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid treatment are important components that may lower the morbidity and mortality of patients in a critical condition.

• 한방안이비인후피부과학회지
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• 제20권2호통권33호
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• pp.36-46
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• 2007

Objective : In this study, the effect of Atractylodes japonica against LPS induced inflammation in mouse microglia BV2 cells was investigated. Method : Microglia BV2 Cells viability was determined using the MTT assay. We used water, ethanol extract from Atractylodes japonica and studied on the anti-inflammatory effect of lipopolysaccharide-induced inflammation using reverse transcription polymerase chain reaction (RT-PCR), western blot, and nitric oxide detection on mouse microglia BV2 cells. Result : The MTT assay revealed that it's extract has no significant cytotoxicity in the microglia BV2 cell. Various solvent extract from Atractylodes japonica inhibited nitrite production, iNOS protein and mRNA expression levels. And also it's extracts significantly reduced lipopolysaccharide-induced COX-2 activation in RT-PCR and western blot in lipopolysaccharide-induced microglia BV2 cells Conclusion : In this study, it's extracts was shown to suppress NO production by inhibiting iNOS expression and COX-2 activity. With this effects of anti-inflammation, we suggests that, it's extracts may be a useful candidate for the development of a drug on the related inflammatory diseases in brain.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.37-51
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• 2005

비만세포는 염증 및 알레르기 반응과 관련하여 우리 몸에서 주요한 작용을 하는 세포이다. 봉독은 현재까지 진통기전에 관련된 모델로 연구가 진행되어 왔으나, 최근에는 항염증이나 항알러지반응 둥에서 면역세포와 관련 한 연구가 진행 중에 있다. 본 연구는 봉독의 주요성분인 melittin과 MCD Peptide가 비만세포주에서의 유전자 발현에 미치는 영향을 연구함으로써 향후 유전자 언구에 관련한 기초를 제시하고자 하였다. 본 연구에서는 사람의 비만세포주를 이용하여, 세포독성 실험을 거쳐서 얻은 유효농도에서 각각 melittin과 MCD Peptide를 처치하고, 이때 변화하는 유전자의 발현양상을 microarray분석기법을 통하여 정보를 얻었다. 실험적 통계에 의하여 global M이 1 또는 -1 이상인 것을 유의한 것으로 보았을 때, melittin에서는 모두 7개 의 유전자가 항진되고, 8개의 유전자가 어제되었다. MCDP에서는 7개의 유전자가 항진되고 17개의 유전자가 억제되었다. 이들 유전자들이 주로 관련하는 체내의 작용은 세포내에서 단백결합, lymphocyte 기능의 활성화, macrophage 항원관련 및 세포핵의 수용체, GABA A receptor 관련물질, cAMP 반응요소와 연관된 단백질, 보체계 8번 및 B-cell 관련물질, 다낭성 신질환에 관련된 단백물질, 염증관련물질, 혈액응고에 영향을 주는 단백물질등과 연관이 되었다. 이러한 분석결과를 통하여 동복에서의 주요약리작용을 담당하는 melittin과 MCD peptide의 작용기전을 밝히는데 보다 유용한 자료를 얻을 수 있었으며, 향후에 봉독의 주요성분 및 전체봉 독액이 항알레르기반응이나 항염증작용에 미치는 영향에 대한 심도있는 연구가 필요할 것으로 사료된다.

• Journal of Nutrition and Health
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• 제54권5호
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• pp.448-458
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• 2021

본 연구는 뽕나무 열매 착즙 분말 (MJ)이 지방세포 분화과정에서 염증에 관여하는 유전자 발현 및 miR-132/143 조절에 미치는 효과에 중점을 두고 조사하였다. MJ는 3T3-L1 지방세포 분화 동안 지질축적이 억제되었고 PPAR-γ, CEBP-α 및 aP2와 같은 지방형성 유전자 발현을 억제하였다. 또한 염증 조절 매개체인 TNF-α, IL-6, MCP-1 및 iNOS 유전자 발현이 MJ 처리에 의해 감소되었다. MJ의 지질 축적 억제 효과는 염증과 지방분화에 관여하는 miR-132/143의 발현 감소와 관련이 있음을 확인하였다. 따라서 MJ는 염증을 동반하는 비만 예방 및 치료에 도움이 될 수 있는 식품 소재로서 가능성이 있음을 시사하고 있다. 그러나 MJ의 주요 성분인 안토시아닌의 생체이용율은 1-2% 미만으로 추정되며 예상되는 표적 조직이나 혈류에서 미량 검출되는 것으로 알려져 있다 [33]. 이를 해결하기 위해서는 생체 내 동물실험을 통한 다각적인 분석이 향후 진행되어야 할 것으로 판단된다.

• Journal of Ginseng Research
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• 제44권2호
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• pp.267-273
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• 2020

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

• Preventive Nutrition and Food Science
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• 제12권3호
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• pp.148-153
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• 2007

Obesity-induced inflammation plays a crucial role in obesity-related pathologies such as type II diabetes and atherosclerosis. Adipose tissue macrophages and the cell-derived proinflammatory chemokines are key components in augmenting inflammatory responses in obesity. Anthocyanins such as cyanidin and $cyanidin-3-O-{\beta}-D-glucoside$ (C3G) are known to elicit anti-inflammatory activities by suppressing the production of proinflammatory mediators such as tumor necrosis factor alpha and nitric oxide in LPS-stimulated macrophages. In the present study, we investigated whether cyanidin and C3G have the potential to suppress the inflammatory responses of adipose cells. Cyanidin and C3G not only suppressed the migration of RAW 264.7 macrophages induced by mesenteric adipose tissue-conditioned medium, but also inhibited the activation of the cells to produce inflammatory chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-related protein-2 (MRP-2) in a dose-dependent manner. Cyanidin and C3G also inhibited the release of MCP-1 and MRP-2 from adipocytes and/or macrophages. These findings suggest that cyanidin and C3G may suppress the inflammatory responses of adipose tissue in obesity.