• IMMUNE NETWORK
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• 제23권1호
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• pp.6.1-6.24
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• 2023

Intestinal microorganisms interact with various immune cells and are involved in gut homeostasis and immune regulation. Although many studies have discussed the roles of the microorganisms themselves, interest in the effector function of their metabolites is increasing. The metabolic processes of these molecules provide important clues to the existence and function of gut microbes. The interrelationship between metabolites and T lymphocytes in particular plays a significant role in adaptive immune functions. Our current review focuses on 3 groups of metabolites: short-chain fatty acids, bile acids metabolites, and polyamines. We collated the findings of several studies on the transformation and production of these metabolites by gut microbes and explained their immunological roles. Specifically, we summarized the reports on changes in mucosal immune homeostasis represented by the Tregs and Th17 cells balance. The relationship between specific metabolites and diseases was also analyzed through latest studies. Thus, this review highlights microbial metabolites as the hidden treasure having potential diagnostic markers and therapeutic targets through a comprehensive understanding of the gut-immune interaction.

• The Plant Pathology Journal
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• 제30권4호
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• pp.343-354
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• 2014

Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.298-303
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• 2009

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

• 디지털융복합연구
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• 제17권8호
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• pp.249-255
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• 2019

제2형 당뇨병은 고혈당이 특징인 대사성 분비 장애로 여러 합병증을 야기하는 질병이며, 장기적인 치료가 필요하기 때문에 매년 많은 의료비를 지출한다. 이를 해결하기 위해 많은 연구들이 있어왔지만, 기존의 연구들은 한 시점에서의 데이터를 학습시켜 예측함으로써 정확도가 높지 않았다. 그래서 본 연구는 제2형 당뇨병 발생 예측에 대한 정확도를 높이기 위하여 RNN을 이용한 모델을 제안하였다. 본 모델을 개발하기 위해 한국인유전체역학조사 지역사회 코호트(안산 안성) 데이터를 이용하였으며, 시간의 흐름에 따른 데이터들을 모두 학습시켜 당뇨병 발생 예측모델을 만들었다. 예측 모델의 성능을 검증하기 위해 기존의 기계 학습 방법인 LR, k-NN, SVM과 정확도를 비교하였다. 비교한 결과 제안한 예측모델의 accuracy는 0.92, AUC는 0.92로 다른 기계 학습 방법보다 높은 정확도를 보였다. 따라서 본 연구에서 제안한 제2형 당뇨병 발생 예측 모델을 활용하여 발병을 조기 예측함으로써 생활습관 개선 및 혈당조절을 통해 당뇨병 발병을 예방하고 늦출 수 있을 것이다.

• 한국산림과학회지
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• 제101권4호
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• pp.640-647
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• 2012

잣나무(Pinus koraiensis) 4년생의 생장특성인자와 관련이 있는 주요 대사물질을 확인하기위한 대사체 분석을 실시하였다. GC/MS로 분리한 105종을 대상으로 길이생장 및 건중량의 생장 특성과의 상관이 있는 대사물질을 분석하였다. Alanine, threonine, oleic acid 및 butanoic acids는 길이생장 및 건중량과 고도의 부의 상관관계가 있었고, 반면 malic acid, xylose, glucose, inositol 및 sucrose는 생장특성과 정의 상관관계가 있었다. 생장이 왕성한 시기에는 생장이 우수한 그룹에서 주지의 아미노산류나 유기산류 함량이 줄어드는 것으로 추정되었으며, 반면 단당류나 sucrose 같은 광합성 산물은 중위 및 하위 그룹에 비교해서 함량이 높은 것으로 나타났다. 특이하게도 박테리아나 균류에서 생성되는 d-turanose의 함량이 4년생 잣나무 묘고생장과 고도의 상관관계(r=0.896, p<0.001)가 있었으며, 이는 근균류와의 관계가 있는 것으로 추정된다. 이러한 인자들은 잣나무 우량개체 선발을 위한 대사 표지자 개발의 기초자료로 이용될 수 있을 것이다.

• 대한예방한의학회지
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• 제21권2호
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• pp.1-13
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• 2017

Objectives : This paper serves to explore current trends of systems biology in Traditional Chinese Medicine (TCM) and examine how it may influence the Traditional Korean medicine. Methods : Literature review method was collectively used to classify Introduction to systems biology, diagnosis and syndrome classification of systems biology in TCM perspective, physiotherapy including acupuncture, herbs and formula functions, TCM systems biology, and directions of academic development. Results : The term 'Systems biology' is coined as a combination of systems science and biology. It is a field of study that tries to understand living organism by establishing a theory based on an ideal model that analyzes and predicts the desired output with understanding of interrelationships and dynamics between variables. Systems biology has an integrated and multi-dimensional nature that observes the interaction among the elements constructing the network. The current state of systems biology in TCM is categorized into 4 parts: diagnosis and syndrome, physical therapy, herbs and formulas and academic development of TCM systems biology and its technology. Diagnosis and syndrome field is focusing on developing TCM into personalized medicine by clarifying Kidney yin deficiency patterns and metabolic differences among five patterns of diabetes and analyzing plasma metabolism and biomarkers of coronary heart disease patients. In the field of physical therapy such as acupuncture and moxibustion, researchers discovered the effect of stimulating acupoint ST40 on gene expression and the effects of acupuncture on treating functional dyspepsia and acute ischemic stroke. Herbs and formulas were analyzed with TCM network pharmacology. The therapeutic mechanisms of Si Wu Tang and its series formulas are explained by identifying potential active substances, targets and mechanism of action, including metabolic pathways of amino acid and fatty acid. For the academic development of TCM systems biology and its technology, it is necessary to integrate massive database, integrate pharmacokinetics and pharmacodynamics, as well as systems biology. It is also essential to establish a platform to maximize herbal treatment through accumulation of research data and diseases-specific, or drug-specific network combined with clinical experiences, and identify functions and roles of molecules in herbs and conduct animal-based studies within TCM frame. So far, few literature reviews exist for systems biology in traditional Korean medicine and they merely re-examine known efficacies of simple substances, herbs and formulas. For the future, it is necessary to identify specific mechanisms of working agents and targets to maximize the effects of traditional medicine modalities. Conclusions : Systems biology is widely accepted and studied in TCM and already advanced into a field known as 'TCM systems biology', which calls for the study of incorporating TCM and systems biology. It is time for traditional Korean medicine to acknowledge the importance of systems biology and present scientific basis of traditional medicine and establish the principles of diagnosis, prevention and treatment of diseases. By doing so, traditional Korean medicine would be innovated and further developed into a personalized medicine.

• 대한장애인치과학회지
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• 제15권1호
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• pp.45-49
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• 2019

Bartter 증후군은 심각한 헨레고리 비후 상행각(TAL)에서의 일차적인 염류(NaCl) 수송 장애로 인하여 심각한 저칼륨혈증을 특징으로 하는 질환이다. 만성 구토로 인한 치아의 부식, 교모, 마모의 구강 내 소견을 보여 구토와 관련된 적절한 칫솔질 및 식이 습관 등에 대한 정기적인 교육과 관찰이 권장되며 교합고경의 회복을 위해 전장관 수복이 추천된다. 치과 치료 시의 스트레스로 인하여 전해질 수치의 불균형이 초래될 가능성이 있어 전신마취 하 치료가 유리할 수 있으며, 전신마취 시 과환기되어 저칼륨혈증이 심화되지 않도록 지속적인 감시를 해야하고 술 후에도 전해질 불균형이 초래되지 않도록 지속적인 감시가 필요하다.

• 생명과학회지
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• 제31권6호
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• pp.595-602
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• 2021

사람의 장내 미생물은 숙주의 대사 조절에서 중요한 역할을 한다. 장내 미생물 균총의 불균형은 비만, 대사 증후군과 밀접하게 병리학적, 생리학적 상호작용을 한다. A. muciniphila는 최근 인간의 대변에서 분리되었으며, 장내 미생물의 약 1-4%를 차지하는 우점균이다. A. muciniphila 유래 외막(external membran) 단백질 Amuc_1100과 세포외 소포(EVs)의 이용은 비만치료를 위한 새로운 전략이 될 수 있다. A. muciniphila는 비만과 같은 대사 장애치료를 위한 차세대 probiotics로 고려되고 있다. F. prausnitzii는 next-generation probiotic로서 건강한 성인의 경우 장내미생물 균총의 약 5%를 차지하며 성인 장 건강의 지표이다. F. prausnitzii는 butyrate-producing bacterium로서 항염증 효과를 나타내며, 면역 질환과 당뇨병 치료를 위한 next-generation probiotics로 기대된다. Postbiotics는 probiotics에 의해 분비되는 세포 상층액에 포함된 대사산물의 복잡한 혼합물이다. 반면, parabiotics는 probiotics를 불활성화 시킨 미생물 세포이다. Paraprobiotics와 postbiotics는 probiotics에 비해 명확한 화학구조(clear chemical structures)와 안전한 투여 용량(safety dose parameters), 장기간의 유통 기간(longer shelf life) 등 많은 장점을 가지고 있어서 probiotics를 대체할 수 있는 잠재력을 가지고 있다. 장 생태계의 불균형을 정상적으로 복원하기 위해서 장내 공생 박테리아(commensal bacteria) 중 next-generation probiotics (NGPs)를 사용하는 것이 가장 자연스런 방법이다. 따라서 next-generation probiotics 를 대상으로 parabiotics와 postbiotics와 같은 새로운 식품이나 약품으로 개발하는 것이 필요하다.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.53-61
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• 2022

This study aimed to increase the targeting ability against PSMA in cell therapy using metabolic glycoengineering and biorthogonal chemistry and to visualize cell trafficking using PET imaging. Cellular membranes of THP-1 cells were decorated with azide(-N₃) using Ac₄ManNAz by metabolic glycoengineering. Engineered THP-1 cells were conjugated with DBCO-bearing fluorophore (ADIBO-Cy5.5) for 1 h at different concentrations and analyzed by confocal fluorescence microscopy and flow cytometry. For PSAM ligand conjugation to THP-1 cells, Ac₄ManNAz treated THP-1 cells were incubated with DBCO-PSMA ligand (ADIBO-GUL) at a final concentration with 100 µM for 1 h. To evaluate the effect on cell recognition, PSMA ligand conjugated THP-1 cells(as effectors) were co-cultured with PSMA positive 22RV1 (as target cells) at 3 : 1 a effector-to-target cell (E/T) ratio. The interaction between THP-1 and 22RV1 was monitored by confocal fluorescence microscopy. For preparing the radiolabeled THP-1, the cells were treated at the activity of ~ 740 kBq of [⁸⁹Zr]Zr(oxinate)₄/5 × 10⁶ cells. Radiolabeled cells were analyzed for determination of cell-associated radioactivity by gamma counting and viability using MTS assay. In the cytotoxicity assay, THP-1 cells did not have any cytotoxicity even when the Ac₄ManNAz concentration was 100 µM. In confocal microscopy and flow cytometry, THP-1 cells were efficiently labeled ADIBO-Cy5.5 in a dose-dependent manner, and the dose of 100 µM was the optimal concentration for the following experiments. The clusters of PSMA ligand-conjugated THP-1 cells and 22RV1 cells were identified, indicating cell-cell recognition over the cell surface between two types of cells. Cell radiolabeling efficiency was 54.5 ± 17.8%. THP-1 labeled with 0.09 ± 0.03 Bq/cell showed no significant cytotoxicity compared to unlabeled THP-1 up to 7 days. We successfully demonstrated that Ac₄ManNAz treated cells were efficiently conjugated with ADIBO-GUL for preparing the PSMA-targeting cells, and [⁸⁹Zr]Zr(oxinate)₄ could be used to label cells without toxicity. It suggested that PSMA-ligand conjugated cell therapy could be improved cell targeting and be monitored by PET imaging.

• 대한한의학회지
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• 제44권2호
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• pp.106-118
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• 2023

Objectives: Network pharmacology is a method of constructing and analyzing a drug-compound-target network to predict potential efficacy and mechanisms related to drug targets. In that large-scale analysis can be performed in a short time, it is considered a suitable tool to explore the function and role of herbal medicine. Thus, we investigated the potential functions and pathways of Chongmyunggongjin-dan (CMGJD) on Alzheimer's disease (AD) via network pharmacology analysis. Methods: Using public databases and PubChem database, compounds of CMGJD and their target genes were collected. The putative target genes of CMGJD and known target genes of AD were compared and found the correlation. Then, the network was constructed using Cytoscape 3.9.1. and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results: The result showed that total 104 compounds and 1157 related genes were gathered from CMGJD. The network consisted of 1157nodes and 10034 edges. 859 genes were interacted with AD gene set, suggesting that the effects of CMGJD are closely related to AD. Target genes of CMGJD are considerably associated with various pathways including 'Positive regulation of chemokine production', 'Cellular response to toxic substance', 'Arachidonic acid metabolic process', 'PI3K-Akt signaling pathway', 'Metabolic pathways', 'IL-17 signaling pathway' and 'Neuroactive ligand-receptor interaction'. Conclusion: Through a network pharmacological method, CMGJD was predicted to have high relevance with AD by regulating inflammation. This study could be used as a basis for effects of CMGJD on AD.