• Title/Summary/Keyword: Co-expression Network

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Flaviviruses Induce Pro-inflammatory and Anti-inflammatory Cytokines from Murine Dendritic Cells through MyD88-dependent Pathway

  • Aleyas, Abi G.;George, Junu A.;Han, Young-Woo;Kim, Hye-Kyung;Kim, Seon-Ju;Yoon, Hyun-A;Eo, Seong-Kug
    • IMMUNE NETWORK
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    • v.7 no.2
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    • pp.66-74
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    • 2007
  • Background: The genus Flavivirus consists of many emerging arboviruses, including Dengue virus (DV), Japanese encephalitis virus (JEV) and West Nile virus (WNV). Effective preventive vaccines remain elusive for these diseases. Mice are being increasingly used as the animal model for vaccine studies. However, the pathogenic mechanisms of these viruses are not clearly understood. Here, we investigated the interaction of DV and JEV with murine bone marrow-derived dendritic cells (bmDC). Methods: ELISA and FACS analysis were employed to investigate cytokine production and phenotypic changes of DCs obtained from bone marrow following flavivirus infection. Results: We observed that these viruses altered the cytokine profile and phenotypic markers. Although both viruses belong to the same family, JEV-infected bmDC produced anti-inflammatory cytokine (IL-10) along with pro-inflammatory cytokines, whereas DV infection induced production of large amounts of pro-inflammatory cytokines (IL-6 and TNF-${\alpha}$) and no IL-10 from murine bmDCs. Both flaviviruses also up-regulated the expression of co-stimulatory molecules such as CD40, CD80 and CD86. JEV infection led to down-regulation of MHC II expression on infected bmDCs. We also found that cytokine production induced by JEV and DV is MyD88-dependent. This dependence was complete for DV, as cytokine production was completely abolished in the absence of MyD88. With regard to JEV, the absence of MyD88 led to a partial reduction in cytokine levels. Conclusion: Here, we demonstrate that MyD88 plays an important role in the pathogenesis of flaviviruses. Our study provides insight into the pathogenesis of JEV and DV in the murine model.

Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms

  • Hanna Lee;Ok-Yi Jeong;Hee Jin Park;Sung-Lim Lee;Eun-yeong Bok;Mingyo Kim;Young Sun Suh;Yun-Hong Cheon;Hyun-Ok Kim;Suhee Kim;Sung Hak Chun;Jung Min Park;Young Jin Lee;Sang-Il Lee
    • IMMUNE NETWORK
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    • v.23 no.6
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    • pp.45.1-45.22
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    • 2023
  • Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Research article Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

  • Lee, Soo-Yeon;Go, Ga-Yeon;Vuong, Tuan Anh;Kim, Jee Won;Lee, Sullim;Jo, Ayoung;An, Jun Min;Kim, Su-Nam;Seo, Dong-Wan;Kim, Jin-Seok;Kim, Yong Kee;Kang, Jong-Sun;Lee, Sang-Jin;Bae, Gyu-Un
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.116-121
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    • 2018
  • Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing hetero-dimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Endometrial profilin 1: A key player in embryo-endometrial crosstalk

  • Lee, Chang-Jin;Hong, Seon-Hwa;Yoon, Min-Ji;Lee, Kyung-Ah;Ko, Jung-Jae;Koo, Hwa Seon;Kim, Jee Hyun;Choi, Dong Hee;Kwon, Hwang;Kang, Youn-Jung
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.2
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    • pp.114-121
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    • 2020
  • Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation. Methods: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells. Results: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency. Conclusion: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells

  • Bae, Yoon-Kyung;Kim, Gee-Hye;Lee, Jae Cheoun;Seo, Byoung-Moo;Joo, Kyeung-Min;Lee, Gene;Nam, Hyun
    • Molecules and Cells
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    • v.40 no.6
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    • pp.386-392
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    • 2017
  • Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, ${\alpha}-smooth$ muscle actin, platelet-derived growth factor receptor ${\beta}$, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the $SDF-1{\alpha}$ and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.

In-silico annotation of the chemical composition of Tibetan tea and its mechanism on antioxidant and lipid-lowering in mice

  • Ning Wang ;Linman Li ;Puyu Zhang;Muhammad Aamer Mehmood ;Chaohua Lan;Tian Gan ;Zaixin Li ;Zhi Zhang ;Kewei Xu ;Shan Mo ;Gang Xia ;Tao Wu ;Hui Zhu
    • Nutrition Research and Practice
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    • v.17 no.4
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    • pp.682-697
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    • 2023
  • BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

  • Lijing Wang;Qiao Yu;Jian Xiao;Qiong Chen;Min Fang;Hongjun Zhao
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.3.1-3.23
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    • 2024
  • Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68+ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

A Study on the Factors Causing Analytical Errors through the Estimation of Uncertainty for Cadmium and Lead Analysis in Tomato Paste (불확도 추정을 통한 토마토 페이스트에서 카드뮴 및 납 분석의 오차 발생 요인 규명)

  • Kim, Ji-Young;Kim, Young-Jun;Yoo, Ji-Hyock;Lee, Ji-Ho;Kim, Min-Ji;Kang, Dae-Won;Im, Geon-Jae;Hong, Moo-Ki;Shin, Young-Jae;Kim, Won-Il
    • Korean Journal of Environmental Agriculture
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    • v.30 no.2
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    • pp.169-178
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    • 2011
  • BACKGROUND: This study aimed to estimate the measurement uncertainty associated with determination of cadmium and lead from tomato paste by ICP/MS. The sources of measurement uncertainty (i.e. sample weight, final volume, standard weight, purity, molecular weight, working standard solution, calibration curve, recovery and repeatability) in associated with the analysis of cadmium and lead were evaluated. METHODS AND RESULTS: The guide to the expression of uncertainty was used for the GUM (Guide to the expression of Uncertainty in Measurement) and Draft EURACHEM/CITAC (EURACHEM: A network of organization for analytical chemistry in Europe/Co-Operation on International Traceability in Analytical Chemistry) Guide with mathematical calculation and statistical analysis. The uncertainty components were evaluated by either Type A or Type B methods and the combined standard uncertainty were calculated by statistical analysis using several factors. Expected uncertainty of cadmium and lead was $0.106{\pm}0.015$ mg/kg (k=2.09) and $0.302{\pm}0.029$ mg/kg (k=2.16), on basis of 95% confidence of Certified Reference Material (CRM) which was within certification range of $0.112{\pm}0.007$ mg/kg for cadmium (k=2.03) and $0.316{\pm}0.021$ mg/kg for lead (k=2.01), respectively. CONCLUSION(s): The most influential components in the uncertainty of heavy metals analysis were confirmed as recovery, standard calibration curve and standard solution were identified as the most influential components causing uncertainty of heavy metal analysis. Therefore, more careful consideration is required in these steps to reduce uncertainty of heavy metals analysis in tomato paste.

Transcriptome Analysis of Longissimus Tissue in Fetal Growth Stages of Hanwoo (Korean Native Cattle) with Focus on Muscle Growth and Development (한우 태아기 6, 9개월령 등심 조직의 전사체 분석을 통한 근생성 및 지방생성 관여 유전자 발굴)

  • Jeong, Taejoon;Chung, Ki-Yong;Park, Woncheol;Son, Ju-Hwan;Park, Jong-Eun;Chai, Han-Ha;Kwon, Eung-Gi;Ahn, Jun-Sang;Park, Mi-Rim;Lee, Jiwoong;Lim, Dajeong
    • Journal of Life Science
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    • v.30 no.1
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    • pp.45-57
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    • 2020
  • The prenatal period in livestock animals is crucial for meat production because net increase in the number of muscle fibers is finished before birth. However, there is no study on the growth and development mechanism of muscles in Hanwoo during this period. Therefore, to find candidate genes involved in muscle growth and development during this period in Hanwoo, mRNA expression data of longissimus in Hanwoo at 6 and 9 months post-conceptional age (MPA) were analyzed. We independently identified differentially expressed genes (DEGs) using DESeq2 and edgeR which are R software packages, and considered the overlaps of the results as final-DEGs to use in downstream analysis. The DEGs were classified into several modules using WGCNA then the modules' functions were analyzed to identify modules which involved in myogenesis and adipogenesis. Finally, the hub genes which had the highest WGCNA module membership among the top 10% genes of the STRING network maximal clique centrality were identified. 913(6 MPA specific DEGs) and 233(9 MPA specific DEGs) DEGs were figured out, and these were classified into five and two modules, respectively. Two of the identified modules'(one was in 6, and another was in 9 MPA specific modules) functions was found to be related to myogenesis and adipogenesis. One of the hub genes belonging to the 6 MPA specific module was axin1 (AXIN1) which is known as an inhibitor of Wnt signaling pathway, another was succinate-CoA ligase ADP-forming beta subunit (SUCLA2) which is known as a crucial component of citrate cycle.

Selective Word Embedding for Sentence Classification by Considering Information Gain and Word Similarity (문장 분류를 위한 정보 이득 및 유사도에 따른 단어 제거와 선택적 단어 임베딩 방안)

  • Lee, Min Seok;Yang, Seok Woo;Lee, Hong Joo
    • Journal of Intelligence and Information Systems
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    • v.25 no.4
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    • pp.105-122
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    • 2019
  • Dimensionality reduction is one of the methods to handle big data in text mining. For dimensionality reduction, we should consider the density of data, which has a significant influence on the performance of sentence classification. It requires lots of computations for data of higher dimensions. Eventually, it can cause lots of computational cost and overfitting in the model. Thus, the dimension reduction process is necessary to improve the performance of the model. Diverse methods have been proposed from only lessening the noise of data like misspelling or informal text to including semantic and syntactic information. On top of it, the expression and selection of the text features have impacts on the performance of the classifier for sentence classification, which is one of the fields of Natural Language Processing. The common goal of dimension reduction is to find latent space that is representative of raw data from observation space. Existing methods utilize various algorithms for dimensionality reduction, such as feature extraction and feature selection. In addition to these algorithms, word embeddings, learning low-dimensional vector space representations of words, that can capture semantic and syntactic information from data are also utilized. For improving performance, recent studies have suggested methods that the word dictionary is modified according to the positive and negative score of pre-defined words. The basic idea of this study is that similar words have similar vector representations. Once the feature selection algorithm selects the words that are not important, we thought the words that are similar to the selected words also have no impacts on sentence classification. This study proposes two ways to achieve more accurate classification that conduct selective word elimination under specific regulations and construct word embedding based on Word2Vec embedding. To select words having low importance from the text, we use information gain algorithm to measure the importance and cosine similarity to search for similar words. First, we eliminate words that have comparatively low information gain values from the raw text and form word embedding. Second, we select words additionally that are similar to the words that have a low level of information gain values and make word embedding. In the end, these filtered text and word embedding apply to the deep learning models; Convolutional Neural Network and Attention-Based Bidirectional LSTM. This study uses customer reviews on Kindle in Amazon.com, IMDB, and Yelp as datasets, and classify each data using the deep learning models. The reviews got more than five helpful votes, and the ratio of helpful votes was over 70% classified as helpful reviews. Also, Yelp only shows the number of helpful votes. We extracted 100,000 reviews which got more than five helpful votes using a random sampling method among 750,000 reviews. The minimal preprocessing was executed to each dataset, such as removing numbers and special characters from text data. To evaluate the proposed methods, we compared the performances of Word2Vec and GloVe word embeddings, which used all the words. We showed that one of the proposed methods is better than the embeddings with all the words. By removing unimportant words, we can get better performance. However, if we removed too many words, it showed that the performance was lowered. For future research, it is required to consider diverse ways of preprocessing and the in-depth analysis for the co-occurrence of words to measure similarity values among words. Also, we only applied the proposed method with Word2Vec. Other embedding methods such as GloVe, fastText, ELMo can be applied with the proposed methods, and it is possible to identify the possible combinations between word embedding methods and elimination methods.