• Journal of Veterinary Science
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• 제21권1호
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• pp.15.1-15.11
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• 2020

The present study evaluated the anti-inflammatory effect of horse oil in 2, 4-dinitrochlorobenzene (DNCB)-treated BALB/c mice. After the application of DNCB, the mice showed atopic dermatitis symptoms, including severe erythema, hemorrhage, and erosion, whereas those symptoms were alleviated by treatment with horse oil. To explain the anti-dermatitis effect of horse oil, the gene expression levels in the healing process in dorsal skin were observed using a cDNA microarray. The cDNA microarray analysis revealed that the expression levels of 30 genes related to the inflammation, including Ccr1, Ccr2, Ccl20, Anxa1, and Hc genes, were up-regulated (higher than 2.0-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. In contrast, the gene expression levels of 28 genes related to inflammation, including chemokine genes Ccl5, Ccl7, Ccl8, Cxcl10, and Cxcl13 genes, were down-regulated (lower than 0.5-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. Overall, the results show that horse oil restores the expression levels of genes related to inflammation that were perturbed by DNCB treatment.

• 대한약침학회지
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• 제27권2호
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• pp.162-171
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• 2024

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

• Animal Bioscience
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• 제35권9호
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• pp.1340-1350
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• 2022

Objective: Luxi Black Head sheep (LBH) is the first crossbreed specialized for meat production and was developed by crossbreeding Black Head Dorper sheep (DP) and Small Tailed Han sheep (STH) in the farming areas of northern China. Research on the genomic variations and selection signatures of LBH caused by continuous artificial selection is of great significance for identifying the genetic mechanisms of important traits of sheep and for the continuous breeding of LBH. Methods: We explored the genetic relationships of LBH, DP, and several Mongolian sheep breeds by constructing phylogenetic tree, principal component analysis and linkage disequilibrium analysis. In addition, we analysed 29 whole genomes of sheep. The genome-wide selection signatures have been scanned with four methods: heterozygosity (H_P), fixation index (F_ST), cross-population extended haplotype homozygosity (XP-EHH) and the nucleotide diversity (𝜃_π) ratio. Results: The genetic relationships analysis showed that LBH appeared to be an independent cluster closer to DP. The candidate signatures of positive selection in sheep genome revealed candidate genes for developmental process (HoxA gene cluster, BCL2L11, TSHR), immunity (CXCL6, CXCL1, SKAP2, PTK6, MST1R), growth (PDGFD, FGF18, SRF, SOCS2), and reproduction (BCAS3, TRIM24, ASTL, FNDC3A). Moreover, two signalling pathways closely related to reproduction, the thyroid hormone signalling pathway and the oxytocin signalling pathway, were detected. Conclusion: The selective sweep analysis of LBH genome revealed candidate genes and signalling pathways associated with developmental process, immunity, growth, and reproduction. Our findings provide a valuable resource for sheep breeding and insight into the mechanisms of artificial selection.

• Genomics & Informatics
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• 제19권1호
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• pp.4.1-4.9
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• 2021

Lip and oral cavity cancer, which can occur in any part of the mouth, is the 11th most common type of cancer worldwide. The major obstacles to patients' survival are the poor prognosis, lack of specific biomarkers, and expensive therapeutic alternatives. This study aimed to identify the main genes and pathways associated with lip and oral cavity carcinoma using network analysis and to analyze its molecular mechanism and prognostic significance further. In this study, 472 genes causing lip and oral cavity carcinoma were retrieved from the DisGeNET database. A protein-protein interaction network was developed for network analysis using the STRING database. VEGFA, IL6, MAPK3, INS, TNF, MAPK8, MMP9, CXCL8, EGF, and PTGS2 were recognized as network hub genes using the maximum clique centrality algorithm available in cytoHubba, and nine potential drug candidates (ranibizumab, siltuximab, sulindac, pomalidomide, dexrazoxane, endostatin, pamidronic acid, cetuximab, and apricoxib) for lip and oral cavity cancer were identified from the DGIdb database. Gene enrichment analysis was also performed to identify the gene ontology categorization of cellular components, biological processes, molecular functions, and biological pathways. The genes identified in this study could furnish a new understanding of the underlying molecular mechanisms of carcinogenesis and provide more reliable biomarkers for early diagnosis, prognostication, and treatment of lip and oral cavity cancer.

• 대한한의학회지
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• 제39권4호
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• pp.126-135
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• 2018

Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and irreversible airflow. This study aimed to evaluate the effects of GHX02 in a COPD-induced mouse model. Methods: The COPD mouse model was established by exposure to cigarette smoke extract and lipopolysaccharide which were administered by intratracheal injection three times with a 7 day interval. GHX02 (100, 200, 400 mg/kg) and all other drugs were orally administrated for 14 days from Day 7 to Day 21. Results: GHX02 significantly decreased the neutrophil counts in bronchoalveolar lavage fluid (BALF) and the number of $CD4^+$, $CD8^+$, $CD69^+$, and $CD11b^+/GR1^+$ cells in BALF and lung cells. GHX02 also suppressed the secretion of tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-17A, macrophage inflammatory protein 2 (MIP2), and chemokine (C-X-C motif) ligand 1 (CXCL-1) in BALF and ameliorated the lung pathological changes. Conclusions: Thus, GHX02 effectively inhibited airway inflammation by inhibiting migration of inflammatory cells and expression of pro-inflammatory cytokines. Therefore, GHX02 may be a promising therapeutic agent for COPD.

• 혜화의학회지
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• 제27권2호
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• pp.11-20
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• 2018

Objectives : Coronary and cerebrovascular disease with high mortality is a major factor in arteriosclerosis. Pro-inflammatory cytokines damage vascular endothelial cells, leading to vascular inflammation. These vascular inflammation can build up cholesterol and thrombus to cause atherosclerosis. Methods : In this study, we researched the effect of ChungHyul-Plus for vascular inflammation in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Change in mRNA expression of inflammatory cytokines (CCL5, CXCL8, CX3CL1, and MCP-1), cell adhesion molecules (VCAM-1 and ICAM-1), and anti-inflammation modulators (KLF2 and eNOS) were quantified by qRT-PCR. Results : ChungHyul-Plus decreased expression of inflammatory cytokines and cell adhesion molecules and increased anti-inflammation modulators expression in $TNF-{\alpha}$ stimulated HUVECs. Conclusions : These results suggest that ChungHyul-Plus can be used in the treatment and prevention of vascular inflammation and arteriosclerosis.

• IMMUNE NETWORK
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• 제13권6호
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• pp.240-248
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• 2013

In this study, we compared the immune cell populations in rheumatoid arthritis (RA) synovial fluid, which shows lymphoid tissue-like structure, with those in tonsils, which are normal secondary lymphoid tissues. Firstly, we found that $CD4^-CD11b^+$ macrophages were the major population in RA synovial fluid and that B cells were the major population in tonsils. In addition, synovial fluid from patients with osteoarthritis, which is a degenerative joint disease, contained $CD4^+CD11b^+$monocytes as the major immune cell population. Secondly, we categorized three groups based on the proportion of macrophages found in RA synovial fluid: (1) the macrophage-high group, which contained more than 80% macrophages; (2) the macrophage-intermediate group, which contained between 40% and 80% macrophages; and (3) the macrophage-low group, which contained less than 40% macrophages. In the macrophage-low group, more lymphoid tissue inducer (LTi)-like cells were detected, and the expression of OX40L and TRANCE in these cells was higher than that in the other groups. In addition, in this group, the suppressive function of regulatory T cells was downregulated. Finally, CXCL13 expression was higher in RA synovial fluid than in tonsils, but CCL21 expression was comparable in synovial fluid from all groups and in tonsils. These data demonstrate that increased lymphocyte infiltration in RA synovial fluid is correlated with an increase in LTi-like cells and the elevation of the chemokine expression.

• Molecules and Cells
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• 제43권11호
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• pp.921-934
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• 2020

Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME^-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME^-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME^-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

• Parasites, Hosts and Diseases
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• 제51권5호
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• pp.583-588
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• 2013

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-${\alpha}$) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

• 한국약용작물학회지
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• 제27권3호
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• pp.218-231
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• 2019

Background: We recently reported that Salvia plebeia R. Br. extracts suppress leukotriene production and effectively inhibit the airway inflammatory response by modulating inflammatory chemokine and cytokine expression. Here, we investigated the synergistic airway anti-inflammation effect of Salvia plebeia and Panax ginseng (Korean red ginseng, KRG) that has been used to treat various immune diseases such as asthma. Methods and Results: To evaluate the synergistic airway anti-inflammatory effect of Salvia plebeia and KRG, we measured the inhibitory effect of monotheraphy with either or co-theraphy with both on leukotriene and reactive oxygen species (ROS) production. Using coal a combustion, fly ash, and diesel exhaust particle (CFD)-induced respiratory disease mouse model, we found that co-theraphy synergistically suppressed airway inflammatory signs such as alveolar wall thickness and collagen fibers deposition, and decreased the number of total cell, $CD11b^+Gr-1^+$ cells, and inflammatory cytokines (IL17A, TNF, MIP-2 and CXCL-1) in bronchoalveolar lavage (BAL) fluid. Conclusions: We confirmed respiratory protection as a therapeutic effect of the Salbia plebeia-KRG 3 : 1 complex (KGC-03-PS) via anti-tracheal muscle contraction and expectorant animal studies using a CFD-induced respiratory disease mouse model.