• BMB Reports
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• v.53 no.11
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7547-7552
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• 2014

The mir-155 family is not only involved in a diversity of cancers, but also as a regulator of the immune system. However, the evolutionary history of this family is still unclear. The present study indicates that mir-155 evolved independently with lineage-specific gain of miRNAs. In addition, arm switching has occurred in the mir-155 family, and alternative splicing could produce two different lengths of ancestral sequences, implying the alternative splicing can also drive evolution for intragenic miRNAs. Here we screened validated target genes and immunity-related proteins, followed by analyzation of the mir-155 family function by high-throughput methods like the gene ontology (GO) and Kyoto Eneyclopedin of Genes and Genemes (KEGG) pathway enrichment analysis. The high-throughput analysis showed that the CCND1 and EGFR genes were outstanding in being significantly enriched, and the target genes cebpb and VCAM1 and the protein SMAD2 were also vital in mir-155-related immune reponse activities. Therefore, we conclude that the mir-155 family is highly conserved in evolution, and CCND1 and EGFR genes might be potential targets of mir-155 with regard to progress of cancers, while the cebpb and VCAM1 genes and the protein SMAD2 might be key factors in the mir-155 regulated immune activities.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4621-4625
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• 2013

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

• The Journal of Korean Medicine
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• v.22 no.3
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• pp.141-155
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• 2001

Objective : The aim of this study is to investigate the effect of Injin fractions on hepatic fibrosis induced by $TGF-{\beta}1$. Method : $TGF-{\beta}1$ mRNA, protein, $TGF-{\beta}1$ receptor, Smad family and PAI-I mRNA were studied in HepG2 cell, and the proliferation, connective tissue growth factor, fibronectin and collagen type I mRNA in T3891 fibroblast by quantitative RT-PCR, ELISA and thymidine incorporation assay. Results : On $TGF-{\beta}1$ mRNA and protein synthesis in HepG2, $H_2O$, butanol and hexane fractions of Injin showed inhibitory effect in a dose-dependent way. In the study on $TGF-{\beta}1$ receptor, Smad family and PAI-1 mRNA in HepG2, $H_2O$, butanol and hexane fraction of Injin showed inhibitory effect on the expression of PAI-1 in a dose-dependent way. On the proliferation of T3891 fibroblast induced by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect. In the study on the factors affected by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect on CTGF, and $H_2O$, butanol, chloroform and hexane fractions showed inhibitory effect on the expression of collagen type I, whereas no fraction showed inhibitory effect on the expression of fibronectin Conclusion : These results show that each fraction of Injin acts as a fibrosis inhibitory factor by itself or in combination, ultimately inhibiting liver cirrhosis.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.243-257
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• 2008

Myostatin, a negative regulator of myogenesis, is shown to function by controlling the proliferation of myoblasts. In this study we show that myostatin is an inhibitor of myoblast differentiation and that this inhibition is mediated through Smad 3. To determine MyoD expression by Dodamtang treatment, we compared the expression pattern of $C_{2}C_{12}$ mouse myoblasts that constitutively express myostatin with control cells. In vitro, increasing concentrations of Dodamtang reversibly prevented the myogenic blockage of myoblasts by myostatin expression. ELISA assay, Western and confocal analysis indicated that treatment of Dodamtang to the low serum culture media increased the levels of MyoD leading to the inhibition of myogenic differentiation by myostatin. The stable transfection of $C_{2}C_{12}$ myoblasts with myostatin expressing constructs did rescue MyoD-induced myogenic differentiation. Consistent with this, the treatment of Dodamtang rescued the expression of a MyoD in $C_{2}C_{12}$ myoblasts treated with myostatin. Taken together, these results suggest that induction of MyoD by Dodamtang inhibits myostatin activity and expression via SMAD3 resulting in the rescue of the myoblasts to differentiate into myotubes. Thus we propose that myostatin action by Dodamtang plays a critical role in myogenic differentiation and that the muscular hyperplasia and hypertrophy seen in animals that blockage of functional myostatin is because of deregulated proliferation and differentiation of myoblasts.

• Development and Reproduction
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• v.24 no.2
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• pp.135-147
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• 2020

Polyvinylidene fluoride (PVDF) is a stable and biocompatible material that has been broadly used in biomedical applications. Due to its piezoelectric property, the electrospun nanofiber of PVDF has been used to culture electroactive cells, such as osteocytes and cardiomyocytes. Here, taking advantage of the piezoelectric property of PVDF, we have fabricated a PVDF nanofiber scaffolds using an electrospinning technique for differentiating human embryonic stem cells (hESCs) into neural precursors (NPs). Surface coating with a peptide derived from vitronectin enables hESCs to firmly adhere onto the nanofiber scaffolds and differentiate into NPs under dual-SMAD inhibition. Our nanofiber scaffolds supported the differentiation of hESCs into SOX1-positive NPs more significantly than Matrigel. The NPs generated on the nanofiber scaffolds could give rise to neurons, astrocytes, and oligodendrocyte precursors. Furthermore, comparative transcriptome analysis revealed the variable expressions of 27 genes in the nanofiber scaffold groups, several of which are highly related to the biological processes required for neural differentiation. These results suggest that a PVDF nanofiber scaffold coated with a vitronectin peptide can serve as a highly efficient and defined culture platform for the neural differentiation of hESCs.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.49 no.6
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• pp.807-814
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• 2016

Fucoidan, one of the dominant sulfated polysaccharides extracted from brown seaweed, possesses a wide range of biological activities. Transforming growth $factor-{\beta}$ ($TGF-{\beta}$) plays a pivotal role in the pathogenesis of pulmonary fibrosis, by stimulating the synthesis of profibrotic factors. In this study, we investigated the in vitro effects of fucoidan on collagen synthesis, ${\alpha}-smooth$ muscle actin (${\alpha}-SMA$) expression, and interleukin (IL)-6 production in $TGF-{\beta}$-stimulated human pulmonary fibroblasts. The expression of type I collagen and ${\alpha}-SMA$ was detected by Western blot, and the production of IL-6 by enzyme-linked immunosorbent assay. $TGF-{\beta}1$ treatment of pulmonary fibroblasts enhanced the expression of ${\alpha}-SMA$, type I collagen, and IL-6 whereas these effects were inhibited in cells pretreated with fucoidan. The activation of Smad2/3, p38 mitogen-activated protein kinases (MAPKs), and Akt was also inhibited in fucoidan-pretreated, $TGF-{\beta}1-stimulated$ human pulmonary fibroblasts. These data demonstrate the anti-fibrotic potential of fucoidan in $TGF-{\beta}-induced$ human pulmonary fibroblasts, via the inhibition of Smad2/3, p38 MAPKs, and Akt phosphorylation. Our results suggest the therapeutic potential of fucoidan in the prevention or treatment of pulmonary fibrosis.

• Journal of Medicine and Life Science
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• v.16 no.3
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• pp.84-89
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• 2019

Docosahexaenoic acid (DHA), a principal of mackerel-derived fermented fish oil, increases the proliferation of dermal papilla cells (DPCs) via the upregulation of cell cycle-associated proteins such as cyclin D1 and cdc2 p34, and might promote hair-growth. However, the intracellular mechanisms that underlie the action of DHA in the proliferation of DPCs have not been investigated fully. In this study, we addressed the action mechanisms of DHA to trigger the activation of anagen in DPCs. DHA activated β-catenin signaling by the increased phosphorylation at serine 552 and serine 675 as well as the translocation and accumulation of activated β-catenin into the nucleus. In the other hand, DHA inhibited canonical TGF-β/Smad signaling by the decreased phosphorylation of Smad2/3. Taken together, the results indicate that DHA might stimulate anagen signaling via the activation of Wnt/β-catenin pathway, while the inactivation of canonical TGF-β signaling pathway in DPCs.

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.148-154
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• 2017

Crinum asiaticum var. japonicum and its active component, norgalanthamine have been reported to have hair growth-promoting effect via the proliferation of dermal papilla cells. In this study, we investigated the other mechanisms of C. asiaticum extract var. japonicum and norgalanthamine on the hair growth. The C. asiaticum var. japonicum extract inhibited $5{\alpha}$-reductase activity by 16%, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia, whereas the C. asiaticum var. japonicum extract didn't function as an opener of the $K_{ATP}$ channel. On the other hand, we examined whether norgalanthamine can inhibit transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway, which is essential in the regression induction of hair growth. Norgalanthamine inhibited the phosphorylation of Smad2/3 on TGF-${\beta}1$-induced canonical pathway in human keratinocyte HaCaT cells. These results suggested that the C. asiaticum var. japonicum extract and norgalanthamine had the potential to influence hair growth through the inhibition of $5{\alpha}$-reductase activity and TGF-${\beta}1$-induced canonical pathway.

• Journal of Preventive Medicine and Public Health
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• v.45 no.4
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• pp.251-258
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• 2012

Objectives: The purpose of this paper was to elucidate the potential methylation levels of adjacent normal and cancer tissues by comparing them with normal colorectal tissues, and to describe the correlations between the methylation and clinical parameters in Korean colorectal cancer (CRC) patients. Methods: Hypermethylation profiles of nine genes (RASSF1, APC, $p16^{INK4a}$, Twist1, E-cadherin, TIMP3, Smad4, COX2, and ABCB1) were examined with 100 sets of cancer tissues and 14 normal colorectal tissues. We determined the hypermethylation at a given level by a percent of methylation ratio value of 10 using quantitative methylation real-time polymerase chain reaction. Results: Nine genes' hypermethylation levels in Korean CRC patient tissues were increased more higher than normal colorectal tissues. However, the amounts of $p16^{INK4a}$ and E-cadherin gene hypermethylation in normal and CRC tissues were not significantly different nor did TIMP3 gene hypermethylation in adjacent normal and cancer tissues differ significantly. The hypermethylation of TIMP3, Ecadherin, ABCB1, and COX2 genes among other genes were abundantly found in normal colorectal tissues. The hypermethylation of nine genes' methylation in cancer tissues was not significantly associated with any clinical parameters. In Cohen's kappa test, it was moderately observed that RASSF1 was related with E-cadherin, and Smad4 with ABCB1 and COX2. Conclusions: This study provides evidence for different hypermethylation patterns of cancer-associated genes in normal and CRC tissues, which may serve as useful information on CRC cancer progression.