• Clinical and Experimental Reproductive Medicine
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• v.34 no.4
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• pp.239-252
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• 2007

Objectives: In the present study, we examined the differentiation potential of human adipose-(HAD) and human umbilical cord-derived mesenchymal like stem cells (HUC) into cardiomyocytes. Methods: Cells were initially exposed to 5-azacytidine for 24h cells and then were cultivated in the presence or absence of activin A, TGF-$\beta$1, or Wnt inhibitor with various combinations of BMP and FGF. Assessment of cardiomyogenic differentiation was made upon the expression of cardiomyocyte-specific genes using RT-PCR. Results: HAD that cultivated in control medium for 4 weeks after 5-azacytidine expose showed new expression of TnT gene and increased expression of Cmlc1 and kv4.3 genes. However, HAD cultivated in the presence of combinations of BMP-4/FGF-4 (B4/F4) and BMP-4/FGF-8 (B4/F8) showed new expression of $\beta$-MHC gene and more increased expression of Cmlc1, TnT, TnI, Kv4.3 genes. Significantly enhanced expression of Cmlc1, TnT, and Kv4.3 genes were also observed compared to that cultivated in the control medium. Treatment of HUC with either 5-azacytidine or combinations of BMP and FGF did not affect the expression profile of these genes. However, when activin A or TGF-$\beta$1 was present in addition to the BMP-2/FGF-8 (B2/F8) after 5-azacytidine exposure, HUC exhibited new expression of $\beta$-MHC gene and increased expression of $\alpha$-CA, TnT and Kv4.3 genes. When Wnt inhibitor was present in addition to BMP and FGF, HUC showed new expression of Cmlc1 gene and increased expression of $\alpha$-CA, TnT, TnI and Kv4.3 genes. Conclusions: Based on these observations, it is suggested that HAD and HUC could differentiate into cardiomyocytes which might be used as therapeutic cells for the heart diseases.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.207-216
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• 2010

Objective: This study was performed to clarify the role of HomeoboxA (HOXA) and its related signaling molecules in the decidualization of primary cultured endometrial cells. Methods: Human endometrial tissues were obtained by curettage of hysterectomy specimens from patients with conditions other than endometrial diseases. Tissues were minced and digested with Trypsin-EDTA for 20 min, $37^{\circ}C$. Cells were cultured with DMEM/F12 medium in $37^{\circ}C$, 5% $CO_2$ incubator for 24 hrs. Cells were treated with HOXA10 siRNA and added transforming growth factor (TGF)-${\beta}1$ (10 ng/mL) for 48 hrs to induces decidualization in vitro. Reverse transcription polymerase chain reaction analysis was accomplished to observe the expression of HOXA10, prolactin, cyclooxygenase (COX)-2, peroxisome proliferatoractivated receptor (PPAR)-$\gamma$, and wingless-type MMTV integration site family (Wnt). Results: HOXA10 expression was increased (1.8 fold vs. non-treated control) in TGF-${\beta}1$ treated cells. Decidualization marker, prolactin, was significantly increased in TGF-${\beta}1$ treated cells compared with HOXA10 siRNA treated cells. Endometrial cell differentiation marker, COX-2 was down-regulated by HOXA10 siRNA even if cells were treated with TGF-${\beta}1$. Wnt4 was down-regulated by treated with HOXA10 siRNA, this expression patters was not changed by TGF-${\beta}1$. Expression of PPAR-$\gamma$ was down regulated by TGF-${\beta}1$ in regardless of HOXA10 siRNA treatment. Conclusion: TGF-${\beta}1$ which is induced by progesterone in endometrial epithelial cells may induces stromal cell decidualization via HOXA10 and Wnt signaling cascade.

• Natural Product Sciences
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• v.21 no.1
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• pp.25-29
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• 2015

In a continuation of our studies to discover bioactive secondary metabolites from marine sources, we further investigated samples from a tryptamine and phenyl-alkane producing sponge, which resulted in the isolation of four uncommon small molecules and five nucleosides. Their structures were determined to be 7,8-dihydroimidazo[1,5-c]pyrimidin-5(6H)-one (1), 5-chlorocavernicolin (2), maleimide-5-oxime (3), 3-methylmaleimide-5-oxime (4), uridine (5), 2'-deoxyuridine (6), thymidine (7), adenine (8), and adenosine (9) by spectroscopic analyses. The isolated compounds were evaluated for inhibitory activity against soluble epoxide hydrolase (sEH) as well as the Wnt/${\beta}$-catenine signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5501-5508
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• 2014

Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/${\beta}$-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.

• Nutritional Sciences
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• v.8 no.1
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• pp.23-27
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• 2005

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

• Korean Journal of Pharmacognosy
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• v.44 no.4
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• pp.384-390
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• 2013

This study was conducted to evaluate the effect of wheat bran on the promotion of hair growth. When rat vibrissa follicles were treated with n-hexane fraction of wheat bran, the hair-fiber lengths of the vibrissa follicles significantly increased. Moreover, n-hexane fraction of wheat bran was found to significantly induce the telogen-anagen transition in C57BL/6 mice. The fraction increased the proliferation of immortalized vibrissa dermal papilla cells (DPCs) in a dose dependent manner. To elucidate the molecular mechanisms in relation to proliferation of DPCs by the fraction of wheat bran, we examined the expression of cell cycle proteins and wnt/${\beta}$-catenin signaling components. Western blot analysis revealed that the proliferation of DPC by n-hexane fraction of wheat bran was accompanied by increased the level of cyclin D1, cyclin E, phospho-CDK2 and phospho-pRB. In addition, the fraction of wheat bran increased the level of phospho(ser552)-${\beta}$-catenin, phospho(ser675)-${\beta}$-catenin and phospho(ser9)-GSK$3{\beta}$. These results suggest that the hair growing potential of wheat bran mediated by proliferation of DPCs via the regulation of cell cycle proteins and Wnt/${\beta}$-catenin signaling.

• Toxicological Research
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• v.26 no.4
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• pp.245-252
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• 2010

Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF)-$\beta$, Wnt, and Notch signaling pathways, have been shown to induce EMT. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Mounting evidence shows that EMT is associated with cell invasion and tumor progression. In this review, we summarize the characteristic features of EMT, pathways leading to EMT, and the role of EMT in cell invasion. Three topics are addressed in this review: (1) Definition of EMT, (2) Signaling pathways leading to EMT, (3) Role of EMT in cell invasion. Understanding the role of EMT in cell invasion will provide valuable information for establishing strategies to develop anti-metastatic therapeutics which modulate malignant cellular processes mediated by EMT.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.933-941
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• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• Journal of Plant Biotechnology
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• v.48 no.2
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• pp.106-114
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• 2021

We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

• Reproductive and Developmental Biology
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• v.30 no.2
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• pp.143-156
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• 2006

Major characteristics of embryonic stem cells (ESCs) are sustaining of sternness and pluripotency by self-renewal. In this report, transcriptional profiles of the molecules in the developmentally important signaling pathways including Wnt, BMP4, $TGF-\beta$, RTK, Hh, Notch, and JAK/STAT signaling pathways were investigated to understand the self-renewal of mouse ESCs (mESCs), J1 line, and compared with the NIH3T3 cell line and mouse embryonic fibroblast (MEF) cells as controls. In the Wnt signaling pathway, the expression of Wnt3 was seen widely in mESCs, suggesting that the ligand may be an important regulator for self-renewal in mESCs. In the Hh signaling pathway, the expression of Gli and N-myc were observed extensively in mESCs, whereas the expression levels of in a Shh was low, suggesting that intracellular molecules may be essential for the self-renewal of mESCs. IGF-I, IGF-II, IGF-IR and IGF-IIR of RTK signaling showed a lower expression in mESCs, these molecules related to embryo development may be restrained in mESCs. The expression levels of the Delta and HESS in Notch signaling were enriched in mESCs. The expression of the molecules related to BMP and JAK-STAT signaling pathways were similar or at a slightly lower level in mESCs compared to those in MEF and NIH3T3 cells. It is suggested that the observed differences in gene expression profiles among the signaling pathways may contribute to the self-renewal and differentiation of mESCs in a signaling-specific manner.