• Journal of Ginseng Research
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• v.47 no.4
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• pp.534-542
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• 2023

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

• Implantology
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• v.18 no.2
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• pp.120-138
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• 2014

Purpose: The purpose of this study was to review the outcomes of a series of studies on tissue regeneration conducted in multiple institutions including the Department of Periodontology, College of Dentistry, Yonsei University. Materials and Methods: Studies were performed divided into the following three subjects; 1) Development of three-dimensional nano-hydroxyapatite (n-HA) scaffold for facilitating drug release and cell adhesion. 2) Synergistic effects of bone marrow-derived mesenchymal stem cells (BMMSC) application simultaneously with platelet-rich plasma (PRP) on HA scaffolds. 3) The efficacy of silk scaffolds coated with n-HA. Also, all results were analyzed by subjects. Results: Hollow hydroxyapatite spherical granules were found to be a useful tool for the drug release and avidin-biotin binding system for cell attachment. Also, BMMSC simultaneously with PRP applied in an animal bone defect model was seen to be more synergistic than in the control group. But, the efficacy of periodontal ligament cells and dental pulp cells with silk scaffolds could not be confirmed in the initial phase of bone healing. Conclusion: The ideal combination of three elements of tissue engineering-scaffolds, cells and signaling molecules could be substantiated due to further investigations with the potentials and limitations of the suggested list of studies.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.123-135
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• 2024

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G₀/G₁ phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

• Journal of Nutrition and Health
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• v.57 no.2
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• pp.171-184
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• 2024

Purpose: Although activating thermogenic adipocytes is a promising strategy to reduce the risk of obesity and related metabolic disorders, emerging evidence suggests that it is difficult to induce adipocyte thermogenesis in obesity. Therefore, this study aimed to investigate the regulation of adipocyte thermogenesis in diet-induced obesity. Methods: Adipose progenitor cells were isolated from the white and brown adipose tissues of control diet (CD) or high-fat diet (HFD) fed mice, and fully differentiated white and brown adipocytes were treated with β-agonists or 18-carbon fatty acids for β-adrenergic activation or peroxisome proliferator-activated receptor (PPAR) activation. Results: Compared to the CD-fed mice, the expression of uncoupling protein 1 (Ucp1) was lower in the white adipose tissue of the HFD-fed mice; however, this was not observed in the brown adipose tissue. The expression of peroxisome proliferator-activated receptor gamma (Pparg) was lower in the brown adipose progenitor cells isolated from HFD-fed mice than in those isolated from the CD-fed mice. Norepinephrine (NE) treatment exerted lesser effect on peroxisome proliferator-activated receptor-γ coactivator (Pgc1a) upregulation in white adipocytes derived from HFD-fed mice than those derived from CD-fed mice. Regardless which 18-carbon fatty acids were treated, the expression levels of thermogenic genes including Ucp1, Pgc1a, and positive regulatory domain zinc finger region protein 16 (Prdm16) were higher in the white adipocytes derived from HFD-fed mice. Oleic acid (OLA) and γ-linolenic acid (GLA) upregulated Pgc1a expression in white adipocytes derived from HFD-fed mice. Brown adipocytes derived from HFD-fed mice had higher expression levels of Pgc1a and Prdm16 compared to their counterparts. Conclusion: These results indicate that diet-induced obesity may downregulate brown adipogenesis and NE-induced thermogenesis in white adipocytes. Also, HFD feeding may induce thermogenic gene expression in white and brown primary adipocytes, and OLA and GLA could augment the expression levels.

• Journal of the Korean Society of Radiology
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• v.83 no.6
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• pp.1385-1393
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• 2022

Metaplastic carcinoma of the breast is a heterogeneous group of neoplasms with mixed epithelial and mesenchymal differentiation. Metaplastic carcinoma of the breast is a rare and aggressive malignancy, with high recurrence and metastasis. Metaplastic carcinoma with chondroid differentiation is an uncommon subtype that tends to have a relatively good prognosis than that of other subtypes. We report the imaging features of three cases of pathologically proven metaplastic carcinoma with chondroid differentiation as follows: a high-density mass with amorphous or coarse heterogeneous calcifications on mammography; a microlobulated or partially indistinct, complex cystic, and solid mass on sonography; and a relatively circumscribed or partially indistinct, irregular mass with heterogeneous T2 high-signal intensity and heterogeneous or rim enhancement with initial fast enhancement and delayed washout on MRI.

• Development and Reproduction
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• v.12 no.3
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• pp.221-229
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• 2008

For the clinical application, it is needed to keep characteristics of stem cells after storage for a long time. In the present study, we examined stem cell properties of human cord-derived stem cells (HUC) after cryopreservation. Cells were isolated from human umbilical cord and cultured in vitro. At passage 2 or 3, HUC were suspended at a concentration of $1.0{\times}10^6/m{\ell}$ in cryomedium consisting of DMSO and FBS. After freezing at $-80^{\circ}C$ overnight, HUC were cryopreserved at $-196^{\circ}C$ nitrogen gas. After 6 months, HUC were thawed and cultured in vitro. Assessment for the stem cell properties was made upon the morphology, population doubling time, and expression profiles of genes and various proteins. Cryopreserved HUC showed more than 70% viability and maintained fibroblast-like morphology similar to HUC before cryopreservation. Throughout the culture, they underwent average 42.8 doublings and produced $6.75{\times}{10^{18}}$ cells. RT-PCR analyses showed that cryopreserved HUC expressed Oct-4, nanog, SCF, NCAM, nestin, GATA-4, BMP4, and HLA-1 genes. They did not express Brachyury and HLA-DR genes. Immunocytochemical studies showed that cryopreserved HUC reacted with antibodies against SSEA-3, -4, Thy-1, vimentin, fibronectin, HCAM, ICAM, HLA-1 proteins. They did not react with antibody against HLA-DR protein. Theses genes and proteins expression patterns of cryopresserved HUC were similar to those of HUC before cryopreservation. These results suggest that cryopreserved HUC could retain proliferative potential and they expressed various genes and proteins similar to HUC before cryopreservation. Thus, cryopreservation might be useful for HUC for future research and clinical application.

• The korean journal of orthodontics
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• v.28 no.1 s.66
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• pp.1-15
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• 1998

Adult wound healing is accompanied with inflammation and eventual scar formation, whereas fetal wounds heal rapidly by mesenchymal proliferation without significant inflammatory cell participation and with minimal or no scar formation. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellualr matrix through its effects on cell function, may play a key role. Therefore the purpose of this study is to investigate the spatial and temporal deposition of several component of extracellular matrix, which are known to be involved with scar formation, in the artificially created cleft lip wound healing of fetuses. The author had undergone hysterotomy and created cleft lip-like defects on fetuses of New Zealand White Rabbit in mid-third trimester(24 days). Fetuses were divided into the repaired group, the unrepaired group and the sham-operated control group. At 1, 2, 3, 5, 7 days after procedure, fetuses were obtained by Caeserem section. After documenting the viability of fetuses, they were photographed to compare size and facial morphology and sectioned for histological examination by H & E stain and spatial and temporal deposition of collagen typeI, III, IV, V and fibronectit laminin by immunohistochemical method. The findings are summarized as follows 1. There were lack of inflammation in the repaired and the unrepaired group during experimental periods. 2. The reepithelialization of the unrepaired group was slower than that of the repaired group. 3. Collagen I, III, V were found from post-op. third day. There were no difference of distribution in the control, the repaired and the unrepaired group. Collagen types I, III, V were present in all groups with restoration of the normal collagen pattern in the fetus. This implies that lack of scarring in fetal wounds is due to the difference of collagen organization pattern within wound and not simply lack of collagen formation. 4. Collagen IV was slightly increased at post-op. third day and decreased after post-op. fifth day. Eventually there were no differences in the control, the repaired and the unrepaired group. Lminin was found at post-op. fifth day and maintained staining density until post-op. seventh day. There were no differences in the control, the repaired and the unrepaired group. According to staining of laminin and collagen type IV in epithelial basement membrane, formation of epithelial basement membrane was not completed until reepithelialization was finished. 5. According to staining of laminin and collagen type IV, there were no increase of neovascularity in the repaired and the unrepaired group. 6. Fibronectin was increased until post-op. third day at fibrin clot, wound base and margin and decreased after post-op. fifth day. Eventually, there were no differences in the control, the repaired and the unrepaired group. So it implies fibronectin plays a role as provisional matrix for fetal wound healing.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.1
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• pp.1-17
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• 1997

The purpose of this study was to investigate the aspects of proliferation and bone nodule formation of osteogenic precursor cells. To determine the effects of ascorbic acid and dexamethasone upon capacity of osteoblast proliferation and bone nodule formation, cells were maintained in the presence of one or some of these additives for up to 30 days. Group I culture was maintained in standard medium(DMEM plus 10% plus antibiotics), group II was maintained in supplemented medium containing dexamethasone, group III was maintained in supplemented medium containing ascorbic acid and sodium-${\beta}$-glycerophosphate, and group IV was maintained in supplemented containing ascorbic acid, sodium-${\beta}$-glycerophosphate and dexamethasone. Morphology of bone nodules was observed with light microscope and electron microscope. The results were as follows: ${\bullet}$ Proliferation capacity of osteoblasts was not affected by single use of dexamethasone, but it was chiefly affected by ascorbic acid. ${\bullet}$ Cellular morphology was fibroblastic appearance initially, but, it was gradually changed to polygonal shape accompanied by confluency stage. ${\bullet}$ Pluripotent mesenchymal cells existed during primary culture, they were differentiated to adipocyte, chondrocyte, osteocyte according to culture condition. ${\bullet}$ Dexamethasone increased bone nodule formation under the condition that the culture was maintained with supplemented medium ascorbic acid and sodium-${\beta}$-glycerophosphate. ${\bullet}$ when the cultures were stained with alizarin red, the group supplemented with dexamethasone, ascorbic acid and sodium-${\beta}$-glycerophosphate showed the marked increase of bone nodule formation, but the group supplemented with ascorbic acid and sodium-${\beta}$-glycerophosphate revealed only small amounts of bone nodules. And the groups cultured without ascorbic acid showed no observed any of bone-like mass independent of dexamethasone addition.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.366-373
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• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Development and Reproduction
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• v.10 no.1
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• pp.63-73
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• 2006

This study aimed to find out suitable culture conditions for the differentiation of human amniotic membrane-derived stem cells(HAM) into hepatocyte-like cells. Almost homogenous population of fibroblast-like cells was successfully isolated from the amniotic membrane. In comparison to the non-coated plates and in the absence of insulin/transferrin/selenium(ITS), HAM cultured on the fibronectin-coated plates and in the presence of ITS showed the more intense immunocytochemical staining against the albumin. Addition of both fibroblast growth factor(FGF)-1 and -2 to the differentiation medium gave stronger staining compared to the treatment with FGF-1 or -2 alone. Periodic acid Schiff's base staining of glycogen and morphological turnover of fibroblast-like appearance of HAM into round shape matched the results of immunocytochemical studies. When the efficiency of two-step culture method was examined on the differentiation of HAM into hepatocyte-like cells, all of the results of immunocytochemical staining, periodic acid Schiff's staining and morphological change exhibited effective hepatic differentiation of HAM compared to the continuous culture method. Immunoblot analyses of HAM- conditioned media against the albumin showed that the culture of HAM in the presence of both ITS and fibronectin always gave a stronger staining intensity than those in the absence of them, and that the addition of ether mixture of FGF-4 and either FGF-2 or transforming growth $factor(TGF)-{\alpha}$ to the culture medium significantly enhanced the albumin secretion by HAM. Based on these observations, it is suggested that HAM could differentiate into hepatocyte-like cells under a culture condition consisting of fibronectin and ITS, and addition of FGF-4 with either one of FGF-2 or $TGF-{\alpha}$ could enhance the hepatic differentiation of HAM.