• Molecules and Cells
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• v.41 no.9
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• pp.868-880
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• 2018

Pancreatic cancer (PC) is one of the most aggressive cancers presenting with high rates of invasion and metastasis, and unfavorable prognoses. The current study aims to investigate whether EZH2/miR-139-5p axis affects epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in PC, and the mechanism how EZH2 regulates miR-139-5p. Human PC and adjacent normal tissues were collected to determine expression of EZH2 and miR-139-5p, and their relationship with clinicopathological features of PC. Human PC cell line was selected, and treated with miR-139-5p mimics/inhibitors, EZH2 vector or shEZH2 in order to validate the regulation of EZH2-mediated miR-139-5p in PC cells. Dual-luciferase report gene assay and chromatin immunoprecipitation assay were employed to identify the relationship between miR-139-5p and EZH2. RT-qPCR and Western blot analysis were conducted to determine the expression of miR-139-5p, EZH2 and EMT-related markers and ZEB1/2. Tumor formation ability and in vitro cell activity were also analyzed. Highly-expressed EZH2 and poorly-expressed miR-139-5p were detected in PC tissues, and miR-139-5p and EZH2 expressions were associated with patients at Stage III/IV, with LNM and highly-differentiated tumors. EZH2 suppressed the expression of miR-139-5p through up-regulating Histone 3 Lysine 27 Trimethylation (H3K27me3). EMT, cell proliferation, migration and invasion were impeded, and tumor formation and LNM were reduced in PC cells transfected with miR-139-5p mimics and shEZH2. MiR-139-5p transcription is inhibited by EZH2 through up-regulating H3K27me3, thereby down-regulation of EZH2 and up-regulation of miR-139-5p impede EMT and LNM in PC. In addition, the EZH2/miR-139-5p axis presents as a promising therapeutic strategy for the treatment of PC.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.396-413
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• 1996

Current acceptable methods for promoting periodontal regeneration are based on removal of diseased soft tissue. root treatment, guided tissue regeneration, introduction of new graft materials and biological mediators. Insulin-like growth factor-I(IGF-I) and Platelet-derived growth factor-BB(PDGF-BB), the members of the polypeptuyde growth factor family have been reported as the biological mediators which regulate a variety cellular matrix biologic activities of wound healing process including the cell proliferation, migration and extracellular matrix synthesis.The purposes of this study is to evaluate the combination effects of IGF-I and PDGF-BB on the cellular activity of the periodontal ligament cells to act as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM containing 10% FBS at the $37^{\circ}C$, 5% CO2 incubator. Author measured the DNA synthetic activity, and total protein, collagen and noncollagenous protein synthetic activities according to the concentration of 10,100ng/ml IGF-I and1,10 ng/ml PDGF-BB in combination. The results were as follows: Significantly increased in the 1 ng/ml PDGF-BB alone compared to the 10 ng/ml PDGF-BB alone(P<0.01) and in the 1 ng/ml PDGF-BB and 10, 100ng/ml IGF-I in combination compared to the 1 ng/ml PDGF-BB alone(P<0.05, P<0.0l). The synthetic activity of the total protein and collagen is significantly increased like to the synthetic activity of the DNA(P<0.05). The synthetic activity of the noncollagenous protein is increased according to the concentration of IGF_I, but not statistically statistically significant(P>0.05). The percent of the collagen is significantly in the 1ng/ml PDGF-BB and 10ng/ml IGF-I in combination compared to the 1ng/ml PDGF-BB alone(P<0.05) and in the 10ng/ml IGF-I in combination compared to the 10ng/ml PDGF-BB alone(P<0.05). The synthetic activity of the DNA is In conclusions, the percent study shows that PDGF-BB and IGF-I in combination have a potentiality to enhance the DNA synthesis and the total protein and collagen synthesis of The periodontal ligament cells, especially it is more significant in the low concentration of PDGF-BB compared to the high one. Thus, the PDGF-BB and IGF-I in combination may have important roles in promotion of periodontal litgment healing, and consequently, may useful for clinical application in periodontal regenerative procedures.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.6
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• pp.743-749
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• 2005

Estrogen is known to play an important role in maintaining bone mass, since the concentration of serum estrogen decrease after menopause and the estrogen deficiency results in bone loss. Phytoestrogens are plant compounds with estrogen-like biological activity, In this study, to investigate the bioactivities of phytoestrogen, which act on bone metabolism, we examined the effect of selected food-borne phytoestrogens (genistein, daidzein and resveratrol) on osteoblast proliferation and IGF-I production using MC3T3-El cells, a mouse calvaria osteoblast-like cell line. Cells were cultured in a serum free medium for 48 hr in the presence of genistein $(10^{-5}\;M)$, daidzein $(10^{-5}\;M)$ and resveratrol $(10^{-5}\;M)$. The effects of genistein, daidzein and resveratrol on the cell proliferation and growth were evaluated by total cell numbers, MTS assay and cell migration assay. Their effect was compared with the $17\beta-estradiol$. Genistein, daidzein and resveratrol exhibited stimulatory effects on the growth of MC3T3-El cells, and the most pronounced effect was shown with daidzein. In addition, these phytoestrogen increased alkaline phosphatase activity of MC3T3-El cells. These effects were similar to that of $17\beta-estradiol$ effects. Moreover, treatment with genistein, daidzein and resveratrol increased production of insulin like growth factor-I (IGF-I) in conditioned media, indicating that the growth promoting effects of these phytoestrogen were related to the changes in production of IGF-I by MC3T3-El cells. These results show that genistein, daidzein and resveratrol have a stimulatory effect on osteoblast function, and that these findings in a cell model may prove relevant to protecting against the loss of bone mass and the development of osteoporosis in human subjects.

• Journal of Embryo Transfer
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• v.12 no.3
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• pp.229-246
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• 1997

Implantation is a most important biological process during pregnancy whereby conceptus establishes its survival as well as maintenance of pregnancy. During the periimplantation period, both uterine endometriurn and conceptus synthesize and secrete a host of growth factors and cytokines which mediate the actions of estrogen and /or progesterone and also exert their steroid-independent actions. Growth factors expressed by the materno-conceptal unit en masse have important roles in cell migration, stimulation or inhibition of cell proliferation, cellular differentiation, maintenance of pregnancy and materno-conceptal communications in an autorcrine /paracrine manner. The present review focuses on the role of the intrauterine IGF system during periimplantation conceptus development. The IGF system comprises of IGF- I and IGF- II ligands, types I and II IGF receptors and six or more IGF-binding proteins(IGFBPs). IGFs and IGFBPs are expressed and secreted by uterine endometrium with tissue, pregnancy stage and species specificities under the influence of estrogen, progesterone and other growth factor(s). Conceptus also synthesizes components of the IGF system beginning from a period between 2-cell and blastocyst stages. Maternal IGFs are utilized by both maternal and conceptal tissues; conceptus-derived growth factors are believed to be taken up primarily by conceptus. IGFs enhance the development of both maternal and conceptal compartments in a wide range of biological processes. They stimulate proliferation and differentiation of endometrial cells and placental precursor cells including decidual transformation from stromal cells, placental formation and the synthesis of some steroid and protein hormones by differentiated endometrial cells or placenta. It is also well-documented in a number of experimental settings that both IGFs stimulate preimplantation embryo development. In slight contrast to these, prenatal mice carrying a null mutation of IGF and /or IGF receptor gene do not exhibit any apparent growth retardation until after implantation. Reason (s) for this discrepancy between the knock-out result and the in vitro ones, however, is not known. IGFBPs, in general, are believed to inhibit IGF action within the materno-conceptal unit, thereby allowing endometrial stromal cell differentiation as well as dampening ex cessive placental invasion into maternal tissue. There is evidence, however, indicating that IGFBP can enhance IGF action depending on environrnental conditions perhaps by directioning IGF ligand to the target cell. There is also a third possibility that certain IGFBPs and their proteolytic fragments may have their own biological activities independent of the IGF. In addition to IGFBPs, IGFBP proteases including those found within the uterine tissue or lumen are thought to enhance IGF bioavailability by degrading their substrates without affecting their bound ligand. In this regard, preliminary results in early pregnant pigs suggest that a partially characterized IGFBP protease activity in uterine luminal fluid enhances intrauterine IGF bioavailability during conceptus morphological development. In summary, a number of in vitro results indicate that IGFs stimulates the development of the rnaterno-conceptal unit during the periimplantation period. IGFBPs appear to inhibit IGF action by sequestering their ligands, whereas IGFBP proteases are thought to enhance intrauterine bioavailability of IGFs. Much is remaining to be clarified, however, regarding the roles of the individual IGF system components. These include in vivo evidence for the role of IGFs in early conceptus development, identification of IGF-regulated genes and their functions, specific roles for individual IGFBPs, identification and characterization of IGFBP proteases. The intrauterine IGF club house thus will be paying a lot of attention to forthcoming results in above and other areas, with its door wide-open!

• Molecules and Cells
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• v.44 no.9
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• pp.658-669
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• 2021

Enhancers have been conventionally perceived as cis-acting elements that provide binding sites for trans-acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncoding RNA expression loci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, THUMPD3-AS1 and LINC01572, led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as THUMPD3-AS1 and LINC01572 (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.

• Food Engineering Progress
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• v.15 no.1
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• pp.1-5
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• 2011

Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.459-466
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• 2021

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

• Journal of Life Science
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• v.31 no.1
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• pp.59-65
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• 2021

Prunus mume Sieb. et Zucc is distributed throughout Asia and has traditionally been used as medicine and food. P. mume is known to contain large amounts of various organic acids, minerals, and phenol components. To date, the trend of P. mume research has focused only on the effects of antioxidant, anticancer and antibacterial, with only a few studies have focused on angiogenesis. Angiogenesis is a common characteristic of metastatic cancer through which oxygen and nutrients are delivered to the cells and tissues. In the present study, angiogenesis-inhibiting activity was investigated by evaluating the total polyphenol and flavonoid contents of the P. mume butanol fraction (PBF) and their ability to inhibit VEGF-induced human umbilical vein endothelial cells (HUVECs) proliferation, migration, invasion, and capillary formation. The polyphenols (12.81 mg GAE/g) and flavonoids (28.4 mg QE/g) of the PBF exhibited high antioxidant activity. The results of this study showed that PBF did not inhibit the proliferation of HUVECs at concentrations of 25-200 ㎍/ml and did not exhibit toxicity to normal cells. However, PBF inhibited the VEGF-induced mobility, invasion, and capillary formation of HUVECs. These results show that PBF inhibits the angiogenesis of HUVECs induced by VEGF. Therefore, PBF could serve as a therapeutic agent for the inhibition of angiogenesis.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.949-965
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• 1996

The main goal of periodontal therapy is to restore the lost periodontal tissue and establish the attachment appratus. Current acceptable therapeutic techniques are included : removal of diseased soft tissue, demineralization of exposed root surface, using the barrier membrane for preventing the downgrowth of gingival epithelial cell, insertion of graft materials as a scaffolding action, and biological mediators for promoting the cell activity. The latest concept one among them has been studied which based on the knowledge of cellular biology of destructed tissue. Platelet-derived growth factor(PDGF) is one of the polypeptide growth factor which have been reported as a biological mediator to regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the influences of the PDGF as biological mediator to periodontal ligament and bone marrow cell. Both right and left maxillary first molar were extracted from rat which had treated with 0.4% ${\beta}-Aminopropionitril$ for 5 days, and feeded until designed date to sacrifice under anesthesisa. Periodontal ligament were removed from the extracted socket of the rat, and cultured with Dulbecco's Modified Essential Medium(DMEM) contained with 10% Fetal Bovine Serum, 100U/ml penicillin, $100{\mu}g/ml$ streptomycin, $0.5{\mu}g/ml$ amphotericin-B. Bone marrow cell were culture from bone marrow suspension with which washed out from femur with same medium. The study was performed to evaluate the effect of PDGF to periodontal ligament and bone cell, cell proliferation rate, total protein synthesis, and alkaline phosphatase activity of rat periodontal ligament(PDL) cell and bone stromal(RBS) cell in vitro. The effects of growth factors on both cells were measured at 3, 5th day after cell culture with (control group) or without growth factors(experimental group). The results were as follows: 1. The tendency of cell proliferation under the influence of PDGF showed more rapid proliferation pattern than control at 3 and 5 days after inoculation. 2. The activity of Alkaline phosphatase revealed 14, 80% increased respectively at 3, 5 days culture than control group. Measurements of ALPase levels indicated that PDL cells had significantly higher activity when compared with that of co-culture groups and GF only(P<0.05). And, ALPase activity in 10 days was higher than that of 7 days(P<0.05). 3. The tendency of formation of the mineralized nodule were observed dose-depend pattern of PDL cells. There was statistically significant difference among group l(PDL 100%), 2(PDL 70%:GF 30%), and 3(PDL 50%:GF 50%)(P<0.01). But, there was no difference among group 3, 4(PDL 30%:GF 70%), and 5(GF 100%). 4. Also, the number of nodule was greater in co-culture of PDL 70% and GF 30% than in culture of PDL 70%(P<0.05). From the above results, it is assumed that the PDGF on PDL cells and RMB cell culture. GF stimulates the cell growth, which is not that of PDL cells but GF. And, the activity of ALPase depends on the ratio of PDL cells, and ALPase may relate to the initial phase of nodule formation. Also, it is thought that the calcified nodule formation principally depends on PDL cells, is inhibited by GF, and affected by cell density. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.785-804
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• 1997

It was well known that calcium sulfate was biocompatible, resorbed rapidly in the body, had potential as a good barrier membrane. Platelet-derived growth factor(PDGF) was one of polypeptide growth factor that had been reported as a biological mediator which regulates activities of wound healing process including the cell proliferation, migration and metabolism. The purpose of this study was to evaluate the effects of a combination of calcium sulfate and PDGF on periodontal ligament cells in vitro to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the premolar tooth extracted for the orthodontic treatment. Cells were cultured in ${\alpha}-MEM$ contained with 20% FBS, at the $37^{\circ}C$, 100% of humidity, 5% $Co_2$ incubator. Cells were inoculated and cultured into 96 well culture plate with $1{\times}10^4cells/well$ of ${\alpha}-MEM$ for 1 day. After discarding the medium, those cells were cultured in ${\alpha}-MEM$ contained with 10% FBS alone(control group), in calcium sulfate(calcium sulfate group), in calcium sulfate treated with 15ng/ml of PDGF-BB(calcium sulfate+PDGF group), in ${\alpha}-MEM$ contained with 10% FBS treated with 15ng/ml of PDGF-BB(PDGF group) for 1, 2, 3 day respectively. And then each group was characterized by examining of the cell counting, MTT assay, collagen synthesis. The results were as follows. 1. In the analysis of cell proliferation by cell counting, both calcium sulfate group and calcium sulfate plus PDGF group showed no stastically significant difference compared to control group, but there was stastically significant difference between PDGF group and calcium sulfate group at 1, 2 day(P<0.05). 2. In the analysis of cell proliferation by MTT assay in calcium sulfate extracts, both calcium sulfate group and calcium sulfate plus PDGF group showed no stastically significant difference compared to control group, but there was stastically significant difference between PDGF group and calcium sulfate group at 2, 3 day, and between calcium sulfate plus PDGF group and calcium sulfate group at 2 day(P