• Journal of Integrative Natural Science
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• v.10 no.2
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• pp.85-94
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• 2017

Fibroblast growth factor receptor (FGFR) belongs to the family of receptor tyrosine kinase. They play important roles in cell proliferation, differentiation, development, migration, survival, wound healing, haematopoiesis and tumorigenesis. FGFRs are reported to cause several types of cancers in humans which make it an important drug target. In the current study, HQSAR analysis was performed on a series of recently reported 1H-Pyrazolo [3,4-b]pyridine derivatives as FGFR antagonists. The model was developed with Atom (A) and bond (B) connection (C), chirality (Ch), hydrogen (H) and donor/acceptor (DA) parameters and with different set of atom counts to improve the model. A reasonable HQSAR model ($q^2=0.701$, SDEP=0.654, NOC=5, $r^2=0.926$, SEE=0.325, BHL=71) was generated which showed good predictive ability. The contribution map depicted the atom contribution in inhibitory effect. A contribution map for the most active compound (compound 24) indicated that hydrogen and nitrogen atoms in the side chains of ring B as well as hydrogen atoms in the side chain of ring C and the nitrogen atom in the ring D contributed positively to the activity in inhibitory effect whereas, the lowest active compound (compound 04) showed negative contribution to inhibitory effect. Thus results of our study can provide insights in the designing potent and selective FGFR kinase inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2499-2506
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• 2016

Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. Materials and Methods: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. Results: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, $THR{\beta}$, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. Conclusions: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations.

• BMB Reports
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• v.51 no.8
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• pp.406-411
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• 2018

Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.

• Journal of Periodontal and Implant Science
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• v.25 no.1
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• pp.133-145
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• 1995

The migration and proliferation of periodontal ligament cells are desired goal of periodontal regeneration therapy. PDGF and $TGF-{\beta}1$ are well known to regulate the cell activity of mesenchymal origin cell. The purpose of this study was to determine the effects of these growth factors on human gingival fibroblast and periodontal ligament cell actvity, and to identify the regulatory effect of $TGF-{\beta}1$ on the response to PDGF by MIT assay. Human gingival fibroblast and periodontal ligament cells were cultured from extracted teeth for non-periodontal reason. Cultured human gingival fibroblast and periodontal ligament cells in vitro were treated with polyperpetide growth factor PDGF and $TGF-{\beta}1$ in both a dose and time - dependent manner. Cell morphology were determined by inverted microscope and cell acitivity were determined by MIT assay. The result of this study demonstrated that PDGF and $TGF-{\beta}1$ were not changed the morphology of these cell compared with control group. PDGF or $TGF-{\beta}1$ increased cell activity of periodontal ligament cell in dose and time dependent manner but gingival fibroblast were decreased to the level of control group at third day. Additionally, incubation with $TGF-{\beta}1$ addition to PDGF resulted in a enhanced cell activity of PDGF. Therefore, cell acitivty of gingival fibroblast were not changed compared with control group. This stiudy demonstrates that PDGF and $TGF-{\beta}1$ are major mitogens for human periodontal ligament cell in vitro, and $TGF-{\beta}1$ is a regulator of cell activity to PDGF in human gingival fibroblast and periodontal ligament cell.

• KSBB Journal
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• v.16 no.3
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• pp.237-240
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• 2001

Epithelial cell migration plays an important role in many physiological processes such as morphogenesis and wound healing, and cell mobility requires the release of the cell from its adhesion site. This is directed, at least in part, by limited proteolysis of matrix molecules by matrix metalloproteinases (MMPs). MMPs are zinc-dependent proteases produced by a variety of cell types, and have a fundamental role in tissue remodelling, tumour invasion and metastasis. In addition, the ability of cells to mediate fibrinolytic agent, plasmin. The purpose of this study was to test if vascular endothlial growth factor (VEGF) can regulate the production of MMPs and plasmin by keratinocyte cells. Supernatants from a human keratinocyte cell line grown in the presence or absence of VEGF (10ng/mL) produced ?2.5 fold increases in cell proliferation, and ?3.0 fold increses in MMP-2 and plasmin levels. Our results suggest that VEGF may modulate keratinocyte cell proliferating activity by increasing the abundance of MMP-2 and plasmin, and indicates a role for VEGF in the regulation of keratinocyte behaviour in wound healing and tissue remodelling.

• Journal of Periodontal and Implant Science
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• v.23 no.1
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• pp.67-76
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• 1993

After periodontal surgery, the potential healing responses were occurred by interaction among junctional epithelium, gingival connective tissue, alveolar bone and periodontal ligament. The only cell that created periodontal regeneration was derived from periodontal ligament. The aim of the study was to evaluate the regenerative effects of the collagen membrane($collacote^{\circ}C$) and autogenous connective tissure graft with periosteum. Experimental periodontitis were created in furcation area of 4 adult dogs with bone removal and gutta percha packing. After 6 weeks later, the gutta percha was removed and experiment was performed divided by 3 groups. 1) Flap operation(control group). 2) Flap operation with collage membrane(Experimental group I). 3) Flap operation with autogenous connective tissue graft with periosteum (Experimental group II). After dogs were sacrificed after two and three weeks, specimens were prepared and stained with hematoxylin-eosin and masson-trichrome stain for light microscopic study. The results were as follows : 1. In all gruoups, connective tissue compartments were increased from two to three weeks especially in experimental group I. 2. Collagen membrane and connective tissue were increased collagen deposits of periodontal ligament. Therefore collagen fiber attached to tooth surface was seen. 3. In al experimental groups, newly forming alveolar bone was seen. 4. Collagen membrane and connective tissue were which prevented proliferation of epithelium, aided connective tissue new attachment and influenced periodontal regeneration.

• Journal of Periodontal and Implant Science
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• v.41 no.1
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• pp.30-43
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• 2011

Purpose: Under different culture conditions, periodontal ligament (PDL) stem cells are capable of differentiating into cementoblast-like cells, adipocytes, and collagen-forming cells. Several previous studies reported that because of the stem cells in the PDL, the PDL have a regenerative capacity which, when appropriately triggered, participates in restoring connective tissues and mineralized tissues. Therefore, this study analyzed the genes involved in mineralization during differentiation of human PDL (hPDL) cells, and searched for candidate genes possibly associated with the mineralization of hPDL cells. Methods: To analyze the gene expression pattern of hPDL cells during differentiation, the hPDL cells were cultured in two conditions, with or without osteogenic cocktails (${\beta}$-glycerophosphate, ascorbic acid and dexamethasone), and a DNA microarray analysis of the cells cultured on days 7 and 14 was performed. Reverse transcription-polymerase chain reaction was performed to validate the DNA microarray data. Results: The up-regulated genes on day 7 by hPDL cells cultured in osteogenic medium were thought to be associated with calcium/iron/metal ion binding or homeostasis (PDE1A, HFE and PCDH9) and cell viability (PCDH9), and the down-regulated genes were thought to be associated with proliferation (PHGDH and PSAT1). Also, the up-regulated genes on day 14 by hPDL cells cultured in osteogenic medium were thought to be associated with apoptosis, angiogenesis (ANGPTL4 and FOXO1A), and adipogenesis (ANGPTL4 and SEC14L2), and the down-regulated genes were thought to be associated with cell migration (SLC16A4). Conclusions: This study suggests that when appropriately triggered, the stem cells in the hPDL differentiate into osteoblasts/cementoblasts, and the genes related to calcium binding (PDE1A and PCDH9), which were strongly expressed at the stage of matrix maturation, may be associated with differentiation of the hPDL cells into osteoblasts/cementoblasts.

• Journal of Microbiology and Biotechnology
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• v.20 no.4
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• pp.803-808
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• 2010

Poly-${\gamma}$-glutamic acid (${\gamma}$-PGA) is a natural edible polypeptide in which glutamate is polymerized via ${\gamma}$-amide linkages. First, we assessed the eye irritancy potential of ${\gamma}$-PGA in rabbits. Additionally, we studied the effects of ${\gamma}$-PGA on corneal wound healing, due to the anti-inflammatory properties and water retaining abilities of ${\gamma}$-PGA. In this study, the effects of ${\gamma}$-PGA on corneal wound healing after an alkali burn were evaluated. Thirty eyes wounded by alkali burning in 30 white rabbits were divided into three groups: group A was treated with 0.1% 5,000 kDa ${\gamma}$-PGA for 2 days; group B was treated with 0.1% hyaluronic acid; and group C was not treated, as a control. The area of corneal epithelial defect was examined at 12, 24, 30, 36, 42, and 48 h after corneal alkali wounding to determine initial wound healing. We found that ${\gamma}$-PGA promoted corneal wound healing, compared with controls, and showed similar effects to hyaluronic acid. These results indicate that ${\gamma}$-PGA stimulates corneal wound healing by an anti-inflammatory effect and enhancing cell migration and cell proliferation. ${\gamma}$-PGA is a promising biomaterial that may be a substitute for hyaluronic acid in corneal wound healing treatment.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.639-645
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• 2001

Angiogenesis is a fundamental process in reproduction and wound healing. Under these condition, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases, and is thought to be indispensible for solid tumor growth and metastsis. The construction of new vascular network is a multistep cascade involving basement membrane degradation, endothelial cell proliferation, endothelial cell migration, and tube formation. Newly reported anti-angiogenic agents in oriental medical field have targeted both specific and multistep stages in the angiogenic process. From recent approach in oriental medical field with several herb medicines including activating blood flow and removing blood stasis medicine(活血化瘀藥), it may be possible in the future to develope specific anti-angiogenic agents that offer a less toxic potential therapy for cancer and angiogenic disease.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.57-70
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• 2012

The apoptotic process of gastric mucosa triggered by induction of proapoptotic gene expression, such as Bax. Stress-inducing factors may affect Bcl-2/Bax ratio and thus the rate of apoptosis through modulation of the expression of both proteins depending upon the experimental model. TGF-${\beta}$ is believed to be essential in wound healing for regulation of cell growth and differentiation and is known to be involved in tissue repair and remodeling. The polypeptide growth factors, such as vascular endothelial growth factor(VEGF), regulate essential cell functions involved in tissue healing including cell proliferation, migration, and differentiation. The purpose of this study was to investigate whether the oral administration of $Hwangyeon-tang$ (HYT) would have protect effects on gastric ulcer in rat. Sprague-Dawley rats (n=40) were randomly divided into 4 groups ; Normal, Saline, Cimetidine and HYT group. The saline, cimetidine and HYT extract were orally administrated to each group and gastric ulcer was induced with HCl/EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In Results, the wound healing of gastric ulcer was promoted by HYT and the significant alterations of BAX/Bcl-2, TGF-${\beta}1$ and VEGF proteins in gastric mucosa were observed. These results suggest that Fritillaria ussuriensis extract promotes wound healing and has protective effects on gastric ulcer in rats.