• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.111-123
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• 2021

Objective: Using domestic cats as a biomedical research model for fertility preservation, the present study aimed to characterize the influences of ovarian tissue encapsulation in biodegradable hydrogel matrix (fibrinogen/thrombin) on resilience to cryopreservation, and static versus non-static culture systems following ovarian tissue encapsulation and cryopreservation on follicle quality. Methods: In experiment I, ovarian tissues (n=21 animals; 567 ovarian fragments) were assigned to controls or hydrogel encapsulation with 5 or 10 mg/mL fibrinogen (5 or 10 FG). Following cryopreservation (slow freezing or vitrification), follicle viability, morphology, density, and key protein phosphorylation were assessed. In experiment II (based on the findings from experiment I), ovarian tissues (n=10 animals; 270 ovarian fragments) were encapsulated with 10 FG, cryopreserved, and in vitro cultured under static or non-static systems for 7 days followed by similar follicle quality assessments. Results: In experiment I, the combination of 10 FG encapsulation/slow freezing led to greater post-thawed follicle quality than in the control group, as shown by follicle viability (66.9%±2.2% vs. 61.5%±3.1%), normal follicle morphology (62.2% ±2.1% vs. 55.2%±3.5%), and the relative band intensity of vascular endothelial growth factor protein phosphorylation (0.58±0.06 vs. 0.42±0.09). Experiment II demonstrated that hydrogel encapsulation promoted follicle survival and maintenance of follicle development regardless of the culture system when compared to fresh controls. Conclusion: These results provide a better understanding of the role of hydrogel encapsulation and culture systems in ovarian tissue cryopreservation and follicle quality outcomes using an animal model, paving the way for optimized approaches to human fertility preservation.

• The Journal of Korean Academy of Prosthodontics
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• v.51 no.2
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• pp.82-89
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• 2013

Purpose: The present study is aimed to evaluate the combined effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) coated onto anodized implants on osseointeration. Materials and methods: Six New Zealand white rabbit were used in this study. Each animal received 4 implants that were either coated with rhBMP-2 and rhVEGF (Study group) or anodized implant (Control group) in both tibia. This was performed using a randomized split-mouth design. A total 24 implants were used. The implant stability quotient (ISQ) value using resonance frequency analyser and removal torque (RTQ) measurement were investigated at 2 and 8 weeks. The t-test was used for statistical analysis (${\alpha}$=.05). Results: Control and study group showed good osseointegration at 8 weeks. The ISQ and RTQ values of study group were significant compared with the control group at 8 weeks (P<.05). However, No statistical significance was observed at 2 weeks (P>.05). Conclusion: It was concluded that rhBMP-2 with rhVEGF coated onto anodized implants can induce better osseointegration at late healing period.

• Journal of Nutrition and Health
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• v.53 no.2
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• pp.111-120
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• 2020

Purpose: Corosolic acid (CA), also known as 2α-hydroxyursolic acid, is present in numerous plants, and is reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells such as osteosarcoma, hepatocellular carcinoma, lung adenocarcinoma, and colon cancer. However, the anti-cancer activity of CA on human breast cancer cells and the underlying mechanisms remain to be elucidated. The present study aimed to investigate the anticancer effects of CA in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, apoptosis marker protein expression, migration, invasion rate, and vascular endothelial growth factor (VEGF) levels were assessed by treating MDA-MB-231 cells to increasing concentrations of CA. Results: The results showed that CA significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. To assess the effect of CA on apoptosis, nuclei of MDA-MB-231 cells were stained with DAPI solution. Chromatin condensation, which indicates apoptosis, was observed to increase dose-dependently. In addition, western-blot analysis revealed elevated levels of the apoptosis marker proteins (Bax and cleaved caspase 3) subsequent to MDA-MB-231 exposure to CA. ROS production was also increased in the CA-induced apoptosis in MDA-MB-231 treated cells. Interestingly, CA exposure resulted in significantly decreased migration and invasion rates in the MDA-MB-231 cells. Data further revealed that exposure to CA markedly decreased the VEGF concentration, thereby contributing to a reduction in angiogenesis. Conclusion: Our results determined that exposure to CA induces anti-proliferation, apoptosis, and ROS production, and suppresses cell migration and invasion rate in MDA-MB-231 cells. Taken together, these results indicate the potential of CA to be applied as an effective chemotherapeutic agent for treating breast cancer.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.281-287
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• 2011

Objective : Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy. Methods : Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31. Results : Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy. Conclusion : While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.

• Molecules and Cells
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• v.40 no.6
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• pp.386-392
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• 2017

Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, ${\alpha}-smooth$ muscle actin, platelet-derived growth factor receptor ${\beta}$, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the $SDF-1{\alpha}$ and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

• Journal of Chest Surgery
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• v.33 no.6
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• pp.494-501
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• 2000

Background: Transmyocardial laser revascularization(TMLR) for revascularizing ischemic myocardium in patients was originally based on the assumption that laser channels remain their patency much longer. But recent studies show that laser channels did not remain open and that TMLR could achieve treatment benefits without long-term channel patency. The angiongencesis is currently thought to be induced by non-specific inflammatory response to mechanical tissue injury. This study is to evaluate hypothesis that various transmyocaridal mechanical revascularization(TMMR) may induce the angiogenic responses similar to that seen with TMLR, and transmyocaridal polymer stent revascularization(TMSR), the polymer stent in the myocardial tissue is hydrolyzed in 2 weeks, may enhance the non-specific inflammatory reaction resulting angiogenesis. Furthermore, polymer myocaridal stent channels remain long-term patency. Material and Method: Eight domestic pigs underwent ligation of the proximal circumflex artery, and 2 weeks later they were randomized to undergo transmycardial acupunctural revascularization (TMPR, Group I) of the left lateral wall with 18-G needle(n=2), to undergo transmyocardial (TMDR, Group II) with industrial 2mm steel drill(n=2), to undergo transmyocardial polymer stent revascularization (TMSR, Group III) after drilling the infarcted myocardium(n=2), the stent is poly(lactic acid-co-glycolic acid), which is self-degradated in the myocardium, and to a control group the ischemic zone was unterated(n=2). All the pigs were sacrificed after 4 weeks TMMR. Sections from the ischemic zone were submitted for vascular endothelial growth factor (VEGF) ELISA and histology. Result: There were makedly increase in the VEGF immunoassay in the ischemic zone of the TMMR group compared to the ischemic zone of the control group(control: each 30.85 and 43.15pg/mg protein, TMPR: each 44.14 and 68.61 pg/mg protein, TMDR: each 65.92 and 78.65 pg/mg protein, TMSR: each 177.39 and 168.87 pg/mg protein). TMSR channels caused greatest VEGF expression than channels made by other group and the polymer stent channels remained vacuole after 4 weeks. Conclusion: Transmyocardial polymer stent revascularization promoted the most angiogenci response by the VEGF immunoassay, although our study did not show the statistical significancy. The channels remained but the flow patency was not verified. Transmyocardial polymer stent revascularization (TMSR) is desirable in future experimental trials and in view of the significant cost implications comparable to that of laser.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.457-461
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• 2018

Corpus luteum (CL) is a transient endocrinal tissue that undergoes repeated formation and regression during the estrous cycle. In this study, we hypothesized that the functional and structural mechanism of angiogenesis is similar between CL and tumor formation. First, we measured mRNA and protein expression of angiogenic receptors (vascular endothelial growth factor receptor-2, VEGFR2; Tie 2) in the early, middle, and late phase CL tissues during the estrous cycle. Ral-interacting protein of 76 kDa (RLIP76) and H-ras mRNA and protein were also expressed in the CL tissues. VEGFR2 and Tie 2 mRNA and protein were expressed in the early and middle phase CLs and decreased in the late phase. H-ras mRNA and protein were expressed in the early and middle phase CLs, but not in the late phase. RLIP76 mRNA was expressed in all phase CLs, and the protein expression was highest in early phase CLs. We suggest that RLIP76 and H-ras, an oncogenic gene, regulate the function of the CL during the estrous cycle, and the proteins will play an important role in the angiogenic mechanism of the CL.

• Toxicological Research
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• v.35 no.4
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• pp.361-369
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• 2019

1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.