• The korean journal of orthodontics
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• v.31 no.1 s.84
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• pp.121-136
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• 2001

This study was performed to analyse the expression of VEGF and it's receptor(VEGFR) in the tension side of the periodontal ligament following orthodontic tooth movement. Upper first molars of Sprague-Dawley rats were moved medially using closed coil spring for 1, 2, 24 hours and 3, 7, 14 days. H&E staining, immunohistochemical staining and in situ hybridization methods were used to analyse the change of the expression of VEGF and VEGFR. The results from this study were as follows : 1. Following tensional force, periodontal ligament showed elongation of fibers, compression and congestion of vessels and regional hemorrhage. These tissue changes were recovered within 3 days of force application. New bone formation was seen after 3 days of force application and continued for the remaining experimental periods. 2. Following tensional force, VEGF and VEGF mRNA expression was increased in the periodontal ligament cells, osteoblasts and cementoblasts. This change was followed by increased vasculature in the periodontal ligament. 3. After 3 days of tensional force, VEGF and VEGF mRNA expression was confined mainly to the osteopaths and the periodontal ligament cells adjacent to the alveolar bone. After 2 weeks of force application, VEGF and VEGF mRNA expression was reduced to the level of control sample. 4. VEGFRs(Flt-1, Flk-1) showed similar expression pattern and it's expression was mainly seen in the endothelial cells and osteoblasts. Following tensional force VEGFR expression was increased in the endothelial cells and osteoblasts. In conclusion, in the tension side of the penodontal ligament, ligament cells, osteoblast and cementoblast showed increased expression of VEGF & VEGF mRNA. It preceded the increase of vasculature and new bone formation. The increased expression of VEGF mRNA in cementoblast may induce periodontal vessels, which distribute mainly the bone side half of periodontal ligament, grow in the direction of tensional force. Increased expression of VEGFR & VEGFR mRNA not only in endothelial cell but in osteoblast, osteocyte and periodontal cells showed VEGF acts not only in paracrine manner but in autocrine one.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.4
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• pp.366-379
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• 2017

In this study, we performed a systematic review and meta-analysis to identify the effects of exercise on endothelial progenitor cells (EPCs) in patients with cardiovascular disease (CVD). We conducted database searches (Cochrane Library, PubMed, EMBASE, ScienceDirect, CINAHL, Scopus, KoreaMed, KISS, RISS, KMBASE) for the effect of exercise on cardiovascular disease, using heart disease, coronary artery disease, heart failure, cardiovascular disease, exercise, motor activity, rehabilitation, and endothelial progenitor cells as the keywords. Of the 539 studies identified, 9 met the inclusion and exclusion criteria. Comprehensive Meta-Analysis version 2.0 was used to analyze the effect size and the publication bias was checked with a funnel plot. Exercise was found to improve the VEGF (vascular endothelial growth factor), CD34+KDR+, and endothelial function, assessed via FMD (flow-mediated dilation), in the exercise vs. control groups, viz. 2.008 (95% CI 0.204-3.812), 1.399 (95% CI 0.310-2.489), and 1.881 (95% CI 0.848-2.914), respectively. Exercise improved the VEGF, number of EPCs, and endothelial function in the CVD patients. Considering the increasing prevalence and mortality rates for cardiovascular disease in Korea, the findings of this study that analyzed the effects of exercise on EPCs might provide guidelines for planning exercise interventions for patients with CVD.

• Korean Journal of Ophthalmology
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• v.32 no.6
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• pp.451-458
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• 2018

Purpose: To investigate the efficacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) treatment of retinopathy of prematurity (ROP). Methods: We performed a retrospective review of intravitreal anti-VEGF (bevacizumab or ranibizumab) treatment of 153 eyes (83 infants) diagnosed with ROP at two tertiary hospitals from June 2011 to January 2017. The primary outcome was the rate of recurrence requiring additional treatment; secondary outcomes included incidence of major complications and final refractive error. Results: A total of 101 eyes were treated with bevacizumab, and 52 with ranibizumab. The bevacizumab and ranibizumab groups were characterized by mean birthweights of $941.8{\pm}296.1$ and $1,257.7{\pm}514.5g$, gestational ages at birth of $26.9{\pm}1.9$ and $28.1{\pm}3.2$ weeks, and postmenstrual ages at treatment of $40.4{\pm}2.4$ and $39.2{\pm}2.3$ weeks, respectively. The two groups differed significantly in birthweights and gestational ages at birth, but not in postmenstrual ages at treatment. The mean follow-up duration was $30.9{\pm}18.4$ months for the bevacizumab group, and $13.9{\pm}12.5$ months for ranibizumab. More cases were classified as zone 1 ROP in the ranibizumab group (44.2% vs. 11.9%, p < 0.001). Major surgical interventions included scleral encircling and vitrectomy (one and two eyes, respectively, both in the bevacizumab group). Retinal detachment was noted in one eye treated with bevacizumab. There was no significant difference in the most recent spherical equivalence for the two groups ($+0.10{\pm}3.66$ and $+0.22{\pm}3.00$ diopters for bevacizumab and ranibizumab, respectively). Univariable analysis revealed that only ROP stage influenced the occurrence of major complications (odds ratio, 9.046; p = 0.012). Conclusions: Intravitreal anti-VEGF treatment of ROP with both bevacizumab and ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence. Ranibizumab achieved similar anatomical outcomes as bevacizumab, without additional risk for major complications.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.264-272
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• 2021

Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.125-134
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• 2010

Objective: The aim of this study was to measure the concentrations of cytokines contained in the hydrosalpingeal fluid and to evaluate the effect on the mouse embryo development with the different cytokine concentration. Methods: The hydrosalpingeal fluids (HSF) were collected during the surgery for hydrosalpinx which was confirmed by hysterosalphingogram. The cytokines in HSF including interleukin (IL)-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, Interferon-$\gamma$ (IFN-$\gamma$), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), monocyte chemotactic protein-1 (MCP-1) were measured by ELISA method. HSF were added up to culture media with 5%, 10%, and 30% concentrations. The blastulation rates were compared. Results: IL-$\alpha$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, IFN-$\bamma$, VEGF, EGF, and MCP-1 were detected, but the concentrations were different from each sample. IL-6 and IL-10 were increased in HSF-1 group, and IFN-$\gamma$, MCP-1, VEGF were increased in HSF-2 compared with normal serum range. The Th1/Th2 ratio of HSF-2 (IFN-$\gamma$:IL10) was highly elevated to 61.64, compared with that of HSF-1 (3.69). The blastulation rate was significantly decreased in HSF-2 group (27.7%) compared those of the HSF-1 group (74%) and control group (76.7%). It showed the trend that the blastulation rate was decreased depending on the concentration HSF of culture media in HSF-2 group, but it was not statistically significant. Conclusion: The composition and concentration of cytokines in each HSF were different, and increased proinflammatory cytokines in HSF might be associated with poor embryonic development. Further study will be needed about the effect of each cytokines in HSF.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3909-3919
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• 2013

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

• Journal of Veterinary Clinics
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• v.22 no.1
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• pp.16-20
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• 2005

The purpose of this study was to compare the antiangiogenic effects of As₄O/sub 6/ to those of As₂O₃ on the rat corneal micropocket model induced by VEGF. 20 ng VEGF impregnated pellets were used for angiogenic inducer on the rat cornea micropocket assay in this study. After ophthalmoscopic examination, Sprague-Dawley rats with normal cornea were implanted VEGF pellet. Total 60 eyes were used in this study. Control group only received VEGF pellet, As₂O₃ group followed oral administration of As₂O₃ at a dose of 50 mg/kg per day after VEGF pellet implantation and As₄O/sub 6/ group followed oral administration of As₄O/sub 6/ at a dose of 50 mg/kg per day after VEGF pellet implantation were classified. The eyes were examined under a surgical microscope daily on postoperative from day 3 to day 9 after pellet implantation. The number, length, clock hour of vascularization, and area of vessels in As₄O/sub 6/ group were significantly less evident than those of control group and As₂O₃ group (P < 0.05). In conclusion, As₄O/sub 6/ had better antiangiogenic effects on the new vessel induced by VEGF in the rat cornea.

• The Journal of Korean Physical Therapy
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• v.15 no.3
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• pp.16-44
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• 2003

Skeletal muscle regeneration is a vital process for various muscle myopathies and muscular adaptation to physiological overload. Angiogenesis is the key event in the process of muscle regeneration, and vascular endothelial growth factor(VEGF) plays an important role in it. The purpose of this study was to evaluate the effect of GaAlAs(830nm) laser and immunoreactivity of VEGF on angiogenesis after muscle contusion injury. Muscle contusion injury was induced in the triceps surae muscle by dropping a metal bead(31.4g). GaAlAs laser irradiation(power 20 mW, frequency 2000 Hz, treatment time 15 min) was applied directly to the skin of injured muscle daily for seven days. The experimental group I was irradiated immediately by laser after injury, whereas the experimental group II was irradiated after 1 day of injury. The control group was non-irradiated. The results of this study were as follows. 1. In morphological observation, there were no significant changes in experimental and control groups for 7 days. At 3 days, however, the splited muscle fibers were observed in experimental groups, and the muscle atrophy and granular tissue viewed at 7 days in control group. 2. The VEGF was expressed in muscle fiber that located in the interspace between gastrocnemius and soleus muscles. As the time coursed, the immunoreactivity of VEGF also seemed to be strong in the individual muscle fibers. 3. The experimental group I & II showed higher immunoreactivity of VEGF than control group(p<0.05). Then, the experimental group I showed higher than group II especially(p<0.05). These data suggest GaAlAs semiconduct diode laser irradiation(830nm) enhanced angiogenesis in the skeletal muscle induced contusion injury, and immediate laser irradiation after injury promoted the angiogenesis greatly than after 1 day of injury.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6565-6570
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• 2014

Objective: To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Methods: Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. Results: the therapeutic effect of rh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rh-endostatin+DP regimen group was obviously lower than single chemotherapy group (P<0.01). The expression of VEGF had positive correlation with BF and BV but negative correlation with MTT. Compared with treatment before for rh-endostatin+DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P<0.05). However, there were no significant differences between treatment before and after treatment in single chemotherapy (P>0.05). Conclusions: Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.