• Archives of Plastic Surgery
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• v.36 no.5
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• pp.519-524
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• 2009

Purpose: This study was conducted to establish the most effective method of cell therapy by comparing and analyzing the level of wound healing after various cell delivery methods. Methods: Human mesenchymal stem cells were administered using 5 different methods on full thickness skin defects which were deliberately created on the back of 4 - week old mice using a 8 mm punch. Different modes of administration, cell suspension, local injection, collagen GAG matrix seeding, fibrin, and hydrogel mix methods were used. In each experiment group, $4{\times}105$ mesenchymal stem cells were administered according to 5 deferent methods, and were not for the corresponding control group. Results: The wound healing rate was fastest in the local injection group. The wound healing rate was relatively slow in the collagen matrix group, however, the number of blood vessels or VEGF increased most in this group. Conclusion: For rapid wound healing through wound contraction, it is advantageous to administer MSC by the local injection method. For the healing process of a wide area, such as a burn, the seeding of cells to collagen matrix is thought to be effective.

• BMB Reports
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• v.52 no.9
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• pp.560-565
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• 2019

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)-induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

• BMB Reports
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• v.57 no.5
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• pp.244-249
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• 2024

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.

• Food Science and Preservation
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• v.23 no.3
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• pp.378-386
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• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

• 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 Microbiology
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• v.44 no.4
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• pp.282-288
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• 2008

Tissue ischemia resulting from the constriction or obstruction of blood vessels leads to an illness that may affect many organs including the heart, brain, and legs. In recent years, considerable progress has been made in the field of therapeutic angiogenesis and the new approaches are expected to cure those "no-option patients" who are unsuited to conventional therapies. Although single angiogenic growth factor may be successful in inducing angiogenesis, combination of multiple growth factors is increasingly sought these days to augment the therapeutic responses. This trend is proper in light of the fact that blood vessel formation is a complex and multi-step process that requires the actions of many different factors. To meet the growing need for functionally significant blood flow recovery in the ischemic tissues, a novel strategy that can provide concerted actions of multiple factors is required. One way to achieve such a goal is to use a transcription factor that can orchestrate the expression of multiple target genes in the ischemic region and thus induce significant level of angiogenesis. Here, a putative transcription factor, cardiac ankyrin repeat protein (CARP), was evaluated in adenoviral vector context for angiogenic activity in human umbilical vein endothelial cells. The results indicated significant increase in proliferation, capillary-like structure formation, and induction of vascular endothelial growth factor, a typical angiogenic gene. Taken together, these results suggest that CARP represents itself as a novel target for therapeutic angiogenesis and warrants further investigation.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.27-37
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• 1990

The extrafetal transfer of $Li^{+}$ in amniotic fluid was studied in 45 pregnant rabbits. LiCl solution was administered either intravenously to mother or directly into the amniotic sac and monitored the appearance and disappearance of $Li^{+}$ in the amniotic fluid, then calculated the transfer rate of $Li^{+}$ of extrafetal origin. To study the transplacental $Li^{+}$ transfer, a solution of 150 mM LiCl was infused continuously via maternal vein (initial dose: 0.7 mmol/kg, maintaining dose: 0.03 mmol/kg/min) and the $Li^{+}$ concentration was measured in maternal blood and amniotic fluid after 60 and 120 minutes of infusion. Change in the volume of aminotic fluid was determined by Congo red dilution method at the same time. Effects of duration of gestation was not considered in this study. Extrafetal transport of $Li^{+}$ into the amniotic fluid was estimated by comparing the $Li^{+}$ concentration and volume of amniotic fluid determined before and after ligating the placental vessels. Extrafetal $Li^{+}$ transport from the amniotic fluid was determined by observing the time dependent disappearance of $Li^{+}$ and Congo red in amniotic fluid after injecting 0.5 ml solution of 15 mM or 90 mM LiCl and 50 mg/ml Congo red. Following are the results obtained: 1) During infusion of LiCl through maternal vein the ratio of the aminotic $Li^{+}$/maternal plasma $Li^{+}$ increased significantly along with the increment of fetal weight. 2) The volume of amniotic fluid of larger fetuses than 20.5 gm increased significantly during administration of LiCl while that of smaller fetuses did not change. 3) After umbilical cord ligation the $Li^{+}$ concentration of amniotic fluid of larger fetuses than 20.5 gm was decreased to $59.9{\pm}10.3%$ and $56.9{\pm}42.9%$ $(mean{\pm}S.D.)$ of those of control group after 60 and 120 minutes of LiCl infusion respectively. In amniotic fluid of smaller fetuses than 20.5 gm, there was no significant difference between control and ligation groups. 4) The disappearance rate of Congo red in the amniotic fluid was $45.2{\pm}8.2%/hr$. 5) The disappearance rate of $Li^{+}$ after intraamniotic injection of LiCl depended on the amount injected. On injecting $7.5\;{\mu}mol$ LiCl, $Li^{+}$ disappeared rapidly from the amniotic fluid and the rates after 60 min and 90 min were $97.0{\pm}2.8,\;98.5{\pm}2.0%$ respectively. On injecting $45\;{\mu}mol$ LiCl, the rates were $56.0{\pm}15.4,\;78.9{\pm}14.5%$ at 60 and 90 min. 6) From the above results it was concluded: a) $Li^{+}$ transfer into the amniotic fluid increased along with the fetal growth and one half of $Li^{+}$ influx is through the extrafetal route even after the maturation of fetal kidney. b) One half of the $Li^{+}$ transfer from the amniotic fluid was through swallowing of fetus, while the remaining half was transfered rapidly through amniotic membrane, which was concentration limited.

• Journal of Nutrition and Health
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• v.47 no.4
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• pp.221-228
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• 2014

Purpose: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. Methods: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. Results: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. Conclusion: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.210-219
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• 2004

Extracellular $K^{+}$ concentration ([ $K^{+}$]$_{0}$ ) can be increased within several mM by the efflux of intracellular $K^{+}$. To investigate the effect of an increase in [ $K^{+}$]$_{0}$ on vascular contractility, we attempted to examine whether extracellular $K^{+}$ might modulate vascular contractility, endothelium-dependent relaxation (EDR) and intracellular $Ca^2$$^{+}$ concentration ([C $a^2$$^{+}$]$_{i}$ ) in endothelial cells (EC). We observed isometric contractions in rabbit carotid, superior mesenteric, basilar arteries and movse aorta. [C $a^2$$^{+}$]$_{i}$ was recorded by microfluorimeter using Fura-2/AM in EC. No change in contractility was recorded by the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM in conduit artery such as rabbit carotid artery. whereas resistant vessels, such as basilar and branches of superior mesenteric arteries (SMA), were relaxed by the increase. In basilar artery, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 1 to 3 mM was bigger than that by the increase from 6 to 12 mM. In contrast, in branches of SMA, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 6 to 12 mM is bigger than that by the increase from 1 to 3 mM. $Ba^2$$^{+}$ (30 $\mu$M) did not inhibit the relaxation by the increase in [ $K^{+}$]$_{0}$ from 1 to 3 mM but did inhibit the relaxation by the increase from 6 to 12 mM. In the mouse aorta without the endothelium or treated with $N^{G}$_nitro-L-arginine (30 $\mu$M), nitric oxide synthesis blocker, the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM did not change the magnitude of contraction induced either norepinephrine or prostaglandin $F_2$$_{\alpha}$. The increase in [ $K^{+}$]$_{0}$ up to 12 mM did not induce contraction of mouse aorta but the increase more than 12 mM induced contraction. In the mouse aorta, EDR was completely inhibited on increasing [ $K^{+}$]$_{0}$ from 6 to 12 mM. In cultured mouse aorta EC, [C $a^2$$^{+}$]$_{i}$ , was increased by acetylcholine or ATP application and the increased [C $a^2$$^{+}$]$_{i}$ , was reduced by the increase in [ $K^{+}$]$_{0}$ reversibly and concentration-dependently. In human umbilical vein EC, similar effect of extracellular $K^{+}$ was observed. Ouabain, a N $a^{+}$ - $K^{+}$ pump blocker, and N $i^2$$^{+}$, a N $a^{+}$ - $Ca^2$$^{+}$ exchanger blocker, reversed the inhibitory effect of extracellular $K^{+}$. In resistant arteries, the increase in [ $K^{+}$]$_{0}$ relaxes vascular smooth muscle and the underlying mechanisms differ according to the kinds of the arteries; $Ba^2$$^{+}$-insensitive mechanism in basilar artery and $Ba^2$$^{+}$ -sensitive one in branches of SMA. It also inhibits [C $a^2$$^{+}$]$_{i}$ , increase in EC and thereby EDR. The initial mechanism of the inhibition may be due to the activation of N $a^{+}$ - $K^{+}$pump. activation of N $a^{+}$ - $K^{+}$pump.p.p.p.