• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.977-982
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• 2006

Purpose : There has been an increasing amount of literature concerning the association between Mycoplasma pneumoniae and asthma pathogenesis. Interleukin(IL)-6 stimulates the differentiation of monocytes, and can promote Th2 differentiation and simultaneously inhibit Th1 polarization. IL-8 is a potent chemoattractant and, it has been suggested, has a role in asthma pathogenesis. Nitric oxide (NO) synthesized by airway epithelium may be important in the regulation of airway inflammation and reactivity. Vascular endothelial growth factor(VEGF) has been reported to be a mediator of airway remodeling in asthma. We investigated the effects of M. pneumoniae on IL-6, IL-8, NO and VEGF production in human respiratory epithelial cells. Methods : A549 cells were cultured and inoculated with M. pneumoniae at a dose of 20 cfu/cell. After infection, the presence of M. pneumoniae in epithelial cell cultures was monitored by immunofluorescence and confirmed by polymerase chain reaction(PCR) detection. IL-6, IL-8 and VEGF were determined by an enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. NO was measured using the standard Griess reaction. Results : In A549 cells, M. pneumoniaeinduced IL-6, IL-8, NO and VEGF release in time-dependent manners. It also induced mRNA expression of IL-6, IL-8 and VEGF in similar manners. Conclusion : These observations suggest that M. pneumoniae might have a role in the pathogenesis of the allergic inflammation of bronchial asthma.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.159-168
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• 2010

Objective: The purpose of this study was to evaluate the correlation between the expression pattern of vascular endothelial growth factor (VEGF) in endometrium and the pathogenesis of endometriosis by investigating VEGF expression patterns and their difference between eutopic endometrium of patients with endometriosis and that of normal controls without endometriosis. Methods: Endometrial sections were obtained from 64 hysterectomy specimens from women under age of 40, who had undergone hysterectomies and had histological evidence of endometriosis, with stage 3 and 4 according to the revised American Society for Reproductive Medicine classification. As for controls, 37 sections were gained from women diagnosed as having cervical intraepithelial neoplasia (CIN) of the uterine cervix and without evidence of pelvic endometriosis or adenomyosis during their operation. The VEGF content was evaluated immunohistochemically in the eutopic endometrium from 64 patients with endometriosis and 37 normal controls. Histological semiquantitative score (H-score) was calculated and compared between study group and control group throughout the menstrual cycle. Results: There was no significant difference in the H-score of VEGF in the eutopic endometrium between patients with endometriosis and controls without endometriosis when compared according to the same phase of the cycle, although the H-score of the study group was significantly higher in the secretory phase than the proliferative phase. Conclusion: The VEGF expression in the eutopic endometrium of women with endometriosis was not different from that of women without endometriosis. This study suggests VEGF expression in eutopic endometrium is unlikely associated with the pathogenesis of endometriosis.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.110-115
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• 2009

Background: A forceps-biopsy is performed to acquire tissue from patients with an endobronchial carcinoma using a flexible bronchoscope. Recently, a cryo-biopsy has also been used to acquire tissue samples. Cryo-biopsy is the diagnostic application of extreme cold for the local destruction of abnormal living tissue. This technique is safe, with no radiation danger, no risk of electrical accidents, and a little risk of bleeding. This study compared a forceps-biopsy with a cryo-biopsy using a flexible bronchoscope, and examined the chemosensitivity and level of VEGF (vascular endothelial growth factor) in the specimens obtained from the cryo-biopsy. Methods: We present a prospective study of 30 consecutive patients who underwent a forceps-biopsy between January 2007 and October 2007 with a mean age of 62.1 years and a male:female ratio of 5 : 1. A flexible bronchoscope was inserted to the area of the abnormal lesions, and a cryo-probe was then applied through the working channel of the flexible bronchoscope. A temperature of approximately -h80 was delivered to the tumor site for 8 seconds. The cryo-biopsy was performed after destroying the tumor mass. Results: The mean size of the tissue from the forceps-biopsy and cryo-biopsy were 2.0${\pm}$1.2 mm and 6.0${\pm}$3.0 mm. A chemosensitivity test was performed on 5 specimens obtained using cryo-biopsy and the level of VEGF was examined in 2 specimens obtained from a cryo-biopsy. There were no side effects in either group. Conclusion: Cryo-biopsy using a flexible bronchoscope is a safe and effective technique for acquiring tissue samples.

• 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.

• Childhood Kidney Diseases
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• v.14 no.2
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• pp.166-173
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• 2010

Purpose : Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. Methods : Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. Results : The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/$D_0$ glucose) were $0.56{\pm}0.13$ and $0.43{\pm}0.11$, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007) and lower 4-hour D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037) than those without haplotype CTGGC. Conclusion : The VEGF genetic polymorphism may influence the peritoneal solute transport.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4571-4576
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• 2015

Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

• Molecules and Cells
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• v.38 no.7
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• pp.663-668
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• 2015

hBMSCs are multipotent cells that are useful for tissue regeneration to treat degenerative diseases and others for their differentiation ability into chondrocytes, osteoblasts, adipocytes, hepatocytes and neuronal cells. In this study, biodegradable elastic hydrogels consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(${\varepsilon}$-caprolactone) (PCL) scaffolds were evaluated for tissue engineering because of its biocompatibility and the ability to control the release of bioactive peptides. The primary cultured cells from human bone marrow are confirmed as hBMSC by immunohistochemical analysis. Mesenchymal stem cell markers (collagen type I, fibronectin, CD54, $integrin1{\beta}$, and Hu protein) were shown to be positive, while hematopoietic stem cell markers (CD14 and CD45) were shown to be negative. Three different hydrogel scaffolds with different block compositions (PEG:PCL=6:14 and 14:6 by weight) were fabricated using the salt leaching method. The hBMSCs were expanded, seeded on the scaffolds, and cultured up to 8 days under static conditions in Iscove's Modified Dulbecco's Media (IMDM). The growth of MSCs cultured on the hydrogel with PEG/PCL= 6/14 was faster than that of the others. In addition, the morphology of MSCs seemed to be normal and no cytotoxicity was found. The coating of the vascular endothelial growth factor (VEGF) containing scaffold with Matrigel slowed down the release of VEGF in vitro and promoted the angiogenesis when transplanted into BALB/c nude mice. These results suggest that hBMSCs can be supported by a biode gradable hydrogel scaffold for effective cell growth, and enhance the angiogenesis by Matrigel coating.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.4
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• pp.66-81
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• 2013

Purpose: This study was carried out to investigate the anti-inflammatory effects of Ligustri Lucidi Fructus water extract (LF) in the lipopolysaccharide (LPS)-induced mouse macrophages RAW 264.7 cell. Methods: Ligustri Lucidi Fructus was extracted with distilled water (2,000 ml) for 2 hours. In order to evaluate cytotoxicity of LF, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. To investigate anti-inflammatory effects of LF, the concentration of nitric oxide (NO) was measured with NO assay, cytokine was measured by Bio-Plex cytokine assay, and intracellular calcium (Ca) was measured with Fluo-4 Ca assay in RAW 264.7 cell. And when p-value is below 0.05, it is judged to have the significant difference statistically (P<0.05). Results: 1. LF showed no cytotoxicity. 2. LF inhibited significantly the production of NO at the concentration of 25, 50 and $100{\mu}g/ml$. 3. LF inhibited significantly the production of interleukin (IL)-4, macrophage inflammatory protein (MIP)-$1{\alpha}$, granulocyte colony stimulating factor (G-CSF) at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 4. LF inhibited significantly the production of granulocyte macrophage-colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) at the concentration of 50, 100 and $200{\mu}g/ml$, the interferon (IFN)-${\gamma}$ at 25, 50 and $100{\mu}g/ml$ respectively. 5. LF inhibited significantly the production of IL-$1{\beta}$ at the concentration of 50 and $200{\mu}g/ml$, the IL-5 at 25 and $100{\mu}g/ml$, the IL-12p70, MIP-$1{\beta}$ at 50 and $100{\mu}g/ml$, the regulated on activation, normal T cell expressed and secrete d (RANTES) at 100 and $200{\mu}g/ml$ respectively. 6. LF inhibited significantly the production of IL-10, interferon gamma-induced protein (IP)-10 at the concentration of $200{\mu}g/ml$. 7. LF inhibited significantly the production of intracellular Ca at the concentration of 25, 50, 100 and $200{\mu}g/ml$. Conclusions: These results suggest that LF has anti-inflammatory effect and immuno-modulating activity.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.223-229
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• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.