• Journal of Ginseng Research
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• 제45권2호
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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.

• International Journal of Vascular Biomedical Engineering
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• 제3권2호
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• pp.1-9
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• 2005

Flow-induced dilation of blood vessel is the result of a series of bioreaction in vascular endothelial cells(VEC). Shear stress change by blood flow in human artery or vein is sensed by the mechanoreceptor and responsible for such a chain reaction. The inositol(1,4,5)-triphophate($IP_3$) is produced in the first stage to elevate permeability of the intercellular membrane to calcium ions by which the cytosolic calcium concentration is consequently increased. This intracellular calcium transient triggers synthesis of EDRF and prostacyclin. The mathematical model of this VEC calcium dynamics is reproduced from the literature. We then use the Computational Fluid Dynamics(CFD) technique to investigate the blood stream dictating the VEC calcium dynamics. The pulsatile blood flow in a stenosed blood vessel is considered here as a part of study on thrombogenesis. We calculate the pulsating shear stress (thus its temporal change) distributed over the stenosed artery that is implemented to the VEC calcium dynamics model. It has been found that the pulsatile shear stress induces larger intracellular $Ca^{2+}$ transient plus much higher amount of EDRF and prostacyclin release in comparison with the steady shear stress case. It is concluded that pulsatility of the physiological shear stress is important to keep the vasodilation function in the stenosed part of the blood vessel.

• 대한두경부종양학회지
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• 제18권1호
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.97-101
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• 2015

Background: The gene for the vascular endothelial growth factor (VEGF), which promotes angiogenesis and permeability, is polymorphic. The aim of the present study was to evaluate the relationship between +936C>T and +404C>G polymorphism of VEGF with risk of esophageal cancer in the Kashmiri population in India. Materials and Methods: 150 esophageal cancer patients and 150 unrelated healthy controls were genotyped for two VGEF SNPs (+405C/G, and +936C/T) using DNA extracted from prospectively collected blood samples by the PCR-RFLP method. Results: For the VEGF +936C>T polymorphism a significant association of CT and combined CT+TT genotypes was observed with increased risk of esophageal cancer (p=0.021; 0.024). For the +405C>G polymorphism we observed significantly increased frequency of GG genotype in cases as compared to controls and also the +405 GG Genotype was observed to have a two fold risk(OR=2.7356; 95%CI=1.1409-6.5593; p=0.020). The combined genotypes of GG-CC and GG-CT of +405C>G and +936C>T were found to be significantly associated with increased risk of esophageal cancer (p=0.0376; 0.0099). Conclusions: From the results of the present study a significant association of +936C>T and +405C>G polymorphisms with increased esophageal cancer risk exists in the Kashmiri population.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권1호
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• pp.27-34
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• 2009

Angiogenesis is essential for solid tumor growth and progression. Among the pro-angiogenetic factors, vascular endothelial growth factor(VEGF), also known as vascular permeability factor, is the most important as a mitogen for vascular endothelium. The VEGF family of molecules currently consists of six growth factors, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor(PlGF). Over-expression of PlGF is associated with angiogenesis under pathological conditions such as ischemia, inflammation, and cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and the up-regulation of PlGF expression in oral squamous cell carcinoma. We studied the immunohistochemical staining of PlGF, PlGF gene expression and a real time quantitative RT-PCR in 20 specimens of 20 patients with oral squamous cell carcinoma. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of PlGF was observed. And the correlation between immunohistopathological PlGF expression and histological differentiation of specimens was significant (Pearson correlation analysis, significance [r] >0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.

• Journal of Korean Neurosurgical Society
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• 제47권3호
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• pp.203-209
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• 2010

Objective : The purpose of study was to evaluate the feasibility of brain magnetic resonance (MR) images of the rat obtained using a 1.5T MR machine in several blood-brain barrier (BBB) experiments. Methods : Male Sprague-Dawley rats were used. MR images were obtained using a clinical 1.5T MR machine. A microcatheter was introduced via the femoral artery to the carotid artery. Normal saline (group 1, n = 4), clotted autologous blood (group 2, n = 4), triolein emulsion (group 3, n = 4), and oleic acid emulsion (group 4, n = 4) were infused into the carotid artery through a microcatheter. Conventional and diffusion-weighted images, the apparent coefficient map, perfusion-weighted images, and contrast-enhanced MR images were obtained. Brain tissue was obtained and triphenyltetrazolium chloride (TTC) staining was performed in group 2. Fluorescein isothiocyanate (FITC)-labeled dextran images and endothelial barrier antigen (EBA) studies were performed in group 4. Results : The MR images in group 1 were of good quality. The MR images in group 2 revealed typical findings of acute cerebral infarction. Perfusion defects were noted on the perfusion-weighted images. The MR images in group 3 showed vasogenic edema and contrast enhancement, representing vascular damage. The rats in group 4 had vasogenic edema on the MR images and leakage of dextran on the FITC-labeled dextran image, representing increased vascular permeability. The immune reaction was decreased on the EBA study. Conclusion : Clinical 1.5T MR images using a rat depicted many informative results in the present study. These results can be used in further researches of the BBB using combined clinical MR machines and immunohistochemical examinations.

• BMB Reports
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• 제45권3호
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• pp.200-205
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• 2012

Enzymatic oxidation of commercially available pyrogallol was efficiently transformed to an oxidative product, purpurogallin. Purpurogallin plays an important role in inhibiting glutathione S-transferase, xanthine oxidase, catechol O-methyltransferase activities and is effective in the cell protection of several cell types. However, the anti-inflammatory functions of purpurogallin are not well studied. Here, we determined the effects of purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatory responses. The results showed that purpurogallin inhibited LPS-mediated barrier hyper-permeability, monocyte adhesion and migration and such inhibitory effects were significantly correlated with the inhibitory functions of purpurogallin on LPS-mediated cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) releases from HUVECs were inhibited by purpurogallin. Given these results, purpurogallin showed its anti-inflammatory activities and could be a candidate as a therapeutic agent for various systemic inflammatory diseases.

• 한국식품과학회지
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• 제42권2호
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• pp.210-216
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• 2010

혈당강하 효과가 있다고 알려진 해당근 추출물을 이용하여 AGEs 생성 저해에 따른 초기 동맥경화증에 대한 효과에 대하여 검토하였다. 먼저 해당근 추출물이 AGEs에 의하여 생성이 촉진된 ROS를 제거하는 효과가 있는지를 확인하기 위하여 항산화 활성을 측정하였다. 총 플라보노이드 함량을 측정한 결과 해당근의 메탄올 추출물은 $128.1{\pm}2.0\;{\mu}g$ quercetin equivalents(QE)/mg DM,총 폴리페놀 함량은 $345.2{\pm}5.7\;{\mu}g$ gallic acid equivalents(GAE)/mg DM으로 나타났다. 환원력 측정을 위한 FRAP assay는 $2.19{\pm}0.1\;mM$ $FeSO_4{\cdot}7H_2O$/mg DM으로 $25.5{\pm}0.3$ $FeSO_4{\cdot}7H_2O$/mg DM 인 ascorbic acid에 비해 약 9% 정도의 환원력을 가지고 있었으며, 전자공여능의 경우 $DPPHSC_{50}$값이 $34.2{\pm}0.1\;{\mu}g$ DM/mL로 대조군인 ascorbic acid의 $6.8{\pm}0.1\;{\mu}g$ DM/mL과 비교하여 약 20% 정도의 높은 항산화력을 갖고 있었다. 또한, HPLC 분석을 통해 해당근 생물 100 g을 기준으로 240 mg의 EGCG와 50 mg의 kaempferol을 함유하는 것으로 나타났다. AGEs에 의해 유도된 HUVEC의 ROS 생성 저해 효과는 해당근 추출물 100, $500\;{\mu}g/mL$ 처리 시 각각 63, 77%로 나타났다. 또한, monocyte adherent assay에서 해당근 추출물은 $100\;{\mu}g/mL$ 처리시 정상을 0%로 하였을 때 AGEs에 의해 유도된 단핵구 부착을 33%, $500\;{\mu}g/mL$ 처리시 약 75% 정도로 농도 의존적으로 부착을 저해하는 것을 관찰할 수 있었으며, 유도되지 않은 HUVEC의 저항은 $113{\Omega}{\cdot}cm^2$ 에서 glycer-AGEs 처리 시 $88{\Omega}{\cdot}cm^2$로 낮아진 것을 해당근 추출물을 $100\;{\mu}g/mL$ 처리 시 약 $102{\Omega}{\cdot}cm^2$, $500\;{\mu}g/mL$ 처리시 약 $106{\Omega}{\cdot}cm^2$로 저항의 감소를 억제하는 것을 관찰할 수 있었다.

• Clinical and Experimental Pediatrics
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• 제51권5호
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• pp.487-491
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• 2008

목 적 : 마이코플라스마 폐렴은 일부 천식의 과거력이 없는 환자에서도 천명, 호흡곤란 등의 증상을 보여 천식의 발생과 관계된다고 한다. VEGF는 천식의 만성 염증 형성에 중요한 역할을 한다. 본 연구는 마이코플라스마 폐렴에서 천명이 동반되는 환아와 천명이 없는 환아에서 혈청 VEGF의 농도가 차이가 있는지 알아보고자 하였다. 방 법 : 2006년 8월부터 2007년 2월까지 고려대학교 안암병원 소아과에 천식의 과거력이 없는 마이코플라스마 폐렴으로 입원한 환아들 중 의사의 청진상 천명음이 처음으로 확인된 환아 9명(천명군)과 천명음이 한번도 없었던 비천명군 63명을 대상으로 혈청 VEGF농도, M. pneumoniae 항체가, 혈액 호산구 염증지표 및 혈청 IgE 농도 등을 측정하였다. 결 과 : 천명군의 혈청 VEGF 농도는 $650.2{\pm}417.9pg/mL$로 비천명군($376.5{\pm}356.2pg/mL$) 보다 높게 나타났고(P=0.049), M. pneumoniae 항체가도 천명군에서 더 높았다(1:1,380 vs. 1:596, P=0.048). 혈청 총IgE 값은 천명군이 591.8 IU/mL, 비천명군이 162.2 IU/mL 이었다(P=0.032). 두 군의 말초혈액 호산구수(천명군 : $263.0/{\mu}L$ vs. 비천명군 : $166.5/{\mu}L$)와 혈청 ECP 농도(천명군 : $22.8{\mu}g/L$ vs. 비천명군 : $17.4{\mu}g/L$)는 유의한 차이가 없었다. 천명군에서 혈청 VEGF 농도는 항체가와 유의한 상관관계를 보였다(r=0.568, P=0.034). 결 론 : 천식의 과거력이 없는 아토피 소아에서 높은 VEGF 농도는 마이코플라스마 폐렴에서 천명 발생과 관계가 있는 것으로 생각할 수 있으며, 이들 환자에서 앞으로 천식 발생 유무에 대한 추적 관찰이 필요하리라 생각한다.

• Clinical and Experimental Pediatrics
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• 제50권10호
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• pp.995-1004
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• 2007

목 적 : 가와사끼병은 전신성 혈관염으로 소아 후천성 심질환의 가장 흔한 원인이다. 혈관내피세포 생성인자는 미세혈관 투과성 및 혈관생성능력을 갖추고 있으며 가와사끼병에서 심장 합병증에 중요한 역할을 하는 것으로 알려져 있다. 가와사끼병에서 임상 양상, 심장 합병증, 감마글로불린 치료에의 반응 여부, 검사실 소견과 VEGF의 상관관계에 대하여 연구하였다. 방 법 : 가와사끼군은 49명을 대상으로 하였고, 대조군은 15명을 대상으로 하였다. 급성기, 아급성기, 회복기로 나누어 측정하였으며, 심장초음파 이상소견 및 감마글로불린 반응군 및 불응군을 정의하였다. 결 과 : 1) 가와사끼군과 대조군은 연령 및 체중에서 통계학적으로 유의한 차이는 없었다. 2) 급성 발열기 가와사끼군에서 혈청 VEGF가 대조군에 비해 유의하게 높았다. 3) 정형적 가와사끼군과 비정형 가와사끼군의 급성기 혈청 VEGF는 유의한 차이가 없었다. 4) 관상동맥 병변이 있는 군과 없는 군 간의 혈청 VEGF는 급성기와 아급성기 및 회복기에서 모두 유의한 차이가 없었다. 5) 심염이 있는 군과 없는 군 간의 혈청 VEGF는 급성기와 아급성기 모두에서 유의한 차이가 없었다. 6) 감마글로불린 반응군이 비반응군에 비해 급성기, 회복기 혈청 VEGF가 높았으나 유의한 차이는 없었고, 아급성기 혈청 VEGF는 불응군이 반응군에 비해 의미있게 높았다. 또한 감마글로불린 불응군 중에서 아급성기 혈청 VEGF가 급성기, 회복기에 비해 유의하게 높았다. 7) 회복기 관상동맥 변화 지속군과 비지속군의 급성기, 아급성기 혈청 VEGF의 차이는 의미 있었으나, 회복기 혈청 VEGF는 유의한 차이가 없었다. 8) 총 발열기간과 급성기 혈청 VEGF 간의 상관관계는 없었으나, 아급성기 혈청 VEGF는 뚜렷한 양의 상관관계를 보였다. 9) 급성기 혈청 VEGF는 적혈구침강속도, C-반응성단백과 양의 상관관계를 보였고 백혈구는 모든 시기의 혈청 VEGF와 뚜렷한 양의 상관관계를 보였다. 10) 급성기, 아급성기 혈청 VEGF는 혈색소와 뚜렷한 음의 상관관계를 보였으며 알부민과도 뚜렷한 음의 상관관계를 보였다. 결 론 : 혈청 VEGF는 가와사끼병의 중증도 판정에 도움을 줄 수 있으며 특히 아급성기 값이 심합병증의 예측인자로 사용 가능할 것으로 보인다. 검사실 소견과의 관계를 통해 염증반응지표와 밀접한 연관이 있는 것으로 생각되며 향후 더 엄격한 진단기준과 더 많은 대상 환아를 기초로 한 지속적인 연구가 필요할 것으로 사료된다.