• Title/Summary/Keyword: Neovascularization

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The In Vitro Promoting Angiogenesis Roles of Exosomes Derived from the Protoscoleces of Echinococcus multilocularis

  • Wenjing Zhou;Xiang Li;Xinqi Yang;Bin Ye
    • Journal of Microbiology and Biotechnology
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    • v.34 no.7
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    • pp.1410-1418
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    • 2024
  • Alveolar echinococcosis (AE) is a persistent parasite condition that causes the formation of tumorlike growths. It is a challenge to treat the disease. These growths need neovascularization to get their oxygen and nutrients, and the disease is prolonged and severe. Considerable research has been conducted on exosomes and their interactions with Echinococcus multilocularis in the context of immunological evasion by the host. However, the extent of their involvement in angiogenesis needs to be conducted. The primary objective of this investigation was to preliminarily explore the effect of exosomes produced from E. multilocularis protoscoleces (PSC-exo) on angiogenesis, to elucidate the mechanism of their roles in the regulation of the downstream pathway of VEGFA activation, and to provide ideas for the development of novel treatments for AE. The study evaluated the impact of PSC-exo increases proliferation, migration, invasion, and tube formation of HUVECs at concentrations of up to 50 ㎍/ml. In addition, the study sought to validate the findings in vivo. This effect involved increased VEGFA expression at gene and protein levels and AKT/mTOR pathway activation. PSC-exo are crucial in promoting angiogenesis through VEGFA upregulation and AKT/mTOR signaling. This research contributes to our knowledge of neovascularization in AE.

The Clinical Significance of Measurement of Serum Vascular Endothelial Growth Factor in Patients with Hemoptysis (객혈환자에서 혈청 Vascular Endothelial Growth Factor 검사의 유용성)

  • Lo, Dae-Keun;Kim, Seung-Joon;Lee, Sook-Young;Kim, Young-Kyoon;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.2
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    • pp.137-144
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    • 2002
  • Background: Hemoptysis is an often alarming presenting symptom and VEGF is a major regulator of both normal and abnormal angiogenesis, including many inflarrunatory diseases. In this report the clinical significance of the serum VEGF level in patients with hemoptysis was investigated. Methods: Thirty-two patients with hemoptysis were evaluated. The estimated amount of hemoptysis, etiology and serum VEGF level was examined at admission and bronchial angiography was performed in 22 patients. In order to objectify the neovascularization status, one point for the presence of the A-V shunt, hypervascularity, vascular tortuosity was designated for a total of 0-3 points. Results: Mean quantity of hemoptysis was $172.4{\pm}270.4ml$. The mean angiographic neovascularization score was $1.23{\pm}0.75$. The serum VEGF level correlated with the quantity of hemoptysis(r=0.524, p=0.002) and with the angiographic neovascularization score(r=0.441, p=0.04). Using the standard diagnostic criterion for massive hemoptysis, the serum VEGF level of patients with massive hemoptysis($642.4{\pm}545.6$ pg/ml, n=13) was found to be higher than that of patients with non-massive hemoptysis($394.6{\pm}225.8$ pg/ml, n=19) (p=0.069). Conclusion: Regardless of the etiology, the serum VEGF may contribute to abnormal neovascularization in patients with hemoptysis. Therefore, it is suggested that serum VEGF measurements may help in predicting a massive hemoptysis.

Correlation between the Rotator Cuff Disease Type and the Adhesive Capsulitis Development Time (회전근개 손상의 특징에 따른 유착성 관절낭염 이환 시기와의 상관관계)

  • Heo, Kwang-Ho;Lee, Chang-Hyung;Min, Ji-Hong;Kim, Soo-Yeon;Park, Yeo Jin;Koo, Bon-Il;Kim, Sang-Hoon;Shin, Yong-Il;Hwang, Eui-Hyoung
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.1
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    • pp.77-82
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    • 2014
  • Objectives Adhesive capsulitis (AC) is a restricted shoulder range of motion. Rotator cuff disease (RCD) has been believed to be a major etiologic factor of AC, however, how soon is the development time from RCD to AC (DTRA) has not been elucidated. The purpose of our study was to evaluate the correlation between the ultrasonographic characteristics of RCD and the DTRA. Methods Total 40 patients who were diagnosed as AC were recruited. The clinical characteristics of RCD were diagnosed by ultrasonography and classified with the Southern California Orthopedic Institute for Rotator Cuff Classification. The correlation was analyzed with Mann-Whitney U test and one-way analysis of variance. Results 60% of full thickness tear and 40% of partial thickness tear patients (10 male and 30 female, mean age of $54.0{\pm}8.4$ years) and 38% of bursitis and 21% of neovascularization were observed. The mean value of DTRA was $74.8{\pm}131.3$ days. There were no correlation between DTRA and gender (p=0.63), location of the partial tear (p=0.63), the severity of the partial thickness tear (p=0.63), full thickness tear (p=0.66) and completeness of the tear (p=0.16). The presence of bursitis or neovascularization was not associated with DTRA (p=0.60, p=0.61). Conclusions Although RCD is a major etiologic factor of AC, the severity, the type of RCD and the presence of bursitis and neovascularization were not statistically correlated with the DTRA in our study. Comprehensive consideration about etiologic factor analysis of AC will be needed with prospective study design for future study.

In-vivo Studies on Effect of Lipo-PGE1 on Neoangiogenesis of Composite Graft in a Rabbit Model (가토모델에서 Lipo-PGE1이 복합조직이식편의 미세혈관신생에 미치는 영향)

  • Park, Ji-Ung;Eo, Su-Rak;Cho, Sang-Hun;Choi, Jong-Sun;Kim, Eo-Jin
    • Archives of Plastic Surgery
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    • v.37 no.6
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    • pp.721-725
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    • 2010
  • Purpose: The survival of composite graft is dependent on three steps, (1) plasmatic imbibitions, (2) inosculation, and (3) neovascularization. Among the many trials to increase the survival rate of composite graft, prostaglandin E1 (PGE1) has beneficial effects on the microcirculatory level with vasodilating, antithrombotic, anti-inflammatory and neoangiogenic properties. Lipo-PGE1 which is lipid microspheres containing PGE1 had developed to compensate the systemic and local side effects of PGE1. This study was proposed to determine whether Lipo-PGE1 administration enhanced the survival of composite graft through neovascularization quantitatively in a rabbit ear model. Methods: Fourteen New Zealand White Rabbits each weighing 3~4 kg were divided in two groups: (1) intravenous Lipo-PGE1 injection group and (2) control group. A $2{\times}1\;cm$ sized, full-thickness rectangular composite graft was harvested in each auricle. Then, the graft was reaaproximated in situ using a 5-0 nylon suture. For the experimental group, $3{\mu}g$/kg/day of Lipo-PGE1 ($5{\mu}g$/mL) was administered intravenously through the marginal vein of the ear for 14 days. The control group was received no pharmacologic treatment. On the 14th postoperative day, composite graft of the ear was harvested and immunochemistry staining used Monoclonal mouse anti-CD 31 antibody was performed. Neoangiogenesis was quantified by counting the vessels that showed luminal structures surrounded by the brown color-stained epithelium and counted from 10 random high-power fields (400x) by independent blinded observer. Statistical analysis (Wilcoxon Signed Ranks test for nonparametric data) was performed using SPSS v12.0, with values of p<0.05 considered significant. Results: The mean number of the microvessels was $15.48{\pm}8.65$ in the experimental group and $9.82{\pm}7.25$ in the control group (p=0.028). Conclusion: The use of Lipo-PGE1 facilitated the neoangiogenesis, resulted in the improvement of the survival rate of graft. On the basis of this results, we could support wider application of Lipo-PGE1 for more effective therapeutic angiogenesis and successful survival in various cases of composite graft in the human.

Hitological Changes on the Wound Healing Process of Alkali Burned Mouse Cornea (알칼리 화상을 입은 마우스 각막에서 상처 치유과정 중 관찰된 조직학적 변화)

  • Lee, Ji-Young;Lee, Koon-Ja
    • Journal of Korean Ophthalmic Optics Society
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    • v.13 no.4
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    • pp.161-169
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    • 2008
  • Purpose: To better understand the corneal regeneration after alkali burn regarding the initial clinical progression and the therapy, we investigated the changes of the multi factors following chemical injury in cornea. Methods: This study was performed to observation on the healing process of alkali burned cornea in aspect of immunohistochemistry by immunofluorescence or H-E staining and TUNEL assay. Results: The results showed that although a healing process occurred after alkali burn, apoptosis of epithelial, stromal and endothelial cells in the cornea was continuously observed. Neovascularization and expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) from limbus and from injured cornea, respectively, were observed after 3 days of alkali burn. Formation of collagen III in corneal stroma and increased expression of chondroitin sulfate are coincident with expression of ${\alpha}$-SMA and transforming growth factor-${\beta}$ (TGF-${\beta}$). Conclusions: These data suggest that medical treatment within 3 days of alkali burn will be effective to inhibit neovascularization and formation of collagen III and chondroitin sulfate. This study extends our immumohistochemical understanding of healing process in alkali burned cornea, and the results get in this study will be cornerstones in the development of therapeutic agent for accelerating renewal of chemical damaged cornea.

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Correlations of Oral Tongue Cancer Invasion with Matrix Metalloproteinases(MMPs) and Vascular Endothelial Growth Factor(VEGF) Expression (Matrix Metalloproteinases(MMPs) 및 Vascular Endothelial Growth Factor(VEGF)의 발현을 통한 구강 설암의 침윤 기전 연구)

  • Kim Se-Heon;Cho Nam-Hoon;Lim Jae-Yul;Kim Ji-Hoon;Kim Jeong-Hong;Chang Jung-Hyun;Choi Eun-Chang
    • Korean Journal of Head & Neck Oncology
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    • v.21 no.1
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    • pp.3-9
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    • 2005
  • Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization

  • Hyun Kim;Yoori Choi;Youngsun Lee;Jae-Kyung Won;Sung Ho Lee;Minseok Suh;Dong Soo Lee;Hyun-Seung Kang;Won-Sang Cho;Gi Jeong Cheon
    • Journal of Korean Neurosurgical Society
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    • v.67 no.2
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    • pp.146-157
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    • 2024
  • Objective : Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. Methods : The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. Results : The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. Conclusion : Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.

Antiangiogenic Effect of 3--O-D-galactopyranosylglyceride Isolated from Chrysanthemum Coronarium L. (개채에서 분리한 3-O--D-galactopyranosylglyceride의 혈관형성 저해효과)

  • Lee Hyun Cheol;Song Ho Chul;Lim Jin Ki;Khil Jae Ho;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1602-1607
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    • 2004
  • 3-O-D-galactopyranosylglyceride (GPG; fatty acids R1, R2 = myristic acid 11.62%, palmitic acid 61.90% and oleic acid 26.48%) was isolated from Chrysanthemum coronarium L that has been used for treating renal and cardiovascular diseases as one of vegetables or medicinal drug. However, little was known about the anti-angiogenic activity of GPG. Thus, anti-angiogenic effect of GPG was evaluated in human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. GPG effectively inhibited bFGF-induced migration and invasion of HUVECs in a concentration-dependent manner, whereas it did not inhibit bFGF-induced proliferation and capillary-like tube formation of HUVECs. To examine the mechanism of anti-angiogenic activity of GPG, gelatin zymography was carried out. GPG downregulated the expression of matrix metalloproteinase-2 in a concentration-dependent manner. Furthermore, GPG significantly disrupted bFGF-induced neovascularization on the chick chorioallantoic membrane assay in vivo. These results suggest that 3-O--D-galactopyranosylglyceride may inhibit neovascularization by inhibiting angiogenic activity of endothelial cells via regulation of matrix metalloproteinase-2 (MMP-2).

The Role of Basic Fibroblast Growth Factor in Moyamoya Disease (모야모야병에서 염기성 섬모 세포 성장 인자의 역할)

  • Kim, Dong-Seok;Choi, Joong-Uhn;Kim, Se-Hyuk;Yang, Kook-Hee;Kim, Hyeun-Sook
    • Journal of Korean Neurosurgical Society
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    • v.30 no.1
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    • pp.5-11
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    • 2001
  • Objectives and Importance : The present study investigated the levels of basic fibroblast growth factor(bFGF) in the CSF of patients with moyamoya disease and its clinical significance. Methods : The levels of bFGF in CSF, taken from 26 hemispheres of 14 moyamoya patients and 20 patients without vascular anomaly(control group), were measured by an enzyme-linked immunosorbent assay. We analyzed the correlation between the level of bFGF and the clinical factors such as age, onset pattern, development of neovascularization, and cerebral circulation. Results : The CSF of moyamoya patients contained a high concentration of bFGF to a significant extent. The bFGF level was apparently elevated in the patients in whom neovascularization from indirect revascularization, such as modified encephalo-duro-arterio-synangiosis(EDAS) was well developed. A linear correlation between the values of bFGF and clinical progression was noted. Conclusions : The elevation of bFGF in moyamoya disease seems to be specific. Clinically, the bFGF level may be considered a useful indicator to predict the efficacy of indirect revascularization.

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The Neovascularization Effect of Bone Marrow Stromal Cells in Temporal Muscle after Encephalomyosynangiosis in Chronic Cerebral Ischemic Rats

  • Kim, Hyung-Syup;Lee, Hyung-Jin;Yeu, In-Seung;Yi, Jin-Seok;Yang, Ji-Ho;Lee, Il-Woo
    • Journal of Korean Neurosurgical Society
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    • v.44 no.4
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    • pp.249-255
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    • 2008
  • Objective : In Moyamoya disease, the primary goal of treatment is to improve collateral circulation through angiogenesis. In the present study, we obtained and sub-cultured bone marrow stromal cells (BMSCs) from rats without a cell-mediated immune response. Then, we injected the labeled BMSCs directly into adjacent temporal muscle during encephalomyosynangiosis (EMS). Three weeks after BMSC transplantation, we examined the survival of the cells and the extent of neovascularization. Methods : We divided 20 rats into a BMSC transplantation group (n=12) and a control group (n=8). Seven days after the induction of chronic cerebral ischemia, an EMS operation was performed, and labeled BMSCs ($1{\times}106^6/100\;{\mu}L$) were injected in the temporal muscle for the transplantation group, while an equivalent amount of culture solution was injected for the control group. Three weeks after the transplantation, temporal muscle and brain tissue were collected for histological examination and western blot analysis. Results : The capillary/muscle ratio in the temporal muscle was increased in the BMSC transplantation group compared to the control group, showing a greater increase of angiogenesis (p<0.05). In the brain tissue, angiogenesis was not significantly different between the two groups. The injected BMSCs in the temporal muscle were vascular endothelial growth factor (VEGF)-positive by immunofluorescence staining. In both temporal muscle and brain tissue, the expression of VEGF by western blot analysis was not much different between the two groups. Conclusion : During EMS in a chronic cerebral ischemia rat model, the injection of BMSCs resulted in accelerated angiogenesis in the temporal muscle compared to the control group.