• Journal of Acupuncture Research
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• v.24 no.5
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• pp.23-32
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• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.

• Journal of Periodontal and Implant Science
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• v.50 no.5
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• pp.327-339
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• 2020

Purpose: The purpose of this study was to examine the local tissue reactions associated with 3 different poly(lactic-co-glycolic acid) (PLGA) prototype membranes and to compare them to the reactions associated with commercially available resorbable membranes in rats. Methods: Seven different membranes-3 synthetic PLGA prototypes (T1, T2, and T3) and 4 commercially available membranes (a PLGA membrane, a poly[lactic acid] membrane, a native collagen membrane, and a cross-linked collagen membrane)-were randomly inserted into 6 unconnected subcutaneous pouches in the backs of 42 rats. The animals were sacrificed at 4, 13, and 26 weeks. Descriptive histologic and histomorphometric assessments were performed to evaluate membrane degradation, visibility, tissue integration, tissue ingrowth, neovascularization, encapsulation, and inflammation. Means and standard deviations were calculated. Results: The histological analysis revealed complete integration and tissue ingrowth of PLGA prototype T1 at 26 weeks. In contrast, the T2 and T3 prototypes displayed slight to moderate integration and tissue ingrowth regardless of time point. The degradation patterns of the 3 synthetic prototypes were similar at 4 and 13 weeks, but differed at 26 weeks. T1 showed marked degradation at 26 weeks, whereas T2 and T3 displayed moderate degradation. Inflammatory cells were present in all 3 prototype membranes at all time points, and these membranes did not meaningfully differ from commercially available membranes with regard to the extent of inflammatory cell infiltration. Conclusions: The 3 PLGA prototypes, particularly T1, induced favorable tissue integration, exhibited a similar degradation rate to native collagen membranes, and elicited a similar inflammatory response to commercially available non-cross-linked resorbable membranes. The intensity of inflammation associated with degradable dental membranes appears to relate to their degradation kinetics, irrespective of their material composition.

• Journal of Korean Academy of Nursing
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• v.36 no.3
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• pp.523-531
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• 2006

Purpose: The purpose of this study was to examine the effects of the ulmus root-bark dressing on tissue regeneration in experimentally-induced pressure ulcers in rats. Method: A randomized pretest/post-test control group time-series study design was used. Thirty-three male Sprague-Dawley rats were used in this study. The rats were anesthetized with 100mg/kg of ketamine. Pressure ulcers were induced at 140mmHg for three hours using a personally-designed pressing apparatus. For four weeks, the ulmus root-bark dressing was applied every other day in the experimental group (n=18) and a wet gauze dressing in the control group (n=15). For data analysis, the statistical program SPSS WIN 12 was used. The wounds were examined by light microscopy andelectron microscopy. Result: There were significant statistical differences in the size of the pressure ulcers as time went by(p=0.006). It should be noted that there were no significant statistical differences in the number of capillaries. Using light microscopy the inflammatory infiltration and neovascularization in the dermis in the experimental group emerged densely in the early stages, but recovered rapidly at the latter stages. In addition, the reepithelization of the epidermis occurred earlier than in the control group. By electron microscopy, the cell organelles of the capillary endothelial cells and the basal lamina of capillaries in the experimental group showed a more rapid maturation during the latter stages, compared with the control group. Conclusion: According to this study, it can be concluded that the ulmus root-bark dressing is effective regarding the healing of pressure ulcers.

• BMB Reports
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• v.53 no.11
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• Molecules and Cells
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• v.38 no.3
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• pp.273-278
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• 2015

The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

• Journal of Veterinary Clinics
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• v.32 no.1
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• pp.108-111
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• 2015

A 7-month-old intact male Maltese dog was presented with a 1.5-month history of glaucoma in the right eye (OD). Ophthalmic examinations revealed a corneal perforation with iris entrapment, corneal edema and neovascularization, and buphthalmos OD. Intraocular pressures were 33 mmHg OD and 19 mmHg in left eye (OS). The right eye was diagnosed with chronic glaucoma and corneal perforation with iris entrapment. Now that the eye was blind, implantation of intraocular silicone prosthesis (ISP) and conjunctival flap were elected to salvage the globe. The corneal perforation healed with the conjunctival pedicle flap and the cornea accommodated the ISP properly. A satisfactory cosmetic result was achieved without complications in the 15 months following the procedure. Therefore, this case report indicates the combined an ISP and a conjunctival flap would be an alternative for the treatment of glaucoma associated with corneal perforation in dogs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3415-3418
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• 2014

Background: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. Materials and Methods: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. Results: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). Conclusions: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas.

• Archives of Reconstructive Microsurgery
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• v.11 no.2
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• pp.125-134
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• 2002

This study was designed to investigate the process of re- or neo-vascularization in the prefabricated cutaneous flap using a skeletonized arteriovenous pedicle implantation. Fourty-eight flaps were divided into six groups of eight flaps, including control group of the conventional epigastric flap. In experimental groups, skin flap was fabricated by subcutaneous implantation of a distally ligated saphenous arteriovenous pedicle in left abdomen. At 2, 4, 6, 8, and 10 weeks after, prefabricated flap was elevated as an island flap based on implanted pedicle and sutured back in place. Three days after flap repositioning, the area of flap viability was quantified, the pattern of flap vascularization was evaluated with microangiography, and the quantification of vessels was assessed histologically. There were statistically significant differences in flap viability between group 2, 3, 4, and the control (p<0.05), with increased survival area in order. But Group 5 and 6 showed higher flap viability as much as the control did. In the microangiographis study, numerous small meander vessels were newly developed in the vicinity of the implanted pedicle just only 2 weeks after pedicle implantation, but neovascularization around the tip of implanted pedicle, and its anastomosis with native vasculatures was more important for overall flap survival, which was usually developed at least 4 weeks after pedicle implantation. Histologically, vessels are evenly spread over all layers of the flap at 6 weeks after pedicle implantation. The quantification of vessels was correlated well with the improvement of flap viability (p<0.05). In conclusion, neo- and re-vascularization around the tip of implanted pedicle was an important factor for overall survival of the prefabricated flap. Therefore, skeletonized pure vascular pedicle transfer, even though it used alone without surrounding was sufficient to get higher flap viability. The optimal duration of pedicle implantation was8 weeks to obtain maximal survival.

• Development and Reproduction
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• v.11 no.3
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• pp.253-261
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• 2007

Lactadherin is a glycoprotein of human milk fat globule membrane that binds to mucin and butyrophilin forming the protein complex. Especially, mucin and lactadherin in human milk efficiently protect infants with poor immune functions right after birth from infections by microorganisms and play important roles for their early survival, growth and development. Lactadherin inhibits the propagation and growth of rotavirus that is a global pathogen causing infants' diarrhea. Recently this protein was known to promote neovascularization and its deficiency related to develop Alzheimer's disease. In this study, the basic biochemical and physiological aspects of lactadherin were investigated. Messenger RNAs were isolated from mammary tissues from Korean women patients to clone a 1.2 kb cDNA and sequenced its DNA to determine its amino acid sequences. The cDNA was cloned to express its 43 kD protein in E. coli, which was confirmed by Western blot. The recombinant protein was purified and injected to 2 rabbits to raise antibodies against it. The semi-purified milk fat globule membrane proteins from Korean women was analyzed by Western blot using the rabbit antibody to give 70, 55, 46, 30 kD bands. Also several polymorphism and SNPs of lactadherin gene from Korean women were observed compared with those of Caucasian women.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.191-198
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• 1998

Objectives: We performed an immunohistochemical study to examine the place of neovascularization in the tumorigenic process of follicular thyroid carcinoma and to determine whether tumor angiogenic activity in follicular carcinoma plays a role in tumor aggression. Materials & Methods: We studied 63 follicular thyroid carcinomas and compared with 22 follicular adenomas. The areas of capsular invasion, vascular invasion and cellular atypism of the tumor were confimed on H & E stains. The paraffin embedded tissues were stained by the use of monoclonal antibodies against Ag CD34. Microvesseles were counted in the area of highest vascular density at 200 times magnification. The microvessel densities(MVD) were analized in relation to histologic type and location of the tumors. Results: There were 59 minimal invasive types and 4 widely invasive types of carcinoma. In the histologic specimens of carcinomas, capsular invasion was identified in all the cases, vascular invasion in 46 and cellular atypism in 24. Mean values of the MVDs of the minimal invasive carcinomas, the widely invasive carcinomas and the adenomas were $263.8{\pm}69.2,\;256.l{\pm}49.3\;and\;241.5{\pm}159.4$, respectively and there was no significant difference between each group. In follicular carcinomas, there was a regional difference of the MVDs. The areas of tumor showing cellular atypism and adjacent to or penetrating the capsule, in which represents the tumorigenic process of carcinoma, had a higher rate of vascularization, than other areas of the tumor(p<0.05). However, these features were not noted in the follicular adenomas. Conclusion: Although there was no significant difference of the MVD between follicular carcinomas and adenomas, there was a regional difference of the MVD within the carcinomas and the values were significantly higher in the more malignant areas, as indicated by cellular atypism and capsular invasion. Therefore, tumor angiogenic activity measured by MVD may play a role in tumor aggression in follicular thyroid carcinoma.