• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.3
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• pp.253-263
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• 1995

Microsurgical vascularized bone transfer has the disadvantages of limitation of available donor sites, loss of donor function, and the possibility of donor site defects or deformity. To overcome these shortage of current microsurgical tissue transfer, the method of creating the neovascularized free flap has been introduced. Potentially, this technique must be an innovation in providing the free vascularized bone grafts that are not limited by natural vascular anatomy. But, as could be imagined technique resulted in unavoidable donor bone defect and additional operation for harvesting the autologous bone. The purpose of this study was to evaluate the efficacy of demineralized allogeneic bone as a possible substitute for autologous bone in fabricating the neo-osseous flap. By histologic, microangiographic and radioisotope method, the viability and vascularity of neo-osseous flap, which has been fabricated using allogeneic bone or autologous bone, was assessed in rat model. After 6 weeks, demineralized allogeneic bone showed consistent bone formation and neovascularization. The clinical and microscopic findings of demineralized allogeneic bone group were inferior to those of autogenous bone with regard to bone regeneration. The amount of bone blood floow per dry weight of demineralized allogeneic bone group was significantly higher than that of autogenous bone, even higher that of control intact iliac bone. In conclusion, findings supported that allogeneic bone could be the potential substitute for autologous bone source in creating a prefabricated neo-osseous flap.

• Natural Product Sciences
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• v.13 no.2
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• pp.128-131
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• 2007

Tumor angiogenesis is a critical step f3r the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffrutiocosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ more than 45% at the concentration of 100 ${\mu}$g/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (${\approx}$ 79% inhibition) and then n-BuOH fraction (${\approx}$ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ at the concentration of 100 ${\mu}$g/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate fur developing anti-angiogenic agent.

• Journal of Veterinary Clinics
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• v.19 no.3
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• pp.333-336
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• 2002

This experiment was carried out to investigate the optimal dose of intravitreal gentamicin that decreases intraocular pressure effectively and minimizes complications in dog. After inhalation anesthesia, gentamicin was injected intravitreally into the left eyes at doses of 10, 15 and 20 mg with 1 mg dexamethasone, respectively. Sterilized isotonic saline and dexamethasone mixture into the right eyes for control. Six dogs were used in each group. Intraocular pressures were measured using applanation tonometer(Mentore, Tono-Pen) until 5 months after injection of gentamicin. Ocular examinations were performed using direct ophthalmoscopy. The ocular volumes of both eyes were measured. Intraocular pressures of eyes injected with 10. 15 and 20 mg of gentamicin were decreased significantly compared with control eyes. Severe corneal opacity and neovascularization occurred in 20 mg treated group. Intraocular hemorrhage was observed in 3 dogs of 20 mg treated group. Ocular volume was significantly decreased(p <0.05) in 20 mg treated group, compared with 10 and 15 mg treated group. It is considered that intravitreal gentamicin injection at dose of 10 mg or 15 mg decrease intraocular pressure effectively and minimize complications such as corneal opacity, hyphema and phthisis bulbus.

• Biomedical Science Letters
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• v.25 no.3
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• pp.282-287
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• 2019

Skin flap necrosis remains a major complication of reconstructive surgery. Euterpe oleracea Mart., popularly known as "acai berry" contains hydroxybenzoic acid, antioxidant polyphenolics and anthocyanins. These and other compounds within the acai berry confer anti-inflammatory and anti-oxidative effects. In this current study, we evaluated the protective effect of acai berry extracts on survival of random-pattern skin flaps in a murine model by histologic analysis. ICR mice were subjected to skin elevation surgery and orally administered acai berry extract (100 mg/kg) daily for 7 days. Tissues were stained with hematoxylin-eosin or Masson's trichrome to observe tissue integrity and collagen deposition. In addition, $TGF-{\beta}$ and VEGF was stained by immunofluorescence to determine anti-inflammatory cell infiltration and neovascularization, respectively. We found a decrease in inflammatory cell infiltration and increase in collagen deposition in the acai berry extract treated mice compared to control mice. Immunofluorescence staining reveal a higher number of $TGF-{\beta}$ positive cells and enhanced VEGF staining in the acai berry extract treated mice. The results from this study indicate that oral uptake of acai berry extract can promote healing and survival of surgical skin flaps in mice providing an augmentative therapeutic approach to enhancing skin flap survival.

• Restorative Dentistry and Endodontics
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• v.48 no.2
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• pp.20.1-20.13
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• 2023

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.197-207
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• 2024

The potential of tivozanib as a treatment for oral squamous cell carcinoma (OSCC) was explored in this study. We investigated the effects of tivozanib on OSCC using the Ca9-22 and CAL27 cell lines. OSCC is a highly prevalent cancer type with a significant risk of lymphatic metastasis and recurrence, which necessitates the development of innovative treatment approaches. Tivozanib, a vascular endothelial growth factor receptor inhibitor, has shown efficacy in inhibiting neovascularization in various cancer types but has not been thoroughly studied in OSCC. Our comprehensive assessment revealed that tivozanib effectively inhibited OSCC cells. This was accompanied by the suppression of Bcl-2, a reduction in matrix metalloproteinase levels, and the induction of intrinsic pathway-mediated apoptosis. Furthermore, tivozanib contributed to epithelial-to-mesenchymal transition (EMT) inhibition by increasing E-cadherin levels while decreasing N-cadherin levels. These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.19-25
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• 2015

Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 ($T{\beta}4$), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by $T{\beta}4$ expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of $T{\beta}4$. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(${\beta}$-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of $T{\beta}4$ expression with $T{\beta}4$-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with $N^G$-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in $T{\beta}4$ expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-$T{\beta}4$ plasmids for $T{\beta}4$ overexpression. Taken together, these results suggest that $T{\beta}4$ could be a regulator for the expression of VEGF via the maintenance of NOS activity.

• Biomaterials and Biomechanics in Bioengineering
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• v.1 no.1
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• pp.27-39
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• 2014

We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres ($500-600{\mu}m$ in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats (n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule's external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

• Archives of Plastic Surgery
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• v.43 no.6
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• pp.491-497
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• 2016

Background Hypertrophic scarring is a pathological condition that occurs after trauma or surgery. Angiogenesis occurs more often with hypertrophic scarring than with normotrophic scarring. The regulation of angiogenesis is one of the key factors in hypertrophic scar management. Vascular endothelial growth factor (VEGF) is an essential factor in the angiogenetic response. This study investigated whether decreasing the level of VEGF is effective for treating hypertrophic scarring. Methods Ten 8-week-old female New Zealand white rabbits were included. Four defects were created on each ear by using a 6-mm punch. Bevacizumab (Avastin, Roche Pharma, Basel, Switzerland) was administered in one ear and normal saline was administered in the other ear. Treatment was administered starting on day 2, every 2 days, until day 14. The levels of VEGF were measured using enzyme-linked immunosorbent assay on day 10 and histologic results were analyzed on day 40. Results Bevacizumab induced-defects showed less hypertrophic scarring when compared with the control group as measured by the scar elevation index (SEI) and loose collagen arrangement. The SEI in the experimental group was $1.89{\pm}0.13$, compared to $1.99{\pm}0.13$ in the control group (n=30, P=0.005). Additionally, the VEGF level was lower ($38.72{\pm}11.03pg$ vs. $82.50{\pm}21.64pg$, n=10, P=0.001) and fewer vessels existed ($8.58{\pm}0.76$ vs. $7.2{\pm}1.20$, n=10, P=0.007). Conclusions Preventing excessive angiogenesis is effective for preventing scar formation, especially with hypertrophic scarring. Although it is not an approach that is sufficient alone for the management of scarring, it may be one of several important strategies for scar treatment.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.2
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• pp.269-278
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• 1996

To overcome the limitations of conventional microsurgical tissue transfer, experimental creation of various neo-flaps using the vessel implantation technique has been reported. We have performed some experiments of fabrication of neo-osseous flap with local vessels and iliac bone slabs to know that the flap vascularity and neo-angiogenesis are achieved enough to microtransfer. As a next step of our previous experiments, the flap viability and the histologic change between the recipient bone and neo-oseous flap was assessed after microsurgical transplantation. The flap was created on the rabbit femoral region(n=25) using femoral vessel and the iliac bone segments($2.5{\times}1.5cm$ in size). Three weeks after neovascularization, the newly formed flap was harvested and microtransferred to the mandibular defect. As a control, contralateral mandibular defect was created and reconstructed with conventional free iliac bone graft. Scintigrams of experimental group performed 3 days after microtransfer showed hot uptake, while that of control poor uptake. Histologic and vital stain labeling study revealed good bone viability and vascularity of neo-osseous flap. In conclusion, prefabricated neo-osseous flap of our model could be transferred to the recipient site with retaining the flap viability and showed advantages over the conventional bone graft in that it was living bone graft.