• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.135-141
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• 2011

Objective: Ovarian angiogenesis plays an important role in folliculogenesis. However, little is known about the expression of angiogenic factors during follicular development according to female age. Stromal cell derived factor-$1{\alpha}$ (SDF-$1{\alpha}$) plays a role in granulosa cell survival and embryo quality as an angiogenic chemokine. Leptin is also involved in folliculogenesis and angiogenesis. This study examined expression of SDF-$1{\alpha}$ and leptin, and their effects on the expression of angiogenic factors in the ovary during follicular development according to female age. Methods: Ovaries were collected from C57BL mice of two age groups (6-9 weeks and 24-26 weeks) at 6, 12, 24, and 48 hours after 5 IU pregnant mare's serum gonadotropin (PMSG) injection. The expression of ovarian SDF-$1{\alpha}$ and leptin mRNA was evaluated by RT-PCR. In the organ culture experiment, the ovaries were cultured in transwell permeable supports with Waymouth's medium treated with various doses of SDF-$1{\alpha}$(50-200 ng/mL) or leptin (0.01-1 ${\mu}g$/mL) for 7 days. Then, mRNA expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and visfatin were examined in the cultured ovaries. Results: Expression of SDF-$1{\alpha}$ and leptin in the ovary was significantly lower in the aged mouse group compared to the young mouse group ($p$ <0.05). Expression of these two factors increased with follicular development after PMSG administration. SDF-$1{\alpha}$ treatment stimulated visfatin expression in a dose-dependent manner, while leptin treatment significantly increased eNOS expression. Conclusion: These results suggest that decrease of ovarian SDF-$1{\alpha}$ and leptin expression may be associated with aging-related reduction of ovarian function. SDF-$1{\alpha}$ and leptin may play a role in follicular development by regulating the expression of angiogenic factors in mouse ovaries.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.136-144
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• 2007

Biotae Orientalis has been widely used for treatment of relaxion of smooth muscle, gastrointestinal hemorrhage and alopecia in Oriental Medicine. This experiment examined the effect of an extracts, obtained from the acetone and MeOH extracts of dried or fresh Biotae Orientalis, on hair growing activity of the C57BL/6N mice after topical application to skin. First, We examined on hair growth activity of extracts of Biotae Orientalis compare to control and 1% minoxidil groups. Second, We investigated on the number of hair follicle and mast cells after topical application of extracts of the Biotae Orientalis to skin for 16 day. Third, We investigated immunoreactive density of vascular endothelial growth factor(VEGF), protein kinase C-${\alpha}$(PKC-${\alpha}$) and stem(mast) cell factor(SCF) in skin of C57BL/6N mice by immunohistochemical methods. I fourth investigated changes of subpopulation of splenocytes and thymocytes in C57BL/6N mice for 16day using laser flow cytometry. The results were as follows : Hair growing effect of acetone and MeOH extracts of dried and fresh Biotae Orientalis was observed in 70%, 90% and 60% in hair removed skin area in 16 day respectively. Immunoreactive density of VEGF and PKC-${\alpha}$ in skin of experimental groups was weakly stained compare to control group in 10 day. Immunoreactive density of stem cell factor in skin of experimental group was heavily stained compare to control group in 10 day. Splenic TH/TC Iymphocytes of lived MeOH extracts group significantly increased compare to control group. TH cells in thymic T lymphocytes were increased compare to control group. These experiment suggest that acetone and MeOH extracts of Biotae Orientalis may be used for topical treatment of alopecia areata.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.2
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• pp.169-180
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• 2022

Streptococcus sp. is generally known as a strain that produces hyaluronic acid. In this study, we focused on ingredients other than hyaluronic acid among several metabolites produced by Streptococcus sp. during cultivation. The hair experimental sample (HAIRCLE^TM) was prepared with Streptococcus sp. culture filtrate under the condition that hyaluronic acid was not produced and the effect on the hair was identified. Tensile strength of hair was tested with a universal testing machine (UTM). Surface properties of a hair were examined with an atomic force microscope (AFM). Our results suggest that HAIRCLE^TM could prevent damage to a hair such as destroyed-cuticle, increased-faction force, and broken-hair. Furthermore, hair-related experiments confirmed that HAIRCLE^TM could promote the expression of hair growth factors VEGF, HGF, and Wnt10b and mitigate male hair loss by inhibiting androgen receptors and TGF-β2 expression. In addition, it was confirmed that the expression of barrier-related factors (INV, CLDN-1) was increased for oxidative stress, and the COX-2 expression, an inflammatory factor, was inhibited, thereby improving damaged scalp barriers and alleviating induced inflammation.

• Archives of Plastic Surgery
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• v.44 no.3
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• pp.194-201
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• 2017

Background Platelet-rich plasma (PRP) contains high concentrations of growth factors involved in wound healing. Hydrogel is a 3-dimensional, hydrophilic, high-molecular, reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. This study aimed to investigate the effects of PRP and hydrogel on wound healing, in combination and separately, in an animal wound model. Methods A total of 64 wounds, with 2 wounds on the back of each nude mouse, were classified into 4 groups: a control group, a hydrogel-only group, a PRP-only group, and a combined-treatment group. All mice were assessed for changes in wound size and photographed on scheduled dates. The number of blood vessels was measured in all specimens. Immunohistochemical staining was used for the analysis of vascular endothelial growth factor (VEGF) expression. Results Differences in the decrease and change in wound size in the combined-treatment group were more significant than those in the single-treatment groups on days 3, 5, 7, and 10. Analysis of the number of blood vessels through histological examination showed a pattern of increase over time that occurred in all groups, but the combined-treatment group exhibited the greatest increase on days 7 and 14. Immunohistochemical staining showed that VEGF expression in the combined-treatment group exhibited its highest value on day 7. Conclusions This experiment demonstrated improved wound healing using a PRP-hydrogel combined treatment compared to either treatment individually, resulting in a decrease in wound size and a shortening of the healing period.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.13-22
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• 2007

Objectives : The differentiation of osteoblasts is controlled by various growth factors and matrix protein expressed in bone. The aim of this study was to investigate the effects of many herbs medicine(KHBJs) for bone healing that induces osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic effects of KHBJs were evaluated by using cell proliferation(WST-8) assay, alkaline phosphatase(ALP) activity assay, colorimetric analysis of vascular endothelial growth factor(VEGF) expression in human osteoblast like SaOS-2 cell. Also, osteogenic activity of KHBJ fractions(KHBJB and KHBJR) by activity guided fractionation were evaluated. Results : About 7 KHBJs had effect on the proliferation of osteoblast like SaOS-2 cells, and dose-dependently increased alkaline phosphatase(ALP) activity. KHBJs markedly increased expression for VEGF. Fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs on osteogenic activity in SaOS-2 cells. Conclusions: This study found that 7 KHBJs had effect on proliferation, ALP activity, and VEGF expression in osteoblast like SaOS-2 cells. These results propose that KHBJs can play an important role in osteoblastic bone formation, and may possibly lead to the development of bone-forming drugs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• Journal of Biosystems Engineering
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• v.39 no.3
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• pp.235-243
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• 2014

Purpose: The aim of this study was to prepare and evaluate a natural material extracted from germinated brown rice (GBR). Herein, we evaluated whether the natural material could positively activate the biological effects seen during bone formation, including enhancement of metabolic activity, osteogenesis, and the expression of vascular endothelial growth factor (VEGF), one of the growth factors in human osteoblast-like cells. Methods: The natural material was created by a hot water extraction process after being soaked for 2~3 days in tap water and dried at $50^{\circ}C$. The material was characterized using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transformed infrared (FTIR) spectroscopy. The biological behaviors of the material were also investigated; we performed tests to assess cell cytotoxicity, metabolic activity, osteogenic markers related to bone formation, and VEGF. Results: The EDX, XRD, and FTIR results for the natural material indicated the presence of organic compounds. The natural material caused positive increases in cell metabolic activity and mineralized bone formation without cytotoxicity. The protein levels in the extract for the $6.25{\mu}g/mL$, $12.25{\mu}g/mL$, $25{\mu}g/mL$, $50{\mu}g/mL$, and $100{\mu}g/mL$ groups were significantly different from that for the control. Conclusions: The GBR-based natural material was easy to prepare and had characteristics of a potential biomaterial. The biocompatibility of this natural material was evaluated using in vitro techniques; our findings indicate that this novel material is promising for agricultural and biological applications.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.181-190
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• 2005

Background & Object : The differentiation of osteoblasts controlled by various growth factors and matrix proteins expression in bone. The aim of this study was to identify the Astragalus membranaceus that may induce the osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic activity of Astragalus membranaceus were evaluated by WST-8 assay, ALP activity, RT-PCR analysis of VEGF, OCN, OPN, Col I mRNA, and ELISA or colorimetric analysis, and mineralization by Alizarin red staining in SaOS-2 cells. Results : Astragalus membranaceus had no effect on viability of osteoblastic cells, and dose dependently increased alkaline phosphatase (ALP) activity. Astragalus membranaceus markedly increased mRNA expression for vascular endothelial growth factor (VEGF), osteocalcin (OCN), osteopontin (OPN), and type I collagen (Col 1) in SaOS-2 cells. Extracellular accumulation of proteins such as VEGF, and Col I was increased in a dose-dependent manner. Also, Astragalus membranaceus significantly induced mineralization in the culture of SaOS-2 cells. Conclusion : This study showed that Astragalus membranaceus not affect on viability, but it enhanced ALP activity, VEGF, bone matrix proteins such as OCN, OPN and Col I, and mineralization in SaOS-2 cells. These results propose that Astragalus membranaceus plays an important role in osteoblastic bone formation, and possibly lead to the development of bone-forming drug.

• Journal of Chest Surgery
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• v.54 no.3
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• pp.191-199
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• 2021

Background: Tracheal replacement is a challenge for thoracic surgeons due to stenosis in the trachea-prosthesis anastomosis. We propose that stenosis occurs due to fibrosis as a result of an abnormal healing process, characterized by an increased expression of wound healing growth factors (vascular endothelial growth factor [VEGF], survivin, and CD31), which promote angiogenesis and decrease apoptosis. We analyzed the immunoreactivity of VEGF, survivin, CD31, and caspase-3 in the development of fibrotic stenosis in prosthetic tracheal replacement. Methods: Fourteen dogs were operated on: group I (n=7) received a 6-ring cervical tracheal segment autograft, while in group II (n=7), a 6-ring segment of the cervical trachea was resected and tracheal continuity was restored with a Dacron prosthesis. The follow-up was 3 months. Immunoreactivity studies for VEGF, survivin, CD31, and caspase-3 were performed. A statistical analysis was done using the Wilcoxon signed rank test. Results: Four animals in group I were euthanized on the 10th postoperative day due to autograft necrosis. Three animals completed the study without anastomotic stenosis. Moderate expression of VEGF (p=0.038), survivin (p=0.038), and CD31 (p=0.038) was found. All group II animals developed stenosis in the trachea-prosthesis anastomotic sites. Microscopy showed abundant collagen and neovascularization vessels. Statistically significant immunoreactive expression of VEGF (p=0.015), survivin (p=0.017), and CD31 (p=0.011) was observed. No expression of caspase-3 was found. Conclusion: We found a strong correlation between fibrosis in trachea-prosthesis anastomoses and excessive angiogenesis, moderate to intense VEGF, CD31, and survivin expression, and null apoptotic activity. These factors led to uncontrolled collagen production.