• 동의생리병리학회지
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• 제36권5호
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• pp.175-180
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• 2022

The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.

• Korean Journal of Acupuncture
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• 제26권2호
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• pp.27-38
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• 2009

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, principally characterized by synovial inflammation of the joints. We previously reported the effect of acupuncture for RA, but the mechanism is still unclear. Various factors such as oxidative stress and angiogenesis were involved in the pathogenesis of RA, and recently, it has also been reported that cytokines also play a major role in RA. Thus, we investigated whether acupuncture could induce any changes in the levels of cytokines including vascular endothelial growth factor (VEGF), angiogenin and epidermal growth factor (EGF) as well as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF) in the sera of RA patients. Methods: The forty three patients who met the American College of Rheumatology (ACR) criteria for RA recruited. The acupuncture group (n=21) underwent 14 sessions of partially individualized acupuncture treatment for 6 weeks, and the control group had no treatment (n=13) over the same periods. We evaluated ESR, CRP and RF. In addition, to find out the mechanism of acupuncture, we assessed the changes of the cytokine activities using protein cytokine array in the sera of the patients. Results: Acupuncture significantly decreased the levels of ESR and CRP, but RF were not changed after 6-week acupuncture treatments. Moreover, acupuncture reduced the levels of VEGF, angiogenin and EGF in the sera of the patients. Interestingly, they were related with angiogenesis, which is an important process in the pathogenesis of RA. The levels of oncostatin, interleukin(IL)-$1{\alpha}$, IL-8, leptin, monocyte chemotactic protein-1, macrophage-derived chemokine, macrophage inflammatory proteins-1, platelet-derived growth factor BB and RANTES were not changed significantly. Conclusions: The effect of acupuncture for reliving RA symptoms can be partially explained by inhibition of angiogenesis factors in the sera of the RA patients.

• Journal of Periodontal and Implant Science
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• 제33권4호
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• pp.573-584
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• 2003

Bone remodeling results from the combined process of bone resorption and new bone formation which is regulated in part by some of Dexamethasone related proliferation & mineralization of cultured bone cell and polypeptide growth factors such as platelet derived growth factor(PDGF), which has been known to be an important local regulator of bone cell activity and participate in normal bone remodeling. To evaluate the effects of Dex and PDGF on bony healing of calvarial defect in rats, 10 ng/ml PDGF were applied on P group and 10 ng/ml PDGF and $10^7$ M Dex were applied PD group. 4 rats in each group were sacrificed at 7, 14. 21 days after operation respectively, and the tissue blocks were prepared for light microscope with H-E for evaluation of overall healing, with TRAP(tartrate resistant acid phosphatase) for evaluation of osteoclastic activity and with immunohistochemical staining for macrophages. The results were as follows : 1. In all group, healing aspects were progressed from 7 days to 21 days in soft and bony tissue, but complete repair were not observed in bony defect 2. PDGF and control group were showed similar bony healing aspect , but bony healing in combination of PDGF-BB and Dex were observed slower aspect compared to PDGF and control group from early healing times. 3. There were no significant difference on activities of osteoclast and macrophages in bony healing between control and experimental group In conclusion, PDGF were not influenced on bony healing of defect and combination of PDGF-BB and Dex were showed slower healing through early healing times. it was considered that Dex compared to PDGF did influenced on early hone formation factors in healing period

• Clinical and Experimental Reproductive Medicine
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• 제29권2호
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• pp.117-127
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• 2002

Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.

• Archives of Plastic Surgery
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• 제49권2호
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• pp.275-284
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• 2022

Background Population aging has led to an increased incidence of pressure ulcers, resulting in a social burden and economic costs. We developed a three-dimensional knitted fabric (3-DKF) with a pressure-reducing function that can be applied topically in the early stages of pressure ulcers to prevent progression. Methods We evaluated the effects of the 3-DKF in a streptozotocin-induced diabetes mellitus pressure ulcer mouse model, and the fabric was preliminarily applied to patients. Twelve-week-old male C57BL/6 mice were used for the animal experiments. In the pressure ulcer mouse model, an ischemia-reperfusion injury was created using a magnet on the dorsa of the mice. Pressure was measured with BodiTrak before and after applying the 3-DKF to 14 patients at risk of sacral pressure ulcers. Results In the 3-DKF-applied mice group, the ulcers were shallower and smaller than those in the control group. Compared with the mice in the control group, the 3-DKF group had lower platelet-derived growth factor-α and neutrophil elastase expression, as parameters related to inflammation, and increased levels of transforming growth factor (TGF)-β1, TGF-β3, proliferating cell nuclear antigen, and α-smooth muscle actin, which are related to growth factors and proliferation. Additionally, typical normal tissue staining patterns were observed in the 3-DKF group. In the preliminary clinical analysis, the average skin pressure was 26.2 mm Hg before applying the 3-DKF, but it decreased to an average of 23.4 mm Hg after 3-DKF application. Conclusion This study demonstrated that the newly developed 3-DKF was effective in preventing pressure ulcers through testing in a pressure ulcer animal model and preliminary clinical application.

• Journal of Periodontal and Implant Science
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• 제26권4호
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• pp.949-965
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• 1996

The main goal of periodontal therapy is to restore the lost periodontal tissue and establish the attachment appratus. Current acceptable therapeutic techniques are included : removal of diseased soft tissue, demineralization of exposed root surface, using the barrier membrane for preventing the downgrowth of gingival epithelial cell, insertion of graft materials as a scaffolding action, and biological mediators for promoting the cell activity. The latest concept one among them has been studied which based on the knowledge of cellular biology of destructed tissue. Platelet-derived growth factor(PDGF) is one of the polypeptide growth factor which have been reported as a biological mediator to regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the influences of the PDGF as biological mediator to periodontal ligament and bone marrow cell. Both right and left maxillary first molar were extracted from rat which had treated with 0.4% ${\beta}-Aminopropionitril$ for 5 days, and feeded until designed date to sacrifice under anesthesisa. Periodontal ligament were removed from the extracted socket of the rat, and cultured with Dulbecco's Modified Essential Medium(DMEM) contained with 10% Fetal Bovine Serum, 100U/ml penicillin, $100{\mu}g/ml$ streptomycin, $0.5{\mu}g/ml$ amphotericin-B. Bone marrow cell were culture from bone marrow suspension with which washed out from femur with same medium. The study was performed to evaluate the effect of PDGF to periodontal ligament and bone cell, cell proliferation rate, total protein synthesis, and alkaline phosphatase activity of rat periodontal ligament(PDL) cell and bone stromal(RBS) cell in vitro. The effects of growth factors on both cells were measured at 3, 5th day after cell culture with (control group) or without growth factors(experimental group). The results were as follows: 1. The tendency of cell proliferation under the influence of PDGF showed more rapid proliferation pattern than control at 3 and 5 days after inoculation. 2. The activity of Alkaline phosphatase revealed 14, 80% increased respectively at 3, 5 days culture than control group. Measurements of ALPase levels indicated that PDL cells had significantly higher activity when compared with that of co-culture groups and GF only(P<0.05). And, ALPase activity in 10 days was higher than that of 7 days(P<0.05). 3. The tendency of formation of the mineralized nodule were observed dose-depend pattern of PDL cells. There was statistically significant difference among group l(PDL 100%), 2(PDL 70%:GF 30%), and 3(PDL 50%:GF 50%)(P<0.01). But, there was no difference among group 3, 4(PDL 30%:GF 70%), and 5(GF 100%). 4. Also, the number of nodule was greater in co-culture of PDL 70% and GF 30% than in culture of PDL 70%(P<0.05). From the above results, it is assumed that the PDGF on PDL cells and RMB cell culture. GF stimulates the cell growth, which is not that of PDL cells but GF. And, the activity of ALPase depends on the ratio of PDL cells, and ALPase may relate to the initial phase of nodule formation. Also, it is thought that the calcified nodule formation principally depends on PDL cells, is inhibited by GF, and affected by cell density. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• 한국식품위생안전성학회지
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• 제26권3호
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• pp.187-191
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• 2011

Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4415-4420
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• 2016

We aimed to investigate any association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL) in the view of cytokines that control inflammation/angiogenesis and their correlation with certain CD markers. NHL patients with or without HCV infection were studied. CD5, CD30, CD3, CD20 and CD45 were immunohistochemically evaluated. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF, and PDGF), tumor necrosis factor (TNF-${\alpha}$), transforming growth factor (TGF-${\beta}$), interleukin-6 (IL-6), IL-8, IL-4, IL-12 and interferon gamma (IFN-${\gamma}$) were detected by enzyme-linked immunosorbent assay (ELISA). HCV+ve NHL patients showed a significant reduction in VEGF, PDGF, IFN-${\gamma}$, CD5 and CD45 and a significant increase in IL-12 and IL-8. In conclusion, there was a significant change in cytokine secretion and expression of CD markers in HCV+ve NHL patients. Based on our results, HCV infection in NHL patients requires more in-depth investigations to explore any role in lymphoma progression.

• Journal of Ginseng Research
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• 제47권2호
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• pp.237-245
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• 2023

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

• 생명과학회지
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• 제31권9호
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• pp.787-795
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• 2021

등골나물은 오랫동안 음식으로 사용되어 왔으며 한방에서 한약재로 사용되어왔으며, 특히 등골나물 추출물은 항염 및 항산화 효과가 보고되었다. 심혈관 질환인 동맥경화증은 동맥 혈관에서 발생하는 만성 염증이며 다양한 질환에 관여하고 있다. 재협착 및 신경병증 증식과 같은 심혈관 질환은 주로 혈관 평활근 세포의 다중 성장인자로 인한 비정상적인 성장과 이동으로 인해 발생하며, 혈소판유래 성장인자는 손상된 혈관벽에서 방출되며 혈관 평활근 세포의 증식 및 이동에 관여한다. 본 연구에서는 혈관 평활근 세포의 비정상적인 증식 및 이동에 대한 등골나물 추출물의 효과를 확인하였고, 혈소판유래 성장인자로 유도된 혈관 평활근 세포내에서 신호전달 경로를 조사하였다. 혈소판유래 성장인자로 유도된 혈관 평활근 세포에서 등골나물 추출물의 전처리는 세포 증식 및 이동을 효과적으로 감소시켰다. 또한, 세포 내 신호전달 경로 AKT, phospholipase C gamma (PLC-γ) 및 mitogen-activated protein kinase (MAPK)의 웨스턴 블롯 실험 결과, 이들 경로의 인산화 억제를 확인하였다. 유세포분석 데이터는 혈관 평활근 세포의 세포주기가 등골나물 추출물에 의해 차단되었음을 보여주었다. 이 결과는 혈소판유래 성장인자가 세포주기와 세포 내 신호전달 인자를 조절하여 혈관 평활근 세포의 증식과 이동을 억제 할 수 있음을 시사한다. 또한, 이는 등골나물 추출물이 혈관 평활근 세포의 비정상적인 증식 및 이동을 차단하여 심혈관 질환 예방에 하나의 소재로 사용될 수 있음을 시사한다.