• Title/Summary/Keyword: BB rat

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Cellular activity and guided bone regenerative effect of drug-loaded biodegradable membranes (약물함유 생체분해성 차폐막의 생채활성도 및 골조직 유도재생 효과)

  • Kim, Won-Kyeong;Choi, Sang-Mook;Han, Soo-Boo;Kwon, Young-Hyuk;Chung, Chong-Pyoung;Lee, Seung-Jin
    • Journal of Periodontal and Implant Science
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    • v.27 no.1
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    • pp.129-150
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    • 1997
  • The purpose of this study was to evaluate the effects of tetracycline(TC}, flurbiprofen, and PDGF-BB loaded biodegradable membranes on the cell-attachment, the activity of loaded PDGF-BB, in vivo release kinetics, and guided bone regenerative potentials. To evaluate the cell attachment to membranes, the number of gingival fibroblasts attached to each membrane(10% TC, 10% flurbiprofen, $200ng/cm^2$ PDGF-BB loaded membranes, drug-unloaded membrane) was counted by coulter counter and the morphologic pattern of attached cells was examined under SEM. To determine whether the activity of loaded PDGF-BB is sustained, the cellular growth and survival rate of gingival fibroblasts was used for both standard PDGF-BB and loaded PDGF-BB. For evaluation of in vivo release kinetics, drug-loaded membranes were implanted on the dorsal skin of the rats. On 1, 3, 7, 10, 14, 21, and 28 days after implantation, the amount of remaining drugs were measured by HPLC assay for TC and flurbiprofen, and by ${\gamma}-scintillation$ counter for $PDGF-BB^{1125}$. For evaluation of guided regenerative potential, the amount of new bone in the calvarial defect(5mm in diameter) of the rat was measured by histomorphometry 1 and 2 weeks after implantation of membranes. The number of cells attached to the PDGF-BB loaded membrane was largest as compared with the other mernbranes.(p< 0.05) The activity of loaded PDGF-BB was not significantly different from the activity of standard PDGF-BB.(p<0.05) After initial burst release of drug during the first 24 hours, drugs were gradually released for 4 weeks. Especially the release rate of PDGF-BB was nearly constant during 4 weeks. PDGF-BB loaded membranes(200, $400ng/cm^2$) were effective in guided bone regeneration as compared with drug-unloaded membrane. These results implicate that drug-loaded biodegradable membranes might be a useful for guided bone regeneration.

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Diol-ginsenosides from Korean Red Ginseng delay the development of type 1 diabetes in diabetes-prone biobreeding rats

  • Ju, Chung;Jeon, Sang-Min;Jun, Hee-Sook;Moon, Chang-Kiu
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.619-626
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    • 2020
  • Background: The effects of diol-ginsenoside fraction (Diol-GF) and triol-ginsenoside fraction (Triol-GF) from Korean Red Ginseng on the development of type 1 diabetes (T1D) were examined in diabetes-prone biobreeding (DP-BB) rats that spontaneously develop T1D through an autoimmune process. Methods: DP-BB female rats were treated with Diol-GF or Triol-GF daily from the age of 3-4 weeks up to 11-12 weeks (1 mg/g body weight). Results: Diol-GF delayed the onset, and reduced the incidence, of T1D. Islets of Diol-GF-treated DP-BB rats showed significantly lower insulitis and preserved higher plasma and pancreatic insulin levels. Diol-GF failed to change the proportion of lymphocyte subsets such as T cells, natural killer cells, and macrophages in the spleen and blood. Diol-GF had no effect on the ability of DP-BB rat splenocytes to induce diabetes in recipients. Diol-GF and diol-ginsenoside Rb1 significantly decreased tumor necrosis factor α production, whereas diol-ginsenosides Rb1 and Rd decreased interleukin 1β production in RAW264.7 cells. Furthermore, mixed cytokine- and chemical-induced β-cell cytotoxicity was greatly inhibited by Diol-GF and diol-ginsenosides Rc and Rd in RIN5mF cells. However, nitric oxide production in RAW264.7 cells was unaffected by diol-ginsenosides. Conclusion: Diol-GF, but not Triol-GF, significantly delayed the development of insulitis and T1D in DP-BB rats. The antidiabetogenic action of Diol-GF may result from the decrease in cytokine production and increase in β-cell resistance to cytokine/free radical-induced cytotoxicity.

Growth Factor Releasing Porous Poly (${\varepsilon}-caprolactone$)-Chitosan Matrices for Enhanced Bone Regenerative Therapy

  • Im, Su-Yeon;Cho, Seon-Hye;Hwang, Jeong-Hyo;Lee, Seung-Jin
    • Archives of Pharmacal Research
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    • v.26 no.1
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    • pp.76-82
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    • 2003
  • Drug releasing porous poly($\varepsilon$-caprolactone) (PCL)-chitosan matrices were fabricated for bone regenerative therapy. Porous matrices made of biodegradable polymers have been playing a crucial role as bone substitutes and as tissue-engineered scaffolds in bone regenerative therapy. The matrices provided mechanical support for the developing tissue and enhanced tissue formation by releasing active agent in controlled manner. Chitosan was employed to enhance hydrophilicity and biocompatibility of the PCL matrices. PDGF-BB was incorporated into PCL-chitosan matrices to induce enhanced bone regeneration efficacy. PCL-chitosan matrices retained a porous structure with a 100-200 $\mu$m pore diameter that was suitable for cellular migration and osteoid ingrowth. $NaHCO_3$ as a porogen was incorporated 5% ratio to polymer weight to form highly porous scaffolds. PDGF-BB was released from PCL-chitosan matrices maintaining therapeutic concentration for 4 week. High osteoblasts attachment level and proliferation was observed from PCL-chitosan matrices. Scanning electron microscopic examination indicated that cultured osteoblasts showed round form and spread pseudopods after 1 day and showed broad cytoplasmic extension after 14 days. PCL-chitosan matrices promoted bone regeneration and PDGF-BB loaded matrices obtained enhanced bone formation in rat calvarial defect. These results suggested that the PDGF-BB releasing PCL-chitosan porous matrices may be potentially used as tissue engineering scaffolds or bone substitutes with high bone regenerative efficacy.

The Inhibitory Effects of Bee Venom and Melittin on the Proliferation of Vascular Smooth Muscle Cells

  • Ha, Seong-Jong;Song, Ho-Sueb
    • Journal of Acupuncture Research
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    • v.23 no.2
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    • pp.139-157
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    • 2006
  • In the present study, I have investigated the bee venom (BV) and melittin (a major component of BV) -mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 50 ng/ml platelet derived growth factor BB (PDGF-BB)-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. I examined the effects on $NF-{\kappa}B$ activation to investigate a possible mechanism for anti-proliferative effects of BV and melittin, the PDGF-BB-induced $I{\kappa}B{\alpha}$ phosphorylation and its degradation were potently inhibited by melittin, and DNA binding activity and nuclear translocation of $NF-{\kappa}B$ p50 subunit in response to the action of PDGF-BB were potently attenuated by melittin. In further investigations, melittin markedly inhibited the PDGF-BB-induced phosphorylation of Akt but not ERK1/2, upstream signals of $NF-{\kappa}B$. Treatment of melittin also potently induced pro-apoptotic protein p53, Bax, and caspase-3 expression, but decreased anti-apoptotic protein Bcl-2 expression. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs through induction of apoptosis via suppressions of $NF-{\kappa}B$ and Akt activation, and enhancement of apoptotic signal pathway. Based on these results, BV acupuncture can be a candidate as a therapeutic method for restenosis and atherosclerosis.

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Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells

  • Tudev, Munkhtsetseg;Lim, Yong;Park, Eun-Seok;Kim, Won-Sik;Lim, Il-Ho;Kwak, Jae-Hwan;Jung, Jae-Kyung;Hong, Jin-Tae;Yoo, Hwan-Soo;Lee, Mi-Yea;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.187-194
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    • 2011
  • Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Interactions of Tricyclic Isoxazole Analogues with ${\alpha}_{2c}$-Adrenoceptor by Homology Modeling (상동성 모델링을 이용한 Tricyclic Isoxazole 유도체와 ${\alpha}_{2c}$-Adrenoceptor의 상호작용)

  • Choi, Kyoung-Seob;Kang, Na-Na;Myung, Pyung-Keun;Sung, Nack-Do
    • YAKHAK HOEJI
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    • v.54 no.4
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    • pp.300-308
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    • 2010
  • Adrenoceptor has been considered to be an important target in psychiatric disorders. Based on x-ray structures of bovine rhodopsin, we established homology model of ${\alpha}_{2c}$-adrenoceptor (ADA2C_rat) and then analyzed docking from binding model of receptor-ligand complex with high-active compound No.29 in tricyclic isoxazole analogues (1-30). We observed that the N (1.907 $\AA$) and O (1.712 $\AA$) atoms of isoxazole ring on the docked ligand (No.29) formed H-bonding interaction with O-H of Ser5.32 and carmeron phenyl ring centroid of tricyclic isoxazole formed $\pi-\pi$ interaction at 3.342 $\AA$ distance with phenyl ring centroid of Phe6.52. According to predictions of blood-brain distribution (logBB) through penetration of blood-brain barrie (BBB) and polar surface area (PSA) of the ligands, the high-active compound No.29 has values of logBB=-0.203, PSA=67.50, respectively. These results suggest that the high-active compound No.29 is a novel anti-depressant with the characteristics such as dopamine and serotonin.

Antioxidant Effects of Berchemia berchemiaefolia in Nerve Pain Models

  • Lee, Gil-Hyun;Hyun, Kyung-Yae;Choi, Seok-Cheol
    • Biomedical Science Letters
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    • v.23 no.4
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    • pp.380-387
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    • 2017
  • Berchemia berchemiaefolia (BB) are climbing plants or small to medium-sized trees that live in Africa, Asia and America. We performed the present study to investigate whether oral administration of Berchemia berchemiaefolia extract (BBE) protects SD rats from pain. The SD rat experimental groups were divided into four groups. Two of the animal model groups were fed on BBE (200 mg/kg or 100 mg/kg). We performed oral acute toxicity test to determine the optimal oral dose of BBE. To explore if BBE alleviated pain in the SD rat, we undertook the tail flick latency test and formalin test. Additionally, we conducted the anti-oxidative test. The findings of the present study suggest that Berchemia berchemiaefolia extract exhibits strong antioxidant and analgesic activities.

Comparative Study of the Inhibitory Effect of Luteolin and Luteolin-7-Glucoside on Rat Aortic Vascular Smooth Muscle Cell Proliferation

  • Kim, Jin-Ho;Kim, Soo-Yeon;Lim, Yong;Pyo, Hyeong-Bae;Park, Byeoung-Soo;Yoo, Hwan-Soo;Yun, Yeo-Pyo
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.102.2-103
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    • 2003
  • It has been previously reported that luteolin and luteolin-7-glucoside displayed the potent anti-oxidant and anti-inflammatory effects, which have also been successful in reducing vascular smooth muscle cells(VSMCs) proliferation. In this study, a possible anti-proliferative effect and its mechanism on rat aortic VSMCs by luteolin and luteolin-7-glucoside were investigated. Luteolin significantly inhibited the platelet-derived growth factor(PDGF)-BB-induced proliferation of rat aortic VSMCs. While luteolin-7-glucoside weakly inhibited the proliferation. (omitted)

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