• Title/Summary/Keyword: Ligand effect

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Bone Healing in Ovariectomized-rabbit Calvarial Defect with Tricalcium Phosphate Coated with Recombinant Human Bone Morphogenetic Protein-2 Genetically Engineered in Escherichia coli

  • Kim, Jung-Han;Kim, Chang-Joo;Shin, Sang-Hun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.36 no.2
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    • pp.37-49
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    • 2014
  • Purpose: This study compares the bone formation ability of tricalcium phosphate (TCP) with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) and assesses TCP as a carrier of rhBMP-2. Methods: Bilateral round defects (diameter: 8.0 mm) were formed in the cranium of eight New Zealand white rabbits. The defects were grafted with TCP only (control group) or with rhBMP-2-coated TCP (experimental group). The animals were sacrificed at 1st week, 2nd week, 4th week, and 8th week postoperatively; two rabbits sacrificed each time. The skulls were harvested and subjected to radiographic and histological examination. Results: Radiologic evaluation showed faster bone remodeling in the experimental group than in the control group. Histologic evaluation (H&E, Masson's trichrome stain) showed rapid bone formation, remodeling and calcification in the 1st and 2nd week in the experimental group. Immunohistochemical evaluation showed higher expression rate of osteoprotegerin, receptor activator of nuclear factor ${\kappa}B$ ligand, and receptor activator of nuclear factor ${\kappa}B$ in the experimental group at the 1st and 2nd week than in the control group. Conclusion: rhBMP-2 coated TCP resulted in rapid bone formation, remodeling, and calcification due to rhBMP-2's osteogenic effect. TCP performed properly as a carrier for rhBMP-2. Thus, the use of an rhBMP-2 coating on TCP had a synergic effect on bone healing and, especially, bone remodeling and maturation.

Effects of Copper (II) Treatment in Soil on Tetracycline Toxicity to Growth of Lettuce (Lactuca sativa L.) (토양에서 상추의 생장에 대한 Tetracycline의 독성에 미치는 구리 (II)의 효과)

  • Lee, Byeongjoo;Min, Hyungi;Kim, Min-Suk;Kim, Jeong-Gyu
    • Ecology and Resilient Infrastructure
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    • v.4 no.1
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    • pp.63-70
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    • 2017
  • Tetracycline (TC) groups, widely used veterinary antibiotics, can enter into environment through animal manure application. TC forms a ligand complex with multivalent metal cations via chelation that can affect sorption and mobility of TC in soil. So far, however, it has been confirmed through the reaction of the soil outside in the aqueous solution and the evaluation of the performance in the soil cultivation process is insufficient. The purpose of this study was to examine effects of copper on TC toxicity to lettuce growth. In this research, $750mg\;kg^{-1}$ of TC and 2.5, 7.5, $17.5mg\;kg^{-1}$ of Cu are treated in soil and lettuce was cultivated in the treated soil. Growth difference of lettuce by treatment was observed. As a result, $750mg\;kg^{-1}$ of TC treated soil showed toxic effect to lettuce and the effect is alleviated by copper treatment.

Steric and Electronic Effects of Tetradentate Nickel(II) and Palladium(II) Complexes toward the Vinyl Polymerization of Norbornene

  • Lee, Dong-Hwan;Lee, Jung-Hwan;Eom, Geun-Hee;Koo, Hyo-Geun;Kim, Cheal;Lee, Ik-Mo
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.1884-1890
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    • 2011
  • A series of Ni(II) and Pd(II) complexes bearing N4-type tetradentate ligands, [Ni($X^1X^2$-6-$Me_2bpb$) 1] and [Pd($X^1X^2$-6-$Me_2bpb$) 2]; 6-$Me_2bpb$ = N,N'-(o-phenylene)bis(6-methylpyridine-2-carboxamidate), $X^1$ = Cl, H, or $CH_3$, $X^2$ = $NO_2$, Cl, F, H, $CH_3$, or $OCH_3$) were designed, synthesized, and characterized to investigate electronic and steric effects of ligand on the norbornene polymerization catalysts. Using modified methylaluminoxanes as an activator, the complexes exhibited high catalytic activities for the polymerization of norbornene and the nickel complexes exhibited better catalytic activity the palladium complexes. Ni complex 1a with $NO_2$ group on the benzene ring showed the highest catalytic activity of $4.9{\times}10^6$ g of PNBEs/$mol_{Ni}{\cdot}h$ and molecular weight of $15.28{\times}10^5$ g/mol with PDI < 2.30. Complexes with electron-withdrawing groups are more thermally stable (> 100 $^{\circ}C$), and tend to afford higher polymerization productivities than the ones having electron-donating groups. Amorphous polynorbornenes were obtained with good solubility in halogenated aromatic solvents. A vinyl addition mechanism has been proposed for the catalytic polymerization.

Effect of dietary legumes on bone-specific gene expression in ovariectomized rats

  • Park, Yongsoon;Moon, Hyoun-Jung;Paik, Doo-Jin;Kim, Deog-Yoon
    • Nutrition Research and Practice
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    • v.7 no.3
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    • pp.185-191
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    • 2013
  • In previous studies, we found that the consumption of legumes decreased bone turnover in ovariectomized rats. The purpose of the present study is to determine whether the protective effects on bone mineral density (BMD) and the microarchitecture of a diet containing legumes are comparable. In addition, we aim to determine their protective actions in bones by studying bone specific gene expression. Forty-two Sprague-Dawley rats are being divided into six groups during the 12 week study: 1) rats that underwent sham operations (Sham), 2) ovariectomized rats fed an AIN-93M diet (OVX), 3) ovariectomized rats fed an AIN-93M diet with soybeans (OVX-S), 4) ovariectomized rats fed an AIN-93M diet with mung beans (OVX-M), 5) ovariectomized rats fed an AIN-93M diet with cowpeas (OVX-C), and 6) ovariectomized rats fed an AIN-93M diet with azuki beans (OVX-A). Consumption of legumes significantly increased BMD of the spine and femur and bone volume of the femur compared to the OVX. Serum calcium and phosphate ratio, osteocalcin, expression of osteoprotegerin (OPG), and the receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) ratio increased significantly, while urinary excretion of calcium and deoxypyridinoline and expression of TNF-${\alpha}$ and IL-6 were significantly reduced in OVX rats fed legumes, compared to OVX rats that were not fed legumes. This study demonstrates that consumption of legumes has a beneficial effect on bone through modulation of OPG and RANKL expression in ovariectomized rats and that legume consumption can help compensate for an estrogen-deficiency by preventing bone loss induced by ovarian hormone deficiency.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

  • Bak, Sun-Uk;Kim, Suji;Hwang, Hae-Jun;Yun, Jung-A;Kim, Wan-Sung;Won, Moo-Ho;Kim, Ji-Yoon;Ha, Kwon-Soo;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.50 no.2
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    • pp.103-108
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    • 2017
  • Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-${\kappa}B$ ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKL-induced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKL-induced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in $HO-1^{+/-}$ cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-${\kappa}B$ activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-${\kappa}B$-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an anti-resorption agent and reduce bone loss by blocking osteoclast differentiation.

Inhibition of Cell Migration by Corticotropin-Releasing Hormone (CRH) in Human Natural Killer Cell Line, NK-92MI (Corticotropin-Releasing Hormone (CRH)에 의한 인간 자연 살해 세포(NK-92MI)의 Migration 억제)

  • Cheon, So-Young;Bang, Sa-Ik;Cho, Dae-Ho
    • IMMUNE NETWORK
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    • v.5 no.4
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    • pp.247-251
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    • 2005
  • Background: Natural killer (NK) cells are CD3 (-) CD14 (-) CD56 (+) lymphocytes. They play an important role in the body's innate immune response. They can induce spontaneous killing of cancer cells or virus-infected cells via the Fas/Fas ligand or the granzyme/perforin systems. The corticotropin-releasing hormone (CRH) is an important regulator for the body's stress response. It promotes proliferation and migration of various cancer cells through the CRH type 1 receptor under stress, and also inhibits NK or T cell activity. However, the relationship of CRH and NK cell migration to the target has not been confirmed. Herein, we study the effect of CRH on NK cell migration. Methods: We used the human NK cell line, NK-92MI, and tested the expression of CRH receptor type 1 on NK-92MI by RT-PCR. This was to examine the effect of CRH on tumor and NK cell migration, thus NK cells (NK-92MI) were incubated with or without CRH and then each CRH treated cell's migration ability compared to that of the CRH untreated group. Results: We confirmed that CRH receptor type 1 is expressed in NK-92MI. CRH can decrease NK cell migration in a time-/dose-dependent manner. Conclusion: These data suggest CRH can inhibit NK cell migration to target cells.

Influence of Citric Acid on the Metal Release of Stainless Steels

  • Mazinanian, N.;Wallinder, I. Odnevall;Hedberg, Y.S.
    • Corrosion Science and Technology
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    • v.14 no.4
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    • pp.166-171
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    • 2015
  • Knowledge of how metal releases from the stainless steels used in food processing applications and cooking utensils is essential within the framework of human health risk assessment. A new European standard test protocol for testing metal release in food contact materials made from metals and alloys has recently been published by the Council of Europe. The major difference from earlier test protocols is the use of citric acid as the worst-case food simulant. The objectives of this study were to assess the effect of citric acid at acidic, neutral, and alkaline solution pH on the extent of metal release for stainless steel grades AISI 304 and 316, commonly used as food contact materials. Both grades released lower amounts of metals than the specific release limits when they were tested according to test guidelines. The released amounts of metals were assessed by means of graphite furnace atomic absorption spectroscopy, and changes in the outermost surface composition were determined using X-ray photoelectron spectroscopy. The results demonstrate that both the pH and the complexation capacity of the solutions affected the extent of metal release from stainless steel and are discussed from a mechanistic perspective. The outermost surface oxide was significantly enriched in chromium upon exposure to citric acid, indicating rapid passivation by the acid. This study elucidates the effect of several possible mechanisms, including complex ion- and ligand-induced metal release, that govern the process of metal release from stainless steel under passive conditions in solutions that contain citric acid.

Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects

  • Kim, Ho-Chul;Song, Jae-Min;Kim, Chang-Joo;Yoon, Sang-Yong;Kim, In-Ryoung;Park, Bong-Soo;Shin, Sang-Hun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.37
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    • pp.16.1-16.7
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    • 2015
  • Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

In silico Analysis on hERG Channel Blocking Effect of a Series of T-type Calcium Channel Blockers

  • Jang, Jae-Wan;Song, Chi-Man;Choi, Kee-Hyun;Cho, Yong-Seo;Baek, Du-Jong;Shin, Kye-Jung;Pae, Ae-Nim
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.251-262
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    • 2011
  • Human ether-a-go-go related gene (hERG) potassium channel blockade, an undesirable side effect which might cause sudden cardiac death, is one of the major concerns facing the pharmaceutical industry. The purpose of this study is to develop an in silico QSAR model which uncovers the structural parameters of T-type calcium channel blockers to reduce hERG blockade. Comparative molecular similarity indices analysis (CoMSIA) was conducted on a series of piperazine and benzimidazole derivatives bearing methyl 5-(ethyl(methyl)amino)-2-isopropyl-2-phenylpentanoate moieties, which was synthesized by our group. Three different alignment methods were applied to obtain a reliable model: ligand based alignment, pharmacophore based alignment, and receptor guided alignment. The CoMSIA model with receptor guided alignment yielded the best results : $r^2$ = 0.955, $q^2$ = 0.781, $r^2_{pred}$ = 0.758. The generated CoMSIA contour maps using electrostatic, hydrophobic, H-bond donor, and acceptor fields explain well the structural requirements for hERG nonblockers and also correlate with the lipophilic potential map of the hERG channel pore.

Dexamethasone Inhibits the Formation of Multinucleated Osteoclasts via Down-regulation of ${\beta}_3$ Integrin Expression

  • Kim, Yong-Hee;Jun, Ji-Hae;Woo, Kyung-Mi;Ryoo, Hyun-Mo;Kim, Gwan-Shik;Baek, Jeong-Hwa
    • Archives of Pharmacal Research
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    • v.29 no.8
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    • pp.691-698
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    • 2006
  • Although glucocorticoids are known to affect osteoclast differentiation and function, there have been conflicting reports about the effect of glucocorticoids on osteoclast formation, leading to the assumption that microenvironment and cell type influence their action. We explored the effect of the synthetic glucocorticoid analog dexamethasone on the formation of osteoclasts. Dexamethasone inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts without affecting the formation of TRAP-positive mononuclear cells in a coculture of mouse osteoblasts and bone marrow cells. Dexamethasone did not inhibit mRNA expression levels of the receptor activator of nuclear factor-kB ligand and osteoprotegerin, the essential regulators of osteoclastogenesis. Dexamethasone down-regulated the expression of ${\beta}_3$ integrin mRNA and protein but did not alter expression of other osteoclast differentiation marker genes. Both dexamethasone and echistatin, a ${\beta}_3$ integrin function blocker, inhibited TRAP-positive multinucleated osteoclast formation but not TRAP-positive mononuclear cell formation. These results suggest that dexamethasone inhibits the formation of multinucleated osteoclasts, at least in part, through the down-regulation of ${\beta}_3$ integrin, which plays an important role in the formation of multinucleated osteoclasts.