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1.
J Am Chem Soc ; 139(26): 8800-8803, 2017 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-28628312

RESUMO

Mononuclear nonheme iron(V)-oxo complexes have been reported previously. Herein, we report the first example of a mononuclear nonheme iron(V)-imido complex bearing a tetraamido macrocyclic ligand (TAML), [(TAML)FeV(NTs)]- (1). The spectroscopic characterization of 1 revealed an S = 1/2 Fe(V) oxidation state, an Fe-N bond length of 1.65(4) Å, and an Fe-N vibration at 817 cm-1. The reactivity of 1 was demonstrated in C-H bond functionalization and nitrene transfer reactions.


Assuntos
Complexos de Coordenação/química , Imidas/química , Ferro/química , Aminação , Heme/química , Ligantes , Compostos Macrocíclicos/química , Estrutura Molecular
2.
J Tissue Eng Regen Med ; 9(4): 447-59, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24764222

RESUMO

This study evaluates whether the combination of the rhBMP-2 and various types of growth factors including EGF, FGF, PDGF and VEGF increases osteoinductivity compared to the single use of rhBMP-2 through in vitro and in vivo study. Cultured human MSCs were treated with rhBMP-2 only or in combination with growth factors. For in vivo evaluation, rhBMP-2 only or with growth factors was implanted into the calvarial defect made on SD rats. Both EGF and PDGF significantly increased both ALP activity and expression level in hMSCs when treated in combination with rhBMP-2 at 3 and 7 days of differentiation and significantly raised the accumulation of the calcium at day 14. Furthermore, micro-CT scanning revealed that the EGF an FGF groups show significantly increased new bone surface ratio compared to the rhBMP-2 only group and, the EGF treatment significantly up regulated percent bone volume and trabecular number at two weeks after the surgery. VEGF treatment also significantly raised trabecular number and FGF treatment significantly increased the trabecular thickness. Histological examination revealed that the EGF combination group showed enhanced bone regeneration than the rhBMP-2 only group two weeks after the implantation. Even though the treatment of rhBMP-2 with PDGF and FGF failed to show enhanced osteogenesis in vitro and in vivo simultaneously, these results suggest that the positive effect of the combination of EGF and rhBMP-2 is expected to induce the bone formation earlier compared to the single use of rhBMP-2 in vitro and in vivo.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Fraturas Ósseas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Animais , Fraturas Ósseas/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia
3.
Genes Nutr ; 7(2): 319-29, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21853335

RESUMO

Ginsenosides, bioactive compounds of Panax Ginseng C.A. Meyer, are divided into protopanaxadiol (PD) and protopanaxtriol (PT). The aim of this study was to evaluate the protective effects of different PD and PT combination ratios on liver inflammation and apoptosis in hyperlipidemic apo E KO mice. R1 (PD/PT = 1, high Rg(1) and Rb(1)) and R2 (PD/PT = 2, high Re and Rd) extracts were intraperitoneally injected by 100 mg/kg/day at the 8th week. R1 and R2 improved atherogenic indices by increasing HDL and lowering total cholesterol (TC) and triacylglyceride (TG) selectively. R1 decreased lipid peroxides (LPO) level in plasma and liver tissue of hyperlipidemic mice, and R2 lowered plasma malondialdehyde(MDA) level. R1 and R2 not only regulated the expression of cyclooxygenase (COX)-2, IκB-α, phopho-ERK 1/2, and phopho-SAPK/JNK levels but also were significantly effective in blocking apoptotic signals, such as caspase-8, -9, as well as the cleavage of PARP in liver. Different combinational treatment of PD and PT extracts might ameliorate the liver inflammation and apoptosis in hyperlipidemic apo E KO mice, which is atherosclerotic animal model.

4.
Biomed Mater ; 6(1): 015008, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21205997

RESUMO

Hydroxyapatite (HA) is an osteoconductive material used as a bone graft extender and demineralized bone matrix (DBM) has been used as a source of osteoinductive factors. A combination of DBM and HA is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of DBM and HA on osteogenesis both in vitro and in vivo using an athymic nude rat abdominal muscle pouch model, and evaluated the possibility of HA as a carrier of DBM. Alkaline phosphatase (ALP) staining, ALP assay and measurements of the mRNA expression of ALP and Runx2 by RT-PCR were performed by transplanting human mesenchymal stem cells onto a plate. Five athymic nude rats each were assigned to one of two experimental groups (DBM/HA putty and only HA, i.e. 15 pouches per group). The muscle pouches were filled with DBM/HA putty or only HA. Radiographs were obtained at weeks 4 and 8, postoperatively. The animals were sacrificed at week 8 postoperatively and high resolution microCT was used to confirm the newly formed mineralized tissue. Each pouch was fixed, embedded, sectioned and processed for hematoxylin and eosin staining. The ALP value of the DBM/HA putty was higher than those of HA and control (p < 0.05, each). The expression of ALP mRNA appeared higher on the DBM/HA putty than on HA and control. MicroCT and histology examinations of the DBM/HA putty demonstrated the presence of newly generated mineralized tissues but there was no mineralized tissue in the HA cases. In conclusion, the DBM/HA putty indicated osteoblastic differentiation in vitro and showed ectopic mineralized tissue formation in the rat abdominal pouch model. These findings indicate that the DBM/HA putty can retain its oteoinductivity and HA can be used as a carrier of DBM.


Assuntos
Matriz Óssea , Substitutos Ósseos , Durapatita , Osteogênese , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Matriz Óssea/química , Substitutos Ósseos/química , Diferenciação Celular , Células Cultivadas , Primers do DNA/genética , Durapatita/química , Expressão Gênica , Humanos , Técnicas In Vitro , Masculino , Teste de Materiais , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Varredura , Porosidade , Ratos , Ratos Nus , Transplante Heterólogo , Microtomografia por Raio-X
5.
Endocrinology ; 150(8): 3800-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19372205

RESUMO

Ectodermal neural cortex (ENC) 1, a member of the kelch family of genes, is an actin-binding protein and plays a pivotal role in neuronal and adipocyte differentiation. The present study was designed to examine the gonadotropin regulation and action of ENC1 during the ovulatory process in immature rats. The levels of ENC1 mRNA and protein were stimulated by LH/human chorionic gonadotropin (hCG) within 3 h both in vivo and in vitro. In situ hybridization analysis revealed that ENC1 mRNA was localized not only in theca/interstitial cells but also in granulosa cells of preovulatory follicles but not of growing follicles in pregnant mare's serum gonadotropin/hCG-treated ovaries. LH-induced ENC1 expression was suppressed by a high dose of protein kinase C inhibitor RO 31-8220 (10 microM) but not by low doses of RO 31-8220 (0.1-1.0 microM), suggesting the involvement of atypical protein kinase C. ENC1 was detected in both nucleus and cytoplasm that was increased by LH/hCG treatment. Both biochemical and morphological analysis revealed that LH/hCG treatment increased actin polymerization within 3 h in granulosa cells. Interestingly, ENC1 physically associated with actin and treatment with cytochalasin D, an actin-depolymerizing agent, abolished this association. Confocal microscopy further demonstrated the colocalization of ENC1 with filamentous actin (F-actin). The present study demonstrates that LH/hCG stimulates ENC1 expression and increases F-actin formation in granulosa cells. The present study further shows the physical association of ENC1 and F-actin, implicating the role of ENC1 in cytoskeletal reorganization during the differentiation of granulosa cells.


Assuntos
Actinas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neuropeptídeos/metabolismo , Proteínas Nucleares/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Animais , Northern Blotting , Western Blotting , Células Cultivadas , Gonadotropina Coriônica/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Imunofluorescência , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Imunoprecipitação , Hibridização In Situ , Técnicas In Vitro , Indóis/farmacologia , Hormônio Luteinizante/farmacologia , Proteínas dos Microfilamentos/genética , Neuropeptídeos/genética , Proteínas Nucleares/genética , Ligação Proteica , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Substâncias para o Controle da Reprodução/farmacologia
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