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1.
Biomaterials ; 238: 119828, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045781

RESUMO

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.


Assuntos
Magnésio , Osteonecrose , Animais , Ácido Ascórbico , Suplementos Nutricionais , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico , Ratos , Esteroides
2.
Phytother Res ; 29(10): 1658-64, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26084208

RESUMO

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 µM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 µM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 µM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.


Assuntos
Glucuronosiltransferase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Schisandra , Animais , Ciclo-Octanos , Dioxóis , Medicamentos de Ervas Chinesas/farmacologia , Interações Ervas-Drogas , Lignanas , Compostos Policíclicos , Ratos , Schisandra/química , Relação Estrutura-Atividade
3.
Zhonghua Yi Xue Za Zhi ; 89(11): 777-81, 2009 Mar 24.
Artigo em Chinês | MEDLINE | ID: mdl-19595109

RESUMO

OBJECTIVE: To compare the effects of different calcium sulfate pellets made by different methods in treating segmental defect of bone. METHODS: Eighty New Zealand white rabbits underwent cutting off a segment in the middle part of radius so as to establish models of radial segmental defect, and than were divided into 4 groups: Group A as control group, Group B with calcium sulfate pellet made by routine method implanted into the defect, Group C with chitosan coated pressed calcium sulfate pellet implanted into the defect, and Group D with chitosan coated pressed calcium sulfate pellet combined with recombinant human bone morphogenetic protein (rhBMP)-2 implanted into the defect: X-ray photography was done every 4 weeks to observe the new bone formation. Four, 8, and 12 weeks 5 rabbits from each group were killed. The defect segments with parts of normal bone at both ends were cut off to undergo fluorescence microscopy and biomechanic three point bending test. RESULTS: X-ray photography and histological examination showed that new bone formation of cortex and reconstruction of marrow cavity were seen in Groups D and C, especially in Group D. The new bone mineralization rate of Group D was significantly higher than that of Group C (P<0.05) which was significantly higher than that of Group B (P<0.01). The anti-bending strength ratio of Group D was (47.5%+/-2.1%, significantly higher than that of Group C [(39.6+/-1.7)%, F=125.3, P<0.01], and the anti-bending strength ratios of Groups D and C were both significantly higher than those of Groups B and A [(23.6+/-3.3)% and (21.3+/-2.7)%]. CONCLUSION: Chitosan coated pressed calcium sulfate pellet shows relatively higher anti-bending strength and slightly slower resorption that closely coincide with the growth rate of new bone. It can be used to restore segmental bone defect, and particularly when combined with rhBMP-2.


Assuntos
Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Sulfato de Cálcio/uso terapêutico , Animais , Sulfato de Cálcio/farmacologia , Implantes de Medicamento , Consolidação da Fratura/efeitos dos fármacos , Regeneração Tecidual Guiada , Coelhos , Rádio (Anatomia)/cirurgia , Engenharia Tecidual/métodos
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