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1.
Biomolecules ; 14(8)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39199295

RESUMO

Due to the limited supply of autologous bone grafts, there is a need to develop more bone matrix materials to repair bone defects. Xenograft bone is expected to be used for clinical treatment due to its exact structural similarity to natural bone and its high biocompatibility. In this study, decellularized antler cancellous bone matrix (DACB) was first prepared, and then the extent of decellularization of DACB was verified by histological staining, which demonstrated that it retained the extracellular matrix (ECM). The bioactivity of DACB was assessed using C3H10T1/2 cells, revealing that DACB enhanced cell proliferation and facilitated cell adhesion and osteogenic differentiation. When evaluated by implanting DACB into nude mice, there were no signs of necrosis or inflammation in the epidermal tissues. The bone repair effect of DACB was verified in vivo using sika deer during the antler growth period as an animal model, and the molecular mechanisms of bone repair were further evaluated by transcriptomic analysis of the regenerated tissues. Our findings suggest that the low immunogenicity of DACB enhances the production of bone extracellular matrix components, leading to effective osseointegration between bone and DACB. This study provides a new reference for solving bone defects.


Assuntos
Chifres de Veado , Osso Esponjoso , Cervos , Camundongos Nus , Osteogênese , Alicerces Teciduais , Animais , Chifres de Veado/química , Alicerces Teciduais/química , Camundongos , Proliferação de Células , Diferenciação Celular , Matriz Extracelular Descelularizada/química , Engenharia Tecidual/métodos , Matriz Extracelular/metabolismo , Regeneração Óssea , Linhagem Celular , Adesão Celular
2.
Chem Asian J ; 17(11): e202200263, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35404509

RESUMO

A pair of enantiomeric ligands, (2R,3R)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((R,R)-L) and (2S,3S)-dibenzyl-2,3-bis(isonicotinoyloxy)succinate ((S,S)-L), are designed and synthesized. Seven copper (II) coordination polymers {[Cu((R,R)-L)Br2 (THF)] ⋅ CH3 CN} n (1 a) and {[Cu((S,S)-L)Br2 (THF)] ⋅ CH3 CN}n (1 b), {[Cu((R,R)-L)Cl2 (THF)] ⋅ CH3 CN}n (2 a) and {[Cu((S,S)-L)Cl2 (THF)] ⋅ CH3 CN}n (2 b), {[Cu((R,R)-L)(NO3 )2 (CH3 CN)]}n (3 a) and {[Cu((S,S)-L)(NO3 )2 (CH3 CN)]}n (3 b), {[Cu((R,R)-L)2 (CH3 CN)2 ](ClO4 )2 ⋅ 3CH3 CN}n (4) were obtained through the assemblies with CuBr2 , CuCl2 ⋅ 2H2 O, Cu(NO3 )2 ⋅ 3H2 O, Cu(ClO4 )2 ⋅ 6H2 O, respectively. Single-crystal X-ray diffraction and circular dichroism analysis demonstrate that 1 a-3 a, 1 b-3 b have a mono chiral one-dimensional (1D) chain-like spiral structure, while 4 have 1D chain-like structure whose metal centers have chiral propeller coordination environment. Ligand structure, anions and solvent systems have a regulatory effect on the formation of chiral helical structure. Further investigation has proved that 1 a can be used as circular dichroism spectrum probe for monitoring L-/D-cysteine and L-/D-penicillamine configuration and concentration in aqueous media based on ligand interchange mechanism.


Assuntos
Cobre , Polímeros , Cobre/química , Cristalografia por Raios X , Ligantes , Polímeros/química , Succinatos , Tartaratos
3.
Food Chem Toxicol ; 60: 252-62, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23911802

RESUMO

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is coupled to polyethylene glycol (PEG) and designed to specifically bind and activate the erythropoietin (EPO) receptor to result in production of red blood cells. This study was designed to evaluate the potential subchronic toxicity of EPO-018B for Cynomolgus monkeys and Sprague-Dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys. The No Observed Adverse Effect Level (NOAEL) for rats and monkeys were both considered to be at least 0.5 mg/kg/day, the minimum toxic dose to be 5.0 mg/kg/day and the severe toxic dose to be more than 50.0 mg/kg/day. The toxicological effects included the exaggerated pharmacology and secondary sequelae that resulted from an erythropoiesis-stimulating agent treatment to healthy animals. Most treatment induced effects were reversible or showed ongoing recovery upon discontinuation of treatment. The anticipated patient population for EPO-018B treatment is targeted to be the anemia patients caused by chronic renal failure or chemotherapy against to cancer and is expected to have an ideal clinical application prospect.


Assuntos
Hematínicos/farmacologia , Peptídeos/farmacologia , Polietilenoglicóis/farmacologia , Animais , Pressão Sanguínea , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Eritropoese/efeitos dos fármacos , Feminino , Injeções Subcutâneas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macaca fascicularis , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão , Peptídeos/efeitos adversos , Peptídeos/farmacocinética , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/metabolismo , Testes de Toxicidade Subcrônica , Urinálise
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