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1.
Clin Chim Acta ; 539: 134-143, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36529269

RESUMO

Gestational diabetes mellitus (GDM), a common complication of pregnancy, is a type of diabetes that is first detected and diagnosed during pregnancy. The incidence of GDM is increasing annually and is associated with many adverse pregnancy outcomes. Early prediction of the risk of GDM and intervention are thus important to reduce adverse pregnancy outcomes. Studies have revealed a correlation between the levels of amino acids, fatty acids, triglycerides, and other metabolites in early pregnancy and the occurrence of GDM. The development of high-throughput technologies used in metabolomics has enabled the detection of changes in the levels of small-molecule metabolites during early pregnancy, which can help reflect the overall physiological and pathological status of the body and explore the underlying mechanisms of the development of GDM. This review sought to summarize current research in this field and provide data for the development of strategies to manage GDM.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/metabolismo , Metabolômica , Resultado da Gravidez , Aminoácidos/metabolismo , Triglicerídeos
2.
J Drug Target ; 29(9): 1016-1028, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33825602

RESUMO

Glioblastoma (GBM) is an aggressive malignancy and therapeutic options are limited due to the presence of the blood-brain barrier (BBB). RVG-29, a 29-amino-acid polypeptide derived from the rabies virus glycoprotein (RVG), has excellent brain-targeted capacity across the BBB. We reduced the size of this peptide to get a15-amino-acid polypeptide (RVG-15), while retaining its brain-targeted capacity across the BBB. First, we synthesized a novel nanocarrier RVG-15-PEG2000-DSPE. Next, DOX-loaded polymeric micelles (DOX RVG-15-PMs) were prepared in an electrostatic interaction-dependent manner. Finally, we evaluated its antitumor benefits in vitro at the cellular level and in vivo using an in situ tumour-bearing mouse model. MALDI-TOF-MS and FTIR spectra confirmed the successful synthesis of the novel nanocarrier. The prepared DOX RVG-15-PMs displayed even size distribution, a high entrapment efficiency and satisfactory in vitro release behaviour. In vitro blank RVG-15-PMs were excellent, safe and highly biocompatible as drug delivery carriers. DOX-loaded micelles were easily taken up by C6 cells and could effectively inhibit cancer development and metastasis. In vivo, DOX RVG-15-PMs delayed weight loss, prevented cancer cell metastasis and accelerated cancer cell apoptosis in tumour-bearing mice. Our novel brain-targeted nanocarrier is highly feasible, while DOX RVG-15-PMs exert significant antiglioma effects, both in vitro and in vivo.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Doxorrubicina/farmacologia , Glioblastoma/tratamento farmacológico , Glicoproteínas/química , Fragmentos de Peptídeos/química , Proteínas Virais/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Cobaias , Camundongos , Camundongos Endogâmicos ICR , Micelas , Nanopartículas , Tamanho da Partícula , Ratos , Distribuição Tecidual
3.
Int J Pharm ; 567: 118485, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260781

RESUMO

Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG2000-COOH to synthesize a novel carrier DSPE-PEG2000-BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG2000-BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 ±â€¯0.17)nm and (-1.27 ±â€¯0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ±â€¯0.49)% and (14.62 ±â€¯0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Canfanos/administração & dosagem , Doxorrubicina/administração & dosagem , Glioblastoma/tratamento farmacológico , Micelas , Nanoestruturas/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Canfanos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Liberação Controlada de Fármacos , Humanos , Masculino , Camundongos Endogâmicos ICR , Nanoestruturas/química , Ratos , Cicatrização/efeitos dos fármacos
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