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1.
EMBO J ; 34(3): 361-78, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25519956

RESUMO

MicroRNAs play important roles in controlling the embryonic stem cell (ESC) state. Although much is known about microRNAs maintaining ESC state, microRNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 microRNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated microRNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel microRNAs responsible for ESC differentiation.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/metabolismo , MicroRNAs/metabolismo , Animais , Células-Tronco Embrionárias/citologia , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , MicroRNAs/genética , Células NIH 3T3 , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Smad/genética , Proteínas Smad/metabolismo
2.
J Mater Chem B ; 8(36): 8395-8404, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32966542

RESUMO

Diabetic wounds are one complication of persistent hyperglycemia and lead to neuropathy and vascular lesions in patients. The promotion of angiogenesis plays an important role in wound healing. Cell-free fat extract (Ceffe) is a cell-free fraction isolated from adipose that is enriched with a range of growth factors, the combination of which can synergistically induce angiogenesis. In this study, we prepared a wound dressing by loading Ceffe with the γ-PGA hydrogel (Ceffe-γ-PGA) to promote the healing of wounds in diabetic mice. The viscosity of Ceffe-γ-PGA was 9.2 pa s, and the water retention rate after 6 hours reached 50%. The slow-release effect of the Ceffe-γ-PGA hydrogel was investigated in vitro in PBS, and the cumulative release rate was 97% after 6 days. Water retention and viscosity analyses revealed that Ceffe-γ-PGA provided a moist environment for the wound surface. The therapeutic effect of the Ceffe-γ-PGA hydrogel on wound healing was studied in vivo in type-II diabetic male db/db mice. After 17 days of wound treatment, the wound area ratio of the Ceffe-γ-PGA group was reduced to 2% of the original, and the capillary density of the Ceffe-γ-PGA group reached 33 mm-2 and was 19 mm-2 higher than that of the untreated group. The cell proliferation rate in the Ceffe-γ-PGA group was 37% higher than that in the untreated group. These results support the use of this system as a promising therapeutic strategy for wound healing in patients with diabetes.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Portadores de Fármacos/química , Hidrogéis/química , Ácido Poliglutâmico/análogos & derivados , Extratos de Tecidos/uso terapêutico , Cicatrização/efeitos dos fármacos , Tecido Adiposo/química , Animais , Diabetes Mellitus Experimental/complicações , Feminino , Humanos , Masculino , Camundongos , Ácido Poliglutâmico/química , Pele/efeitos dos fármacos , Pele/patologia
3.
Biosens Bioelectron ; 173: 112816, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33221506

RESUMO

A highly sensitive quenching molecular imprinting (MIP) photoelectrochemical (PEC) sensor was proposed to detect acrylamide (AM) by using the photoactive composite of ZnO and polypyrrole (PPy) as the PEC signal probe. ZnO, with high electron mobility, excellent chemical and thermal stability as well as good biocompatibility, was selected as the photoelectrically active material. A polypyrrole film was formed on the nanodisk ZnO by electrochemical polymerization, and the recognition site of AM was left on the surface of the PPy film by elution, enabling the specific detection of AM. The transfer of electrons will be hindered when AM is adsorbed on the ZnO/PPy nanocomposites surface, which results in the decrease of photocurrent signal. The proposed molecularly imprinted PEC sensor exhibits significant detection performance of AM in the range of 10-1 M-2.5 × 10-9 M with a LOD of 2.147 × 10-9 M (S/N = 3). The use of photoelectrochemical technology combined with molecular imprinting technology enables the PEC sensor to have excellent selectivity, superior repeatability, preferable stability, low cost, and easy construction, providing a new method for the detection of AM. The high recovery rate in the detection of real samples of potato chips and biscuits indicates that the proposed PEC sensor has potential in monitoring the emerging food safety risks.

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