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1.
Dev Cell ; 59(12): 1506-1522.e11, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38582082

RESUMO

The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying mechanism remains poorly understood. Here, we identified the transcription factor (TF), specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 controls CT generation and the establishment of trophoblast stem cells (TSCs) and identified msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to alter the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a regulator of the human trophoblast lineage and implied its role in placental development and the pathogenies of placental diseases.


Assuntos
Diferenciação Celular , Proteínas de Homeodomínio , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/citologia , Feminino , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Gravidez , Placenta/metabolismo , Placenta/citologia , Linhagem da Célula , Placentação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Células-Tronco/metabolismo , Células-Tronco/citologia , Sequências Reguladoras de Ácido Nucleico/genética , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia
2.
J Nat Prod ; 86(5): 1284-1293, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37137291

RESUMO

Nine new chromane-type meroterpenoids, including the rare nor-meroterpenoid sargasilol A (1) and the eight meroditerpenoids sargasilols B-I (2-9), were isolated from a China Sea collection of the brown alga Sargassum siliquastrum, together with six known analogues (10-15). The structures of the new chromanes were identified by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 1-3 and 6-15 exhibited inhibition against LPS-induced NO production in BV-2 microglial cells, and 1, with a shorter carbon chain, was the most active one. Compound 1 was established as an anti-neuroinflammatory agent through targeting the IKK/IκB/NF-κB signaling pathway. As such, the chromanes from brown algae could provide promising anti-neuroinflammatory lead compounds for further structural modification.


Assuntos
Phaeophyceae , Sargassum , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Phaeophyceae/química , Sargassum/química , Transdução de Sinais
3.
Cytometry A ; 101(8): 682-691, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35332996

RESUMO

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are both pluripotent stem cells from early embryos. Another type of pluripotent stem cells, which are similar with EpiSCs and derive from pre-implantation embryos in feeder-free and chemically defined medium containing Activin A and basic fibroblast growth factors (bFGF), is termed as AFSCs. The pluripotency and self-renewal maintenance of ESCs rely on Leukemia inhibitory factor (LIF)/STAT/BMP4/SMAD signaling, while the pluripotency and self-renewal maintenance of EpiSCs and AFSCs rely on bFGF and Activin/Nodal signaling. However, the establishment efficiency of AFSCs lines is low. In this study, we stimulated early embryos by 2i/LIF (CHIR99021 + PD0325901 + LIF) and Activin A + bFGF respectively, to change the cell fate in inner cell mass (ICM). The "fate changed embryos" by 2i/LIF can efficiently produce AFSCs in feeder-free and chemically defined medium, but the efficiency of embryos treated with Activin A + bFGF were poor. The AFSCs from fate-changed embryos share similar molecular characteristics with conventional AFSCs and EpiSCs. Our results suggest that the advanced stimulation of 2i/LIF and the premature stimulation of Activin A + bFGF contribute to capturing the pluripotent stem cells in early embryos, and the FGF/MAPK signaling dominate early embryo development. Our study provides a new approach to capturing pluripotency from pre-implantation embryos.


Assuntos
Camadas Germinativas , Células-Tronco Pluripotentes , Animais , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias , Camadas Germinativas/metabolismo , Camundongos , Transdução de Sinais/fisiologia
4.
Chem Asian J ; 12(23): 3016-3026, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-28963810

RESUMO

In recent years, low-bandgap polymers have attracted much attention in a wide range of fields. The synthesis of these compounds has been focused on three factors according to the Roncali bandgap theory: 1) the degree of bond-length alternation (Eδr ), 2) the aromatic resonance energy of the cycle (ERes ), and 3) the substituted groups (ESub ). Herein, we have designed and prepared low-bandgap polymers in a different way by using the factors Eθ (the deviation from planarity of the polymer chain) and EInt (the interaction of the molecular chains in the solid state). Thus, three polycyclic aromatic hydrocarbons with different spatial constructions, based on hexaphenylbenzene derivatives, were prepared in this work: linear (P1-OX), V (P2-OX), and zigzag (P3-OX) types. These well-defined polymers exhibited interesting optical and electrochemistry behavior due to their different extents of planarity. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry gave the incremental orderly molecular weight distributions of P1, P2, and P3, the weight-average molecular weights (M‾w ) of which were 9000, 5500, and 69 000, respectively. Their lamellar layer structures and π-π intermolecular stacking were demonstrated by using two-dimensional grazing-incidence X-ray diffraction, which revealed the edge-on chain conformation. Finally, the materials were perfectly adapted to fabricate high-performance organic field-effect transistor devices, which revealed that these compounds could have great prospects as semiconductors.

5.
ACS Appl Mater Interfaces ; 8(12): 7938-47, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26974338

RESUMO

Series of graphene molecules with varied emission colors have been prepared by oxidative cyclodehydrogenation using anhydrous ferric chloride (FeCl3) as the catalyst under mild conditions. By controlling the oxidation time in the initial step only, molecules with different fluorescence colors are conveniently obtained. New colors can be recorded evidently because of the stepwise and controllable process, which highly related to the conjugation length. Blue emissive starting compounds in the solid state can be transformed into orange upon brief oxidation, whereas green emissive oligomers are varied to red with an emission wavelength redshift about 123 nm. Cyclic voltammetry measurements performed can give the corresponding data, which verify the results drawn from the UV and PL spectroscope. The gradual change of conjugation length with tunable emission is confirmed in the MALDI-TOF study as well. Further characterizations indicate that the graphene molecules possess satisfactory optical properties, which are highly emissive both in solution and in the solid state because of the alkyl group. In addition, the good thermal stability and the self-assembly of graphene molecules suggest that they are promising candidates for high-tech applications. Furthermore, the fabricated field-effect transistors possess the nice performance, whose mobilities are about 0.57 cm(2) V(-1) s(-1) with an on-off ratio of 1 × 10(4) and 0.81 cm(2) V(-1) s(-1) with an on-off ratio of 1 × 10(3), respectively.

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