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1.
Theranostics ; 11(16): 7640-7657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335955

RESUMO

Background: Since primary prostate cancer (PCa) can advance to the life-threatening metastatic PCa, exploring the molecular mechanisms underlying PCa metastasis is crucial for developing the novel targeted preventive strategies for decreasing the mortality of PCa. RNA N6-methyladenosine (m6A) is an emerging regulatory mechanism for gene expression and its specific roles in PCa progression remains elusive. Methods: Western blotting, quantitative real-time PCR and immunohistochemical analyses were used to detect target gene expression in PCa cells in vitro and prostate tissues from patients. RNA immunoprecipitation was conducted to analyze the specific binding of mRNA to the target protein. Migration and invasion assays were used to assess the migratory capacities of cancer cells. The correlation between target gene expression and survival rate of PCa patients was analyzed based the TCGA database. Results: We found that total RNA N6-methyladenosine (m6A) modification levels were markedly upregulated in human PCa tissues due to increased expression of methyltransferase like 3 (METTL3). Further studies revealed that the migratory and invasive capacities of PCa cells were markedly suppressed upon METTL3 knockdown. Mechanistically, METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells. Conclusions: Our findings highlight the role of METTL3 in modulating invasion and metastasis of PCa cells, providing insight into promising therapeutic strategies for hindering PCa progressing to deadly metastases.


Assuntos
Metiltransferases/genética , Neoplasias da Próstata/metabolismo , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica/fisiologia , Humanos , Masculino , Metiltransferases/metabolismo , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteases Específicas de Ubiquitina/genética
2.
Exp Neurol ; 344: 113805, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34242631

RESUMO

Mild behavioral impairment (MBI), which can include compulsive behavior, is an early sign of Alzheimer's disease (AD), but its underlying neural mechanisms remain unclear. Here, we show that 3-5-month-old APP/PS1 mice display obsessive-compulsive disorder (OCD)-like behavior. The number of parvalbumin-positive (PV) interneurons and level of high gamma (γhigh) oscillation are significantly decreased in the striatum of AD mice. This is accompanied by enhanced ß-γhigh coupling and firing rates of putative striatal projection neurons (SPNs), indicating decorrelation between PV interneurons and SPNs. Local field potentials (LFPs) simultaneously recorded in prefrontal cortex (PFC) and striatum (Str) demonstrate a decrease in γhigh-band coherent activity and spike-field coherence in corticostriatal circuits of APP/PS1 mice. Furthermore, levels of GABAB receptor (GABABR), but not GABAA receptor (GABAAR), and glutamatergic receptors, were markedly reduced, in line with presymptomatic AD-related behavioral changes. These findings suggest that MBI occurs as early as 3-5 months in APP/PS1 mice and that altered corticostriatal synchronization may play a role in mediating the behavioral phenotypes observed.

3.
Bioresour Technol ; 249: 983-991, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29145126

RESUMO

In this paper, the effects of temperature and CO2 content on CO2 reduction (utilization) efficiency and physicochemical properties of pyrolysis/gasification biochar briquettes were investigated. The CO2 reduction (utilization) efficiency (CRE) reached the peak value of 74.9% in a 10% CO2/90% N2 atmosphere at 600 °C. The crackings of hydroxyl, CC bonds, methyl and methylene groups of biochars briquette were enhanced by high temperature and CO2. The increase of CO2 concentration was beneficial for developing biochar microporosity, but not conductive to enhance higher heating value, volume density and durability of biochar briquette. To get a higher CRE and make feasible biochar briquettes are the primary goal for this work. Therefore, the optimal introduced CO2 to biomass ratio is calculated to be 135 g/kg for experiments done with 10% CO2 with N2 at 600 °C.


Assuntos
Carvão Vegetal , Madeira , Biomassa , Dióxido de Carbono , Temperatura
4.
Sci Rep ; 7(1): 2406, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28546556

RESUMO

To improve the recovery of copper, the viscosity of copper molten slag is decreased by the reduction of magnetic iron, which, in turn, accelerates the settling and separation of copper droplets from the slag. A new technology is proposed in which waste cooking oil is used as a reductant to reduce magnetic iron in the copper smelting slag and consequently reduce carbon emissions in the copper smelting process. A kinetic model of the reduction of magnetic iron in copper slag by waste cooking oil was built using experimental data, and the accuracy of the model was verified. The results indicated that the magnetic iron content in the copper slag decreased with increasing reduction time and an increase in temperature more efficiently reduced magnetic iron in the copper slag. The magnetic iron in the copper slag gradually transformed to fayalite, and the viscosity of the copper molten slag decreased as the magnetic iron content decreased during the reduction process. The reduction of magnetic iron in the copper molten slag using waste cooking oil was a first-order reaction, and the rate-limiting step was the mass transfer of Fe3O4 through the liquid boundary layer.


Assuntos
Cobre , Gorduras Insaturadas na Dieta/análise , Ferro , Algoritmos , Cobre/química , Ferro/química , Cinética , Modelos Teóricos , Temperatura , Viscosidade , Difração de Raios X
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