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AIM: To investigate whether atorvastatin treatment could prevent Aß1-42 oligomer (AßO)-induced synaptotoxicity and memory dysfunction in rats, and to elucidate the mechanisms involved in the neuroprotective actions of atorvastatin. METHODS: SD rats were injected with AßOs (5 nmol, icv). The rats were administrated with atorvastatin (10 mg·kg(-1)·d(-1), po) for 2 consecutive weeks (the first dose was given 5 d before AßOs injection). The memory impairments were evaluated with Morris water maze task. The expression of inflammatory cytokines in the hippocampus was determined using ELISA assays. The levels of PSD-95 and p38MAPK proteins in rat hippocampus were evaluated using Western blot analysis. For in vitro experiments, cultured rat hippocampal neurons were treated with AßOs (50 nmol/L) for 48 h. The expression of MAP-2 and synaptophysin in the neurons was detected with immunofluorescence. RESULTS: The AßO-treated rats displayed severe memory impairments in Morris water maze tests, and markedly reduced levels of synaptic proteins synaptophysin and PSD-95, increased levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and p38MAPK activation in the hippocampus. All these effects were prevented or substantially attenuated by atorvastatin administration. Pretreatment of cultured hippocampal neurons with atorvastatin (1 and 5 µmol/L) concentration-dependently attenuated the AßO-induced synaptotoxicity, including the loss of dendritic marker MAP-2, and synaptic proteins synaptophysin and PSD-95. Pretreatment of the cultured hippocampal neurons with the p38MAPK inhibitor SB203580 (5 µmol/L) blocked the AßO-induced loss of synaptophysin and PSD-95. CONCLUSION: Atorvastatin prevents AßO-induced synaptotoxicity and memory dysfunction through a p38MAPK-dependent pathway.
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Péptidos beta-Amiloides/metabolismo , Anticolesterolemiantes/uso terapéutico , Ácidos Heptanoicos/uso terapéutico , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/uso terapéutico , Pirroles/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Atorvastatina , Células Cultivadas , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/patologíaRESUMEN
The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning.
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AIM: To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. METHODS: Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 µmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3ß (GSK-3ß) in the cortical neurons were evaluated using Western blotting analyses. RESULTS: Atorvastatin (0.05-10 µmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 µmol/L) and wortmannin (5 µmol/L), Akt inhibitor tricribine (1 µmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 µmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 µmol/L). Moreover, atorvastatin (10 µmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 µmol/L) significantly increased the phosphorylated GSK-3ß level in the cortical neurons, which was prevented by both LY294002 and tricribine. CONCLUSION: These results suggest that activation of both the PI3K/Akt/mTOR and Akt/GSK-3ß signaling pathways is responsible for the atorvastatin-induced neurite outgrowth in cultured cortical neurons.
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Glucógeno Sintasa Quinasa 3/metabolismo , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neuritas/efectos de los fármacos , Neuronas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirroles/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Atorvastatina , Células Cultivadas , Corteza Cerebral/citología , Activación Enzimática/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta , Neuritas/metabolismo , Neuritas/ultraestructura , Neuronas/citología , Neuronas/metabolismo , Neuronas/ultraestructura , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
This research was designed to detect the function of low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) in breast cancer (BC). Our results revealed that LRP8 was highly expressed in BC tissues and cell lines compared with human normal breast tissues. The poor prognosis of patients with BC was associated with the up-regulation of LRP8 while inversely connected with overexpression of miR-1262. Functionally, LRP8 depletion in BC cells impaired the proliferative, clonogenic, invasive, and migratory capabilities, which was consistent with the effects of upregulated miR-1262. Bioinformatics prediction and luciferase reporter assay confirmed that miR-1262 was an upstream factor for LRP8 and negatively regulated the expression of LRP8. Further experiments illustrated that the co-transfection of miR-1262 antamir and si-LRP8 could significantly suppress the promoting impacts caused by the transfection of miR-1262 antamir alone. These findings highlighted that LRP8 accelerated the BC development by contributing cellular aggressiveness, which was modulated by miR-1262.
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Neoplasias de la Mama , Proteínas Relacionadas con Receptor de LDL , MicroARNs , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Relacionadas con Receptor de LDL/genética , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , Regulación hacia ArribaRESUMEN
In this report, corncob residue, the main by-product in the furfural industry, is used as a precursor to prepare porous carbon by a simple and direct thermal treatment: one-step activation without pre-carbonization. As a consequence, the corncob residue derived porous carbon achieves a high surface area of 1210 m(2) g(-1) after ash-removal. The carbon material has the advantages of low cost and low environmental impact, with a superior electrochemical performance compared to those polymer-based synthetic carbons as electrode material for a supercapacitor. The carbon electrode exhibits a high capacitance of 314 F g(-1) in 6M KOH electrolyte. The corresponding sample also shows a superb cycling stability. Almost no capacitance decay was observed after 100,000 cycles. The excellent electrochemical performance is due to the combination of a high specific surface area with a fraction of mesopores and highly stable structure.
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Carbono/química , Capacidad Eléctrica , Residuos/análisis , Zea mays/química , Espectroscopía Dieléctrica , Técnicas Electroquímicas , Electrodos , Electrólitos/química , Nitrógeno/aislamiento & purificación , Porosidad , TemperaturaRESUMEN
The assembly of commercial silica colloids in the presence of 1,6-diaminohexane and their subsequent encapsulation by poly(benzoxazine) have been used to produce coral-like porous carbons. The pyrolysis of the polymer followed by the removal of the silica produces a carbon with a continuous skeleton that contains spherical medium-size pores as "reservoirs" with a structure similar to a bunch of grapes. The total volume and the diameter of the "reservoir" pores are tunable. The coral-like morphology and the pore structure of the carbons make them suitable for use as electrode materials for supercapacitors and lithium-ion batteries. As supercapacitor electrodes, they exhibit excellent long-term cycle stability (almost no capacitance fading after 20,000 cycles at a current density of 1 A g(-1)) and good rate capability with capacitance retention of 88% (from 0.1 A g(-1) to 5 A g(-1)). Meanwhile, as a matrix for the encapsulation of SnO2 nanoparticles for Li-ion storage, the electrodes also show a high specific capacity and good cycling stability, i.e., 900 mA h g(-1) after 50 charge-discharge cycles. The good electrochemical performance of such carbons shows that they are promising candidate electrode materials for electrochemical energy storage.
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The songs of Japanese marsh warblers (Megalurus pryeri) were recorded during May to July in 2009 at Shuangtaihekou Nature Reserve, Liaoning, China. Based on song characteristics, songs were divided into three types: courtship songs, alarm calls or contact calls. We analyzed and measured four parameters from 543 verses recorded from 20 males. The parameters were: duration of verse, number of syllables, duration of syllable, and interval of syllable. Verses of courtship song are formed of two verses, the first part's rhythm is more and more quick with time; the main body part is formed with complex syllables. Alarm calls and contact calls are simple, and formed with simple and repeat syllables. All songs contained 38 syllable types (six syllable types of the first part included). Acoustic features of the courtship song were statistically different, as was the calls of each individual.