RESUMEN
Over the last decade, the roles of ß-arrestins in the treatment of neuropsychological diseases have become increasingly appreciated. Fluoxetine is the first selective serotonin reuptake inhibitor developed and is approved for the clinical treatment of depression. Emerging evidence suggests that fluoxetine can directly combine with the 5-HT receptor, which is a member of the G protein-coupled receptor (GPCR) family, in addition to suppressing the serotonin transporter. In this study, we prepared a chronic mild stress (CMS)-induced depression model with ß-arrestin2-/- mice and cultured adult neural stem cells (ANSCs) to investigate the involvement of the 5-HT receptor-ß-arrestin axis in the pathogenesis of depression and in the therapeutic effect of fluoxetine. We found that ß-arrestin2 deletion abolished the fluoxetine-mediated improvement in depression-like behaviors and monoamine neurotransmitter levels, although ß-arrestin2 knockout did not aggravate CMS-induced changes in mouse behaviors and neurotransmitters. Notably, the ß-arrestin2-/- mice had a shortened dendritic length and reduced dendritic spine density, as well as decreased neural precursor cells, compared to the WT mice under both basal and CMS conditions. We further found that ß-arrestin2 knockout decreased the number of proliferating cells in the hippocampal dentate gyrus and suppressed the proliferative capability of ANSCs in vitro. Moreover, ß-arrestin2 knockout aggravated the impairment of cell proliferation induced by corticosterone and further blocked the fluoxetine-mediated promotion of mouse hippocampal neurogenesis. Mechanistically, we found that the 5-HT2BR-ß-arrestin2-PI3K/Akt axis is essential to maintain the modulation of hippocampal neurogenesis in depressed mice. Our study may provide a promising target for the development of new antidepressant drugs.
Asunto(s)
Antidepresivos/uso terapéutico , Giro Dentado/efectos de los fármacos , Depresión/tratamiento farmacológico , Fluoxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Arrestina beta 2/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Espinas Dendríticas/genética , Giro Dentado/metabolismo , Depresión/metabolismo , Técnicas de Inactivación de Genes , Masculino , Ratones Endogámicos C57BL , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neurotransmisores/metabolismo , Transducción de Señal/efectos de los fármacos , Arrestina beta 2/genéticaRESUMEN
Discovering the underlying mechanisms between carbon metabolism and carbon balance of human-natural system is of important theoretical and practical significance for reducing regional carbon emissions and promoting low-carbon development. Taking Xiamen-Zhangzhou-Quanzhou region from 2000 to 2020 as an example, we constructed the framework of spatial network model of land carbon metabolism based on carbon flow, and inquired into the spatial and temporal heterogeneity in the carbon metabolic structure, function and ecological relationships by using the ecological network analysis. The results showed that the dominant negative carbon transitions related with land use changes came from the conversion of cultivated land to industrial and transportation land, and that the high value areas of negative carbon flow were mainly distributed in the areas with relatively developed industries in the middle and east parts of Xiamen-Zhangzhou-Quanzhou region. Competition relationships were the dominant type and the spatial expansion was obvious, which led to the decreases of the integral ecological utility index and affected the regional carbon metabolic balance. The ecological network hierarchy of driving weight changed from a pyramid structure to a relatively more regular structure, with the producer contributing the most. The ecological network hie-rarchy of pull weight changed from a pyramid structure to an inverted pyramid structure, mainly due to the excessive increase of industrial and transportation land weights. Low-carbon development should focus on the sources of negative carbon transitions caused by land use conversion and its comprehensive impacts on carbon metabolic balance, to formulate differentiated low-carbon land use patterns and carbon emission reduction policies.
Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Humanos , Conservación de los Recursos Naturales/métodos , Carbono , Industrias , Homeostasis , China , CiudadesRESUMEN
BACKGROUND: CD146 is a tight junction-associated molecule involved in maintaining endothelial barrier, and balancing immune-inflammation response, in cardiovascular disease. Notably, peripheral CD146+ cells significantly upsurge under vessel dyshomeostasis such as acute myocardial injury (AMI), appearing to be a promising therapeutic target. In this study, with a new view of gene correlation, we aim at deciphering the complex underlying mechanism of CD146+ cells' impact in the development of AMI. METHODS: Transcription dataset GSE 66,360 of CD146+ blood cells from clinical subjects was downloaded from NCBI. Pearson networks were constructed and the clustering coefficients were calculated to disclose the differential connectivity genes (DCGs). Analysis of gene connectivity and gene expression were performed to reveal the hub genes and hub gene clusters followed by gene enrichment analysis. RESULTS AND CONCLUSIONS: Among the total 23,520 genes, 27 genes out of 126 differential expression genes were identified as DCGs. These DCGs were found in the periphery of the networks under normal condition, but transferred to the functional center after AMI. Moreover, it was revealed that DCGs spontaneously crowded together into two functional models, CCL20 cluster and NR4A3 cluster, influencing the CD146-mediated signaling pathways during the pathology of AMI for the first time.
Asunto(s)
Biomarcadores/sangre , Antígeno CD146/sangre , Quimiocina CCL20/metabolismo , Proteínas de Unión al ADN/metabolismo , Redes Reguladoras de Genes , Infarto del Miocardio/patología , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Quimiocina CCL20/genética , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica , Humanos , Infarto del Miocardio/sangre , Infarto del Miocardio/genética , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genéticaRESUMEN
The title compound, {[Co(C(14)H(16)N(5)O(3))(2)]·2H(2)O}(n) or [Co(ppa)(2)]·2H(2)O}(n), where ppa denotes the 8-ethyl-5-oxo-2-(piperazin-1-yl)-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carb-ox-yl-ate anion, was synthesized under hydro-thermal conditions. The Co(II) atom (site symmetry ) exhibits a distorted trans-CoN(2)O(4) octa-hedral geometry defined by two monodentate N-bonded and two bidentate O,O'-bonded ppa anions. The extended two-dimensional structure is a square grid, which is consolidated by N-Hâ¯O hydrogen bonds. The disordered uncoordinated water mol-ecules occupy cavities within the grid.
RESUMEN
A novel reagentless amperometric uric acid biosensor based on functionalized multi-wall carbon nanotubes (MWCNTs) with tin oxide (SnO2) nanoparticles has been developed. This was successfully applied to assay uric acid levels from an in vivo microdialysis sampling. Compared with unfunctionalized or traditional carboxylic acid (-COOH)-functionalized MWCNTs, the MWCNTs-SnO2 electrode exhibited higher electrocatalytic oxidation to uric acid. Here, MWCNTs-SnO2 may act as an efficient promoter, and the system exhibited a linear dependence on the uric acid concentration over the range from 1.0 x 10(-7) to 5.0 x 10(-4) mol L(-1). In addition, there was little ascorbic acid interference. The high sensitivity of the MWCNTs-SnO2 modified enzyme electrode enabled the monitoring of trace levels of uric acid in dialysate samples in rat striatum.
Asunto(s)
Técnicas Biosensibles/métodos , Cuerpo Estriado/química , Nanotubos de Carbono/química , Compuestos de Estaño/química , Urato Oxidasa/química , Ácido Úrico/análisis , Animales , Electroquímica , Masculino , Microscopía Electrónica de Transmisión , Nanotubos de Carbono/ultraestructura , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
An electrochemical method suitable for the simultaneous measurement of cerebral glucose, lactate, L-glutamate and hypoxanthine concentrations from in vivo microdialysis sampling has been successfully performed for the first time using a neutral red-doped silica (NRDS) nanoparticle-derived enzyme sensor system. These uniform NRDS nanoparticles (about 50 +/- 3 nm) were prepared by a water-in-oil (W/O) microemulsion method, and characterized by a TEM technique. The neutral red-doped interior maintained its high electron-activity, while the exterior nano-silica surface prevented the mediator from leaching out into the aqueous solution, and showed high biocompability. These nanoparticles were then mixing with the glucose oxidase (GOD), lactate oxidase (LOD), L-glutamate oxidase (L-GLOD) or xanthine oxidase (XOD), and immobilized on four glassy carbon electrodes, respectively. A thin Nafion film was coated on the enzyme layer to prevent interference from molecules such as ascorbic acid and uric acid in the dialysate. The high sensitivity of the NRDS modified enzyme electrode system enables the simultaneous monitoring of trace levels of glucose, L-glutamate, lactate and hypoxanthine in diluted dialysate samples from a rat striatum.