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1.
Brain Behav Immun ; 68: 183-196, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29061364

RESUMEN

Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia. Here, we polarized primary microglia with IFNγ and show that the characteristic increases in tumor necrosis factor-α (TNFα) and nitric oxide synthase 2 (NOS2) were accompanied by increased glycolysis and an increase in the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3, an enzyme that plays a significant role in driving glycolysis. These changes were associated with increased expression of ferritin and retention of iron in microglia. Significantly, retention of iron in microglia increased TNFα expression and also increased glycolysis suggesting that increased intracellular iron concentration may drive the metabolic and/or inflammatory changes. Analysis of microglia prepared from wildtype mice and from transgenic mice that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) revealed genotype-related increases in glycolysis, accompanied by increased PFKFB3, and an increase in the expression of ferritin. The data indicate a distinct metabolic signature of inflammatory microglia from APP/PS1 mice that are also distinguishable by their iron handling profiles.


Asunto(s)
Microglía/inmunología , Microglía/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Ferritinas/metabolismo , Glucólisis/fisiología , Inflamación/metabolismo , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Hierro/metabolismo , Lipopolisacáridos/metabolismo , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfofructoquinasa-2/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba
2.
Chirality ; 29(8): 403-408, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28608629

RESUMEN

Chirality strongly influences many biological properties of materials, such as cell accumulation, enzymatic activity, and toxicity. In the past decade, it has been shown that quantum dots (QDs), fluorescent semiconductor nanoparticles with unique optical properties, can demonstrate optical activity due to chiral ligands bound on their surface. Optically active QDs could find potential applications in biomedical research, therapy, and diagnostics. Consequently, it is very important to investigate the interaction of QDs capped with chiral ligands with living cells. The aim of our study was to investigate the influence of the induced chirality of Mn-doped ZnS QDs on the viability of A549 cells. These QDs were stabilized with D- and L-cysteine using a ligand exchange technique. The optical properties of QDs were studied using UV-Vis, photoluminescence (PL), and circular dichroism (CD) spectroscopy. The cytotoxicity of QDs was investigated by high content screening analysis. It was found that QDs stabilized by opposite ligand enantiomers, had identical PL and UV-Vis spectra and mirror-imaged CD spectra, but displayed different cytotoxicity: QDs capped with D-cysteine had greater cytotoxicity than L-cysteine capped QDs.

3.
Appl Opt ; 54(31): F222-31, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-26560611

RESUMEN

We review the history of ultraviolet and extreme ultraviolet spectroscopy with a specific focus on such activities at the Naval Research Laboratory and on studies of the extended solar corona and solar-wind source regions. We describe the problem of forecasting solar energetic particle events and discuss an observational technique designed to solve this problem by detecting supra-thermal seed particles as extended wings on spectral lines. Such seed particles are believed to be a necessary prerequisite for particle acceleration by heliospheric shock waves driven by a coronal mass ejection.

4.
Sci Rep ; 8(1): 2860, 2018 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-29434252

RESUMEN

The hot injection synthesis of nanomaterials is a highly diverse and fundamental field of chemical research, which has shown much success in the bottom up approach to nanomaterial design. Here we report a synthetic strategy for the production of anisotropic metal chalcogenide nanomaterials of different compositions and shapes, using an optimised hot injection approach. Its unique advantage compared to other hot injection routes is that it employs one chemical to act as many agents: high boiling point, viscous solvent, reducing agent, and surface coordinating ligand. It has been employed to produce a range of nanomaterials, such as CuS, Bi2S3, Cu2-xSe, FeSe2, and Bi4Se3, among others, with various structures including nanoplates and nanosheets. Overall, this article will highlight the excellent versatility of the method, which can be tuned to produce many different materials and shapes. In addition, due to the nature of the synthesis, 2D nanomaterial products are produced as monolayers without the need for exfoliation; a significant achievement towards future development of these materials.

5.
Chem Commun (Camb) ; 53(49): 6657-6660, 2017 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-28585625

RESUMEN

Here we report a new low temperature dry ice carbonation approach for the synthesis of carbonate-based nano- and micro-particulate materials, which enables the preparation of monodispersed calcium carbonate nanoparticles and microspheres with very high purity phases.

6.
J Mater Chem B ; 5(33): 6701-6727, 2017 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32264322

RESUMEN

In this review we present new concepts and recent progress in the application of semiconductor quantum dots (QD) as labels in two important areas of biology, bioimaging and biosensing. We analyze the biologically relevant properties of QDs focusing on the following topics: QD surface treatment and stability, labeling of cellular structures and receptors with QDs, incorporation of QDs in living cells, cytotoxicity of QDs and influence of the biological environment on the biological and optical properties of QDs. Initially, we consider utilization of QDs as agents in high-resolution bioimaging techniques that can provide information at the molecular levels. The diverse range of modern live-cell QD-based imaging techniques with resolution far beyond the diffraction limit of light is examined. In each technique, we discuss the pros and cons of QD use and deliberate how QDs can be further engineered to facilitate their application in the respective imaging techniques and to produce significant improvements in resolution. Then we review QD-based point-of-care bioassays, bioprobes, and biosensors designed in different formats ranging from analytic biochemistry assays and ELISA, to novel point-of-care smartphone integrated QD-based biotests. Here, a wide range of QD-based fluorescence bioassays with optical transduction, elecrochemiluminescence and photoelectrochemical assays are discussed. Finally, this review provides an analysis of the prospects of application of QDs in selected important areas of biology.

7.
Toxicol Res (Camb) ; 5(1): 180-187, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30090336

RESUMEN

Encapsulation of Quantum Dots (QDs) has become an essential factor which regulates particles cytotoxicity, as well as physical and chemical stability. Negatively charged cellular membranes have a great affinity to nanoparticles with surface molecules carrying positive charge, hence creating perfect conditions for fast and aggressive intracellular penetration. The preference for non-charged outer shells is topical in QD design and various applications. In the current paper we develop gelatination as a prominent coating approach to create neutrally passivated QDs with improved biocompatibility. We have revealed the trends in particle's uptake, accumulation, intracellular localisation and retaining time as well as RAW264.7 monocyte cell fate and immune responses. Also the difference in particle endocytosis kinetics and dynamics has been shown to depend on the QD core size. The intracellular QD content along with cell responses at the population level was quantified by flow cytometry.

8.
Arch Pharm Res ; 21(6): 657-63, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9868533

RESUMEN

The enzyme responsible for the synthesis of nitric oxide (NO) from L-arginine in mammalian tissues is known as nitric oxide synthase (NOS) (EC.1.14.13.39). In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic acinar cells. Treatment of rat pancreatic acinar cells with cholecystokinin-octapeptide (CCK-OP) resulted in an increase in the arginine conversion to citrulline, the amount of NOx, the release of amylase, and the level of cGMP. Especially, CCK-OP-stimulated increase of arginine to citrulline transformation, the amount of NOx and cGMP level were completely counteracted by the inhibitor of NOS, NG-monomethyl-L-arginine (MMA), by contrast, that of amylase release was partially reduced. Furthermore, MMA-induced decrease of NOS activity and amylase release showed dose-dependent pattern. The data on the time course of CCK-OP-induced citrulline formation and cGMP rise indicate that NOS and guanylate cyclase were activated by treatment of CCK-OP. However, the mechanism of agonist-stimulated guanylate cyclase activation in acinar cells remains unknown. Therefore, activation of NOS is one of the early events in receptor-mediated cascade of reactions in pancreatic acinar cells and NO, not completely, but partially mediate pancreatic enzyme exocrine secretion.


Asunto(s)
GMP Cíclico/farmacología , Óxido Nítrico/fisiología , Páncreas/metabolismo , Amilasas/metabolismo , Animales , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Óxido Nítrico/análisis , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa/análisis , Ratas , Sincalida/farmacología , Factores de Tiempo , omega-N-Metilarginina/farmacología
9.
Arch Pharm Res ; 20(3): 239-46, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18975158

RESUMEN

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that N(G)-monomethyl-L-arginine (MMA) and N(G), N(G)-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.

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