RESUMEN
The present study investigated immune stimulatory effects of Cladosiphon okamuranus-derived fucoidan to activate murine macrophage-like cell line RAW264, and the functional relationship with zymosan, a Saccharomyces cerevisiae-derived ß-glucan. The production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in RAW264 cells were remarkably enhanced in the presence of 10⯵g/mL fucoidan, and the stimulatory effects of fucoidan were maximally augmented in combinational treatment with 500â¯ng/mL zymosan, whereas any TLR ligands had no those effects. Confocal microscopic analyses suggested that fucoidan bound on plasma membrane, and it was estimated that some cell surface molecules acted as receptor for fucoidan because cytochalasin D, an inhibitor of phagocytosis, did not affect the immune enhancing activities, whereas methyl-ß-cyclodextrin (MßCD), a general agent for disruption of lipid rafts, diminished that. Furthermore, it was revealed that the additive effects of zymosan on the immune activation with fucoidan was thought to be mediated by dectin-1 based on the results with dectin-1-knockdown RAW264â¯cells. All of results suggested that fucoidan and some kinds of ß-glucan would cooperatively reinforce the activity of innate immune cells via interactive receptor crosstalk.
Asunto(s)
Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Polisacáridos/farmacología , beta-Glucanos/farmacología , Animales , Sinergismo Farmacológico , Macrófagos/inmunología , Ratones , Phaeophyceae/química , Polisacáridos/química , Células RAW 264.7 , Saccharomyces cerevisiae/química , Algas Marinas/química , beta-Glucanos/químicaRESUMEN
During the past decade, research into superconducting quantum bits (qubits) based on Josephson junctions has made rapid progress. Many foundational experiments have been performed, and superconducting qubits are now considered one of the most promising systems for quantum information processing. However, the experimentally reported coherence times are likely to be insufficient for future large-scale quantum computation. A natural solution to this problem is a dedicated engineered quantum memory based on atomic and molecular systems. The question of whether coherent quantum coupling is possible between such natural systems and a single macroscopic artificial atom has attracted considerable attention since the first demonstration of macroscopic quantum coherence in Josephson junction circuits. Here we report evidence of coherent strong coupling between a single macroscopic superconducting artificial atom (a flux qubit) and an ensemble of electron spins in the form of nitrogen-vacancy colour centres in diamond. Furthermore, we have observed coherent exchange of a single quantum of energy between a flux qubit and a macroscopic ensemble consisting of about 3 × 10(7) such colour centres. This provides a foundation for future quantum memories and hybrid devices coupling microwave and optical systems.
RESUMEN
Sulfated saccharides exhibit diverse physiological activities, but a lack of any convenient assay hinders their evaluation. Herein, an assay for the analysis of sulfated saccharides is described using 1H nuclear magnetic resonance (NMR) spectroscopy by employing ligands that can form ionic complexes with the sulfate groups. Based on the change in the chemical shift (Δδ) of the ligands by sulfated mono- to tetrasaccharide, imidazole was found to be a good ligand, showing the maximum Δδ; neutral saccharides do not show any change in the δ value. A marked and constant downfield δ value observed was changed dramatically at a molar ratio of >1:1 (imidazole:sulfated saccharides), allowing a sulfate content estimation based on the concentration of imidazole at the Δδ inflection point. By the proposed ligand-aided 1H NMR assay, the sulfate content of natural sulfated polysaccharide, fucoidan, was non-destructively estimated to be 2.1 mmol/g-fucoidan.
Asunto(s)
Imidazoles/química , Oligosacáridos/química , Sulfatos/análisis , Ligandos , Estructura Molecular , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
The 14-membered macrolide erythromycin A expresses three distinct biological properties, including antibacterial activity, gastrointestinal motor-stimulating activity and anti-inflammatory and/or immunomodulatory effects. Although low-dose, long-term therapy using 14- and 15-membered macrolides displaying anti-inflammatory and/or immunomodulatory activity effectively treats diffuse panbronchiolitis and chronic sinusitis, bacterial resistance may emerge. To address this issue, we developed the 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900) that promotes monocyte to macrophage differentiation, a marker for anti-inflammatory and/or immunomodulatory effects, without possessing antibacterial activity. In this article, we report that the new macrolide derivative (8R,9S) -de(3'-N-methyl)-3'-N-(p-chlorobenzyl)-de(3-O-cladinosyl)-3-dehydro-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A 12,13-carbonate (EM939) exhibited stronger promotive activity for monocyte to macrophage differentiation than that of the parent compound EM900 in addition to reduced cytotoxicity toward THP-1 cells and antibacterial inactivity. In a cigarette-smoking model used to simulate chronic obstructive pulmonary disease (COPD), the EM900 derivatives significantly attenuated lung and alveolar inflations, functionally and histologically, via oral administration. Because of these marked therapeutic effects, non-antibiotic EM900 derivatives may become central to the treatment of chronic inflammatory diseases such as COPD.
Asunto(s)
Antiinflamatorios/farmacología , Macrólidos/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Eritromicina/análogos & derivados , Eritromicina/química , Eritromicina/farmacología , Eritromicina/uso terapéutico , Cobayas , Pulmón/patología , Macrólidos/síntesis química , Macrólidos/uso terapéutico , Macrófagos/efectos de los fármacos , Macrófagos/patología , Pruebas de Sensibilidad Microbiana , Monocitos/efectos de los fármacos , Monocitos/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Fumar/efectos adversosRESUMEN
Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits â¼200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.
Asunto(s)
Quitinasas/antagonistas & inhibidores , Macrólidos/química , Macrólidos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Serratia marcescens/enzimología , Bacterias/efectos de los fármacos , Bacterias/enzimología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Quitinasas/metabolismo , Cristalografía por Rayos X , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Modelos Moleculares , Infecciones por Serratia/tratamiento farmacológico , Infecciones por Serratia/microbiología , Serratia marcescens/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
We analyzed the Josephson bifurcation amplifier (JBA) readout process of a superconducting qubit quantum mechanically by calculating the dynamics of the density operator of a driven nonlinear oscillator and a qubit coupled system during the measurement process. In purely quantum cases, bifurcation is impossible. Introducing decoherence enables us to reproduce the bifurcation with a finite hysteresis. When a qubit is initially in a superposition state, we have observed the qubit-probe (JBA) entangled state, and it is divided into two separable states at the moment the JBA transition begins. This corresponds to "projection." To readout the measurement result, however, we must wait until the two JBA states are macroscopically well separated. The waiting time is determined by the strength of the decoherence in the JBA.