Visualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopyvisualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopy

Recent developments in the field of biophotonics facilitate the raise of interest to inorganic nanoparticles (NPs) doped with Nd 3+ ions, because of their near-infrared (NIR) absorption. These NPs are interesting bioimaging probes for deep tissue visualization, while they can also act as local thermometers in biological tissues. Despite the good possibilities for visualization of NPs with Nd 3+ ions in NIR spectral range, difficulties arise when studying the cellular uptake of these NPs using commercially available fluorescence microscopy systems, since the selection of suitable luminescence detectors is limited. However, Nd 3+ ions are able to convert NIR radiation into visible light, showing upconversion properties. In this paper we found optimal parameters to excite upconversion luminescence of Nd 3+ :LaF 3 NPs in living cells and to compare the distribution of the NPs inside the cell culture of human macrophages THP-1 obtained by two methods. Firstly, by detecting the upconversion luminescence of the NPs in VIS under NIR multiphoton excitation using laser scanning confocal microscopy and secondly, using transmission electron microscopy

Influence of ABCB1 and CYP3A5 gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke

Alexander Valerevich Kryukov,1 Dmitry Alekseevich Sychev,1 Denis Anatolevich Andreev,2 Kristina Anatolievna Ryzhikova,1 Elena Anatolievna Grishina,1 Anastasia Vladislavovna Ryabova,1 Mark Alekseevich Loskutnikov,3 Valeriy Valerevich Smirnov,4 Olga Dmitrievna Konova,1 Irina Andreevna Matsneva,2 Pavel Olegovich Bochkov1 1Russian Medical Academy of Continuous Professional Education, Moscow, Russia; 2Department of General Medicine, Sechenov First Moscow State Medical University, Moscow, Russia; 3L.A. Vorohobov City Clinical Hospital, Moscow, Russia; 4NRC Institute of Immunology FMBA of Russia, Moscow, Russia Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at -70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class. Keywords: cardioembolic stroke, atrial fibrillation, non-vitamin K anticoagulants, apixaban, pharmacokinetics, pharmacogenetic

Nuclear import of an intact preassembled proteasome particle

Nuclear targeting of intact proteasome particles was tested in the Xenopus egg extract system. Both the 26S proteasome holoenzyme and the 20S core particle were targeted to the nuclear envelope but could not enter the nucleus. A novel proteolytically active 20S+ particle was actively imported into the nucleoplasm in a Ran-independent fashion

OBSERVATION OF A HIGH-ENERGY COSMIC-RAY FAMILY CAUSED BY A CENTAURO-TYPE NUCLEAR-INTERACTION IN THE JOINT EMULSION CHAMBER EXPERIMENT AT THE PAMIRS

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NUCLEAR-INTERACTIONS OF SUPER HIGH-ENERGY COSMIC-RAYS OBSERVED IN MOUNTAIN EMULSION CHAMBERS

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