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Blood–brain barrier and laser technology for drug brain delivery

Journal of Innovative Optical Health Sciences 2017年第5期10卷 27-38页

作者： Oxana v.Semyachkina-Glushkovskaya Arkady S.Abdurashitov Elena I.Saranceva Eketerina G.Borisova Alexander A.Shirokov nikita v.navolokin Saratov State University 83 Astrakhanskaya Str.Saratov 410012 Russia Institute of Electronics Bulgarian Academy of Sciences TsarigradskoChaussee 72 Sofia 1784Bulgaria Institute of Biochemistry and Physiology of Plants and Microorganisms Russian Academy of Sciences 13 Prospekt EntuziastovSaratov 410049Russia Saratov State Medical University Saratov 410010 Russia

Here,we discuss an important problem in medicine as development of efctive strategies for brain drug *** problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system(CNS).We show three interfaces of anatomical side of BBB and two functional types of BBB一physical and transporter *** this protective mechanism is essential for health of CNS,it also creates a hindrance to the entry of drugs into the *** BBB was discovered over 100 years ago but till now,there is no efective methods for brain drug *** ane more than 70 approaches for overcoming BBB incuding physical,chenical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasi venes,challenge in performing,very costly or lim-itation of drug *** therapy(PDT)is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer ***,the application of PDT is considered as a potential promising tool for brain drug delivery via opening of ***,we show the first sucoessful experimental results in this field discussing the adventures and disadv antages of PDT-related BBB disruption as well as altematives to overcome these limitations and possi ble mechanisms with new pathways for brain clearance via gly mphatic and lymphatic systems.

关键词： Blood-brain barrier laser technologies photodynamic therapy brain drug delivery

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Tumor cell death visualization of renal cell carcinoma under the combined effect of the Gratiola officinalis extract and cyclophosphamide using fluorescent staining methods

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Journal of Innovative Optical Health Sciences 2021年第5期4卷 46-52页

作者： Artyom Mylnikov nikita navolokin Dmitry Mudrak Natalya Polukonova Alla Bucharskaya Galina Maslyakova Saratov State Medical University named after V.I.Razumovsky 112 Bolshaya Kazachia Street Saratov 410012Russia National Research Saratov State University 83 Astrakhanskaya Street Saratov 410012Russia National Research Tomsk State University 36 Lenin Avenue Tomsk 634050Russia

Objective of the study:We used fluorescence imaging methods of apoptosis and necrosis in human renal carcinoma A498 tumor cells in vitro to reveal the indicated forms of cell death under the combined effect of flavonoid-containing extract of Gratiola officinalis and cytostatic(cyclo-phosphamide).Materials and methods:The dyes were propidium iodide and acridine orange,which were used in the"alive and dead"*** test helped us to identify the total number of dead cells in the forms of necrosis and apoptosis and the number of cells in which apoptosis had started,it was characterized by the appearance of apoptotic bodies or nucleus ***:We found the most pronounced cytotoxic activity at the ratio of extract of Gratiola officinalis and cyclophosphamide concentrations of 1∶*** number of living cells decreased when exposed to the ratio of extract and cytostatic concentrations of 2∶*** the ratio of concentration of the extract relative to the cytostatic increased to 3∶1,the cytostatic activity of the extract began to appear,the total number of tumor cells *** number of cells with nucleus pyknosis and the number of cells with apoptosis signs significantly increased at a 3∶1 ratio of extract and cytostatic concentrations,which confirms the presence of pro-apoptotic activity of the studied *** trend indicates the dependence of a certain form of cell death(apoptosis,necrosis)on the ratio of extract and cytostatic doses,and it also demon-strates the cytostatic and cytotoxic effects of this ***:Fluorescence methods of investigation in the"alive and dead"test allowed us to visualize the forms of cell death of human kidney carcinoma A498 by combined exposure to the fiavonoid-containing extract of Gratiola officinalis and cytostatic(cyclophosphamide)24 h after *** found that the combination with a concentration ratio of the extract and cyclophosphamide of 3:1 has the greatest effectiveness due to stimulation of t

关键词： A498 cell line Gratiola officinalis extract antitumor activity cytostatic activity flavonoids fluorescent methods kidney cancer

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Large-scale error-tolerant programmable interferometer fabricated by femtosecond laser writing

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Photonics Research 2024年第3期12卷 I0028-I0040页

作者： ILYA KONDRATYEv vERONIKA IvANOvA SUREN FLDZHYAN ARTEM ARGENCHIEv nikita KOSTYUCHENKO SERGEY ZHURAvITSKII NIKOLAY SKRYABIN IvAN DYAKONOv MIKHAIL SAYGIN STANISLAv STRAUPE ALEXANDER KORNEEv SERGEI KULIK Quantum Technology Centre and Faculty of Physics M.V.Lomonosov Moscow State UniversityMoscow 119991Russia Russian Quantum Center Moscow 121205Russia Laboratory of Quantum Engineering of Light South Ural State UniversityChelyabinsk 454080Russia

We introduce a programmable eight-port interferometer with the recently proposed error-tolerant architecture capable of performing a broad class of *** interferometer has been fabricated with femtosecond laser writing,and it is the largest programmable interferometer of this kind to *** have demonstrated its advantageous error tolerance by showing an operation in a broad wavelength range from 920 to 980 nm,which is particularly relevant for quantum photonics due to efficient photon sources existing in this wavelength *** work highlights the importance of developing novel architectures of programmable photonics for information processing.

关键词： interferometer laser femtosecond

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Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels:Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment

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Journal of Innovative Optical Health Sciences 2018年第4期11卷 98-107页

作者： Olga Pavlova Alexander Shirokov Alexander Fomin nikita navolokin Andrey Terskov Alexander Khorovodov Anton Namykin Alexey Pavlov valery Tuchin Oxana Semyachkina-Glushkovskaya Interdisciplinary Center of Critical Technologies in Medicine Saratov State University 83 Astrakhanskaya Str.Saratov 410012Russia Institute of Biochemistry and Physiology of Plants and Microorganisms Russian Academy of Sciences13 Entuziastov Ave.Saratov 410049Russia Saratov State Medical University 112 Bolshaya Kazachia Str. Saratov 410012Russia Department of Optics and Biophotonics Saratov State University 83 Astrakhanskaya Str.Saratov 410012Russia Yuri Gagarin State Technical University of Saratov 77 Politechnicheskaya Str. Saratov 410054Russia Laboratory of Laser Diagnostics of Technical and Living Systems Institute of Precision Mechanics and Control of RAS 24 Rabochaya Str.Saratov 410028Russia Laboratory of Biophotonics Tomsk State University 36 Lenin's Ave.Tomsk 634050Russia

Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the other hand,drug brain delivery via the BBB is a big challenge in glioma *** limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma ***,we present in vrivo and er vrivo study of the BBB disruption and glioma cells(GCs)migration in rats using fuorescence and confocal *** uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells,where the BBB was impermeable for high weight *** migr ation of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages *** mechanisms underlying glioma progression remain umknown but there is an evidence that the sympathetic nervous system(SNS)via activation of vascular beta2-adrenoreceptors(B2-ADRs)can play an important role in tumor *** results clearly show an increase in the expression of vascular B2-ADRs and production of the beta arrestin-1-co-factor of B2-ADRs signaling pathway in rats with *** blockade of B2-ADRs reduces the BBB disruption,macrophages infiltration,GCs migration and increases survival *** data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis。

关键词： Glioma macrophages blood-brain barrier beta-2 adrenoreceptors bet a arrestin-1

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Alterations of morphology of lymphoid organs and peripheral blood indicators under the influence of gold nanoparticles in rats

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Journal of Innovative Optical Health Sciences 2016年第1期9卷 47-56页

作者： Alla B.Bucharskaya Svetlana S.Pakhomy Olga v.Zlobina Galina N.Maslyakova Olga v.Matveeva Irina O.Bugaeva nikita A.navolokin Boris N.Khlebtsov vladimir A.Bogatyrev Nikolai G.Khlebtsov valery v.Tuchin Saratov State Medical University 112 B.Kazach'ya str.Saratov 410012Russia Institute of Biochemistry and Physiology of Plants and Microorganisms RAS 13 Entuziastov Prospekt.Saratov 410049Russia Saratov State University 83 Astrakhanskaya str.Saratov 410012Russia§Institute of Precise Mechanics and Control of Russian Academy of Sciences 24Rabochaya str.Saratov 410028Russia Interdisciplinary Laboratory of Biophotonics Tomsk State University 36 Lenina str.Tomsk 634050Russia

At present,gold nanoparticles(GNPs)are widely used in biomedical applications such as cancer diagnostics and ***,the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant ***,we report the effects of prolonged peroral administration of GNPs with different sizes(2,15 and 50 nm)on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory *** experiment was conducted on 24 white mongrel male rats weighing 180–220 g,gold nanospheres sizes 2,15 and 50nm were administered orally for 15 days at a dosage of 190g/kg of animal body *** GNPs were conjugated with polyethylene glycol to increase their biocompatibility and *** size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood,especially pronounced after administration of GNPs with size of 50 *** stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone *** signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes,which were showed as the increasing number of immunoblasts and large *** quantitative changes of cellular component morphology of lymphoid organs due to activation of migration,proliferation and di®erentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

关键词： Gold nanoparticles lymphoid organs morphological changes bone marrow examination

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The morphological changes in the internal organs of laboratory animals after prolonged oral administration of gold nanoparticles

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 74-84页

作者： Alla B.Bucharskaya Galina N.Maslyakova Svetlana S.Pakhomy Olga v.Zlobina Irina O.Bugaeva nikita A.navolokin Boris N.Khlebtsov vladimir A.Bogatyrev Nikolai G.Khlebtsov valery v.Tuchin Saratov State Medical University n.a.v.I.Razumovsky 410012 Saratov Russia Institute of Biochemistry and Physiology of Plants and Microorganisms RAS 410049 Saratov Russia Research-Educational Institute of Optics and Biophotonics Saratov National Research State University 410012 Saratov Russia Institute of Precision Mechanics and Control RAS 410028 Saratov Russia Interdisciplinary Laboratory of Biophotonics Tomsk National Research State University 634050 TomskRussia

Recently gold nanoparticles(GNPs)have been actively studied as photot hermal converters,drug carriers,and imaging agents in a wide range of applications in cancer diagnosis and ther *** prolonged peroral administration of GNPs in a range of sizes was performed to investigate the morphological changes and their reversibility in the internal organs of laboratory *** this study,GNP's with average diameters of 2 nm,15 nm and 50nm were administered during 30 days,and the reversibility of morphological changes was investigated 14 days after *** the prolonged administration of GNPs,the severity of morphological changes in the liver,kidney,spleen and lymph nodes depended on the nanoparticle ***,50 nm nano-particles caused the most pronounced dystrophic and necrobiotic effects,whereas the smallest 2 nm nanoparticles caused proliferative *** importantly,the development of patho-logical processes was reversible,as evidenced by the gradual restoration of the organ structure at 14 days after the end of GNPs administration.

关键词： Gold nanoparticles prolonged peroral administration morphological changes reversibility.

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Highly selective/enantioselective Pt-ReOx/C catalyst for hydrogenation of L-malic acid at mild conditions

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Journal of Energy Chemistry 2018年第3期27卷 903-912页

作者： Bair S.Bal'zhinimaev Eugene A.Paukshtis Alexey P.Suknev nikita v.Makolkin Boreskov Institute of Catalysis SB RA5 Prospect Akademika Lavrentieva5Novosibirsk 630090Russia

The catalyst preparation strategy was based on a strict introduction sequence of rhenium and platinum precursors and their strong interaction with carbon support resulted in the formation of 0.5 nm Pt-Re Ox species of atomic dispersion, where platinum is metallic, while monolayer rhenium is partially oxidized（Re2＋）. The reaction kinetics was studied taking into account the process of L-malic acid association leading to the formation of inactive cyclic oligomeric species. High TOFs（ca. 50 h-1）, selectivities（ca. 99%）and stability of Pt-Re Ox/C catalysts in aqueous-phase hydrogenation of L-malic acid, which are close to those of the homogeneous pincer type complexes, were revealed at mild conditions（T = 90–130 ℃）. Taking into account that（i） hydrogenation reaction occurred 2–3 orders of magnitude faster than its racemization and（ii） association of L-malic acid dominates at low temperatures and in a concentrated solution,special reaction conditions that allow obtaining chemically and optically（ee 〉 99%） pure（S）-3-hydroxy-γ-butyrolactone and（S）-1,2,4-butanetriol were found. Basing on HAADF-STEM, EDX, XPS, and kinetic studies, the structure of active species and basic reaction pathways are proposed.

关键词： L-malic acid Hydrogenation Enantioselectivity Platinum Rhenium Atomic dispersion

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Mechanism of the Initial Stage of Thermal Decomposition of Nitroguanidine

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火炸药学报 2023年第1期46卷 31-40页

作者： Boris E.Krisyuk Danila A.Markin Timofey M.Sypko viktor v.Zakharov nikita v.Chukanov Boris L.Korsunskiy Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry Russian Academy of Sciences142432prosp.Academician Semenov1ChernogolovkaMoscow RegionRussia Plekhanov Russian University of Economics Department of Chemistry and Physics36 Stremyanny laneMoscow 117997Russia Lomonosov Moscow State University Faculty of Fundamental Physical and Chemical engineeringGSP-11 Leninskie Goryp.51Moscow 119991Russia N.N.Semenov Federal Research Center for Chemical Physics Russian Academy of Science 4 Kosygina StreetBuilding 1Moscow 119991Russia

A theoretical and experimental study of the thermal decomposition of nitroguanidine(NQ) has been carried out. various thermolysis channels were studied by quantum chemistry methods at the CCSD(or DLPNO-CCSD) level using the aug-cc-pvDZ basis set. It is shown that the lowest activation enthalpies(170-180kJ/mol) are characteristic of the reactions of NO2abstraction from the initial NQ and the reaction channel with the transfer of oxygen from the nitro group to carbon in the limiting stage. Additionally, the thermolysis of NQ was studied experimentally in a nonisothermal mode with heating rates from 1 to 10K/min. In these experiments, the weight loss of the sample, thermal effects, and mass spectra of the products were recorded. An analysis of the experimental data confirmed the results of a theoretical study of the mechanism of thermal decomposition of NQ. The main thermolysis products are N2O, HNCO, NH3, and NO2, which fully corresponds to quantum chemical calculations.

关键词： primary thermolysis steps quantum-chemical calculation mass spectrometry DSC TG

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Calcium Carbide:From Elemental Carbon to Isotope-Economic Synthesis of^(13)C_(2)-Labeled Heterocycles

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Chinese Journal of Chemistry 2023年第21期41卷 2810-2818页

作者： Maria S.Ledovskaya vladimir v.voronin nikita R.valov Dmitriy E.Samoylenko Saint Petersburg State University Institute of ChemistryUniversitetsky prospect 26Peterhof198504 Russia

^(13)C-Carbon is the most available source of *** is a relatively inexpensive solid material,which can be easily converted to calcium carbide-^(13)C_(2).In current work,Ca^(13)C_(2)was used for in situ generation of^(13)C_(2)-acetylene in 1,3-dipolar cycloaddition and[4+2]cycloaddition *** the first time,1H-1,2,3-triazoles-4,5-^(13)C_(2)and isoxazoles-4,5-^(13)C_(2)were synthesized using calcium carbide-^(13)C_(2).A Diels-Alder type cycloaddition of 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine and Ca^(13)C_(2)was investigated,and the best way for the synthesis of 3,6-di(pyridin-2-yl)pyridazine-4,5-^(13)C_(2)was proposed for the first *** we perform a detailled description of NMR spectra of^(13)C_(2)-labeled triazoles,isoxazoles and 3,6-di(pyridin-2-yl)pyridazine.

关键词： Isotopic labeling Cycloaddition Click chemistry Sustainable Chemistry Calcium carbide

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Generation of synchronized x-rays and mid-infrared pulses by Doppler-shifting of relativistically intense radiation from near-critical-density plasmas

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Matter and Radiation at Extremes 2023年第2期8卷 6-13页

作者： nikita A.Mikheytsev Artem v.Korzhimanov Lobachevsky State University of Nizhny Novgorod 603022 Nizhny NovgorodRussia Federal Research Center Institute of Applied Physics of the Russian Academy of Sciences 603950 Nizhny NovgorodRussia

It is shown that when relativistically intense ultrashort laser pulses are reflected from the boundary of a plasma with a near-critical density,the Doppler frequency shift leads to generation of intense radiation in both the high-frequency(up to the x-ray)and low-frequency(mid-infrared)*** efficiency of energy conversion into the wavelength range above 3μm can reach several percent,which makes it possible to obtain relativistically intense pulses in the mid-infrared *** pulses are synchronized with high harmonics in the ultraviolet and x-ray ranges,which opens up opportunities for high-precision pump–probe measurements,in particular,laser-induced electron diffraction and transient absorption spectroscopy.

关键词： pump intense relativistic

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