Search

Determination of the iron oxide nanoparticles (IONPs) local temperature during laser heating is important in the aspect of laser phototherapy. We have carried out theoretical modeling of IONPs local electromagnetic (EM) field enhancement and heating under the laser action near individual IONPs and ensembles of IONPs with different sizes, shapes and chemical phases. For experimental determination of IONPs temperature, we used fluorescence thermometry with rhodamine B (RhB) based on its lifetime. Depending on the IONPs shape and their location in space, a significant change in the spatial distribution of the EM field near the IONPs surface is observed. The local heating of IONPs in an ensemble reaches sufficiently high values; the relative change is about 35 °C for Fe2O3 NPs. Nevertheless, all the studied IONPs water colloids showed heating by no more than 10 °C. The heating temperature of the ensemble depends on the thermal conductivity of the medium, on which the heat dissipation depends. During laser scanning of a cell culture incubated with different types of IONPs, the temperature increase, estimated from the shortening of the RhB fluorescence lifetime, reaches more than 100 °C. Such “hot spots” within lysosomes, where IONPs predominantly reside, lead to severe cellular stress and can be used for cell therapy.

In this work, we used Mossbauer spectroscopy as a new approach for experimental quantification of the self-diffusion coefficient (DMossbauer) and hydrodynamic (HD) size of iron-containing nanoparticles (NPs) in complex crowded solutions, mimicking cell cytoplasm. As a probe, we used 9 nm cobalt ferrite NPs (CFNs) dispersed in solutions of bovine serum albumin (BSA) with a volume fraction (φBSA) of 0-0.2. Our results show that the broadening of Mossbauer spectra is highly sensitive to the diffusion of CFNs, while when φBSA = 0.2, the CFN-normalized diffusivity is reduced by 86% compared to that of a protein-free solution. CFN colloids were also studied by dynamic light scattering (DLS). Comparison of the experimental data shows that DLS significantly underestimates the diffusion coefficient of CFNs and, consequently, overestimates the HD size of CFNs at φBSA > 0, which cannot be attributed to the formation of the BSA monolayer on the surface of CFNs.

To date, the phylogeny of Rickettsia spp. from basal groups is based on the small number of identified species. Thus, the finding of "Candidatus Rickettsia mendelii" in 2016 is of great interest. In this study, "Ca. R. mendelii" was first identified in the Asian region in a new carrier, Ixodes pavlovskyi. "Candidatus R. mendelii", along with "Candidatus Rickettsia tarasevichiae", were found in Ixodes ticks collected on Russky Island (the Far East), where I. pavlovskyi coexists with I. persulcatus. To establish the taxonomic position of "Ca. R. mendelii", a detailed genetic study was carried out. "Candidatus R. mendelii" was genotyped by five genetic fragments (16S rRNA, gltA, and ompB genes, groESL operon, and 23S-5S IGS region); among them, the ompB gene, groESL operon and 23S-5S IGS region were sequenced for the first time. In addition, "Ca. R. tarasevichiae" was genetically characterized by eight genetic loci (16S rRNA, gltA, ompA, ompB, sca4, htrA genes, groESL operon, and 23S-5S IGS region), of which the sca4 gene was first determined. Phylogenetic analysis indicated that regardless of analyzed genetic loci, "Ca. R. mendelii" formed a separate well-supported cluster on each phylogenetic tree. Phylogenetic analysis based on concatenated sequences of gltA, ompB, and groEL gene fragments (total length of 3191 bp) demonstrated that "Ca. R. mendelii", like Rickettsia bellii, is a basal group of Rickettsia.

The nonstandard nature of intracellular motion is associated with a considerable content of macromolecules and is largely due to the phenomenon of abnormal diffusion. Features of the motion of nanoparticles in concentrated protein solutions that simulate cytoplasm are studied on a nanosecond time scale by means of Mossbauer spectroscopy. A comparative analysis is performed of the nano- and macro-viscosity of the media.

An approach to the analysis of intracellular motion with nanosecond temporal resolution, based on the Mossbauer study of particles incorporated into a cell, has been developed. A possibility of applying magnetic nanoparticles as probes for studying in vitro the cytoplasm properties is analyzed. Two types of aqueous colloids of nanoparticles enriched with the 57Fe isotope are synthesized, and their cytotoxicity and biodegradation resistance under living cell conditions are investigated by an example of breast cancer cell line. It is found that the particles barely undergo any changes characteristic of biodegradation processes during their 120-h incubation in cells, although intracellular oxidation of divalent iron in the particle composition is observed. This result indicates possibility of using these particles for in vitro Mossbauer studies.

The monograph reveals the history of the creation of the European Union and its current situation, which is characterized by instability and lack of genuine unity. In an effort to integrate everything and everyone in a short time, European leaders and officials have overestimated their strength. Meanwhile, every European country retains its identity and is in no hurry to give it up. Russia and the participants of integration interstate associations should learn lessons from the fate of the European Union: not to force rapprochement, not to encroach on the state sovereignty of its members, to respect the opinion of ordinary people. The publication is intended for specialists in the field of European politics, European law, international relations, as well as for a wide range of readers interested in the political life of Europe.

In the range of 800–1200 K, both experiments and kinetic modeling demonstrate a significant difference in the dependence of the ignition delay time of methane and hydrogen on pressure and temperature, with the complex influence of these parameters on the autoignition delay time of methane–hydrogen–air mixtures. In connection with the prospects for the widespread use of methane–hydrogen mixtures in energy production and transport, a detailed analysis of their ignition at temperatures below 1000 K, the most important region from the point of view of their practical application, is carried out. It is shown that such a complex behavior is associated with the transition in this temperature range from low-temperature mechanisms of oxidation of both methane and hydrogen, in which peroxide radicals and molecules play a decisive role, to high-temperature mechanisms of their oxidation, in which simpler radicals dominate. A kinetic interpretation of the processes occurring in this case is proposed.

Magnetic nanoparticles are widely used in various fields of biomedicine. They can combine both therapy and diagnostics modalities thus opening many opportunities for their application. In our work, we have evaluated their ability to work as contrast agents for magnetic resonance imagining and drug delivery systems for photosensitizers. We have shown that after formation of human serum albumin retains ability to bind photosensitizers and they do not lose their optical properties. To obtain stable water solution suitable for long term storage we have additionally modified human serum albumin with polyethylene glycol. It was shown that such modification allows to increase overall stability over time.

Biodegradation of nanoparticles includes the destruction of a stabilizing coating and the accompanying change in interparticle interaction, as well as the direct destruction of the inorganic nuclei of particles. These processes lead to characteristic changes in the shape of the Mossbauer spectra of iron oxide nanoparticles. In this work, we investigated the in vitro biodegradation of 57Fe-based magnetic nanoparticles with the aid of Mossbauer spectroscopy. For this purpose, two types of magnetic nanoparticles enriched with the 57Fe isotope were synthesized. Copolymer Pluronic F-127 and citric acid were used to stabilize nanoparticles in aqueous medium. Moreover, synthesized nanoparticles were analyzed by physicochemical methods and investigated for cytotoxicity. The study of magnetic nanoparticles biodegradation was performed on 4 T1 cell culture (breast cancer). We measured Mossbauer spectra of nanoparticles incubated with 4 T1 cells and spectra of control nanoparticle samples at different conditions. The analysis of spectra was carried out in the many-state relaxation model formalism. The study revealed that after 120-hours incubation of nanoparticles in cells, they did not undergo measurable changes typical of biodegradation processes. Nevertheless, we noted intense intracellular oxidation of ferrous iron of synthesized nanoparticles to the ferric phase. The results obtained indicate the possibility of using the obtained nanoparticles in Mossbauer in vitro studies.

Magnetic hyperthermia is one of the most effective methods for treatment of cancer. In this work we discuss synthesis of magnetic iron oxide nanorods (IONRds) and their application for enhanced magnetic hyperthermia. By microwave irradiation the monodisperse water-soluble IONRds with clear morphology were obtained. Magnetic measurements showed that such IONRds have high value of coercivity (141 Oe). Moreover, hyperthermia experiments with synthesized samples were carried out. At the frequency and field strength of alternating magnetic field (AMF) f = 261 kHz H = 20 kA m−1 the specific absorption rate (SAR) and intrinsic loss power (ILP) values were equal to 147 W g−1 and 1.4 nHm2 kg−1 respectively, which confirms the efficiency of synthesized nanorods in hyperthermia applications.

Magnetic resonance imaging (MRI) is widely used to diagnose cancer and study patterns and effectiveness of nanocarrier delivery of anticancer drugs. Accumulation of nanoparticles in a tumor varies widely in a given population; it is also highly dependent on biological factors, which remain largely unstudied. In recent years, there was developed a hypothesis that suggests that MRI can be used to predict response to nanoformulations-based anticancer therapy since it provides data on accumulation of MRI contrast agents in the tumor. Pilot tests prove feasibility of the approach based on this hypothesis, however, there is a number of conceptual and technical problems and limitations that hamper its introduction into the routine clinical practice. This article discusses the advantages and disadvantages of methods to stratify tumors by level of nanoparticles accumulation. Further research in this field would facilitate development of effective algorithms of personalized treatment with anticancer drugs delivered by nanoparticles.

This work is devoted to studying the effects of non-magnetic shell coating on nanoparticles in a low frequency alternating magnetic field (LF AMF) on tumor cells in vitro. Two types of iron oxide nanoparticles with the same magnetic core with and without silica shells were synthesized. Nanoparticles with silica shells significantly decreased the viability of PC3 cancer cells in a low frequency alternating magnetic field according to the cytotoxicity test, unlike uncoated nanoparticles. We showed that cell death results from the intracellular membrane integrity failure, and the calcium ions concentration increase with the subsequent necrosis. Transmission electron microscopy images showed that the uncoated silica nanoparticles are primarily found in an aggregated form in cells. We believe that uncoated nanoparticles lose their colloidal stability in an acidic endosomal environment after internalization into the cell due to surface etching and the formation of aggregates. As a result, they encounter high endosomal macromolecular viscosity and become unable to rotate efficiently. We assume that effective rotation of nanoparticles causes cell death. In turn, silica shell coating increases nanoparticles stability, preventing aggregation in endosomes. Thus, we propose that the colloidal stability of magnetic nanoparticles inside cells is one of the key factors for effective magneto-mechanical actuation.

Remote control of cells and single molecules by magnetic nanoparticles in nonheating external magnetic fields is a perspective approach for many applications such as cancer treatment and enzyme activity regulation. However, the possibility and mechanisms of direct effects of small individual magnetic nanoparticles on such processes in magneto-mechanical experiments still remain unclear. In this work, we have shown remote-controlled mechanical dissociation of short DNA duplexes (18-60 bp) under the influence of nonheating low-frequency alternating magnetic fields using individual 11 nm magnetic nanoparticles. The developed technique allows (1) simultaneous manipulation of millions of individual DNA molecules and (2) evaluation of energies of intermolecular interactions in short DNA duplexes or in other molecules. Finally, we have shown that DNA duplexes dissociation is mediated by mechanical stress and produced by the movement of magnetic nanoparticles in magnetic fields, but not by local overheating. The presented technique opens a new avenue for high-precision manipulation of DNA and generation of biosensors for quantification of energies of intermolecular interaction.

Iron oxide nanoparticles (IONs) are frequently used in various biomedical applications, in particular as magnetic resonance imaging contrast agents in liver imaging. Indeed, number of IONs have been withdrawn due to their poor clinical performance. Yet comprehensive understanding of their interactions with hepatocytes remains relatively limited. Here we investigated how iron oxide nanocubes (IO-cubes) and clusters of nanocubes (IO-clusters) affect distinct human hepatic cell lines. The viability of HepG2, Huh7 and Alexander cells was concentration-dependently decreased after exposure to either IO-cubes or IO-clusters. We found similar cytotoxicity levels in three cell lines triggered by both nanoparticle formulations. Our data indicate that different expression levels of Bcl-2 predispose cell death signaling mediated by nanoparticles. Both nanoparticles induced rather apoptosis than autophagy in HepG2. Contrary, IO-cubes and IO-clusters trigger distinct cell death signaling events in Alexander and Huh7 cells. Our data clarifies the mechanism by which cubic nanoparticles induce autophagic flux and the mechanism of subsequent toxicity. These findings imply that the cytotoxicity of ION-based contrast agents should be carefully considered, particularly in patients with liver diseases.

This article deals with ensuring the development of the legal framework of public relations in the sphere of freedom of conscience and religion, creating and modernizing means of protecting human and civil rights and freedoms.

Epidemiological surveys reflect a negative trend in functional indicators for children’s physical health. In recent surveys it is experimentally proved that unlike other methods of training, high-intensity interval training (HIIT) produces prevailing positive effect onto the indicators of physical and functional condition of children with poor health. However, the review of studies suggests that the stated idea turns to be controversial. There is the evidence of possible negative effects of intense physical activity due to the low level biological reliability of adaptation mechanisms and other anatomical and physiological characteristics of children. Therefore, it is necessary to provide a scientifically based conceptual model of timeline for children’s health training in which the central health impetus will be HIIT.

Magnetic hyperthermia (MHT) is a promising approach for cancer therapy. However, a systematic MHT characterization as function of temperature on the therapeutic efficiency is barely analyzed. Here, we first perform comparative temperature-dependent analysis of the cobalt ferrite nanoparticles-mediated MHT effectiveness in two murine tumors models - breast (4T1) and colon (CT26) cancer in vitro and in vivo. The overall MHT killing capacity in vitro increased with the temperature and CT26 cells were more sensitive than 4T1 when heated to 43 °C. Well in line with the in vitro data, such heating cured non-metastatic CT26 tumors in vivo, while only inhibiting metastatic 4T1 tumor growth without improving the overall survival. High-temperature MHT (>47 °C) resulted in complete 4T1 primary tumor clearance, 25-40% long-term survival rates, and, importantly, more effective prevention of metastasis comparing to surgical extraction. Thus, the specific MHT temperature must be defined for each tumor individually to ensure a successful antitumor therapy.

An original mathematic model of a main live-steam-line heating system for the 6 MW turbine is reviewed. The present model is composed from a system of ODE with divergences and constant coefficients, along with an object structure is shown, numerical values of parameters are determined. The transfer function method is used for the model analysis, which is necessary for the main problem resolving. It consists of a discrete control algorithm construction to provide an appropriate heat transition process of an aperiodic type with quality performance required. The con- trol algorithm is based on the functional minimization condition, which is used here as the minimum energy speed up the process. The gradient method and etalon-model method are also used to get an optimal system stage. Due to methods applied, a main variable parameter influence on a system performance is analyzed, optimal adjustment value is retrieved, which allows you to provide the required quality for the heating system performance in all operating modes.

The scientific and technical literature addressing the synthesis of anisotropic iron-oxide nanoparticles of various shapes (cubic, rod-like, clustered, etc.) sized from 10 to 100 nm and their application for diagnostic magnetic resonance imaging (MRI) of tissues and organs is analyzed. The analysis indicates that the nanoparticle shape, size, and surface chemistry affect considerably relaxation parameters T1 and T2. Thus, cubic iron-oxide nanoparticles had the greatest T2 values. Furthermore, rod-like and octapodal nanoparticles also exhibit rather high T2 values so that they can be used as contrast agents for diagnostic MRI.

Magnetic nanoparticle size is one of the key factors determining its magnetic and biological properties. Herein, we report a synthesis of magnetite uniform-sized cubic nanoparticles with 10, 15 and 20 nm edge lengths for magnetic resonance imaging (MRI). The structure and physicochemical properties of obtained magnetite nanocubes (MNCbs) were studied by multiple methods. MNCbs conjugated with Pluronic F-127 exhibited high colloidal stability in aqueous medium. Synthesized MNCbs demonstrated improved T2-relaxation comparing to commercially available contrast agents proving that these nanocubes can be used for MRI.

Currently, the bacterial etiology infectious diseases still remain a global health problem. Most of them are caused by gram-negative pathogenic microorganisms. The traditional method of infectious diseases treatment is based on the use of antibiotics. However, the rapid development of the resistance of pathogenic microorganisms to existing antibiotics forces to seek alternatives to traditional therapy. One of such alternatives is the therapy with bacteriophage endolysins - bacteriolytic enzymes capable of destroying the bacterial cell wall by hydrolyzing the peptidoglycan. Endolysins are highly specific for certain pathogens. The main limitation of their use towards gram- negative bacteria is the presence of an outer membrane in the latter preventing the penetration of lytic enzyme to its substrate. The effectiveness of endolysin penetration can be increased by destabilizing the outer membrane of gram-negative bacteria

The reason for this review based on the results of many meta- analyses is the great assessed difference in the methods of most studies in e-Health, telemedicine and tele-rehabilitation. It consists of different understanding of new terms, using different hard- and software, including criteria, different methodology of patient’s treatment and its evaluation. This status suggests that first of all m-Health/e-Health requires a unique ontology of terms using and methodology of studies comparing. In this review we try to describe shortly the most significant points of modern e-Health field of medicine. The basic parts include methodology of review formation, tele-communication implementation results, tele-education, interactive questioning, tele-consultation, telemedicine diagnosis, tele-monitoring, rehabilitation and tele-rehabilitation, gamification, acceptability of mobile electronic devices and software in e-Health and planning studies. At the end of the review the new ontological structure of digital medicine is presented.

Developing nanocarriers that accumulate in targeted organs and are harmlessly eliminated still remains a big challenge. Nanoparticles (NP) biodistribution is governed by their size, composition, surface charge and coverage. The current thinking in bionanotechnology is that renal clearance is limited by glomerular basement membrane pore size (≈6 nm), although there is a growing evidence that NP exceeding the threshold can also be excreted with urine. Here we compare biodistribution of PEGylated 140 nm iron oxide cubes and clusters with a special focus on renal accumulation and excretion. Atomic emission spectroscopy, fluorescent microscopy and magnetic resonance imaging revealed rapid and transient accumulation of magnetic NP in kidney. Using intravital microscopy we tracked in real time NP translocation from peritubular capillaries to basal compartment of tubular cells and subsequent excretion to the lumen within 60 min after systemic administration. Transmission electron microscopy revealed persistence of intact full-sized NP in urine 2 h post injection. The results suggest that translocation through peritubular endothelium to tubular epithelial cells is an alternative mechanism of renal clearance enabling excretion of NP above glomerular cut-off size.

Recently neutrophil-based nanoparticles (NP) drug delivery systems have gained considerable attention in cancer therapy. Numerous studies have been conducted to identify optimal NP parameters for passive tumor targeting, while there is a fundamental dearth of knowledge about the factors governing cell-mediated delivery. Here, using intravital microscopy and magnetic resonance imaging we describe accumulation dynamics of 140 nm magnetic cubes and clusters in murine breast cancer (4T1) and colon cancer (CT26) models. Notwithstanding rapid clearance from the blood flow, NP readily accumulated in tumors at later time points. Both NP types were captured mostly by intravascular neutrophils immediately after injection and transmigration of NP-bound neutrophils through the vessel wall was first shown in real-time. A dramatic drop in NP accumulation upon Ly6G and Gr1 depletion further confirmed neutrophils role as biocarrier for targeting tumors. Of note, for shorter circulating NP cell-dependent delivery route was more impactful, while the accumulation of longer circulating counterpart was less compromised by neutrophil depletion. Neutrophil-mediated transport was also shown to depend on tumor type being more efficient in neutrophil-rich tumors. Revealing NP characteristics and host factors influencing neutrophil-based tumor targeting will help to rationally design novel drug delivery systems for improved cancer treatment.

This work is dedicated to the synthesis and characterization of antibody labeled magnetic nanoparticles as promising tool for biomedical applications. Single core magnetic nanoparticles were synthesized by thermal decomposition technique, followed by surface modification with ligand based on polyethylene glycol derivative. Fluorochrome-labeled species-specific antibodies were covalently conjugated to MNPs through a polyethylene glycol linker. The immunofluorescent analysis showed the successful binding of anti-α-tubulin or anti-β-catenin antibodies conjugated MNPs to α-tubulin and β-catenin in 4T1 cells of mouse breast cancer.

In the process of physiological activity of the body, a wide range of toxic metabolites is formed, in particular, hydrogen peroxide, superoxide and hydroxyl radical, which have a destructive effect on cells and cell membranes. One of the natural body protection mechanisms is the enzyme catalase, which accelerates the decomposition of constantly formed hydrogen peroxide to the final products, while oxidizing low molecular alcohols and nitrites, involved in the process of cellular respiration and does not require energy for activation. Catalase activity in blood and tissues is a marker of metabolic disorders. Catalase is localized mainly in the peroxisomes and cytoplasm of the cell, saturates the erythrocytes, liver and kidneys. Catalase activity allows assessing the level of endotoxicosis in the body. In order to study the relationship of the distribution of catalase concentration in serum and rat tissues, the following tasks were solved: the concentration of catalase in serum and tissues of the liver, brain, heart, as well as in skeletal muscle tissues of rats was determined; the correlation of catalase concentration distribution in blood serum and tissues of rat was revealed. The paper presents the results of nonparametric correlation analysis to assess the relationship of catalase activity distribution in serum and tissues of small experimental animals.

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM−1·s−1) compared with magnetic nanoclusters (MNCl, 104 mM−1·s−1) and magnetic nanorods (MNRd, 51 mM−1·s−1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.

To improve the water solubility of the anticancer drug candidate LCTA-2034 (A1), we investigated the formation of complexes of this anthrax[2,3-b]furan congener with the solubilizing 2-hydroxypropyl derivative of β-cyclodextrin HP-βCD (Cavitron®). The interaction of A1 with HP-βCD resulted in the inclusion complex A1/HP-βCD in 1:1 stoichiometry. The A1/HP-βCD complex was used to develop a prototype of a lyophilised drug formulation with enhanced (> 10-fold) aqueous solubility than A1 and a long-term stability. The use of HP-βCD decreased the acute toxicity of A1 by > 30%. The A1/HP-βCD drug formulation as well as A1 in equal doses (5 × 30 mg/kg) to increase the lifespan by up to 140% for mice with i.p. transplanted P388 leukaemia. Furthermore, the A1/HP-βCD formulation demonstrated a significant and reliable antitumor efficacy in a Р388/ADR drug resistant leukaemia and B16/F10 melanoma, proving a perspective of investigations of toxicology, biodistribution and pharmacokinetics.