Cytotoxicity control of silicon nanoparticles by biopolymer coating and ultrasound irradiation for cancer theranostic applications.

Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed the lower cytotoxicity of the dextran-coated NPs in comparison with uncoated ones, especially for high concentrations of about 2 mg ml-1. Efficient uptake of the NPs by cancer cells was found using bioimaging in the optical transmittance and photoluminescence modes. Treatment of the cells with uptaken SiNPs by therapeutic ultrasound for 5-20 min resulted in a strong decrease in the number of living cells, while the total number of cells remained nearly unchanged. The obtained data indicate a 'mild' effect of the combined action of ultrasonic irradiation and SiNPs on cancer cells. The observed results reveal new opportunities for controlling the photoluminescent and sonosensitizing properties of silicon-based NPs for applications in the diagnostics and mild therapy of cancer.

Silicon Nanoparticles as Amplifiers of the Ultrasonic Effect in Sonodynamic Therapy.

The possibility of using mesoporous silicon nanoparticles as amplifiers (sensitizers) of therapeutic ultrasonic exposure were studied experimentally in vitro and in vivo. The combination of nanoparticles and ultrasound led to a significant inhibition of Hep-2 cancer cell proliferation and Lewis lung carcinoma growth in mice. These results indicated good prospects of using silicon nanoparticles as sensitizers for sonodynamic therapy of tumors.

[EFFECT OF PULSE-PERIODIC CORONA DISCHARGE ON VIABILITY OF ESCHERICHIA COLI M17 CELLS IN BIOFILMS].

AIM: Detection of bactericidal effect of pulse-periodic corona discharge (PPCD) on cells and biofilms of Escherichia coli M17. MATERIALS AND METHODS: A gas-discharge device was created based on PPCD in air with power supply parameters: amplitude values of voltage of 30 - 60 kV, pulse repetition rate of 250 - 400 kHz. Ultrastructure changes in cells and biofilms of E. coli M17, affected by PPCD, generated in air, were studied by typical methods of transmission electron microscopy. RESULTS: Disturbances of integrity of surface and abyssal structures of biofilms, as well as changes of morphological properties of E. coli M17 cells, characteristic for sub-lethal heat impact, were detected. Destructive changes of bacterial cells were developed by formation of focal disturbance of cytoplasmic membrane, extension of periplasmic space, formation of globular structures, characteristic for heat effect, and destruction of cytoplasm. CONCLUSION: Bactericidal effect of PPCD on E. coli M17 cells as part of biofilms was shown. Destructive morphological changes in cells and biofilms of E. coli M17 after the effect of PPCD were detected for the first time on electron-microscopic level.

A new reliable reference gene UBA52 for quantitative real-time polymerase chain reaction studies in pyloric cecal tissues of the starfish Asterias rubens.

The starfish Asterias rubens is one of the most abundant echinoderm species in the White, Barents, North, and Baltic Seas. This species is an important component of marine ecosystems and a model object for certain biological studies, in particular those requiring quantitative estimation of gene expression. As a rule, expression at the transcriptional level is estimated by real-time qPCR using the ΔΔCt method, which allows the comparison of the copy number of target gene transcripts in samples with unknown mRNA/cDNA concentration. Application of this method requires normalization of the results relative to genes with stable expression levels (reference genes). The identification of reference genes is still a challenging task since data of this kind are missing for certain taxa, whereas the use of "standard" endogenous control genes without additional tests might lead to erroneous conclusions. We performed a preliminary analysis of the expression of many housekeeping genes in the pyloric ceca of A. rubens by high-throughput sequencing under normal and heat shock conditions. For one of them, the ubiquitin gene UBA52, low variation of expression (not greater than 2-fold) was shown using real-time qPCR. Tissues of pyloric ceca of normal adults and underyearlings and of adults after heat shock were used. The data obtained suggest that the UBA52 gene may be used as reference for normalization of gene expression at the mRNA level in the starfish A. rubens and probably in closely related species.

Angiotensin receptor-neprilysin inhibitors and cardiac remodeling.

The aim of this study was to determine how sacubitril/valsartan compared with valsartan in an outpatient setting affects left ventricular remodeling in heart failure with reduced ejection fraction and functional (or secondary) mitral regurgitation (SMR) due to the effect of dual inhibition of the renin-angiotensin system and neprilysin. The outpatient study included 90 patients with chronic SMR who were followed up for 12 months. They received sacubitril/valsartan or valsartan instead of the more commonly used angiotensin-converting enzyme inhibitor enalapril for heart failure, in addition to standard medical therapy for heart failure. The difference in NT-proBNP change between groups was the primary endpoint. Changes in effective regurgitation orifice area, left ventricular ejection fraction, left ventricular end-systolic and end-diastolic volume indices, left atrial volume index, E/e' index, and exercise tolerance on the 6-minute walk test were secondary endpoints. In the treatment efficacy analysis, NT-proBNP levels decreased significantly by 37% in the sacubitril/valsartan group and by 11% in the valsartan group (P<0.001). Ejection fraction and exercise tolerance (increase in walking distance in the 6-min test) increased in the sacubitril/valsartan group (P<0.05). Also, in this group, the effective area of the regurgitation orifice, the left atrial volume index, the E/e' index, and the indices of the end-systolic and end-diastolic volume of the left ventricle (P<0.05) decreased more pronouncedly. Compared with valsartan, treatment with sacubitril/valsartan led to a significant improvement in cardiac remodeling in patients with SMR and heart failure with reduced ejection fraction.

Fundamental nonambipolarity of electron fluxes in 2D plasmas.

It is demonstrated that in two-dimensional plasmas there is in general a vortex component of the electron motion, which means that electron and ion fluxes do not satisfy the ambipolarity condition.

Effects of nanostructurized silicon on proliferation of stem and cancer cell.

In vitro experiments showed that stem and cancer cells retained their viability on the surface of porous silicon with 10-100 nm nanostructures, but their proliferation was inhibited. Silicon nanoparticles of 100 nm in size obtained by mechanical grinding of porous silicon films or crystal silicon plates in a concentration below 1 mg/ml in solution did not modify viability and proliferation of mouse fibroblast and human laryngeal cancer cells. Additional ultrasonic exposure of cancer cells in the presence of 1 mg/ml silicon nanoparticles added to nutrient medium led to complete destruction of cells or to the appearance of membrane defects blocking their proliferation and initiating their apoptotic death.

Formation of inverse electron distribution function and absolute negative conductivity in nonlocal plasma of a dc glow discharge.

The inversion of the electron energy distribution function (EEDF) at low energies and the absolute negative electron conductivity are predicted and confirmed by numerical modeling of a direct current glow discharge in argon. It is shown that, in contrast to the local approximation used earlier for searching the inverse EEDF, in a real gas-discharge plasma, the formation of the EEDF is significantly affected by the terms with spatial gradients in the Boltzmann kinetic equation. In analogy with the inverse population of excited states in lasers, such a medium will amplify electromagnetic waves.

Publisher Correction: Ambipolar field role in formation of electron distribution function in gas discharge plasma.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Angiotensin receptor-neprilysin inhibitors and cardiac remodeling

The aim of this study was to determine how sacubitril/valsartan compared with valsartan in an outpatient setting affects left ventricular remodeling in heart failure with reduced ejection fraction and functional (or secondary) mitral regurgitation (SMR) due to the effect of dual inhibition of the renin-angiotensin system and neprilysin. The outpatient study included 90 patients with chronic SMR who were followed up for 12 months. They received sacubitril/valsartan or valsartan instead of the more commonly used angiotensin-converting enzyme inhibitor enalapril for heart failure, in addition to standard medical therapy for heart failure. The difference in NT-proBNP change between groups was the primary endpoint. Changes in effective regurgitation orifice area, left ventricular ejection fraction, left ventricular end-systolic and end-diastolic volume indices, left atrial volume index, E/e' index, and exercise tolerance on the 6-minute walk test were secondary endpoints. In the treatment efficacy analysis, NT-proBNP levels decreased significantly by 37% in the sacubitril/valsartan group and by 11% in the valsartan group (P<0.001). Ejection fraction and exercise tolerance (increase in walking distance in the 6-min test) increased in the sacubitril/valsartan group (P<0.05). Also, in this group, the effective area of the regurgitation orifice, the left atrial volume index, the E/e' index, and the indices of the end-systolic and end-diastolic volume of the left ventricle (P<0.05) decreased more pronouncedly. Compared with valsartan, treatment with sacubitril/valsartan led to a significant improvement in cardiac remodeling in patients with SMR and heart failure with reduced ejection fraction.

Ambipolar field role in formation of electron distribution function in gas discharge plasma.

It is shown that the local approximation for electron distribution function (EDF) determination at plasma periphery, where the ambipolar field is dominant, is not applicable even at high pressures when the characteristic plasma size exceeds the energy relaxation length of the electrons R > λ ε . Therefore, consistent results can be obtained only when solving the complete kinetic equation in both energy and spatial variables (i.e. it is necessary to solve nonlocal kinetic equation).

Laser-synthesized oxide-passivated bright Si quantum dots for bioimaging.

Crystalline silicon (Si) nanoparticles present an extremely promising object for bioimaging based on photoluminescence (PL) in the visible and near-infrared spectral regions, but their efficient PL emission in aqueous suspension is typically observed after wet chemistry procedures leading to residual toxicity issues. Here, we introduce ultrapure laser-synthesized Si-based quantum dots (QDs), which are water-dispersible and exhibit bright exciton PL in the window of relative tissue transparency near 800 nm. Based on the laser ablation of crystalline Si targets in gaseous helium, followed by ultrasound-assisted dispersion of the deposited films in physiological saline, the proposed method avoids any toxic by-products during the synthesis. We demonstrate efficient contrast of the Si QDs in living cells by following the exciton PL. We also show that the prepared QDs do not provoke any cytoxicity effects while penetrating into the cells and efficiently accumulating near the cell membrane and in the cytoplasm. Combined with the possibility of enabling parallel therapeutic channels, ultrapure laser-synthesized Si nanostructures present unique object for cancer theranostic applications.

Modification of a nonlocal electron energy distribution in a bounded plasma.

It is demonstrated experimentally, in a pulsed discharge, that it is possible to modify the "tail" of a nonlocal electron energy distribution (EED) without significantly changing the electron density and temperature (mean energy). The EED tail is modified by changing the potential of a small portion of the plasma boundary and/or by changing the volume creation rate of electrons with energies in the range of the tail of the EED. The discussed effects are a direct result of the nonlocal nature of the EED and have applications to a number of basic research issues associated with discharges under nonequilibrium conditions. As an example, we discuss the possibility of utilizing these methods to measure electron impact excitation cross sections from the metastable states of atoms, which are difficult to measure by other means. The experiments have been conducted in an argon and argon-nitrogen pulsed rf inductively coupled plasma discharge.

The effect of melittin on proliferation and death of thymocytes.

The effect of melittin, an activator of phospholipase A2, on proliferation and death of rat thymocytes in a broad concentration range was studied. Cell proliferation was estimated by the accumulation of colchicin metaphases, necrotic death was determined from lysis and staining of cells with trypan blue, and apoptosis was assessed from the type of DNA fragmentation, the amount of fragmented DNA, and the percentage of cells with subdiploid DNA. It was shown that low melittin concentrations (below 5 microg/ml) stimulate thymocyte proliferation. At high melittin concentrations, thymocytes die by the primary necrosis type. Throughout the concentration range studied, melittin does not produce apoptosis in thymocytes. Conversely, high melittin concentrations even inhibit thymocyte apoptosis in the control and after irradiation. An inhibitor of RNA synthesis actinomycin D does not affect thymocyte death in the presence of melittin. It is concluded that the activation of phospholipase A2 can induce necrosis but not apoptosis and thus is not a necessary step in the signaling cascade that initiates apoptosis in thymocytes.

The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor cells.

The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor P-388 cells in a broad concentration range was studied. Cell proliferation was estimated by the metaphase frequency and the proportion of cells in S phase; cell death was determined from lysis, staining of cells with trypan blue, nuclear damage, percentage of cells with subdiploid DNA and the type of DNA fragmentation. It was shown that low concentrations of phospholipase A2 and lipoxygenase inhibitors stimulated the proliferation of P-388 cells. At higher concentrations, the inhibitors suppressed cell proliferation by blocking the G1-S transition and induced cell death of the apoptosis type. Indomethacin, an inhibitor of cyclooxygenase, did not initiate cell death, nor did it affect the proliferation of P-388 cells at concentrations of up to 10 microM.

Electron-distribution-function cutoff mechanism in a low-pressure afterglow plasma.

A model is developed for self-consistent simulations of transient phenomena in a low-pressure afterglow plasma. The model is based on the nonlocal approach which allows a kinetic description of the plasma decay under nonquasistationary conditions. Such conditions arise when collisions (mainly electron-electron) are not sufficient for the electron distribution function (EDF) to follow changes in the self-consistent electric fields and the ion density once the power is turned off. As a result, collisions cannot provide the electron and ion particle balance by allowing electrons to flow out of the potential well. A cutoff mechanism is suggested that provides such a balance during the transient period--from the glow, stationary plasma to the quasistationary, afterglow plasma. This mechanism is essential for determining correctly the self-consistent wall potential (and hence the energy of ions impinging upon the wall surface) and other parameters, such as diffusion cooling, which is the most important cooling mechanism at low pressures. These phenomena are modeled using the time-dependent nonlocal electron Boltzmann equation with a nonlinear electron-electron collision operator. A numerical treatment is made by extending Rockwood's method for finite-difference discretization of this operator in the total energy formulation. The model calculates self-consistently the temporal evolution of the nonlocal EDF and the electric potentials in the plasma and the wall sheath. Strongly non-Maxwellian EDF's are predicted and it is observed that, depending on plasma conditions, the transient period maybe rather long, of order of the ambipolar diffusion time, lower pressures resulting in longer transient times. The proposed approach can be applied to model self-consistently pulsed plasmas during both the power-on and power-off periods, including the breakdown period.

Paradoxical nonmonotonic behavior of excitation-rate spatial profiles in bounded plasmas.

Paradoxical nonmonotonic behavior of spatial profiles of excitation rates in bounded plasmas have been analyzed. It is shown that the effect is related to the nonlocal character of the electron distribution function.

Anomalously high near-wall sheath potential drop in a plasma with nonlocal fast electrons.

It is demonstrated for the first time that the presence of a small number of fast, nonlocal electrons can dramatically change the thickness of and electric field in the near-wall sheath. Even if the density of the nonlocal fast group, , is much less than the density of the bulk electrons, n(b) (n(f) approximately 10(-5) n(b)), the near-wall potential can increase dramatically resulting in a comparable increase in the sheath thickness. Because of this low fractional density, the average energy (electron temperature ) of all electrons is little changed from that of the bulk, yet the near-wall potential drop can increase to tens of T(e)/e. More importantly, due to the nonlocal nature of this group of electrons, the near-wall sheath potential is found to be independent of and is determined only by the energy of the fast group.