CuO Nanoparticles Reduce Toxicity and Enhance Bioaccumulation of Cadmium and Lead in the Cells of the Microalgae Desmodesmus communis.

The removal of pollutants, including heavy metals, from the aquatic environment is an urgent problem worldwide. Actively developing nanotechnology areas is becoming increasingly important for solving problems in the field of the remediation of aquatic ecosystems. In particular, methods for removing pollutants using nanoparticles (NPs) are proposed, which raises the question of the effect of a combination of NPs and heavy metals on living organisms. In this work, we investigated the role of CuO-NPs in changing the toxicity of Cd and Pb salts, as well as the bioaccumulation of these elements in a culture of the microalga Desmodesmus communis. It was found that CuO-NPs at concentrations of 10, 100, and 1000 µg L-1 had no effect on the viability of microalgae cells. On the 14th day of the experiment, Cd at a concentration of 1 mg L-1 reduced the viability index by 30% and, when combined with CuO-NPs, by 25%, i.e., CuO-NPs slightly reduced the toxic effect of Cd. At the same time, in this experiment, when CuO-NPs and Cd were used together, the level of oxidative stress increased, including on the first day in mixtures with 1 mg L-1 Cd. Under the influence of Pb, the cell viability index decreased by 70% by the end of the experiment, regardless of the metal concentration. The presence of CuO-NPs slightly reduced the toxicity of Pb in terms of viability and reactive oxygen species (ROS). At the same time, unlike Cd, Pb without NPs caused ROS production on the first day, whereas the addition of CuO-NPs completely detoxified Pb at the beginning and had a dose-dependent effect on mixtures at the end of the experiment. Also, the introduction of CuO-NPs slightly reduced the negative effect of Pb on pigment synthesis. As a molecular mechanism of the observed effects, we prioritized the provocation of oxidative stress by nanoparticles and related gene expression and biochemical reactions of algae cells. Analysis of the effect of CuO-NPs on the Cd and Pb content in microalgae cells showed increased accumulation of heavy metals. Thus, when algae were cultured in an environment with Cd and CuO-NPs, the Cd content per cell increased 4.2 times compared to the variant where cells were cultured only with Cd. In the case of Pb, the increase in its content per one cell increased 6.2 times when microalgae were cultured in an environment containing CuO-NPs. Thus, we found that CuO-NPs reduce the toxic effects of Cd and Pb, as well as significantly enhance the bioaccumulation of these toxic elements in the cells of D. communis microalgae. The results obtained can form the basis of technology for the nanobioremediation of aquatic ecosystems from heavy metals using microalgae.

The Conditions Matter: The Toxicity of Titanium Trisulfide Nanoribbons to Bacteria E. coli Changes Dramatically Depending on the Chemical Environment and the Storage Time.

In this work, we present an analysis of the antibacterial activity of TiS3 nanostructures in water and 0.9% NaCl solution suspensions. TiS3 nanoribbons 1-10 µm long, 100-300 nm wide, and less than 100 nm thick were produced by the direct reaction of pure titanium powder with elemental sulphur in a quartz tube sealed under vacuum. For the toxicity test of a bioluminescent strain of E. coli we used concentrations from 1 to 0.0001 g L-1 and also studied fresh suspensions and suspensions left for 24 h. The strongest toxic effect was observed in freshly prepared water solutions where the luminescence of bacteria decreased by more than 75%. When saline solution was substituted for water or when the solutions were stored for 24 h it resulted in a considerable decrease in the TiS3 antibacterial effect. The toxicity of TiS3 in water exceeded the toxicity of the reference TiO2 nanoparticles, though when saline solution was used instead of water the opposite results were observed. In addition, we did not find a relationship between the antibacterial activity of water suspensions of nanoribbons and the stability of their colloidal systems, which indicates an insignificant contribution to the toxicity of aggregation processes. In 0.9% NaCl solution suspensions, toxicity increased in proportion to the increase in the zeta potential. We suppose that the noted specificity of toxicity is associated with the emission of hydrogen sulphide molecules from the surface of nanoribbons, which, depending on the concentration, can either decrease or increase oxidative stress, which is considered the key mechanism of nanomaterial cytotoxicity. However, the exact underlying mechanisms need further investigation. Thus, we have shown an important role of the dispersion medium and the period of storage in the antibacterial activity of TiS3 nanoribbons. Our results could be used in nanotoxicological studies of other two-dimensional nanomaterials, and for the development of novel antibacterial substances and other biomedical applications of this two-dimensional material.

Assessment of the Tolerance of a Chlorophyte Desmodesmus to CuO-NP for Evaluation of the Nanopollution Bioremediation Potential of This Microalga.

Broad application of CuO nanoparticles (CuO-NP) for industrial and household purposes leads to a continuous increase in their discharge to, and, hence, ever-increasing environmental hazards for aquatic ecosystems. Microalgae-based technologies hold promise for bioremediation of diverse hazardous micropollutants (HMP), including NP, from wastewater. In this study, we tested the ability of the green microalga Desmodesmus sp. to accumulate CuO-NP or their components. We also assessed the tolerance of this microalga to the environmentally relevant concentrations of CuO-NP. Using scanning electron microscopy, we demonstrated that the average size of CuO-NP was 50-100 nm, and their purity was confirmed with elemental composition analysis. Tests of the colloidal suspensions of CuO-NP showed that the hydrodynamic diameter of CuO-NP and their aggregates was below 100 nm. Flow cytometry analysis showed that CuO-NP at a concentration of 100 µg L-1 slightly inhibited the viability of microalgae cells and led to an increase in their oxidative stress. The assessment of the condition of photosystem II showed that CuO-NP exert a multifaceted effect on the photosynthetic apparatus of Desmodesmus sp., depending on the concentration of and the exposure to the CuO-NP. Desmodesmus sp. turned to be relatively tolerant to CuO-NP. In addition, the ICP-MS method revealed increased bioaccumulation of copper by microalgae cells in the experimental groups. The outcomes of this study indicate that the Desmodesmus sp. has a significant potential for bioremoval of the copper-based nanostructured HMP from an aquatic environment.

Graphene Oxide Nanosurface Reduces Apoptotic Death of HCT116 Colon Carcinoma Cells Induced by Zirconium Trisulfide Nanoribbons.

Due to their chemical, mechanical, and optical properties, 2D ultrathin nanomaterials have significant potential in biomedicine. However, the cytotoxicity of such materials, including their mutual increase or decrease, is still not well understood. We studied the effects that graphene oxide (GO) nanolayers (with dimensions 0.1-3 µm and average individual flake thickness less than 1 nm) and ZrS3 nanoribbons (length more than 10 µm, width 0.4-3 µm, and thickness 50-120 nm) have on the viability, cell cycle, and cell death of HCT116 colon carcinoma cells. We found that ZrS3 exhibited strong cytotoxicity by causing apoptotic cell death, which was in contrast to GO. When adding GO to ZrS3, ZrS3 was significantly less toxic, which may be because GO inhibits the effects of cytotoxic hydrogen sulfide produced by ZrS3. Thus, using zirconium trisulfide nanoribbons as an example, we have demonstrated the ability of graphene oxide to reduce the cytotoxicity of another nanomaterial, which may be of practical importance in biomedicine, including the development of biocompatible nanocoatings for scaffolds, theranostic nanostructures, and others.

Synthesis, Toxicity Assessment, Environmental and Biomedical Applications of MXenes: A Review.

MXenes are a family of two-dimensional (2D) composite materials based on transition metal carbides, nitrides and carbonitrides that have been attracting attention since 2011. Combination of electrical and mechanical properties with hydrophilicity makes them promising materials for biomedical applications. This review briefly discusses methods for the synthesis of MXenes, their potential applications in medicine, ranging from sensors and antibacterial agents to targeted drug delivery, cancer photo/chemotherapy, tissue engineering, bioimaging, and environmental applications such as sensors and adsorbents. We focus on in vitro and in vivo toxicity and possible mechanisms. We discuss the toxicity analogies of MXenes and other 2D materials such as graphene, mentioning the greater biocompatibility of MXenes. We identify existing barriers that hinder the formation of objective knowledge about the toxicity of MXenes. The most important of these barriers are the differences in the methods of synthesis of MXenes, their composition and structure, including the level of oxidation, the number of layers and flake size; functionalization, test concentrations, duration of exposure, and individual characteristics of biological test objects Finally, we discuss key areas for further research that need to involve new methods of nanotoxicology, including predictive computational methods. Such studies will bring closer the prospect of widespread industrial production and safe use of MXene-based products.

Influence of Copper Oxide Nanoparticles on Gene Expression of Birch Clones In Vitro under Stress Caused by Phytopathogens.

Recently, metal oxide nanoparticles (NPs) have attracted attention as promising components for the protection and stimulation of plant microclones in tissue culture in vitro. However, the effect of NPs on the genetic mechanisms underlying plant adaptive responses remains poorly understood. We studied the effect of column-shaped CuO NPs 50 nm in diameter and 70-100 nm in length at a concentration of 0.1-10 mg/L on the development of phytopathogenic fungi Alternaria alternata, Fusarium oxysporum, and Fusarium avenaceum in culture, as well as on the infection of downy birch micro-clones with phytopathogens and the level of genes expression associated with the formation of plant responses to stress induced by microorganisms. CuO NPs effectively suppressed the development of colonies of phytopathogenic fungi A. alternata and F. avenaceum (up to 68.42% inhibition at 10 mg/L CuO NPs) but not the development of a colony of F. oxysporum. Exposure to the NPs caused multidirectional responses at the level of plant genes transcription: 5 mg/L CuO NPs significantly increased the expression level of the LEA8 and MYB46 genes and decreased the expression of DREB2 and PAL. Infection with A. alternata significantly increased the level of MYB46, LEA8, PAL, PR-1, and PR-10 transcripts in birch micro-clones; however, upon exposure to a medium with NPs and simultaneous exposure to a phytopathogen, the expression of the MYB46, PR-1, and PR-10 genes decreased by 5.4 times, which is associated with a decrease in the pathogenic load caused by the effect of NPs and the simultaneous stimulation of clones in vitro. The results obtained can be used in the development of preparations based on copper oxide NPs for disinfection and stimulation of plant phytoimmunity during clonal micropropagation of tree crops.

Relationship between Thermal Diffusivity and Mechanical Properties of Wood.

This paper describes an experimental study of the relationships between thermal diffusivity and mechanical characteristics including Brinell hardness, microhardness, and Young's modulus of common pine (Pinus sylvestris L.), pedunculate oak (Quercus robur L.), and small-leaf lime (Tilia cordata Mill.) wood. A dependence of Brinell hardness and thermal diffusivity tensor components upon humidity for common pine wood is found. The results of the measurement of Brinell hardness, microhardness, Young's modulus, and main components of thermal diffusivity tensor for three perpendicular cuts are found to be correlated. It is shown that the mechanical properties correlate better with the ratio of longitude to transversal thermal diffusivity coefficients than with the respective individual absolute values. The mechanical characteristics with the highest correlation with the abovementioned ratio are found to be the ratio of Young's moduli in longitude and transversal directions. Our technique allows a comparative express assessment of wood mechanical properties by means of a contactless non-destructive measurement of its thermal properties using dynamic thermal imaging instead of laborious and material-consuming destructive mechanical tests.

Graphene Nanoribbons: Prospects of Application in Biomedicine and Toxicity.

Graphene nanoribbons are a type of graphene characterized by remarkable electrical and mechanical properties. This review considers the prospects for the application of graphene ribbons in biomedicine, taking into account safety aspects. According to the analysis of the recent studies, the topical areas of using graphene nanoribbons include mechanical, chemical, photo- and acoustic sensors, devices for the direct sequencing of biological macromolecules, including DNA, gene and drug delivery vehicles, and tissue engineering. There is evidence of good biocompatibility of graphene nanoribbons with human cell lines, but a number of researchers have revealed toxic effects, including cytotoxicity and genotoxicity. Moreover, the damaging effects of nanoribbons are often higher than those of chemical analogs, for instance, graphene oxide nanoplates. The possible mechanism of toxicity is the ability of graphene nanoribbons to damage the cell membrane mechanically, stimulate reactive oxidative stress (ROS) production, autophagy, and inhibition of proliferation, as well as apoptosis induction, DNA fragmentation, and the formation of chromosomal aberrations. At the same time, the biodegradability of graphene nanoribbons under the environmental factors has been proven. In general, this review allows us to conclude that graphene nanoribbons, as components of high-precision nanodevices and therapeutic agents, have significant potential for biomedical applications; however, additional studies of their safety are needed. Particular emphasis should be placed on the lack of information about the effect of graphene nanoribbons on the organism as a whole obtained from in vivo experiments, as well as about their ecological toxicity, accumulation, migration, and destruction within ecosystems.

In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration.

Silver nanoparticles (AgNPs) are the most widely studied antimicrobial nanomaterials. However, their use in biomedicine is currently limited due to the availability of data that prove the nanosilver toxicity associated primarily with oxidative stress development in mammalian cells. The surface modification of AgNPs is a potent technique of improvement of their biocompatibility. The synthetic or natural compounds that combine zero or low toxicity towards human and animal organisms with inherent antimicrobial properties are the most promising stabilizing agents, their use would also minimize the risks of microorganisms developing resistance to silver-based materials. We used a simple technique to obtain 30-60 nm AgNPs stabilized with benzyldimethyl[3-myristoylamine)-propyl]ammonium chloride monohydrate (BAC)-a well-known active ingredient of many antibacterial drugs. The objective of the study was to assess the AgNPs-BAC entero- and hepatotoxicity to CBF1 mice upon enteral administration. The animals were exposed to 0.8-7.5 mg/kg doses of AgNPs-BAC in the acute and to 0.05-2.25 mg/kg doses of AgNPs-BAC in the subacute experiments. No significant entero- and hepatotoxic effects following a single exposure to doses smaller than 4 mg/kg were detected. Repeated exposure to the doses of AgNPs-BAC below 0.45 mg/kg and to the doses of BAC below 0.5 mg/kg upon enteral administration also led to no adverse effects. During the acute experiment, the higher AgNPs-BAC dose resulted in increased quantities of aminotransferases and urea, as well as the albumin-globulin ratio shift, which are indicative of inflammatory processes. Besides, the relative mass of the liver of mice was smaller compared to the control. During the subacute experiment, the groups treated with the 0.25-2.25 mg/kg dose of AgNPs-BAC had a lower weight gain rate compared to the control, while the groups treated with the 2.25 mg/kg dose of AgNPs-BAC showed statistically significant variations in the blood serum transaminases activity, which indicated hepatosis. It should be noted that the spleen and liver of the animals from the groups treated with the 0.45 and 2.25 mg/kg dose of AgNPs-BAC were more than two times smaller compared to the control. In the intestines of some animals from the group treated with the 2.25 mg/kg dose of AgNPs-BAC small areas of hyperemia and enlarged Peyer's patches were observed. Histological examination confirmed the initial stages of the liver and intestinal wall inflammation.

Nanotoxicity of ZrS3 Probed in a Bioluminescence Test on E. coli Bacteria: The Effect of Evolving H2S.

Materials from a large family of transition metal trichalcogenides (TMTCs) attract considerable attention because of their potential applications in electronics, optoelectronics and energy storage, but information on their toxicity is lacking. In this study, we investigated the toxicity of ZrS3, a prominent TMTC material, toward photoluminescent E. coli bacteria in a bioluminescence test. We found that freshly prepared ZrS3 suspensions in physiological saline solution with concentrations as high as 1 g/L did not exhibit any toxic effects on the bacteria. However, ZrS3 suspensions that were stored for 24 h prior to the bioluminescence tests were very toxic to the bacteria and inhibited their emission, even at concentrations down to 0.001 g/L. We explain these observations by the aqueous hydrolysis of ZrS3, which resulted in the formation of ZrOx on the surface of ZrS3 particles and the release of toxic H2S. The formation of ZrOx was confirmed by the XPS analysis, while the characteristic H2S smell was noticeable for the 24 h suspensions. This study demonstrates that while ZrS3 appears to be intrinsically nontoxic to photoluminescent E. coli bacteria, it may exhibit high toxicity in aqueous media. The results of this study can likely be extended to other transition metal chalcogenides, as their toxicity in aqueous solutions may also increase over time due to hydrolysis and the formation of H2S. The results of this study also demonstrate that since many systems involving nanomaterials are unstable and evolve over time in various ways, their toxicity may evolve as well, which should be considered for relevant toxicity tests.

Versatile synthesis of PHMB-stabilized silver nanoparticles and their significant stimulating effect on fodder beet (Beta vulgaris L.).

Silver nanoparticles (AgNPs) are well-known bactericidal agents. However, information about the influence of AgNPs on the morphometric parameters and biochemical status of most important agricultural crops is limited. The present study reports the influence of AgNPs stabilized with cationic polymer polyhexamethylene biguanide hydrochloride (PHMB) on growth, development, and biochemical status of fodder beet Beta vulgaris L. under laboratory and greenhouse conditions. PHMB-stabilized AgNPs were obtained via sodium borohydride reduction of silver nitrate in an aqueous solution. The average diameter of thus prepared AgNPs was 10 nm. It appears that the results of experiments with laboratory-grown beets in the nanosilver-containing medium, where germination of seeds and growth of roots were suppressed, do not correlate with the results of greenhouse experiments. The observed growth-stimulating action of PHMB-stabilized AgNPs can be explained by the change of activity of oxidases and, consequently, by the change of auxins amount in plant tissues. In beets grown in the presence of PHMB-stabilized AgNPs no negative deviations of biological parameters from normal values were registered. Furthermore, the SEM/EDS examination revealed no presence of silver in the tissues of the studied plants.

Considerable Variation of Antibacterial Activity of Cu Nanoparticles Suspensions Depending on the Storage Time, Dispersive Medium, and Particle Sizes.

Suspensions of Cu nanoparticles are promising for creating the new class of alternative antimicrobial products. In this study we examined copper nanoparticles of various sizes obtained by the method of wire electric explosion: nanopowder average size 50 nm (Cu 50) and 100 nm (Cu 100). The paper presents the complex study of the influence of physicochemical properties such as particle size and concentration of the freshly prepared and 24-hour suspensions of Cu nanoparticles in distilled water and physiological solution upon their toxicity to bacteria E. coli M-17. Ionic solution of Cu(2+) and sodium dichloroisocyanurate was used for comparison study. It has been shown that decrease in the nanoparticle size leads to changes in the correlation between toxicity and concentration as toxicity peaks are observed at low concentrations (0.0001⋯0.01 mg/L). It has been observed that antibacterial properties of Cu 50 nanoparticle suspensions are ceased after 24-hour storage, while for Cu 100 suspensions no correlation between antibacterial properties and storage time has been noted. Cu 100 nanoparticle suspensions at 10 mg/L concentration display higher toxicity at substituting physiological solution for water than Cu 50 suspensions. Dependence of the toxicity on the mean particle aggregates size in suspension was not revealed.

Effects of different trends on the development and outcome of early kidney allograft dysfunction.

OBJECTIVES: To show the effects of different factors on development and outcome of early kidney allograft dysfunction. MATERIALS AND METHODS: Two hundred thirty-one kidney transplant recipients were divided into 2 groups: group 1 (125 patients transplanted from 1999-2004) and group 2 (106 patients transplanted from 2008-2013). Age range was 12 to 62 years (group 1) and 7 to 71 years (group 2). Deceaseddonor transplant was more frequent in group 1 (76.8%), and living-donor transplant in group 2 (68.8%). In group 1, transplant was performed for glomerulonephritis or pyelonephritis; in group 2, additional risk factors (18 patients) included diabetes (11 patients), systemic lupus erythematosus (5 patients), amyloidosis (1 patient), and aortic and mitral valve replacement because of bacterial endocarditis (1 patient). In groups 1 and 2, immunosuppression after transplant included cyclosporine, mycophenolate mofetil, and steroids; patients in group 2 also had induction with anti-CD25 monoclonal antibodies. RESULTS: Primary graft function occurred in 89 patients in group 1 (71.2%) and 83 patients in group 2 (78.3%). Immediately after transplant, delayed graft function included anuria, oliguria, adequate amount of urine, and secondary delayed function (several days of polyuria followed by decreased urine output). Ischemia was a leading cause of delayed renal graft function. Anuria after living-donor transplant was a sign of vascular thrombosis. Rejection was the main cause of secondary delayed graft function, which occurred in only group 1. Survival at 1 year in patients with delayed graft function was 80% in group 1 and 100% in group 2 because of the absence of septic complications. CONCLUSIONS: Despite extension of indications, primary functioning of kidney transplants and patient survival increased. Improved care enables long-term rehabilitation of recipients and expanding criteria for kidney transplant.