Metabolite responses of cucumber on copper toxicity in presence of fullerene C60 derivatives.

Copper (Cu) toxicity in crops is a result of excessive release of Cu into environment. Little is known about mitigation of Cu toxicity through the application of carbon-based nanomaterials including water-soluble fullerene C60 derivatives. Two derivatives of fullerene were examined: polyhydroxylated C60 (fullerenol) and arginine C60 derivative. In order to study the response of Cu-stressed plants (Cucumis sativus L.) to these nanomaterials, metabolomics analysis by gas chromatography-mass spectrometry (GC-MS) was performed. Excess Cu (15 µM) caused substantial increase in xylem sap Cu, retarded dry biomass and leaf chlorosis of hydroponically grown cucumber. In Cu-stressed leaves, metabolomes was disturbed towards suppression metabolism of nitrogen (N) compounds and activation metabolism of hexoses. Also, upregulation of some metabolites involving in antioxidant defense system, such as ascorbic acid, tocopherol and ferulic acid, was occurred in Cu-stressed leaves. Hydroponically added fullerene adducts decreased the xylem sap Cu and alleviated Cu toxicity with effectiveness has been most pronounced for arginine C60 derivative. Metabolic responses of plants subjected to high Cu with fullerene derivatives were opposite to that observed under Cu alone. Fatty acids up-regulation (linolenic acid) and antioxidant molecules (tocopherol) down-regulation might indicate that arginine C60 adduct can alleviate Cu induced oxidative stress. Although fullerenol slightly improved cucumber growth, its effect on metabolic state of Cu-stressed plants was not statistically significant. We suggest that tested fullerene C60 adducts have a potential to prevent Cu toxicity in plants through a mechanism associated with their capability to restrict xylem transport of Cu from roots to shoot, and to maintain antioxidative properties of plants.

Pervaporation Membranes Based on Polyelectrolyte Complex of Sodium Alginate/Polyethyleneimine Modified with Graphene Oxide for Ethanol Dehydration.

Pervaporation is considered the most promising technology for dehydration of bioalcohols, attracting increasing attention as a renewable energy source. In this regard, the development of stable and effective membranes is required. In this study, highly efficient membranes for the enhanced pervaporation dehydration of ethanol were developed by modification of sodium alginate (SA) with a polyethylenimine (PEI) forming polyelectrolyte complex (PEC) and graphene oxide (GO). The effect of modifications with GO or/and PEI on the structure, physicochemical, and transport characteristics of dense membranes was studied. The formation of a PEC by ionic cross-linking and its interaction with GO led to changes in membrane structure, confirmed by spectroscopic and microscopic methods. The physicochemical properties of membranes were investigated by a thermogravimetric analysis, a differential scanning calorimetry, and measurements of contact angles. The theoretical consideration using computational methods showed favorable hydrogen bonding interactions between GO, PEI, and water, which caused improved membrane performance. To increase permeability, supported membranes without treatment and cross-linked were developed by the deposition of a thin dense layer from the optimal PEC/GO (2.5%) composite onto a developed porous substrate from polyacrylonitrile. The cross-linked supported membrane demonstrated more than two times increased permeation flux, higher selectivity (above 99.7 wt.% water in the permeate) and stability for separating diluted mixtures compared to the dense pristine SA membrane.

Development and Study of Novel Ultrafiltration Membranes Based on Cellulose Acetate.

Recently, increasing attention of researchers in the field of membrane technology has been paid to the development of membranes based on biopolymers. One of the well-proven polymers for the development of porous membranes is cellulose acetate (CA). This paper is devoted to the study of the influence of different parameters on ultrafiltration CA membrane formation and their transport properties, such as the variation in coagulation bath temperature, membrane shrinkage (post-treatment at 80 °C), introduction to casting CA solution of polymers (polyethylene glycol (PEG), polysulfone (PS), and Pluronic F127 (PL)) and carbon nanoparticles (SWCNTs, MWCNTs, GO, and C60). The structural and physicochemical properties of developed membranes were studied by scanning electron and atomic force microscopies, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and contact angle measurements. The transport properties of developed CA-based membranes were evaluated in ultrafiltration of bovine serum albumin (BSA), dextran 110 and PVP K-90. All developed membranes rejected 90% compounds with a molecular weight from ~270,000 g/mol. It was shown that the combination of modifications (addition of PEG, PS, PL, PS-PL, and 0.5 wt% C60) led to an increase in the fluxes and BSA rejection coefficients with slight decrease in the flux recovery ratio. These changes were due to an increased macrovoid number, formation of a more open porous structure and/or thinner top selective, and decreased surface roughness and hydrophobization during C60 modification of blend membranes. Optimal transport properties were found for CA-PEG+C60 (the highest water-394 L/(m2h) and BSA-212 L/(m2h) fluxes) and CA-PS+C60 (maximal rejection coefficient of BSA-59%) membranes.

Application of carbon nanostructures in biomedicine: realities, difficulties, prospects.

The review systematizes data on the wide possibilities of practical application of carbon nanostructures. Much attention is paid to the use of carbon nanomaterials in medicine for the visualization of tumors during surgical interventions, in the creation of cosmetics, as well as in agriculture in the creation of fertilizers. Additionally, we demonstrate trends in research in the field of carbon nanomaterials with a view to elaborating targeted drug delivery systems. We also show the creation of nanosized medicinal substances and diagnostic systems, and the production of new biomaterials. A separate section is devoted to the difficulties in studying carbon nanomaterials. The review is intended for a wide range of readers, as well as for experts in the field of nanotechnology and nanomedicine.

Protective role of fullerenol and arginine C60 fullerene against copper toxicity in cucumber.

Copper (Cu), when in excess, is one of the most toxic and hazardous metals to all living organisms, including plants. Engineered nanomaterials have the potential for increasing crop protection. However, the protective role of fullerenes (carbon-based nanoparticles with wide application in various areas) against Cu toxicity in plants is, so far, understudied. The present study investigated whether fullerenes can potentially alleviate Cu toxicity in plants (Cucumis sativus L.). Two water-soluble fullerene C60 derivatives were examined: fullerenol [C60(OH)22-24] and arginine-functionalized fullerene [C60(C6H13N4O2)8H8], under controlled conditions using hydroponics. Plants treated with 15 µM of Cu exhibited typical symptoms of Cu toxicity: impaired growth, leaf chlorosis, reduced photosynthetic activity, nutritional imbalances, and enhanced lipid peroxidation. These symptoms were alleviated in the presence of fullerene derivatives with arginine C60 having the more pronounced effect. Improved cucumber Cu tolerance was attributable to Cu buffering in the root zone (roots and medium), which caused a dramatic decline in Cu transport towards leaves and the elimination of oxidative damage. The Cu removal efficacy of arginine C60 was much greater than that of fullerenol. These fullerenes acted in a dose-dependent manner and removed Cu selectively without significant modification of the bioavailability of other essential nutrients. Treatment with free arginine did not affect Cu immobilization or Cu toxicity. These results suggest that the surface chemistry of the fullerene core is important for the protection of plants under excessive Cu conditions. The information offered a new approach to preparing promising practical materials for alleviating Cu toxicity in plants with potential application in fields.

C60 adduct with L-arginine as a promising nanomaterial for treating cerebral ischemic stroke.

The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C60-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C60-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C60-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes.

Modification Approaches of Polyphenylene Oxide Membranes to Enhance Nanofiltration Performance.

Presently, water pollution poses a serious threat to the environment; the removal of organic pollutants from resources, especially dyes, is very important. Nanofiltration (NF) is a promising membrane method to carry out this task. In the present work, advanced supported poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) membranes were developed for NF of anionic dyes using bulk (the introduction of graphene oxide (GO) into the polymer matrix) and surface (the deposition of polyelectrolyte (PEL) layers by layer-by-layer (LbL) technique) modifications. The effect of PEL combinations (polydiallyldimethylammonium chloride/polyacrylic acid (PAA), polyethyleneimine (PEI)/PAA, and polyallylamine hydrochloride/PAA) and the number of PEL bilayers deposited by LbL method on properties of PPO-based membranes were studied by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle measurements. Membranes were evaluated in NF of food dye solutions in ethanol (Sunset yellow (SY), Congo red (CR), and Alphazurine (AZ)). The supported PPO membrane, modified with 0.7 wt.% GO and three PEI/PAA bilayers, exhibited optimal transport characteristics: ethanol, SY, CR, and AZ solutions permeability of 0.58, 0.57, 0.50, and 0.44 kg/(m2h atm), respectively, with a high level of rejection coefficients-58% for SY, 63% for CR, and 58% for AZ. It was shown that the combined use of bulk and surface modifications significantly improved the characteristics of the PPO membrane in NF of dyes.

Covalent conjugates based on nanodiamonds with doxorubicin and a cytostatic drug from the group of 1,3,5-triazines: Synthesis, biocompatibility and biological activity.

We report the synthesis of covalent conjugates of nanodiamonds with doxorubicin and a cytostatic drug from the class of 1,3,5-triazines. The obtained conjugates were identified using a number of physicochemical methods (IR-spectroscopy, NMR-spectroscopy, XRD, XPS, TEM). As a result of our study, it was found that ND-СONH-Dox and ND-COO-Diox showed good hemocompatibility, since they did not affect plasma coagulation hemostasis, platelet functional activity, and erythrocyte membrane. The ND-COO-Diox conjugates are also capable of binding to human serum albumin due to the presence of ND in their composition. In the study of the cytotoxic properties of ND-СONH-Dox and ND-COO-Diox in the T98G glioblastoma cell line, indicating that ND-СONH-Dox and ND-COO-Diox demonstrate greater cytotoxicity at lower concentrations of Dox and Diox in the composition of the conjugates compared to individual drugs; the cytotoxic effect of ND-COO-Diox was statistically significantly higher than that of ND-СONH-Dox at all concentrations studied. Greater cytotoxicity at lower concentrations of Dox and Diox in the composition of conjugates compared to individual cytostatics makes it promising to further study the specific antitumor activity and acute toxicity of these conjugates in models of glioblastoma in vivo. Our results demonstrated that ND-СONH-Dox and ND-COO-Diox enter HeLa cells predominantly via a nonspecific actin-dependent mechanism, while for ND-СONH-Dox a clathrin-dependent endocytosis pathway. All data obtained provide that the synthesized nanomaterials show a potential application as the agents for intertumoral administration.

Uncertainty Estimation for Quantitative Agarose Gel Electrophoresis of Nucleic Acids.

This paper considers the evaluation of uncertainty of quantitative gel electrophoresis. To date, such uncertainty estimation presented in the literature are based on the multiple measurements performed for assessing the intra- and interlaboratory reproducibility using standard samples. This paper shows how to estimate the uncertainty in cases where we cannot study scattering components of the results. The first point is dedicated to a case where we have standard samples (the direct expressions are shown). The second point considers the situation when standard samples are absent (the algorithm for estimating the lower bound for uncertainty is discussed). The role of the data processing algorithm is demonstrated.

Pathogenetic role and clinical significance of interleukin-1ß in cancer.

In recent years, pro-oncogenic mechanisms of the tumour microenvironment (ТМЕ) have been actively discussed. One of the main cytokines of the TМЕ is interleukin-1 beta (IL-1ß), which exhibits proinflammatory properties. Some studies have shown an association between an increase in IL-1ß levels and tumour progression. The purpose of this review is to analyse the pathogenic mechanisms induced by IL-1ß in the TМЕ, as well as the diagnostic significance of the presence of IL-1ß in patients with cancer and the efficacy of treatment with IL-1ß inhibitors. According to the literature, IL-1ß can induce an increase in tumour angiogenesis due to its effects on the differentiation of epithelial cells, pro-angiogenic molecule secretion and expression of adhesion molecules, thus increasing tumour growth and metastasis. IL-1ß is also involved in the suppression of anti-tumour immune responses. The expression and secretion of IL-1ß has been noted in various types of tumours. In some clinical studies, an elevated level of IL-1ß was found to be associated with low efficacy of anti-cancer therapy and a poor prognosis. In most experimental and clinical studies, the use of IL-1ß inhibitors contributed to a decrease in tumour mass and an increase in the response to anti-tumour drugs.

Biocompatibility and biological activity of C70 fullerene adduct with L-threonine (C70(C4H9NO3)2).

The aim of this work is to synthesise and study the biocompatibility and biological activity of the C70 fullerene adduct with l-threonine (C70-Thr). The obtained adduct was identified using a complex of physicochemical methods, namely, 13C NMR spectroscopy, IR spectroscopy, thermogravimetric analysis, electron spectroscopy, elemental analysis, and high-performance liquid chromatography. The study of biocompatibility and biological activity of the C70-Thr adduct included the study of haemocompatibility (haemolysis, platelet aggregation, plasma coagulation haemostasis, binding to human serum albumin, esterase activity), antiradical activity, cytotoxicity, cell proliferation, and interaction with DNA (determination of the DNA binding constant and genotoxicity).

Study of biocompatibility, cytotoxic activity in vitro of a tetrazole-containing derivative of 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine.

The hydrolytic stability, hemocompatibility, antioxidant properties and in vitro cytotoxic activity of {5-[(4,6-di(aziridin-1-yl)-1,3,5-triazin-2-yl)amino]-2,2-dimethyl-1,3-dioxan-5-yl}methyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate have been studied. 1H NMR spectroscopy showed that this tetrazole-containing derivative of 1,3,5-triazine is stable in neutral (pH 7) and alkaline (pH 10) media; hydrolysis of the dioxane cycle occurs in an acidic environment (pH 3). It has been established that {5-[(4,6-di(aziridin-1-yl)-1,3,5-triazin-2-yl)amino]-2,2-dimethyl-1,3-dioxan-5-yl}methyl-2-(5-phenyl-2H-tetrazol-2-yl)acetate is hemocompatible, exhibits antioxidant properties, but does not show antiradical activity over the entire range of concentrations. In turn, the study of cytotoxic activity in vitro showed that the tetrazole-containing derivative of 1,3,5-triazine has an effect on the cell lines of human alveolar basal epithelium adenocarcinoma A549 (IC50 41.3 µmol l-1), human ovarian teratocarcinoma PA-1 (IC50 10.6 µmol l-1), hepatocarcinoma Huh7 (IC50 19.9 µmol l-1), cervical cancer HeLa (IC50 3.7 µmol l-1), and human embryonic kidney HEK293 (IC50 15.8 µmol l-1). It was suggested one of the possible mechanism of substance 2 cytotoxicity via HIF pathway inhibition.

Novel PDMS-b-PPO Membranes Modified with Graphene Oxide for Efficient Pervaporation Ethanol Dehydration.

Purification and concentration of bioalcohols is gaining new status due to their use as a promising alternative liquid biofuel. In this work, novel high-performance asymmetric membranes based on a block copolymer (BCP) synthesized from polydimethylsiloxane (PDMS) and poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) were developed for enhanced pervaporation dehydration of ethanol. Improvement in dehydration performance was achieved by obtaining BCP membranes with a "non-perforated" porous structure and through surface and bulk modifications with graphene oxide (GO). Formation of the BCP was confirmed by Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies. The changes to morphology and physicochemical properties of the developed BCP and BCP/GO membranes were studied by scanning electron (SEM) and atomic force (AFM) microscopies, thermogravimetric analysis (TGA) and contact angle measurements. Transport properties of the developed membranes were evaluated by the pervaporation dehydration of ethanol over a wide concentration range (4.4-70 wt.% water) at 22 °C. The BCP (PDMS:PPO:2,4-diisocyanatotoluene = 41:58:1 wt.% composition) membrane modified with 0.7 wt.% GO demonstrated optimal transport characteristics: 80-90 g/(m2h) permeation flux with high selectivity (76.8-98.8 wt.% water in the permeate, separation factor of 72-34) and pervaporation separation index (PSI) of 5.5-2.9.

Novel Mixed Matrix Membranes Based on Polyphenylene Oxide Modified with Graphene Oxide for Enhanced Pervaporation Dehydration of Ethylene Glycol.

Ethylene glycol (EG) is widely used in various economic and industrial fields. The demand for its efficient separation and recovery from water is constantly growing. To improve the pervaporation characteristics of a poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) membrane in dehydration of ethylene glycol, the modification with graphene oxide (GO) nanoparticles was used. The effects of the introduction of various GO quantities into the PPO matrix on the structure and physicochemical properties were studied by Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, scanning electron (SEM) and atomic force (AFM) microscopies, thermogravimetric analysis (TGA), swelling experiments, and contact angle measurements. Two types of membranes based on PPO and PPO/GO composite were developed: dense membranes and supported membranes on a fluoroplast substrate (MFFC). Transport properties of the developed membranes were evaluated in the pervaporation dehydration of EG in a wide concentration range (10-90 wt.% and 10-30 wt.% water for the dense and supported membranes, respectively). The supported PPO/GO(0.7%)/MFFC membrane demonstrated the best transport properties in pervaporation dehydration of EG (10-30 wt.% water) at 22 °C: permeation flux ca. 15 times higher compared to dense PPO membrane-180-230 g/(m2·h)), 99.8-99.6 wt.% water in the permeate. The membrane is suitable for the promising industrial application.

A novel method for multiplex protein biomarker analysis of human serum using quantitative MALDI mass spectrometry.

In this work, we have extended our previously proposed approach for determining protein concentrations in human serum (using MALDI-TOF mass spectrometry) to include simultaneous analysis of several proteins associated with acute inflammation (alpha-2-macroglobulin, fetuin-A, serum amyloid A1). This technique can be used to diagnose systemic inflammation and provides results in 4-5 h. The developed approach was verified using standard immunological methods (ELISA). Samples from 87 individuals, in specific groups, were used for testing and validation: control; inflammatory soft tissue disease accompanied by sepsis; influenza A infection; or COVID-19. The feasibility of differentiating patient groups with the aforementioned conditions was analyzed using a combination of the inflammatory markers described. For fetuin-A and serum amyloid A1, diagnostically significant concentration ranges were established.

Biocompatibility, antioxidant activity and collagen photoprotection properties of C60 fullerene adduct with L-methionine.

Functionalization of the fullerene core with amino acids has become a new and promising direction in the field of nanochemistry. The biologic activity of water-soluble fullerene derivatives is based on such properties as lipophilicity, electron deficiency and photosensitivity. The complex of above-mentioned properties can be used to develop protection of biomolecules (in particular, proteins) from external physical and chemical influences. Thus, development and up-scaling of synthesis procedures, as well as investigation of the biological properties of these derivatives, are extremely important. This paper presents new data on the biocompatibility studies of C60 fullerene adduct with L-methionine (C60[C5H11NO2S]3; C60-Met). Antiradical activity, binding to human serum albumin (HSA), collagen and deoxyribonucleic acid (DNA), hemocompatibility, photodynamic properties, genotoxicity and cytotoxicity were studied. In addition, it was found that C60-Met increases the photostability of the collagen molecule, and this effect is dose-dependent.

Graphene oxide enriched with oxygen-containing groups: on the way to an increase of antioxidant activity and biocompatibility.

The article is dedicated to the comprehensive biocompatibility investigation of synthesised graphene oxide (GO) enriched with oxygen-containing functional groups (⁓85%). GO was synthesised through a modified Hummers and Offeman's method and characterised using 13C NMR, Raman, and IR spectroscopy, XRD, HRTEM, along with size dimensions and ζ-potentials in aqueous dispersions. Biocompatibility study included tests on haemocompatibility (haemolysis, platelet aggregation, binding to human serum albumin and its esterase activity), antioxidant activity (2,2-diphenyl-1-picrylhydrazyl reaction, NO-radical uptake, Radachlorin photobleaching, photo-induced haemolysis), genotoxicity using DNA comet assay, as well as metabolic activity and proliferation of HEK293 cells.

Graphene Oxide of Extra High Oxidation: A Wafer for Loading Guest Molecules.

We present a new modification of graphene oxide with very high content (85 wt %) of oxygen-containing functional groups (hydroxy, epoxy, lactol, carboxyl, and carbonyl groups) that forms stable aqueous dispersion in up to 9 g·L-1 concentration solutions. A novel faster method of the synthesis is described that produces up to 1 kg of the material and allows controlling the particle size in solution. The synthesized compound was characterized by various physicochemical methods and molecular dynamics modeling, revealing a unique structure in the form of a multilayered wafer of several sheets thick, where each sheet is highly corrugated. The ragged structure of the sheets forms pockets with hindered mobility of water that leads to the possibility of trapping guest molecules.

In Vitro and In Silico Investigation of Water-Soluble Fullerenol C60(OH)24: Bioactivity and Biocompatibility.

Light fullerenes, C60 and C70, have significant potential in biomedical applications due to their ability to absorb reactive oxygen species, inhibit the development of tumors, inactivate viruses and bacteria, and as the basis for developing systems for targeted drug delivery. However, the hydrophobicity of individual fullerenes complicates their practical use; therefore, creating water-soluble derivatives of fullerenes is increasingly important. Currently, the most studied soluble adducts of fullerenes are polyhydroxy fullerenes or fullerenols. Unfortunately, investigations of fullerenol biocompatibility are fragmental. They often lack reproducibility both in the synthesis of the compounds and their biological action. We here investigate the biocompatibility of a well-defined fullerenol C60(OH)24 obtained using methods that minimize the content of impurities and quantitatively characterize the product's composition. We carry out comprehensive biochemical and biophysical investigations of C60(OH)24 that include photodynamic properties, cyto- and genotoxicity, hemocompatibility (spontaneous and photo-induced hemolysis, platelet aggregation), and the thermodynamic characteristics of C60(OH)24 binding to human serum albumin and DNA. The performed studies show good biocompatibility of fullerenol C60(OH)24, which makes it a promising object for potential use in biomedicine.

Fullerenol changes metabolite responses differently depending on the iron status of cucumber plants.

The unique properties of carbon-based nanomaterials, including fullerenol, have attracted great interest in agricultural and environmental applications. Iron (Fe) is an essential micronutrient for major metabolic processes, for which a shortage causes chlorosis and reduces the yield of many crops cultivated worldwide. In the current study, the metabolic responses of Cucumis sativus (a Strategy I plant) to fullerenol treatments were investigated depending on the Fe status of plants. Cucumber plants were grown hydroponically, either with [+FeII (ferrous) and +FeIII (ferric)] or in Fe-free (-FeII and -FeIII) nutrient solution, with (+F) or without (-F) a fullerenol supply. Iron species-dependent effects were observed in either Fe-fed or Fe-starved plants, with alteration of metabolites involved in the metabolism of carbohydrates, amino acids, organic acids, lipophilic compounds. Metabolic perturbations triggered by fullerenol in the FeIII-treated plants were in the opposite kind from those in the FeII-treated plants. Whereas in the FeIII-fed plants, fullerenol activated the metabolisation of carbohydrates and amino acids, in the FeII-fed plants, fullerenol activated the metabolisation of lipophilic compounds and repressed the metabolisation of carbohydrates and amino acids. In FeIII-deficient plants, fullerenol stimulated the metabolism of C3 carboxylates and lipophilic compounds while repressing the metabolism of amino acids, hexoses and dicarboxylates, while in FeII-deficient plants, activations of the metabolism of amino acids and dicarboxylates and repression of sterol metabolism by fullerenol were observed. The results indicated that the valence state of Fe sources is of importance for re-programming metabolome responses in cucumber to fullerenol either in Fe-sufficient or Fe-deficient conditions. These investigations are significant for understanding fullerenol interactions and risk assessment in plants with different Fe statuses.