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In order to control pathogenic microorganisms, three polymer compositions were prepared and tested. First, a water-soluble positively charged polycomplex was synthesized via the electrostatic binding of anionic polyacrylic acid to an excess of polyethylenimine to enhance the biocidal activity of the polycation. Second, an aqueous solution of AgNO 3 was added to the polycomplex, thus forming a ternary polycation-polyanion-Ag 1+ complex with an additional antimicrobial effect. Third, the resulting ternary complex was subjected to UV irradiation, which ensured the conversion of Ag 1+ ions into Ag nanoparticles ranging in size mainly from 10 to 20 nm. Aqueous solutions of the polymer compositions were added to suspensions of the Gram-positive bacteria S. aureus and the Gram-negative bacteria P. aeruginosa , with the following main results: (a) Upon the addition of the binary polycomplex, 30% or more of the cells survived after 20 h. (b) The ternary complex killed S. aureus bacteria but was ineffective against P. aeruginosa bacteria. (c) When the ternary complex with Ag nanoparticles was added, the percentage of surviving cells of both types did not exceed 0.03%. The obtained results are valuable for the development of antibacterial formulations.

The purpose of this work was to quantitatively characterize the effectiveness of oxidative phosphorylation uncouplers and decoupling agents in functionally active mitochondria, taking into account their content in the hydrophobic region of the inner membrane of these organelles. When conducting theoretical studies, it is accepted that uncouplers and decouplers occupy part of the volume of mitochondria to exhibit their activity, which is defined as the effective volume. The following quantities characterizing the action of these reagents are considered: (1) concentrations of reagents that cause double stimulation of mitochondrial respiration in state 4 ( C 200 ); (2) effective distribution coefficient ( E MW ) - the ratio of the amount of reagents in the effective volume of mitochondria and the water volume; (3) the relative amount of reagents associated with the effective volume of mitochondria ( U M / U T ); (4) specific activity of reagents localized in the effective volume of mitochondria ( A M ). We have developed methods for determining these values, based on an analysis of the dependence of the rate of mitochondrial respiration on the concentration of uncouplers and decoupling agents at two different concentrations of mitochondrial protein in the incubation medium. During experimental studies, we compared the effects of the classical protonophore uncouplers 2,4-dinitrophenol (DNP) and сarbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), the natural uncouplers lauric and palmitic acids, and the natural decouplers α,ω-tetradecanedioic (TDA) and α,ω-hexadecanedioic (HDA) acids that differ both in the structure of the molecule and in the degree of solubility in lipids. Using the developed methods, we have clarified the dependence of the degree of activity of these uncouplers and decoupling agents on the distribution of their molecules between the effective volume of mitochondria and the water volume., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

VBIT-4 is a new inhibitor of the oligomerization of VDAC proteins of the outer mitochondrial membrane preventing the development of oxidative stress, mitochondrial dysfunction, and cell death in various pathologies. However, as a VDAC inhibitor, VBIT-4 may itself cause mitochondrial dysfunction in healthy cells. The article examines the effect of VBIT-4 on the functional activity of rat liver mitochondria and cell cultures. We have demonstrated that high concentrations of VBIT-4 (15-30 μM) suppressed mitochondrial respiration in state 3 and 3U DNP driven by substrates of complex I and II. VBIT-4 induced depolarization of organelles fueled by substrates of complex I but not complex II of the respiratory chain. VBIT-4 has been found to inhibit the activity of complexes I, III, and IV of the respiratory chain. Molecular docking demonstrated that VBIT-4 interacts with the rotenone-binding site in complex I with similar affinity. 15-30 μM VBIT-4 caused an increase in H 2 O 2 production in mitochondria, decreased the Ca 2+ retention capacity, but increased the time of Ca 2+ -dependent mitochondrial swelling. We have found that the incubation of breast adenocarcinoma (MCF-7) with 30 μM VBIT-4 for 48 h led to the decrease of the mitochondrial membrane potential, an increase in ROS production and death of MCF-7 cells. The mechanism of action of VBIT-4 on mitochondria and cells is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Duchenne muscular dystrophy is caused by loss of the dystrophin protein. This pathology is accompanied by mitochondrial dysfunction contributing to muscle fiber instability. It is known that mitochondria-targeted in vivo therapy mitigates pathology and improves the quality of life of model animals. In the present work, we applied mitochondrial transplantation therapy (MTT) to correct the pathology in dystrophin-deficient mdx mice. Intramuscular injections of allogeneic mitochondria obtained from healthy animals into the hind limbs of mdx mice alleviated skeletal muscle injury, reduced calcium deposits in muscles and serum creatine kinase levels, and improved the grip strength of the hind limbs and motor activity of recipient mdx mice. We noted normalization of the mitochondrial ultrastructure and sarcoplasmic reticulum/mitochondria interactions in mdx muscles. At the same time, we revealed a decrease in the efficiency of oxidative phosphorylation in the skeletal muscle mitochondria of recipient mdx mice accompanied by a reduction in lipid peroxidation products (MDA products) and reduced calcium overloading. We found no effect of MTT on the expression of mitochondrial signature genes ( Drp1 , Mfn2 , Ppargc1a , Pink1 , Parkin ) and on the level of mtDNA. Our results show that systemic MTT mitigates the development of destructive processes in the quadriceps muscle of mdx mice.

This study investigated food safety issues as perceived by food companies and food safety authorities in six countries in Europe and Central Asia. A total of 66 companies and 16 authorities participated in the survey. The results provide important insights related to what the main food safety priorities are, how they are addressed in the countries that participated in the survey, and what the role of the main stakeholders is in the food value chain. Almost 50% of food companies identified 'food fraud' as the most influential food safety attribute. One-third of food safety authorities recognized 'food safety management system' as the most influential food safety attribute. Principal component analysis separated food safety statements into two dimensions named 'food safety hazards and risks' and 'food safety system'. Although there are slight differences in food safety statements between the two stakeholders, i.e., food companies and food safety authorities, it is the country of origin that plays a more important role in understanding their views. Food companies will need to implement a systemic approach and transform the entire food value chain continuum while considering new food safety challenges. It is expected that food safety authorities will have to play a more proactive role in the future.

Background: This investigation provides an important insight into Eurasian consumers' food safety beliefs and trust issues influenced by the COVID-19 pandemic. An online survey was conducted in 15 European and Asian countries involving more than 4000 consumers., Results: It has confirmed that different socioeconomic characteristics, cultural aspects and education levels shape food safety perceptions within Eurasian countries. The COVID-19 pandemic influenced their beliefs and trust in food safety, which is relatively low on average. However, it is significantly higher for European consumers (especially European Union ones) compared to their Asian counterparts. Both Asian and European respondents agreed that food fraud and climate changes represent a food safety issue. However, European consumers were less concerned regarding the food safety of genetically modified foods and meat and dairy analogs/hybrids. Asian consumers were, to a greater extent, worried about the risk of getting COVID-19 from food, restaurants, food retail establishments and home food deliveries., Conclusion: Eurasian consumers have put their greatest extent of trust, when food safety assurance is concerned, into food scientists and food producers holding a food safety certificate. Broadly, they are uncertain to what extent their federal governments and food inspectors are competent, able and efficient in ensuring food safety. Higher education of Eurasian consumers was followed by increased food safety confidence in all parts of the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

This work considers the main indicators of the oxidative phosphorylation efficiency in mitochondria: the ADP/O and H + /O ratios. Three groups of modulators that reduce the efficiency of oxidative phosphorylation are compared: protonophore uncouplers, cyclic redox compounds, and decouplers. It is noted that some of them are considered effective therapeutic agents. The paper analyzes the authors' original data on the mechanism of action of natural decouplers, represented by long-chain α,ω-dioic acids, as antioxidants. In conclusion, we discuss the hypothesis of their participation in the rescue of hepatocytes in various disorders of carbohydrate and lipid metabolism., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The present work shows the cytotoxic effects of novel conjugates of ursolic, oleanolic, maslinic, and corosolic acids with the penetrating cation F16 on cancer cells (lung adenocarcinoma A549 and H1299, breast cancer cell lines MCF-7 and BT474) and non-tumor human fibroblasts. It has been established that the conjugates have a significantly enhanced toxicity against tumor-derived cells compared to native acids and also demonstrate selectivity to some cancer cells. The toxic effect of the conjugates is shown to be due to ROS hyperproduction in cells, induced by the effect on mitochondria. The conjugates caused dysfunction of isolated rat liver mitochondria and, in particular, a decrease in the efficiency of oxidative phosphorylation, a decrease in the membrane potential, and also an overproduction of ROS by organelles. The paper discusses how the membranotropic- and mitochondria-targeted effects of the conjugates may be related to their toxic effects.

It is now generally accepted that the role of bile acids in the organism is not limited to their participation in the process of food digestion. Indeed, bile acids are signaling molecules and being amphiphilic compounds, are also capable of modifying the properties of cell membranes and their organelles. This review is devoted to the analysis of data on the interaction of bile acids with biological and artificial membranes, in particular, their protonophore and ionophore effects. The effects of bile acids were analyzed depending on their physicochemical properties: namely the structure of their molecules, indicators of the hydrophobic-hydrophilic balance, and the critical micelle concentration. Particular attention is paid to the interaction of bile acids with the powerhouse of cells, the mitochondria. It is of note that bile acids, in addition to their protonophore and ionophore actions, can also induce Ca 2+ -dependent nonspecific permeability of the inner mitochondrial membrane. We consider the unique action of ursodeoxycholic acid as an inducer of potassium conductivity of the inner mitochondrial membrane. We also discuss a possible relationship between this K + ionophore action of ursodeoxycholic acid and its therapeutic effects.

The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H + concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Foodborne infections are an important global health problem due to their high prevalence and potential for severe complications. Bacterial contamination of meat during processing at the enterprise can be a source of foodborne infections. Polymeric coatings with antibacterial properties can be applied to prevent bacterial contamination. A composite coating based on fluoroplast and Ag 2 O NPs can serve as such a coating. In present study, we, for the first time, created a composite coating based on fluoroplast and Ag 2 O NPs. Using laser ablation in water, we obtained spherical Ag 2 O NPs with an average size of 45 nm and a ζ-potential of -32 mV. The resulting Ag 2 O NPs at concentrations of 0.001-0.1% were transferred into acetone and mixed with a fluoroplast-based varnish. The developed coating made it possible to completely eliminate damage to a Teflon cutting board. The fluoroplast/Ag 2 O NP coating was free of defects and inhomogeneities at the nano level. The fluoroplast/Ag 2 O NP composite increased the production of ROS (H 2 O 2 , OH radical), 8-oxogualnine in DNA in vitro, and long-lived active forms of proteins. The effect depended on the mass fraction of the added Ag 2 O NPs. The 0.01-0.1% fluoroplast/NP Ag 2 O coating exhibited excellent bacteriostatic and bactericidal properties against both Gram-positive and Gram-negative bacteria but did not affect the viability of eukaryotic cells. The developed PTFE/NP Ag 2 O 0.01-0.1% coating can be used to protect cutting boards from bacterial contamination in the meat processing industry.

Bacterial contamination of meat products during its preparation at the enterprise is an important problem for the global food industry. Cutting boards are one of the main sources of infection. In order to solve this problem, the creation of mechanically stable coatings with antibacterial activity is one of the most promising strategies. For such a coating, we developed a composite material based on "liquid" Teflon and zinc oxide nanoparticles (ZnO-NPs). The nanoparticles obtained with laser ablation had a rod-like morphology, an average size of ~60 nm, and a ζ-potential of +30 mV. The polymer composite material was obtained by adding the ZnO-NPs to the polymer matrix at a concentration of 0.001-0.1% using the low-temperature technology developed by the research team. When applying a composite material to a surface with damage, the elimination of defects on a micrometer scale was observed. The effect of the composite material on the generation of reactive oxygen species (H 2 O 2 , •OH), 8-oxoguanine in DNA in vitro, and long-lived reactive protein species (LRPS) was evaluated. The composite coating increased the generation of all of the studied compounds by 50-200%. The effect depended on the concentration of added ZnO-NPs. The antibacterial and antibiofilm effects of the Teflon/ZnO NP coating against L. monocytogenes , S. aureus , P. aeruginosa , and S. typhimurium , as well as cytotoxicity against the primary culture of mouse fibroblasts, were studied. The conducted microbiological study showed that the fluoroplast/ZnO-NPs coating has a strong bacteriostatic effect against both Gram-positive and Gram-negative bacteria. In addition, the fluoroplast/ZnO-NPs composite material only showed potential cytotoxicity against primary mammalian cell culture at a concentration of 0.1%. Thus, a composite material has been obtained, the use of which may be promising for the creation of antibacterial coatings in the meat processing industry.

Due to the presence of cationic units interpolyelectrolyte complexes (IPECs) can be used as a universal basis for preparation of biocidal coatings on different surfaces. Metallopolymer nanocomposites were successfully synthesized in irradiated solutions of polyacrylic acid (PAA) and polyethylenimine (PEI), and dispersions of non-stoichiometric IPECs of PAA-PEI containing silver ions. The data from turbidimetric titration and dynamic light scattering showed that pH 6 is the optimal value for obtaining IPECs. Metal polymer complexes based on IPEC with a PAA/PEI ratio equal to 3/1 and 1/3 were selected for synthesis of nanocomposites due to their aggregative stability. Studies using methods of UV-VIS spectroscopy and TEM have demonstrated that the size and spatial organization of silver nanoparticles depend on the composition of polymer systems. The average sizes of nanoparticles are 5 nm and 20 nm for complexes with a molar ratio of PAA/PEI units equal to 3/1 and 1/3, respectively. The synthesized nanocomposites were applied to the glass surface and exhibited high antibacterial activity against both gram-positive ( Staphylococcus aureus ) and gram-negative bacteria ( Salmonella ). It is shown that IPEC-Ag coatings demonstrate significantly more pronounced biocidal activity not only in comparison with macromolecular complexes of PAA-PEI, but also coatings of PEI and PEI based nanocomposites.

This paper demonstrates the membranotropic effect of modified levopimaric acid diene adducts on liver mitochondria and lecithin liposomes. We found that the derivatives dose-dependently reduced the efficiency of oxidative phosphorylation of mitochondria due to inhibition of the activity of complexes III and IV of the respiratory chain and protonophore action. This was accompanied by a decrease in the membrane potential in the case of organelle energization both by glutamate/malate (complex I substrates) and succinate (complex II substrate). Compounds 1 and 2 reduced the generation of H 2 O 2 by mitochondria, while compound 3 exhibited a pronounced antioxidant effect on glutamate/malate-driven respiration and, on the other hand, caused ROS overproduction when organelles are energized with succinate. All tested compounds exhibited surface-active properties, reducing the fluidity of mitochondrial membranes and contributing to nonspecific permeabilization of the lipid bilayer of mitochondrial membranes and swelling of the organelles. Modified levopimaric acid diene adducts also induced nonspecific permeabilization of unilamellar lecithin liposomes, which confirmed their membranotropic properties. We discuss the mechanisms of action of the tested compounds on the mitochondrial OXPHOS system and the state of the lipid bilayer of membranes, as well as the prospects for the use of new modified levopimaric acid diene adducts in medicine.

Antibiotic resistance in microorganisms is an important problem of modern medicine which can be solved by searching for antimicrobial preparations of the new generation. Nanoparticles (NPs) of metals and their oxides are the most promising candidates for the role of such preparations. In the last few years, the number of studies devoted to the antimicrobial properties of silver oxide NPs have been actively growing. Although the total number of such studies is still not very high, it is quickly increasing. Advantages of silver oxide NPs are the relative easiness of production, low cost, high antibacterial and antifungal activities and low cytotoxicity to eukaryotic cells. This review intends to provide readers with the latest information about the antimicrobial properties of silver oxide NPs: sensitive organisms, mechanisms of action on microorganisms and further prospects for improving the antimicrobial properties.

Bacterial antibiotic resistance is one of the most serious modern biomedical problems that prioritizes the search for new agents to combat bacterial pathogens. It is known that nanoparticles of many metals and metal oxides can have an antibacterial effect. However, the antibacterial efficacy of aluminum oxide nanoparticles has been studied little compared to the well-known antimicrobial properties of nanoparticles of oxides of metals such as zinc, silver, iron, and copper. In this review, we have focused on the experimental studies accumulated to date demonstrating the antibacterial effect of aluminum oxide nanoparticles. The review discusses the main ways of synthesis and modification of these nanoparticles, provides the proposed mechanisms of their antibacterial action against gram-positive and gram-negative bacteria, and also compares the antibacterial efficacy depending on morphological characteristics. We have also partially considered the activity of aluminum oxide nanoparticles against water microalgae and fungi. In general, a more detailed study of the antibacterial properties of aluminum oxide nanoparticles is of great interest due to their low toxicity to eukaryotic cells.

A case study of ordinal data from human organoleptic examination (sensory analysis) of drinking water obtained in an interlaboratory comparison of 49 ecological laboratories is described. The recently developed two-way ordinal analysis of variation (ORDANOVA) is applied for the first time for the treatment of responses on the intensity of chlorine and sulfurous odor of water at 20 and 60 °C, which is classified into the six categories from 'imperceptible' to 'very strong'. The one-way ORDANOVA is used for the analysis of the 'salty taste' intensity of the water. A decomposition of the total variation of the ordinal data and simulation of the multinomial distribution of the data-relative frequencies in different categories allowed the determination of the statistical significance of the difference between laboratories in classifying chlorine or sulfurous odor intensity by categories, while the effect of temperature was not significant. No statistical difference was found between laboratories on salty taste intensity. The capabilities of experts to identify different categories of the intensity of the odor and taste are also evaluated. A comparison of the results obtained with ORDANOVA and ANOVA showed that ORDANOVA is a more useful and reliable tool for understanding categorical data such as the intensity of drinking water odor and taste.

The present work shows that the rate of free respiration of liver mitochondria (in the absence of ATP synthesis (state 4) during the oxidation of succinate is 1.7 times higher than during the oxidation of glutamate with malate. In turn, in the case of oxidation of ferrocyanide with ascorbate, this value is 3.1 times greater than in the case of succinate oxidation. A similar pattern is also observed upon stimulation of free respiration by low concentrations (5 and 10 μM) of the protonophore uncoupler 2,4-dinitrophenol (DNP). It is found that the passive leakage rate of protons in state 4 is the same if the H + /O ratios are 10, 6, and 2 upon the oxidation of glutamate with malate, succinate, and ferrocyanide with ascorbate, respectively. At these values of the H + /O ratio, low concentrations of DNP stimulate passive proton leakage equally during the oxidation of these respiration substrates. In the case of succinate oxidation, bypassing complex III by N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) to the maximum degree, as well as switching this complex completely to idle mode by α,ω-hexadecanedioic acid (HDA) cause a 3-fold stimulation of respiration in state 4. We conclude that at mitochondrial free respiration the values of the H + /2e - ratio for complexes I, III, and IV of the respiratory chain are 4, 4, and 2, respectively. It is assumed that the free respiration of mitochondria is carried out by simple diffusion of protons through the inner membrane, and the rate of this diffusion depends on the total number of protons released by the complexes of the electron transport chain into the intermembrane space., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

S-15176 difumarate salt, a derivative of the anti-ischemic metabolic drug trimetazidine, has been intensively studied for its impact on cellular metabolism in animal models of ischemia-reperfusion injury of the liver, heart, spinal cord, and other organs. Despite evidence of some reduction in oxidative damage to cells, the results of therapy with S-15176 have been mostly disappointing, possibly because of the lack of data on its underlying mechanisms. Here, we aimed to investigate in more detail the role of complexes I-IV of the electron transport chain and membrane permeability transition in mitochondrial toxicity associated with S-15176. Using rat thymocyte and liver mitochondria, we demonstrated that: (1) acute exposure to S-15176 (10 to 50 μM) dose-dependently decreased the mitochondrial membrane potential; (2) S-15176 suppressed the ADP-stimulated (State 3) and uncoupled (State 3U DNP ) respiration of mitochondria energized with succinate or malate/glutamate, but not ascorbate/TMPD, and increased the resting respiration (State 4) when using all the substrate combinations; (3) S-15176 directly inhibited the activity of the respiratory complex III; (4) low doses of S-15176 diminished the rate of H 2 O 2 production by mitochondria; (5) at concentrations of above 30 μM, S-15176 reduced calcium retention capacity and contributed to mitochondrial membrane permeabilization. Taken together, these findings suggest that S-15176 at tissue concentrations reached in animals can impair mitochondrial function through suppression of the cytochrome bc 1 complex and an increase in the nonspecific membrane permeability.

Microbial antibiotic resistance is an important global world health problem. Recently, an interest in nanoparticles (NPs) of silver oxides as compounds with antibacterial potential has significantly increased. From a practical point of view, composites of silver oxide NPs and biocompatible material are of interest. A borosiloxane (BS) can be used as one such material. A composite material combining BS and silver oxide NPs has been synthesized. Composites containing BS have adjustable viscoelastic properties. The silver oxide NPs synthesized by laser ablation have a size of ~65 nm (half-width 60 nm) and an elemental composition of Ag 2 O. The synthesized material exhibits strong bacteriostatic properties against E. coli at a concentration of nanoparticles of silver oxide more than 0.01%. The bacteriostatic effect depends on the silver oxide NPs concentration in the matrix. The BS/silver oxide NPs have no cytotoxic effect on a eukaryotic cell culture when the concentration of nanoparticles of silver oxide is less than 0.1%. The use of the resulting composite based on BS and silver oxide NPs as a reusable dry disinfectant is due to its low toxicity and bacteriostatic activity and its characteristics are not inferior to the medical alloy nitinol.

Surface-enhanced Raman spectroscopy (SERS) is a promising tool that can be used in the detection of molecular changes triggered by disease development. Cardiovascular diseases (CVDs) are caused by multiple pathologies originating at the cellular level. The identification of these deteriorations can provide a better understanding of CVD mechanisms, and the monitoring of the identified molecular changes can be employed in the development of novel biosensor tools for early diagnostics. We applied plasmonic SERS nanosensors to assess changes in the properties of erythrocytes under normotensive and hypertensive conditions in the animal model. We found that spontaneous hypertension in rats leads (i) to a decrease in the erythrocyte plasma membrane fluidity and (ii) to a decrease in the mobility of the heme of the membrane-bound hemoglobin. We identified SERS parameters that can be used to detect pathological changes in the plasma membrane and submembrane region of erythrocytes.

A low-temperature technology was developed for producing a nanocomposite based on poly (lactic-co-glycolic acid) and zinc oxide nanoparticles (ZnO-NPs), synthesized by laser ablation. Nanocomposites were created containing 0.001, 0.01, and 0.1% of zinc oxide nanoparticles with rod-like morphology and a size of 40-70 nm. The surface of the films from the obtained nanomaterial was uniform, without significant defects. Clustering of ZnO-NPs in the PLGA matrix was noted, which increased with an increase in the concentration of the dopant in the polymer. The resulting nanomaterial was capable of generating reactive oxygen species (ROS), such as hydrogen peroxide and hydroxyl radicals. The rate of ROS generation increased with an increase in the concentration of the dopant. It was shown that the synthesized nanocomposite promotes the formation of long-lived reactive protein species, and is also the reason for the appearance of a key biomarker of oxidative stress, 8-oxoguanine, in DNA. The intensity of the process increased with an increase in the concentration of nanoparticles in the matrix. It was found that the nanocomposite exhibits significant bacteriostatic properties, the severity of which depends on the concentration of nanoparticles. In particular, on the surface of the PLGA-ZnO-NPs composite film containing 0.001% nanoparticles, the number of bacterial cells was 50% lower than that of pure PLGA. The surface of the composite is non-toxic to eukaryotic cells and does not interfere with their adhesion, growth, and division. Due to its low cytotoxicity and bacteriostatic properties, this nanocomposite can be used as coatings for packaging in the food industry, additives for textiles, and also as a material for biomedicine.

Food products may be a source of Salmonella , one of the main causal agents of food poisoning, especially after the emergence of strains resistant to antimicrobial preparations. The present work dealt with investigation of the occurrence of resistance to antimicrobial preparations among S. enterica strains isolated from food. The isolates belonged to 11 serovars, among which Infantis (28%), Enteritidis (19%), and Typhimurium (13.4%) predominated. The isolates were most commonly resistant to trimethoprim/sulfamethoxazole ( n = 19, 59.38%), cefazolin ( n = 15, 46.86%), tetracycline ( n = 13, 40.63%), and amikacin ( n = 9, 28.13%). Most of the strains (68.75%) exhibited multiple resistance to commonly used antibiotics. High-throughput sequencing was used to analyse three multidrug-resistant strains (resistant to six or more antibiotics). Two of them (SZL 30 and SZL 31) belonged to S. Infantis, while one strain belonged to S. Typhimurium (SZL 38). Analysis of the genomes of the sequenced strains revealed the genes responsible for antibiotic resistance. In the genomes of strains SZL 30 and SZL 31 the genes of antibiotic resistance were shown to be localized mostly in integrons within plasmids, while most of the antibiotic resistance genes of strain SZL 38 were localized in a chromosomal island (17,949 nt). Genomes of the Salmonella strains SZL 30, SZL 31, and SZL 38 were shown to contain full-size pathogenicity islands: SPI-1, SPI-2, SPI-4, SPI-5, SPI-9, SPI-11, SPI-13, SPI-14, and CS54. Moreover, the genome of strain SZL 38 was also found to contain the full-size pathogenicity islands SPI-3, SPI-6, SPI-12, and SPI-16. The emergence of multidrug-resistant strains of various Salmonella serovars indicates that further research on the transmission pathways for these genetic determinants and monitoring of the distribution of these microorganisms are necessary.

A method for obtaining a stable colloidal solution of silver oxide nanoparticles has been developed using laser ablation. The method allows one to obtain nanoparticles with a monomodal size distribution and a concentration of more than 10 8 nanoparticles per mL. On the basis of the obtained nanoparticles and the PLGA polymer, a nanocomposite material was manufactured. The manufacturing technology allows one to obtain a nanocomposite material without significant defects. Nanoparticles are not evenly distributed in the material and form domains in the composite. Reactive oxygen species (hydrogen peroxide and hydroxyl radical) are intensively generated on the surfaces of the nanocomposite. Additionally, on the surface of the composite material, an intensive formation of protein long-lived active forms is observed. The ELISA method was used to demonstrate the generation of 8-oxoguanine in DNA on the developed nanocomposite material. It was found that the multiplication of microorganisms on the developed nanocomposite material is significantly decreased. At the same time, the nanocomposite does not inhibit proliferation of mammalian cells. The developed nanocomposite material can be used as an affordable and non-toxic nanomaterial to create bacteriostatic coatings that are safe for humans.

The present study describes the synthesis of pyridinium derivatives of betulin, including new 4-methyl- and 3,5-methyl-pyridinium analogs, their effect on artificial membrane systems (liposomes), cytotoxicity in models of prokaryotic (E. coli K-12 MG1655) and eukaryotic cells (rat thymocytes), as well as their effect on the functioning of membrane systems of rat liver mitochondria. We have shown that the presence of methyl groups in the pyridine ring of compounds determines the ability of the derivatives to effectively permeabilize the artificial membrane of lecithin liposomes for the fluorescent probe sulforhodamine B. The 4-methyl- and 3,5-methyl-pyridinium analogs inhibit the growth of E. coli K-12 MG1655 and, at the same time, did not have a cytotoxic effect on rat thymocytes. However, in the latter case, we noted a decrease in the mitochondrial potential of cells. The studied compounds reduced the functional activity of mitochondria, suppressing the activity of complexes of the respiratory chain and reducing the membrane potential. In addition, compounds containing methyl groups in the p- and m-positions of the pyridine ring were also able to permeabilize the inner membrane of mitochondria, causing them to swell. In this case, the most lipophilic compound containing two methyl substituents at the m-position of the pyridine fragment was most effective and had a protonophore effect on mitochondria. The paper discusses the dependence of the membranotropic and biological actions of the quaternized pyridine derivatives of betulin on their structure and lipophilicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is one of the key microelements and plays an important role in the function of living systems of different hierarchies. Iron abundance and its physiological functions bring into question the ability of iron compounds at the same concentrations, on the one hand, to inhibit the microbial growth and, on the other hand, to positively affect mammalian cells. At present, multiple studies have been published that show the antimicrobial effect of IONPs against Gram-negative and Gram-positive bacteria and fungi. Several studies have established that IONPs have a low toxicity to eukaryotic cells. It gives hope that IONPs can be considered potential antimicrobial agents of the new generation that combine antimicrobial action and high biocompatibility with the human body. This review is intended to inform readers about the available data on the antimicrobial properties of IONPs, a range of susceptible bacteria, mechanisms of the antibacterial action, dependence of the antibacterial action of IONPs on the method for synthesis, and the biocompatibility of IONPs with eukaryotic cells and tissues.

The paper examines the molecular mechanisms of the cytotoxicity of conjugates of betulinic acid with the penetrating cation F16. The in vitro experiments on rat thymocytes revealed that all the obtained F16-betulinic acid derivatives showed more than 10-fold higher cytotoxicity as compared to betulinic acid and F16. In this case, 0.5-1 μM of all conjugates showed mitochondria-targeted action, inducing superoxide overproduction and reducing the mitochondrial potential of cells. Experiments on isolated rat liver mitochondria revealed the ability of conjugates to dose-dependently reduce the membrane potential of organelles, as well as the intensity of respiration and oxidative phosphorylation, which is also accompanied by an increase in the production of hydrogen peroxide by mitochondria. It was shown that these actions of derivatives may be due to several effects: the reversion of ATP synthase, changes in the activity of complexes of the respiratory chain and permeabilization of the inner mitochondrial membrane. All compounds also demonstrated the ability to induce aggregation of isolated rat liver mitochondria. Using the model of lecithin liposomes, we found that the F6 conjugate (2 μM) induces the permeability of vesicle membranes for the fluorescent probe sulforhodamine B. High concentrations (25 μM) of the F6 derivative have been found to induce dynamic processes in the liposome membrane leading to aggregation and/or fusion of vesicle membranes. The paper discusses the relationship between the mitochondria-targeted effects of F16-betulinic acid conjugates and their cytotoxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This work demonstrates the effects of a newly synthesized conjugate of the plant triterpenoid betulin and the penetrating cation F16 used for mitochondrial targeting. The resulting F16-betulin conjugate revealed a mitochondria-targeted effect, decreasing the mitochondrial potential and inducing superoxide overproduction in rat thymocytes in vitro . It has been suggested that this may cause the cytotoxic effect of the conjugate, which significantly exceeds the effectiveness of its precursors, betulin and F16. Using isolated rat liver mitochondria, we found that the F16-betulin conjugate has a surface-active effect on mitochondrial membranes, causing organelle aggregation. This effect of the derivative resulted in a dose-dependent decrease in mitochondrial transmembrane potential, as well as suppression of respiration and oxidative phosphorylation, especially in the case of nicotinamide adenine dinucleotide (NAD)-fueled organelles. In addition, the F16-betulin conjugate caused an increase in H 2 O 2 generation by mitochondria fueled with glutamate and malate. These effects of the derivative can presumably be due to the powerful suppression of the redox activity of complex I of the mitochondrial electron transport chain. The paper discusses how the mitochondria-targeted effects of the F16-betulin conjugate may be related to its cytotoxic effects.

This study provides an important insight into the response of food safety systems during the first months of the pandemic, elevating the perspective of preventing Covid-19 within conventional food safety management systems. A multi-country survey was conducted in 16 countries involving 825 food companies. Based on the results of the survey, it is obvious that the level of maturity of a food safety system in place is the main trigger in classifying companies and their responses to the pandemic challenge. Staff awareness and hygiene are the two most important attributes in combating Covid-19, opposed to temperature checking of workers in food establishment and health protocols from the World Health Organization, recognized as attributes with limited salience and importance. Companies confirmed implementation of more restrictive hygiene procedures during the pandemic and the need for purchasing more additional personal protective equipment. Retailers were identified as the food supply chain link mostly affected by the pandemic opposed to food storage facilities ranked as least affected. During this challenging period, all companies declared that food safety has not been compromised at any moment. It is important to note that less than a half of the food companies had documented any emergency plans associated with pandemics and health issues in place., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

The paper shows that natural α,ω-dioic acid, α,ω-hexadecanedioic acid (HDA), is able to stimulate the respiration of succinate-fueled rat liver mitochondria in state 4 without induction of proton conductivity of the inner membrane. This effect of HDA is less pronounced in glutamate/malate-fueled mitochondria, as well as in the case of ascorbate/TMPD or ascorbate/ferrocyanide substrate systems, which transfer electrons directly to cytochrome c. It is noted that HDA-induced stimulation of respiration is not associated with damage to the inner membrane in a part of mitochondria and with shunting of electrons through the bc 1 complex. Therefore, HDA can be considered as a natural decoupling agent. Specific inhibitors of the bc 1 complex (antimycin A and myxothiazole) as well as malonate and dithionitrobenzoate were used in the inhibitory analysis. These and other experiments have shown that during the oxidation of succinate in liver mitochondria, the decoupling effect of HDA is mainly carried out at the level of the bc 1 complex. We hypothesized that HDA is capable of promoting the cyclic transport of protons within the bc 1 complex and thus switch this complex to the idle mode of operation (intrinsic uncoupling of the bc 1 complex). Induction of free respiration in liver mitochondria by HDA at the level of the bc 1 complex is considered as one of the "rescue pathways" of hepatocytes in various pathological conditions, accompanied by disorders of carbohydrate and lipid metabolism and increased oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

An electrospark technology has been developed for obtaining a colloidal solution containing nanosized amorphous carbon. The advantages of the technology are its low cost and high performance. The colloidal solution of nanosized carbon is highly stable. The coatings on its basis are nanostructured. They are characterized by high adhesion and hydrophobicity. It was found that the propagation of microorganisms on nanosized carbon coatings is significantly hindered. At the same time, eukaryotic animal cells grow and develop on nanosized carbon coatings, as well as on the nitinol medical alloy. The use of a colloidal solution as available, cheap and non-toxic nanomaterial for the creation of antibacterial coatings to prevent biofilm formation seems to be very promising for modern medicine, pharmaceutical and food industries.

The paper considers the effects of plant triterpenoid betulin and its derivative betulonic acid on rat liver mitochondria and liposomes. It was found that betulonic acid and, to a lesser extent, betulin, activate mitochondrial respiration in states 2 and 4 and inhibit ADP- and DNP-stimulated (uncoupled) respiration. The effect of betulonic acid resulted in a significant decrease of the respiratory control and ADP/O ratios and decrease in Δψ. The effects of both compounds were most pronounced in the case of succinate-fueled mitochondrial respiration. This may include both the possible protonophore effect of betulonic acid and the inhibition of respiratory chain complexes by both compounds. Both agents enhanced H 2 O 2 production in succinate-fueled mitochondria, while betulonic acid exerted an antioxidant effect with NAD-dependent substrates. Betulin was found to induce mitochondrial aggregation, but had no effect on membrane permeability. A similar pattern was found on liposomes. As revealed by the laurdan generalized polarization (GP) technique, betulin increased laurdan GP in lecithin liposomes, indicating a decrease in membrane fluidity. Measurements of GP as a function of fluorescence excitation wavelength gave an ascending line for high concentrations of betulin, which can be interpreted as phase heterogeneity of the lipid/betulin system. High concentrations of betulin (> 60 mol%) was also demonstrated to cause permeabilization of lecithin liposomes. Betulonic acid was much less effective in inducing the aggregation of mitochondria and liposomes and had no effect on membrane permeability. The possible mechanisms of betulin and betulonic acid effect on rat liver mitochondria and liposomes are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Theoretical and experimental studies have revealed that that in the liver mitochondria an increase in the rate of free respiration in state 3 induced by protonophore uncouplers 2,4-dinitrophenol and сarbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone is equal to or slightly greater than the increase in respiration rate in state 4 induced by these uncouplers. In contrast to these protonophore uncouplers, the decoupler α,ω-tetradecanedioic acid, increasing the rate of respiration in state 4, does not significantly affect the rate of free respiration in state 3. We have proposed quantitative indicators that allow determining the constituent part of the rate of respiration in state 4, associated with the decoupling effect of the uncoupler. Using the example of palmitic acid, we have found out the fundamental possibility of the simultaneous functioning of uncouplers by two mechanisms: as protonophores and as decouplers. The data obtained contradict the delocalized version of Mitchell's chemiosmotic theory, but are in complete agreement with its local version. It can be assumed that the F 0 F 1 -ATP synthase and nearby respiratory chain complexes form a local zone of coupled respiration and oxidative ATP synthesis (zones of oxidative phosphorylation). The uncoupler-induced stimulation of mitochondrial free respiration of mitochondria in state 3 is mainly due to the return of protons to the matrix in local zones, where the generation of a proton motive force (Δр) by respiratory chain complexes is associated with various transport processes, but not with ATP synthesis (zones of protonophore uncoupling). In contrast, respiratory stimulation in state 4 by decouplers is realized in local zones of oxidative phosphorylation by switching the respiratory chain complexes to the idle mode of operation in the absence of ATP synthesis.

Anti-influenza drugs and vaccines have a limited effect due to the high mutation rate of virus genome. The direct impact on the conservative virus genome regions should significantly improve therapeutic effectiveness. The RNA interference mechanism (RNAi) is one of the modern approaches used to solve this problem. In this work, we have investigated the antiviral activity of small interfering RNA (siRNA) against the influenza A/PR/8/34 (H1N1), targeting conserved regions of NP and PA. Polycations were used for intracellular siRNA delivery: chitosan's derivatives (methylglycol and quaternized chitosan), polyethyleneimine, lipofectamine, and hybrid organic/non-organic microcapsules. A comparative study of these delivery systems with fluorescent labeled siRNA was conducted. The antiviral activity of three small interfering RNAs targeting the NP (NP-717, NP-1496) and PA (PA-1630) influenza A viruses genes was demonstrated, depending on the chosen carrier. The most effective intracellular delivery and antiviral activity were observed for hybrid microcapsules.

The aim of this work was to study the sensitivity of Chinese and Russian female consumers to androstenone and skatole and to identify their preference for pork patties from entire male pigs compared with those from castrated pigs. One-hundred-twenty women in each country were enrolled. The sensitivity of the consumers to both compounds was tested using smell strips and triangular tests. Pairwise tests were performed comparing patties from castrated male pigs with patties from boars with different levels of androstenone and skatole. Approximately 70% of the Russian and 60% of the Chinese consumers were sensitive to skatole and 37% and 32% were sensitive to androstenone, respectively. Nevertheless, a higher percentage of sensitive Russian consumers compared to Chinese consumers disliked the smell of both compounds. In Russia, the consumers' preferences were higher for patties with low levels of both compounds, while no differences were found in China. In both countries, consumers who were sensitive to skatole also preferred patties with low levels of both compounds. Thus, the levels of androstenone and skatole affect boar patty preferences., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A great enhancement in Raman scattering (SERS) from heme-containing submembrane biomolecules inside intact erythrocytes and functional mitochondria is demonstrated for the first time using silver-silica beads prepared using a new method involving aerosol pyrolysis with aqueous diamminesilver(i) hydroxide as a unique source of plasmonic nanoparticles for SiO 2 microspheres. The recorded SERS spectra reveal a set of characteristic peaks at 750, 1127, 1170, 1371, 1565, 1585 and 1638 cm -1 , resulting from the normal group vibrations of the pyrrole rings, methine bridges and side radicals in the heme molecules. The SERS spectra of functional mitochondria are sensitive to the activity of the mitochondrial electron transport chain, thus making the method a novel label-free approach to monitor the redox state and conformation of cytochromes in their natural cell environment. The developed nanocomposites are highly suitable for the analysis of biological objects due to their robust synthesis and superior spatial and temporal signal reproducibility, which was preserved for a period of at least one year.

Selective study of the electron transport chain components in living mitochondria is essential for fundamental biophysical research and for the development of new medical diagnostic methods. However, many important details of inter- and intramembrane mitochondrial processes have remained in shadow due to the lack of non-invasive techniques. Here we suggest a novel label-free approach based on the surface-enhanced Raman spectroscopy (SERS) to monitor the redox state and conformation of cytochrome c in the electron transport chain in living mitochondria. We demonstrate that SERS spectra of living mitochondria placed on hierarchically structured silver-ring substrates provide exclusive information about cytochrome c behavior under modulation of inner mitochondrial membrane potential, proton gradient and the activity of ATP-synthetase. Mathematical simulation explains the observed enhancement of Raman scattering due to high concentration of electric near-field and large contact area between mitochondria and nanostructured surfaces.

The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and brain dopamine system in predisposed to depressive-like behavior ASC (Antidepressant Sensitive Cataleptics) mice in comparison with the parental "nondepressive" CBA mice was studied. In 7days after administration (800ng, i.c.v.) GDNF decreased escape latency time and the path traveled to reach hidden platform in Morris water maze in ASC mice. GDNF enhanced depressive-like behavioral traits in both "nondepressive" CBA and "depressive" ASC mice. In CBA mice, GDNF decreased functional response to agonists of D1 (chloro-APB hydrobromide) and D2 (sumanirole maleate) receptors in tail suspension test, reduced D2 receptor gene expression in the substantia nigra and increased monoamine oxydase A (MAO A) gene expression in the striatum. GDNF increased D1 and D2 receptor genes expression in the nucleus accumbens of ASC mice but failed to alter expression of catechol-O-methyltransferase, dopamine transporter, MAO B and tyrosine hydroxylase genes in both investigated mouse strains. Thus, GDNF produced long-term genotype-dependent effect on behavior and the brain dopamine system. GDNF pretreatment (1) reduced D1 and D2 receptors functional responses and D2 receptor gene expression in s. nigra of CBA mice; (2) increased D1 and D2 receptor genes expression in n. accumbens of ASC mice and (3) improved spatial learning in ASC mice. GDNF enhanced depressive-like behavior both in CBA and ASC mice. The data suggest that genetically defined variance in the cross-talk between GDNF and brain dopamine system contributes to the variability of GDNF-induced responses and might be responsible for controversial GDNF effects., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and on the serotonin (5-HT) system of a mouse strain predisposed to depressive-like behavior, ASC/Icg (Antidepressant Sensitive Cataleptics), in comparison with the parental "nondepressive" CBA/Lac mice was studied. Within 7 days after acute administration, GDNF (800 ng, i.c.v.) decreased cataleptic immobility but increased depressive-like behavioral traits in both investigated mouse strains and produced anxiolytic effects in ASC mice. The expression of the gene encoding the key enzyme for 5-HT biosynthesis in the brain, tryptophan hydroxylase-2 (Tph-2), and 5-HT1A receptor gene in the midbrain as well as 5-HT2A receptor gene in the frontal cortex were increased in GDNF-treated ASC mice. At the same time, GDNF decreased 5-HT1A and 5-HT2A receptor gene expression in the hippocampus of ASC mice. GDNF failed to change Tph2, 5-HT1A , or 5-HT2A receptor mRNA levels in CBA mice as well as 5-HT transporter gene expression and 5-HT1A and 5-HT2A receptor functional activity in both investigated mouse strains. The results show 1) a GDNF-induced increase in the expression of key genes of the brain 5-HT system, Tph2, 5-HT1A , and 5-HT2A receptors, and 2) significant genotype-dependent differences in the 5-HT system response to GDNF treatment. The data suggest that genetically defined cross-talk between neurotrophic factors and the brain 5-HT system underlies the variability in behavioral response to GDNF., (Copyright © 2013 Wiley Periodicals, Inc.)

In the course of structure-function investigations of lipids a phosphatidylcholine molecule with short and rigid tails, di-2,4-hexadienoylphosphatidylcholine (DiSorbPC), was synthesized and studied in comparison with its saturated analog, dihexanoylphosphatidylcholine (DHPC). Conjugated double bonds in the acyl chains in DiSorbPC reduce considerably the number of possible conformers of the lipid within an aggregate. This leads to impaired packing of unsaturated acyl chains and thus, to a surprisingly high (115 Å(2)) area per molecule for DiSorbPC at the air-water interface and failure to form micelles of regular size and shape. Details on DiSorbPC aggregation and packing provided by a set of experimental techniques combined with molecular dynamics simulations are presented., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)