Search

It is well-known that non-covalent interactions play an essential role in the functioning of biomolecules in living organisms. The significant attention of researchers is focused on the mechanisms of associates formation and the role of the chiral configuration of proteins, peptides, and amino acids in the association. We have recently demonstrated the unique sensitivity of chemically induced dynamic nuclear polarization (CIDNP) formed in photoinduced electron transfer (PET) in chiral donor–acceptor dyads to non-covalent interactions of its diastereomers in solutions. The present study further develops the approach for quantitatively analyzing the factors that determine the association by examples of dimerization of the diastereomers with the RS, SR, and SS optical configurations. It has been shown that, under the UV irradiation of dyads, CIDNP is formed in associates, namely, homodimers (SS-SS), (SR-SR), and heterodimers (SS-SR) of diastereomers. In particular, the efficiency of PET in homo-, heterodimers, and monomers of dyads completely determines the forms of dependences of the CIDNP enhancement coefficient ratio of SS and RS, SR configurations on the ratio of diastereomer concentrations. We expect that the use of such a correlation can be useful in identifying small-sized associates in peptides, which is still a problem.

Glycyrrhizic acid (GA) is the active ingredient in licorice root, which exhibits a wide range of biological activities, including anti-inflammatory and antiviral activities. In particular, the virus-inhibiting effect of GA on SARS-associated coronavirus was demonstrated. In addition, GA was found to be capable of increasing bioaccessibility of other drugs when used together. All these effects can be based on the ability of GA to incorporate into cell membranes and change their physical and functional properties. One of the possible mechanisms of the antiviral action of GA against COVID-19 is also considered to be the prevention of fusion of the virus envelope with the plasma membrane of the host cell. The interaction of GA with model lipid membranes was studied by the NMR method. Different factors influencing the incorporation of the GA molecule into the lipid bilayer (phospholipid structure, pH of the medium) were examined.

Introduction. The article deals with the Crimean period (August 1941 – June 1942) in the life of Basan Badminovich Gorodovikov, Hero of the Soviet Union and a major military and political figure of Kalmykia. The present article aims at describing and analyzing this less-known period of his biography, which was significant and full of dramatic events. Data and research methods. For the purposes of this research, the author has used a wide range of archival materials, as well as memoirs of participants of the partisan movement in the Crimea (including unpublished papers). Results. The author describes the first battles in the north of the Crimea in which Gorodovikov’s regiment was engaged; then, its retreat into the mountains and transition to partisans, the creation of a partisan detachment and the actions behind enemy lines. The activities of Gorodovikov’s detachment are shown against the general background of the partisan movement in the Crimea; special attention given to the discussion of warfare under the specific conditions on the peninsula. The article focuses on the role of the military personnel, especially at the first stage of the partisan movement, revealing, among other things, the problems in the relationship between the command staff of the 48th cavalry division and the partisan leaders in the Crimea. For the first time, the article sheds light on the history of awarding Gorodovikov with the Order of the Red Banner, which was the first award of the Crimean partisans. The dramatic story of his evacuation from the partisan forest to the “Bol´shaia zemlia” is also documented in detail; with previously unknown documents and materials introduced in this paper. The undertaken research allows to conclude that the Crimean period in the life of Gorodovikov was one of the most dramatic in his biography. During a difficult period for the Crimea, he became the commander of one of the most successful partisan detachments, which after he left was officially named after him, its first commander. Notably, Gorodovikov was among the first Crimean partisans to be awarded a military order and to get a promotion in rank and in office.

Electron transfer plays a crucial role in ROS generation in living systems. Molecular oxygen acts as the terminal electron acceptor in the respiratory chains of aerobic organisms. Two main mechanisms of antioxidant defense by exogenous antioxidants are usually considered. The first is the inhibition of ROS generation, and the second is the trapping of free radicals. In the present study, we have elucidated both these mechanisms of antioxidant activity of glycyrrhizin (GL), the main active component of licorice root, using the chemically induced dynamic nuclear polarization (CIDNP) technique. First, it was shown that GL is capable of capturing a solvated electron, thereby preventing its capture by molecular oxygen. Second, we studied the effect of glycyrrhizin on the behavior of free radicals generated by UV irradiation of xenobiotic, NSAID—naproxen in solution. The structure of the glycyrrhizin paramagnetic intermediates formed after the capture of a solvated electron was established from a photo-CIDNP study of the model system—the dianion of 5-sulfosalicylic acid and DFT calculations.

Natural bioactive compounds have recently emerged as a current strategy for Alzheimer’s disease treatment. Carotenoids, including astaxanthin, lycopene, lutein, fucoxanthin, crocin and others are natural pigments and antioxidants, and can be used to treat a variety of diseases, including Alzheimer’s disease. However, carotenoids, as oil-soluble substances with additional unsaturated groups, suffer from low solubility, poor stability and poor bioavailability. Therefore, the preparation of various nano-drug delivery systems from carotenoids is a current measure to achieve efficient application of carotenoids. Different carotenoid delivery systems can improve the solubility, stability, permeability and bioavailability of carotenoids to a certain extent to achieve Alzheimer’s disease efficacy. This review summarizes recent data on different carotenoid nano-drug delivery systems for the treatment of Alzheimer’s disease, including polymer, lipid, inorganic and hybrid nano-drug delivery systems. These drug delivery systems have been shown to have a beneficial therapeutic effect on Alzheimer’s disease to a certain extent.

To exploit aqueous-soluble formulation and improve the anticoccidial activity of 4,4′-dinitrocarbanilide (DNC, active component of nicarbazin), this paper prepared DNC/GA/PVP K30 solid dispersion (SD) with glycyrrhizic acid (GA) and polyvinylpyrrolidone (PVP) K30 by a mechanical ball milling method without using any organic solvent. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy were used for the solid state characterization. High performance liquid chromatography, critical micelle concentration, particle characterization, and transmission electron microscopy were used to evaluate the behavior in aqueous solution. In addition, the oral bioavailability, tissue distribution, and anticoccidial activity of DNC/GA/PVP K30 SD were investigated as well. Compared with free drug, the novel formulation not only improved the solubility and dissolution rate of DNC, but also inhibited the fecal output of oocysts and enhanced the therapeutic effect of coccidiosis. According to the experiment results, the DNC/GA/PVP K30 SD increased 4.64-fold in oral bioavailability and dramatically enhanced the concentration in liver which provided a basis for further research in schistosomiasis. In summary, our findings suggested that DNC/GA/PVP K30 SD may have promising applications in the treatment of coccidiosis.

Introduction. It is known that relations between the Mordovians and Turkic-speaking tribes began in the 4th century AD. The Mordovian people contacted with the Tatars, who were known as Mishars. The article considers the phonetic systems of Mordovian and Tatar-Mishars language in a comparative aspect. Materials and Methods. Descriptive, typological and comparative methods allow us to analyze the topology of the two phonetic systems. The research material is the system of vowels and consonants of Mordovian and Tatar-Mishars languages. Results and Discussion. The results present the use of vowels and consonants in the Moksha, Erzia, and Tatar-Mishar languages. Their functions are analyzed in both languages. Conclusion. The research materials show that in the use of vowels and consonants can differ not only between Mordovian languages and the language of the Tatars-Mishars, but also between Moksha and Erzia.

Introduction: the article considers the development of the Uralic sonorous consonants in the common Mordovian, modern Mordovian (Moksha and Erzya) languages and their dialects. Information about the use of a group of these consonants in modern Moksha and Erzya word forms is also considered. Taking into account the research of the leading Finno-Ugric experts, the authors of the article express their opinion on the appearance of deaf sonorous consonants R, R’, L, L’, J used in the modern Moksha language along with the sonorous consonants r, r’, l, l’, j. The specific development of the Ural ŋ in the common Mordovian, Moksha and Erzya languages is described. Objective: to give a complete picture of the development of the ancient Ural sonorous consonants in the common Mordovian, Moksha and Erzya languages. Research materials: ancient system of sonorous consonants in the proto-Uralic language (data presented in the works of P. Sammallahti, Z. Keresztes, L. P. Gruzov, as well as in various dictionaries), and sonorous consonants in the common Mordovian, Moksha, and Erzya languages. Results and novelty of the research: the authors consider various points of view of well-known Finno-Ugric scholars (B. Collinder, L. Posti, P. Haidu, P. Sammalahti) about the presence of the system of sonorous in the proto-Uralic language; their development in the common Mordovian, Moksha and Erzya languages is studied. Particular attention is paid to the emergence of «deaf sonorous» consonants in the Moksha language, as well as the use of nasal ŋ in the Mordovian literary languages and their dialects. The study can be used for teaching the discipline «Historical grammar of Mordovian languages». The scientific novelty of the research is that the development of the system of sonorous consonants of the proto-Uralic language in the Mordovian languages is studied for the first time.

In this review, we provide an illustration of the idea discussed in the literature of using model compounds to study the effect of substitution of L- for D-amino acid residues in amyloid peptides. The need for modeling is due to the inability to study highly disordered peptides by traditional methods (high-field NMR, X-ray). At the same time, the appearance of such peptides, where L-amino acids are partially replaced by D-analogs is one of the main causes of Alzheimer’s disease. The review presents examples of the use diastereomers with L-/D-tryptophan in model process—photoinduced electron transfer (ET) for studying differences in reactivity and structure of systems with L- and D-optical isomers. The combined application of spin effects, including those calculated using the original theory, fluorescence techniques and molecular modeling has demonstrated a real difference in the structure and efficiency of ET in diastereomers with L-/D-tryptophan residues. In addition, the review compared the factors governing chiral inversion in model metallopeptides and Aβ42 amyloid.

The damage of cell membranes induced by photosensitive drugs has attracted the significant attention of researchers in various fields of medicine. Ketoprofen (KP) is known to be the most photosensitive among the nonsteroidal anti-inflammatory drugs. The phototoxic side effects of KP and other non-steroidal anti-inflammatory drugs are associated with the action of free radicals, but there is insufficient information about the nature of these radicals. In the present study, free radicals formed upon KP irradiation within lipid membranes were studied using nuclear magnetic resonance (NMR) and chemically induced dynamic nuclear polarization (CIDNP) methods, as well as a molecular dynamics simulation. Our study confirmed the effective penetration of KP into the lipid bilayer and showed a significant effect of the nature of the medium on the photolysis mechanism. While, in a homogeneous solution, the main channel of KP photolysis is free radical-mediated monomolecular decomposition with formation of radical pairs of benzyl and CO2H● radicals, then, in the lipid membrane, the reaction route shifts towards the bimolecular reaction of KP photoreduction. In addition, the effect of the presence an electron donor (the amino acid tryptophan) on lipid oxidation has been studied. It was found that photoreaction of KP with tryptophan proceeds more efficiently than with lipid molecules.

The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.

Optical isomers of short peptide Lysine-Tryptophan-Lysine (Lys-{L/D-Trp}-Lys) and Lys-Trp-Lys with an acetate counter-ion were used to study photoinduced intramolecular and intermolecular processes of interest in photobiology. A comparison of L- and D-amino acid reactivity is also the focus of scientists’ attention in various specialties because today, the presence of amyloid proteins with D-amino acids in the human brain is considered one of the leading causes of Alzheimer’s disease. Since aggregated amyloids, mainly Aβ42, are highly disordered peptides that cannot be studied with traditional NMR and X-ray techniques, it is trending to explore the reasons for differences between L- and D-amino acids using short peptides, as in our article. Using NMR, chemically induced dynamic nuclear polarization (CIDNP) and fluorescence techniques allowed us to detect the influence of tryptophan (Trp) optical configuration on the peptides fluorescence quantum yields, bimolecular quenching rates of Trp excited state, and the photocleavage products formation. Thus, compared with the D-analog, the L-isomer shows a greater Trp excited state quenching efficiency with the electron transfer (ET) mechanism. There are experimental confirmations of the hypothesis about photoinduced ET between Trp and the CONH peptide bond, as well as between Trp and another amide group.

Deferasirox is an orally active, lipophilic iron chelating drug used on thousands of patients worldwide for the treatment of transfusional iron overload. The essential transition metals iron and copper are the primary catalysts of reactive oxygen species and oxidative damage in biological systems. The redox effects of deferasirox and its metal complexes with iron, copper and other metals are of pharmacological, toxicological, biological and physiological importance. Several molecular model systems of oxidative damage caused by iron and copper catalysis including the oxidation of ascorbic acid, the peroxidation of linoleic acid micelles and the oxidation of dihydropyridine have been investigated in the presence of deferasirox using UV-visible and NMR spectroscopy. Deferasirox has shown antioxidant activity in all three model systems, causing substantial reduction in the rate of oxidation and oxidative damage. Deferasirox showed the greatest antioxidant activity in the oxidation of ascorbic acid with the participation of iron ions and reduced the reaction rate by about a 100 times. Overall, deferasirox appears to have lower affinity for copper in comparison to iron. Comparative studies of the antioxidant activity of deferasirox and the hydrophilic oral iron chelating drug deferiprone in the peroxidation of linoleic acid micelles showed lower efficiency of deferasirox in comparison to deferiprone.

Graphical abstract, Highlights • Glycyrrhizic acid (GA), saponin of licorice shows wide range of biological activity. • Mechanism of GA activity on the cell and molecular level is rarely discussed. • GA activity could be caused by the cell membrane modification., Glycyrrhizic acid is the main active component of Licorice root which has been known in traditional Chinese and Japanese medicine since ancient times. In these cultures glycyrrhizic acid (GA) is one of the most frequently used drugs. However, only in 21-st century a novel unusual property of the GA to enhance the activity of other drugs has been discovered. The review describes briefly the experimental evidences of wide spectrum of own biological activities of glycyrrhizic acid as well as discusses the possible mechanisms of the ability of GA to enhance the activity of other drugs. We have shown that due to its amphiphilic nature GA is able to form self-associates in aqueous and non-aqueous media, as well as water soluble complexes with a wide range of lipophilic drugs. The main purpose of our review is to focus reader's attention on physicochemical studies of the molecular mechanisms of GA activity as a drug delivery system (DDS). In our opinion, the most intriguing feature of glycyrrhizic acid which might be the key factor in its therapeutic activity is the ability of GA to incorporate into the lipid bilayer and to increase the membrane fluidity and permeability. The ability of biomolecules and their aggregates to change the properties of cell membranes is of great significance, from both fundamental and practical points of view.

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation.

Aim: Physicochemical and pharmacological study of the supramolecular inclusion complexes of the hypotensive drug nifedipine (NF) with the larch polysaccharide arabinogalactan (AG). Materials & methods: The NF:AG complexes were obtained and their physicochemical properties were studied. Their hypotensive action and pharmacokinetic profiles were evaluated in rats with normal and elevated arterial blood pressure. Results: In both rat lines the NF:AG complex decreased the arterial blood pressure at a lower dose than free NF (1.75 mg/kg of NF in complex compared with 3.5 mg/kg of free NF) and has a better pharmacokinetic profile than free NF. Conclusion: The use of the NF:AG complex is an effective way to sufficiently enhance and hasten NF’s hypotensive action.

Herein, we describe two novel strategies for the synthesis of esters, as achieved under high-speed ball-milling (HSBM) conditions at room temperature. In the presence of I2 and KH2PO2, the reactions afford the desired esterification derivatives in 45% to 91% yields within 20 min of grinding. Meanwhile, using KI and P(OEt)3, esterification products can be obtained in 24% to 85% yields after 60 min of grinding. In addition, the I2/KH2PO2 protocol was successfully extended to the late-stage diversification of natural products showing the robustness of this useful approach. Further application of this method in the synthesis of inositol nicotinate was also discussed.

Carotenoids are indispensable molecules for life. They are present everywhere in plants, algae, bacteria whom they protect against free radicals and oxidative stress. Through the consumption of fruits and vegetables and some carotenoid-containing fish, they are introduced into the human body and, similarly, protect it. There are numerous health benefits associated with the consumption of carotenoids. Carotenoids are antioxidants but at the same time they are prone to oxidation themselves. Electron loss from the carotenoid forms a radical cation. Furthermore, proton loss from a radical cation forms a neutral radical. In this mini-review, we discuss carotenoid radicals studied in our groups by various physicochemical methods, namely the radical cations formed by electron transfer and neutral radicals formed by proton loss from the radical cations. They contain many similar hyperfine couplings due to interactions between the electron spin and numerous protons in the carotenoid. Different EPR and ENDOR methods in combination with DFT calculations have been used to distinguish the two independent carotenoid radical species. DFT predicted larger coupling constants for the neutral radical compared to the radical cation. Previously, INDO calculations miss assigned the large couplings to the radical cation. EPR and ENDOR have aided in elucidating the physisorb, electron and proton transfer processes that occur when carotenoids are adsorbed on solid artificial matrices, and predicted similar reactions in aqueous solution or in plants. After years of study of the physicochemical properties of carotenoid radicals, the different published results start to merge together for a better understanding of carotenoid radical species and their implication in biological systems. Up until 2008, the radical chemistry in artificial systems was elucidated but the correlation between quenching ability and neutral radical formation was an inspiration to look for these radical species in vivo. In addition, the EPR spin-trapping technique has been applied to study inclusion complexes of carotenoids with different delivery systems.

Photoinduced elementary processes in chiral linked systems, consisting of drugs and tryptophan (Trp) residues, attract considerable attention due to several aspects. First of all, these are models that allow one to trace the full and partial charge transfer underlying the binding of drugs to enzymes and receptors. On the other hand, Trp fluorescence is widely used to establish the structure and conformational mobility of proteins due to its high sensitivity to the microenvironment. Therefore, the study of mechanisms of Trp fluorescence quenching in various systems has both fundamental and practical interest. An analysis of the photo-chemically induced dynamic nuclear polarization (CIDNP) and Trp fluorescence quenching in (R/S)-ketoprofen-(S)-tryptophan ((S/R)-KP-(S)-Trp) dyad carried out in this work allowed us to trace the intramolecular reversible electron transfer (ET) and obtain evidence in favor of the resonance energy transfer (RET). The fraction of dyad&rsquo, s singlet excited state, quenched via ET, was shown to be 7.5 times greater for the (S,S)-diastereomer than for the (R,S) analog. At the same time, the ratio of the fluorescence quantum yields shows that quenching effectiveness of (S,S)-diastereomer to be 5.4 times lower than for the (R,S) analog. It means that the main mechanism of Trp fluorescence quenching in (S/R)-KP-(S)-Trp dyad is RET.

Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in a medical practice especially for increasing the iron absorption and as an adjuvant therapeutic in the iron chelation therapy, but its mode of action and implications in the iron metabolism and toxicity are not yet clear. In this study, we used UV&ndash, Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ &harr, Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron&ndash, ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4&ndash, 5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.

Chemotherapy is currently the principal method for treating many malignancies. Thus, the development of improved antitumor drugs with enhanced efficacy and selectivity remains a high priority. Recent Advances: Anthracycline antibiotics (AAs), for example, doxorubicin, daunomycin, and mitomycin C, belong to an important family of antitumor agents widely used in chemotherapy. These compounds are all quinones. They are, thus, capable of being reduced by appropriate chemicals or reductases. One of their important properties is that under aerobic conditions their reduced forms undergo oxidation, with concomitant generation of reactive oxygen species (ROS), namely, superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals. The presence of metal ions is essential for the generation of ROS by AAs in biological systems.A fundamental shortcoming of the AAs is their high cardiotoxicity. We have proposed, and experimentally realized, a new type of quinones that is capable of coordinating metal ions. We have demonstrated in vitro that they can be reduced by electron transfer chains and glutathione with concomitant generation of ROS. They can also produce ROS under photo-excitation. The mechanisms of these reactions have been characterized by using nuclear magnetic resonance and electron paramagnetic resonance.To enhance their therapeutic effectiveness, and decrease cardiotoxicity and other side effects, we intend to conjugate the quinone chelators with monoclonal antibodies and peptide hormones that are specifically targeted to receptors on the cancer cell surface. Some such candidates have already been synthesized. An alternative approach for delivery of our compounds involves the use of specific peptide-based nanoparticles. In addition, our novel approach for treating malignancies is also suitable for photodynamic therapy. Antioxid. Redox Signal. 28, 1394-1403.

The saponin glycyrrhizin from liquorice root shows the ability to enhance the therapeutic activity of other drugs when used as a drug delivery system. Due to its amphiphilic properties, glycyrrhizin can form self-associates (dimers, micelles) and supramolecular complexes with a wide range of hydrophobic drugs, which leads to an increase in their solubility, stability and bioavailability. That is why the mechanism of the biological activity of glycyrrhizin is of considerable interest and has been the subject of intensive physical and chemical research in the last decade. Two mechanisms have been proposed to explain the effect of glycyrrhizin on drug bioavailability, namely, the increase in drug solubility in water and enhancement of the membrane permeability. Interest in the membrane-modifying ability of glycyrrhizic acid (GA) is also growing at present due to its recently discovered antiviral activity against SARS-CoV-2 Bailly and Vergoten (2020) [1]. In the present study, the passive permeability of the DOPC lipid membrane for the calcium channel blocker nifedipine was elucidated by parallel artificial membrane permeability assay (PAMPA) and full atomistic molecular dynamics (MD) simulation with free energy calculations. PAMPA experiments show a remarkable increase in the amount of nifedipine (NF) permeated with glycyrrhizin compared to free NF. In previous studies, we have shown using MD techniques that glycyrrhizin molecules can integrate into the lipid bilayer. In this study, MD simulation demonstrates a significant decrease in the energy barrier of NF penetration through the lipid bilayer in the presence of glycyrrhizin both in the pure DOPC membrane and in the membrane with cholesterol. This effect can be explained by the formation of hydrogen bonds between NF and GA in the middle of the bilayer.

Carotenoids are natural dyes and antioxidants widely used in food processing and in therapeutic formulations. However, their practical application is restricted by their high sensitivity to external factors such as heat, light, oxygen, metal ions and processing conditions, as well as by extremely low water solubility. Various approaches have been developed to overcome these problems. In particular, it was demonstrated that application of supramolecular complexes of “host-guest” type with water-soluble nanoparticles allows minimizing the abovementioned disadvantages. From this point of view, nanoencapsulation of carotenoids is an effective strategy to improve their stability during storage and food processing. Also, nanoencapsulation enhances bioavailability of carotenoids via modulating their release kinetics from the delivery system, influencing the solubility and absorption. In the present paper, we present the state of the art of carotenoid nanoencapsulation and summarize the data obtained during last five years on preparation, analysis and reactivity of carotenoids encapsulated into various nanoparticles. The possible mechanisms of carotenoids bioavailability enhancement by multifunctional delivery systems are also discussed.

Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (&lt, 0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na2GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO3. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by 1H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na2GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na2GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.

Glycyrrhizic acid (GA) is a triterpene glycoside extracted from licorice root. Due to its amphiphilicity GA is capable of forming complexes with a variety of hydrophobic molecules, substantially increasing their solubility. GA can enhance the therapeutic effects of various drugs. It was hypothesized that the increased bioavailability of the drug by GA is not only due to increased solubility, but also to enhancement of drug permeability through cell membranes. In this study the interaction of GA with POPC liposomes and model DOPC, POPC and DPPC bilayers was investigated by NMR with addition of shift reagents and MD simulations. This work helps to better understand the mechanism of enhanced drug bioavailability in the presence of GA. NMR and MD reveal that GA does penetrate into the lipid bilayer. NMR shows that GA changes the mobility of lipids. GA is predominantly located in the outer "half-layer" of the liposome and that the middle of the hydrophobic tails is the preferred location. GA freely passes through the bilayer surface to the inner part bringing a few water molecules. Also both approaches indicate pore formation in the presence of GA. The GA interaction with membranes is an additional aspect of the biological activity of GA-based drug delivery systems.

Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.

The presented study is devoted to monitoring the technical and technological state of electric power complex facilities. As part of the study, the basic principles of monitoring and examining the state of equipment were analyzed, the process and procedure for monitoring the status of equipment and structures of the electric power complex were examined. The work analyzed the periods of preparation for the heating season of the Russian electric power industry, as a result of which it was revealed that the number of violations at electric power facilities was increasing, and the equipment of the federal districts was not fully prepared for the heating season by the readiness index. The work revealed that for almost all indicators of heat supply, water supply and sanitation, the number of violations and incidents during the heating period is increasing. At the end of the study, measures were presented that will ensure the stability and reliability of energy supply to consumers.

The short-lived paramagnetic particles formed during the UV irradiation of nonsteroidal anti-inflammatory drug - ketoprofen (KP) have been investigated using chemically induced dynamic nuclear polarization (CIDNP). This study answers the questions about the nature of paramagnetic particles which can be responsible for KP phototoxic effects. Phototoxic side effects of NSAIDs, according modern point of view, are associated with the action of free radicals, however, there is insufficient information regarding the nature of the radical species. In contrast, most ketoprofen photodegradation schemes include carbanion as a precursor of products. CIDNP effects analysis has shown that all the major products of KP photodegradation can form via radical pairs (RPs) involving benzyl (2′), ketyl (3′) and CO2H or CO2− free radicals and solvated electron. Radical ways of KP photodegradation include: decarboxylation via RP with benzyl radical formation (I) in non-aqueous solution and both, (I) and photoreduction with formation of ketyl radicals in the presence of water. Moreover, it was found that the photoinduced radical decarboxylation of KP represents a reversible process.

Since carotenoids are highly hydrophobic, air- and light-sensitive hydrocarbon compounds, developing methods for increasing their bioavailability and stability towards irradiation and reactive oxygen species is an important goal. Application of inclusion complexes of "host-guest" type with polysaccharides and oligosaccharides such as arabinogalactan, cyclodextrins and glycyrrhizin minimizes the disadvantages of carotenoids when these compounds are used in food processing (colors and antioxidant capacity) as well as for production of therapeutic formulations. Cyclodextrin complexes which have been used demonstrated enhanced storage stability but suffered from poor solubility. Polysaccharide and oligosaccharide based inclusion complexes play an important role in pharmacology by providing increased solubility and stability of lipophilic drugs. In addition they are used as drug delivery systems to increase absorption rate and bioavailability of the drugs. In this review we summarize the existing data on preparation methods, analysis, and chemical reactivity of carotenoids in inclusion complexes with cyclodextrin, arabinogalactan and glycyrrhizin. It was demonstrated that incorporation of carotenoids into the "host" macromolecule results in significant changes in their physical and chemical properties. In particular, polysaccharide complexes show enhanced photostability of carotenoids in water solutions. A significant decrease in the reactivity towards metal ions and reactive oxygen species in solution was also detected.

The unilocular echinococcosis (hydatid disease)is the severe chronic parasitic disease, helminthiasis caused by the larval stage of the tapeworm Echinococcus granulosus, characterized by the development of parasitic cysts in the liver, rarely in the lungs and in other organs and tissues. The etiology of the disease, characterized by the pathogen and its development cycle, final and intermediate hosts, structure and morphology of the hydatid cyst. They describe the geographic distribution of helminth infections, pathogenesis, immunity, clinical picture, echinococcosis of the liver (asymptomatic, uncomplicated stage and stage of complications), echinococcosis of the lungs (the initial stage and the stage of developed clinical picture), other bodies. Clinical observation of unilocular echinococcosis in a 10 year old girl and a 9 year old boy. Diagnosis includes epidemiological, anamnestic and clinical data, changes in laboratory parameters, instrumental methods, diagnostic methods, immunodiagnostics, parasitological diagnosis. The surgery remains the main method of treatment. They described pharmacological therapy with albendazole in combination with a surgical method and as an involuntary self-treatment. A detailed clinical examination of patients after treatment, epidemiology of helminth infections and the major modern preventive measures.