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This work was focused on the role of silicon (Si) in amelioration of manganese (Mn) toxicity caused by elevated production of hydroxyl radicals (·OH) in the leaf apoplast of cucumber (Cucumis sativus L.). The plants were grown in nutrient solutions with adequate (0.5 μM) or excessive (100 μM) Mn concentrations with or without Si being supplied. The symptoms of Mn toxicity were absent in the leaves of Si-treated plants subjected to excess Mn, although the leaf Mn concentration remained extremely high. The apoplastic concentration of free Mn2+ and H2O2 of high Mn-treated plants was significantly decreased by Si treatment. Si supply suppressed the Mn-induced increased abundance of peroxidase (POD) isoforms in the leaf apoplastic fluid, and led to a rapid suppression of guaiacol-POD activity under excess Mn. The spin-trapping reagent 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide was used to detect ·OH by electron paramagnetic resonance spectroscopy. Although supplying Si markedly decreased the accumulation of ·OH in the leaf apoplast with excess Mn, adding monosilicic acid to the Mn2+/H2O2 reaction mixture did not directly affect the Fenton reaction in vitro. The results indicate that Si contributes indirectly to a decrease in ·OH in the leaf apoplast by decreasing the free apoplastic Mn2+, thus regulating the Fenton reaction. A direct inhibitory effect of Si on guaiacol-POD activity (demonstrated in vitro) may also contribute to decreasing the POD-mediated generation of ·OH. [ABSTRACT FROM PUBLISHER]

Abstract: The availability of sophisticated diagnostic methods such as MRI has contributed to the increased use of imaging technologies in therapy and diagnostic studies. However, gastrointestinal tract MRI generally shows poor results because of the lack of suitable contrast agents. The iron oxide is traditionally popular material for MRI gastrointestinal studies because of its well-known superparamagnetic properties. On the other hand, it has many disadvantages which include black bowel, side effects of diarrhea and, from an important analytical standpoint, the presence of artifacts arising from clumping. When paramagnetic iron concentrates, it may become ferromagnetic, drastically altering its imaging properties. Other paramagnetic species, represented by gadolinium, also seem to be potentially suitable agents for these studies. Nevertheless, this metal itself cannot be used in humans because of its toxic properties. Therefore, there is clearly a need for orally effective, well tolerated agents that can be used in humans for digestive imaging studies. This MRI contrast should be useful for visualizing the anatomy of the digestive tract and particularly to differentiate between normal and pathological states, such as tumors. The solution has been proposed as zeolites or smectites (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials could have problems of leakage of paramagnetic ions causing the appearance of the number side-effects. We propose the usage of the pillaring method for paramagnetic metal encapsulation in bentonites. By that way, paramagnetic cations like Fe+3, Mn+2 and Gd+3 are introduced between clay mineral layers as polyoxo cations. After calcination, these polyoxo cations grow to be pillars (oxides of these metals) which are incorporated into the clay mineral matrix which prevents ion-leaching and dangerous side-effects. In this study we show that paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal relaxation times of fluids in contact with the clay minerals. [Copyright &y& Elsevier]

The aim of the study was to establish whether hydroxyl radicals (•OH) were produced in UV-irradiated aqueous solutions of uranyl salts. The production of •OH was studied in uranyl acetate and nitrate solutions by an EPR spin trap method over a wide pH range, with variation of the uranium concentrations. The production of •OH in uranyl solutions irradiated with UV was unequivocally demonstrated for the first time using the EPR spin-trapping method. The production of •OH can be connected to speciation of uranium species in aqueous solutions, showing a complex dependence on the solution pH. When compared with the results of radiative de-excitation of excited uranyl (*UO22+) by the quenching of its fluorescence, the present results indicate that the generation of hydroxyl radicals plays a major role in the fluorescence decay of *UO22+. The role of the presence of carbonates and counter ions pertinent to environmental conditions in biological systems on the production of hydroxyl radicals was also assessed in an attempt to reveal the mechanism of *UO22+ de-excitation. Various mechanisms, including •OH production, are inferred but the main point is that the generation of •OH in uranium containing solutions must be considered when assessing uranium toxicity. [ABSTRACT FROM AUTHOR]

Abstract: The hydroxyl radical ( OH) has detrimental biological activity due to its very high reactivity. Our experiments were designed to determine the effects of equimolar concentrations of glucose, fructose and mannitol and three phosphorylated forms of fructose (fructose-1-phosphate (F1P); fructose-6-phosphate (F6P); and fructose-1,6-bis(phosphate) (F16BP)) on OH radical production via the Fenton reaction. EPR spectroscopy using spin-trap DEPMPO was applied to detect radical production. We found that the percentage inhibition of OH radical formation decreased in the order F16BP>F1P>F6P>fructose>mannitol=glucose. As ketoses can sequester redox-active iron thus preventing the Fenton reaction, the Haber–Weiss-like system was also employed to generate OH, so that the effect of iron sequestration could be distinguished from direct OH radical scavenging. In the latter system, the rank order of OH scavenging activity was F16BP>F1P>F6P>fructose=mannitol=glucose. Our results clearly demonstrate that intracellular phosphorylated forms of fructose have more scavenging properties than fructose or glucose, leading us to conclude that the acute administration of fructose could overcome the body’s reaction to exogenous antioxidants during appropriate therapy in certain pathophysiological conditions related to oxidative stress, such as sepsis, neurodegenerative diseases, atherosclerosis, malignancy, and some complications of pregnancy. [Copyright &y& Elsevier]

Abstract: An analysis of the H2O2-induced breakdown and transformation of different keto-monosaccharides at physiological concentrations reveals that glycolate and other short-chained carbohydrates and organic acids are produced. Depletion of monosaccharides and glycolate synthesis occurs at increased rates as the length of the carbohydrate chain is decreased, and is significantly increased in the presence of trace amounts of Fe2+ ions (10μM). Rates of monosaccharide depletion (initial concentration of 3mM) observed were up to 1.55mmolh−1 in the case of fructose, and 2.59mmolh−1 in the case of dihydroxyacetone, depending upon pH, H2O2 concentration, temperature and the presence or absence of catalytic amounts of Fe2+. Glycolate was produced by dihydroxyacetone cleavage at rates up to 0.45mmolh−1 in the absence, and up to 1.88mmolh−1 in the presence of Fe2+ ions (pH8). Besides glycolate, other sugars (ribose, glyceraldehyde, glucose), glucitol (sorbitol) and organic acids (formic and 2-oxogluconic acid) were produced in such H2O2-induced reactions with fructose or dihydroxyacetone. EPR measurements demonstrated the participation of the OH radical, especially at higher pH. Presence of metal ions at higher pH values, resulting in increased glycolate synthesis, was accompanied by enhanced hydroxyl radical generation. Observed changes in intensity of DEPMPO-OH signals recorded from dihydroxyacetone and fructose reactions demonstrate a strong correlation with changes in glycolate yield, suggesting that OH radical formation enhances glycolate synthesis. The results presented suggest that different mechanisms are responsible for the cleavage or other reactions (isomerisation, auto- or free-radical-mediated oxidation) of keto-monosaccharides depending of experimental conditions. [Copyright &y& Elsevier]

Plant plasma membranes are known to produce superoxide radicals, while the production of the hydroxyl radical, previously detected in complex plant tissues, is thought to occur in the cell wall. The mechanism of production of superoxide radicals by plant plasma membranes is, however, under dispute. It is shown, using electron paramagnetic resonance spectroscopy with a 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide spin-trap capable of differentiating between radical species, that isolated purified plasma membranes from maize roots produce hydroxyl radicals besides superoxide radicals. The results argue in favour of superoxide production through an oxygen and diphenylene iodonium-sensitive, NADH-dependent superoxide synthase mechanism, as well as through other unidentified mechanism(s). The hydroxyl radical is produced by an oxygen-insensitive, NADH-stimulated mechanism, which is enhanced in membranes in which the superoxide synthase is incapacitated by substrate removal or inhibition. [ABSTRACT FROM PUBLISHER]

Honey bees play a pivotal role in shaping ecosystems and sustaining human health as both pollinators and producers of health‐promoting products. However, honey bee colony mortality is on the rise globally, driven by various factors, including parasites, pesticides, habitat loss, poor nutrition, and climate change. This has far‐reaching consequences for the environment, economy, and human welfare. While efforts to address these issues are underway, the current progress in electron paramagnetic resonance (EPR) instrumentation affords using the immense potential of this magnetic resonance technique to study small samples such as honey bees. This paper presents the pioneering 2D in vivo EPR imaging experiment on a honey bee, revealing the ongoing redox‐status of bees' intestines. This way, by monitoring the spatio‐temporal changes of the redox‐active spin‐probes' EPR signal, it is possible to gain access to valuable information on the course of ongoing bees' pathologies and the prospect of following‐up on the efficiency of applied therapies. Employing a selection of diverse spin‐probes could further reveal pH levels and oxygen concentrations in bee tissues, allowing a noninvasive assessment of bee physiology. This approach offers promising strategies for safeguarding pollinators and understanding their biology, fostering their well‐being and ecological harmony. Research Highlights: Honey bees face rising mortality from parasites, pesticides, and climate change. This paper introduces original use of in vivo electron paramagnetic resonance imaging (EPRI) method to explore redox processes in honey bee intestines, advancing our understanding of these vital insects' health. [ABSTRACT FROM AUTHOR]

Para-aminodiphenylamine (p-ADPA) was successfully polymerized by simple, economical and environmentally improved procedure. Magnetite nanoparticles (Fe 3 O 4 NPs) were found to successfully catalyze the oxidation of p-ADPA in the presence of hydrogen peroxide (H 2 O 2), an eco-friendly and clean oxidant, with a very small amount of ammonium peroxydisulfate (APS) as an initiator. In this manner, the amount of by-products occurring during the reaction is drastically reduced. The oxidation of p-ADPA proceeded also in the absence of Fe 3 O 4 NPs, but far more slowly than the catalyzed process. The influence of the mass ratio Fe 3 O 4 NPs/p-ADPA on the properties of products was systematically studied by different characterization techniques. Spectroscopic measurements (UV-Vis-NIR, FTIR, Raman, EPR) indicate that the polymerization products are polyaniline emeraldine salt-like polymers and their measured electrical conductivity is one of the highest values reported in the literature for p-ADPA oligomerization/polymerization products (1.8∙10-2 S cm-1). X-ray powder diffraction (XRPD) measurements revealed highly crystalline structure of Poly(p-ADPA) samples synthesized with Fe 3 O 4 NPs, while scanning electron microscopy (SEM) showed layered and prismatic-shaped particles as prevailing in their morphology. [ABSTRACT FROM AUTHOR]

• Magnetite nanoparticles (Fe3O4 NPs) were successfully used as a catalyst for aniline polymerization. • For aniline oxidation environmentally-friendly oxidant hydrogen peroxide was used. • Electroconducting polyaniline (PANI) in good yield was synthesized using small amount of Fe3O4 NPs. • Without Fe3O4 NPs, under the same other conditions, the reaction did not give PANI. • Effect of Fe3O4 NPs/aniline mass ratio and the reaction time on properties of PANI was studied. Nowadays, there is a growing interest to find environmentally-friendly, simple and economical routes for the synthesis of polyaniline (PANI), one of the most important conducting polymers. For the oxidative polymerization approach hydrogen peroxide (H 2 O 2) is highly recommended oxidant due to ecological aspects, since the product of its reduction is only water. However, its usage as an oxidant, aimed to produce conductive PANI with reasonable reaction rate, needs a catalyst. Here we report the preparation of conductive PANI in good yield by the oxidative polymerization of aniline using magnetite nanoparticles (Fe 3 O 4 NPs) as a catalyst and H 2 O 2 as an oxidant, with added very small amount of ammonium peroxydisulfate as the initiator. Synthesized Fe 3 O 4 NPs (size 10–50 nm) were characterized by X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). It was found that without Fe 3 O 4 NPs, under otherwise same conditions, the reaction product is not PANI. The effect of mass ratio Fe 3 O 4 NPs/aniline and polymerization time on the structure and physicochemical properties of prepared PANI was studied by various techniques. FTIR, Raman, UV–vis-NIR and electrical conductivity measurements confirmed the existence of conducting emeraldine salt form of PANI. XRPD revealed unchanged crystalline structure of Fe 3 O 4 NPs upon polymerization and semi-crystalline structure of PANI. EPR spectra showed peaks assigned to PANI and Fe 3 O 4 NPs. Described simple, environmentally improved synthetic route opens possibilities for the syntheses of conductive PANI-like polymers from other aromatic amines by using environmentally-friendly oxidant H 2 O 2 and Fe 3 O 4 NPs catalyst which can replace more expensive catalysts such as peroxidase enzymes. [ABSTRACT FROM AUTHOR]

Introduction: Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. The authors conducted this pilot study based n large number of patients reports that they were less anxious and felt better overall by migrating to sunnier environments. Aim: We estimated the impact of the total sunshine hours per month on daily exposure of the population to benzodiazepine anxiolytic on a monthly basis in the Republic of Serbia. Material and Methods: We conducted a retrospective academic IV phase study, which tested the correlation of time series of monthly sold benzodiazepine anxiolytics in pharmacies and total sunshine hours per month in the Republic of Serbia, from January 2014 to May 2019. Results: According to the seasons, we did not find any difference in the increase of the population exposure to benzodiazepines. A difference was found between bromazepam consumption compared to cumulative monthly. Bromazepam consumption was negatively correlated with the cumulative monthly sunshine hours. The cutoff value for bromazepam was 131.45 cumulative monthly sunshine hours. Conclusion: This is the first pharmaco-epidemiologic study to prove that the population’s exposure to benzodiazepines, in addition to the implicit health and economic effects on physicians’ prescribing habits for these drugs, can be independently linked to the cumulative effects of monthly sunshine hours on the population. No difference in benzodiazepine consumption was found in relation to the seasons (spring/summer vs autumn/winter). In months where sunshine hours was ≥135.45, the need for bromazepam was significantly reduced. Seasonal variation of climatic effects of total monthly sunshine hours is significantly correlated with the population’s need for benzodiazepines with anxiolytic effects longer than 12 hours. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is a naturally occurring element which is ubiquitous in the environmentcomprising 0.1% of the Earth’s crust. Mn is an essential micronutrient for plant growth with awide range of important physiological functions. Its availability in soil is directlyproportional to pH and redox potential, so the reducing conditions (poorly drained and acidicsoils) increase Mn bioavailability, uptake and tissue accumulation leading to toxicitysymptoms such as chlorosis and brown spots, initially visible on older leaves. Although it iswell established that silicon (Si) greatly improves Mn tolerance of many plant species, thephysiological and molecular mechanism of this effect is poorly understood. In this regard, theeffect of Si, when supplied as 1.5 mM silicic acid, on the plant growth and theappearance of Mn-toxicity symptoms in the leaves of cucumber plants (Cucumis sativusL. cv. Chinese long) grown at Mn excess (100 μM) was studied. In Mn treatedplants, Si improved biomass production and alleviated symptoms of Mn toxicitycompared with non-Si treated plants. Although bulk tissue Mn concentrations weresimilar in Si treated and non-treated plants, the apoplastic concentration of freeMn2+ and H2O2 of Mn-treated plants was signi?cantly decreased by Si treatment.These results suggest that Si nutrition does affect neither the metal uptake nor itstranslocation from root to shoot. Inert depositions of Si in the leaf cell walls of cucumber(known as Si-accumulating species), that enhanced cell wall stability, simultaneouslyare Mn2+-binding sites which contribute to decrease of harmful free Mn activitywithin the plant tissue. The effect of Si nutrition on the compartmentation of leaf Mnwas also veri?ed by the less destructive electron paramagnetic resonance (EPR)spectroscopy. Application of Si slightly decreased an EPR signal of free Mn2+ fromthe apoplastic ?uid and bulk tissue of plants subjected to high Mn concentrations.Hydroxyl radicals (OH) were recorded by EPR spin-trapping method using a reagentDEPMPO, where intensity of the EPR signals of DEPMPO/OH adducts of Si treatedplants was lower regardless of the Mn supply. Additionally, Si supply led to a rapidsuppression of guaiacol-POD activity under excess Mn in the leaf apoplastic ?uid whichwas visually confirmed by isoelectric focusing. Taking into account this Mn-Siinteraction, phytoextraction process on sites contaminated with Mn could be significantlyimproved by Si application. Unfortunately, most metal hyperaccumulator plantsare characterized with slow growth rate and low biomass. Addition of Si couldelevate their biomass production combined with metal-toxicity protection withoutaffecting metal uptake and the long-distance root to shoot translocation, so theexcess Mn from the soil could be easily removed by harvesting shoot biomass. [ABSTRACT FROM AUTHOR]

Introduction: Tretinoin has a variety of skin-beneficial properties. However, when used at the dosages required to get the best outcomes, it also has significant adverse effects. Aim: Side-effects caused by tretinoin could be avoided or minimized by integratingit into lecithin liposomes, which have long-term stability and the ability to penetrate into the deep layers of skin. Material and Methods: Electron paramagnetic resonant spectroscopy imaging (EPRI) was used to study deep skin penetration of hydrogenated lecithin liposomes containing tretinoin, into the porcine skin. To make liposomes EPR-detectable, they were spin-labeled using 16-doxylstearic acid. This paper is a part of an academic (non commercial) study. Results and Conclusion: EPRI proved to be a powerful technique for tracking the spatial distribution of liposomes in the tissue (skin), with the potential to be applied in pharmaceutical trials. To the best of our knowledge, herein it was used for the first time to track the distribution of tretinoin liposomes through the skin. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are a class of plant hormones that play important roles in regulating various physiological and developmental processes in plants. One of the most effective BRs involved in modulating crop growth is 24-epibrassinolide (24-EBL). The effects of different concentrations of 24-EBL on various biochemical and biophysical parameters critical to early growth stages and seedling development were investigated using two maize hybrids, 'ZP 434' (a new-generation hybrid) and 'ZP 704' (an older-generation hybrid). The evaluation of results is based on measurements of germination percentage, morphometric parameters, redox status, comparative analysis of thermodynamic parameters (such as Gibbs free energy, enthalpy, entropy), and the concentration of specific sugars in different parts of maize seedlings. The results indicate that the germination and initial growth of maize seedlings are influenced by the flow of crucial sugars from the remaining seed (as a source of nutrients) towards the plumule and radicle (as sink organs). Furthermore, alterations in Gibbs free energy play a significant role in these sugar transfers within the maize seedlings. The seed germination was most affected by the highest concentrations of 24-EBL, showing inhibitory effects, whereas lower and moderate concentrations of exogenously added 24-EBL exhibited a beneficial influence on the initial phases of seedling growth. The mentioned approach gives new insights into source–sink relationships and can be used as a quantitative measure of the germination energy, which until now has been a qualitative criterion in seed science. [ABSTRACT FROM AUTHOR]

Glassy carbon electrode was modified with different synthesized hybrid clay-based materials and tested in alkaline solution with and without H 2 O 2 . The hybrid materials were obtained by immobilizing hemoglobin (Hb) on acid activated (AA) clay, or on AA clay modified with different sodium dodecyl sulfate (SDS) loadings. The obtained materials were characterized using DR UV–vis and ESR spectroscopy, elemental analysis, and SEM. The characterization confirmed higher degree of hemoglobin incorporation in the presence of SDS. The presence of SDS on the surface of clay particles resulted in the partial oxidation/denaturation of hemoglobin and formation of hemichrome. Cyclic voltammetry was used for the investigation of the electrochemical behavior of immobilized hemoglobin in alkaline solution. Two cathodic peaks at −0.45 V and −0.70 V were recorded and ascribed to the reduction of heme Fe(III)/Fe(II), and formation of HbFe(I) – highly reduced form of hemoglobin − respectively. The latter peak reflects hemoglobin denaturation. The presence of H 2 O 2 in the alkaline solution increased current intensities corresponding to both peaks (−0.45 V and −0.7 V). Linear response of peak current intensity vs. H 2 O 2 concentration was monitored for all investigated samples within different H 2 O 2 concentration ranges. The AA-SDS1.0-Hb electrode exhibited the highest current response with linear regression equation in the following form: I(μA) = 7.99 + 1.056 × [H 2 O 2 ] (mM) (R = 0.996). The limit of detection of 28 μM was estimated using the 3 sigma method. Different modified electrodes exhibited different degrees of denaturation resistance. The obtained values of Michaelis-Menten constant indicated that prolonged cycling in the presence of SDS increases protein denaturation. [ABSTRACT FROM AUTHOR]

Catechins are transformed into dinitrosocatechins (diNOcats) and then oxidized to the quinones by salivary nitrite under conditions simulating the stomach. This manuscript deals with formation of stable radicals in the NO group of diNOcat during nitrite-induced oxidation of (+)-catechin and diNOcat at pH 2. We postulated two mechanisms for the stable radical formation; one is nitrous acid-induced oxidation of diNOcat in the A-ring, and the other intermolecular charge transfer from the A-ring of diNOcat and/or diNOcat quinone to the quinone moiety of the B-ring of diNOcat quinone. In addition, an unstable phenoxyl radical, which might be transformed into quinone, was also produced, accompanying the formation of the stable radical on the NO group. Taking the above results into account, we mainly focus on the adverse effects of the radicals and quinone, which may be produced from (+)-catechin in the stomach under the conditions of high salivary nitrite concentrations. [ABSTRACT FROM AUTHOR]

Introduction: Liposomes are small, spherical artificial vesicles that can be created from cholesterol and natural non-toxic phospholipids. Due to their size, hydrophobic and hydrophilic character (besides biocompatibility), liposomes are promising drug delivery systems. Topic: Liposomal formulations of non-steroidal anti-inflammatory drugs (NSAIDs) can be used in all population groups (children, adults, and the elderly) which gives them a wide range of applications. NSAIDs oral administration is associated with severe adverse effects in the gastrointestinal tract such as epigastric pain, heartburn, nausea, diarrhea, vomiting, peptic ulcer, and hepatic impairment. It has been observed in clinical trials, that liposomal formulations enhanced the drug permeability and the percentage of accumulated dose in the skin compared to control conventional gel formulations. Liposomal gel controls ibuprofen release and drug permeability in vitro and has shown a permeability pattern conducive to maintaining constant drug levels. Application: So far, liposomes containing sodium diclofenac, indomethacin, aceclofenac, and related NSAIDs have been produced in laboratory conditions. Liposomal technology is most commonly applied in cosmetology, cancer therapy and yet unexplored application possibilities for liposomes, such as therapy for Alzheimer’s disease. Although varying in size and structure, they all possess certain common advantages – increased dermal availability of lipophilic drugs and their targeted delivery onto the required location. Liposomes have been proven highly effective in terms of retaining the NSAIDs in the synovial cavity, mostly because of their size and chemical composition. Undesirable therapy effects, fast clearance, and exposure to nontargeted sites could be minimized by administering NSAIDs using liposomes as carriers. Side effects and complications associated with the long-term oral and intramuscular applications of NSAIDs could especially be avoided using their liposomal formulations. Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects, improving bioavailability and patient compliance. A few NSAIDs are experimentally formulated in liposomes having improved pharmacokinetic characteristics. Further clinical investigations will show their pharmaco-dynamic effects. The in vitro release and ex vivo permeation (permeability) study showed a prolonged diclofenac release with high permeation flux. Conclusion: The use of liposomes as drug carriers becomes a notable positive step in the treatment of inflammatory, pain-causing, and rheumatic diseases. Liposomes present an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address the different delivery considerations. The main objectives for the development of NSAIDs in liposomal carriers are deeper penetration of the active substance, fewer side effects, better and longer effect, the ability to change the characteristics of both the drug and the carrier, and adequate dose adjustment. Despite several challenges that accordingly still need to be addressed, liposomal drug formulations have significant health-promoting potential. Despite the encouragement of NSAID development and research studies, it still takes a long time for liposomal NSAID formulations to become available for everyday use. [ABSTRACT FROM AUTHOR]

We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O 2 •−), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy-limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N -acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH 4 Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy. [Display omitted] • Graphene quantum dots (GQD) protect SH-SY5Y cells from sodium nitroprusside (SNP). • GQD inhibit SNP-induced apoptotic death of SH-SY5Y neuronal cells. • Quenching of NO and.•OH contributes to GQD-mediated protection from SNP toxicity • GQD induce autophagy associated with reduced Akt/mTOR signaling. • GQD-induced autophagy is cytoprotective independently of their antioxidant activity. [ABSTRACT FROM AUTHOR]

Introduction: Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. Since these drugs have a potential for rapid anxiolytic effect and sedation, as well as driver capability impairment, there is a lack data of safety of benzodiazepines in traffic accidents. The aim: To make an assessment of the interconnection of time series of traffic accidents outcomes with time series of benzodiazepine anxiolytic consumption in the Republic of Serbia. Methods: This paper is a part of IV phase academic study regarding the factors potentially affecting benzodiazepine consumption and effects. We conducted a pharmaco-epidemiological time series analysis study of monthly sold benzodiazepine anxiolytics in pharmacies and indicators of the crush road outcome on a monthly basis in the Republic of Serbia. The research was performed from January 2014 to December 2018. Results: Applying ARIMAX modeling we found a significantly link between DID of alprazolam with monthly total traffic accident, a high stochastic regression positive association of DID of diazepam with the dependent variable monthly total traffic accident, the prediction of monthly fatalities of traffic accident or traffic accident with severe or slight injuries per total traffic accident we have demonstrated positive influence of DID of alprazolam in second-order autoregressive and moving average model with constant. In prediction of monthly fatalities traffic accident, a significant positive influence of DID of benzodiazepines (all together) in auto-regression model without constant was demonstrated. Conclusion: Consumption of both long-acting (over 12 h) and short-acting benzodiazepines together with all other causes highly determined the total number of traffic accidents on a monthly basis in 2014-2018 in the Republic of Serbia. An assessment of the interconnection of time series of traffic accidents outcomes with time series of benzodiazepine anxiolytic consumption in the Republic of Serbia we found a significant positive influence of DID of benzodiazepines on traffic accidents outcomes. In total, all used benzodiazepines increase the number of fatal traffic accidents by 8.5 fold per month. Alprazolam additionally contributed with about ten percent (9.7%) to the frequency of traffic accidents on a monthly basis. Measures to prevent traffic accidents at all levels should be effective immediately in order to achieve positive results timely. The authors suggest that the great responsibility is rais- ing awareness of compliance with traffic regulations with doctors who prescribe benzodiazepines. [ABSTRACT FROM AUTHOR]

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet–visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy. [ABSTRACT FROM AUTHOR]

Liposomes are promising drug's delivery systems due to decreased toxicity of the liposome-encapsulated drug, but wider clinical application requires their more efficient tumor targeting with uptake, controlled drug release and higher shelf life. The unique metabolic characteristics of cancer cells based on higher demand for energy and therefore increased glucose utilization were exploited in the design of glucose modified liposomes (GML) with the aim to provide increased tumor targeting via glucose transporters and increased ability of drug delivery into tumor cells. Tumor accumulating potential of GML and non-glucose liposomes (NGL) were investigated on CT26 and LS174T tumor-bearing mice by simple and reliable radiotracer method using 177Lu as radioactive marker. Both liposomes, GML and NGL were radiolabeled in high radiolabeling yield, showing high in vitro stability in biological media, as the main prerequisite for the biodistribution studies. Tumors displayed significantly better accumulation of 177Lu-GML with the maximum uptake 6 h post-injection (5.8 ± 0.2%/g in LS174T tumor and 5.1 ± 0.5%/g in CT26 tumor), compared to negligible uptake of 177Lu-NGL (0.6 ± 0.1%/g in LS174T tumor and 0.9 ± 0.2%/g in CT26 tumor). Results of comparative biodistribution studies of 177Lu-NGL and 177Lu-GML indicate that increased accumulation of GML is enabled by glucose transporters and subsequent endocytosis, resulting in their prolonged retention in tumor tissues (up to 72 h). Direct radiolabeling of liposomes with 177Lu may be used not only for biodistribution studies using radiotracking, but also for cancer treatment. [Display omitted] • Glucose modified liposomes show potential as cancer targeting drug delivery system. • Simple labeling procedure with 177Lu allows for precise in vivo/vitro measurements. • Significantly larger tumor uptake compared to control group. • Possible theranostic application in combination with drugs and/or radioisotopes • Straightforward procedure for glucose functionalization of liposomes [ABSTRACT FROM AUTHOR]

Introduction: Comprising of a unique combination of bioactive polyphenol compounds, grapes are shown to have a beneficial effect on the skin as well as the whole body. They exhibit high antioxidative and antiradical activity through mechanisms of heavy metals chelation, scavenging reactive oxygen species, inhibiting lipid peroxidation, and preserving the integrity of the cell membranes. In the winemaking industry, after crushing and pressing, grape pomace (stems, seeds, pulp, and skin) is removed as a by-product. This valuable source of bioactive compounds is often treated as animal food, compost, raw material in the brewery, but unfortunately mostly disposed of as unusable waste. Aim: The aim of this study was to compare redox properties of absolute EtOH, 50% EtOH, and H2 O grape wine skin extracts in a way of scavenging DPPH radicals, showing that biowaste obtained from grape wineskins could be used as an immense source of bioactive compounds with high antiradical activity. Material and Methods: Electron Paramagnetic Resonance (EPR) spectroscopy was used to detect the activity of grape skin extracts toward DPPH radicals and UHPLC-DAD MS/MS analysis to separate, identify and quantify their active components. Results: The results show that Cabernet Sauvignon and Pinot Blanc grape skin extracts have unexpectedly large potential to remove DPPH radicals from the system. Having in mind the concentration of redox-active components obtained by UHPLC-DAD MS/MS analysis and presented EPR results, there is strong evidence that primarily quercetin 3-O-glucoside, as well as kaempferol 3-O-glucoside, isorhamnetin 3-O-glucoside, kaempferol 7-O-glucoside supplemented with catechin and rutin are responsible for the antioxidative capacity of extracts. Conclusions: This study demonstrates that extracts obtained from grape skins, initially intended as biowaste, exhibit high antiradical activity. The largest quantity of the most redox-active components could be found in 50% EtOH extracts, which we propose to be the starting material for making potent redox-active cosmetic products and dietary supplements. [ABSTRACT FROM AUTHOR]

In this paper, the relationship of structure, type of oxygen defects, valence states of Cr and Ru, and electrochemical properties of La 0.7 Sr 0.3 Cr 1-X Ru X O 3 (0 < x < 0.1) perovskite-type oxides were studied. The samples were synthesized by a conventional solid-state reaction method and characterized by powder X-ray diffraction, X-ray fluorescence spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and electron paramagnetic resonance spectroscopy. The electrochemical performance of these samples was evaluated towards the detection of 4-nitrophenol and strongly depends on the concentration of ruthenium incorporated in the crystal lattice. A new La 0.7 Sr 0.3 Cr 0.925 Ru 0.075 O 3 electrocatalyst with a wide linear concentration range (25–5000 mM) and a detection limit of 8 mM was obtained. These results provide an opportunity for its application in the analysis of real water samples. Image 1 • The orthorhombic perovskite structure and phase formation were confirmed by X-ray diffraction. • The crystallite size is no significant change with the increase of Ru content. • The limit of detection of La 0.7 Sr 0.3 Cr 1-x Ru x O 3 (x = 0.075) is 8 μM. • Perovskite with Ru (x = 0.075) showed a very broad linear range with a satisfactory limit of detection. • La 0.7 Sr 0.3 Cr 1-x Ru x O 3 (x = 0.075) can be considered a good sensor for detection 4-nitrophenol. [ABSTRACT FROM AUTHOR]

TiO2 prolatenanospheroids (PNSs) may be photosensitizers (PSs), which act by catalyzation of hydroxyl radical (∙OH) formation upon light illumination. ∙OH might, in turn, contribute to killing of cancer cells. On the other hand, there is great concern about toxicity in the dark of TiO2 nanoparticles in general. In this work, we have investigated the biocompatibility of TiO2 PNSs of the anatase crystal form (length between 100 and 300 nm and width 50 nm) in the dark with immune cells and light-induced cytotoxicity on several cancer cell lines. The effects of the treatment of different cell lines with several concentrations of TiO2 PNSs suspensions showed the specifics of cells' viability and the intracellular localization. The results of in vitro studies obtained by cytotoxicity assays adjusted to individual cell lines' metabolism point towards the biocompatibility of TiO2 PNSs at low and moderate concentrations in the dark, which neither kill the cells, nor induce activation of the immune system cells. Laser scanning confocal microscopy revealed that PNSs are taken up by cells, and insight into the intracellular distribution was obtained in this study. [ABSTRACT FROM AUTHOR]

Pure and a series of Fe3+ doped zirconia nanopowders were synthesized combining colloidal chemistry and solvothermal method from organometallic precursors in order to correlate doping and properties of zirconia matrix. After annealing of washed nanopowders at 600 °C, detailed characterization was performed using X-ray diffraction, UV/Vis absorption and luminescence, infrared and electron paramagnetic spectroscopy, transmission electron microscopy and BET measurements. Zirconia samples had mixed monoclinic and tetragonal crystalline phase; increasing Fe3+ ions concentration was followed by increasing of tetragonal phase share. In the sample with highest Fe3+ concentration, hematite can be detected. Also, UV/Vis spectrophotometry showed that Fe3+ doping lowers effective band gap of zirconia matrix from 4.5 eV (bulk value) to 2.1 eV for doped/nanocomposite samples. EPR measurements proved presence of dopant and showed that isolated Fe3+ ions in zirconia matrix exist in both crystalline phases; monoclinic and tetragonal (g ~ 4.8 and g ~ 4.27–4.2, respectively) surroundings. Zirconia samples were also successfully used as photocatalysts for photocatalytic degradation of 2, 4, 6, trichlorophenol. [ABSTRACT FROM AUTHOR]

In Medicago truncatula , nitrate, acting as a signal perceived by NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER FAMILY 6.8 (MtNPF6.8), inhibits primary root growth through a reduction of root cell elongation. Since reactive oxygen species (ROS) produced and converted in root tip (O 2 •− → H 2 O 2 → •OH) have been reported to control cell elongation, the impact of nitrate on the distribution of these ROS in the primary root of M. truncatula was analyzed. We found that nitrate reduced the content of O 2 •−, H 2 O 2 and •OH in the root tip of three wild type genotypes sensitive to nitrate (R108, DZA, A17), inhibition of root growth and O 2 •− accumulation being highly correlated. Nitrate also modified the capacity of R108 root tip to produce or remove ROS. The ROS content decrease observed in R108 in response to nitrate is linked to changes in peroxidase activity (EC1.11.1.7) with an increase in peroxidative activity that scavenge H 2 O 2 and a decrease in hydroxylic activity that converts H 2 O 2 into •OH. These changes impair the accumulation of H 2 O 2 and then the accumulation of •OH, the species responsible for cell wall loosening and cell elongation. Accordingly, nitrate inhibitory effect was abolished by externally added H 2 O 2 or mimicked by KI, an H 2 O 2 scavenger. In contrast, nitrate has no effect on ROS production or removal capacities in npf6.8-2, a knockdown line insensitive to nitrate, affected in the nitrate transporter MtNPF6.8 (in R108 background) by RNAi. Altogether, our data show that ROS are mediators acting downstream of MtNPF6.8 in the nitrate signaling pathway. Image 1 • Nitrate triggers a decrease in ROS content in primary root tip of sensitive genotypes. • Nitrate inhibition of both root growth and O 2.•− accumulation are correlated • The decrease in ROS induced by nitrate is orchestrated by cell wall peroxidase. • Nitrate has no effect on ROS content in primary root tip of npf6.8-2 knockdown line. • ROS mediate the nitrate signal downstream of the nitrate transporter MtNPF6.8 [ABSTRACT FROM AUTHOR]

Raman scattering (RS), Fourier transform infrared (FTIR) and electron paramagnetic resonance (EPR) spectroscopic measurements on β -MnO 2 and α -K x MnO 2 nanorods were performed. The infrared spectrum of β -MnO 2 is sensitive towards the particle sizes, while the Raman spectrum is sensitive towards the presence of nonstoichiometric and disordered MnO 2- δ on the surface of nanorods. EPR measurements show the appearance of two types of Mn 4+ ions having different local environment: (i) Mn 4+ ions in Mn 4+ -rich environment and (ii) Mn 4+ ions in mixed-valence Mn 4+ /Mn 3+ environment that match up with region of nonstoichiometric MnO 2- δ . Observed bands in vibrational spectra of tetragonal hollandite-type α -K x MnO 2 are considered to be mainly due to the vibration modes of Mn O frameworks. The EPR spectra of α -K x MnO 2 nanorods contain two signals that can be attributed to Mn 4+ ions in Mn 4+ -rich environment and Mn 4+ ions in mixed-valence Mn 4+ /Mn 3+ environment close to K + ions. [ABSTRACT FROM AUTHOR]

Although chlorogenic acid ( 5CQA ) is an important ingredient of various foods and beverages, mechanisms of its antioxidative action have not been fully clarified. Besides electron spin resonance experiment, this study includes thermodynamic and mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and single electron transfer – proton transfer (SET-PT) mechanisms of 5CQA in benzene, ethanol, and water solutions. The calculations were performed using the M06-2X/6-311++G(d,p) level of theory and CPCM solvation model. It was found that SET-PT is not a plausible antioxidative mechanism of 5CQA . RAF pathways are faster, but HAT yields thermodynamically more stable radical products, indicating that in acidic and neutral media 5CQA can take either HAT or RAF pathways. In basic environment (e.g. at physiological pH) SPLET is the likely antioxidative mechanism of 5CQA with extremely high rate. [ABSTRACT FROM AUTHOR]

Albumin is the most abundant plasma protein and as such has been the subject of many studies using a variety of techniques. One of them, capable of monitoring the conformational changes and the binding capacity of proteins, is electron paramagnetic resonance spectroscopy (EPR) spin labeling. To date, albumin has been investigated using a number of different spin labels, mostly spin-labeled fatty acids (SLFAs). However, albumin can bind up to seven equivalents of fatty acids, making it difficult to determine which parts of the molecule undergo conformational changes. To obtain information from a specific site on a protein, spin labels that bind to free cysteine residues may be used. In this work, the applicability of such a label, 3-maleimido proxyl (5-MSL), was evaluated for monitoring conformational changes of bovine serum albumin (BSA) at different temperatures and pH values. Also, the effect of ethanol, reactive oxygen species (hydrogen peroxide and superoxide radical), and the binding of ligands specific for albumin, namely fatty acids, and several drugs were evaluated. The results indicate that the labeling of albumin at its free cysteine residue (Cys-34) using 5-MSL may successfully be used for the detection of conformational changes, even in the case of the subtle alterations induced by ligand binding. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1 G93A ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP). Additionally, the redox status of the two brain regions previously implicated in disease pathology, brainstem and hippocampus, was investigated by spectrophotometric biochemical assays. The EPR results indicated that among the three spin probes, 3CP is the most suitable for reporting the intracellular redox status changes, as Tempol was reduced in vivo within minutes (t 1/2 =2.0±0.5 min), thus preventing reliable kinetic modeling, whereas 3CxP reduction kinetics gave divergent conclusions, most probably due to its membrane impermeability. It was observed that the reduction kinetics of 3CP in vivo, in the head of preALS and ALS SOD1 G93A rats was altered compared to the controls. Pharmacokinetic modeling of 3CP reduction in vivo, revealed elevated tissue distribution and tissue reduction rate constants indicating an altered brain tissue redox status, and possibly BBB disruption in these animals. The preALS and ALS brain tissue homogenates also showed increased nitrilation, superoxide production, lipid peroxidation and manganese superoxide dismutase activity, and a decreased copper-zinc superoxide dismutase activity. The present study highlights in vivo EPR spectroscopy as a reliable tool for the investigation of changes in BBB permeability and for the unprecedented in vivo monitoring of the brain tissue redox status, as early markers of ALS. [ABSTRACT FROM AUTHOR]

Naturally occurring flavonoids, delphinidin, pelargonidin and malvin, were investigated experimentally and theoretically for their ability to scavenge hydroxyl and nitric oxide radicals. Electron spin resonance (ESR) spectroscopy was used to determine antiradical activity of the selected compounds and M05-2X/6-311+G(d,p) level of theory for the calculation of reaction enthalpies related to three possible mechanisms of free radical scavenging activity, namely HAT, SET-PT and SPLET. The results obtained show that the molecules investigated reacted with hydroxyl radical via both HAT and SPLET in the solvents investigated. These results point to HAT as implausible for the reaction with nitric oxide radical in all the solvents investigated. SET-PT also proved to be thermodynamically unfavourable for all three molecules in the solvents considered. [ABSTRACT FROM AUTHOR]

We report the successful, low temperature synthesis of pure and Fe-doped titania nanoparticle (NP) powders, using organic Ti- and Fe-precursors. The properties of the synthesized titania based materials were obtained using XRD, UV/vis and EPR spectroscopy and BET measurements. The doping of TiO 2 induced a shift in the absorption threshold towards the visible spectral range, compared to pure titania. The process of annealing induced an increase in crystallinity and particle sizes in the obtained materials. The photocatalytic activity, using simulated Solar light (Vitalux lamp), of our samples was checked by following the photodegradation reaction of Rhodamine B and trichlorophenole as model compounds. [ABSTRACT FROM AUTHOR]

Abstract: The choice of the spin-trap that is to be applied in any EPR study represents the crossroad between a comprehensive investigation and an “ordinary” quantification of production of radicals. So, the scope of our study was to compare the performance of different spin-traps for qualitative analysis of radical-generating systems, and their ability to recognize previously unnoticed radicals. In addition, we present a brief account of the difficulties involved in the detection of oxygen-centered radicals in chemical and biological systems accompanied by the rationale for using the EPR spin-trapping technique in quantitative studies of such reactive species. Certain technical aspects of EPR experiments related to efficient trapping of free radicals in biochemical systems are also discussed. As an example we present here results obtained using EPR spectroscopy and the spin-trap DEPMPO, which show that the Fenton reaction, as well as various biological systems generate a previously unappreciated hydrogen (/ce:simple-para> [Copyright &y& Elsevier]