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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.

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.

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.

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.

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 raising awareness of compliance with traffic regulations with doctors who prescribe benzodiazepines.

Global climate change, environmental pollution, and frequent pesticide use severely reduce bee populations, greatly challenging beekeeping. Pesticides such as deltamethrin, a pyrethroid insecticide commonly used to control mosquitoes, can kill individual bees and entire colonies, depending on the exposure. Due to mosquito resistance to pyrethroid insecticides, components that enhance their effect are commonly used. This study explores the potential of Agaricus bisporus mushroom extract in mitigating oxidative stress in bees triggered by pesticides and Nosema ceranae infection. Our findings indicate that A. bisporus extract significantly reduced mortality rates of bees and spore counts of N. ceranae . Furthermore, the extract demonstrated antioxidant properties that lower enzyme activity related to oxidative stress (CAT, SOD, and GST) and MDA concentration, which is linked to lipid peroxidation. These results indicate that natural extracts like A. bisporus can aid bee health by mitigating the effects of pesticides and pathogens on honey bees, thus improving biodiversity.

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., (© 2024 Wiley Periodicals LLC.)

This study examined the antiradical activity of three synthesized coumarin derivatives: ( E )-3-(1-((2-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate ( A 1 -OH ), ( E )-3-(1-((3-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate ( A 2 -OH ), and ( E )-3-(1-((4-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate ( A 3 -OH ) against HOO•/O2•- radical species. The investigation included electron spin resonance (ESR) measurements and a DFT kinetic study. Thermodynamic and kinetic parameters of antiradical mechanisms-Formal Hydrogen Atom Transfer ( f -HAT), Radical Adduct Formation (RAF), Sequential Proton Loss followed by Electron Transfer (SPLET), and Single-Electron Transfer followed by Proton Transfer (SET-PT)-were evaluated using the Quantum Mechanics-based test for Overall Free Radical Scavenging Activity (QM-ORSA) under physiological conditions. ESR results indicated antiradical activity decreased in the sequence A 1 -OH (58.7%) > A 2 -OH (57.5%) > A 3 -OH (53.1%). Kinetic analysis revealed the f -HAT mechanism dominated HOO • inactivation. A newly formulated Sequential Proton Loss followed by Radical Adduct Formation (SPL-RAF) mechanism described interactions with O 2 •- . The activity toward O 2 •- was A 2 -OH (1.26 × 10 6 M -1 s -1 ) > A 3 -OH (7.71 × 10 5 M -1 s -1 ) > A 1 -OH (4.22 × 10 5 M -1 s -1 ). Molecular docking and dynamics studies tested inhibitory capability against enzymes producing reactive species: Lipoxygenase (LOX), Myeloperoxidase (MPO), NAD(P)H oxidase (NOX), and Xanthine Oxidase (XOD). Affinity to enzymes decreased in the order: XOD > LOX > NOX > MPO.

As part of this study, the mechanisms of the antioxidant activity of previously synthesized coumarin-trihydrobenzohydrazine derivatives were investigated: ( E )-2,4-dioxo-3-(1-(2-(2″,3″,4″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate ( 1 ) and ( E )-2,4-dioxo-3-(1-(2-(3″,4″,5″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate ( 2 ). The capacity of the compounds to neutralize HO • was assessed by EPR spectroscopy. The standard mechanisms of antioxidant action, Hydrogen Atom Transfer (HAT), Sequential Proton Loss followed by Electron Transfer (SPLET), Single-Electron Transfer followed by Proton Transfer (SET-PT), and Radical Adduct/Coupling Formation (RAF/RCF) were examined using the QM-ORSA methodology. It was estimated that the newly synthesized compounds, under physiological conditions, exhibited antiradical activity via SPLET and RCF mechanisms. Based on the estimated overall rate constants ( k overall ), it can be concluded that 2 exhibited a greater antiradical capacity. The obtained values indicated a good correlation with the EPR spectroscopy results. Both compounds exhibit approximately 1.5 times more activity in comparison to the precursor compound used in the synthesis (gallic acid).

Sorghum grain ( Sorghum bicolor L. Moench) is a gluten-free cereal with excellent nutritional value and is a good source of antioxidants, including polyphenols, as well as minerals with proven health benefits. Herein, the phenolic composition, elemental profile, and antioxidant activity of sixteen food-grade sorghum grains ( S1 - S16 ) grown under agroecological conditions in Serbia were determined. Nine phenolic compounds characteristic of sorghum grains, such as luteolinidin, 5-methoxyluteolinidin, luteolidin derivative, luteolidin glucoside, apigeninidin, 7-methoxyapigeninidin, apigeninidin glucoside, and cyanidin derivative, were quantified. The antioxidant potential of the analyzed sorghum grains was evaluated by UV/Vis (DPPH, ABTS, and FRAP) and Electron Paramagnetic Resonance spectroscopy (hydroxyl and ascorbyl radical scavenging assays). The content of macro- and microelements was determined by Inductively Coupled Plasma Optical Emission spectroscopy. Theoretical daily intakes of selected major and trace elements were assessed and compared with the Recommended Daily Allowance or Adequate Intake. Sample S8 had the highest amount of phenolic compounds, while S4 , S6 , and S8 exhibited the strongest antioxidative potential. The sorghum studied could completely satisfy the daily needs of macro- (K, Mg, and P) and microelements (Se, Zn, Fe). Pattern recognition techniques confirmed the discrimination of samples based on phenolic profile and elemental analysis and recognized the main markers responsible for differences between the investigated samples. The reaction between hydroxyl radicals and luteolinidin/apigeninidin was investigated by Density Functional Theory and thermodynamically preferred mechanism was determined.

Coumarin derivatives are a class of compounds with pronounced biological activities that depend primarily on the present substituents. Four 3-methoxycarbonylcoumarin derivatives with substituents of different electron-donating/electron-withdrawing abilities (Br, NO 2 , OH, and OMe) were investigated structurally by NMR, IR, and UV-VIS spectroscopies and density functional theory methods. The appropriate level of theory (B3LYP-D3BJ/6-311++G(d,p) was selected after comparing similar compounds' experimental and theoretical structural parameters. The natural bond orbital and quantum theory of atoms in molecules were employed to investigate the intramolecular interactions governing stability. The electronic effects of substituents mostly affected the aromatic ring that the substituents are directly attached to. The antioxidant properties were investigated by electron paramagnetic resonance spectroscopy towards HO • , and the percentages of reduction were between 13% ( 6-Br ) and 23% ( 6-OMe ). The protein binding properties towards transport proteins were assessed by spectrofluorimetry, molecular docking, and molecular dynamics (MD). The experimentally determined binding energies were well reproduced by molecular docking, showing that the spontaneity of ibuprofen binding was comparable to the investigated compounds. The flexibility of HSA in MD simulations depended on the substituents. These results proved the importance of electronic effects for the protein binding affinities and antioxidant properties of coumarin derivatives.

Spiked centaury ( Centaurium spicatum ) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.

The present study provides, for the first time, a physicochemical and biochemical characterization of the redox processes associated with the ripening of Solanum dulcamara L. (bittersweet) berries. Electron Paramagnetic Resonance Spectroscopy (EPRS) and Imaging (EPRI) measurements of reactive oxygen species (ROS) were performed in parallel with the tissue-specific metabolic profiling of major antioxidants and assessment of antioxidant enzymes activity. Fruit transition from the mature green (MG) to ripe red (RR) stage involved changes in the qualitative and quantitative content of antioxidants and the associated cellular oxidation and peroxidation processes. The skin of bittersweet berries, which was the major source of antioxidants, exhibited the highest antioxidant potential against DPPH radicals and nitroxyl spin probe 3CP. The efficient enzymatic antioxidant system played a critical protective role against the deleterious effects of progressive oxidative stress during ripening. Here, we present the EPRI methodology to assess the redox status of fruits and to discriminate between the redox states of different tissues. Interestingly, the intracellular reoxidation of cell-permeable nitroxide probe 3CP was observed for the first time in fruits or any other plant tissue, and its intensity is herein proposed as a reliable indicator of oxidative stress during ripening. The described noninvasive EPRI technique has the potential to have broader application in the study of redox processes associated with the development, senescence, and postharvest storage of fruits, as well as other circumstances in which oxidative stress is implicated.

This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical ( HL ). The binding of HL to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl. The results showed that the hydrogel is an efficient HL reservoir as it retained 60% of the ligand during 11 days of dialysis in physiological saline. Furthermore, upon incubation with Colo 205 human colon adenocarcinoma cells for 3 days, the HL /HSA hydrogel did not exhibit cytotoxic activity, demonstrating that it is also an efficient ligand depot in the presence of living cells. It was observed that the percentage of HL release is independent of its initial concentration in the hydrogel, suggesting that HSA possesses a specific binding site for the ligand, most likely Sudlow site 2, as predicted by molecular docking. The intrinsic property of albumin to bind and transport various substances, including hydrophobic drugs, may be fine-tuned by appropriate physical/chemical hydrogel preparation procedures, providing optimal drug delivery.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, C-doped TiO 2 nanoparticles (C-TiO 2 ) 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 TiO 2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO 2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO 2 . 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-TiO 2 . We have also confirmed blue light-induced C-TiO 2 -catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO 2 /blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO 2 /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-TiO 2 /blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy., (© 2021. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the research focus from Aβ to other pathological features of the disease., Objective: The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy., Methods: In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibiting different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectroscopy was employed to investigate the brain metal content., Results: This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-mediated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model., Conclusion: The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neuronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spectroscopy application in preclinical studies of neurodegenerative diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The liposomal integration method, in conjunction with electron paramagnetic resonance (EPR) spectroscopy, has been presented for the investigation of antioxidant activity of selected water-insoluble compound towards biologically relevant free radicals. This method was applied to avarol, a sesquiterpenoid hydroquinone isolated from the marine sponge Dysidea avara . The antioxidant activity of water-insoluble avarol towards • OH, O 2 •- and NO • radicals was attained by its incorporation into the DPPC liposomes bilayer, and towards ascorbyl radicals in the organic solvent. Avarol's activity towards • OH, O 2 •- , NO • and ascorbyl radicals was 86.2%, 50.9%, 23.6% and 61.8%, respectively, showing its significant radical scavenging potential.

Interacting Quantum Atoms methodology is used for a detailed analysis of hydrogen abstraction reaction from hydroquinone by methoxy radical. Two pathways are analyzed, which differ in the orientation of the reactants at the corresponding transition states. Although the discrepancy between the two barriers amounts to only 2 kJ/mol, which implies that the two pathways are of comparable probability, the extent of intra-atomic and inter-atomic energy changes differs considerably. We thus demonstrated that Interacting Quantum Atoms procedure can be applied to unravel distinct energy transfer routes in seemingly similar mechanisms. Identification of energy components with the greatest contribution to the variation of the overall energy (intra-atomic and inter-atomic terms that involve hydroquinone's oxygen and the carbon atom covalently bound to it, the transferring hydrogen and methoxy radical's oxygen), is performed using the Relative energy gradient method. Additionally, the Interacting Quantum Fragments approach shed light on the nature of dominant interactions among selected fragments: both Coulomb and exchange-correlation contributions are of comparable importance when considering interactions of the transferring hydrogen atom with all other atoms, whereas the exchange-correlation term dominates interaction between methoxy radical's methyl group and hydroquinone's aromatic ring. This study represents one of the first applications of Interacting Quantum Fragments approach on first order saddle points. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Stacking interactions in thymine dimers are studied with density functional theory. According to our calculations, six dimers of comparable stability can be prepared at low temperature, but dimerization is impossible at room temperature due to the large entropy contribution that accompanies it. Analysis of vibrational anharmonic coupling terms shows that each of the dimers exhibits distinct vibrational dynamics. Properties of electron density in the intermolecular region are used to analyze neutral stacked species and their ionized forms. Bond paths and critical points in the intermolecular region are identified, but a simple relationship between binding energy and total electron density in the intermolecular critical points could not be found due to an uneven electron distribution in the binding region. The reduced density gradient was confirmed to be a useful tool for analysis of weak stacking interactions. Those interactions also affect vertical and adiabatic ionization energies, which are computed to be slightly lower for the dimers compared to the monomer.