Binding of the commonly used antioxidants (quercetin, resveratrol, and dihydrolipoic acid) to major circulating proteins – spectroscopic and in silico docking and molecular dynamic simulation studies

Poor bioavailability and reduced stability are the main drawbacks to efficiently utilizing many naturally occurring antioxidants, so their binding to circulatory proteins is essential. This work investigated whether major human circulatory proteins, besides albumin, including transferrin, alpha-2-macroglobulin, and fibrinogen, bind widely consumed antioxidants and food supplements, including quercetin, trans-resveratrol, and dihydrolipoic acid, thus filling the gap of detailed pharmacokinetic properties of these food supplements. Detailed examination of the protein structural and functional changes that occur upon ligand binding was analyzed by spectroscopic methods and in silico docking and molecular dynamic simulation studies on the model that consists of the protein/antioxidant pair with the highest affinity constant. It was found that alpha-2-macroglobulin binds trans-resveratrol with the highest affinity (Ka of 4.5 x 104 M−1). In silico results revealed four potential binding sites between trans-resveratrol and alpha-2-macroglobulin, with hydrogen bonds being crucial for binding, while other observed interactions (primarily aromatic interactions) are of secondary importance. The binding of trans-resveratrol to alpha-2-macroglobulin leads to mutual protection of both molecules from oxidative stress and significantly increased hidrosolubility of resveratrol, both of which could serve to increase the bioavailability and bioactivity of resveratrol in circulation.on-line firs

Study of the Effect of Supersaturation Changes on the Growth of {100} KDP Crystal Faces

This study investigates the growth of {100} KDP crystal faces under varying supersaturation conditions of 6.2–14.7%. The findings indicate that the positions of growth rate maxima differ between experiments where supersaturation increases or decreases, with higher rates associated with decreasing supersaturation. Surface analysis via SEM and AFM revealed that higher supersaturation resulted in greater roughness. The growth rate on supersaturation dependence R(σ) for both types of experiments was best described by parabolic and power law models, indicating spiral growth. A significant percentage of crystal faces exhibited an exponent n > 2, suggesting the relevance of the multiple nucleation model. Additional analysis excluded the suggested model in favor of the polynuclear model. No significant difference was found between the arithmetic means of n values for both types of experiments, suggesting that for the investigated supersaturation range, the growth mechanism of {100} KDP crystal faces is independent of growth history

Influence of duty cycle in the pulsating current regime on morphology and structure of copper coatings

In this investigation, the copper coatings were electrodeposited from the basic acid sulphate bath on Si(111) wafer using pulsating current (PC) regime. An adhesion/nucleation layer of chromium and gold was sputtered on silicon wafer samples before electrochemical deposition process. Copper coatings obtained with variations of duty cycle (θ) in the range (15−50 %), i.e. with variating average current densities between 15 and 70 mA·cm−2, and keeping the current density amplitude constant (100 mA·cm−2). The thickness of the copper coatings was 40 μm. The aim of investigation was to calculate grain size of deposits and to investigate the impact of square waves PC regime and duty cycle to obtain uniform compact coatings suitable for potential application in MEMS devices. Copper coatings obtained in the range of the duty cycles between 15 and 50 % were characterized by scanning electron microscope (SEM), atomic force microscope (AFM) and X-ray diffraction (XRD). The XRD analysis of the obtained Cu coatings confirmed their nano-structural grain size. The average grain size was in the 29.95-38.58 nm range according to Debye-Scherrer analysis method applied to XRD patterns. The average roughness parameter of Cu coatings obtained after AFM analysis was in the 100−150 nm range. As the duty cycle increased from 15 % to 50 %, the regularity and size of the Cu grains decreased. With a 50 % duty cycle, the fine-grained structures are created. The crystal structure of electrodeposited Cu coatings modified from the strong (220) to the strong (111) preferred orientation, and the coatings' shape changed from large-grained to fine-grained as the average current density increased. The best structural and morphology characteristics were observed for the Cu coating with fine-grained and nano-size grains synthesized with a 50 % of duty cycle, pause duration of 5 ms, and at an average current density of 50 mA·cm−2

Hydrogen evolution on Ir nanoparticles supported by glassy carbon and graphene nanoplatelets

This study reports on the electrocatalytic activity of Ir nanoparticles (NPs) supported by glassy carbon (GC) and graphene nanoplatelets (GNPs) for the hydrogen evolution reaction (HER) in an acid solution. Ir/GC and Ir/GNPs catalysts were obtained by the electrochemical deposition of Ir on the two supports under the same conditions. SEM imaging revealed small, barely visible, Ir NPs highly dispersed on GC and located mainly on the edges of graphene plates on GNPs support. According to XPS analysis, the amount of the deposited Ir was 1.3 at% (15.9 wt%) in Ir/GC and 1.4 at% (16.5 wt%) in Ir/GNPs. Ir/GNPs catalyst has shown a higher HER activity, and potential for 10 mA/cm2 of −0.064 V, compared to −0.073 V for Ir/GC. The 32 mV/dec Tafel slope for Ir/GC and 38 mV/dec for Ir/GNPs indicate the Volmer-Tafel and Volmer-Heyrovski reaction pathways, respectively

Effects of Polypropylene and Polyethylene Terephthalate Microplastics on Trypsin Structure and Function

Ingestion is one of the main exposure routes of humans and animals to microplastics (MPs). During digestion, MPs can interact with both gastrointestinal enzymes and food proteins. This study investigated the adsorption of trypsin onto polypropylene (PP) and polyethylene terephthalate (PET) MPs, the influence of MPs on trypsin structure and activity, and the in vitro trypsin digestibility of bovine meat extract (BME) sarcoplasmic proteins and BME α-Gal-carrying allergens (α-GalA) in the presence of PP and PET MPs. Trypsin, BME and α-GalA proteins interact with MPs, resulting in the formation of a soft (SC) and hard (HC) corona. This interaction is dynamic, leading to the adsorption and desorption of protein through time. Trypsin adsorption onto MPs results in slight structural changes in the SC and bulk solution, while a trypsin fraction residing in the HC loses most of its specific activity. The presence of MPs slightly slows down the digestibility of proteins with a mass of 38 kDa, while it does not affect the digestion of α-GalA. According to our results, it is unlikely that realistic concentrations of MPs in the intestine would have significant effects on meat extract proteins’ and allergens’ digestibility by trypsin. We confirmed that during trypsin digestion, the corona on PP and PET MP is composed of BME sarcoplasmic proteins and allergenic α-Gal-carrying proteins

Food-derived bioactive pigment phycocyanobilin binds to SARS-CoV-2 spike protein both covalently and noncovalently affecting its conformation and functionality

Phycocyanobilin (PCB), tetrapyrrole chromophore of Spirulina phycocyanin, is bilirubin analog and weak thiol-modifying agent. SARS-CoV-2 spike protein (SP) has bilirubin binding pocket, lacks free sulfhydryl, but it has two pairs of functionally important semi-stable disulfides reactive towards thiol-modifying agents. We investigated covalent and noncovalent binding of PCB to SP and its receptor-binding domain (RBD) and impact of covalent PCB conjugation to RBD on structure and binding to human angiotensin-converting enzyme 2 (ACE-2). PCB shows high-affinity for SP (Ka = 2.1 × 107 M−1), moderate-affinity for RBD (Ka = 8.4 × 104 M−1) and binds covalently to SP and RBD in reaction involving thiols. PCB binding alters RBD conformation. Molecular docking identified two binding sites of PCB to SP, bilirubin/biliverdin binding site and hydrophobic pocket of RBD in vicinity of Cys432, preferential target for covalent binding in in silico covalent docking of PCB to RBD. Redox proteomics mapped reactive Cys432, Cys391 and Cys525 in RBD. PCB-modified RBD exhibited reduced ability to bind to ACE-2. This is the first study demonstrating PCB reactivity towards semi-stable disulfides of proteins lacking free sulfhydryl groups. PCB may affect functionality and structure of SP and its RBD by noncovalent and covalent binding

Phytochemical investigation of euphorbia lucida: isolation and characterization of scoparone

Euphorbia lucida Waldst. & Kit. (known locally as “tall spurge”) is a herbaceous perennial plant with a strong spindle-shaped root. It grows in marshy meadows and coastal shrublands, on moist, sandy soils [1]. Its natural habitat the Balkans and Central Europe. In Serbia, it can be found on Fruska Gora, as well as in Belgrade (Ada Ciganlija, Makis). The use of E. lucida in traditional medicine is not as widespread as with other species of this genus, but there are ethyl records of its use in the southern Africa region. As with other species of the Euphorbia genus, caution should be exercised when using this species in traditional medicine due to the potential toxicity of its metabolites. E. lucida has been minimally phytochemically investigated to date, and this study represents one of the few reports on its secondary metabolites. Using a hexane/acetate extract of the latex, chromatographic methods were applied to isolate the metabolite scoparone. The structure of the isolated metabolite was determined based on NMR data and confirmed through GC-MS analysis. Previous research has demonstrated that scoparone exhibits a diverse range of pharmacological activities, suggesting its potential as a versatile therapeutic agent [2]. Given its diverse biological activities, scoparone may contribute to the development of novel therapeutic applications

Unveiling the paleosalinity constraints on southern peri-Pannonian Lower Miocene lacustrine systems in Serbia and Bosnia and Herzegovina: Lopare (Dinaride Lake System) versus Toplica basin (Serbian Lake System)

Early Neogene saline lakes were widely developed across Central Paratethys, particularly across its „Dinaride-Anatolide“ landbridge (area of Dinarides, Balkans). The constraints on Lopare (western part of Jadar block; eastern Bosnia and Herzegovina) and Toplica (Jastrebac Mt., central Serbia) Neogene paleolakes provide a better understanding of deep-time climate evolution. The study focused on early Neogene paleolacustrine configuration, paleogeography, and the factors affecting a considerable paleosalinity increase. The study integrated available records on the predominantly Lower Miocene sedimentary sequence by analyzing and interpreting several paleosalinity markers (inorganic geochemical proxies, mineralogical data). The constraints on paleosalinity markers are afterward coupled with rather complex tectonic inferences. The two wellbores drilled in the Lopare and Toplica basins expose Neogene sections from which the critical paleosalinity markers are extracted (drillhole depths up to 350 and 1000 m, respectively). The mineral searlesite (NaBSi2O5(OH)2), and high B/Ga, markers of alkaline and arid paleoenvironmental lacustrine conditions, suggested intense evaporation (frequent drought periods). The evaporation was associated with paleoclimatic conditions during the Miocene Climatic Optimum. The Early Neogene arid climate and frequent evaporation episodes resulted in significant salinization of the Lower Miocene Lopare lacustrine sequence. The salinity in the Lopare sequence changed its character between brackish and saline, as evidenced by S/TOC and Ca/(Ca + Fe) ratios (TOC—Total Organic Carbon). At the same time, the salinity in the early Toplica basin was significantly lower and characterized by freshwater and brackish environments. The salinity variations between Toplica and Lopare were further exposed by Fe/(Ca + Mg), (Al + Fe)/(Ca + Mg), and C-value, yielding the change in the (paleo)water column. These markers further indicated the influence of warm climate conditions, consistent with the Miocene paleoclimatic record. Regarding paleogeography and Early Neogene tectonics, the results showed that before the Middle Miocene Badenian transgression, the Paratethyan Sea had no interference with the investigated intramontane lacustrine basins

Synthesis and antinociceptive activity of long-known but unexplored nitro-fentanyl derivatives

Fentanyl and related 4-anilidopiperidines are the most potent and clinically important analgesics for the treatment of severe acute and chronic pain. Many fentanyl derivatives have been made so far to obtain new analgesics with improved pharmacological profile. However, of simple nitro fentanyl derivatives only the meta isomer was reported, while ortho and para isomers proved to be synthetically challenging. We report here for the first time the synthesis of ortho and para-nitro-fentanyl. The most arduous step in the synthesis was the acylation of nitroaniline precursor, where the ortho and para positioned nitro group with strong electron-withdrawing and/or steric effects led to an extremely low nucleophilicity of anilino nitrogen. To address this problem electrophilic conditions had to be enhanced using strong acylating agent i.e. propionyl chloride or bromide, and bases such as Et3N or pyridine in a polar, aprotic solvent such as N,N-dimethylformamide (DMF). Indeed, under these conditions, acylation step afforded title products in excellent yields. The in vivo pharmacological evaluation demonstrated that regioisomerism plays a role in the potency and the onset of action of these compounds. The ortho-nitro derivative emerged as the most effective analgesic, exhibiting approximately 50 times less potency than fentanyl, comparable to morphine. Furthermore, it demonstrated a faster onset of action than fentanyl while maintaining a similar duration of effect. These traits indicate that it may be well-suited for treating severe acute pain and breakthrough pain in chronic pain conditions. Ortho-nitro fentanyl is henceforth worthy of further evaluation in toxicity and safety pharmacology studies

Supplementary material to "The intra-Mesozoic bauxite-bearing truncations of the peri-Neotethyan realm (Dinarides/Vardar Zone): A multidisciplinary approach shedding new light on the Neocimmerian event"

Once coupled with global eustatic levels, bauxites, breccias, unconformities, and hiatuses are significant markers of compressional geodynamics. Most Balkan intra-Mesozoic bauxites, embedded within widespread Triassic carbonate parental sequences, are dominantly distributed in the tectonically exhumed broader Neotethyan realm (Dinarides s.l.). The same mid-Mesozoic stratigraphic interval within the Vardar Zone contains fewer bauxites (East Vardar Zone), exposing abundant corresponding depositional truncations, with occasional nappe stacking configuration and metamorphism. This study, which initially acquired data from a large number of mid-Mesozoic unconformities, carbonate breccias, and similar age bauxites spreading across Dinarides s.l., Serbia, Bosnia and Herzegovina, Montenegro, Croatia (Inner and External Dinarides, Western and East Vardar Zone), including Hellenides in Greece, has provided valuable paleogeographic and geodynamic insights. The findings of this study, combined with the available mineralogical and geochemical data, deformation, including the resulting provenances of intra-Mesozoic bauxite deposits, have led to a complex and intriguing discussion on the tectonic origin of similar age unconformities across Dinaride-Hellenide and Vardar Zone Neotethyan regions. These Dinaride-Hellenide intra-Mesozoic unconformities, carbonate breccias, and widespread bauxites are a fascinating puzzle as no study deals with the complex and controversial processes of repeated regional-scale uplifts, erosion, and bauxite formation. The ambiguity revolves around the geodynamic origin of the Jurassic ophiolites in the first place and its connection with mid-Mesozoic Cimmerian orogenic events (Neocimmerian stage). Thus, the Triassic – Jurassic(Lower Cretaceous) Inner Dinaride Ophiolite belt is particularly interesting accounting for the absence of the latest Jurassic – earliest Cretacous stratigraphic interval. Many of the bauxite ores are produced on Middle Triassic to Jurassic parental limestones, whereby the hiatus can last until the beginning of the Upper Cretaceous. The Triassic rifting and opening of “Dinaric Tethys”, which likely caused the pre-Neocimmerian Late Triassic shoulder uplift of early passive margins, continued into the Jurassic mid-oceanic spreading. The Triassic and Jurassic-aged zircon grains in bauxites, including new data extracted from the bauxite geochemical database, corroborate a volcanic parental affinity originating from exposed Jurassic volcanic rocks. The new geochemical analysis allowed the separation of ultramafic from mafic bauxite sources, whereby acidic sources are absent or well hidden within Inner Dinarides. Bauxite deposits at the southern edge of the Inner Dinaride area show an abundance of incompatible Mn, demonstrating a significant transgressional Oxfordian eustatic high-stand episode (precipitation of Mn on top of submerged paleokarst/bauxites). This, a Red Sea-type small ocean basin with a NE-vergent suprasubduction (“Dinaric Tethys”), lasted until the end of the Jurassic (also dated by metamorphic imprints). The tectonic exhumation processes of Inner Dinaride ophiolites involving the Neocimmerian compressive event caused the widespread uplift episode in the latest Jurassic – earliest Cretaceous, occasionally lasting until the Albian (Austrian unconformity). As a result, mid-Mesozoic long-lasting hiatuses allowed intense weathering of numerous uplifted parental limestone sites, frequently producing at least two cycles of laterites and bauxite ores. The Neocimmerian episode includes the limited length (shorter cross- lithospheric across-strike width) of the latest Jurassic ophiolite obduction on top of abutting continental crust, inclusive of the onset of Lower Cretaceous Vranduk turbidites (another marker of the closing “Dinaric Tethys”).Belongs to [https://cer.ihtm.bg.ac.rs/handle/123456789/8218