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The study of palladium-catalyzed amination of bromobenzene with aromatic and heterocyclic amines, widely used in the synthesis of organic semiconductors, was performed. The best conditions for the coupling of aryl bromides with carbazole, diphenylamine, phenoxazine, phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, and their derivatives have been developed. Based on the results, nine new star-shaped organic semiconductors, exhibiting up to 100% fluorescent quantum yield in the 400-550 nm range, have been synthesized in good yields. The TDDFT calculations of the absorption spectra revealed a good correlation with experimental results and slight solvatochromic effects with a change in the polarity of the solvent.

The most popular drugs used to prevent osteoporosis that causes low mineral density and weakened microstructure of bones are bisphosphonates. Bisphosphonates can be administered in several ways, but each delivery method has drawbacks. Due to this, new methods of their delivery are being sought. Titanium implants coated with calcium titanate were prepared in this work as carriers for bisphosphonates. Such a modification has been proposed in order to improve the therapeutic properties of the implant. Slow release of the drug at a constant level will positively affect the recovery process and osteointegration. Furthermore, the drug will be slowly released very close to the area affected by osteoporosis. These studies were confirmed, using a variety of methods: EDS and XPS (to examine surface modification and drug sorption), Raman mapping (to proof the presence of the drug on the entire surface of the material) and UV-VIS spectroscopy (to determine bisphosphonate sorption and release profile). It was proved that the active substance (sorbed on the implant) could be completely released upon contact with body fluids within a month. The obtained results will allow for the production of endoprostheses dedicated to patients with osteoporosis in the future.

There is a strong need to search for more effective compounds with bone anti-resorptive properties, which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite (HA), this study used three forms of ceramic materials, two of which are bone-stimulating materials, to assess the suitability of new active substances with anti-resorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA (a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction (MINE) device (a polymer inert skeleton), respectively, were used. The affinity of risedronate (a standard compound) and sixteen aminomethylenebisphosphonates (new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorption–desorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability., Graphical abstract Image 1, Highlights • Three methods for assessing the suitability of new active substances with anti-resorptive properties. • Investigation of the interactions between antiresorptive drugs and hydroxyapatite. • Sorption and desorption of risedronate and sixteen aminomethylenebisphosphonates.

OBJECTIVE The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported. APPROACH AND RESULTS The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p

Titanium(IV) oxide is one of the most widely investigated photocatalysts. However, separation of nano-sized particulate titania might result in profitless technologies for commercial applications. Additionally, bare titania is almost inactive under the Vis range of solar spectrum due to its wide bandgap. Therefore, the present study aims to prepare novel core-interlayer-shell TiO2 magnetic photocatalysts modified with metal nanoparticles (Pt, Cu), which exhibit both photocatalytic and magnetic properties, making it easily separable within the magnetic field. Accordingly, the core–shell structure of Fe3O4@SiO2/TiO2 was obtained in water/TX100/cyclohexane microemulsion. Platinum and copper were photodeposited on four TiO2 templates and characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), specific surface area (BET) measurement and diffuse reflectance spectroscopy (DR-UV/Vis). Photoactivity was studied in the reaction of phenol, acetic acid, and methanol degradation under UV/Vis irradiation, using both polychromatic and monochromatic irradiation (action spectrum analysis). The core-interlayer-shell structure of Pt and Cu modified magnetic photocatalysts was confirmed using scanning transmission electron microscopy (STEM). Magnetic photocatalysts modified with platinum and copper revealed improved photoactivity both in oxidation and reduction photocatalytic reactions, as compared to unmodified Fe3O4@SiO2/TiO2 photocatalysts. Finally, the correlation between physicochemical properties and photocatalytic activities of Fe3O4@SiO2/TiO2-Pt/Cu photocatalysts was investigated. For the first time, the effect of metals’ loading on the efficiency of phenol degradation and mineralization (TOC removal), and quantum efficiency of reaction in the presence of magnetic photocatalysts were analyzed. It was found that phenol can be efficiently decomposed (ca. 100%) during 60 min of UV/Vis irradiation for the photocatalyst recovered within the magnetic field during three subsequent degradation cycles.

Titania (titanium(IV) oxide) is a highly active, stable, cheap and abundant photocatalyst, and is thus commonly applied in various environmental applications. However, two main shortcomings of titania, i.e., charge carrier recombination and inactivity under visible-light (vis) irradiation, should be overcome for widespread commercialization. Accordingly, titania has been doped, surface modified and coupled with various ions/compounds, including narrower bandgap semiconductors, such as oxides of copper and silver. Unfortunately, these oxides are not as stable as titania, and thus loss of activity under long-term irradiation (photo-corrosion) has been observed. Therefore, this study has focused on the preparation of stable coupled photocatalysts, i.e., CuxO@TiO2 core–shell nanostructures, by the microemulsion method from commercial Cu2O as a core and TiO2 (ST01-fine anatase) as a shell. The photocatalysts have been characterized by DRS, SEM, TEM, XRD, XPS and reversed double-beam photo-acoustic spectroscopy (RDB-PAS) methods, and activity tests under UV (anaerobic dehydrogenation of methanol and oxidative decomposition of acetic acid) and vis (phenol oxidation) irradiation. The higher activities of coupled photocatalysts than their counterparts have been found in all studied systems under UV/vis irradiation. Moreover, long-term experiments (10 h) have shown high stability of CuxO@TiO2. However, the change of oxidation state of copper has also been observed, i.e., to negative and positive values, confirming the charge transfer according to the Z-scheme under UV irradiation and type-II heterojunction under vis irradiation, respectively. The property-governed activity and the mechanism have been discussed in detail.

W artykule opisano wysoce wydajne międzyniciowe fotozszywanie dupleksu DNA zawierającego 5-chloro-2′-deoksy-4-tiourydynę (ClSdU) w jednej nici, przebiegające w dwuetapowej kaskadzie fotochemicznej, polegające na tworzeniu w pierwszym etapie reakcji odwracalnego termicznie wiązania kowalencyjnego pomiędzy ClSdU i tymidyną w nici docelowej i późniejszą konwersję do stabilnego termicznie fluorescencyjnego międzyniciowego crosslinku. Wyniki te pokazują, że ClSdU ma ogromny potencjał, aby stać się cennym czynnikiem fotosieciującym DNA.

The blends of synthetic and natural polymers are extensively investigated as materials for medical applications. Synthetic component usually ensures appropriate mechanical and physical properties w...

Aronia melanocarpa E. berries are a valuable component of the healthy diet. They are extremely high in phenolics exhibiting strong antioxidant properties. However, not much information is available on the chemical composition and bioactive potential of chokeberry leaves. Therefore, the analyses of sugars and phenolics of extracts from chokeberry leaves collected from June to October were performed using spectroscopic (NMR) and chromatographic (HPLC-DAD/RI, GC-MS) methods. The leaf extracts contained a significant amount of sorbitol, especially those made of leaves collected since June to July (avg. 145.2 mg/g d.w.). The average contents of Cya-3-Gal and chlorogenic acids in the extracts were at 0.52 mg g d.w. and up to 13.1 mg/g d.w., respectively. Chokeberry leaf extracts from green and red leaves were subjected to the in vitro study on human umbilical vein endothelial cells (HUVCs). Both extracts suppressed TNF-α-induced surface expression of ICAM-1 and VCAM-1 molecules, and exhibited anti-adhesive and anti-inflammatory properties. Green and red leaves may foster a therapeutic potential in the prevention of atherosclerosis and other pathological events involving leucocyte adhesion. That is why chokeberry leaves can be considered as a promising component of functional foods owing to the high content of chlorogenic acids and sorbitol.

Glutamine is an astroglia-derived precursor of the neurotransmitter glutamate, and its astroglia-to-neuron transfer is controlled by distinct glutamine transporters on the astrocytic and neuronal sites. In this study, we focused on the role of astrocytic glutamine efflux-mediating system N transporter SN1 in the maintenance of glutamatergic neurotransmission by analyzing the electrophysiological parameters ex vivo in the brain slices from control mice and mice in which vivo-morpholino technique was used to diminish SN1 protein. The glutamatergic transmission was characterized by electrophysiological recordings, ultrastructure of neuron terminals, and determination of proteins related to glutamate synaptic transmission: synaptophysin, synaptotagmin, and vit1A. The space-restricted ∼51,5% reduction of SN1 protein did not affect the expression of the neuronal glutamine transporter SAT2. SN1 depletion resulted in a reduction of field potentials (FPs), unaltered frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs), and presented a tendency towards a decrease of long-term potentiation (LTP). Ultrastructurally, preserved number of synaptic vesicles, primarily localized centrally of the cell body, correlates with unchanged levels of synaptic proteins. Collectively, the study indicates that glutamatergic transmission proceeds relatively independently of the SN1 - mediated glutamine transfer to the synapse.

RNA G-quadruplexes fold almost exclusively into parallel-stranded structures and thus display much less structural diversity than their DNA counterparts. However, also among RNA G-quadruplexes peculiar structural elements can be found which are capable of reshaping the physico-chemical properties of the folded structure. A striking example is provided by a uridine tetrad (U-tetrad) placed on the 3′-terminus of the tetramolecular G-quadruplex. In this context, the U-tetrad adopts a unique conformation involving chain reversal and is responsible for a tremendous stabilization of the G-quadruplex (ΔTm up to 30°C). In this report, we attempt to rationalize the origin of this stabilizing effect by concurrent structural, thermal stability, and molecular dynamics studies of a series of G-quadruplexes with subtle chemical modifications at their 3′-termini. Our results provide detailed insights into the energetics of the “reversed” U-tetrad motif and the requirements for its formation. They point to the importance of the 2′OH to phosphate hydrogen bond and preferential stacking interactions for the formation propensity and stability of the motif.

Two types of exfoliated graphitic carbon nitride (GCN) with similar morphology but different surface properties were fabricated and tested as photocatalysts in acetaldehyde and dyes (Acid Red 18 and Rhodamine B) decomposition processes. Both samples were synthesized via exfoliation of the bulk GCN in the assistance of strong oxidant. Their surface modification was tuned by annealing at different temperature: 250 and 350 °C providing two samples assigned to GCN_250 and GCN_350, respectively. The samples exhibited similar thickness, lateral size, surface area and band gap energy but their photoactivity differed greatly. Exfoliated materials showed different photocatalytic activity depending on the type of dye (anionic or cationic). The Acid Red degradation by GCN_250 with positively charged surface was 1.8-times higher in respect to negatively charged GCN_350, whereas the Rhodamine B decomposition by GCN_350 was 1.4-times higher in comparison to GCN_250. Furthermore, GCN_250 exhibited superior photoactivity towards acetaldehyde decomposition in comparison with GCN_350 under visible light irradiation. This study provides knowledge on GCN surface properties in photocatalytic activity toward both water and volatile pollutant degradation.

The present study aimed to evaluate the cytotoxicity and its mechanism of five synthetic methoxy stilbenes, namely 3,4,4ʹ-trimethoxy, 3,4,2ʹ-trimethoxy, 3,4,2ʹ,4ʹ-tetramethoxy, 3,4,2ʹ,6ʹ-tetramethoxy, and 3,4,2ʹ,4ʹ,6ʹ-pentamethoxy-trans-stilbenes (MS), in comparison with resveratrol (RSV). Human promyelocytic (HL-60) and monocytic leukemia (THP-1) cells were treated with the tested compounds for 24 h, and cytotoxicity, cell cycle distribution, and apoptosis were evaluated. Significant differences were found in the susceptibility of these cell lines to all stilbenes, including RSV. The THP-1 cells were more resistant to cytotoxic activity of these compounds than HL-60 cells. Among the tested stilbenes, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS exhibited higher cytotoxicity toward both cell lines than RSV and the other methoxy stilbenes. This activity might be related to cell cycle arrest at the G2/M phase and induction of apoptosis. In this regard, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS at highest concentrations increased the p53 protein level particularly in HL-60 cells. Moreover, treatment with these derivatives increased the ratio of the proapoptotic Bax protein to the antiapoptotic Bcl-xl protein, suggesting the induction of apoptosis through the intrinsic mitochondrial pathway in both cell lines. Further studies are required to fully elucidate the mechanism of these activities.

Purpose The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI. Methods The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography. Results 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4–221.0) vs. 201.8 (156.5–299.9) vs. 118.5 (73.4–198.7); p Conclusion Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required.

Glycerol monostearate solid lipid nanoparticles (SLN) were produced by hot high-pressure homogenization technique to load alpha-pinene, citral, geraniol or limonene. SLN were composed of 1wt.% monoterpene, 4wt.% of Imwitor® 900K as a solid lipid and 2.5wt.% of Poloxamer188 as a surfactant. Empty SLN consisted of 5wt.% of Imwitor® 900K and 2.5wt.% of Poloxamer188. The mean particles size (Z-Ave) and polydispersity index (PDI) of SLN were analyzed by dynamic light scattering (DLS), while the zeta potential (ZP) of each formulation were measured by electrophoretic light scattering. LUMiSizer® was applied to calculate the velocity distribution in the centrifugal field and instability index. Drug release profile from SLN was analyzed using Franz cell diffusion cells assayed by UVVis spectrophotometry, whereas the gas chromatography technique was applied to determine the encapsulation parameters of volatile monoterpenes. The matrix state, polymorphism and phase behavior of SLN were studied by X-ray diffraction (XRD, low and wide angles) and differential scanning calorimetry (DSC). Selected monoterpenes were successfully loaded in glycerol monostearate SLN. A burst release profile within the first 15min was observed for all formulations, being the modified release profile dependent on the type of monoterpene and on the encapsulation efficiency., The authors acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference [M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020] (strategic fund), co-financed by FEDER, under the Partnership Agreement [PT2020]., info:eu-repo/semantics/publishedVersion

We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome. Supplementary information Supplementary information accompanies this paper at 10.1186/s13059-020-01969-6.

Herein, two different photocatalytic composites based on ordered (OCS) and disordered (DCS) mesoporous hollow carbon spheres and graphitic carbon nitride (gCN) have been successfully fabricated through facile acid treatment. The influence of carbon shell morphology of the spheres on gCN loading and photocatalytic H2 production under simulated solar light irradiation has been revealed. The amount of evolved H2 was ~6.2 (OCS/gCN) and ~5.3 (DCS/gCN) times higher in comparison to pristine gCN. It was found that graphitic carbon nitride was much more homogenously supported onto ordered mesoporous carbon spheres than disordered ones. The deposition of gCN onto ordered carbon spheres was found to be more efficient to increase carrier concentration, enhance photogenerated charge carrier transport and separation. It is assigned to the formation of the graphitic carbon nitride/carbon heterojunction facilitating the contact surface between the two phases of hybrid. Therefore, via tuning of the morphology of carbon shell being a host for gCN it was possible to find more promising candidate as a photocatalyst in H2 production under solar light irradiation.

Among the for the first time reported Cr-containing high entropy La1−xSrx(Co,Cr,Fe,Mn,Ni)O3−δ (x = 0, 0.1, 0.2, 0.3, 0.4 and 0.5) perovskite-type oxides, the selected Sr-doped La0.7Sr0.3(Co,Cr,Fe,Mn,Ni)O3−δ material is documented to possess attractive properties as a candidate air electrode material for Solid Oxide Fuel Cells (SOFCs). Nanosized powders of the considered oxides are obtained using a modified Pechini sol–gel method. In the formed solid solution with a simple perovskite structure the strontium solubility limit is found to be at least x = 0.3. Room temperature (RT) structural data indicate the presence of rhombohedral structural distortion (Rc symmetry) in the materials. High-temperature structural studies for the selected La0.7Sr0.3(Co,Cr,Fe,Mn,Ni)O3−δ indicate the occurrence of a phase transition to an aristotype Pmm structure at ca. 800 °C. The linear thermal expansion coefficient in the RT-1000 °C range is found to be moderate, 16.0(3) × 10−6 K−1. The results of impedance spectroscopy measurements support the semiconducting-type behavior of the electrical conductivity for all single-phase materials, in a temperature range of RT-1000 °C. The maximum recorded conductivity for the La0.7Sr0.3(Co,Cr,Fe,Mn,Ni)O3−δ composition exceeds 16 S cm−1 in the 900–1000 °C range, being suitable for application. Furthermore, chemical stability toward the La0.8Sr0.2Ga0.8Mg0.2O3−δ (LSGM) electrolyte is proven. Considering the presence of chromium, typically deleterious to the performance, the measured value of the total cathodic polarization resistance for the La0.7Sr0.3(Co,Cr,Fe,Mn,Ni)O3−δ-based electrode, being 0.126 Ω cm−2 at 900 °C, seems to be very attractive. The results obtained for a button-type fuel cell indicate power densities at a level of 550 mW cm−2 at 900 °C. Therefore, it can be considered that the high entropy-based approach enables to propose alternative SOFC air electrode materials, with otherwise inaccessible chemical compositions.

The effect of hexadecyltrimethylammonium bromide (CTAB) addition on the crystal structure, morphology, and magnetic properties of co-precipitated hexagonal barium ferrite was investigated. For a fixed amount of surfactant, different Fe3+ concentrations and Fe3+/Ba2+ ratios were used to optimize the formation of single-phase barium ferrite particles. The results indicated that the obtained ferrite particles exhibited coercivity changes similar to those of superparamagnetic particles with larger than theoretically calculated particle sizes. This results from the softening of the material due to the size reduction of the grains and incorporation of excess barium, localized on the surface of the particles. Therefore, lowering the energy barrier required to reverse the magnetization was observed, while high magnetization saturation was preserved. The precipitation of barium ferrite particles from a surfactant-rich solution allowed control of BaFe12O19 magnetic properties without introducing any modifications inside the crystal structure.

By varying the steric and electronic surroundings of the hydrogen-bonding motif, the novel chiral Cinchona-alkaloid based selenoureas were developed. Acting as bifunctional catalysts, they were applied in the Michael reactions of dithiomalonate and nitrostyrene providing chiral adducts with up to 96% ee. The asymmetric Michael–-hemiacetalization reaction of benzylidene pyruvate and dimedone, performed with the assistance of 5 mol% of selenoureas, furnished the product with up to 93% ee and excellent yields. The effectiveness of the new hydrogen-bond donors was also proved in solvent-free reactions under ball mill conditions, supporting the sustainability of the devised catalytic protocol.

Stinging nettle (Urtica dioica L.) is a good source of biologically active compounds with proven beneficial health effects. This study aimed to investigate the effect of nettle herb supplementation on chemical composition, including the content of selected minerals and pigments, the in vitro glycemic response, and the cooking and sensory quality of extruded pasta. Tagliatelle-shaped pasta was produced under semi-technical scale by partial replacement of durum wheat semolina with 0, 1, 2, 3, 4, and 5% of lyophilized nettle. The partial substitution with freeze-dried nettle caused a statistically significant (p ≤ 0.05) increase in the content of minerals, especially calcium, iron, potassium, and magnesium in the products. The calcium content in the pasta fortified with 5%-addition of stinging nettle was 175.9 mg 100 g−1 and this concentration was 5.8 times higher than in the control sample. At the same time, high content of chlorophylls and carotenoids (237.58 µg g−1 and 13.35 µg g−1, respectively) was noticed. Enriching pasta with a 0–5% addition of stinging nettle resulted in a statistically significant (p ≤ 0.05) increase in the content of the total dietary fiber (TDF) (from 5.1 g 100 g−1 to 8.82 g 100 g−1) and the insoluble dietary fiber (IDF) (from 2.29 g 100 g−1 to 5.63 g 100 g−1). The lowest hydrolysis index of starch (HI = 17.49%) and the lowest glycemic index (GI = 49.31%) were noted for the pasta enriched with 3% nettle.

Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD., This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODER/COMPETE)—project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020. The work is also supported by the National Science Centre within the MINIATURA 4 for a single research activity (grant no: 2020/04/X/ST5/00789) and by the START 2021 Program of the Foundation for Polish Science (FNP) granted to Aleksandra Zielínska, info:eu-repo/semantics/publishedVersion

Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

The incorporation of prebiotics in fermented milk products is one of the best ways to promote health benefits while improving their sensory characteristics at the same time. The aim of this study was to evaluate the effects of the addition of fructose and oligofructose (1% and 2%) on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products inoculated with indigenous probiotic starter cultures of Lactobacillus isolated from Polish traditional fermented foods. The samples were evaluated during 35 days of refrigerated storage. The oligofructose and fructose caused increases in the populations of bacteria in comparison to the control fermented milk products without the addition of saccharides. The degrees of acidification in different fermented milk samples, as well as their viscosity, firmness, syneresis, and color attributes, changed during storage. The highest overall sensory quality levels were observed for the samples supplemented with L. brevis B1 and oligofructose. This study is the first attempt to compare the influences of different sugar sources on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products.

In this work, two-component dialdehyde chitosan/hyaluronic acid scaffolds were developed and characterized. Dialdehyde chitosan was obtained by one-step synthesis with chitosan and sodium periodate. Three-dimensional scaffolds were prepared by the lyophilization method. Fourier transform infrared spectroscopy (FTIR) was used to observe the chemical structure of scaffolds and scanning electron microscopy (SEM) imaging was done to assess the microstructure of resultant materials. Thermal analysis, mechanical properties measurements, density, porosity and water content measurements were used to characterize physicochemical properties of dialdehyde chitosan/hyaluronic acid 3D materials. Additionally, human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF) and human melanoma cells (A375 and G-361) were used to evaluate cell viability in the presence of subjected scaffolds. It was found that scaffolds were characterized by a porous structure with interconnected pores. The scaffold composition has an influence on physicochemical properties, such as mechanical strength, thermal resistance, porosity and water content. There were no significant differences between cell viability proliferation of all scaffolds, and this observation was visible for all subjected cell lines.

Black cumin (Nigella sativa, NS) is included in the Ranunculaceae family and is classified as a medicinal plant due to very high levels of various bioactive compounds. They determine its therapeutic effects, including anti-inflammatory, anti-allergic, anti-cancer, hypoglycemic, antioxidant, hypotensive, hypolipidemic, and immunomodulating properties. The results of scientific studies indicate a supporting role of black cumin in the treatment of autoimmune diseases, including rheumatoid arthritis, due to the health-promoting properties of its bioactive ingredients. The aim of the current article is to analyze the results of scientific publications on the role of bioactive ingredients contained in black cumin in the treatment of rheumatoid arthritis.

Eudragit S100-coated chitosan microspheres (S100Ch) are proposed as a new oral delivery system for green tea polyphenon-60 (PP60). PP60 is a mixture of polyphenolic compounds, known for its active role in decreasing oxidative stress and metabolic risk factors involved in diabetes and in other chronic diseases. Chitosan-PP60 microspheres prepared by an emulsion cross-linking method were coated with Eudragit S100 to ensure the release of PP60 in the terminal ileum. Different core&ndash, coat ratios of Eudragit and chitosan were tested. Optimized chitosan microspheres were obtained with a chitosan:PP60 ratio of 8:1 (Ch-PP608:1), rotation speed of 1500 rpm, and surfactant concentration of 1.0% (m/v) achieving a mean size of 7.16 &micro, m. Their coating with the enteric polymer (S100Ch-PP60) increased the mean size significantly (51.4 &micro, m). The in vitro modified-release of PP60 from S100Ch-PP60 was confirmed in simulated gastrointestinal conditions. Mathematical fitting models were used to characterize the release mechanism showing that both Ch-PP608:1 and S100Ch-PP60 fitted the Korsmeyers&ndash, Peppas model. The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 &micro, g/mL and 154.4 &micro, g/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.

In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) and zirconium(IV) acetylacetonate (Zr(acac)4), as co-initiator and catalyst, respectively. The structure, molecular weight (Mn) and molecular weight distribution (Đ) of the synthesized materials was studied in detail using nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques, the optimal synthesis conditions were determined. The structure corresponded well to the theoretical assumptions. The produced hydrogels demonstrated a sharp sol–gel transition at temperature close to physiological value, forming a stable gel with good mechanical properties at 37 °C. The kinetics and mechanism of in vitro 5-FU release were characterized by zero order, first order, Higuchi and Korsmeyer–Peppas mathematical models. The obtained results indicate good release control, the kinetics were generally defined as first order according to the predominant diffusion mechanism, and the total drug release time was approximately 12 h. The copolymers were considered to be biodegradable and non-toxic, the resulting hydrogels appear to be promising as short-term LDDSs, potentially useful in antitumor therapy.

Edible insects are gaining attention as a novel food, however, studies with their use in food are still limited. This study aimed to determine the chemical composition, physical parameters, sensory acceptance, and biological properties of muffins enriched with different levels of cricket (Gryllodes sigillatus) and mealworm (Tenebrio molitor) flours. The approximate composition was analyzed, along with the physical and textural properties, color, and consumer acceptance. Moreover, the antioxidant properties, starch digestibility, and glycemic index were determined in vitro. As we expected, the protein content in muffins supplemented with insect flour increased, while the carbohydrates content decreased. Moreover, the total phenolic content and antioxidant capacity against ABTS·+ and DPPH· increased correspondingly as the percentage of insect flour in the muffins increased. The estimated glycemic index was lower for the fortified muffins than the control (p &lt, 0.05). Additionally, enriched muffins were accepted by consumers, and their taste positively surprised respondents (p &lt, 0.05). Therefore, the results obtained are satisfactory as regards the use of insects for the supplementation of traditional products, and further research into the addition of insects to other nutrient matrices is needed. Furthermore, examining the effect of insect addition on in vivo food biological activity is highly desirable.

Hairy root lines were established through the infection of Agrobacterium rhizogenes strain (A4) from shoot tips and leaves of Rehmannia elata N. E. Brown ex Prain (Orobanchaceae). Seven lines of hairy roots were selected on the basis of morphology and biomass increase in liquid Woody Plant Medium (WPM) supplemented with sucrose (30 g/L) without growth regulators. The transgenic status of the roots was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) using rolB and rolC specific primers. After 30 days of growth the highest fresh weight (FW) and dry weight (DW) were determined in the S1 hairy root line (9.97 g/flask and 0.88 g/flask, respectively). UHPLC was then used to measure the accumulation of iridoid glycosides (aucubin, harpagide, harpagoside) and phenylethanoid glycosides (verbascoside and isoverbascoside) in selected hairy root lines. Among the iridoid glycosides, the highest amounts of aucubin (0.2 mg/g DW) and harpagide (1.57 mg/g DW) were detected in the S1 line, and harpagoside (0.09 mg/g DW) in the L14 line. Among the phenylethanoid glycosides, the highest levels of verbascoside (17.35 mg/g DW) and isoverbascoside (˜ 2 mg/g DW) were identified in the S1 root line. Catalpol, catalposide and loganin could not be detected in any tested hairy root line.

The photocatalytic deactivation of volatile organic compounds and mold fungi using TiO2 modified with mono- and bimetallic (Pt, Cu, Ag) particles is reported in this study. The mono- and bimetal-modified (Pt, Cu, Ag) titanium(IV) oxide photocatalysts were prepared by chemical reduction method and characterized using XRD, XPS, DR/UV-Vis, BET, and TEM analysis. The effect of incident light, type and content of mono- and bimetallic nanoparticles deposited on titanium(IV) oxide was studied. Photocatalytic activity of as-prepared nanocomposites was examined in the gas phase using LEDs array. High photocatalytic activity of Ag/Pt-TiO2 and Cu/Pt-TiO2 in the reaction of toluene degradation resulted from improved efficiency of interfacial charge transfer process, which was consistent with the fluorescence quenching effect revealed by photoluminescence (PL) emission spectra. The photocatalytic deactivation of Penicillium chrysogenum, a pathogenic fungi present in the indoor environment, especially in a damp or water-damaged building using mono- and bimetal-modified (Pt, Cu, Ag) titanium(IV) oxide was evaluated for the first time. TiO2 modified with mono- and bimetallic NPs of Ag/Pt, Cu, and Ag deposited on TiO2 exhibited improved fungicidal activity under LEDs illumination than pure TiO2 .

Purine metabolism is crucial for efficient ATP resynthesis during exercise. The aim of this study was to assess the effect of lifelong exercise training on blood purine metabolites in ageing humans at rest and after exhausting exercise. Plasma concentrations of hypoxanthine (Hx), xanthine (X), uric acid (UA) and the activity of erythrocyte hypoxanthine-guanine phosphoribosyl transferase (HGPRT) were measured in 55 sprinters (SP, 20‒90 years), 91 endurance runners (ER, 20‒81 years) and 61 untrained participants (UT, 21‒69 years). SP had significantly lower levels of plasma purine metabolites and higher erythrocyte HGPRT activity than ER and UT. In all three groups, plasma purine levels (except UA in UT) significantly increased with age (1.8‒44.0% per decade). HGPRT activity increased in SP and ER (0.5‒1.0%), while it remained unchanged in UT. Hx and X concentrations increased faster with age than UA and HGPRT levels. In summary, plasma purine concentration increases with age, representing the depletion of skeletal muscle adenine nucleotide (AdN) pool. In highly-trained athletes, this disadvantageous effect is compensated by an increase in HGPRT activity, supporting the salvage pathway of the AdN pool restoration. Such a mechanism is absent in untrained individuals. Lifelong exercise, especially speed-power training, limits the age-related purine metabolism deterioration.

Twenty-nine Lactobacillus plantarum strains isolated from different types of Polish regional cheeses (Oscypek and Korycinski) were assessed for selected probiotic properties and anti-staphylococcal activity. Most of the tested L. plantarum strains were considered safe. Whole bacterial cultures (WBC) and cell-free supernatants (CFSs) of L. plantarum strains inhibited growth of Staphylococcus aureus (average inhibition growth zones were 2.8 mm ± 1.2 and 2.8 mm ± 1.1 respectively). Moreover, almost all neutralized, catalase-treated cell-free supernatants (CFN) of L. plantarum cultures also exhibited slight anti-staphylococcal activity in vitro. The most promising strains Os4 and Kor14 were selected for further study. Both strains were able to survive during digestive gastro-intestinal passage model. Live cells of L. plantarum Os4 and Kor14 caused the strongest inhibition of S. aureus adhesion to Caco-2 cells comparing with CFN and heat-killed bacterial cells. S. aureus and L. plantarum (Os4 or Kor14) co-cultured in skim milk resulted in growth inhibition of S. aureus in both 8 °C and 37 °C incubation temperatures. Observed abilities, demonstrated for L. plantarum Os4 and Kor14, confirms that these strains could be used in the food industry as protective cultures. Electronic supplementary material The online version of this article (10.1007/s12602-019-09587-w) contains supplementary material, which is available to authorized users.

Oxymatrine is the alkaloid derived from the root of Sophora species. This compound is proven to exhibit anti-viral, anti-asthmatic, anti-fibrotic and anti-inflammatory properties. Additionally, oxymatrine is able to promote cancer cells apoptosis and inhibit their proliferation. The aim of this study was to present the influence of oxymatrine on non-small cell lung cancer cells. The results indicate, that this agent induces dose-dependent cell death mainly through ER stress-induced apoptosis pathway. We also suggest that the oxymatrine reduces the metastatic potential by inhibition of the EMT process, as A549 cells treated with chosen doses of the compound were characterized by a decrease in the expression of the N-cadherin, vimentin and the elevation of E-cadherin level. Moreover, the study broadens the knowledge on so far poorly understood aspect of the influence of oxymatrine on the cytoskeleton structure.

The fluorochrome JC-1 is mainly used in mammalian cells to estimate mitochondrial membrane potential (MMP) as a stress marker, with far less data being available for plants or green algae. To address this, we have validated the possibility for changes in MMP to be used as a sensitive stress indicator in the green alga Chlamydomonas reinhardtii. To optimize the method, we analyzed the conditions for applicable MMP determination, including the proper buffer, excitation/emission wavelengths, and solvent (dimethyl sulfoxide, DMSO) influence on the fluorescence signal, and evaluated usefulness of the method for toxicological research. Our results have allowed us to develop a complete protocol for the estimation of MMP changes in C. reinhardtii. Statistical analyses have confirmed the reproducibility, sensitivity, and applicability of this method for toxicological studies.

This is the first report of the effect of the ILs cation type (imidazolium, pyridinium and pyrrolidinium) on the morphology, surface properties and photoactivity of BiOX semiconductors type obtained by solvothermal method in glycerol. The various ionic liquids (IL) cation type as a halogen source and templating agent for the synthesis of the bismuth oxyhalides nanoparticles has been systematically investigated. The role of ILs in synthesis of the semiconductors was loosening of the structure and increasing the particle size of semiconductors. It was also found that ILs increased specific surface area and pore volume of bismuth oxyhalides. Rhodamine B and 5-fluorouracil were used as the model contaminates to evaluate the adsorption capacity and photooxidation performance of studied BiOX. Removal of chromium (VI) from acidic solution were demonstrated photoreduction ability of BiOX. Generally the activity of bismuth oxyhalides was better for the samples prepared with ILs, although the increase in activity was different for various ionic liquids. The changes of band gap structure were major causes of the enhanced photocatalytic activity of bismuth oxyhalides with ILs as the halogen source.

Agastache rugosa (Fischer & C.A.Meyer) O.Kuntze (Lamiaceae) is an East Asian medicinal and aromatic plant. It is rich in polyphenolic compounds such as rosmarinic, chlorogenic, ferulic acids and apigenin glycosides. in vitro shoot cultures were used to study influence of various factors on polyphenol profile using Ultra Performance Liquid Chromatography coupled to high resolution mass spectrometry (UPLC-ESI-qTOF-MS). Large differences in the morphology and polyphenol profile were observed in experiments with various illumination (white fluorescent lamps or white and photosynthetically active radiation LEDs) and supplementation with plant growth regulators and amino acids. Shoots were cultured on the MS basal agar medium with or without plant growth regulators (6-benzylaminopurine - BA, indole-3-acetic acid – IAA), or supplemented with different concentrations of phenylpropanoid biosynthesis precursor - l -phenylalanine or an amino acid mixture (casein hydrolysate). The composition of polyphenols in methanolic extracts was analyzed using UPLC-DAD-qTOF-MS. Three phenolic acids: cryptochlorogenic acid, feruloyl-quinic acid, rosmarinic acid, a rosmarinic acid methyl ester and two isomeric ferulic acid glucosides, as well as one flavonoid – an apigenin derivative were detected. Rosmarinic acid (RA) was the most abundant compound found in the analyzed plant material. Supplementation with amino acids resulted in highest content of RA in shoots cultured for 196 days on media containing either low concentration (1 mg/L) of l -phenylalanine or two of the highest - 20, 50 mg/L. The effect of casein hydrolysate supplementation was noticed from the beginning of shoot culture and reached maximum of 23.3 mg/g on 140 day. On the other hand, shoots that were growing under different illumination produced over 20 mg/g dw of RA after 70 days of culture. In conclusion, the production of phenolic compounds in A. rugosa in vitro shoots was influenced by the age of the shoot cultures, illumination regime and amino acids supplementation.

Introduction. Betatrophin is primarily produced in the liver and regulates the metabolism of triglycerides. Its elevated concentration might be associated with an increased risk of type 2 diabetes. The aim of the study was to evaluate the impact of betatrophin on beta cell function and to compare the concentration of betatrophin in patients newly diagnosed with type 1 diabetes mellitus (T1DM including LADA), type 2 diabetes mellitus (T2DM) and a control group (CG) of healthy volunteers. Patients and methods. The study included 210 patients with newly diagnosed diabetes (70 with T1DM, 140 with T2DM) and 70 CG. To evaluate the relationship between betatrophin and insulin secretion, a glucagon stimulation test was conducted. Results. Serum betatrophin concentrations were signi­ficantly elevated in T1DM and T2DM in comparison to the control group (3.47 [Q1 = 2.28, Q3 = 4.54] in T1DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001; 3.12 [Q1 = 1.89, Q3 = 4.48] in T2DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001). No statistically significant differences in betatrophin concentration were observed between the T1DM and T2DM groups. Significant correlations were established between betatrophin, triglyceride (TG) and high-density lipopro­tein (HDL) levels in all study participants, and C-peptide in the T1DM group. Conclusions. Betatrophin concentration was signi­ficantly elevated in patients with newly diagnosed T1DM and T2DM, compared to the control group and could be a biomarker of diabetes. Our study provided evidence which supports the impact of betatrophin on lipid metabolism. The positive correlation between betatrophin and C-peptide in the T1DM group suggests that betatrophin is associated with insulin secretion in T1DM.

In dermal drug delivery, the influence of the chemical structure of the carriers on their penetration mechanisms is not yet fully understood. This is a key requirement in order to design highly efficient delivery systems. In this study, neutron reflectivity is used to provide insights into the interactions between thermoresponsive N-isopropylacrylamide based nanogels, cross-linked with 10%, 20% and 30% N,N'-methylenebisacrylamide, and skin lipid multi-bilayers models. Ceramide lipid multi-bilayers and ceramide/cholesterol/behenic acid mixed lipid multi-bilayers were used for this work. The results indicated that in both multi-bilayers the lipids were depleted by the nanogels mainly through hydrophobic interactions. The ability of nanogels to associate with skin lipids to form water-dispersible complexes was found to be a function of the percentage cross-linker. An enhanced depletion of lipids was further observed in the presence of benzyl alcohol, a well-known skin penetration enhancer.

A TiO2–ZnO binary oxide system (with molar ratio TiO2:ZnO = 8:2) was synthesized by a hydrothermal method, assisted by calcination at temperatures of 500, 600 and 700 °C, using zinc citrate as the precursor of ZnO. The morphology (SEM, TEM), crystalline structure (XRD, Raman spectroscopy), diffuse reflectance spectra (DRS), chemical surface composition (EDXRF), porous structure parameters (low-temperature N2 sorption) and characteristic functional groups (FT-IR) of the TiO2–ZnO oxide materials were comprehensively analyzed. The novelty of this work is the observation of the coexistence of the crystalline structures of anatase and ZnTiO3 in TiO2–ZnO oxide materials. Moreover, it is shown that the obtained materials absorb visible radiation. The key stage of the study was the evaluation of the photocatalytic activity of the TiO2–ZnO binary oxide systems in the degradation of model organic pollutants: C.I. Basic Red 1, C.I. Basic Violet 10, C.I. Basic Blue 3 and 4-nitrophenol. For all synthesized materials, a high efficiency of degradation of the model organic impurities was demonstrated. The results show that the synthesized products may be materials of interest for use in the degradation of organic pollutants. Moreover, the kinetics of the photocatalytic degradation of selected organic compounds were determined based on the Langmuir–Hinshelwood equation, assuming a pseudo-first-order (PFO) reaction.

Introduction Histamine is the major mediator of IgE- and non-IgE-mediated allergic reactions upon allergen or hapten contact. Reduced histamine degradation capacity was associated with atopic eczema as well as with non-immunological histamine intolerance. Higher blood serum histamine level concomitant with decreased intestinal diamine oxidase activity were observed in patients with food allergy. Aim To evaluate the relationship between patients' blood diamine oxidase (DAO) activity/histamine status and their reactivity to time-resolved histamine skin prick test in respect to vulnerability to allergic diseases. Material and methods Fifty-three patients were examined with skin prick tests (SPT) and patch tests for suspected presence of either IgE- or non-IgE-mediated allergy. All individuals were skin prick tested with histamine and the resolution of the wheal was monitored for 50 min. Blood DAO activity and histamine concentration were measured with a radio-extraction radioimmunoassay. Results Time-resolved histamine skin prick testing revealed presence of wheals which were 35% larger in diameter in 47% of examined subjects at 20 min of the test. These patients exhibited significantly compromised time-course wheal resolution (wheal ≥ 3 mm at 50 min) compared to a group of patients with the normal-rate of wheal resolution (wheal = 0 mm at 50 min). Within a group of subjects exhibiting impaired wheal resolution, 61% of patients were diagnosed allergic compared to 50% in a group of patients with a normal rate of wheal resolution. Finally, allergic patients were characterized by a significantly lower DAO activity and higher histamine content compared to healthy subjects. Conclusions The results of this study indicate that patients with IgE- or non-IgE-mediated allergy are likely to have low DAO blood activity and may concomitantly suffer from histamine intolerance. Furthermore, our results suggest that allergic patients are more likely to develop an excessive SPT reaction. Our results emphasize caution in interpretation of the SPT results in allergic patients with diagnosed histamine intolerance or histamine/DAO activity imbalance.

Introduction Staphylococcus aureus constitutes the most pathogenic species within the staphylococcal genus. Humans remain the major reservoirs of this pathogen which colonizes mostly anterior nares of healthy individuals. Aim To investigate the effect of fennel essential oil (FEO) and trans-anethole (tA) on antibacterial activity of mupirocin (MUP) against S. aureus strains isolated from asymptomatic carriers. Material and methods The content of the FEO was analysed with use of the GC-MS method. The research done on 43 S. aureus isolates with different resistance patterns, obtained from nasal vestibule. Antibacterial activity of MUP in combination with FEO or tA was examined using the agar dilution method and E-test method. The data analysis was done with the Pearson's χ2 test. Results The chemical composition of FEO was consistent with the European Pharmacopoeia (EP) for the main constituent - tA (77.9%) according to the EP recommendations. Macrolide-lincosamide-streptogramin B resistance phenotype was prevalent among 39.5% of S. aureus isolates. FEO concentrations of 2.0% and 2.5% revealed antibacterial activity against 76.7% of isolates, whereas tA inhibited S. aureus growth at concentrations > 4.0%. The MIC values for MUP combined with FEO as well as for MUP combined with tA were < 0.064 µg/ml for 79.1% and 86.0% of S. aureus isolates, respectively. Conclusions Our experiment revealed FEO and tA influence on MUP effectiveness. The combination of MUP with FEO as well as MUP with tA are worth considering to implement in S. aureus eradication procedures. These findings will be useful in designing efficient antistaphylococcal agents which can limit the emergence of antibiotic resistance.

Acute liver failure (ALF) is associated with deregulated nitric oxide (NO) signaling in the brain, which is one of the key molecular abnormalities leading to the neuropsychiatric disorder called hepatic encephalopathy (HE). This study focuses on the effect of ALF on the relatively unexplored endothelial NOS isoform (eNOS). The cerebral prefrontal cortices of rats with thioacetamide (TAA)-induced ALF showed decreased eNOS expression, which resulted in an overall reduction of NOS activity. ALF also decreased the content of the NOS cofactor, tetrahydro-L-biopterin (BH4), and evoked eNOS uncoupling (reduction of the eNOS dimer/monomer ratio). The addition of the NO precursor L-arginine in the absence of BH4 potentiated ROS accumulation, whereas nonspecific NOS inhibitor L-NAME or EDTA attenuated ROS increase. The ALF-induced decrease of eNOS content and its uncoupling concurred with, and was likely causally related to, both increased brain content of reactive oxidative species (ROS) and decreased cerebral cortical blood flow (CBF) in the same model.

In this contribution, the hydrogen evolution reaction and photodegradation of Rhodamine B (RhB) dye were studied using urea-based polymeric carbon nitride (PCN) as photocatalyst. The effects of calcination temperature and heating rate of the PCN on structural, morphological, optical, photoelectrochemical, and photocatalytic properties were addressed. Different properties were found to be crucial in boosting photocatalytic performance dependending on the reaction type. The highest efficiency in hydrogen evolution was observed in the presence of PCN characterized by the superior charge transport and charge lifetime properties arising from higher degree of structural arrangement and lower defect content in comparison to that of other photocatalysts. However, photocatalytic degradation of RhB was the most powerful when the catalyst exhibited the highest specific surface area as a key parameter determining its efficiency, although it presented lower charge transport and charge carrier properties.

Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities, glutathione (GSH) level, and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.

Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to N-acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.e., chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as several chitinase-like proteins (YKL-40, YKL-39, oviductin, and stabilin-interacting protein). The latter lack enzymatic activity but still display oligosaccharides-binding ability. The physiologic functions of chitinases are still unclear, but they have been shown to be involved in the pathogenesis of various human fibrotic and inflammatory disorders, particularly those of the lung (idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, sarcoidosis, and asthma) and the gastrointestinal tract (inflammatory bowel diseases (IBDs) and colon cancer). In this review, we summarize the current knowledge about chitinases, particularly in IBDs, and demonstrate that chitinases can serve as prognostic biomarkers of disease progression. Moreover, we suggest that the inhibition of chitinase activity may be considered as a novel therapeutic strategy for the treatment of IBDs.

Mechanochemical and in-solution synthesis of caffeine complexes with α-, β-, and γ-cyclodextrins was optimized. It was found that short-duration, low-energy cogrinding, and evaporation (instead of freeze-drying) are effective methods for the formation and isolation of these complexes. The products obtained, their pure components, and their mixtures were examined by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), FT-IR and Raman spectroscopy. Moreover, molecular modeling provided an improved understanding of the association process between the guest and host molecules in these complexes. The complexes were found to exhibit high toxicity in zebrafish (Danio rerio) embryos, in contrast to pure caffeine and cyclodextrins at the same molar concentrations. HPLC measurements of the caffeine levels in zebrafish embryos showed that the observed cytotoxicity is not caused by an increased caffeine concentration in the body of the organism, as the concentrations are similar regardless of the administered caffeine form. Therefore, the observed high toxicity could be the result of the synergistic effect of caffeine and cyclodextrins.

One of the most common pathogens among yeasts is Candida albicans, which presents a serious health threat. The study aimed to check the antifungal properties of trans-anethole and eugenol with selected antifungal medicines (AMs) against C. albicans clinical isolates. The checkerboard method was used to tests of interactions between these compounds. Achieved results indicated that eugenol showed synergistic and additive activities with miconazole and econazole against investigated clinical isolates, respectively. Moreover, the combination - trans-anethole - miconazole also showed an additive effect against two clinical isolate. We tried to relate the results to changes in C. albicans cell sheaths under the influence of essential oils compounds (EOCs) performing the Fourier transform infrared spectra analysis to confirm the presence of particular chemical moieties in C. albicans cells. Nevertheless, no strong relationships was observed between synergistic and additive actions of used EOC-AMs combinations and chemical moieties in C. albicans cells.