Design cytotoxicity: The effect of silver nanoparticles stabilized by selected antioxidants on melanoma cells.

Silver nanoparticles (AgNPs) prepared and stabilized by diverse biologically active substances seem to be especially useful in diverse biological and medical applications. The combination of AgNPs with bioactive substances, such as antioxidants, can lead to the development of new systems of desired anticancer properties. In this research, AgNPs were prepared with the use of diverse antioxidant combinations including gallic acid (GA), (-)-epicatechin-3-gallate (EGCG), and caffeine (CAF). The insightful physicochemical characteristic revealed that each type of AgNPs exhibited spherical shape, comparable size distribution and negative surface charge. Surface-enhanced Raman spectroscopy (SERS) delivered the information about the chemistry of AgNP stabilizing layers, which turned out to be a crucial factor tuning toxicity of AgNPs toward murine B16 melanoma cells (B16-F0) and human skin melanoma (COLO 679) cells. EGCGAgNPs were the most cytotoxic among all the investigated AgNPs. They strongly reduced the activity of mitochondria, damaged cell membrane integrity, and penetrated inside the cells causing DNA damage. In turn, the toxicity of GAAgNPs strongly manifested via the induction of oxidative stress in the cells. It was found that CAFGAAgNPs exhibited the lowest toxicity toward the melanoma cells, which proved that a proper combination of antioxidants enable to prepare AgNPs of differentiated toxicity. It was established that human skin melanoma cells were significantly more sensitive to AgNPs than the murine melanoma cells.

Biocidal Activity of Tannic Acid-Prepared Silver Nanoparticles towards Pathogens Isolated from Patients with Exacerbations of Chronic Rhinosinusitis.

The microbiome's significance in chronic rhinosinusitis (CRS) is unclear. Antimicrobials are recommended in acute exacerbations of the disease (AECRS). Increasing rates of antibiotic resistance have stimulated research on alternative therapeutic options, including silver nanoparticles (AgNPs). However, there are concerns regarding the safety of silver administration. The aim of this study was to assess the biological activity of tannic acid-prepared AgNPs (TA-AgNPs) towards sinonasal pathogens and nasal epithelial cells (HNEpC). The minimal inhibitory concentration (MIC) for pathogens isolated from patients with AECRS was approximated using the well diffusion method. The cytotoxicity of TA-AgNPswas evaluated using an MTT assay and trypan blue exclusion. A total of 48 clinical isolates and 4 reference strains were included in the study (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiellaoxytoca, Acinetobacter baumannii, Serratia marcescens, Enterobacter cloacae). The results of the studies revealed that the MIC values differed between isolates, even within the same species. All the isolates were sensitive to TA-AgNPs in concentrations non-toxic to human cells during 24 h exposition. However, 48 h exposure to TA-AgNPs increased toxicity to HNEpC, narrowing their therapeutic window and enabling 19% of pathogens to resist the TA-AgNPs' biocidal action. It was concluded that TA-AgNPs are non-toxic for the investigated eukaryotic cells after short-term exposure and effective against most pathogens isolated from patients with AECRS, but sensitivity testing may be necessary before application.

Antioxidant-modulated cytotoxicity of silver nanoparticles.

The properties of silver nanoparticles (AgNPs) synthesized using compounds exhibiting biological activity seem to constitute an interesting issue worthy of examination. In these studies, two types of AgNPs were synthesized by a chemical reduction method using well-known antioxidants: gallic acid (GA) and ascorbic acid (AA). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the AgNPs were spherical. The average size was equal to 26 ± 6 nm and 20 ± 7 nm in the case of ascorbic acid-silver nanoparticles (AAgNPs) and gallic acid-silver nanoparticles (GAAgNPs), respectively. Surface-enhanced Raman spectroscopy (SERS) confirmed that the AgNPs were not stabilized by pure forms of applied antioxidants. Changes in mitochondrial activity and secretion of inflammatory and apoptosis mediators after the exposure of human promyelocytic (HL-60) and histiocytic lymphoma (U-937) cells to the AgNPs were studied to determine the impact of stabilizing layers on nanoparticle toxicity. The GAAgNPs were found to be more toxic for the cells than the AAgNPs. Their toxicity was manifested by a strong reduction in mitochondrial activity and induction of the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-9. The addition of pure antioxidants to the AgNP suspensions was found to influence their toxicity. There was a significant positive effect in the case of the mixture of AA with AAgNPs and GA with GAAgNPs. The results obtained suggest that the presence of stabilizing agents adsorbed on the surface of AgNPs is the main factor in shaping their toxicity. Nevertheless, the toxic effect can be also tuned by the introduction of free antioxidant molecules to the AgNP suspensions.

Gold substrates of controlled roughness and electrokinetic properties formed by nanoparticle deposition.

The kinetics of positively charged gold nanoparticle self-assembly on oxidized silicon substrates (wafers) under diffusion-controlled transport was studied using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The latter technique allowed the roughness parameters of the monolayer (root mean square) to be determined as a function of the particle coverage. These results were adequately interpreted in terms of a theoretical model developed for surfaces covered by features of spherical shape considering the tip convolution effect. The stability and the electrokinetic characteristics (zeta potential) of the monolayers were also acquired using streaming potential measurements. It was shown that the inversion of the negative zeta potential of the bare substrate (overcharging) occurs at the particle coverage equal to 0.15, and for larger coverages positive zeta potential values were asymptotically attained. Additionally, the desorption kinetics of the particles was investigated by the streaming potential method, which confirmed the stability of the monolayers for a broad range of pHs. It was argued that these results enable to develop an efficient method for the preparation of gold sensors exhibiting a well-controlled surface roughness and electrostatic charge comprising both negative and positive values.

Gold Nanoparticle Layers on Polystyrene Microspheres of Controlled Structure and Electrokinetic Properties.

Formation of positively charged gold nanoparticle layers on polystyrene microparticles (PSMs600) was studied using the electrokinetic and the concentration depletion methods based on atomic force microscopy (AFM) and scanning electron microscopy (SEM) imaging. Primarily, the dependence of electrophoretic mobility of microparticles on the gold nanoparticle concentration in the suspension was measured. These results were quantitatively interpreted in terms of the three-dimensional electrokinetic model. This allowed to derive a formula for calculating the coverage of nanoparticles under in situ conditions whose validity was confirmed by direct SEM imaging of deposited gold nanoparticles (AuNPs). Additionally, the maximum coverage of gold nanoparticles for various ionic strengths was determined using a concentration depletion method based on AFM imaging of residual particles deposited on the silica substrate. The maximum coverage increased with ionic strength attaining a value of 0.35 for the ionic strength of 3 × 10-3 M. This effect was attributed to the decreasing range of lateral electrostatic interactions among deposited particles. The electrokinetic properties of the gold nanoparticle layers were also evaluated in pH cycling experiments that confirmed their stability. Beyond significance to basic science, the new data acquired in this work confirm the feasibility of preparing gold nanoparticle layers on polymer microparticles characterized by a controlled structure, coverage, and electrokinetic properties.

Hematite/silica nanoparticle bilayers on mica: AFM and electrokinetic characterization.

Quantitative studies on self-assembled hematite/silica nanoparticle (NP) bilayers on mica were performed by applying scanning electron microscopy (SEM), atomic force microscopy (AFM), and streaming potential measurements. The coverage of the supporting hematite layers was adjusted by changing the bulk concentration of the suspension and the deposition time. The coverage was determined by direct enumeration of deposited particles from AFM images and SEM micrographs. Afterward, silica nanoparticle monolayers were assembled under diffusion-controlled transport. A unique functional relationship was derived connecting the silica coverage with the hematite precursor layer coverage. The formation of the hematite monolayer and the hematite/silica bilayer was also monitored in situ by streaming potential measurements. It was confirmed that the zeta potential of the bilayers was independent of the supporting layer coverage, exceeding 0.15. These measurements were theoretically interpreted in terms of the general electrokinetic model that allowed for deriving a formula for calculating nanoparticle coverage in the bilayers. Additionally, from desorption experiments, the interactions among hematite/silica particles in the bilayers were determined using DLVO theory. These results facilitate the development of a robust method of preparing nanoparticle bilayers with controlled properties, with potential applications in catalytic processes.

Toxicological effects of three types of silver nanoparticles and their salt precursors acting on human U-937 and HL-60 cells.

The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO3, CH3COOAg and AgClO4) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60. For both cell lines, silver salts are more toxic than the corresponding nanoparticles. Cell viability after treatment with the two forms of silver (salt/particle) is dependent on silver dose and degree of cells differentiation. Addition of the silver salt of doses greater than 5 mg/L results in decreased cell viability by over 60%, whereas nanoparticles' addition reduces cell viability on average by 30%. On the basis of the determined LD50 values it can be stated that for the tested cells the most toxic are AgClO4 and TAC. Production of nitric oxide, which is a mediator of inflammation, is the greatest after treatment of the cells by TAC. Different interactions of studied nanoparticles with albumin has been found and it was shown that addition of albumin to the cells treated by nanoparticles reduces their toxic effects. Obtained by us highly purified, mono-disperse AgNPs exhibit diverse effects relative to the biological systems, depending on the precursor salt used.

Kinetics of silver nanoparticle deposition at PAH monolayers: reference QCM results.

The deposition kinetics of silver nanoparticles on Au/SiO2 /PAH substrate was studied under in situ conditions using the QCM method and the ex situ SEM imaging. Because of low dissipation, the Sauerbrey equation was used for calculating the mass per unit area (coverage). Measurements were done for various bulk suspension concentrations, flow rates, and ionic strengths. It was shown that particle deposition for the low coverage regime is governed by the bulk mass transfer step that results in a linear increase of the coverage with the time. A comparison of QCM and SEM results showed that the hydration of the silver monolayers was negligible. This allowed one to derive a universal kinetic equation that describes the mass transfer rates in the cell as a function of the bulk concentration, flow rate, and diffusion coefficient. Measurements were also performed for longer times and for various ionic strengths where the deposition kinetics and the maximum coverage of particles were determined. The experimental data confirmed a significant increase in the maximum coverage with ionic strength. This was interpreted as due to the decreasing range of the electrostatic interactions among deposited particles. These results were adequately interpreted in terms of the extended random sequential adsorption (eRSA) model. Additionally, it was shown that the QCM data matched the ex situ SEM results, indicating that the monolayer hydration was also negligible for higher coverage range. These results derived for the model silver nanoparticle system can be exploited as reference data for the interpretation of protein adsorption kinetics where the dry mass is needed in order to assess the extent of hydration.

Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers.

AIM: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers. METHODS: The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value). RESULTS: All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports. CONCLUSIONS: In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.

Spectroscopic studies under properties of chlorpromazine conjugated to gold nanoparticles.

Scientific studies have demonstrated that conjugates of anticancer drugs with metal nanoparticles (MeNPs) lead to a more effective deactivation of tumor cells compared to free drugs. Similarly, it has been established that conjugates of antibiotics with MeNPs exhibit higher biocidal activity against bacteria than their unbound counterparts. However, limited information is available regarding conjugates formed from drugs other than anticancer and antibiotics. Therefore, our research aims to develop synthesis methods for conjugates of chlorpromazine (CPZ), a neuroleptic, with gold nanoparticles (AuNPs). CPZ-AuNP conjugates were prepared through a ligand exchange reaction conducted on the surface of quasi-spherical, negatively charged citrate-stabilized TC-AuNPs with an average size of 55 ± 5 nm. UV-vis spectroscopy was employed to determine the stability range of the conjugates under controlled conditions of pH and ionic strength. Based on electrokinetic measurements, it was observed that the zeta potential of CPZ-AuNP conjugates strongly depends on the amount of CPZ adsorbed on the TC-AuNP surface. Additionally, the conjugates exhibited an isoelectric point at pH 8.8. Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRA) were employed to elucidate the adsorption structure of CPZ on TC-AuNPs. The interpretation of the spectra was conducted based on the Raman and FTIR spectra of CPZ, along with calculations performed using Density Functional Theory (DFT). The results indicated that CPZ primarily interacts with the TC-AuNP surface through the angularly oriented phenothiazine ring and the propylene bridge. Furthermore, it was demonstrated that the C-N-C fragment is perpendicular to the surface of the TC-AuNP with which it interacts. The findings from this analysis suggest the potential for further research on the use of these conjugates in biomedical applications.

The impact of various forms of silver nanoparticles on the rhizosphere of wheat (Triticum aestivum L.) - Shifts in microbiome structure and predicted microbial metabolic functions.

The study investigated the effects of different silver nanoparticles (AgNPs) on the soil microbiome and wheat growth. For comparison purposes, a commercial fungicide and silver nitrate (AgNO3) were used. The results revealed three distinct groups of nanoparticles based on their impacts. Small-size AgNPs (10 nm) with a negative charge, as well as fungicide had limited effects on the microbiome, similar to the no-treatment control. Bigger in size (30-60 nm) and a negative charge AgNPs showed the most beneficial effects on soil microbiota shifts. These AgNPs increased the abundance of bacteria with beneficial traits such as nitrogen-fixing, urease, protease, and lignin degradation bacteria. The third type of AgNPs had a positive charge of nanostructure and influenced specific microbial populations, increasing the abundance of anaerobic and autotrophic groups of microorganisms, which could be assessed as a harmful shift for plants growth promotions and was similar to the AgNO3 treatment. Overall, the study emphasized the potential of AgNPs in agriculture not only as biocidal. The conducted study proved that AgNPs with bigger size/negative charge, used in low concentration can have a surprisingly stimulating effect on the positive characteristics of the rhizosphere microbiome. Moreover, the surface charge of AgNPs is a significant factor affecting microbial activity of wheat rhizosphere soil, which in this treatment is significantly similar to the AgNO3 treatment.

Exploring the nanoscale: AFM-IR visualization of cysteine adsorption on gold nanoparticles.

This study focuses on the adsorption process of L-cysteine (Cys), a sulfur-containing amino acid, onto monolayers of gold nanoparticles (AuNPs) prepared through distinct protocols on mica substrates. Two types of AuNPs were prepared using two different methods: the first employed a physical approach, which combined the Inert Gas Condensation (IGC) technique with the magnetron sputtering method, while the second utilized a chemical method involving the reduction of tetrachloroauric acid with trisodium citrate (TC). The characterization of AuNPs was performed using transmission electron microscopy (TEM) and atomic force microscopy (AFM), of up to 5 ± 1.3 nm for bare AuNPs obtained through vacuum techniques, and up to 12 ± 5 nm for negatively charged, citrate-stabilized TCAuNPs(-). The application of spectroscopic techniques based on the surface-enhanced effects allows for describing the adsorption process in both micro- and nanoscale systems: Cys/bare AuNPs and Cys/ TCAuNPs(-). The commonly used surface-enhanced Raman spectroscopy (SERS) technique provided insights into adsorption behaviours at the microscale level. In the case of TCAuNPs(-), an interaction involving the lone electron pair of sulfur (S) atom and metal surface, while on the bare AuNPs, S is adsorbed on the surface, but the cleavage of the SH group is not discernible. Nanoscale analysis was complemented using AFM combined with the surface-enhanced infrared absorption spectroscopy (AFM-SEIRA) technique. AFM-SEIRA map indicated the formation of hot spot which were predominantly located between aggregated TCAuNPs(-) and on specific NPs surfaces (area between NPs and gold-coated tip). Results from the SERS and AFM-SEIRA techniques were in good agreement, underscoring the comprehensive understanding achieved through the chosen experimental approach regarding the Cys interactions with layers of AuNPs.

Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects.

The disposition and biotransformation of (14)C-radiolabeled mavoglurant were investigated in four healthy male subjects after a single oral dose of 200 mg. Blood, plasma, urine, and feces collected over 7 days were analyzed for total radioactivity, mavoglurant was quantified in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and metabolite profiles were generated in plasma and excreta by high-performance liquid chromatography (HPLC) and radioactivity detection. The chemical structures of mavoglurant metabolites were characterized by LC-MS/MS, wet-chemical and enzymatic methods, NMR spectroscopy, and comparison with reference compounds. Mavoglurant was safe and well tolerated in this study population. Mavoglurant absorption was ≥50% of dose reaching mean plasma Cmax values of 140 ng/ml (mavoglurant) and 855 ng-eq/ml (total radioactivity) at 2.5 and 3.6 hours, respectively. Thereafter, mavoglurant and total radioactivity concentrations declined with mean apparent half-lives of 12 and 18 hours, respectively. The elimination of mavoglurant occurred predominantly by oxidative metabolism involving primarily 1) oxidation of the tolyl-methyl group to a benzyl-alcohol metabolite (M7) and subsequently to a benzoic acid metabolite (M6), and 2) oxidation of the phenyl-ring leading to a hydroxylated metabolite (M3). The subjects were mainly exposed to mavoglurant and seven main metabolites, which combined accounted for 60% of (14)C-AUC0-72 h (area under the concentration-time curve from time 0 to infinity). The primary steps of mavoglurant metabolism observed in vivo could partially be reproduced in vitro in incubations with human liver microsomes and recombinant cytochrome P450 enzymes. After 7 days, the mean balance of total radioactivity excretion was almost complete (95.3% of dose) with 36.7% recovered in urine and 58.6% in feces.

Controlled release of silver nanoparticles from monolayers deposited on PAH covered mica.

Systematic studies of silver particle deposition kinetics under diffusion transport on poly(allylamine hydrochloride) (PAH) modified mica were carried out. Monolayer coverage, quantitatively determined by AFM and SEM, was regulated within broad limits by adjusting the deposition time and the ionic strength. The stability of obtained silver films was determined in controlled release experiments also carried out under diffusion transport for pronged time periods reaching 240 h. The decrease in the surface coverage of particles was followed by SEM and AFM imaging. The role of particle size, ionic strength, and temperature was systematically studied. It was determined that particle release kinetics was enhanced by increase in ionic strength and temperature, whereas the effect of particle size was less significant. These results were theoretically interpreted in terms of the random sequential adsorption model (RSA), which allowed one to determine the equilibrium adsorption constant Ka and the binding energy (energy minimum depth). For particles of the average size 15 nm and T = 298 K, the energy varied between -16.9 kT for ionic strength 0.1 M and -18.8 kT for ionic strength 10(-4) M. For the largest nanoparticles 54 nm, the energy varied between -17.7 kT for ionic strength 0.1 M and -20.8 kT for ionic strength 10(-4) M. These results suggest that the interactions between surface and nanoparticles are mainly controlled by electrostatic attraction between ion pairs. Our studies indicate that there is a possibility of a controlled release of silver nanoparticles from films formed at solid substrates, which can be significant for biological application, e.g., in respect to antibacterial activity.

Quantitative and qualitative analyses of drug adsorption on silver nanoparticle monolayers: QCM, SERS, and TEIRA nanospectroscopy studies.

In this study for the first time, surface-enhanced Raman spectroscopy (SERS) and tip-enhanced infrared (TEIRA) nanospectrocopy together with a quartz crystal microbalance (QCM) are postulated as powerful tools for comprehensive qualitative and quantitative analyses of drug/metal nanocarrier conjugates. The development of efficient drug/carrier systems requires that the stability of the drug/carrier connection be estimated and the number of drug molecules immobilized on the carrier surface be determined. Thus, such a characterization study is highly desirable. Here, the SERS technique was applied to identify how erlotinib, a drug applied in non-small cell lung cancer (NSCLC) therapy, interacts with silver nanoparticles (AgNPs) that are considered as drug carriers. These investigations indicate that in the erlotinib/AgNP suspension, the drug strongly connects with the NPs mainly through the phenylacetylene moiety. The QCM was used to prepare an AgNP monolayer with a monitored degree of coverage and to perform controlled erlotinib adsorption as a next step. The results indicate that the drug forms a stable layer on the AgNP monolayer and also show the amount of the erlotinib molecules which underwent immobilization on the metal nanosurface. Simultaneously, it was identified how the erlotinib layer adsorbs on the AgNP monolayer using TEIRA nanospectroscopy with ultra-high spatial resolution. The obtained results show that the phenylacetylene, ethoxy, and methoxy moieties are mainly responsible for the drug/AgNP monolayer connection. Additionally, the performed studies also try to explain the surface-enhanced phenomena that occur during the TEIRA experiments and attempt to prove the statement that the "tip-enhanced" effect plays a crucial role in the detection of the thin erlotinib layer deposited on the AgNP monolayer.

Silver nanoparticles affect wheat (Triticum aestivum L.) germination, seedling blight and yield.

The aim of the study was to evaluate the effect of two types of negatively charged quasi-spherical silver nanoparticles (AgNPs) at concentrations of 10, 20 and 30mgL-1 and silver ions at a concentration of 30mgL-1 on the growth, selected physiological aspects and yielding of wheat (Triticum aestivum L.) cv. Tybalt, and on plant resistance to seedling blight. Seed germination, α-amylase activity in seeds, morphology and infestation of seedlings by pathogens were assessed in a hydroponic treatment. Growth rate, PSII efficiency, heading and yield of the same plants were then analysed in pot culture. Results showed that the AgNPs and silver ions had a negative effect on roots, but reduced seedling blight and improved leaf area compared to the control. In addition, the AgNPs reduced with sodium borohydride in the presence of trisodium citrate at concentrations of 10 and 20mgL-1 stimulated germination, α-amylase activity and shoot length, which was not observed in the case of silver ions and the AgNPs reduced with sodium hypophosphite in the presence of sodium hexametaphosphate. In a pot experiment, the AgNPs improved plant growth, PSII efficiency, accelerated heading and increased yield-related parameters compared with the control. Results revealed the interaction strength in the following order: TCSB-AgNPs>SHSH-AgNPs>silver ions. TCSB-AgNPs in the lowest concentration had the most favourable effect, indicating their great potential for use in improving wheat cultivation.

Physicochemical Nature of SARS-CoV-2 Spike Protein Binding to Human Vimentin.

Vimentin, a protein that builds part of the cytoskeleton and is involved in many aspects of cellular function, was recently identified as a cell surface attachment site for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study investigated the physicochemical nature of the binding between the SARS-CoV-2 S1 glycoprotein receptor binding domain (S1 RBD) and human vimentin using atomic force microscopy and a quartz crystal microbalance. The molecular interactions of S1 RBD and vimentin proteins were quantified using vimentin monolayers attached to the cleaved mica or a gold microbalance sensor as well as in its native extracellular form present on the live cell surface. The presence of specific interactions between vimentin and S1 RBD was also confirmed using in silico studies. This work provides new evidence that cell-surface vimentin (CSV) functions as a site for SARS-CoV-2 virus attachment and is involved in the pathogenesis of Covid-19, providing a potential target for therapeutic countermeasures.

Pharmacokinetics of fingolimod (FTY720) and a combined oral contraceptive coadministered in healthy women: drug-drug interaction study results.

BACKGROUND: Fingolimod has a novel mechanism of action in multiple sclerosis, being a first-in-class sphingosine 1-phosphate receptor modulator. Because of a potential risk of fetal toxicity based on animal studies, women of childbearing potential are advised to take effective contraceptive measures during and for 2 months after stopping fingolimod therapy. To assess whether the efficacy of a combined oral contraceptive (OC) could be compromised during fingolimod therapy, a steady-state, drug-drug interaction study of fingolimod with ethinylestradiol/levonorgestrel was performed in healthy female volunteers. OBJECTIVE: To assess the interaction between fingolimod 0.5 mg once daily and ethinylestradiol 30 µg/ levonorgestrel 150 µg once daily at a steady state. METHODS: 31 healthy women received the combined OC only on Days 1 - 14, followed by OC plus fingolimod on Days 15 - 28. RESULTS: In the presence of fingolimod, ethinylestradiol pharmacokinetics were unchanged, and levonorgestrel maximum plasma concentration at steady state and area under the concentration-time curve during a dosing interval increased by factors of 1.10 (90% CI 1.05 - 1.16) and 1.22 (90% CI 1.18 - 1.27), respectively. CONCLUSIONS: Fingolimod therapy does not alter the pharmacokinetics of the combined OC ethinylestradiol/ levonorgestrel to a clinically significant degree. Ethinylestradiol/levonorgestrel does not alter the pharmacokinetics of fingolimod. Women receiving fingolimod therapy are able to use a combined OC as a means of effective birth control.

Surface properties-dependent antifungal activity of silver nanoparticles.

Silver nanoparticles (AgNPs) exhibit unusual biocidal properties thanks to which they find a wide range of applications in diverse fields of science and industry. Numerous research studies have been devoted to the bactericidal properties of AgNPs while less attention has been focused on their fungicidal activity. Our studies were therefore oriented toward determining the impact of AgNPs characterized by different physicochemical properties on Fusarium avenaceum and Fusarium equiseti. The main hypothesis assumed that the fungicidal properties of AgNPs characterized by comparable morphology can be shaped by stabilizing agent molecules adsorbed on nanoparticle surfaces. Two types of AgNPs were prepared by the reduction of silver ions with sodium borohydride (SB) in the presence of trisodium citrate (TC) or cysteamine hydrochloride (CH). Both types of AgNPs exhibited a quasi-spherical shape. Citrate-stabilized AgNPs (TCSB-AgNPs) of an average size of 15 ± 4 nm were negatively charged. Smaller (12 ± 4 nm), cysteamine-capped AgNPs (CHSB-AgNPs) were characterized by a positive surface charge and higher silver ion release profile. The phytopathogens were exposed to the AgNPs in three doses equal to 2.5, 5 and 10 mg L-1 over 24 and 240 h. Additionally, the impact of silver ions delivered in the form of silver nitrate and the stabilizing agents of AgNPs on the fungi was also investigated. The response of phytopathogens to these treatments was evaluated by determining mycelial growth, sporulation and changes in the cell morphology. The results of our studies showed that CHSB-AgNPs, especially at a concentration of 10 mg L-1, strongly limited the vegetative mycelium growth of both species for short and long treatment times. The cell imaging revealed that CHSB-AgNPs damaged the conidia membranes and penetrated into the cells, while TCSB-AgNPs were deposited on their surface. The fungistatic (lethal) effect was demonstrated only for silver ions at the highest concentration for the F. equiseti species in the 240 h treatment. The number of spores of both Fusarium species was significantly reduced independently of the type of silver compounds used. Generally, it was found that the positively charged CHSB-AgNPs were more fungicidal than negatively charged TCSB-AgNPs. Thereby, it was established that the stabilizing agents of AgNPs and surface charge play a crucial role in the shaping of their fungicidal properties.

Chemical Structure of Stabilizing Layers of Negatively Charged Silver Nanoparticles as an Effector of Shifts in Soil Bacterial Microbiome under Short-Term Exposure.

In this work, we have assessed the exposure of soil bacteria from potato monoculture to three types of silver nanoparticles (AgNPs) as well as silver ions (Ag+ ions) delivered in the form of silver nitrate and a commercially available fungicide. The diversity of the soil microbial community, enzymatic activity, and carbon source utilization were evaluated. It was found that only the fungicide significantly limited the abundance and activity of soil bacteria. Silver ions significantly reduced bacterial metabolic activity. In turn, one type of AgNPs prepared with the use of tannic acid (TA) increased bacterial load and activity. There was found in all AgNPs treated soils (1) a greater proportion of all types of persistent bacteria, i.e., Bacillus, Paenibacillus, and Clostridium; (2) a visible decrease in the proportion of Nocardioides, Arthrobacter, and Candidatus Solibacter; (3) almost complete depletion of Pseudomonas; (4) increase in the number of low-frequency taxa and decrease in dominant taxa compared to the control soil. Despite the general trend of qualitative changes in the bacterial community, it was found that the differences in the chemical structure of the AgNP stabilizing layers had a significant impact on the specific metabolic activity resulting from qualitative changes in the microbiome.