PURPOSE: Convalescent plasma (CP) collected from people who recovered from COVID-19 became a rapidly available treatment modality in numerous countries, including the Czech Republic. The aims of our study were to evaluate the effectiveness and safety of CP in the treatment of COVID-19. METHODS: This retrospective observational study involved six Czech hospitals. This study enrolled patients with and without CP treatment who were hospitalized between April 2020 and April 2021. Propensity score matching and logistic regression analysis were performed to evaluate the influence of CP administration and its timing on the in-hospital survival of COVID-19 patients. RESULTS: A total of 1,498 patients were enrolled in the study; 406 (27%) were administered CP, and 1,092 (73%) were not treated with CP. The propensity score-matched control group consisted of 1,218 subjects. The survival of patients treated with CP was 79%, while that of patients in the matched control group was 62% (P<0.001). Moreover, the chance of survival was significantly greater when CP was administered within three days after the onset of COVID-19 symptoms than when CP was administered after four or more days (87% vs. 76%, P <0.001). In addition, adverse effects related to CP administration were recorded in only 2% of patients and were considered mild in all patients. CONCLUSIONS: Our study demonstrated that the administration of CP was safe and possibly associated with positive effects that were more pronounced if CP was administered within the first three days after the onset of COVID-19 symptoms.
- Klíčová slova
- COVID-19, Convalescent plasma, Outcome, SARS-CoV-2,
- MeSH
- COVID-19 * terapie mortalita MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- pasivní imunizace * metody MeSH
- protilátky virové krev MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři MeSH
- sérologická léčba covidu-19 * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- protilátky virové MeSH
Modern drug formulations often require, besides the active drug molecule, auxiliaries to enhance their pharmacological properties. Tailor-made, biocompatible polymers covalently connected to the drug molecule can fulfill this function by increasing its solubility, reducing its toxicity, and guiding it to a specific target. If targeting membrane-bound proteins, localization of the drug close to the cell membrane and its target is beneficial to increase drug efficiency and residence time. In this study, we present the synthesis of highly defined, branched polymeric structures with membrane-binding properties. One to three hydrophilic poly(ethylene oxide) or poly(2-ethyloxazoline) side chains were connected via a peptoid backbone using a two-step iterative protocol for solid-phase peptoid synthesis. Additional groups, e.g., a hydrophobic anchor for membrane attachment, were introduced. Due to the nature of solid-phase synthesis, the number and order of the side chains and additional units can be precisely defined. The method proved to be versatile for the generation of multifunctional, branched polymeric structures of molecular weights up to approximately 7000 g mol-1. The behavior of all compounds towards biological membranes and cells was investigated using liposomes as cell membrane models, HEK293 and U251-MG cell lines, and red blood cells, thereby demonstrating their potential value as drug auxiliaries with cell membrane affinity.
- Publikační typ
- časopisecké články MeSH
We report the design, synthesis, and in vitro evaluation of stimuli-responsive nanoscale micelles that can be activated by light to induce a cytotoxic effect. Micelles were assembled from amphiphilic units made of a photoactivatable ferrocenyl linker, connected on one side to a lipophilic chain, and on the other side to a hydrophilic pegylated chain. In vitro experiments indicated that pristine micelles ("off" state) were nontoxic to MCF-7 cancer cells, even at high concentrations, but became potent upon photoactivation ("on" state). The illumination process led to the dissociation of the micelles and the concomitant release of iron species, triggering cytotoxicity.
- Klíčová slova
- cancer, ferrocene, micelles, nanomedicine, oxidative stress, phototherapy,
- MeSH
- antitumorózní látky * MeSH
- fototerapie MeSH
- metaloceny farmakologie MeSH
- micely * MeSH
- železnaté sloučeniny * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky * MeSH
- ferrocene MeSH Prohlížeč
- metaloceny MeSH
- micely * MeSH
- železnaté sloučeniny * MeSH
In many regions of Europe, large wild herbivores alter forest community composition through their foraging preferences, hinder the forest's natural adaptive responses to climate change, and reduce ecosystem resilience. We investigated a widespread European forest type, a mixed forest dominated by Picea abies, which has recently experienced an unprecedented level of disturbance across the continent. Using the forest landscape model iLand, we investigated the combined effect of climate change and herbivory on forest structure, composition, and carbon and identified conditions leading to ecosystem transitions on a 300-year timescale. Eight climate change scenarios, driven by Representative Concentration Pathways 4.5 and 8.5, combined with three levels of regeneration browsing, were tested. We found that the persistence of the current level of browsing pressure impedes adaptive changes in community composition and sustains the presence of the vulnerable yet less palatable P. abies. These development trajectories were tortuous, characterized by a high disturbance intensity. On the contrary, reduced herbivory initiated a transformation towards the naturally dominant broadleaved species that was associated with an increased forest carbon and a considerably reduced disturbance. The conditions of RCP4.5 combined with high and moderate browsing levels preserved the forest within its reference range of variability, defining the actual boundaries of resilience. The remaining combinations of browsing and climate change led to ecosystem transitions. Under RCP4.5 with browsing effects excluded, the new equilibrium conditions were achieved within 120 years, whereas the stabilization was delayed by 50-100 years under RCP8.5 with higher browsing intensities. We conclude that forests dominated by P. abies are prone to transitions driven by climate change. However, reducing herbivory can set the forest on a stable and predictable trajectory, whereas sustaining the current browsing levels can lead to heightened disturbance activity, extended transition times, and high variability in the target conditions.
- Klíčová slova
- European temperate forests, ecological resilience, ecosystem modelling, forest dynamics, large wildlife herbivores, natural disturbances,
- MeSH
- býložravci * MeSH
- ekosystém * MeSH
- klimatické změny MeSH
- lesy MeSH
- uhlík MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- uhlík MeSH
Bioactive moieties designed to bind to cell membrane receptors benefit from coupling with polymeric carriers that have enhanced affinity to the cell membrane. When bound to the cell surface, such carriers create a "2D solution" of a ligand with a significantly increased concentration near a membrane-bound receptor compared to a freely water-soluble ligand. Bifunctional polymeric carriers based on amphiphilic triblock copolymers were synthesized from 2-pent-4-ynyl oxazoline, 2-nonyl oxazoline and 2-ethyl oxazoline. Their self-assembly and interactions with plasma proteins and HEK 293 cells were studied in detail. The affinity of these triblock copolymers to HEK 293 cell membranes and organ tissues was tunable by the overall hydrophobicity of the polymer molecule, which is determined by the length of the hydrophobic and hydrophilic blocks. The circulation time and biodistribution of three representative triblock copolymers were monitored after intravenous administration to C57BL/6 albino mice. A prolonged circulation time was observed for polymers with longer hydrophobic blocks, despite their molecular weight being below the renal threshold.
- Klíčová slova
- Amphiphilic triblock polyoxazoline, Biodistribution in vivo, Blood proteins, Drug delivery, HEK 293 cells, Isothermal titration calorimetry,
- MeSH
- buněčná membrána MeSH
- cytoplazma MeSH
- HEK293 buňky MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- ligandy MeSH
- micely * MeSH
- myši MeSH
- polymery * chemie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ligandy MeSH
- micely * MeSH
- poly(2-oxazoline) MeSH Prohlížeč
- polymery * MeSH
MOTIVATION: Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target. HYPOTHESIS: We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation. EXPERIMENTS: In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering. FINDINGS: We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.
- Klíčová slova
- Amyloid fibrils, Amyloidosis, Gradient copolymers, Lysozyme, Poly(2-oxazoline),
- MeSH
- amyloid * MeSH
- amyloidogenní proteiny MeSH
- amyloidóza * MeSH
- kalorimetrie MeSH
- lidé MeSH
- polymery MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amyloid * MeSH
- amyloidogenní proteiny MeSH
- polymery MeSH
Since the time of Faraday's experiments, the optical response of plasmonic nanofluids has been tailored by the shape, size, concentration, and material of nanoparticles (NPs), or by mixing different types of NPs. To date, water-based liquids have been the most extensively investigated host media, while polymers, such as poly(ethylene glycol) (PEG), have frequently been added to introduce repulsive steric interactions and protect NPs from agglomeration. Here, we introduce an inverse system of non-aqueous nanofluids, in which Ag and Cu NPs are dispersed in PEG (400 g mol-1), with no solvents or chemicals involved. Our single-step approach comprises the synthesis of metal NPs in the gas phase using sputtering-based gas aggregation cluster sources, gas flow transport of NPs, and their deposition (optionally simultaneous) on the PEG surface. Using computational fluid dynamics simulations, we show that NPs diffuse into PEG at an average velocity of the diffusion front of the order of μm s-1, which is sufficient for efficient loading of the entire polymer bulk. We synthesize yellow Ag/PEG, green Cu/PEG, and blue Ag/Cu/PEG nanofluids, in which the color is given by the position of the plasmon resonance. NPs are prone to partial agglomeration and sedimentation, with a slower kinetics for Cu. Density functional theory calculations combined with UV-vis data and zeta-potential measurements prove that the surface oxidation to Cu2O and stronger electrostatic repulsion are responsible for the higher stability of Cu NPs. Adopting the De Gennes formalism, we estimate that PEG molecules adsorb on the NP surface in mushroom coordination, with the thickness of the adsorbed layer L < 1.4 nm, grafting density σ < 0.20, and the average distance between the grafted chains D > 0.8 nm. Such values provide sufficient steric barriers to retard, but not completely prevent, agglomeration. Overall, our approach offers an excellent platform for fundamental research on non-aqueous nanofluids, with metal-polymer and metal-metal interactions unperturbed by the presence of solvents or chemical residues.
- Publikační typ
- časopisecké články MeSH
Extensive road construction works recently took place in the remote eastern part of the Peruvian Cordillera Blanca, aiming at a better connection of isolated mountain communities with regional administrative centres. Here we document and characterize landslides associated with these road construction efforts in the Río Lucma catchment, Peru. We show that a total area of 321,332 m2 has been affected by landslides along the 47.1 km of roads constructed between 2015 and 2018. While landslides downslope the roads (48.2%) and complex landslides crossing the roads (46.4%) were the most frequent landslide types in relation to the position of the road; slide-type movement (60.7%) prevails over the flow-type movement (39.3%). Timewise, we found that 75.0% of landslides were observed simultaneously with road construction work, while the remaining 25.0% occurred up to seven months after the roads had been constructed. We plotted the lagged occurrence of these subsequent landslides against precipitation data, showing that 85.7% of them were observed during the wet season (November to April). We conclude that the majority of mapped landslides were directly associated with road constructions and that the road constructions also may set preconditions for landslides, which mainly occurred during the subsequent wet season.
- MeSH
- sesuvy půdy * MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Peru MeSH
Silver nanoparticles are versatile platforms with a variety of applications in the biomedical field. In this framework, their presence in biological media inevitably leads to the interaction with proteins thus conducting to the formation of biomolecular coronas. This feature alters the identity of the nanomaterial and may affect many biological events. These considerations motivated the investigation of protein adsorption onto the surface of polymer-stabilized AgNPs. The metallic colloids were coated by polyethyleneimine (PEI), polyvinylpyrrolidone (PVP), and poly(2-vinyl pyridine)-b-poly(ethylene oxide) (PEO-b-P2VP), and nanoparticle-protein interaction was probed by using a library of analytical techniques. The experimental data revealed a higher extent of protein adsorption at the surface of AgNPs@PVP whereas PEO-b-P2VP coating conducted to the least amount. The main component of the protein coronas was evidenced to be bovine serum albumin (BSA), which is indeed the protein at the highest abundancy in the model biological media. We have further demonstrated reduced cytotoxicity of the silver colloids coated by biomolecular coronas as compared to the pristine counterparts. Nevertheless, the protein coatings did not notably reduce the antimicrobial performance of the polymer-stabilized AgNPs. Accordingly, although the protein-repelling property is frequently targeted towards longer in vivo circulation of nanoparticles, we herein underline that protein coatings, which are commonly treated as artifacts to be avoided, may indeed enhance the biological performance of nanomaterials. These findings are expected to be highly relevant in the design of polymer-stabilized metallic colloids intended to be used in healthcare.
- Klíčová slova
- Antimicrobial properties, Cytotoxicity, Nano-bio interface, Protein corona, Silver colloids,
- MeSH
- antibakteriální látky farmakologie MeSH
- ethylenoxid MeSH
- koloidy MeSH
- kovové nanočástice * MeSH
- polyethylenimin farmakologie MeSH
- polymery farmakologie MeSH
- povidon farmakologie MeSH
- proteinová korona * metabolismus MeSH
- pyridiny MeSH
- sérový albumin hovězí MeSH
- stříbro farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- ethylenoxid MeSH
- koloidy MeSH
- polyethylenimin MeSH
- polymery MeSH
- povidon MeSH
- proteinová korona * MeSH
- pyridiny MeSH
- sérový albumin hovězí MeSH
- stříbro MeSH
Tree rings provide valuable insight into past environmental changes. This study aimed to evaluate perturbations in tree ring width (TRW) and δ15N alongside soil acidity and nutrient availability gradients caused by the contrasting legacy of air pollution (nitrogen [N] and sulphur [S] deposition) and tree species (European beech, Silver fir and Norway spruce). We found consistent declines of tree ring δ15N, which were temporarily unrelated to the changes in the TRW. The rate of δ15N change in tree rings was related to the contemporary foliar carbon (C) to phosphorus (P) ratio. This observation suggested that the long-term accumulation of 15N depleted N in tree rings, likely mediated by retained N from deposition, was restricted primarily to stands with currently higher P availability. The shifts observed in tree-ring δ15N and TRW suggest that acidic air pollution rather than changes in stand productivity determined alteration of N and C cycles. Stable N isotopes in tree rings provided helpful information on the trajectory of the N cycle over the last century with direct consequences for a better understanding of future interactions among N, P and C cycles in terrestrial ecosystems.
- Klíčová slova
- Eutrophication, Forest productivity, Isotope, Phosphorus, Tree species, nitrogen,
- MeSH
- buk (rod) * MeSH
- dusík MeSH
- ekosystém MeSH
- izotopy dusíku analýza MeSH
- izotopy uhlíku analýza MeSH
- lesy MeSH
- smrk * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dusík MeSH
- izotopy dusíku MeSH
- izotopy uhlíku MeSH
