With the emergence of nano-enabled medical devices (MDs) for the use in human medicine, ensuring their safety becomes of crucial importance. Hemocompatibility is one of the major criteria for ...approval of all MDs in contact with blood (e.g. vascular grafts, stents, or valves). Silver nanoparticles (AgNPs) are among the most used nanomaterials for MDs due to their biocidal activity; however, detailed knowledge on their hemostatic effects is still lacking.
This study aimed to evaluate comprehensively AgNPs effects on hemostasis in human blood by exploiting combination of affordable and clinically relevant techniques.
Differently stabilized AgNPs were prepared using sodium bis(2-ethylhexyl)sulphosuccinate (AOT), polyvinylpyrrolidone (PVP), poly-L-lysine (PLL), and bovine serum albumin (BSA) as coating agents. They were tested for hemolytic activity, induction of platelet aggregation, plasmatic coagulation, thrombin generation, and hemostasis in whole blood.
All AgNPs were found to cause dose-dependent hemolysis. The BSA-, AOT-, and PVP-coated AgNPs delayed plasmatic coagulation, while only PLL-AgNPs inhibited plasmatic coagulation, induced platelet activation, and interfered with hemostasis by delaying clotting time and decreasing clot firmness in whole blood.
Obtained results demonstrate that a combination of different techniques should be used for reliable assessment of AgNPs hemostatic effects highlighting the need for a standardized approach in sampling and experimental protocols.
Despite increasing use of silver nanoparticles (AgNPs) in different medicinal products, knowledge about their effects on hemostasis and platelets functionality is still scarce. Published scientific ...reports provide neither data on oxidative stress response of platelets to AgNPs nor information about the effects of AgNPs physicochemical properties on functionality and activation of platelets. This study aimed to explore the role of AgNPs surface functionalization on cell viability, particle uptake, oxidative stress response, and activation of platelets. Small sized, spherical AgNPs were surface functionalized by negatively charged sodium bis(2-ethylhexyl) sulphosuccinate (AOT), neutral polymer polyvinylpyrrolidone (PVP), positively charged polymer poly-l-lysine (PLL) and bovine serum albumin (BSA). Platelet viability, activation and particle uptake were evaluated by flow cytometry. Oxidative stress response was evaluated by measuring the levels of intracellular glutathione (GSH), peroxy and superoxide radicals using assays based on fluorescence dies. Cytotoxicity and uptake of AgNPs to platelets were found to be dose-dependent in a following order PLL-AgNP >> > BSA-AgNP > AOT-AgNP > PVP-AgNP. Particle internalization was further confirmed by transmission electron microscopy. Treatment of platelets with AgNPs induced superoxide radical formation, depletion of GSH and hyperpolarization of the mitochondrial membrane. Small, but statistically significant increase of P-selectin expression in cells treated with all AgNPs compared to non-treated controls evidenced AgNPs-induced activation of platelets. Increased PAC-1 expression was found only in platelets treated with PLL-AgNPs. Obtained results demonstrate that different surface decoration of AgNPs determines their biological effects on platelets highlighting the importance of careful design of AgNPs-based medicinal products regarding their biocompatibility and functionality.
Synopsis: Surface functionalization of silver nanoparticles (AgNPs) determines their interaction with platelets affecting cell viability, particle uptake, oxidative stress response, and platelets activation. Display omitted
•Response of platelets to silver nanoparticles (AgNPs) was evaluated.•Surface functionalization of AgNPs determines their effects on platelets.•Cytotoxicity and uptake of AgNPs in platelets is dose-dependent.•Mild activation of platelets by AgNPs was observed by P-selectin expression.•PAC-1 expression was found only for platelets treated by positively charged AgNPs.
Silver nanoparticles (AgNPs) are one of the most investigated metal-based nanomaterials. Their biocidal activity boosted their application in both diagnostic and therapeutic medical systems. It is ...therefore crucial to provide sound evidences for human-related safety of AgNPs. This study aimed to enhance scientific knowledge with regard to biomedical safety of AgNPs by investigating how their different surface properties affect human immune system.
preparation, characterization and stability evaluation was performed for four differently coated AgNPs encompassing neutral, positive and negative agents used for their surface stabilization. Safety aspects were evaluated by testing interaction of AgNPs with fresh human peripheral blood mononuclear cells (hPBMC) by means of particle cellular uptake and their ability to trigger cell death, apoptosis and DNA damages through induction of oxidative stress and damages of mitochondrial membrane.
all tested AgNPs altered morphology of freshly isolated hPBMC inducing apoptosis and cell death in a dose- and time-dependent manner. Highest toxicity was observed for positively-charged and protein-coated AgNPs. Cellular uptake of AgNPs was also dose-dependently increased and highest for positively charged AgNPs. Intracellularly, AgNPs induced production of reactive oxygen species (ROS) and damaged mitochondrial membrane. Depending on the dose, all AgNPs exhibited genotoxic potential.
this study provides systematic and comprehensive data showing how differently functionalized AgNPs may affect the human immune system. Presented results are a valuable scientific contribution to safety assessment of nanosilver-based blood-contacting medical products.
The interaction of silver nanoparticles (AgNPs) with the immune system has not yet been sufficiently elucidated even though they belong to the most investigated and exploited group of nanomaterials. ...This study aimed to evaluate immunomodulatory effect of four different AgNPs on human peripheral blood mononuclear cells (hPBMCs). Fresh hPBMCs were exposed to the small sized (~ 10 nm) AgNPs immediately after isolation from the whole blood of healthy volunteers. The study considered coating-, time- and dose-dependent response of hPBMSc and stimulation of both early and intermediate activation of lymphocytes and monocytes using flow cytometry. The AgNPs differed in surface charge and were stabilised with polyvinyl pyrrolidone (PVP), poly-L-lysine (PLL), bis(2-ethylhexyl) sulfosuccinate sodium (AOT) or blood serum albumin (BSA). Response of hPBMCs to coating agents and ionic Ag form was evaluated to distinguish their effect from the AgNPs action as they may be released from the nanosurface. There was no significant effect of any tested AgNPs on relative count of hPBMCs subpopulations. The T-cells and monocytes were not activated after treatment with AgNPs, but the highest concentration of PLL- and BSA-AgNPs decreased density of CD4 and CD8 markers on T-helper and T-cytotoxic cells, respectively. The same AgNPs activated B- and NK-cells. Ionic Ag activated T-, B- and NK-cells, but at very higher concentration, whereas only PLL exhibited immunomodulatory activity. This study evidenced immunomodulatory activity of AgNPs that may be fine-tuned by the design of their surface functionalization.
Graphic abstract
U ovom radu istražena je učinkovitost hladne i tople (Soxhlet) ekstrakcije ulja iz suhe tvari liofiliziranih maslinovih tijesta (bez koštice i s košticom) te iz sjemenki ploda masline sorte Leccino. ...Istražen je i utjecaj ekstrakcije na sadržaj ukupnih fenolnih tvari i orto-difenola u dobivenim uljima. U maslinovim tijestima i sjemenkama određen je udio ukupnih fenola i antioksidacijski kapacitet (IC50). Hladna i topla ekstrakcija pokazale su se podjednako učinkovite u izdvajanju ulja iz liofiliziranih maslinovih tijesta, dok je topla ekstrakcija bila učinkovitija u izdvajanju ulja iz sjemenki. Maslinova tijesta bez koštice imala su najveći udio fenolnih tvari (12,9 mg g-1 s.t.) od tri ispitivana biljna materijala. Stoga su i ulja dobivena iz njih, osobito ona dobivena toplom ekstrakcijom, sadržavala najveće udjele ukupnih fenola (396,7 mg kg-1) i orto-difenola (206,3 mg kg-1). U odnosu na maslinova tijesta, sjemenke su imale statistički značajno niži udio ukupnih fenola te višestruko niži antioksidacijski kapacitet. Rezultati su potvrdili da se uklanjanjem koštice smanjuje negativni utjecaj peroksidaza iz sjemenki na fenolne tvari u tijestu i ulju, te upućuju da se primjenom tople ekstrakcije povećava topljivost fenolnih tvari iz biljnog materijala u ulju.
Intercellular communication via chemical signaling proceeds with both spatial and temporal components, but analytical tools, such as microfabricated electrodes, have been limited to just a few probes ...per cell. In this work, we use a nonphotobleaching fluorescent nanosensor array based on single-walled carbon nanotubes (SWCNTs) rendered selective to dopamine to study its release from PC12 neuroprogenitor cells at a resolution exceeding 20,000 sensors per cell. This allows the spatial and temporal dynamics of dopamine release, following K⁺ stimulation, to be measured at exceedingly high resolution. We observe localized, unlabeled release sites of dopamine spanning 100 ms to seconds that correlate with protrusions but not predominately the positive curvature associated with the tips of cellular protrusions as intuitively expected. The results illustrate how directionality of chemical signaling is shaped by membrane morphology, and highlight the advantages of nanosensor arrays that can provide high spatial and temporal resolution of chemical signaling.
The release of oil into the environment represents a pervasive problem stemming from oil exploration, accidents, transportation and releases from landfills, storage facilities or industrial plants. ...Compared to conventional and costly techniques, bioremediation is an attractive and promising alternative, as it can selectively degrade pollution without affecting the natural features of the site and the flora and fauna living there. In this study, the isolation, identification and characterization of autochthonous bacterial strains from a crude oil-contaminated soil sample was carried out under batch conditions over a period of 28 days. The initial colony forming units value for bacteria was 1.15 × 109/g of soil. The results show that the activity of bacteria was highest at a pH of 7.25. Based on morphology, biochemical tests and an analysis of MALDI TOF, isolated autochthonous bacterial species were identified as Bacillus megaterium, Bacillus licheniformis, Bacillus cereus and Pseudomonas chlororaphis. Since allochthonous bacteria are not highly efficient in a new environment due to their low adaptability and competition with indigenous microorganisms, these autochthonous microorganisms play a pivotal role in enhancing the bioremediation process on an applicable, industrial scale. This advancement aligns with the principles of sustainable development and the green economy, as purified soil is suitable for rational reuse in the environment.
Abstract Citrin deficiency (CD) is a recessive, liver disease caused by sequence variants in the SLC25A13 gene encoding a mitochondrial aspartate–glutamate transporter. CD manifests as different ...age‐dependent phenotypes and affects crucial hepatic metabolic pathways including malate–aspartate‐shuttle, glycolysis, gluconeogenesis, de novo lipogenesis and the tricarboxylic acid and urea cycles. Although the exact pathophysiology of CD remains unclear, impaired use of glucose and fatty acids as energy sources due to NADH shuttle defects and PPARα downregulation, respectively, indicates evident energy deficit in CD hepatocytes. The present review summarizes current trends on available and potential treatments for CD. Baseline recommendation for CD patients is dietary management, often already present as a self‐selected food preference, that includes protein and fat‐rich food, and avoidance of excess carbohydrates. At present, liver transplantation remains the sole curative option for severe CD cases. Our extensive literature review indicated medium‐chain triglycerides (MCT) as the most widely used CD treatment in all age groups. MCT can effectively improve symptoms across disease phenotypes by rapidly supplying energy to the liver, restoring redox balance and inducing lipogenesis. In contrast, sodium pyruvate restored glycolysis and displayed initial preclinical promise, with however limited efficacy in adult CD patients. Ursodeoxycholic acid, nitrogen scavengers and L ‐arginine treatments effectively address specific pathophysiological aspects such as cholestasis and hyperammonemia and are commonly administered in combination with other drugs. Finally, future possibilities including restoring redox balance, amino acid supplementation, enhancing bioenergetics, improving ureagenesis and mRNA/DNA‐based gene therapy are also discussed.
Degrees of non-standardness Vuković, Teodora; Escher, Anastasia; Sonnenhauser, Barbara
International journal of corpus linguistics,
06/2022, Letnik:
27, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract
A corpus-based method for assessing a range of dialect-standard variation is presented for identifying samples exhibiting the highest prevalence of dialect features. This method provides ...insight into areal and inter-speaker variation and allows the extraction of maximally non-standard manifestations of the dialect, which may then be sampled and used for the study of language change and variation. The focus is on a non-standard Torlak variety, which has undergone considerable change under the influence of standard Serbian. The degree of variation is assessed by measuring the frequencies of five distinguishing linguistic features: accent position, dative reflexive
si
, auxiliary omission in the compound perfect, the post-positive article, and analytic case marking in the indirect object and possessive. Locations subject to the greatest and least influence of the standard are revealed using hierarchical clustering. A positive correlation between the frequencies of occurrence reveals which non-standard feature is the best predictor of the others.
Gastroezofagealni refluks predstavlja vraćanje sadržaja želuca u jednjak, ponekad praćeno regurgitacijom i/ili povraćanjem. Refluks je patološki ako dovodi do značajnih (zabrinjavajućih) simptoma ...i/ili komplikacija (gastroezofagealna refluksna bolest, GERB). Simptomi refluksne bolesti nisu specifični, ovise o dobi djeteta i povezanost s refluksom je ponekad teško dokazati. U svakog djeteta sa simptomima refluksne bolesti i upozoravajućim znacima trebalo bi obradom isključiti mogući drugi uzrok tegoba. Višekanalna intraluminalna impedancija jednjaka koristi se u određivanju korelacije simptoma s refluksnim događajima, procjene učinkovitosti antisekretorne terapije i razlikovanja ne-erozivne refluksne bolesti, hipersenzitivnog jednjaka i funkcijske žgaravice. Pasaža probavnog sustava i ultrazvuk abdomena koriste se u isključivanju anatomskih anomalija. Ezofagogastroduodenoskopija s biopsijama sluznice glavna je pretraga za procjenu komplikacija refluksne bolesti i isključivanja druge bolesti sluznice gornjeg dijela probavnog sustava, a manometrija jednjaka u slučaju sumnje u poremećaj
motiliteta. Pokusna primjena inhibitora protonske pumpe (IPP) tijekom 4 – 8 tjedana moguća je u djece s tipičnim simptomima refluksne bolesti (žgaravica, retrosternalna ili epigastrična bol), ali se ne preporučuje u dojenčadi i djece s ekstraezofagealnim simptomima. Nefarmakološko liječenje refluksne bolesti uključuje zagušćivanje obroka, položajne mjere, modifikaciju volumena i učestalosti obroka i primjenu ekstenzivnog hidrolizata tijekom 2 – 4 tjedna u dojenčadi koja su na prehrani dojenačkim mliječnim pripravkom. Antacide/alginate ne bi trebalo koristiti za kronično liječenje dojenčadi i djece s refluksnom bolesti. Inhibitori protonske pumpe preporučuju se kao prva linija terapija erozivnog ezofagitisa povezanog s refluksom, a inhibitori H2-receptora u slučaju njihove nedostupnosti ili kontraindikacije za njihovu primjenu. Isključenje drugih uzroka tegoba preporučuje se u djece koja ne reagiraju na optimalnu terapiju tijekom 4 – 8 tjedana. Terapiju baklofenom trebalo bi razmotriti prije kirurškog liječenja nakon neuspjele primjene drugih farmakoloških mjera. Antirefluksnu operaciju (uključujući fundoplikaciju) trebalo bi razmotriti u djece sa životno ugrožavajućim komplikacijama refluksne bolesti nakon neuspjeha farmakološkog liječenja, refraktornim simptomima i u slučaju neophodne dugotrajne farmakoterapije GERB-a.
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