The Turkevich method was optimized to prepare gold nanoparticles (AuNP) stabilized by polyethyleneglycol (PEG) for μCT. Using various independent modalities, we thoroughly characterized the optimized PEG-AuNPs. Here, we show that PEG-AuNPs are retained in the blood and provide a high contrast in the high-resolution μCT imaging of blood vessels and inner organs. The biodistribution is characterized by prolonged circulation in the blood and accumulation in the liver, spleen and skin. The accumulation of AuNP in the skin resulted in the blue discoloration of eyes and the whole skin. In vitro experiments using a leukemic monocyte THP-1 cell line model expressing high levels of NLRP3 demonstrated that the NLRP3inflammasome was not activated by PEG AuNP. Over 9 months, the mice were scanned by μCT and were in good health. Scans in mice using PEG-stabilized AuNPs in this study were sharper, with a higher contrast, when compared to a commercial contrasting agent at the same dose. The PEG-AuNPs were morphologically and chemically stable for at least two years when stored in the refrigerator.
- Publikační typ
- časopisecké články MeSH
Barium and strontium are often used as proxies of marine productivity in palaeoceanographic reconstructions of global climate. However, long-searched biological drivers for such correlations remain unknown. Here, we report that taxa within one of the most abundant groups of marine planktonic protists, diplonemids (Euglenozoa), are potent accumulators of intracellular barite (BaSO4), celestite (SrSO4), and strontiobarite (Ba,Sr)SO4. In culture, Namystinia karyoxenos accumulates Ba2+ and Sr2+ 42,000 and 10,000 times higher than the surrounding medium, forming barite and celestite representing 90% of the dry weight, the greatest concentration in biomass known to date. As heterotrophs, diplonemids are not restricted to the photic zone, and they are widespread in the oceans in astonishing abundance and diversity, as their distribution correlates with environmental particulate barite and celestite, prevailing in the mesopelagic zone. We found diplonemid predators, the filter-feeding zooplankton that produces fecal pellets containing the undigested celestite from diplonemids, facilitating its deposition on the seafloor. To the best of our knowledge, evidence for diplonemid biomineralization presents the strongest explanation for the occurrence of particulate barite and celestite in the marine environment. Both structures of the crystals and their variable chemical compositions found in diplonemids fit the properties of environmentally sampled particulate barite and celestite. Finally, we propose that diplonemids, which emerged during the Neoproterozoic era, qualify as impactful players in Ba2+/Sr2+ cycling in the ocean that has possibly contributed to sedimentary rock formation over long geological periods. IMPORTANCE We have identified that diplonemids, an abundant group of marine planktonic protists, accumulate conspicuous amounts of Sr2+ and Ba2+ in the form of intracellular barite and celestite crystals, in concentrations that greatly exceed those of the most efficient Ba/Sr-accumulating organisms known to date. We propose that diplonemids are potential players in Ba2+/Sr2+ cycling in the ocean and have possibly contributed to sedimentary rock formation over long geological periods. These organisms emerged during the Neoproterozoic era (590 to 900 million years ago), prior to known coccolithophore carbonate biomineralization (~200 million years ago). Based on reported data, the distribution of diplonemids in the oceans is correlated with the occurrence of particulate barite and celestite. Finally, diplonemids may provide new insights into the long-questioned biogenic origin of particulate barite and celestite and bring more understanding of the observed spatial-temporal correlation of the minerals with marine productivity used in reconstructions of past global climate.
- MeSH
- baryum MeSH
- minerály MeSH
- oceány a moře MeSH
- plankton MeSH
- síran barnatý * MeSH
- stroncium * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- oceány a moře MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Nanodiamonds (ND), especially fluorescent NDs, represent potentially applicable drug and probe carriers for in vitro/in vivo applications. The main purpose of this study was to relate physical-chemical properties of carboxylated NDs to their intracellular distribution and impact on membranes and cell immunity-activation of inflammasome in the in vitro THP-1 cell line model. Dynamic light scattering, nanoparticle tracking analysis, and microscopic methods were used to characterize ND particles and their intracellular distribution. Fluorescent NDs penetrated the cell membranes by both macropinocytosis and mechanical cutting through cell membranes. We proved accumulation of fluorescent NDs in lysosomes. In this case, lysosomes were destabilized and cathepsin B was released into the cytoplasm and triggered pathways leading to activation of inflammasome NLRP3, as detected in THP-1 cells. Activation of inflammasome by NDs represents an important event that could underlie the described toxicological effects in vivo induced by NDs. According to our knowledge, this is the first in vitro study demonstrating direct activation of inflammasome by NDs. These findings are important for understanding the mechanism(s) of action of ND complexes and explain the ambiguity of the existing toxicological data.
- MeSH
- buněčná membrána účinky léků metabolismus ultrastruktura MeSH
- dynamický rozptyl světla MeSH
- elektronová mikroskopie MeSH
- fluorescence MeSH
- inflamasomy účinky léků imunologie metabolismus MeSH
- intravitální mikroskopie metody MeSH
- kathepsin B imunologie metabolismus MeSH
- konfokální mikroskopie MeSH
- lidé MeSH
- lyzozomy účinky léků imunologie metabolismus ultrastruktura MeSH
- mikroskopie atomárních sil MeSH
- nanodiamanty aplikace a dávkování chemie MeSH
- pinocytóza MeSH
- protein NLRP3 imunologie metabolismus MeSH
- THP-1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. METHODS: Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. RESULTS: Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. CONCLUSION: This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes.
- MeSH
- antipsychotika aplikace a dávkování škodlivé účinky MeSH
- magnetická rezonanční tomografie MeSH
- mozkový krevní oběh účinky léků MeSH
- olanzapin aplikace a dávkování škodlivé účinky MeSH
- potkani Sprague-Dawley MeSH
- rozvrh dávkování léků MeSH
- senzorimotorický kortex krevní zásobení diagnostické zobrazování účinky léků MeSH
- velikost orgánu účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The inhalation or application of nanoparticles (NPs) has serious impacts on immunological reactivity. However, the effects of NPs on the immune system are influenced by numerous factors, which cause a high variability in the results. Here, mice were exposed to a three month continuous inhalation of copper oxide (CuO) NPs, and at different time intervals (3, 14, 42 and 93 days), the composition of cell populations of innate and adaptive immunity was evaluated in the spleen by flow cytometry. The ability of spleen cells from exposed and control mice to respond to stimulation with T- or B-cell mitogens by proliferation and by production of cytokines IL-2, IL-6, IL-10, IL-17 and IFN-γ was characterized. The results showed that the inhalation of CuO NPs predominantly affects the cells of innate immunity (changes in the proportion of eosinophils, neutrophils, macrophages and antigen-presenting cells) with a minimal effect on the percentage of T and B lymphocytes. However, the proliferative and secretory activity of T cells was already significantly enhanced after 3 days from the start of inhalation, decreased on day 14 and normalized at the later time intervals. There was no correlation between the impacts of NPs on the cells of innate and adaptive immunity. The results have shown that the inhalation of CuO NPs significantly alters the composition of cell populations of innate immunity and modulates the proliferation and production of cytokines by cells of the adaptive immune system. However, the immunomodulatory effects of inhaled NPs strongly depend on the time of inhalation.
- MeSH
- adaptivní imunita účinky léků MeSH
- aplikace inhalační MeSH
- cytokiny biosyntéza MeSH
- kinetika MeSH
- měď aplikace a dávkování toxicita MeSH
- modely u zvířat MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nanočástice toxicita MeSH
- přirozená imunita účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The great potential of scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) is in detection of unusual chemical elements included in ancient human dental calculus to verify hypotheses about life and burial habits of historic populations and individuals. Elemental spectra were performed from archeological samples of three chosen individuals from different time periods. The unusual presence of magnesium, aluminum, and silicon in the first sample could confirm the hypothesis of high degree of dental abrasion caused by particles from grinding stones in flour. In the second sample, presence of copper could confirm that bronze jewelery could lie near the buried body. The elemental composition of the third sample with the presence of lead and copper confirms the origin of individual to Napoleonic Wars because the damage to his teeth could be explained by the systematic utilization of the teeth for the opening of paper cartridges (a charge with a dose of gunpowder and a bullet), which were used during the 18th and the 19th century AD. All these results contribute to the reconstruction of life (first and third individual) and burial (second individual) habits of historic populations and individuals.
Thirteen samples of ancient human dental calculus were analyzed by scanning electron microscopy (SEM). Samples came from ten adults from the necropolis Znojmo-Hradiště which is dated to the Great Moravian period (the end of the 9th and beginning of the 10th century AD). SEM allowed observation and measurement of the excavated calculus objects with submicrometer resolution. Therefore it was possible to estimate plant/vegetable fibers and all bacterial morphological types like rods, cocci, spirals and filamentous forms. This confirms high oral bacterial diversity of medieval agriculturalists which is in agreement with recent molecular studies, but without destruction of samples and with lower costs. Presence of plant/vegetable fibers in dental calculus validated the vegetable part of the diet of early medieval Slavs found directly in excavated human skeletons.
- Klíčová slova
- Morava (Česko),
- MeSH
- archeologie metody MeSH
- Bacteria izolace a purifikace MeSH
- dějiny starověku MeSH
- exhumace MeSH
- lidé MeSH
- mikroskopie elektronová rastrovací metody MeSH
- tělesné pozůstatky MeSH
- zubní kámen * mikrobiologie MeSH
- Check Tag
- dějiny starověku MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH