Nanoparticles (NPs) have a wide use in various field of industry and in medicine, where they represent a promise for their antimicrobial effects. Simultaneous application of NPs and therapeutic stem cells can speed up tissue regeneration and improve healing process but there is a danger of negative impacts of NPs on stem cells. Therefore, we tested effects of four types of metal antimicrobial NPs on characteristics and function properties of mouse mesenchymal stem cells (MSCs) in vitro. All types of tested NPs, i.e. zinc oxide, silver, copper oxide and titanium dioxide, exerted negative effects on the expression of phenotypic markers, metabolic activity, differentiation potential, expression of genes for immunoregulatory molecules and on production of cytokines and growth factors by MSCs. However, there were apparent differences in the impact of individual types of NPs on tested characteristics and function properties of MSCs. The results showed that individual types of NPs influence the activity of MSCs, and thus the use of metal NPs during tissue regeneration and in combination with stem cell therapy should be well considered.

• MeSH
• antiinfekční látky * MeSH
• buněčná diferenciace MeSH
• hojení ran MeSH
• kovové nanočástice * toxicita   MeSH
• mezenchymální kmenové buňky * MeSH
• myši MeSH
• nanočástice * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Negative impacts of nanomaterials on stem cells and cells of the immune system are one of the main causes of an impaired or slowed tissue healing. Therefore, we tested effects of four selected types of metal nanoparticles (NPs): zinc oxide (ZnO), copper oxide (CuO), silver (Ag), and titanium dioxide (TiO2) on the metabolic activity and secretory potential of mouse mesenchymal stem cells (MSCs), and on the ability of MSCs to stimulate production of cytokines and growth factors by macrophages. Individual types of nanoparticles differed in the ability to inhibit metabolic activity, and significantly decreased the production of cytokines and growth factors (interleukin-6, vascular endothelial growth factor, hepatocyte growth factor, insulin-like growth factor-1) by MSCs, with the strongest inhibitory effect of CuO NPs and the least effect of TiO2 NPs. The recent studies indicate that immunomodulatory and therapeutic effects of transplanted MSCs are mediated by macrophages engulfing apoptotic MSCs. We co-cultivated macrophages with heat-inactivated MSCs which were untreated or were preincubated with the highest nontoxic concentrations of metal NPs, and the secretory activity of macrophages was determined. Macrophages cultivated in the presence of both untreated MSCs or MSCs preincubated with NPs produced significantly enhanced and comparable levels of various cytokines and growth factors. These results suggest that metal nanoparticles inhibit therapeutic properties of MSCs by a direct negative effect on their secretory activity, but MSCs cultivated in the presence of metal NPs have preserved the ability to stimulate cytokine and growth factor production by macrophages.

• MeSH
• cytokiny MeSH
• kovové nanočástice * MeSH
• mezenchymální kmenové buňky * MeSH
• myši MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The maternal diet during pregnancy affects neonatal health status. The objective of this study was to assess the nutritional quality of the maternal diet, and its contamination by persistent organic pollutants (POPs), in pregnant women living in two areas of the Czech Republic with different levels of air pollution, and subsequently to assess the relationship of these two factors with birth weight and neonatal oxidative stress. To determine the level of oxidative stress, 8-isoprostane concentrations in umbilical cord plasma were measured. The overall nutritional quality of the maternal diet was not optimal. Of the nutritional factors, protein intake proved to be the most significant showing a positive relationship with birth weight, and a negative relationship with the oxidative stress of newborns. Dietary contamination by persistent organic pollutants was low and showed no statistically significant relationship with birth weight. Only one of the 67 analyzed POPs, namely the insecticide dichlorodiphenyltrichloroethane (DDT), showed a statistically significant positive relationship with the level of neonatal oxidative stress.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: To study the impact of oxidative damage associated with particulate matter< 2.5 μm (PM2.5) during prenatal period on the cognitive development in five years old children. METHODS: Two cohorts of children aged five years, born in the years 2013 and 2014, were studied for their cognitive development in the polluted district Karvina and the control district Ceske Budejovice. Exposure to PM2.5 in the ambient air was measured for each mother during the 3rd trimester of pregnancy. Oxidative damage was determined from the level of biomarkers at delivery in mothers ́ and newborns ́ urine as 8-oxo-7,8-dihydro-2 ́-deoxyguanosine (8-oxodG) and in plasma as 15-F2t-isoprostane levels (15-F2t-IsoP). The Bender Visual Motor Gestalt Test (BG test) and the Raven Colored Progressive Matrices (RCPM test) were used as psychological cognitive tests. RESULTS: Average concentrations of PM2.5 ± SD in the 3rd trimester of mothers ́ pregnancies were 37.7 ± 14.7 μg/m3 and 17.1 ± 4.8 μg/m3 in Karvina and Ceske Budejovice, respectively (p < 0.001). The maternal level of 15-F2t-IsoP in plasma at the time of delivery was significantly associated with the results of the RCPM test (p < 0.05) and the BG test (p < 0.05) in five years old children. CONCLUSIONS: Lipid peroxidation in maternal plasma at the time of delivery has an adverse effect on the results of psychological cognitive tests in five years old children.

• MeSH
• 8-hydroxy-2'-deoxyguanosin MeSH
• dítě MeSH
• kognice MeSH
• látky znečišťující vzduch * škodlivé účinky   MeSH
• lidé MeSH
• novorozenec MeSH
• oxidační stres MeSH
• pevné částice škodlivé účinky   MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• vitaminy MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = -1.92, p = 8.30 × 10-4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.

• MeSH
• celogenomová asociační studie MeSH
• dospělí MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA účinky léků   MeSH
• policie * MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Air pollution caused by road traffic has an unfavorable impact on the environment and also on human health. It has previously been shown, that complete gasoline emissions lead to toxic effects in cell models originating from human airways. Here we focused on extractable organic matter (EOM) from particulate matter, collected from gasoline emissions from fuels with different ethanol content. We performed cytotoxicity evaluation, quantification of mucin and extracellular reactive oxygen species (ROS) production, DNA breaks detection, and selected gene deregulation analysis, after one and five days of exposure of human bronchial epithelial model (BEAS-2B) and a 3D model of the human airway (MucilAirTM). Our data suggest that the longer exposure had more pronounced effects on the parameters of cytotoxicity and mucin production, while the impacts on ROS generation and DNA integrity were limited. In both cell models the expression of CYP1A1 was induced, regardless of the exposure period or EOM tested. Several other genes, including FMO2, IL1A, or TNF, were deregulated depending on the exposure time. In conclusion, ethanol content in the fuels did not significantly impact the toxicity of EOM. Biological effects were mostly linked to xenobiotics metabolism and inflammatory response. BEAS-2B cells were more sensitive to the treatment.

• MeSH
• benzin * MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• histony metabolismus   MeSH
• interleukin-1alfa genetika   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• oxygenasy genetika   MeSH
• pevné částice toxicita   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• TNF-alfa genetika   MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Outdoor air pollution is classified as carcinogenic to humans and exposure to it contributes to increased incidence of various diseases, including cardiovascular, neurological or pulmonary disorders. Vehicle engine emissions represent a significant part of outdoor air pollutants, particularly in large cities with high population density. Considering the potentially negative health impacts of engine emissions exposure, the application of reliable test systems allowing assessment of the biological effects of these pollutants is crucial. The exposure systems should use relevant, preferably multicellular, cell models that are treated with the complete engine exhaust (i.e. a realistic mixture of particles, chemical compounds bound to them and gaseous phase) at the air-liquid interface. The controlled delivery and characterization of chemical and/or particle composition of the exhaust should be possible. In this mini-review we report on such exposure systems that have been developed to date. We focus on a brief description and technical characterization of the systems, and discuss the biological parameters detected following exposure to a gasoline/diesel exhaust. Finally, we summarize and compare findings from the individual systems, including their advantages/limitations.

• MeSH
• benzin analýza   toxicita   MeSH
• látky znečišťující vzduch analýza   toxicita   MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• výfukové emise vozidel analýza   toxicita   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   analýza   MeSH
• znečištění ovzduší škodlivé účinky   analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• srovnávací studie MeSH

The evaluation of the frequency of micronuclei (MN) is a broadly utilised approach in in vitro toxicity testing. Nevertheless, the specific properties of nanomaterials (NMs) give rise to concerns regarding the optimal methodological variants of the MN assay. In bronchial epithelial cells (BEAS-2B), we tested the genotoxicity of five types of NMs (TiO2: NM101, NM103; SiO2: NM200; Ag: NM300K, NM302) using four variants of MN protocols, differing in the time of exposure and the application of cytochalasin-B combined with the simultaneous and delayed co-treatment with NMs. Using transmission electron microscopy, we evaluated the impact of cytochalasin-B on the transport of NMs into the cells. To assess the behaviour of NMs in a culture media for individual testing conditions, we used dynamic light scattering measurement. The presence of NMs in the cells, their intracellular aggregation and dispersion properties were comparable when tests with or without cytochalasin-B were performed. The genotoxic potential of various TiO2 and Ag particles differed (NM101 < NM103 and NM302 < NM300K, respectively). The application of cytochalasin-B tended to increase the percentage of aberrant cells. In conclusion, the comparison of the testing strategies revealed that the level of DNA damage induced by NMs is affected by the selected methodological approach. This fact should be considered in the interpretation of the results of genotoxicity tests.

• Publikační typ
• časopisecké články MeSH

A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016-2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation.

• MeSH
• CpG ostrůvky MeSH
• dospělí MeSH
• epigeneze genetická * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• nanočástice škodlivé účinky   MeSH
• nemoci z povolání chemicky indukované   epidemiologie   genetika   MeSH
• pracovní expozice škodlivé účinky   MeSH
• regulace genové exprese účinky léků   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Asthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes - T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) - warrants clarification. OBJECTIVES: To explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype). METHODS: In a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma-overweight/obese (OV/OB) combined outcomes. RESULTS: The non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9-11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7-428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG. CONCLUSIONS: Ambient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.

• MeSH
• 8-hydroxy-2'-deoxyguanosin moč   MeSH
• benzopyren analýza   MeSH
• bronchiální astma krev   epidemiologie   patofyziologie   moč   MeSH
• dinoprost analogy a deriváty   krev   MeSH
• dítě MeSH
• fenotyp MeSH
• kojenec MeSH
• kotinin moč   MeSH
• látky znečišťující vzduch analýza   MeSH
• lidé MeSH
• mladiství MeSH
• plíce patofyziologie   MeSH
• předškolní dítě MeSH
• studie případů a kontrol MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH