Lomljivost telomera u bolničkih radnika profesionalno izloženih niskim dozama ionizirajućega zračenja

AbstractBiološki učinci ionizirajućega zračenja (IZ) pripisuju se oštećenjima DNA i indirektnim učincima kroz povećanu proizvodnju reaktivnih vrsta kisika. Iako se telomere rabe kao pokazatelji radioosjetljivosti, o njihovu ponašanju kao odgovoru na ionizirajuće zračenje u uvjetima profesionalne izloženosti i dalje se raspravlja. U ovom radu željeli smo istražiti duljinu i strukturu telomera u bolničkih radnika koji su profesionalno izloženi ionizirajućem zračenju te povezati te nalaze s oksidacijskim biomolekulama i kromosomskim aberacijama. Uzorci krvi izloženih ispitanika i zdravih kontrola uzeti su za analizu tijekom rutinskoga godišnjeg zdravstvenog pregleda. Osim kromosomskih aberacija, u uzorcima plazme izmjereni su i parametri oksidacijskoga stresa [prooksidacijska/antioksidacijska ravnoteža (PAB), lipidna peroksidacija i 8-okso-dG], a procjena duljine i strukture telomera provedena je metodom Q-FISH na metafaznim kromosomima. Analiza kromosomskih aberacija pokazala je da od 34 ispitanika njih 14 ima kromosomske aberacije (skupina 1), a 20 nije imalo aberacije (skupina 2). Nije bilo značajne razlike u spolu ili dobi ni u duljini telomera između skupina. Međutim, incidencija lomljivih telomera bila je značajno veća u objema skupinama ispitanika izloženih IZ-u u usporedbi s kontrolnim ispitanicima. Produkti peroksidacije lipida i 8-okso-dG također su bili značajno viši u objema skupinama. Učestalost lomljivih telomera u pozitivnoj je korelaciji (statistički značajna) s razinama 8-okso-dG

miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes

Introduction: Genetic studies of congenital anomalies of the kidney and urinary tract (CAKUT) have demonstrated variable penetrability and expressivity of the associated genetic defects. Previously, it was shown that deletions of 17q12 and 22q11.2 regions were specific for kidney anomalies (KA) while 16p11.2 and 1q21.1 loci showed extensive pleiotropy in CAKUT phenotypes. CNVs affecting miRNA gene dosage have been described to have functional influence on gene expression. We aimed to conduct comprehensive in silico analysis using publicly available databases to analyze miRNA content of CAKUT-associated CNVs in quoted chromosomal loci with regard to pleiotropy. Methods: Extensive literature review was conducted to collect data about pathogenic rCNVs associated with CAKUT. UCSC genome browser tool was employed for mapping miRNAs onto collected rCNV regions. Results: Analysis of CNVs in CAKUT included four studies counting more than 2500 patients. In further analysis we included 191 patients harboring pathogenic CNVs. Surprisingly, CAKUT pleiotropic regions (16p11.2, 1q21.2) did not contain any miRNA. 22q11.2 showed the densest miRNAs content (n = 21). Conclusions: Absence of miRNAs may potentially pronounce the pleiotropy of the CAKUT genetic defects, thus leading to the variety of phenotypes. Contrary, abundancy of miRNAs in 22q11.2 might be associated with reproducible phenotype, such as KA, producing the functional effect when deleted. This assumption agrees with recent results of miRNA expression variability in 22q11.2 deletion syndrome.54th European Society of Human Genetics (ESHG) Conference; August 28-31, 2021; Virtual ConferenceAbstracts from the 54th European Society of Human Genetics (ESHG) Conference: e-Poster

Characterization of mechanically activated ZrO2-C powder mixtures

Mechanical activation represents a very useful technique for powder processing prior to sintering process. First of all, it makes powders homogenized, leads to attrition of powder particles, and makes powder mixtures more reactive. Secondly, it can lead to mechano-chemical reaction, and finally, lowering of sintering time and temperature. Mixtures of ZrO2 and C were mechanically activated by high-energy ball milling. Powders were milled for times from 0 to 120 minutes in air atmosphere. Mechanically activated powder mixtures were characterized by various techniques, such as particle size analysis (PSA), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, and diffraction scanning calorimetry along with thermo gravimetry (DSC-TGA). As milling time increased, surface area of powders increased, indicating significant particle size reduction. Mechanical activation for 15 minutes provides the best balance between particle size reduction and reactivity for the powders

Plasma Induced DNA Damage: Comparison with the Effects Of Ionizing Radiation And Establishing Effective Treatment Doses

Atmospheric pressure plasma sources such as the plasma needle are being used for wound and chronic wound healing, cancer cell removal, stem cell manipulations, in dermatology, surgery, dentistry, etc. [1,2]. In our previous work we have optimized plasma needle parameters to efficiently sterilize E. Coli and S. Aureus in planktonic samples without causing damage to the peripheral blood mesenchymal stem cells used as a model for surrounding tissue [3]. Plasma treatments of human periodontal ligament mesenchymal stem cells have led to a promotion of osteogenic differentiation without affecting cell viability [4]. These results can be important for dentistry, especially for possible support or alternative to conventional regenerative procedures, such as guided tissue regeneration, the use of bone replacement grafts, and application of exogenous growth factors or proteins. Besides the promising short term effects of atmospheric non-thermal plasma on cells, it is necessary to study the long term effects, like for example DNA damage in order to prevent undesirable effects

Factors effecting the induction of rat forestomach hyperplasia induced by Swedish oral smokeless tobacco (snus)

Long term exposure to oral smokeless tobacco may induce lesions in the oral cavity characterized by a hyperplastic epithelium. The possible role of nicotine and the physical properties of oral tobacco for developing these lesions, as well as of dysplasia and neoplasia is unclear. Low nitrosamine Swedish snus as well as non-genotoxic butylated hydroxyanisole induces increased cellular proliferation in the rat forestomach epithelia. Using this model, we report here on the effects of nicotine, pH, and particle size. Snus with different properties had no impact on oxidative stress as determined by 8-oxo-7,8-dihydro-2′-deoxyguanosine, or on interleukin IL-1b. Whereas BHA boosted IL-6, probably due to the presence of nicotine. there was no significant enhancement of cell divisions with increasing particle size, although in individual samples the variations in proliferation rates increased greatly with increasing particle size. Conforming to human experience, the enhanced cell proliferation caused by snus was found to be completely reversible. A cacao bean extract had a protective action similar to that previously found for blueberries. The main cause of the observed tobacco induced cell proliferation could be mechanical irritation, possibly in combination with nicotine, whereas within the studied range, pH did not affect the rate of cell division. © 201

Characterization of MgAl2O4 sintered ceramics

Single phase MgAl2O4 was made from a one-to-one molar ratio of MgO and Al2O3 powders mixed using ball-milling. Mixtures of MgO and Al2O3 were subsequently treated in planetary ball mill for 30, 60, 90 and 120 minutes in air. The aim of this study was to examine phase composition, microstructure, and densification behavior of sintered specimens. After sintering in dilatometer at 1500 °C, the powder was converted to single phase MgAl2O4. The results show that mechanical activation improved the densification behavior of MgAl2O4 sintered specimens, and it reduced the onset temperature for sintering by approx. 100 oC. Based on dilatometer data, powders were subsequently densified at 1450 oC by hot pressing. Almost аll specimens exhibited full density, while sample activated for 30 minutes showed the fastest densification rate

Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT

Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches

Prolonged exposure to mesoporous silica decrease cell viability in vitro

„Contemporary Materials 2021“ : XIV International Scientific Conference : programme and book of abstracts : September 9-10, 2021; Banja Luka, Bosnia and Herzegovin

Characterization of MgAl2O4 Sintered Ceramics

Single phase MgAl2O4 was made from a one-to-one molar ratio of MgO and Al2O3 powders mixed using ball-milling. Mixtures of MgO and Al2O3 were subsequently treated in planetary ball mill for 30, 60, 90 and 120 minutes in air. The aim of this study was to examine phase composition, microstructure, and densification behavior of sintered specimens. After sintering in dilatometer at 1500 degrees C, the powder was converted to single phase MgAl2O4. The results show that mechanical activation improved the densification behavior of MgAl2O4 sintered specimens, and it reduced the onset temperature for sintering by approx. 100 degrees C. Based on dilatometer data, powders were subsequently densified at 1450 degrees C by hot pressing. Almost all specimens exhibited full density, while sample activated for 30 minutes showed the fastest densification rate

Effect of Mechanical Activation on the Densification Behavior of MgAl2O4 Spinel

Magnesium aluminate and other alumina-based spinels attract attention due to their high hardness, high mechanical strength, and low dielectric constant. MgAl2O4 was produced by solid-state reaction between MgO and a-Al2O3 powders. Mechanical activation was used to increase the reactivity of powders and decrease the sintering temperatures. Mechanical activation of mixed powders was performed in a high-energy planetary ball mill in air for 30, 60, 90, and 120 minutes. The resulting powders were characterized to determine the effect of activation on surface area, particle size, and crystallinity. Mechanical activation decreased particle size, increased surface area, and increased the width of peaks in x-ray diffraction. Dilatometry was used to monitor densification behavior up to 1500 °C. For non-activated powders, sintering started at approximately 1400 °C, while for activated powders, the onset temperature decreased to about 1340 °C. Mechanical activation is an efficient method to improve the densification behaviour of MgAl2O4 produced from mixed oxide powders