BACKGROUND: Hyperbaric oxygen (HBO2) therapy can have a positive effect on wound healing, angiogenesis and blood flow. No prior study has described the effects of HBO2 therapy and gene expression of this process. The goal of our research was to show the effects of HBO2 and its impact at the molecular level on angiogenesis, proliferation, differentiation, oxidative stress, inflammation, and extracellular matrix formation. Live animal subjects were used for simulating the process of wound healing under standard conditions and under the influence of HBO2. METHODS: Two experimental groups were created using injured rabbits (N=24), one group (N=12) treated with hyperbaric therapy twice a day and one (N=12) with standard wound care management. Wounds were surgical, uninfected, and in healthy animal test subjects. We compared the whole genomic analysis of the transcriptome with the use of microarray technology at three intervals during treatment. RESULTS: The induction of the wounds in rabbit skin increased expression of hundreds of genes in both treatment groups. The numbers of elevated and decreased genes gradually reduced as the wound healed. Gene expression analysis showed elevated expression of several genes associated with inflammation in both groups of injured animals. Genes connected to the process of angiogenesis, proliferation, differentiation, oxidative stress and extracellular matrix formation were without statistically significant changes. CONCLUSION: The evidence did not support that HBO2 had any significant effect on gene expression during wound healing. Additionally, there was no evidence to support that there were changes in gene expression in either treatment group.

• Klíčová slova
• wound healing, gene expression, hyperbaric oxygen therapy, microarray analysis,
• MeSH
• chirurgická rána genetika   terapie   MeSH
• čipová analýza tkání metody   MeSH
• exprese genu * MeSH
• hojení ran genetika   MeSH
• hyperbarická oxygenace * MeSH
• králíci MeSH
• kůže zranění   MeSH
• messenger RNA analýza   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA MeSH

OBJECTIVE: The regulator of G-protein signaling (RGS) molecules represent a class of proteins that modulate the signaling activity of G-protein coupled receptors. Regulator of G-protein signaling 4 (RGS4) is of particular interest in schizophrenia due to reported downregulation of RGS4 transcripts in schizophrenia as well as a connection between RGS4 and a number of receptors implicated in schizophrenia. The mechanism of RGS4 involvement in the pathophysiology of this illness is not clear. METHODS: To elucidate thise role of RGS4 in pathophysiology of schizophrenia, we silenced RGS4 using siRNAs in human neuroblastoma cell lines and we studied the effects of differential RGS4 expression by microarray. RESULTS AND CONCLUSION: The cell lines with downregulated expression of RGS4 showed 67 genes with changed expression (30 underexpressed and 37 overexpressed). We have detected three subgroups of genes which might be implicated in schizophrenia pathophysiology: histone genes, which suggest epigenetic mechanisms of the disease; genes for transcription factors associated with other genes relevant to schizophrenia pathology (BDNF and DISCI1) and a heterogeneous group containing genes for G-proteins (GPR50 and GPR64) and calcium binding proteins.

• MeSH
• buněčné linie MeSH
• down regulace MeSH
• genetická transkripce MeSH
• genom lidský genetika   MeSH
• histony genetika   MeSH
• kultivované buňky MeSH
• lidé MeSH
• malá interferující RNA farmakologie   MeSH
• mikročipová analýza MeSH
• mozkový neurotrofický faktor genetika   MeSH
• neurony účinky léků   metabolismus   MeSH
• proteiny nervové tkáně genetika   MeSH
• proteiny RGS genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• schizofrenie genetika   MeSH
• stanovení celkové genové exprese MeSH
• umlčování genů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ADGRG2 protein, human MeSH Prohlížeč
• GPR50 protein, human MeSH Prohlížeč
• histony MeSH
• malá interferující RNA MeSH
• mozkový neurotrofický faktor MeSH
• proteiny nervové tkáně MeSH
• proteiny RGS MeSH
• receptory spřažené s G-proteiny MeSH
• RGS4 protein MeSH Prohlížeč

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey's P value <0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.

• MeSH
• analýza hlavních komponent MeSH
• apoptóza genetika   MeSH
• demografie MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• dospělí MeSH
• genom lidský genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA krev   genetika   MeSH
• mikročipová analýza * MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory hlavy a krku krev   genetika   patologie   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• signální transdukce genetika   MeSH
• spinocelulární karcinom krev   genetika   patologie   MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• nádorový supresorový protein p53 MeSH

The Teplice area in the Czech Republic is a mining district where elevated levels of air pollution including airborne carcinogens, have been demonstrated, especially during winter time. This environmental exposure can impact human health; in particular children may be more vulnerable. To study the impact of air pollution in children at the transcriptional level, peripheral blood cells were subjected to whole genome response analysis, in order to identify significantly modulated biological pathways and processes as a result of exposure. Using genome-wide oligonucleotide microarrays, we investigated differential gene expression in children from the Teplice area (n=23) and compared them with children from the rural control area of Prachatice (n=24). In an additional approach, individual gene expressions were correlated with individual peripheral blood lymphocyte micronuclei frequencies, in order to evaluate the linkage of individual gene expressions with an established biomarker of effect that is representative for increased genotoxic risk. Children from the Teplice area showed a significantly higher average micronuclei frequency than Prachatice children (p=0.023). For considerable numbers of genes, the expression differed significantly between the children from the two areas. Amongst these genes, considerable numbers of genes were observed to correlate significantly with the frequencies of micronuclei. The main biological process that appeared significantly affected overall was nucleosome assembly. This suggests an effect of air pollution on the primary structural unit of the condensed DNA. In addition, several other pathways were modulated. Based on the results of this study, we suggest that transcriptomic analysis represents a promising biomarker for environmental carcinogenesis.

• MeSH
• dítě MeSH
• genomika MeSH
• látky znečišťující vzduch * MeSH
• lidé MeSH
• mikrojádra chromozomálně defektní * MeSH
• regulace genové exprese * MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• vystavení vlivu životního prostředí MeSH
• znečištění ovzduší * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch * MeSH

BACKGROUND: Recently, we used cell-free assays to demonstrate the toxic effects of complex mixtures of organic extracts from urban air particles (PM2.5) collected in four localities of the Czech Republic (Ostrava-Bartovice, Ostrava-Poruba, Karvina and Trebon) which differed in the extent and sources of air pollution. To obtain further insight into the biological mechanisms of action of the extractable organic matter (EOM) from ambient air particles, human embryonic lung fibroblasts (HEL12469) were treated with the same four EOMs to assess changes in the genome-wide expression profiles compared to DMSO treated controls. METHOD: For this purpose, HEL cells were incubated with subtoxic EOM concentrations of 10, 30, and 60 μg EOM/ml for 24 hours and global gene expression changes were analyzed using human whole genome microarrays (Illumina). The expression of selected genes was verified by quantitative real-time PCR. RESULTS: Dose-dependent increases in the number of significantly deregulated transcripts as well as dose-response relationships in the levels of individual transcripts were observed. The transcriptomic data did not differ substantially between the localities, suggesting that the air pollution originating mainly from various sources may have similar biological effects. This was further confirmed by the analysis of deregulated pathways and by identification of the most contributing gene modulations. The number of significantly deregulated KEGG pathways, as identified by Goeman's global test, varied, depending on the locality, between 12 to 29. The Metabolism of xenobiotics by cytochrome P450 exhibited the strongest upregulation in all 4 localities and CYP1B1 had a major contribution to the upregulation of this pathway. Other important deregulated pathways in all 4 localities were ABC transporters (involved in the translocation of exogenous and endogenous metabolites across membranes and DNA repair), the Wnt and TGF-β signaling pathways (associated particularly with tumor promotion and progression), Steroid hormone biosynthesis (involved in the endocrine-disrupting activity of chemicals), and Glycerolipid metabolism (pathways involving the lipids with a glycerol backbone including lipid signaling molecules). CONCLUSION: The microarray data suggested a prominent role of activation of aryl hydrocarbon receptor-dependent gene expression.

• MeSH
• exprese genu účinky léků   MeSH
• fibroblasty cytologie   účinky léků   fyziologie   MeSH
• látky znečišťující vzduch chemie   metabolismus   farmakologie   MeSH
• lidé MeSH
• mikročipová analýza MeSH
• organické látky chemie   metabolismus   farmakologie   MeSH
• oxidace-redukce MeSH
• pevné částice chemie   metabolismus   farmakologie   MeSH
• plíce cytologie   MeSH
• stanovení celkové genové exprese MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• organické látky MeSH
• pevné částice MeSH

To define the molecular response of Acidithiobacillus ferrooxidans under pH up-shift, temporal gene expression profiles were examined by using whole-genome DNA microarrays for A. ferrooxidans. Approximately 30% of the 3,132 genes represented on the microarray were significantly upregulated over a 160-min period, while about 14% were significantly downregulated. Our results revealed that A. ferrooxidans showed potential self-protection and self-regulation performance in response to pH up-shift stress. Many genes involved in regulation of membrane components were differentially expressed under the pH up-shift stress. Likewise, most of genes involved in phosphate metabolism, sulfur assimilation, and CO(2) fixation were obviously induced. Conversely, the transcription of a polyphosphate kinase gene (AFE1210) associated with phosphate storage was significantly repressed, which probably stemmed from the depletion of polyphosphate. Besides, most of the genes involved in hydrogen uptake were significantly induced, whereas many genes involved in nitrogen fixation were obviously repressed, which suggested that hydrogen uptake and nitrogen fixation could contribute to cytoplasmic pH homeostasis.

• MeSH
• Acidithiobacillus genetika   metabolismus   MeSH
• bakteriální geny * MeSH
• fixace dusíku genetika   MeSH
• fosfáty metabolismus   MeSH
• fyziologický stres MeSH
• genom bakteriální * MeSH
• koncentrace vodíkových iontů MeSH
• oxid uhličitý metabolismus   MeSH
• proteomika metody   MeSH
• průmyslová mikrobiologie metody   MeSH
• regulace genové exprese u bakterií fyziologie   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• síra metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• vodík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfáty MeSH
• oxid uhličitý MeSH
• síra MeSH
• vodík MeSH

Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05) mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA) project and identified 60% (402) of the downregulated and 74% (469) of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• karcinom z renálních buněk genetika   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• nádory ledvin genetika   mortalita   patologie   MeSH
• prognóza MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Spojené státy americké epidemiologie   MeSH

Prenatal exposure to air pollution is associated with intrauterine growth restriction and low birth weight. Gene expression changes in newborns in relation to air pollution have not been sufficiently studied. We analyzed whole genome expression in cord blood leukocytes of 202 newborns from diverse localities of the Czech Republic, differing among other factors in levels of air pollution: the district of Karvina (characterized by higher concentration of air pollutants) and Ceske Budejovice (lower air pollution levels). We aimed to identify differentially expressed genes (DEGs) and pathways in relation to locality and concentration of air pollutants. We applied the linear model to identify the specific DEGs and the correlation analysis, to investigate the relationship between the concentrations of air pollutants and gene expression data. An analysis of biochemical pathways and gene set enrichment was also performed. In general, we observed modest changes of gene expression, mostly attributed to the effect of the locality. The highest number of DEGs was found in samples from the district of Karvina. A pathway analysis revealed a deregulation of processes associated with cell growth, apoptosis or cellular homeostasis, immune response-related processes or oxidative stress response. The association between concentrations of air pollutants and gene expression changes was weak, particularly for samples collected in Karvina. In summary, as we did not find a direct effect of exposure to air pollutants, we assume that the general differences in the environment, rather than actual concentrations of individual pollutants, represent a key factor affecting gene expression changes at delivery. Environ. Mol. Mutagen. 59:401-415, 2018. © 2018 Wiley Periodicals, Inc.

• Klíčová slova
• PM2.5, air pollution, benzo[a]pyrene, cord blood, microarray, prenatal exposure,
• MeSH
• fetální krev účinky léků   metabolismus   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• monitorování životního prostředí * MeSH
• novorozenec MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• regulace genové exprese účinky léků   genetika   MeSH
• stanovení celkové genové exprese metody   MeSH
• těhotenství MeSH
• vystavení vlivu životního prostředí MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• polycyklické aromatické uhlovodíky MeSH

Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.

• MeSH
• anotace sekvence MeSH
• autoimunita MeSH
• autoprotilátky biosyntéza   genetika   MeSH
• CD antigeny genetika   imunologie   MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 1. typu genetika   imunologie   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• humorální imunita MeSH
• interleukin-1 genetika   imunologie   MeSH
• kojenec MeSH
• leukocyty mononukleární imunologie   metabolismus   patologie   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• primární buněčná kultura MeSH
• přirozená imunita MeSH
• receptory CCR3 genetika   imunologie   MeSH
• regulace genové exprese imunologie   MeSH
• rodina MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• toll-like receptory genetika   imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí 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
• Názvy látek
• autoprotilátky MeSH
• CCR3 protein, human MeSH Prohlížeč
• CD antigeny MeSH
• interleukin-1 MeSH
• receptory CCR3 MeSH
• toll-like receptory MeSH

Alterations in the genome that lead to changes in DNA sequence copy number are characteristic features of solid tumors. We used CGH+SNP microarray and HPV-FISH techniques for detailed screening of copy number alterations (CNAs) in a cohort of 26 patients with cervical carcinoma (CC). This approach identified CNAs in 96.2% (25/26) of tumors. Array-CGH discovered CNAs in 73.1% (19/26) of samples, HPV-FISH experiments revealed CNAs in additional 23.1% (6/26) of samples. Common gains of genetic sequences were observed in 3q (50.0%), 1q (42.4%), 19q (23.1%), while losses were frequently found in 11q (30.8%), 4q (23.1%) and 13q (19.2%). Chromosomal regions involved in loss of heterozygosity were observed in 15.4% of samples in 8q21, 11q23, 14q21 and 18q12.2. Incidence of gain 3q was associated with HPV 16 and HPV 18 positive samples and simultaneous presence of gain 1q (P = 0.033). We did not found a correlation between incidence of CNAs identified by array-CGH and HPV strain infection and incidence of lymph node metastases. Subsequently, HPV-FISH was used for validation of array-CGH results in 23 patients for incidence of hTERC (3q26) and MYC (8q24) amplification. Using HPV-FISH, we found chromosomal lesions of hTERC in 87.0% and MYC in 65.2% of specimens. Our findings confirmed the important role of HPV infection and specific genomic alterations in the development of invasive cervical cancer. This study also indicates that CGH+SNP microarrays allow detecting genome-wide CNAs and copy-neutral loss of heterozygosity more precisely, however, it may be less sensitive than FISH in samples with low level clonal CNAs.

• Klíčová slova
• CGH+SNP microarrays, Cervical carcinoma, HPV-FISH, copy number alterations, whole-genome profiling,
• MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• infekce papilomavirem komplikace   genetika   MeSH
• karcinom genetika   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory děložního čípku genetika   virologie   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů metody   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• srovnávací genomová hybridizace metody   MeSH
• stanovení celkové genové exprese metody   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• ztráta heterozygozity genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH