Karcinóm endometria predstavuje významnú gynekologickú malignitu s celosvetovo stúpajúcou sa incidenciou. Pomocou sekvenovania RNA v tejto pilotnej štúdii sme v nádorových tkanivách v porovnaní so zdravým tkanivom identifikovali 2 483 rozdielne exprimovaných génov, zahrňujúcich proteín kódujúce gény, gény pre nekódujúce RNA a pseudogény. V našej štúdii sme sa zamerali na porovnanie proteín kódujúce gény. Analýza hlavných zložiek odhalila zhlukovanie na základe histologického stupňa. Analýza molekulárnej dráhy zdôraznila downreguláciu signalizácie Wnt a AGE-RAGE spolu so zvýšenou reguláciou dráh regulácie bunkového cyklu. Tieto zistenia poskytujú molekulárny náhľad na endometriálny karcinóm a identifikujú potenciálne biomarkery a terapeutické ciele pre zlepšenie stratégie klinického manažmentu.

Uterine endometrioid cancer represents a significant gynecological malignancy with a rising global incidence. Using RNA sequencing,in our pilot study we identified 2,483 differentially expressed genes, comprising protein-coding genes, genes for non-coding RNAs, and pseudogenes, in tumor tissues compared to healthy counterparts. In our study we focused on comparism of proteing-coding genes. Principal Component Analysis revealed clustering based on histological grade. Pathway analysis highlighted the downregulation of Wnt and AGE-RAGE signaling, alongside the upregulation of cell cycle regulation pathways. These findings provide molecular insights into endometrioid cancer and suggest potential biomarkers and therapeutic targets for improved management strategies.

During SARS-CoV-2 infection, the virus transforms the infected host cell into factories that produce new viral particles. As infection progresses, the infected cells undergo numerous changes in various pathways. One of these changes is the occurrence of a cytokine storm, which leads to severe symptoms. In this study, we examined the transcriptomic changes caused by COVID-19 by analyzing RNA-seq data obtained from COVID-19-positive patients as well as COVID-19-negative donors. RNA-seq data were collected for the purpose of identification of potential biomarkers associated with a different course of the disease. We analyzed the first datasets, consisting of 96 samples to validate our methods. The objective of this publication is to report the pilot results. To explore potential biomarkers related to disease severity, we conducted a differential expression analysis of human transcriptome, focusing on COVID-19 positivity and symptom severity. Given the large number of potential biomarkers we identified, we further performed pathway enrichment analysis with terms from Kyoto Encyclopedia of Genes and Genomics (KEGG) to obtain a more profound understanding of altered pathways. Our results indicate that pathways related to immune processes, response to infection, and multiple signaling pathways were affected. These findings align with several previous studies that also reported the influence of SARS-CoV-2 infection on these pathways.

• MeSH
• biologické markery MeSH
• COVID-19 * genetika   MeSH
• genomika MeSH
• lidé MeSH
• SARS-CoV-2 genetika   MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 HLA-G 5'URR variants, sHLA-G level and clinical variables in glioma patients. METHODS: We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The HLA-G 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA. RESULTS: Haploblock within HLA-G 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls (p < 0.05). No correlation of HLA-G 5'URR variants with sHLA-G plasma level was found. Analysis of HLA-G 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers (p = 0.04). CONCLUSION: Our results suggest genetic association of HLA-G 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.

• MeSH
• alely MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy MeSH
• HLA-G antigeny * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický * genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

The inability to predict the evolution of the COVID-19 epidemic hampered abilities to respond to the crisis effectively. The cycle threshold (Ct) from the standard SARS-CoV-2 quantitative reverse transcription-PCR (RT-qPCR) clinical assay is inversely proportional to the amount of SARS-CoV-2 RNA in the sample. We were interested to see if population Ct values could predict future increases in COVID-19 cases as well as subgroups that would be more likely to be affected. This information would have been extremely helpful early in the COVID-19 epidemic. We therefore conducted a retrospective analysis of demographic data and Ct values from 2,076,887 nasopharyngeal swab RT-qPCR tests that were performed at a single diagnostic laboratory in the Czech Republic from April 2020 to April 2022 and from 221,671 tests that were performed as a part of a mandatory school surveillance testing program from March 2021 to March 2022. We found that Ct values could be helpful predictive tools in the real-time management of viral epidemics. First, early measurement of Ct values would have indicated the low viral load in children, equivalent viral load in males and females, and higher viral load in older individuals. Second, rising or falling median Ct values and differences in Ct distribution indicated changes in the transmission in the population. Third, monitoring Ct values and positivity rates would have provided early evidence as to whether prevention measures are effective. Health system authorities should thus consider collecting weekly median Ct values of positively tested samples from major diagnostic laboratories for regional epidemic surveillance.

• MeSH
• COVID-19 * epidemiologie   diagnóza   MeSH
• dítě MeSH
• lidé MeSH
• retrospektivní studie MeSH
• RNA virová genetika   analýza   MeSH
• SARS-CoV-2 * genetika   MeSH
• senioři MeSH
• virová nálož MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease affecting 1 in 8,000 newborns. The majority of patients carry bi-allelic variants in the survival of motor neuron 1 gene (SMN1). SMN1 is located in a duplicated region on chromosome 5q13 that contains Alu elements and is predisposed to genomic rearrangements. Due to the genomic complexity of the SMN region and genetic heterogeneity, approximately 50% of SMA patients remain without genetic diagnosis that is a prerequisite for genetic treatments. In this work we describe the diagnostic odyssey of one SMA patient in whom routine diagnostics identified only a maternal heterozygous SMN1Δ(7-8) deletion. METHODS: We characterized SMN transcripts, assessed SMN protein content in peripheral blood mononuclear cells (PBMC), estimated SMN genes dosage, and mapped genomic rearrangement in the SMN region. RESULTS: We identified an Alu-mediated deletion encompassing exons 2a-5 of SMN1 on the paternal allele and a complete deletion of SMN1 on the maternal allele as the cause of SMA in this patient. CONCLUSION: Alu-mediated rearrangements in SMN1 can escape routine diagnostic testing. Parallel analysis of SMN gene dosage, SMN transcripts, and total SMN protein levels in PBMC can identify genomic rearrangements and should be considered in genetically undefined SMA cases.

• MeSH
• delece genu * MeSH
• elementy Alu MeSH
• genetické testování metody   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• předškolní dítě MeSH
• protein přežití motorických neuronů 1 genetika   metabolismus   MeSH
• sekvenční analýza DNA metody   MeSH
• spinální svalová atrofie diagnóza   genetika   MeSH
• western blotting metody   MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase signaling activity, involved in many cellular functions including cell growth and differentiation. Germ line loss-of-function mutations in EGFR lead to a severe neonatal skin disorder (Online Mendelian Inheritance in Man #131550). We report 18 premature Roma children from 16 families with birthweights ranging 440-1470 g and multisystem diseases due to the homozygous mutation c.1283G˃A (p.Gly428Asp) in EGFR. They presented with thin, translucent, fragile skin (14/15), skin desquamation (10/17), ichthyosis (9/17), recurrent skin infections and sepsis (9/12), nephromegaly (10/16) and congenital heart defects (7/17). Their prognosis was poor, and all died before the age of 6 months except one 13-year-old boy with a severe skin disorder, dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. Management of ion and water imbalances and extremely demanding skin care may improve the unfavorable outcome of such patients.

• MeSH
• dentinogenesis imperfecta diagnóza   genetika   mortalita   MeSH
• dítě MeSH
• erbB receptory nedostatek   genetika   MeSH
• homozygot MeSH
• ichtyóza diagnóza   genetika   mortalita   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace ztráty funkce MeSH
• nemoci ledvin vrozené   diagnóza   genetika   mortalita   MeSH
• novorozenec nedonošený MeSH
• novorozenec s velmi nízkou porodní hmotností MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Romové genetika   MeSH
• sekvenování exomu MeSH
• stupeň závažnosti nemoci MeSH
• syndrom MeSH
• vrozené srdeční vady diagnóza   genetika   mortalita   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

The broad fish tapeworm Dibothriocephalus latus is a causative agent of human food-borne disease called diphyllobothriosis. Medical importance, scattered geographical distribution and unknown origin of D. latus in Europe and North America make this species to be an interesting model for population genetics. Microsatellite markers were originally designed by library screening using NGS approach and validated as tools for future studies on population genetics of D. latus. Out of 122 candidates selected after NGS analysis, 110 yielded PCR products of the expected size, and in 78 of them, a declared repetitive motif was confirmed by Sanger sequencing. After the fragment analysis, six loci were proved to be polymorphic and tested for observed (Ho) and expected (He) heterozygosity, and deviations from Hardy-Weinberg equilibrium (HWE). They promise future application in studies on genetic interrelationships, origin and migratory routes of this medically important emerging tapeworm.

• MeSH
• Diphyllobothrium klasifikace   genetika   MeSH
• genetická variace * MeSH
• genotypizační techniky metody   MeSH
• mikrosatelitní repetice * MeSH
• populační genetika metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH

Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.

• MeSH
• dospělí MeSH
• exony MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• minisatelitní repetice MeSH
• oxid dusnatý fyziologie   MeSH
• prepulsní inhibice genetika   MeSH
• schizofrenie genetika   MeSH
• senzorický gating genetika   MeSH
• synthasa oxidu dusnatého, typ I genetika   MeSH
• úleková reakce genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Fascioloides magna (Trematoda: Fasciolidae) is an important liver parasite of a wide range of free-living and domestic ruminants; it represents a remarkable species due to its large spatial distribution, invasive character, and potential to colonize new territories. The present study provides patterns of population genetic structure and admixture in F. magna across all enzootic regions in North America and natural foci in Europe, and infers migratory routes of the parasite on both continents. METHODS: In total, 432 individuals from five North American enzootic regions and three European foci were analysed by 11 microsatellite loci. Genetic data were evaluated by several statistical approaches: (i) the population genetic structure of F. magna was inferred using program STRUCTURE; (ii) the genetic interrelationships between populations were analysed by PRINCIPAL COORDINATES ANALYSIS; and (iii) historical dispersal routes in North America and recent invasion routes in Europe were explored using MIGRATE. RESULTS: The analysis of dispersal routes of the parasite in North America revealed west-east and south-north lineages that partially overlapped in the central part of the continent, where different host populations historically met. The exact origin of European populations of F. magna and their potential translocation routes were determined. Flukes from the first European focus, Italy, were related to F. magna from northern Pacific coast, while parasites from the Czech focus originated from south-eastern USA, particularly South Carolina. The Danube floodplain forests (third and still expanding focus) did not display relationship with any North American population; instead the Czech origin of the Danube population was indicated. A serial dilution of genetic diversity along the dispersion route across central and eastern Europe was observed. The results of microsatellite analyses were compared to previously acquired outputs from mitochondrial haplotype data and correlated with past human-directed translocations and natural migration of the final cervid hosts of F. magna. CONCLUSIONS: The present study revealed a complex picture of the population genetic structure and interrelationships of North American and European populations, global distribution and migratory routes of F. magna and an origin of European foci.

• MeSH
• celosvětové zdraví MeSH
• Fasciolidae klasifikace   genetika   izolace a purifikace   MeSH
• genotypizační techniky MeSH
• infekce červy třídy Trematoda epidemiologie   přenos   MeSH
• mikrosatelitní repetice MeSH
• vysoká zvěř * MeSH
• zoonózy epidemiologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Severní Amerika epidemiologie   MeSH