Blood filtration and formation of primary urine in the kidney glomerulus is provided by a specialized membrane called slit diaphragm located between well-branched pedicels of podocytes. Actually, the slit diaphragm is a protein supercomplex, whose disruption can cause failure of renal filtration, and patients usually manifest nephrotic syndrome. Recently, familial forms of nephrotic syndrome have been described which arise from malfunction of mutated proteins making up the slit diaphragm. In 2005 it was found that one of the proteins present in this complex was non-selective cation channel TRPC6. The aim of this work was to screen mutations and polymorphisms of the TRPC6 gene in a group of 64 Czech patients with nephrotic syndrome and subsequently, on the basis of these data, evaluate the role of mutations in the TRPC6 gene in Czech population. The analysis was performed by the PCR method followed by direct sequencing and high-resolution melting method. We have not identified any mutations in our group of patients. Two additional single nucleotide polymorphisms - p.P15S and p.A404V - were detected along with nucleotide changes that did not result in amino acid changes and with a few intronic changes. P.P15S heterozygotes were more frequent in patients with steroid-resistant FSGS than in steroid- sensitive patients (29 % versus 12.1 %). To conclude, we did not find any probable disease-causing mutation in the TRPC6 gene in the cohort of 64 Czech patients. The p.P15S polymorphism might have some influence on the therapeutic response of FSGS patients.

• MeSH
• dospělí MeSH
• fokálně segmentální glomeruloskleróza genetika   MeSH
• kationtové kanály TRPC genetika   MeSH
• kationtový kanál TRPC6 MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoidní nefróza genetika   MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA * MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• kationtové kanály TRPC MeSH
• kationtový kanál TRPC6 MeSH
• TRPC6 protein, human MeSH Prohlížeč

BACKGROUND: Mutations in INF2 are frequently responsible for focal segmental glomerulosclerosis (FSGS), which is a common cause of end stage renal disease (ESRD); additionally, they are also connected with Charcot-Marie-Tooth neuropathy. INF2 encodes for inverted formin 2. This protein participates in regulation of the dynamics of the actin cytoskeleton, involving not only the polymerisation, but also the depolymerisation of filaments. The present study is the first mutational analysis of INF2 done in the Czech Republic. METHODS: Mutational analysis of INF2 was performed on 109 patients (mean age at onset 41.44 ± 18.91 years) with FSGS or minimal change disease (MCD); and also in 6 patients without renal biopsy who had already developed chronic kidney disease (CKD)/ESRD at the time of diagnosis. We used high resolution melting method (HRM), with subsequent Sanger sequencing, in suspect samples from HRM analysis. The HRM method is an effective method for the screening of large cohorts of patients. RESULTS: Two pathogenic mutations (p.Arg214His and p.Arg218Gln) were detected in INF2. The first (p.Arg214His) was identified in the FSGS patient with a positive family history. The second mutation (p.Arg218Gln) was found in two brothers with ESRD of unknown etiology. The most frequent sequence change was the substitution p.P35P, the incidence of which corresponded with the frequencies available in the ExAC Browser and gnomAD Browser databases. This analysis also detected different exonic and intronic changes that probably did not influence the phenotype of the included patients. CONCLUSIONS: The INF2 mutational screening is useful in familial FSGS cases as well as in patients with an unknown cause for their ESRD, but with a positive family history. INF2 seems to be not only the cause of FSGS, but also of ESRD of unknown etiology. Our study has confirmed that the HRM analysis is a very useful method for the identification of single nucleotide substitutions.

• Klíčová slova
• End stage renal disease, Focal segmental glomerulosclerosis, High resolution melting method, INF2, Minimal change disease,
• MeSH
• Charcotova-Marieova-Toothova nemoc genetika   metabolismus   MeSH
• chronické selhání ledvin genetika   metabolismus   MeSH
• dospělí MeSH
• exony genetika   MeSH
• fenotyp MeSH
• fokálně segmentální glomeruloskleróza genetika   metabolismus   MeSH
• forminy MeSH
• introny genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• mikrofilamentové proteiny genetika   metabolismus   MeSH
• mutace genetika   MeSH
• mutační analýza DNA metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• forminy MeSH
• INF2 protein, human MeSH Prohlížeč
• mikrofilamentové proteiny MeSH

• MeSH
• aktivace lymfocytů * MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• lipoidní nefróza imunologie   MeSH
• lymfocyty klasifikace   imunologie   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• tvorba rozet MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

AIM: The recurrence rate of colorectal cancer remains high even after radical surgery. Existing criteria for administering adjuvant treatment lack sufficient precision, often leading to undertreatment or overtreatment. This study investigates circulating tumour cells (CTCs) as a potential prognostic biomarker to improve the accuracy of patient selection. METHODS: Forty-six colorectal cancer patients without distant metastases who underwent radical surgery were enrolled in this prospective study conducted at Tomas Bata Hospital in Zlín. The study protocol was approved by the hospital's Ethics Committee. Circulating tumour cells (CTCs) were measured in peripheral blood samples collected preoperatively, on the second postoperative day, and one month after surgery. CTCs were detected and characterized using semiautomated microscopy. Comprehensive clinicopathological data were recorded as part of standardized perioperative care. The prognostic significance of CTCs was evaluated based on the time to recurrence (TTR) parameter. RESULTS AND CONCLUSION: Growing evidence from circulating tumour cell (CTC) research supports their potential role as a valuable biomarker in cancer management. In this study involving stage I-III colorectal cancer patients, a recurrence rate of 20% was observed among individuals with detectable CTCs, whereas no recurrence occurred in patients with a sustained absence of CTCs. Despite this apparent difference, the time to recurrence (TTR) did not differ significantly between the groups (log-rank test, P=0.175). Although the result was not statistically significant, the observed trend suggests a possible prognostic value of CTCs that merits investigation in a larger cohort. Furthermore, neither individual time-point measurements nor dynamic changes in CTC levels demonstrated a significant correlation with TTR.

• Klíčová slova
• circulating tumour cells, colorectal cancer, minimal residual disease, prognosis, time to recurrence,
• Publikační typ
• časopisecké články MeSH

Freshwater diversity is declining at an alarming rate worldwide, and climate change is a key driver. However, attributing biological shifts solely to climate warming remains challenging because of confounding anthropogenic stressors. Peatbogs, being highly conserved, strictly protected, and minimally disturbed, offer a unique study system to isolate climate effects. We compared odonate assemblages in 27 Central European raised and transitional bogs between two sets of standardized surveys approximately 20 years apart (1998-2006 and 2020-2024). During this period, the mean annual air temperature has increased by 1.23°C. We tracked species richness, composition, taxonomic diversity, and functional traits (thermal tolerance, conservation value indicators, and selected morphological and life-history traits) and also examined phylogenetic patterns of species turnover. Although species richness remained stable, assemblage composition shifted markedly from cold-adapted, vulnerable bog specialists toward warm-adapted habitat generalists with lower conservation value. Notably, Ponto-Mediterranean species and those with a lower upper elevational limit increased their occupancy. Although the phylogenetic signal across the evolutionary tree of odonates was low, implying that the responses of the species to climate change were independent of their phylogenetic position, we revealed frequent genus-level replacements. These findings reinforce the position of odonates as a model group for detecting climate-driven changes in freshwater communities. Our study has revealed that climate warming alone can trigger profound reorganization of insect communities in inherently stable peatbog habitats. Specific traits linked to vulnerability (e.g., thermal index, red list status) and specialization proved to be promising predictors of future shifts in odonatofauna of temperate peatlands. The pronounced changes documented here may precede irreversible transformations of these unique ecosystems, highlighting the urgency of monitoring bog habitats and maintaining their stability under ongoing global change.

• Klíčová slova
• Dragonfly Biotic Index, European Red List, Odonata, Species Temperature Index, climate change, raised and transitional bogs, temperate peatlands, trait‐based approach,
• MeSH
• biodiverzita * MeSH
• fylogeneze MeSH
• klimatické změny * MeSH
• mokřady * MeSH
• vážky * fyziologie   MeSH
• zachování přírodních zdrojů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

In mantle cell lymphoma (MCL), minimal residual disease (MRD) is an indicator of the disease outcome. Quantitative methods used so far do not provide a suitable molecular marker in 30-70% patients with MCL (depending on the technique used). We tested cyclin D1 as a marker for quantitative MRD monitoring. The real-time PCR of cyclin D1 mRNA was performed in 144 bone marrow (BM) specimens including 95 BMs from MCL patients, 39 BMs from patients with other B-cell non-Hodgkin's lymphomas and 10 BMs from healthy volunteer donors. In 73 BMs obtained from 20 MCL patients we examined the cyclin D1 level during the treatment and follow-up period. We detected a cyclin D1 overexpression exclusively in BMs infiltrated with MCL, including minimal residual infiltration. Dynamics of cyclin D1 correlated with the patient's clinical status in 69/73 BMs. Individual monitoring of patients during the disease course showed cyclin D1 quantitative changes accompanying either the disease relapse or a successful treatment response or the disease-free survival (remission) and it showed a predictive significance. Cyclin D1 detection is a promising approach for the quantitative MRD monitoring in MCL patients, and the individual monitoring of the cyclin D1 dynamics represents a suitable indicator of the disease course.

• MeSH
• cyklin D1 genetika   metabolismus   MeSH
• dospělí MeSH
• kostní dřeň metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk diagnóza   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• prediktivní hodnota testů MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• reziduální nádor diagnóza   metabolismus   MeSH
• senioři MeSH
• senzitivita a specificita 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
• cyklin D1 MeSH
• messenger RNA MeSH
• nádorové biomarkery MeSH

In large cohort studies, due to the time-consuming nature of the measurement of movement biomechanics, more than one evaluator needs to be involved. This may increase the potential occurrence of error due to inaccurate positioning of markers to the anatomical locations. The purpose of this study was to determine the reliability and objectivity of lower limb segments length by multiple evaluators in a large cohort study concerning healthy aging in an industrial environment. A total of eight evaluators performed marker placements on five participants on three different days. Evaluators placed markers bilaterally on specific anatomical locations of the pelvis, thigh, shank and foot. On the right foot, markers were placed in anatomical locations to define a multi-segmental foot model. The position of the marker at the anatomical locations was recorded by a motion capture system. The reliability and objectivity of lower limb segment lengths was determined by the intraclass correlation coefficient of a two-way random model and of the two-way mixed model, respectively. For all evaluators for all segments, the average reliability and objectivity was greater than 0.8, except for the metatarsus segment (0.683). Based on these results, we can conclude that multiple evaluators can be engaged in a large cohort study in the placement of anatomical markers.

• Klíčová slova
• lower limb, minimal detectable change, multi-segment foot model, optoelectronic stereophotogrammetry, standard error of measurement,
• MeSH
• biomechanika MeSH
• chůze (způsob) MeSH
• kohortové studie MeSH
• lidé MeSH
• reprodukovatelnost výsledků MeSH
• zdravé stárnutí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Deoxynivalenol (DON) is a mycotoxin frequently found in cereals, and pigs are one of the most sensitive farm species to DON. The aim of this study was to determine the effects of DON in very low doses on peripheral blood mononuclear cells (PBMC) and on particular lymphocyte subpopulations. The cells were exposed to 1, 10 and 100 ng/mL of DON and lymphocyte viability, proliferation, and cytokine (Interleukin (IL)-1β, IL-2, IL-8, IL-17, Interferon (IFN) γ and tumor necrosis factor (TNF) α production were studied. Cells exposed to DON for 5 days in concentrations of 1 and 10 ng/mL showed higher viability compared to control cells. After 18 h of DON (100 ng/mL) exposure, a significantly lower proliferation after mitogen stimulation was observed. In contrast, an increase of spontaneous proliferation induced by DON (100 ng/mL) was detected. After DON exposure, the expression of cytokine genes decreased, with the exception of IL-1β and IL-8, which increased after 18 h exposure to 100 ng/mL of DON. Among lymphocyte subpopulations, helper T-cells and γδ T-cells exhibiting lower production of IL-17, IFNγ and TNFα were most affected by DON exposure (10 ng/mL). These findings show that subclinical doses of DON lead to changes in immune response.

• Klíčová slova
• PBMC, animal health, cytokines, deoxynivalenol, immunotoxicity, lymphocytes, pig, subclinical dose,
• MeSH
• cytokiny biosyntéza   genetika   MeSH
• exprese genu účinky léků   MeSH
• kultivované buňky MeSH
• leukocyty mononukleární účinky léků   imunologie   MeSH
• podskupiny lymfocytů účinky léků   imunologie   MeSH
• prasata MeSH
• proliferace buněk účinky léků   MeSH
• trichotheceny toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• deoxynivalenol MeSH Prohlížeč
• trichotheceny MeSH

INTRODUCTION: The aim of this study was to retrospectively analyse the ultrasound findings in the axillary lymph nodes in breast cancer patients with morphological changes that required biopsy. In most cases the morphological changes were minimal. MATERIALS AND METHODS: Between January 2014 and September 2019 examination of axillary lymph nodes with subsequent core-biopsy was performed in 185 breast cancer patients at the Department of Radiology. Lymph node metastases were detected in 145 cases, while in the remaining 40 cases benign changes or normal lymph node (LN) histology was observed. Ultrasound morphological characteristics and the sensitivity and specificity were evaluated retrospectively. Seven ultrasound characteristics were evaluated - diffuse cortical thickening, focal cortical thickening, absence of the hilum, cortical non-homogeneities, L/T ratio (longitudinal to transverse axis), type of vascularization and perinodal oedema. RESULTS AND CONCLUSION: It is a diagnostic challenge to recognize metastases in the lymph nodes with minimal morphological changes. The most specific signs are non-homogeneities in the cortex of the lymph node as well as the absence of fat hilum and perinodal oedema. Metastases are significantly more frequent in LNs with a lower L/T ratio, in LNs with perinodal oedema and with a peripheral type of vascularization. Biopsy of these lymph nodes is necessary to confirm or exclude metastases, especially if it affects the type of treatment.

• Klíčová slova
• breast cancer, lymph node, metastases, ultrasound,
• MeSH
• axila MeSH
• lidé MeSH
• lymfatické metastázy * diagnostické zobrazování   patologie   MeSH
• lymfatické uzliny * krevní zásobení   diagnostické zobrazování   patologie   MeSH
• nádory prsu * diagnostické zobrazování   patologie   MeSH
• patologická angiogeneze diagnostické zobrazování   patologie   MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• ultrasonografie * metody   statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with early switch to the monocytic lineage and loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced switch detectable by flow cytometry (FC). Using exome and RNA sequencing, switch was found to positively correlate with three different genetic subtypes: PAX5-P80R mutation (5 cases with switch out of 5), rearranged DUX4 (DUX4r; 30 cases of 41) and rearranged ZNF384 (ZNF384r; 4 cases of 10). Expression profiles or phenotypic patterns correlated with genotypes, but within each genotype they could not identify cases who subsequently switched. If switching was not taken into account, the B-cell-oriented FC assessment underestimated the minimal residual disease level. For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the B-cell phenotype. Discordance on day 33 was observed in all the DUX4r, PAX5-P80R and ZNF384r subtypes. Importantly, despite the substantial phenotypic changes, possibly even challenging the appropriateness of BCP-ALL therapy, the monocytic switch was not associated with a higher incidence of relapse and poorer prognosis in patients undergoing standard ALL treatment.

• MeSH
• aktivátorový protein specifický pro B-buňky genetika   MeSH
• akutní lymfatická leukemie * MeSH
• B-lymfocyty MeSH
• imunofenotypizace MeSH
• lidé MeSH
• mutace MeSH
• pre-B-buněčná leukemie * diagnóza   genetika   MeSH
• reziduální nádor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktivátorový protein specifický pro B-buňky MeSH
• PAX5 protein, human MeSH Prohlížeč