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The vast majority of studies focusing on the effects of endurance exercise on hematological parameters and leukocyte gene expression were performed in adult men, so our aim was to investigate these changes in young females. Four young (age 15.3 ± 1.3 yr) elite female athletes completed an exercise session, in which they accomplished the cycling and running disciplines of a junior triathlon race. Blood samples were taken immediately before the exercise, right after the exercise, and then 1, 2, and 7 days later. Analysis of cell counts and routine biochemical parameters were complemented by RNA sequencing (RNA-seq) to whole blood samples. The applied exercise load did not trigger remarkable changes in either cardiovascular or biochemical parameters; however, it caused a significant increase in the percentage of neutrophils and a significant reduction in the ratio of lymphocytes immediately after exercise. Furthermore, endurance exercise induced a characteristic gene expression pattern change in the blood transcriptome. Gene set enrichment analysis (GSEA) using the Reactome database revealed that the expression of genes involved in immune processes and neutrophil granulocyte activation was upregulated, whereas the expression of genes important in translation and rRNA metabolism was downregulated. Comparison of a set of immune cell gene signatures (ImSig) and our transcriptomic data identified 15 overlapping genes related to T-cell functions and involved in podosome formation and adhesion to the vessel wall. Our results suggest that RNA-seq to whole blood together with ImSig analysis are useful tools for the investigation of systemic responses to endurance exercise.

A klinikai gyakorlatban elterjedt sztatinterápia mellékhatásai során leggyakrabban izompanaszokkal találkozunk. Ennek legsúlyosabb formája a rhabdomyolysis, amely potenciálisan életveszélyes következményekkel járhat. Az állapot kezelése mellett az etiológia tisztázása minden esetben szükséges. Egyes hajlamosító állapotok mellett a sztatinok metabolizációjának sérülése lehet a kulcsmozzanat. Esetünkben nem gyógyszer-interakció, hanem a sztatin májon keresztüli kiürülésének gátlása vezetett rhabdomyolysis kialakulásához és derített fényt egy addig tünetmentes betegségre.

Összefoglaló. A Bouveret-szindróma egy bilioenteralis fistulán keresztül a vékonybélbe – az esetek 85%-ában a duodenumba – jutó nagy epekő okozta bélelzáródást jelenti. Leggyakrabban idős nők körében fordul elő. Jelen közleményünk célja e kórkép tüneteinek, diagnosztikájának és terápiás lehetőségeinek ismertetése egy esetbemutatás kapcsán. A 79 éves nőbeteg felvételi hasi panaszainak hátterében típusos gyomorkimenet-obstrukciós szindrómát okozó, a duodenumban beékelődött epekő, Bouveret-szindróma igazolódott. A diagnózist az elvégzett natív hasi röntgen és hasi ultrahangvizsgálatok már felvetették, de megerősítésére további képalkotó vizsgálatot (hasi CT) és endoszkópos beavatkozást végeztünk. Ezt követően sebészeti beavatkozás történt, melynek során a cholecystoduodenalis fistula zárása és az epekő eltávolítása után a beteg gyógyultan távozott. Közleményünkben a diagnózisfelállítás idejének fontosságáról, illetve a terápiás lehetőségekről számolunk be, valamint szeretnénk felhívni a figyelmet az epekő okozta gyomorürülési zavar ezen ritka formájára. Orv Hetil. 2021; 162(49): 1982–1986. Summary. Bouveret syndrome is a rare form of bowel obstruction resulting to the small intestine – in 85% of the cases to the duodenum – caused by a gallstone from a bilioenteral fistula. It occurs most commonly in elderly women. The aim of the present study is to describe the symptoms, diagnostic and therapeutic options of Bouveret syndrome due to our case report. The background of epigastric pain of the 79-year-old woman was the typical gastric outlet obstruction syndrome caused by Bouveret syndrome with an impacted gallstone into the duodenum. This diagnosis was suggested by abdominal X-ray and abdominal ultrasound; however, it was confirmed with abdominal computer tomography and upper gastrointestinal endoscopy. This was followed by surgical intervention to close the cholecystoduodenal fistula and remove the gallstone, finally the cured patient was discharged. In our study, we summarize the importance of timely diagnosis and therapeutic options, respectively, furthermore, draw attention to this rare form of gallstone-caused gastric outlet obstruction syndrome. Orv Hetil. 2021; 162(49): 1982–1986.

IntroductionIncreased oxidative/nitrative stress is characteristic not only in pathologic, but also in healthy pregnancy. High uterine artery pulsatility index (UtAPI) at the end of the first trimester is associated with altered placentation and elevated risk for adverse pregnancy outcomes. We aimed to examine the relationship of systemic oxidative/nitrative stress and uterine artery pulsatility index in the first trimester and their correlation to pregnancy outcomes.Material and methodsHealthy pregnant women were recruited at 12–13th gestational week ultrasound examination; UtAPI was determined by color Doppler ultrasound. Patients were divided into high (UtAPI ≥ 2.3) (n = 30) and low (n = 31) resistance groups, and pregnancies were followed until labor. Systemic oxidative/nitrative stress was estimated by measuring total peroxide level, total antioxidant capacity and nitrotyrosine level.ResultsPlasma total peroxide level was significantly lower (2,510 ± 39 µM vs. 2,285 ± 59 µM), total antioxidant capacity was higher (781 ± 16 mM CRE vs. 822 ± 13 mM CRE) in the high UtAPI group, which were accompanied by lower birth weight (3,317 ± 64 vs. 3,517 ± 77 g, P < 0.05). Plasma total peroxide level showed a negative correlation (by Pearson) to UtAPI (P < 0.01) and positive correlation to birth weight (P < 0.05).ConclusionsAccording to our results, lower systemic oxidative stress showed correlation with high UtAPI measured between the 12–13th weeks of gestation. We also found significant differences in the birth weight of healthy newborns; therefore it is worth examining this relationship in pathological pregnancies.

Supplementary Methods Description of Echocardiography and 3D measurements Supplemantary Table S1 Effects of endurance exercise on cardiac structural, systolic, and diastolic function parameters were evaluated by echocardiography. Supplementary Table S2 The endurance exercise had no significant effect on the tested serum and urine parameters Routine laboratory parameters in serum and urine samples were measured at the Department of Laboratory Medicine, University of Debrecen. Supplementary Table S3 In order to assess the effect of endurance exercise on gene expression pattern, total RNA samples were isolated from peripheral blood samples of each participant at five different time points. RNA sequencing was used to identify the presence and determine the quantity of RNA transcripts in the samples. In our RNA-Seq data 10891 transcripts were identified in the five separate sets of samples, out of them 2795 showed significantly different expression in at least one pairwise comparison of the five different sample acquisition time points based on their ANOVA P

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.

Exposure to physiological estrogens or xenoestrogens (e.g., zearalenone or bisphenol A) increases the risk for cancer. However, little information is available on their significance in ovarian cancer. We present a comprehensive study on the effect of estradiol, zearalenone and bisphenol A on the phenotype, mRNA, intracellular and cell-free miRNA expression of human epithelial ovarian cell lines. Estrogens induced a comparable effect on the rate of cell proliferation and migration as well as on the expression of estrogen-responsive genes (GREB1, CA12, DEPTOR, RBBP8) in the estrogen receptor &alpha, (ER&alpha, )-expressing PEO1 cell line, which was not observable in the absence of this receptor (in A2780 cells). The basal intracellular and cell-free expression of miR200s and miR203a was higher in PEO1, which was accompanied with low ZEB1 and high E-cadherin expression. These miRNAs showed a rapid but intermittent upregulation in response to estrogens that was diminished by an ER&alpha, specific antagonist. The role of ER&alpha, in the regulation of the MIR200B-MIR200A-MIR429 locus was further supported by publicly available ChIP-seq data. MiRNA expression of cell lysates correlated well with cell-free miRNA expression. We conclude that cell-free miR200s might be promising biomarkers to assess estrogen sensitivity of ovarian cells.

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein&ndash, protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGF&beta, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

CD24 is a small molecular weight cell-surface protein and an independent marker for poor prognosis in the different type of cancers. We aimed to determine the expression of CD24 in plasma, exosomes and ovarian tissue samples of serous ovarian cancer patients. We collected tissue and blood samples from 21 cases of serous ovarian cancer and eight healthy controls. We used silica adsorption method for isolation of RNA. The cDNA was synthesized using quantitative real-time PCR. We used beta-globin as a housekeeping gene for the normalization of the data. Protein-protein and miRNA networking were analyzed. There was a significant difference in the expression of CD24 in ovarian tissue between controls and patients (0.16 ± 0.32 vs. 44.97 ± 68.06; p 0.01), while CD24 did not show expression in each plasma and exosome samples. There was a correlation in the expression of CD24 and FIGO grading between controls and patients. CD24 expression was detected in exosomes in 38.1% of patients, mainly with FIGO III, and in their plasma in 9.5% of cases. Our network analysis shows LYN, SELP, FGR, and NPM1 proteins are interacting with CD24. Our study demonstrates higher expression of CD24 in ovarian cancer patients' tissue samples, and there is an association with FIGO classification. However, CD24 showed expression only in some cell-free plasma and exosome samples.

Ovarian cancer is the fifth most common cause of cancer death among women that is mostly due to the difficulty of early diagnosis. Circulating miRNAs proved to be reliable biomarkers in various cancers. We screened 9 miRNAs, which are involved in epithelial-mesenchymal transition, in the plasma samples of patients with malignant (n = 28) or non-malignant (n = 12) ovarian tumors and disease-free healthy volunteers (n = 60) by qRT-PCR. The expression levels of miR200a, miR200b, miR200c, miR141, miR429, miR203a, miR34b (p 0.001) and miR34a (p 0.01) were significantly higher in the malignant samples than in healthy controls. MiR203a, miR141 (p 0.01), miR200a and miR429 (p 0.05) levels were also higher in malignant compared to non-malignant samples. ROC-AUC was the highest in the case of miR200c: 0.861 (95%CI = 0.776-0.947). Spearman's rank correlation analysis revealed positive correlation between the plasma levels of the studied miRNAs that was the highest between miR200b and miR200c (r

MicroRNAs play an essential role in the regulation of gene expression and tumor development. Single nucleotide polymorphism (SNP) can be observed in miRNAs and could influence gene expression. We aimed to identify miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in ovarian cancer patients and controls. 75 patients and 75 controls were involved. DNA was isolated from blood samples. MiR-146a rs2910164 and miR-196a-2 rs11614913 were determined by LightSnip kit. We used melting curve analysis for allele classification. Network analysis was made to find common target genes. We detected 72.67% G allele frequency of miR-146a rs2910164 in controls and 82.00% in patients group (p = 0,053). GG, GC and CC genotypes occurred with 53.33%, 38.67% and 8.00% among controls, with 65.33%, 33.33% and 1.33% among patients, (p = 0.0917). Allele C of miR-196a-2 rs11614913 occurred in 59.33% of controls and in 67.33% of patients (p = 0.15). CC, CT and TT genotypes occurred with 37.33%, 44.00%, and 18.67% frequency in controls, with 46.67%; 41.33% and 12.00% in patients (p = 0.3815). Network analysis found ATG9A, LBR, MBD4 and RUFY2 genes to be targets for both miRNAs. SNPs of miR-146a and miR-196a-2 showed no significant differences between patients and controls. More investigations are required to clarify the exact role of these SNPs in ovarian cancer.

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1–2% of the general population. Some common variants located in or next to PITX2 and NEURL1 genes are proved to play role in the occurrence of AF. The aim of our study was to investigate whether rs2595104 in the 4q25 chromosome region and rs6584555 SNP in the NEURL1 gene on chromosome 10 is associated with AF in a Caucasian population. We genotyped DNA samples of 76 AF patients and 77 healthy controls using quantitative real-time PCR followed by melting curve analysis. The minor A allele frequency of rs2595104 in PITX2 was 0.38 and 0.44 in the control group and in AF patients, respectively. There was no significant difference in allele and genotype distribution between the two groups (p = 0.52). The allele frequency based log additive odds ratio is 1.22 (C.I. = 0.76–1.94; p = 0.42). The frequency of minor rs6584555 C allele in NEURL1 was 0.22 in the control group and 0.23 in AF patients. Again there were no significant differences in allele and genotype frequencies between AF patients and controls (p = 0.92). The log additive odds ratio is 1,15 (C.I. = 0.66–2.01; p = 0,63). The heterozygous genotype of rs2595104 had the highest frequency compared to the other genotypes in both groups. In case of the rs6584555 SNP the homozygous genotype of the major allele (TT) had the highest frequency in both groups (0.59). The frequency of homozygous genotype for risk allele had the lowest frequency for both SNPs [rs2595104 (AA): 0.19 in patients, 0.12 in controls; rs6584555 (CC): 0.05 in patients, 0.03 in controls]. We did not find significant association between SNP rs2595104 and rs6584555 andAF. We performed a protein-protein network analysis to assess functional connection among the protein products. The proteins coded by PITX2 and NEURL1 are connected indirectly via CTNNB1 and either JAG1 or DLL4 proteins. These interactive proteins are components of two major channels of cell communication pathways, the Wnt and Notch signaling pathways.

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Cholesteatoma is an epidermal cyst with still unknown pathomechanism. The aim of the current study was to investigate molecular differences in the background of the hyperproliferative property and aggressive behavior typical of the cholesteatoma epithelium. The expression of three cytokeratin genes (KRT1, KRT10 and KRT19), the matrix metalloproteinase 9 gene (MMP9) and the tumor suppressor TP53 gene was measured by qRT-PCR in surgical samples of pediatric and adult cholesteatoma cases and their expression level was compared to that of normal skin samples from the retroauricular region of control individuals. Cholesteatoma samples were stratified according to the age of onset and recurrence for more detailed analysis. Our results showed identical expression pattern for KRT1 and KRT10, their expression was higher in pediatric cases than in adults, especially in pediatric recurrent samples. The expression level of KRT19 was inversely proportional to that of KRT1/KRT10, it was lower in the more invasive recurrent cases both in our pediatric and adult groups. As it was expected from the bone destructive behavior of cholesteatoma, a significantly elevated expression of MMP9 was measured in cholesteatoma samples, the highest level was found in adult recurrent cases. Low expression levels characterize the TP53 gene without significant differences in our samples. These findings demonstrate that cytokeratin expression distinguishes between pediatric/adult, nonrecurrent/recurrent cases, suggesting that distinct differentiation state and cell division potential characterize these cholesteatoma cases. KRT19 with a tumor suppressor potential might restrict the recurrence of cholesteatoma. The differences observed in gene expression profiles between cholesteatoma and control samples support the notion that cholesteatoma is a cystic lesion with tumor-like behavior because it is characterized by invasive, destructive growth and high tendency for recurrence.