The increased interest in assisted reproduction through in vitro fertilization (IVF) leads to an urgent need to identify biomarkers that reliably highly predict the success of pregnancy. Despite advances in diagnostics, treatment, and IVF approaches, the 30% success rate of IVF seems insurmountable. Idiopathic infertility does not have any explanation for IVF failure especially when a patient is treated with a healthy competitive embryo capable of implantation and development. Since appropriate intercellular communication is essential after embryo implantation, the emergence of the investigation of embryonic secretome including short non-coding RNA (sncRNA) molecules is crucial. That's why biomarker identification, sncRNAs secreted during the IVF process into the blastocyst's cultivation medium, by the implementation of artificial intelligence opens the door to a better understanding of the bidirectional communication between embryonic cells and the endometrium and so the success of the IVF. This study presents a set of promising new sncRNAs which are revealed to predictively distinguish a high-quality embryo, suitable for an embryo transfer in the IVF process, from a low-quality embryo with 86% accuracy. The identified exact combination of miRNAs/piRNAs as a non-invasively obtained biomarker for quality embryo determination, increasing the likelihood of implantation and the success of pregnancy after an embryo transfer.
Cardiovascular comorbidities are independent risk factors for mortality in dialysis patients. MicroRNA signaling has an important role in vascular aging and cardiac health, while physical activity is a primary nonpharmacologic treatment for cardiovascular comorbidities in dialysis patients. To identify the relationships between muscle function, miRNA signaling pathways, the presence of vascular calcifications and the severity of cardiovascular comorbidities, we initially enrolled 90 subjects on hemodialysis therapy and collected complete data from 46 subjects. A group of 26 subjects inactiv group (INC) was monitored during 12 weeks of physical inactivity and another group of 20 patients exercise group (EXC) was followed during 12 weeks of intradialytic, moderate intensity, resistance training intervention applied three times per week. In both groups, we assessed the expression levels of myo-miRNAs, proteins, and muscle function (MF) before and after the 12-week period. Data on the presence of vascular calcifications and the severity of cardiac comorbidities were collected from the patients' EuCliD® records. Using a full structural equitation modelling of the total study sample, we found that the higher the increase in MF was observed in patients, the higher the probability of a decrease in the expression of miR-206 and TRIM63 and the lower severity of cardiac comorbidities. A reduced structural model in INC patients showed that the higher the decrease in MF, the higher the probability of the presence of calcifications and the higher severity of cardiac comorbidities. In EXC patients, we found that the higher the increase in MF, the lower the probability of higher severity of cardiovascular comorbidities.
- MeSH
- cévní endotel metabolismus MeSH
- cvičení fyziologie MeSH
- dialýza ledvin * MeSH
- kardiovaskulární nemoci krev genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza krev genetika MeSH
- sedavý životní styl MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- stárnutí krev genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Adrenal incidentalomas (AI) are very common and mostly they are non-functioning adenomas (NFA). NFAs are often associated with insulin resistance and metabolic syndrome. Several biomarkers, including certain growth factors, may participatein the pathogenesis ofmetabolic changes in patients with adrenal adenomas.Patients with NFA and age-matched control subjects were enrolled in the study. Data on age, gender, presence of metabolic syndrome or its components were obtained for each subject. Blood samples were obtained and glycemia, insulinemia, lipid profile, and selected growth factor levels were measured. Forty-three patients with NFA and 40 controls were included in the study. Differences were not found in the metabolic syndrome and its components prevalence or in the biochemical profile between patients and the control group. Significant differences were noticed in the levels of IGF1, IGF2, and IGFBP3 (p=0.016, p=0.005, p=0.004, respectively), but there were no differences in VEGF or EGF concentrations. In NFA patients, an association between glycemia and EGF levels was present (p=0.026). No significant correlations between tumor size and insulin or growth factor concentrations were present in AI patients. Significantly higher serum IGF1, IGF2, and IGFBP3 concentrations in NFA patients may support the role of the IGF axis in the pathogenesis of adrenocortical lesions.No correlation between IGFs or IGFBP3 and parameters of glucose or lipid metabolism was found. Present results may support the role of the growth hormone axis rather than hyperinsulinemia and insulin resistance in the pathogenesis of adrenocortical adenomas.
- MeSH
- adenom kůry nadledvin krev patologie MeSH
- adrenokortikální nádory krev patologie MeSH
- dospělí MeSH
- epidermální růstový faktor krev MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- insulinu podobný růstový faktor II metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol 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
The miRNA-206 and miRNA-23a play an important role in muscle tissue hypertrophy, regeneration and atrophy. Both of these miRNAs have been highlighted as promising adaptation predictors; however, the available evidence on associations is inconclusive. Therefore, our aim was to assess the expression levels of these two miRNAs as predictors of change in muscle function during strength training and physical inactivity among dialysed patients. For this purpose, 46 haemodialysis patients were monitored for 12-weeks of either intradialytic strength training (EXG, n = 20) or physical inactivity during dialysis (CON, n = 26). In both groups of patients, we assessed the baseline expression levels of miRNA-23a and miRNA-206 and the isometric force generated during hip flexion (HF) contraction before and after the 12-week period. Among the EXG group, the expression of miRNA-206 predicted the change in HF (R2 = 0.63, p = 0.0005) much more strongly than the expression of miRNA-23a (R2 = 0.21, p = 0.027). Interestingly, baseline miRNA-23a (R2 = 0.30, p = 0.006) predicted the change in HF much more than miRNA-206 (p = ns) among the CON group. Our study indicates that the baseline expression of miRNA-206 could predict the response to strength training, while miRNA-23a could serve as a potential predictive marker of functional changes during physical inactivity in dialysis patients.
- MeSH
- biologické markery analýza MeSH
- dialýza ledvin metody MeSH
- fyziologická adaptace MeSH
- kondiční příprava zvířat * MeSH
- kosterní svaly metabolismus patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA analýza genetika MeSH
- odporový trénink * MeSH
- sedavý životní styl * MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
Východiská: Malígny melanóm je jedným z najagresívnejších druhov rakoviny. Melanóm primárne vzniká z pigment produkujúcich buniek melanocytov, ktoré sa vyznačujú špecifickými mechanizmami prežívania. Kľúčové postavenie v metabolizme melanómu má transkripčný faktor asociovaný s mikroftalmiou (microphthalmia-associated transcription factor – MITF-M). MITF-M sa zapája do regulácie expresie veľkého počtu génov riadiacich procesy melanogenézy, proliferácie, diferenciácie a prežitia melanocytov. Expresia tohto transkripčného faktora v melanocytoch je aktivovaná niekoľkými signálnymi cestami, pričom blokovanie jeho expresie, alebo funkcie môže znamenať poruchu v regulácii antiapoptotických mechanizmov. MITF-M taktiež ovplyvňuje aktivitu matrixovej metaloproteinázy 14 (matrix metalloproteinase – MMP14), ktorá je zodpovedná za zmenu tvaru melanocytov a za zvýšenie ich pohyblivosti a invazivity. V ľudských melanocytoch s invazívnym fenotypom bola zistená veľmi nízka hladina expresie MITF-M, čo naznačuje že tento transkripčný faktor pôsobí ako supresor metastatického procesu. V rakovinových bunkách s nízkou hladinou expresie cytozolového/nukleárneho β-katenínu, vzniká malé množstvo proteínu MITF-M, ktorý nedokáže inhibovať transkripciu MMP 14. Tento enzým katalyzuje degradáciu laminínu a fibronektínu, čím dochádza k zmene tvaru melanocytov, k zvýšemiu ich pohyblivosti a invazivity. Ciele: Táto prehľadová práca popisuje regulačnú dráhu aktivácie MITF-M, jeho zapojenie do proliferácie transformovaných melanocytov ako aj jeho úlohu pri zvyšovaní invazivity malígneho melanómu. Detailné pochopenie mechanizmov fungovania signálnej dráhy MITF-M je vysoko aktuálnou témou a môže pomôcť pri vývoji nových tak diagnostických, ako aj terapeutických aplikácií pri liečbe pacientov s malígnym melanómom.
Background: Malignant melanoma is one of the most aggressive types of cancers. Melanoma is derived from pigment-producing cells, melanocytes, which are characterized by a specific survival mechanism. Microphthalmia-associated transcription factor (MITF-M) plays a role in the metabolism of melanoma and is involved in the regulation of the expression of multiple genes mediating processes such as melanogenesis, proliferation, differentiation, and melanocyte survival. The expression of this transcription factor in melanocytes is activated by several signaling pathways, and reduced expression or function of MITF-M can cause the dysregulation of anti-apoptotic mechanisms. MITF-M is also involved in matrix metalloproteinase 14 (MMP14) activity, which is responsible for shape changes in melanocytes and increases in their motility and invasiveness. Very low levels of expression of MITF-M are found in human melanocytes with an invasive phenotype, indicating that this transcription factor acts as a suppressor of the metastatic process. Cancer cells with low expression of cytosolic/nuclear β-catenin have a small amount of MITF-M 14 that is insufficient to inhibit MMP transcription. The enzyme catalyzes the degradation of laminin and fibronectin, thereby changing the shape of melanocytes, which leads to their increased mobility and invasiveness. Aims: This review describes the regulatory pathway of MITF-M activation, its involvement in the proliferation of transformed melanocytes, and its role in increasing the invasiveness of malignant melanoma. A detailed understanding of the MITF-M signaling pathway is highly topical and could help to develop new diagnostic and therapeutic applications for patients with malignant melanoma.
- MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- melanocyty metabolismus MeSH
- melanom * genetika metabolismus MeSH
- nádorová transformace buněk * metabolismus MeSH
- nádory kůže genetika metabolismus MeSH
- proliferace buněk MeSH
- transkripční faktor spojený s mikroftalmií * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: This study describes the effect of rapid tumor growth of patients suffering from various grades of malignant ductal breast carcinoma associated with the gene expression of ECM protein emilin 1, in correlation with the number of gene copies of emilin 1 and degradation of tumor tissue proteins. METHODS: A total of 40 examined patients participated in the experiment (controls, n = 10, grades GI-GIII, each n = 10). After isolation of total mRNA, transcription of mRNA into the cDNA was performed. Quantification of gene expression changes was detected by the real-time PCR method. Analysis at the protein level was performed via Western blot method. RESULTS: During the detection of changes at the mRNA level, a significantly decreased level of emilin 1 in tumor tissues with grade II (about 54 ± 8 % lower than control) was identified. Protein-level analysis indicated an increased level of emilin 1 in tumors with grade I in comparison with control samples (about 10 ± 3 %). CONCLUSION: Obtained results demonstrated that the suppressive role of emilin 1 is related to the grade of growing breast tumors, and associated with increased hypoxia in the tumor microenvironment followed by elevated unfolding and degradation of tissue proteins.
- MeSH
- duktální karcinom prsu genetika metabolismus MeSH
- exprese genu MeSH
- genová dávka MeSH
- komplementární DNA genetika metabolismus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- membránové glykoproteiny biosyntéza genetika MeSH
- messenger RNA genetika metabolismus MeSH
- nádory prsu genetika metabolismus MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Plodová voda predstavuje biologickú tekutinu, ktorá v určitých medziach odráža metabolický stav plodu, preto štúdium jej zložiek a ich zmien v jednotlivých týždňoch tehotenstva poskytuje užitočné informácie o raste a dozrievaní plodu za fyziologických, ale aj patologických podmienok. Koncentrácia glukózy v plodovej vode je prediktívny marker hmotnosti vyvíjajúceho sa plodu, marker intrauterinnej infekcie, ktorý odráža zrelosť plodu, metabolický stav matky, ale môže súvisieť aj s niektorými vrodenými poruchami. V našej štúdii sme pomocou diagnostických prúžkov v plodovej vode v rôznych týždňoch tehotenstva sledovali rôzne parametre ako špecifická hmotnosť, proteíny, nitrity, pH, leukocyty, a hladinu glukózy. Veľmi zaujímavé výsledky sme získali pri semikvantitatívnom vyhodnotení koncentrácie glukózy. Za fyziologických podmienok koncentrácia glukózy negatívne koreluje s týždňom gravidity, na základe čoho možno predvídať potenciálne využitie rýchlych strip testov aj v klinickej praxi v prípade dostupnosti plodovej vody.
Amniotic fluid represent a biological fluid, which reflect metabolic state of the fetus, the study of its components and their changes in different gestational weeks provide useful information about the growth and maturation of the fetus under physiological, as well as pathological conditions. Concentration of glucose in amniotic fluid is considered as predictive marker of fetus weight, of intrauterine infection, it reflects the fetal maturity, maternal metabolic state, but is also connected with some births defects. In our study, we focused on the detection of specific gravity, proteins, nitrites, pH, leukocytes and glucose level in amniotic fluid, in different weeks of pregnancy by diagnostic strips. Very interesting results were obtained in the semi-quantitative evaluation of glucose concentration. Under physiological conditions the glucose concentration in amniotic fluid progressively decreases with weeks of pregnancy, on the basis of which it is foreseeable potential use of rapid-strip tests and in clinical practice, where available amniotic fluid.
Východiská: Malígny melanóm patrí k najzhubnejším nádorovým ochoreniam zo všetkých nádorov kože mužov aj žien. Pravdepodobnosť vzniku malígneho melanómu závisí od vplyvu vonkajších faktorov a vzájomnej deregulácii interakcií genotypu a fenotypu. V súčasnosti sa čoraz väčšia pozornosť venuje štúdiu interakcií aktívnej formy vitamínu D3 s receptorom, ako aj inhibičnému účinku polymorfizmov receptoru vitamínu D3 na viaceré signálne dráhy zapojené do proliferačných a metastatických procesov. Ciele: Táto prehľadová práca sa zameriava na popísanie vzťahu medzi faktormi, ktoré pôsobia na vznik maligného melanómu ovplyvnením Hedgehog signálnej dráhy (HH). Sumarizuje súčasné poznatky zaoberajúce sa malígnym melanómom v spojení s úlohou aktívnej formy vitamínu D3 pri väzbe na receptor vitamínu D3 (VDR) a vplyvu polymorfizmov VDR na inhibíciu HH. Pochopenie daných mechanizmov a kritické zhodnotenie poznatkov sú dôležité pre aplikáciu primárnej, ako aj sekundárnej prevencie, respektíve pri použití chemoprevenčných látok vhodných pre predchádzanie vzniku malígneho melanómu.
Background: Malignant melanoma is one of the most aggressive cutaneous tumors in men and women. The risk of developing a malignant melanoma depends on several external factors along with deregulation of mutual interaction of genotype and phenotype. Nowadays, growing attention is focused on the study of the interactions of the active form of vitamin D3 with its receptor and inhibitory effect of vitamin D3 receptor polymorphisms on multiple signaling pathways involved in proliferative and metastatic processes. Objectives: This review article addresses the relationship between factors involved in the development of malignant melanoma through Hedgehog signaling pathway (HH). It summarizes current knowledge of malignant melanoma in regard to the role of the active form of vitamin D3 binding to vitamin D3 receptor (VDR), as well as it describes the influence of polymorphisms of VDR on the inhibition of HH. Understanding of these mechanisms and critical assessment of available data is beneficial to both primary and secondary prevention of malignant melanoma particularly by means of chemo‑preventive substances. Key words: vitamin D3 – Hedgehog signalisation – melanoma – calcitriol – skin cancer This work was supported by by the grant DIAGONKO ITMS: 26220220153. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers. Submitted: 21. 12. 2013 Accepted: 25. 2. 2014
- Klíčová slova
- Hedgehog signalizace,
- MeSH
- cholekalciferol chemie metabolismus MeSH
- kalcitriol chemie metabolismus MeSH
- lidé MeSH
- melanom * etiologie metabolismus MeSH
- polymorfismus genetický * MeSH
- proteiny hedgehog metabolismus MeSH
- receptory kalcitriolu * genetika metabolismus MeSH
- signální transdukce MeSH
- vitamin D metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
