Cíl studie: V reprodukčním období ženy dochází k opakovaným a častým strukturálním a funkčním proměnám endometria. Schopnost regenerace, remodelace a diferenciace je předpokladem receptivity endometria, implantace a vývoje embrya. Důležitým faktorem těchto procesů je vzájemná přeměna mezenchymálního a epiteliálního fenotypu endometriálních buněk – epiteliálně- -mezenchymální transice (EMT = epitelial-mesenchymal transition) a mezenchymálně-epiteliální transice (MET = mesenchymal-epithelial transition). Cílem práce je prezentovat současné poznatky o vzájemné přeměně epiteliálních a mezenchymální buněk děložní sliznice a jejich možném vlivu na poruchy plodnosti. Typ studie: Přehledová práce. Název a sídlo pracoviště: Gynekologicko-porodnická klinika Lékařské fakulty Masarykovy univerzity a FN Brno; Porodnicko-gynekologická klinika FN a LF UP Olomouc. Metodika: Literární rešerše databáze PubMed publikované do února 2019 s termíny zaměřenými na „endometrial receptivity“, „embryo implantation“, „endometrial regeneration“, „mesenchymal–epithelial transition/transformation“. Výsledky: Bylo prokázáno, že stromální buňky se podílejí na regeneraci nejen stromatu, ale také epitelu endometria. V průběhu decidualizace působením ovariálních steroidů a dalších faktorů probíhá MET, fibroblasty stromatu získávají postupně vlastnosti epiteliálních buněk – morfologicky i funkčně (sekreční endoplazmatické retikulum, pevné intercelulární spoje). V průběhu implantace embrya vlivem interakce trofoblastu s decidualizovaným endometriem dochází k přeměně epiteliálních buněk na mezenchymální (EMT), které jsou schopny migrace a regulace pronikajícího trofoblastu. Závěr: Vzájemná přeměna stromálních a epiteliálních buněk endometria je nezbytná pro fyziologickou funkci děložní sliznice včetně implantace a vývoje embrya.
Objective: During reproductive age of a woman, endometrium undergoes frequent stuctural and functional changes. Abilities of regeneration, remodelation and differentiation are precondition of endometrial receptivity and implantation and development of an embryo. These processes are conditioned by mutual transformation between mesenchymal and epithelial fenotype of endometrial cells: epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). The aim of this study is to present contemporary knowledge of transformation between epithelial and mesenchymal endometrial cells and its influence on human fertility. Design: Review article. Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk university and University Hospital Brno; Department of Obstetrics and Gynecology, University Hospital Faculty of Medicine, Palacky University, Olomouc. Methods: PubMed was searched for articles in English indexed until February 2019 with terms of „endometrial receptivity“, „embryo implantation“, „endometrial regeneration“, „mesenchymal-epithelial transition/ transformation“. Results: It has been proved, that mesenchymal stromal cells participate on regeneration of not only the endometrial stroma, but also of the epithelium. During endometrial decidualisation under influence of ovarian steroids, the MET is under way. Stromal fibroblasts gain the morfological and functional properties of epithelial cells. During implantaion of an embryo, the trofoblast interacts with decidualised endometrium. Epithelial cells transform into mesenchymal (EMT), which mediate the growth of trofoblast. Conclusion: Mutual transformation between stromal and epithelial cells in essential for normal function of endometrium and implantation and development of an embryo.
- Keywords
- mezenchymálněepiteliální transformace buněk, receptivita endometria, regenerace endometria,
- MeSH
- Endometrium * physiology MeSH
- Embryo Implantation MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Values of the calcium retention capacity (CRC) of rat liver mitochondria are highly dependent on the experimental conditions used. When increasing amounts of added calcium chloride are used (1.25-10 nmol), the values of the CRC increase 3-fold. When calcium is added in 75 s intervals, the CRC values increase by 30 % compared with 150 s interval additions. CRC values are not dependent on the calcium/protein ratio in the measured sample in our experimental design. We also show that a more detailed evaluation of the fluorescence curves can provide new information about mitochondrial permeability transition pore opening after calcium is added.
- MeSH
- Biological Transport MeSH
- Mitochondria, Liver metabolism MeSH
- Liver metabolism MeSH
- Rats MeSH
- Mitochondrial Membranes metabolism MeSH
- Permeability MeSH
- Mitochondrial Permeability Transition Pore metabolism MeSH
- Mitochondrial Membrane Transport Proteins metabolism MeSH
- Calcium metabolism MeSH
- Research Design MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
3 s. ; 30 cm
- MeSH
- Occupational Health Services trends MeSH
- Socioeconomic Factors MeSH
- Geographicals
- Europe MeSH
- Conspectus
- Veřejné zdraví a hygiena
- NML Fields
- management, organizace a řízení zdravotnictví
- věda a výzkum
- NML Publication type
- publikace WHO
Autoři shrnují matematickou metodu získání tranzitních funkcí a časů u dynamické scintigrafie ledvin. Počítají se minimální, střední a maximální tranzitní časy pro celou ledvinu, parenchym a pánvičku. Na základě hodnot a diference těchto časuje možno stanovit, zda je porucha na úrovni parenchymu nebo dutého systému (dilatace nebo obstrukce), což může významně přispět k diferenciální diagnostice příčin nefro- a uropatií.
The authors summarize briefly the mathematical method for obtaining transit functions and times in dynamic renal scintigraphy. They work out minimal, medium and maximal transit times for the whole kidney, the parenchyma and pelvis. Based on values and the differences of these times, it is possible to assess whether the disorder is at the parenchymatous level or in the hollow system (dilatation or obstruction). This can contribute in a significant way to the differential diagnosis of causes of nephropathies and uropathies.
In mammals, the conserved telomere binding protein Rap1 serves a diverse set of nontelomeric functions, including activation of the NF-kB signaling pathway, maintenance of metabolic function in vivo, and transcriptional regulation. Here, we uncover the mechanism by which Rap1 modulates gene expression. Using a separation-of-function allele, we show that Rap1 transcriptional regulation is largely independent of TRF2-mediated binding to telomeres and does not involve direct binding to genomic loci. Instead, Rap1 interacts with the TIP60/p400 complex and modulates its histone acetyltransferase activity. Notably, we show that deletion of Rap1 in mouse embryonic stem cells increases the fraction of two-cell-like cells. Specifically, Rap1 enhances the repressive activity of Tip60/p400 across a subset of two-cell-stage genes, including Zscan4 and the endogenous retrovirus MERVL. Preferential up-regulation of genes proximal to MERVL elements in Rap1-deficient settings implicates these endogenous retroviral elements in the derepression of proximal genes. Altogether, our study reveals an unprecedented link between Rap1 and the TIP60/p400 complex in the regulation of pluripotency.
- MeSH
- Genome MeSH
- Mouse Embryonic Stem Cells metabolism MeSH
- Mice MeSH
- Telomere-Binding Proteins * genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Mammals genetics MeSH
- Telomere * metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Mitochondria play an important role in the cell aging process. Changes in calcium homeostasis and/or increased reactive oxygen species (ROS) production lead to the opening of mitochondrial permeability transition pore (MPTP), depolarization of the inner mitochondrial membrane, and decrease of ATP production. Our work aimed to monitor age-related changes in the Ca2+ ion effect on MPTP and the ability of isolated rat liver mitochondria to accumulate calcium. The mitochondrial calcium retention capacity (CRC) was found to be significantly affected by the age of rats. Measurement of CRC values of the rat liver mitochondria showed two periods when 3 to 17-week old rats were tested. 3-week and 17-week old rats showed lower CRC values than 7-week old animals. Similar changes were observed while testing calcium-induced swelling of rat liver mitochondria. These findings indicate that the mitochondrial energy production system is more resistant to calcium-induced MPTP opening accompanied by the damaging effect of ROS in adult rats than in young and aged animals.
- MeSH
- Mitochondria, Liver metabolism MeSH
- Rats, Wistar MeSH
- Mitochondrial Permeability Transition Pore metabolism MeSH
- Aging metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The mitochondrial permeability transition pore (MPTP) is a calcium-dependent, ion non-selective membrane pore with a wide range of functions. Although the MPTP has been studied for more than 50 years, its molecular structure remains unclear. Short-term (reversible) opening of the MPTP protects cells from oxidative damage and enables the efflux of Ca2+ ions from the mitochondrial matrix and cell signaling. However, long-term (irreversible) opening induces processes leading to cell death. Ca2+ ions, reactive oxygen species, and changes in mitochondrial membrane potential regulate pore opening. The sensitivity of the pore to Ca2+ ions changes as an organism ages, and MPTP opening plays a key role in the pathogenesis of many diseases. Most studies of the MPTP have focused on elucidating its molecular structure. However, understanding the mechanisms that will inhibit the MPTP may improve the treatment of diseases associated with its opening. To evaluate the functional state of the MPTP and its inhibitors, it is therefore necessary to use appropriate methods that provide reproducible results across laboratories. This review summarizes our current knowledge of the function and regulation of the MPTP. The latter part of the review introduces two optimized methods for evaluating the functional state of the pore under standardized conditions.
Binary and ternary amorphous transition metal (TM) nitrides and oxides are of great interest because of their suitability for diverse applications ranging from high-temperature machining to the production of optical filters or electrochromic devices. However, understanding of bonding in, and electronic structure of, these materials represents a challenge mainly due to the d electrons in their valence band. In the present work, we report ab initio calculations of the structure and electronic structure of ZrSiN materials. We focus on the methodology needed for the interpretation and automatic analysis of the bonding structure, on the effect of the length of the calculation on the convergence of individual quantities of interest and on the electronic structure of materials. We show that the traditional form of the Wannier function center-based algorithm fails due to the presence of d electrons in the valence band. We propose a modified algorithm, which allows one to analyze bonding structure in TM-based systems. We observe an appearance of valence p states of TM atoms in the electronic spectra of such systems (not only ZrSiN but also NbO(x) and WAuO), and examine the importance of the p states for the character of the bonding as well as for facilitating the bonding analysis. The results show both the physical phenomena and the computational methodology valid for a wide range of TM-based ceramics.
Cystic fibrosis (CF) is a monogenetic disease resulting from mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene encoding an anion channel. Recent evidence indicates that CFTR plays a role in other cellular processes, namely in development, cellular differentiation and wound healing. Accordingly, CFTR has been proposed to function as a tumour suppressor in a wide range of cancers. Along these lines, CF was recently suggested to be associated with epithelial-mesenchymal transition (EMT), a latent developmental process, which can be re-activated in fibrosis and cancer. However, it is unknown whether EMT is indeed active in CF and if EMT is triggered by dysfunctional CFTR itself or a consequence of secondary complications of CF. In this study, we investigated the occurrence of EMT in airways native tissue, primary cells and cell lines expressing mutant CFTR through the expression of epithelial and mesenchymal markers as well as EMT-associated transcription factors. Transepithelial electrical resistance, proliferation and regeneration rates, and cell resistance to TGF-β1induced EMT were also measured. CF tissues/cells expressing mutant CFTR displayed several signs of active EMT, namely: destructured epithelial proteins, defective cell junctions, increased levels of mesenchymal markers and EMT-associated transcription factors, hyper-proliferation and impaired wound healing. Importantly, we found evidence that the mutant CFTR triggered EMT was mediated by EMT-associated transcription factor TWIST1. Further, our data show that CF cells are over-sensitive to EMT but the CF EMT phenotype can be reversed by CFTR modulator drugs. Altogether, these results identify for the first time that EMT is intrinsically triggered by the absence of functional CFTR through a TWIST1 dependent mechanism and indicate that CFTR plays a direct role in EMT protection. This mechanistic link is a plausible explanation for the high incidence of fibrosis and cancer in CF, as well as for the role of CFTR as tumour suppressor protein.
- MeSH
- Cystic Fibrosis metabolism pathology MeSH
- Epithelial-Mesenchymal Transition MeSH
- HEK293 Cells MeSH
- Nuclear Proteins metabolism MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Oncogenes genetics MeSH
- Cystic Fibrosis Transmembrane Conductance Regulator metabolism MeSH
- Twist-Related Protein 1 metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
