Endometrióza je velmi komplikované chronické onemocnění s vysokou prevalencí mezi ženami fertilního věku, které výrazným způsobem ovlivňuje kvalitu jejich života i schopnost otěhotnět. V klinické praxi se stále častěji setkáváme s pokročilými stadii onemocnění, zejména ve formě hluboké endometriózy, která mohou vést nejen k výrazným symptomům, ale i orgánovému postižení. Cílem článku je shrnout současné poznatky o patologických procesech vedoucích k fibrózním změnám, jež stojí za nejzávažnějšími nálezy. Zároveň je teoretickým základem běžícího výzkumného projektu zaměřeného na identifikaci molekulárních markerů stojících právě za nejtěžšími formami endometriózy, které by mohly pomoci v predikci progrese onemocnění.

Endometriosis is a complex chronic disorder with a high prevalence among women of reproductive age, significantly affecting both their quality of life and ability to conceive. In clinical settings, there is an increasing incidence of advanced disease stages, particularly deep infiltrating endometriosis, which not only produces severe clinical symptoms, but also results in organ involvement. This article aims to synthesize current insights into the pathological mechanisms underlying fibrotic remodelling, which is associated with the most severe manifestations of the disease. Furthermore, it provides the theoretical framework for an ongoing research project aimed at identifying molecular biomarkers implicated in the most advanced forms of endometriosis, with the potential to enhance prediction of disease progression.

• MeSH
• biologické markery metabolismus   MeSH
• endometrióza * diagnóza   genetika   komplikace   MeSH
• fibróza * diagnóza   etiologie   genetika   MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 analýza   MeSH
• molekulární patologie metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

One of the key features of eukaryotic cells is the separation of nuclear and cytoplasmic compartments by a double-layer nuclear envelope. This separation is crucial for timely regulation of gene expression, mRNA biogenesis, cell cycle, and differentiation. Since transcription takes place in the nucleus and the major part of translation in the cytoplasm, proper distribution of biomolecules between these two compartments is ensured by nucleocytoplasmic shuttling proteins - karyopherins. Karyopherins transport biomolecules through nuclear pores bidirectionally in collaboration with Ran GTPases and utilize GTP as the source of energy. Different karyopherins transport different cargo molecules that play important roles in the regulation of cell physiology. In cancer cells, this nucleocytoplasmic transport is significantly dysregulated to support increased demands for the import of cell cycle-promoting biomolecules and export of cell cycle inhibitors and mRNAs. Here, we analysed genomic, transcriptomic and proteomic data from published datasets to comprehensively profile karyopherin genes in hepatocellular carcinoma. We have found out that expression of multiple karyopherin genes is increased in hepatocellular carcinoma in comparison to the normal liver, with importin subunit α-1, exportin 2, importin subunit β-1 and importin 9 being the most over-expressed. More-over, we have found that increased expression of these genes is associated with higher neoplasm grade as well as significantly worse overall survival of liver cancer patients. Taken together, our bioinformatic data-mining analysis provides a comprehensive geno-mic and transcriptomic landscape of karyopherins in hepatocellular carcinoma and identifies potential members that could be targeted in order to develop new treatment regimens.

• MeSH
• aktivní transport - buněčné jádro MeSH
• buněčné jádro metabolismus   MeSH
• hepatocelulární karcinom * genetika   metabolismus   MeSH
• karyoferiny genetika   metabolismus   MeSH
• lidé MeSH
• nádory jater * genetika   metabolismus   MeSH
• prognóza MeSH
• proteomika MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Focal adhesions are specific types of cellular adhesion structures through which both mechanical force and regulatory signals are transmitted. Recently, the existence of focal adhesions in 3D environment has been questioned. Using a unique life-like model of dermis-based matrix we analysed the presence of focal adhesions in a complex 3D environment. Although the dermis-based matrix constitutes a 3D environment, the interface of cell-to-matrix contacts on thick bundled fibres within this matrix resembles 2D conditions. We call this a quasi-2D situation. We suggest that the quasi-2D interface of cell-to-matrix contacts constituted in the dermis-based matrix is much closer to in tissue conditions than the meshed structure of mostly uniform thin fibres in the gel-based matrices. In agreement with our assumption, we found that the cell adhesion structures are formed by cells that invade the dermis-based matrix and that these structures are of similar size as focal adhesions formed on fibronectin-coated coverslips (2D). In both 2D situation and the dermis-based matrix, we observed comparable vinculin dynamics in focal adhesions and comparable enlargement of the focal adhesions in response to a MEK inhibitor. We conclude that focal adhesions that are formed in the 3D environment are similar in size and dynamics as those seen in the 2D setting.

• MeSH
• buněčné kultury * MeSH
• butadieny farmakologie   MeSH
• fokální adheze účinky léků   metabolismus   ultrastruktura   MeSH
• FRAP MeSH
• konfokální mikroskopie MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy kinas antagonisté a inhibitory   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nitrily farmakologie   MeSH
• škára účinky léků   metabolismus   MeSH
• Sus scrofa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH