Q88354033
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Glial cells expressing neuron-glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2-expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single-cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch-clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein-4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN-positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron-like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.
- MeSH
- antigeny metabolismus MeSH
- astrocyty metabolismus MeSH
- ischemie mozku * metabolismus MeSH
- mozek metabolismus MeSH
- myši transgenní MeSH
- myši MeSH
- nervové kmenové buňky * metabolismus MeSH
- neuroglie metabolismus MeSH
- oligodendroglie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Systémová onkologická léčba metastazujícího kolorektálního karcinomu je v současnosti založena na chemoterapii kombinované s cílenou léčbou indikovanou podle přítomnosti aktivačních mutací v signální dráze EGFR-RAS-RAF, a to bez ohledu na histologickou podskupinu nádoru. V kazuistice popisujeme pacienta s mucinózní variantou kolorektálního karcinomu, který ve třetí linii léčby velmi dobře zareagoval na trifluridin/tipiracil. Ve stručném přehledu uvádíme základní charakteristiky tohoto histologického subtypu, který představuje 5-15 % všech případů, je charakterizován vysokou produkcí extracelulárního mucinu a je v souvislosti s nižší léčebnou odpovědí na chemoterapii spojován s horší prognózou. Dále poukazujeme na časný výskyt neutropenie jako potenciálního prediktivního ukazatele při léčbě trifluridinem/tipiracilem.
Systemic oncologic treatment of metastatic colorectal carcinoma is currently based on chemotherapy in combination with targeted therapy based on the presence of activating mutations in the EGFR-RAS-RAF pathway, regardless of the histological subgroup of the tumor. In this case report, we describe a patient with a mucinous variant of colorectal carcinoma who responded very well to trifluridine/tipiracil in the third-line treatment. We briefly review the basic features of this histologic subtype, which accounts for 5-15% of all cases, is characterized by high extracellular mucin production, and is associated with a poorer prognosis related to a lower response to chemotherapy. We also point to the early occurrence of neutropenia as a potential predictive marker in trifluridine/tipiracil treatment.
- Klíčová slova
- tipiracil,
- MeSH
- fixní kombinace léků MeSH
- kolorektální nádory * diagnóza farmakoterapie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- senioři MeSH
- trifluridin farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
The signalling pathway elicited by hepatocyte growth factor (HGF) and its receptor c-Met is indispensable for liver development and regeneration. It has been described that c-Met is released from the cell surface by a disintegrin and metalloprotease 10 (ADAM10) resulting in a soluble c-Met form known as sMet. Using the human hepatocellular HepG2 and hepatic stellate cell LX2 lines we show that sMet is released from the cell surface of liver cells by both ADAM17 and ADAM10, with ADAM17 appearing to be the major proteinase. Moreover, using a mouse model of 3,5-diethoxycarbonyl- 1,4-dihydroxycollidine (DDC)-induced hepatobiliary obstruction we show that serum levels of sMet correlate well with the liver damage state and consecutive regeneration as well as with established markers of liver damage such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin. However, sMet exhibited remarkably better correlation with liver damage and inflammation than did serum tumour necrosis factor α (TNF-α), whose shedding is also mediated by ADAM proteolytic activity. Our results indicate that the proteolytic activity of ADAM10/17 is essential for regulating HGF/c-Met signalling during acute liver damage and following regeneration and that the differential serum levels of sMet together with expression of c-Met/HGF might be a useful indicator not only for damage, but also for ongoing liver regeneration.
- MeSH
- alanintransaminasa krev MeSH
- aspartátaminotransferasy krev MeSH
- bilirubin metabolismus MeSH
- biologické markery metabolismus MeSH
- buňky Hep G2 MeSH
- hepatocyty metabolismus patologie MeSH
- jaterní hvězdicovité buňky metabolismus patologie MeSH
- játra metabolismus patologie MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nemoci jater krev metabolismus patologie MeSH
- proteiny ADAM metabolismus MeSH
- protoonkogenní proteiny c-met krev metabolismus MeSH
- rozpustnost MeSH
- sekretasy metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
