Porucha autistického spektra (PAS) a schizofrénia majú genetický základ, ale významnú úlohu v etiopatogenéze zohrávajú aj faktory prostredia. Jedným z nich môže byť infekčné ochorenie, ktoré matka prekoná počas tehotenstva. Vyplýva to predovšetkým z epidemiologických štúdií, podľa ktorých prenatálna infekcia za určitých okolností zvyšuje riziko vzniku PAS a schizofrénie u potomkov. Animálne experimenty naznačujú, že kľúčovú úlohu tu zohráva najmä imunitná odpoveď matky na infekciu, predovšetkým v podobe cytokínovej búrky. Výsledný efekt prenatálnej infekcie však závisí od viacerých rizikových a protektívnych faktorov na strane matky i plodu, ako aj od charakteristík pôsobiacej infekcie. V prípade COVID-19 zatiaľ pre krátkosť času takéto štúdie absentujú, no vzhľadom na jeho infekčný charakter a najmä vysoký výskyt nie je neopodstatnené uvažovať o možnom riziku. Cieľom našej práce bolo zosumarizovať výsledky epidemiologických a animálnych štúdií súvisiacich s inými infekciami a na ich základe uvažovať, či COVID-19 počas tehotenstva môže predstavovať riziko pre vznik PAS alebo schizofrénie u potomkov.

Autism spectrum disorder (ASD) and schizophrenia have a genetic basis, but environmental factors also play a significant role in their etiopathogenesis. One of them may be an infectious disease in the mother during pregnancy. This is indicated mainly by the epidemiological studies, in which a prenatal infection has been shown to increase under certain circumstances the risk of ASD and schizophrenia in the offspring. Animal experiments indicate that the immune response of the mother plays a key role here, especially in the form of a cytokine storm. However, the resulting effect of the prenatal infection depends on several risk and protective factors on the side of the mother and the fetus, as well as on the characteristics of the infections. In case of COVID-19, due to the shortness of time, such studies are absent, however, due to its infectious nature, and predominantly its high prevalence rates, it is reasonable to consider this disease as a potential risk. The objective of our paper was to summarize results of epidemiological and animal studies in respect to other infections and, based on that, to analyse whether COVID-19 during pregnancy represents a risk for the development of ASD or schizophrenia in the offspring.

• MeSH
• COVID-19 patologie   MeSH
• cytokiny analýza   fyziologie   MeSH
• infekční komplikace v těhotenství * imunologie   patologie   MeSH
• lidé MeSH
• modely u zvířat MeSH
• myši MeSH
• poruchy autistického spektra * etiologie   MeSH
• rizikové faktory MeSH
• schizofrenie etiologie   MeSH
• zpožděný efekt prenatální expozice imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

We explored possibility that sodium/calcium exchanger 1 (NCX1) is involved in pH modulation and apoptosis induction in GYY4137 treated cells. We have shown that although 10 days treatment with GYY4137 did not significantly decreased volume of tumors induced by colorectal cancer DLD1 cells in nude mice, it already induced apoptosis in these tumors. Treatment of DLD1 and ovarian cancer A2780 cells with GYY4137 resulted in intracellular acidification in a concentration-dependent manner. We observed increased mRNA and protein expression of both, NCX1 and sodium/hydrogen exchanger 1 (NHE1) in DLD1-induced tumors from GYY4137-treated mice. NCX1 was coupled with NHE1 in A2780 and DLD1 cells and this complex partially disintegrated after GYY4137 treatment. We proposed that intracellular acidification is due to uncoupling of NCX1/NHE1 complex rather than blocking of the reverse mode of NCX1, probably due to internalization of NHE1. Results might contribute to understanding molecular mechanism of H2S-induced apoptosis in tumor cells.

• MeSH
• apoptóza účinky léků   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• morfoliny farmakologie   MeSH
• myši nahé MeSH
• nádorové buněčné linie MeSH
• organothiofosforové sloučeniny farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• pumpa pro výměnu sodíku a vápníku metabolismus   MeSH
• sodíko-vodíkový výměnný transportér 1 metabolismus   MeSH
• sulfan metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Knowledge about the expression and thus a role of enzymes that produce endogenous H2S - cystathionine-β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient's samples, microarray and immunohistochemistry was used. METHODS: To determine the physiological importance, we used RCC4 stable cell line derived from clear cell renal cell carcinoma, where apoptosis induction by a mixture of five chemotherapeutics with/without silencing of H2S-producing enzymes was detected. Immunofluorescence was used to determine each enzyme in the cells. RESULTS: In clear cell renal cell carcinomas, expression of H2S-producing enzymes was mostly decreased compared to a part of kidney that was distal from the tumor. To evaluate a potential role of H2S-producing enzymes in the apoptosis induction, we used RCC4 stable cell line. We have found that silencing of cystathionine-β-synthase and cystathionine γ-lyase prevented induction of apoptosis. Immunofluorescence staining clearly showed that these enzymes were upregulated during apoptosis in RCC4 cells. CONCLUSION: Based on these results we concluded that in clear cell renal cell carcinoma, reduced expression of the H2S-producing enzymes, mainly cystathionine γ-lyase, might contribute to a resistance to the induction of apoptosis. Increased production of the endogenous H2S, or donation from the external sources might be of a therapeutic importance in these tumors.

• MeSH
• apoptóza * MeSH
• cystathionin-beta-synthasa genetika   metabolismus   MeSH
• cystathionin-gama-lyasa genetika   metabolismus   MeSH
• dospělí MeSH
• karcinom z renálních buněk patologie   chirurgie   MeSH
• ledviny metabolismus   patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory ledvin patologie   chirurgie   MeSH
• nefrektomie MeSH
• RNA interference MeSH
• senioři MeSH
• sulfan metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH