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001-es BibID:	BIBFORM078491
035-os BibID:	(cikkazonosító)1661 (PMID)30135684 (WoS)000441059500001 (Scopus)85054929775
Első szerző:	Than Nándor Gábor (szülész-nőgyógyász)
Cím:	Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia / Nandor Gabor Than, Roberto Romero, Adi Laurentiu Tarca, Katalin Adrienna Kekesi, Yi Xu, Zhonghui Xu, Kata Juhasz, Gaurav Bhatti, Ron Joshua Leavitt, Zsolt Gelencser, Janos Palhalmi, Tzu Hung Chung, Balazs Andras Gyorffy, Laszlo Orosz, Amanda Demeter, Anett Szecsi, Eva Hunyadi-Gulyas, Zsuzsanna Darula, Attila Simor, Katalin Eder, Szilvia Szabo, Vanessa Topping, Haidy El-Azzamy, Christopher LaJeunesse, Andrea Balogh, Gabor Szalai, Susan Land, Olga Torok, Zhong Dong, Ilona Kovalszky, Andras Falus, Hamutal Meiri, Sorin Draghici, Sonia S. Hassan, Tinnakorn Chaiworapongsa, Manuel Krispin, Martin Knöfler, Offer Erez, Graham J. Burton, Chong Jai Kim, Gabor Juhasz, Zoltan Papp
Dátum:	2018
ISSN:	1664-3224
Megjegyzések:	Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This sine qua non of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different "omics," clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. Moreover, first trimester maternal blood from preterm preeclamptic patients in vitro dysregulated trophoblastic gene expression. Placental transcriptomics of women with preterm preeclampsia identified distinct gene modules associated with maternal or fetal disease. Placental "virtual" liquid biopsy showed that the dysregulation of these disease gene modules originates during the first trimester. In vitro experiments on hub transcription factors of these gene modules demonstrated that DNA hypermethylation in the regulatory region of ZNF554 leads to gene down-regulation and impaired trophoblast invasion, while BCL6 and ARNT2 up-regulation sensitizes the trophoblast to ischemia, hallmarks of preterm preeclampsia. In summary, our data suggest that there are distinct maternal and placental disease pathways, and their interaction influences the clinical presentation of preeclampsia. The activation of maternal disease pathways can be detected in all phenotypes of preeclampsia earlier and upstream of placental dysfunction, not only downstream as described before, and distinct placental disease pathways are superimposed on these maternal pathways. This is a paradigm shift, which, in agreement with epidemiological studies, warrants for the central pathologic role of preexisting maternal diseases or perturbed maternal-fetal-placental immune interactions in preeclampsia. The description of these novel pathways in the "molecular phase" of preeclampsia and the identification of their hub molecules may enable timely molecular characterization of patients with distinct preeclampsia phenotypes.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk preeclampsia
Megjelenés:	Frontiers in Immunology. - 9 (2018), p. 1-41. -
További szerzők:	Romero, Roberto Tarca, Adi Laurentiu Kékesi Katalin Adrienna Xu, Yi Xu, Zhonghui Juhász Kata Bhatti, Gaurav Leavitt, Ron Joshua Gelencsér Zsolt Pálhalmi János Chung, Tzu Hung Győrffy Balázs Orosz László (1984-) (szülész-nőgyógyász) Demeter Amanda Szécsi Anett Hunyadi-Gulyás Éva Darula Zsuzsanna Simor Attila Eder Katalin Szabó Szilvia Topping Vanessa El-Azzamy, Haidy LaJeunesse, Christopher Balogh Andrea Szalai Gábor Land, Susan Török Olga (1956-) (szülész-nőgyógyász, humángenetikus) Dong, Zhong Kovalszky Ilona Falus András Meiri, Hamutal Draghici, Sorin Hassan, Sonia S. Chaiworapongsa, Tinnakorn Krispin, Manuel Knöfler, Martin Erez, Offer Burton, Graham J. Kim, Chong Jai Juhász Gábor (ELTE) Papp Zoltán (1942-) (szülész-nőgyógyász, genetikus)
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001-es BibID:	BIBFORM118894
035-os BibID:	(cikkazonosító)1329236 (WoS)001152827800001 (Scopus)85186581723
Első szerző:	Tóth Eszter Lilla
Cím:	Case report : Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss / Tóth Eszter Lilla, Orbán-Kálmándi Rita, Bagoly Zsuzsa, Lóczi Linda, Deli Tamás, Török Olga, Molnár Sarolta, Baráth Sándor, Singh Parvind, Hevessy Zsuzsanna, Katona Éva, Fagyas Miklós, Szabó Attila Ádám, Molnár Szabolcs, Krasznai Zoárd Tibor
Dátum:	2024
ISSN:	1664-3224
Megjegyzések:	Background: SARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn't been described so far. Besides knowledge gaps in the pathomechanism leading to stillbirth in COVID-19 pregnancies, currently, no prognostic biomarker is available to identify pregnant patients who are at imminent risk of COVID-19-associated maternal and fetal complications, requiring immediate medical attention. Case: Here we report the case of a 28-year-old SARS-CoV-2 infected pregnant patient, admitted to our hospital at 28 weeks of gestation with intrauterine fetal loss. The presence of SARS-CoV-2 placentitis was confirmed by immunohistological evaluation of the placenta. She had only mild upper respiratory symptoms and her vital signs were within reference throughout labor and postpartum. The stillborn infant was delivered per vias naturales. Fibrinogen concentrate was administered before and after labor due to markedly decreased fibrinogen levels (1.49 g/l) at admission and excessive bleeding during and after delivery. Although coagulation screening tests were not alarming at admission, the balance of hemostasis was strikingly distorted in the patient. As compared to healthy age- and gestational age-matched pregnant controls, increased D-dimer, low FVIII activity, low FXIII level, marked hypocoagulability as demonstrated by the thrombin generation assay, together with shortened clot lysis and decreased levels of fibrinolytic proteins were observed. These alterations most likely have contributed to the increased bleeding observed during labor and in the early postpartum period. Interestingly, at the same time, only moderately altered inflammatory cytokine levels were found at admission. Serum ACE2 activity did not differ in the patient from that of age- and gestational age-matched healthy controls, suggesting that despite previous speculations in the literature, ACE2 may not be used as a potential biomarker for the prediction of COVID-19 placentitis and threatening fetal loss in SARS-CoV-2-infected pregnancies. Conclusions: Although based on this case report no prognostic biomarker could be identified for use in pregnant patients with imminent risk of fetal loss associated with COVID-19 placentitis, the above-described hemostasis alterations warrant awareness of postpartum hemorrhagic complications and could be helpful to identify patients requiring intensified medical attention.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok esettanulmány folyóiratcikk COVID 19 fetal death hemostasis placenta case report stillbirth
Megjelenés:	Frontiers in Immunology. - 15 (2024), p. 1-10. -
További szerzők:	Orbán-Kálmándi Rita Angéla (1993-) (klinikai laboratóriumi kutató) Bagoly Zsuzsa (1978-) (orvos) Lóczi Linda Deli Tamás (1979-) (szülész-nőgyógyász, endokrinológus szakorvos) Török Olga (1956-) (szülész-nőgyógyász, humángenetikus) Deliné Molnár Sarolta (1990-) (patológus) Baráth Sándor (1977-) (biológus) Singh, Parvind (1995-) (PhD hallgató) Hevessy Zsuzsanna (1966-) (laboratóriumi szakorvos) Katona Éva (1961-) (klinikai biokémikus) Fagyas Miklós (1984-) (orvos) Szabó Attila Ádám (1996-) (orvos) Molnár Szabolcs (1987-) (szülész-nőgyógyász szakorvos) Krasznai Zoárd Tibor (1973-) (szülész-nőgyógyász, gyermeknőgyógyász)
Pályázati támogatás:	NKFI FK128582 Egyéb TKP 2021 EGA-19 Egyéb ÚNKP 22-3-II-DE-167 Egyéb ÚNKP-23-5-DE-482 Egyéb POST-COVID2021-33 Egyéb
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