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001-es BibID:BIBFORM079715
035-os BibID:(WOS)000470970000010 (PMID)31185026 (Scopus)85067077554 (cikkazonosító)e0217548
Első szerző:Josifovska, Natasha (Biológus)
Cím:Clinical and molecular markers in retinal detachment : From hyperreflective points to stem cells and inflammation / Natasha Josifovska, Xhevat Lumi, Mária Szatmari-Tóth, Endre Kristóf, Greg Russell, Richárd Nagymihály, Natalia Anisimova, Boris Malyugin, Miriam Kolko, Domagoj Ivastinović, Goran Petrovski
Dátum:2019
ISSN:1932-6203
Megjegyzések:PURPOSE: Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment. METHODS: 12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ? 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin). RESULTS: OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs. CONCLUSIONS: Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Plos One. - 14 : 6 (2019), p. e0217548. -
További szerzők:Lumi, Xhevat Szatmári-Tóth Mária (1987-) (molekuláris biológus) Kristóf Endre (1987-) (általános orvos) Russell, Greg Nagymihály Richárd (1989-) (klinikai laboratóriumi kutató) Anisimova, Natalia Malyugin, Boris Kolko, Miriam Ivastinović, Domagoj Petrovski, Goran (1975-) (orvos)
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001-es BibID:BIBFORM069234
035-os BibID:(cikkazonosító)e0172189 (WOS)000395983500029 (Scopus)85014323809
Első szerző:Thangaraju, Kiruphagaran
Cím:Genomic variants reveal differential evolutionary constraints on human transglutaminases and point towards unrecognized significance of transglutaminase 2 / Thangaraju Kiruphagaran, Király Róbert, Demény Máté A., Mótyán János András, Fuxreiter Mónika, Fésüs László
Dátum:2017
ISSN:1932-6203
Megjegyzések:Transglutaminases (TGMs) catalyze Ca2+-dependent transamidation of proteins with specified roles in blood clotting (F13a) and in cornification (TGM1, TGM3). The ubiquitous TGM2 has well described enzymatic and non-enzymatic functions but in-spite of numerous studies its physiological function in humans has not been defined. We compared data on non-synonymous single nucleotide variations (nsSNVs) and loss-of-function variants on TGM1-7 and F13a from the Exome aggregation consortium dataset, and used computational and biochemical analysis to reveal the roles of damaging nsSNVs of TGM2. TGM2 and F13a display rarer damaging nsSNV sites than other TGMs and sequence of TGM2, F13a and TGM1 are evolutionary constrained. TGM2 nsSNVs are predicted to destabilize protein structure, influence Ca2+ and GTP regulation, and non-enzymatic interactions, but none coincide with conserved functional sites. We have experimentally characterized six TGM2 allelic variants detected so far in homozygous form, out of which only one, p.Arg222Gln, has decreased activities. Published exome sequencing data from various populations have not uncovered individuals with homozygous loss-of-function variants for TGM2, TGM3 and TGM7. Thus it can be concluded that human transglutaminases differ in harboring damaging variants and TGM2 is under purifying selection suggesting that it may have so far not revealed physiological functions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Plos One. - 12 : 3 (2017), p. 1-24. -
További szerzők:Király Róbert (1975-) (biológus) Demény Máté Ágoston (1976-) (molekuláris biológus) Mótyán János András (1981-) (biokémikus, molekuláris biológus) Fuxreiter Mónika (1969-) (kutató vegyész) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:NK-105046
OTKA
NN-106562
OTKA
TÁMOP-4.2.2.A-11/1/KONV-2012-0023
TÁMOP
MTA-LP2012-41
Egyéb
RH/885/2013
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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