@article{MTMT:34385416, title = {Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes}, url = {https://m2.mtmt.hu/api/publication/34385416}, author = {Sundaramurthi, Husvinee and Tonelotto, Valentina and Wynne, Kieran and O'Connell, Fiona and O’Reilly, Eve and Costa-Garcia, Marcel and Kovácsházi, Csenger and Kittel, Ágnes and Marcone, Simone and Blanco, Alfonso and Pállinger, Éva and Hambalkó, Szabolcs and Piulats Rodriguez, Jose Maria and Ferdinandy, Péter and O'Sullivan, Jacintha and Matallanas, David and Jensen, Lasse D. and Giricz, Zoltán and Kennedy, Breandán N.}, doi = {10.12688/openreseurope.15973.2}, journal-iso = {OPEN RES EUROPE}, journal = {OPEN RESEARCH EUROPE}, volume = {3}, unique-id = {34385416}, abstract = {Background Uveal melanoma is a poor prognosis cancer. Ergolide, a sesquiterpene lactone isolated from Inula Brittanica , exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo ; and 2) to understand the molecular mechanism of ergolide action. Methods Ergolide bioactivity was screened via long-term proliferation assay in UM/MUM cells and in zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by ergolide within whole cell or extracellular vesicle (EVs) lysates of the OMM2.5 MUM cell line. Protein expression was analyzed by immunoblots and correlation analyses to UM patient survival used The Cancer Genome Atlas (TCGA) data. Results Ergolide treatment resulted in significant, dose-dependent reductions (48.5 to 99.9%; p <0.0001) in OMM2.5 cell survival in vitro and of normalized primary zebrafish xenograft fluorescence (56%; p <0.0001) in vivo , compared to vehicle controls. Proteome-profiling of ergolide-treated OMM2.5 cells, identified 5023 proteins, with 52 and 55 proteins significantly altered at 4 and 24 hours, respectively ( p <0.05; fold-change >1.2). Immunoblotting of heme oxygenase 1 (HMOX1) and growth/differentiation factor 15 (GDF15) corroborated the proteomic data. Additional proteomics of EVs isolated from OMM2.5 cells treated with ergolide, detected 2931 proteins. There was a large overlap with EV proteins annotated within the Vesiclepedia compendium. Within the differentially expressed proteins, the proteasomal pathway was primarily altered. Interestingly, BRCA2 and CDKN1A Interacting Protein (BCCIP) and Chitinase Domain Containing 1 (CHID1), were the only proteins significantly differentially expressed by ergolide in both the OMM2.5 cellular and EV isolates and they displayed inverse differential expression in the cells versus the EVs. Conclusions Ergolide is a novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling of OMM2.5 cellular/EV lysates identified candidate pathways elucidating the action of ergolide and putative biomarkers of UM, that require further examination.}, year = {2023}, eissn = {2732-5121}, orcid-numbers = {Sundaramurthi, Husvinee/0000-0002-0041-0451; Tonelotto, Valentina/0000-0001-7441-2700; Costa-Garcia, Marcel/0000-0002-1930-6048; Kovácsházi, Csenger/0000-0003-0283-9486; Kittel, Ágnes/0000-0002-6888-7731; Pállinger, Éva/0000-0002-5789-0951; Ferdinandy, Péter/0000-0002-6424-6806; Matallanas, David/0000-0002-2360-3141; Giricz, Zoltán/0000-0003-2036-8665; Kennedy, Breandán N./0000-0001-7991-4689} } @article{MTMT:34371433, title = {MiR-200b categorizes patients into pancreas cystic lesion subgroups with different malignant potential}, url = {https://m2.mtmt.hu/api/publication/34371433}, author = {Benke, Márton and Zeöld, Anikó and Kittel, Ágnes and Khamari, Delaram and Hritz, István and Horváth, Miklós and Keczer, Bánk and Borka, Katalin and Szűcs, Ákos and Wiener, Zoltán}, doi = {10.1038/s41598-023-47129-1}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34371433}, issn = {2045-2322}, abstract = {Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Benke, Márton/0000-0002-8438-7438; Hritz, István/0000-0002-8763-6006; Horváth, Miklós/0000-0003-0661-3388; Borka, Katalin/0000-0002-8956-0770; Wiener, Zoltán/0000-0001-7056-4926} } @article{MTMT:33667258, title = {Acidification of blood plasma facilitates the separation and analysis of extracellular vesicles}, url = {https://m2.mtmt.hu/api/publication/33667258}, author = {Mladenović, Danilo and Khamari, Delaram and Kittel, Ágnes and Koort, Kairi and Buzás, Edit Irén and Zarovni, Nataša}, doi = {10.1016/j.jtha.2023.01.007}, journal-iso = {J THROMB HAEMOST}, journal = {JOURNAL OF THROMBOSIS AND HAEMOSTASIS}, volume = {21}, unique-id = {33667258}, issn = {1538-7933}, keywords = {IMMUNOASSAY; Lipoproteins; Blood plasma; Extracellular vesicles}, year = {2023}, eissn = {1538-7836}, pages = {1032-1042}, orcid-numbers = {Buzás, Edit Irén/0000-0002-3744-206X} } @article{MTMT:33070261, title = {Small extracellular vesicle DNA-mediated horizontal gene transfer as a driving force for tumor evolution: Facts and riddles}, url = {https://m2.mtmt.hu/api/publication/33070261}, author = {Valcz, Gábor and Újvári, Beáta and Buzás, Edit Irén and Krenács, Tibor and Spisák, Sándor and Kittel, Ágnes and Tulassay, Zsolt and Igaz, Péter and Takács, István and Molnár, Béla}, doi = {10.3389/fonc.2022.945376}, journal-iso = {FRONT ONCOL}, journal = {FRONTIERS IN ONCOLOGY}, volume = {12}, unique-id = {33070261}, issn = {2234-943X}, abstract = {The basis of the conventional gene-centric view on tumor evolution is that vertically inherited mutations largely define the properties of tumor cells. In recent years, however, accumulating evidence shows that both the tumor cells and their microenvironment may acquire external, non-vertically inherited genetic properties via horizontal gene transfer (HGT), particularly through small extracellular vesicles (sEVs). Many phases of sEV-mediated HGT have been described, such as DNA packaging into small vesicles, their release, uptake by recipient cells, and incorporation of sEV-DNA into the recipient genome to modify the phenotype and properties of cells. Recent techniques in sEV separation, genome sequencing and editing, as well as the identification of new secretion mechanisms, shed light on a number of additional details of this phenomenon. Here, we discuss the key features of this form of gene transfer and make an attempt to draw relevant conclusions on the contribution of HGT to tumor evolution.}, year = {2022}, eissn = {2234-943X}, orcid-numbers = {Valcz, Gábor/0000-0002-7109-3529; Buzás, Edit Irén/0000-0002-3744-206X; Krenács, Tibor/0000-0001-9164-065X; Tulassay, Zsolt/0000-0003-2452-6640; Igaz, Péter/0000-0003-2192-554X; Takács, István/0000-0002-7810-4833; Molnár, Béla/0000-0001-6655-7942} } @article{MTMT:32813061, title = {Activated polymorphonuclear derived extracellular vesicles are potential biomarkers of periprosthetic joint infection}, url = {https://m2.mtmt.hu/api/publication/32813061}, author = {Sallai, Imre and Marton, Nikolett and Szatmári, Attila and Kittel, Ágnes and Nagy, György and Buzás, Edit Irén and Khamari, Delaram and Komlósi, Zsolt and Kristóf, Katalin and Drahos, László and Turiák, Lilla and Sugár, Simon Nándor and Veres, Dániel and Kendoff, Daniel and Zahár, Ákos and Skaliczki, Gábor}, doi = {10.1371/journal.pone.0268076}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {17}, unique-id = {32813061}, issn = {1932-6203}, abstract = {Background Extracellular vesicles (EVs) are considered as crucial players in a wide variety of biological processes. Although their importance in joint diseases or infections has been shown by numerous studies, much less is known about their function in periprosthetic joint infection (PJI). Our aim was to investigate activated polymorphonuclear (PMN)-derived synovial EVs in patients with PJI. Questions/Purposes (1) Is there a difference in the number and size of extracellular vesicles between periprosthetic joint aspirates of patients with PJI and aseptic loosening? (2) Are these vesicles morphologically different in the two groups? (3) Are there activated PMN-derived EVs in septic samples evaluated by flow cytometry after CD177 labelling? (4) Is there a difference in the protein composition carried by septic and aseptic vesicles? Methods Thirty-four patients (n = 34) were enrolled into our investigation, 17 with PJI and 17 with aseptic prosthesis loosening. Periprosthetic joint fluid was aspirated and EVs were separated. Samples were analysed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) and flow cytometry (after Annexin V and CD177 labelling). The protein content of the EVs was studied by mass spectrometry (MS). Results NTA showed particle size distribution in both groups between 150 nm and 450 nm. The concentration of EVs was significantly higher in the septic samples (p = 0.0105) and showed a different size pattern as compared to the aseptic ones. The vesicular nature of the particles was confirmed by TEM and differential detergent lysis. In the septic group, FC analysis showed a significantly increased event number both after single and double labelling with fluorochrome conjugated Annexin V (p = 0.046) and Annexin V and anti-CD177 (p = 0.0105), respectively. MS detected a significant difference in the abundance of lactotransferrin (p = 0.00646), myeloperoxidase (p = 0.01061), lysozyme C (p = 0.04687), annexin A6 (p = 0.03921) and alpha-2-HS-glycoprotein (p = 0.03146) between the studied groups. Conclusions An increased number of activated PMN derived EVs were detected in the synovial fluid of PJI patients with a characteristic size distribution and a specific protein composition. The activated PMNs-derived extracellular vesicles can be potential biomarkers of PJI. Copyright: © 2022 Sallai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, year = {2022}, eissn = {1932-6203}, orcid-numbers = {Sallai, Imre/0000-0003-4123-1289; Marton, Nikolett/0000-0002-7351-6361; Nagy, György/0000-0003-1198-3228; Buzás, Edit Irén/0000-0002-3744-206X; Komlósi, Zsolt/0000-0002-4149-1497; Kristóf, Katalin/0000-0002-5189-4636; Drahos, László/0000-0001-9589-6652; Sugár, Simon Nándor/0000-0001-9728-5732; Veres, Dániel/0000-0002-9687-3556; Skaliczki, Gábor/0000-0002-8555-5114} } @article{MTMT:32667372, title = {Blood–brain barrier dysfunction in l-ornithine induced acute pancreatitis in rats and the direct effect of l-ornithine on cultured brain endothelial cells}, url = {https://m2.mtmt.hu/api/publication/32667372}, author = {Walter, Fruzsina and Harazin, András and Tóth, Andrea and Veszelka, Szilvia and Santa Maria, Anaraquel and Barna, Lilla and Kincses, András and Biczo, G and Balla, Zsolt and Kui, Balázs and Maléth, József and Cervenak, László and Tubak, Vilmos and Kittel, Ágnes and Rakonczay, Zoltán and Deli, Mária Anna}, doi = {10.1186/s12987-022-00308-0}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {19}, unique-id = {32667372}, issn = {2045-8118}, year = {2022}, eissn = {2045-8118}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Harazin, András/0000-0002-0904-5606; Santa Maria, Anaraquel/0000-0003-3505-5477; Maléth, József/0000-0001-5768-3090; Cervenak, László/0000-0003-0166-8697; Tubak, Vilmos/0000-0002-6141-3920; Rakonczay, Zoltán/0000-0002-1499-3416; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32611202, title = {Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice}, url = {https://m2.mtmt.hu/api/publication/32611202}, author = {Hegyesi, Hargita and Pállinger, Éva and Mecsei, Szabina and Hornyák, Balázs and Kovácsházi, Csenger and Brenner, Gábor and Giricz, Zoltán and Pálóczi, Krisztina and Kittel, Ágnes and Tóvári, József and Turiák, Lilla and Khamari, Delaram and Ferdinandy, Péter and Buzás, Edit Irén}, doi = {10.1007/s00018-021-04125-w}, journal-iso = {CELL MOL LIFE SCI}, journal = {CELLULAR AND MOLECULAR LIFE SCIENCES}, volume = {79}, unique-id = {32611202}, issn = {1420-682X}, year = {2022}, eissn = {1420-9071}, orcid-numbers = {Hegyesi, Hargita/0000-0002-8800-5169; Pállinger, Éva/0000-0002-5789-0951; Kovácsházi, Csenger/0000-0003-0283-9486; Brenner, Gábor/0000-0001-7886-2960; Giricz, Zoltán/0000-0003-2036-8665; Pálóczi, Krisztina/0000-0001-7065-3582; Kittel, Ágnes/0000-0002-6888-7731; Tóvári, József/0000-0002-5543-3204; Turiák, Lilla/0000-0002-2139-8156; Ferdinandy, Péter/0000-0002-6424-6806; Buzás, Edit Irén/0000-0002-3744-206X} } @article{MTMT:32289889, title = {Extracellular vesicle release and uptake by the liver under normo- and hyperlipidemia}, url = {https://m2.mtmt.hu/api/publication/32289889}, author = {Németh, Krisztina and Varga, Zoltán and Lenzinger, Dorina and Visnovitz, Tamás and Koncz, Anna and Hegedűs, Nikolett and Kittel, Ágnes and Máthé, Domokos and Szigeti, Krisztián and Lőrincz, Péter and O'Neill, Clodagh and Dwyer, Róisín and Liu, Zhonglin and Buzás, Edit Irén and Tamási, Viola}, doi = {10.1007/s00018-021-03969-6}, journal-iso = {CELL MOL LIFE SCI}, journal = {CELLULAR AND MOLECULAR LIFE SCIENCES}, volume = {78}, unique-id = {32289889}, issn = {1420-682X}, abstract = {Liver plays a central role in elimination of circulating extracellular vesicles (EVs), and it also significantly contributes to EV release. However, the involvement of the different liver cell populations remains unknown. Here, we investigated EV uptake and release both in normolipemia and hyperlipidemia. C57BL/6 mice were kept on high fat diet for 20-30 weeks before circulating EV profiles were determined. In addition, control mice were intravenously injected with 99mTc-HYNIC-Duramycin labeled EVs, and an hour later, biodistribution was analyzed by SPECT/CT. In vitro, isolated liver cell types were tested for EV release and uptake with/without prior fatty acid treatment. We detected an elevated circulating EV number after the high fat diet. To clarify the differential involvement of liver cell types, we carried out in vitro experiments. We found an increased release of EVs by primary hepatocytes at concentrations of fatty acids comparable to what is characteristic for hyperlipidemia. When investigating EV biodistribution with 99mTc-labeled EVs, we detected EV accumulation primarily in the liver upon intravenous injection of mice with medium (326.3 ± 19.8 nm) and small EVs (130.5 ± 5.8 nm). In vitro, we found that medium and small EVs were preferentially taken up by Kupffer cells, and liver sinusoidal endothelial cells, respectively. Finally, we demonstrated that in hyperlipidemia, there was a decreased EV uptake both by Kupffer cells and liver sinusoidal endothelial cells. Our data suggest that hyperlipidema increases the release and reduces the uptake of EVs by liver cells. We also provide evidence for a size-dependent differential EV uptake by the different cell types of the liver. The EV radiolabeling protocol using 99mTc-Duramycin may provide a fast and simple labeling approach for SPECT/CT imaging of EVs biodistribution.}, keywords = {Kupffer cell; hepatocyte; extracellular vesicle; Liver sinusoidal endothelial cells; Extracellular particles}, year = {2021}, eissn = {1420-9071}, pages = {7589-7604}, orcid-numbers = {Németh, Krisztina/0000-0002-3825-2137; Varga, Zoltán/0000-0002-5741-2669; Visnovitz, Tamás/0000-0002-7962-5083; Koncz, Anna/0000-0003-2511-2394; Hegedűs, Nikolett/0000-0003-1122-1872; Lőrincz, Péter/0000-0001-7374-667X; Buzás, Edit Irén/0000-0002-3744-206X; Tamási, Viola/0000-0001-7419-5603} } @article{MTMT:32282104, title = {Helium Conditioning Increases Cardiac Fibroblast Migration Which Effect Is Not Propagated via Soluble Factors or Extracellular Vesicles}, url = {https://m2.mtmt.hu/api/publication/32282104}, author = {Jelemenský, Marek and Kovácsházi, Csenger and Ferenczyová, Kristína and Hofbauerová, Monika and Kiss, Bernadett and Pállinger, Éva and Kittel, Ágnes and Sayour, Viktor Nabil and Görbe, Anikó and Pelyhe, Csilla and Hambalkó, Szabolcs and Kindernay, Lucia and Barančík, Miroslav and Ferdinandy, Péter and Barteková, Monika and Giricz, Zoltán}, doi = {10.3390/ijms221910504}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {32282104}, issn = {1661-6596}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Kovácsházi, Csenger/0000-0003-0283-9486; Hofbauerová, Monika/0000-0003-3309-128X; Kiss, Bernadett/0000-0001-7631-4418; Pállinger, Éva/0000-0002-5789-0951; Görbe, Anikó/0000-0003-4908-1094; Pelyhe, Csilla/0000-0001-6267-4527; Ferdinandy, Péter/0000-0002-6424-6806; Barteková, Monika/0000-0002-5210-5184; Giricz, Zoltán/0000-0003-2036-8665} } @article{MTMT:32189675, title = {Formation of a protein corona on the surface of extracellular vesicles in blood plasma}, url = {https://m2.mtmt.hu/api/publication/32189675}, author = {Tóth, Eszter Ágnes and Turiák, Lilla and Visnovitz, Tamás and Cserép, Csaba and Türk-Mázló, Anett and Sódar, Barbara and Försönits, András and Petővári, Gábor and Sebestyén, Anna and Komlósi, Zsolt and Drahos, László and Kittel, Ágnes and Nagy, György and Bácsi, Attila and Dénes, Ádám and Song Gho, Yong and Szabó-Taylor, Katalin and Buzás, Edit Irén}, doi = {10.1002/jev2.12140}, journal-iso = {J EXTRACELLULAR VESICL}, journal = {JOURNAL OF EXTRACELLULAR VESICLES}, volume = {10}, unique-id = {32189675}, year = {2021}, eissn = {2001-3078}, orcid-numbers = {Visnovitz, Tamás/0000-0002-7962-5083; Cserép, Csaba/0000-0001-5513-2471; Sódar, Barbara/0000-0002-8803-7304; Försönits, András/0000-0002-9298-8890; Petővári, Gábor/0000-0002-1957-2864; Sebestyén, Anna/0000-0001-8814-4794; Komlósi, Zsolt/0000-0002-4149-1497; Drahos, László/0000-0001-9589-6652; Nagy, György/0000-0003-1198-3228; Szabó-Taylor, Katalin/0000-0002-4763-3521; Buzás, Edit Irén/0000-0002-3744-206X} }