@article{MTMT:35491593, title = {The effect of mucoadhesive polymers on ocular permeation of thermoresponsive in situ gel containing dexamethasone–cyclodextrin complex}, url = {https://m2.mtmt.hu/api/publication/35491593}, author = {Szalai, Boglárka and Budai-Szűcs, Mária and Kovács, Anita and Berkó, Szilvia and Gróf, Ilona and Deli, Mária Anna and Katona, Gábor and Balogh, György Tibor and Jójártné Laczkovich, Orsolya}, doi = {10.1016/j.ijpharm.2024.124848}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {667}, unique-id = {35491593}, issn = {0378-5173}, year = {2024}, eissn = {1873-3476}, orcid-numbers = {Budai-Szűcs, Mária/0000-0001-5187-5702; Kovács, Anita/0000-0001-5593-1329; Berkó, Szilvia/0000-0002-3842-8876; Deli, Mária Anna/0000-0001-6084-6524; Katona, Gábor/0000-0003-1564-4813; Balogh, György Tibor/0000-0003-3347-1880} } @article{MTMT:34950078, title = {Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability}, url = {https://m2.mtmt.hu/api/publication/34950078}, author = {Du, Wenjia and Chen, Huanhuan and Gróf, Ilona and Lemaitre, Lucien and Bocsik, Alexandra and Perdyan, Adrian and Mieczkowski, Jakub and Deli, Mária Anna and Hortobágyi, Tibor and Wan, Qi and Glebov, Oleg O.}, doi = {10.1038/s41380-024-02626-1}, journal-iso = {MOL PSYCHIATR}, journal = {MOLECULAR PSYCHIATRY}, unique-id = {34950078}, issn = {1359-4184}, year = {2024}, eissn = {1476-5578}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524; Hortobágyi, Tibor/0000-0001-5732-7942} } @article{MTMT:34856989, title = {Synergistic induction of blood–brain barrier properties}, url = {https://m2.mtmt.hu/api/publication/34856989}, author = {Porkoláb, Gergő and Mészáros, Mária and Szecskó, Anikó and Vigh, Judit Piroska and Walter, Fruzsina and Figueiredo, Ricardo and Kálomista, Ildikó and Hoyk, Zsófia and Vizsnyiczai, Gaszton and Gróf, Ilona and Jan, Jeng-Shiung and Gosselet, Fabien and Pirity, Melinda and Vastag, Monika and Hudson, Natalie and Campbell, Matthew and Veszelka, Szilvia and Deli, Mária Anna}, doi = {10.1073/pnas.2316006121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {34856989}, issn = {0027-8424}, abstract = {Blood–brain barrier (BBB) models derived from human stem cells are powerful tools to improve our understanding of cerebrovascular diseases and to facilitate drug development for the human brain. Yet providing stem cell–derived endothelial cells with the right signaling cues to acquire BBB characteristics while also retaining their vascular identity remains challenging. Here, we show that the simultaneous activation of cyclic AMP and Wnt/β-catenin signaling and inhibition of the TGF-β pathway in endothelial cells robustly induce BBB properties in vitro. To target this interaction, we present a small-molecule cocktail named cARLA, which synergistically enhances barrier tightness in a range of BBB models across species. Mechanistically, we reveal that the three pathways converge on Wnt/β-catenin signaling to mediate the effect of cARLA via the tight junction protein claudin-5. We demonstrate that cARLA shifts the gene expressional profile of human stem cell–derived endothelial cells toward the in vivo brain endothelial signature, with a higher glycocalyx density and efflux pump activity, lower rates of endocytosis, and a characteristic endothelial response to proinflammatory cytokines. Finally, we illustrate how cARLA can improve the predictive value of human BBB models regarding the brain penetration of drugs and targeted nanoparticles. Due to its synergistic effect, high reproducibility, and ease of use, cARLA has the potential to advance drug development for the human brain by improving BBB models across laboratories.}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Figueiredo, Ricardo/0000-0003-3024-1254; Vizsnyiczai, Gaszton/0000-0003-3245-3736; Jan, Jeng-Shiung/0000-0002-8379-404X; Gosselet, Fabien/0000-0002-0481-5026; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:34691003, title = {17-Oxime ethers of oxidized ecdysteroid derivatives modulate oxidative stress in human brain endothelial cells and dose-dependently might protect or damage the blood-brain barrier}, url = {https://m2.mtmt.hu/api/publication/34691003}, author = {Vágvölgyi, Máté and Laczkó, Dávid and Santa Maria, Anaraquel and Vigh, Judit Piroska and Walter, Fruzsina and Berkecz, Róbert and Deli, Mária Anna and Tóth, Gábor and Hunyadi, Attila}, doi = {10.1371/journal.pone.0290526}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {19}, unique-id = {34691003}, issn = {1932-6203}, abstract = {20-Hydroxyecdysone and several of its oxidized derivatives exert cytoprotective effect in mammals including humans. Inspired by this bioactivity of ecdysteroids, in the current study it was our aim to prepare a set of sidechain-modified derivatives and to evaluate their potential to protect the blood-brain barrier (BBB) from oxidative stress. Six novel ecdysteroids, including an oxime and five oxime ethers, were obtained through regioselective synthesis from a sidechain-cleaved calonysterone derivative 2 and fully characterized by comprehensive NMR techniques revealing their complete 1 H and 13 C signal assignments. Surprisingly, several compounds sensitized hCMEC/D3 brain microvascular endothelial cells to tert -butyl hydroperoxide (tBHP)-induced oxidative damage as recorded by impedance measurements. Compound 8 , containing a benzyloxime ether moiety in its sidechain, was the only one that exerted a protective effect at a higher, 10 μM concentration, while at lower (10 nM– 1 μM) concentrations it promoted tBHP-induced cellular damage. Brain endothelial cells were protected from tBHP-induced barrier integrity decrease by treatment with 10 μM of compound 8 , which also mitigated the intracellular reactive oxygen species production elevated by tBHP. Based on our results, 17-oxime ethers of oxidized ecdysteroids modulate oxidative stress of the BBB in a way that may point towards unexpected toxicity. Further studies are needed to evaluate any possible risk connected to dietary ecdysteroid consumption and CNS pathologies in which BBB damage plays an important role.}, year = {2024}, eissn = {1932-6203}, orcid-numbers = {Vágvölgyi, Máté/0000-0002-2233-9422; Santa Maria, Anaraquel/0000-0003-3505-5477; Walter, Fruzsina/0000-0001-8145-2823; Berkecz, Róbert/0000-0002-9076-2177; Deli, Mária Anna/0000-0001-6084-6524; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:34673907, title = {Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives}, url = {https://m2.mtmt.hu/api/publication/34673907}, author = {Deli, Mária Anna and Porkoláb, Gergő and Kincses, András and Mészáros, Mária and Szecskó, Anikó and Kocsis, Anna and Vigh, Judit Piroska and Valkai, Sándor and Veszelka, Szilvia and Walter, Fruzsina and Dér, András}, doi = {10.1039/d3lc00996c}, journal-iso = {LAB CHIP}, journal = {LAB ON A CHIP}, volume = {24}, unique-id = {34673907}, issn = {1473-0197}, year = {2024}, eissn = {1473-0189}, pages = {1030-1063}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524; Valkai, Sándor/0000-0001-8479-8141; Walter, Fruzsina/0000-0001-8145-2823} } @article{MTMT:34473973, title = {Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability}, url = {https://m2.mtmt.hu/api/publication/34473973}, author = {Rust, Ruslan and Holm, Mea M. and Egger, Matteo and Weinmann, Oliver and van, Rossum Danielle and Walter, Fruzsina and Santa Maria, Anaraquel and Gronnert, Lisa and Maurer, Michael A. and Kraler, Simon and Akhmedov, Alexander and Cideciyan, Rose and Luscher, Thomas F. and Deli, Mária Anna and Herrmann, Inge K. and Schwab, Martin E.}, doi = {10.1177/0271678X231216270}, journal-iso = {J CEREBR BLOOD F MET}, journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM}, volume = {44}, unique-id = {34473973}, issn = {0271-678X}, abstract = {Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability.}, keywords = {INHIBITION; NEURITE OUTGROWTH; PROTEINS; SYNAPTIC PLASTICITY; Hematology; Blood-Brain Barrier; stroke; Exosomes; Exosomes; nanoparticle tracking analysis; Endocrinology & Metabolism; axonal regeneration; BRAIN-BARRIER; Nogo-A; Corticospinal tract; S1PR2}, year = {2024}, eissn = {1559-7016}, pages = {938-954}, orcid-numbers = {Rust, Ruslan/0000-0003-3376-3453; Walter, Fruzsina/0000-0001-8145-2823; Santa Maria, Anaraquel/0000-0003-3505-5477; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:34401353, title = {Design, Optimization, and Application of a 3D-Printed Polymer Sample Introduction System for the ICP-MS Analysis of Nanoparticles and Cells}, url = {https://m2.mtmt.hu/api/publication/34401353}, author = {Kajner, Gyula and Bélteki, Ádám and Cseh, Martin and Geretovszky, Zsolt and Ajtai, Tibor and Barna, Lilla and Deli, Mária Anna and Pap, Bernadett and Maróti, Gergely and Galbács, Gábor}, doi = {10.3390/nano13233018}, journal-iso = {NANOMATERIALS-BASEL}, journal = {NANOMATERIALS}, volume = {13}, unique-id = {34401353}, abstract = {Commonly used sample introduction systems for inductively coupled plasma mass spectrometry (ICP-MS) are generally not well-suited for single particle ICP-MS (spICP-MS) applications due to their high sample requirements and low efficiency. In this study, the first completely 3D-printed, polymer SIS was developed to facilitate spICP-MS analysis. The system is based on a microconcentric pneumatic nebulizer and a single-pass spray chamber with an additional sheath gas flow to further facilitate the transport of larger droplets or particles. The geometry of the system was optimized using numerical simulations. Its aerosol characteristics and operational conditions were studied via optical particle counting and a course of spICP-MS measurements, involving nanodispersions and cell suspensions. In a comparison of the performance of the new and the standard (quartz microconcentric nebulizer plus a double-pass spray chamber) systems, it was found that the new sample introduction system has four times higher particle detection efficiency, significantly better signal-to-noise ratio, provides ca. 20% lower size detection limit, and allows an extension of the upper limit of transportable particle diameters to about 25 µm.}, year = {2023}, eissn = {2079-4991}, orcid-numbers = {Cseh, Martin/0000-0002-5303-0188; Geretovszky, Zsolt/0000-0002-7878-9174; Deli, Mária Anna/0000-0001-6084-6524; Maróti, Gergely/0000-0002-3705-0461; Galbács, Gábor/0000-0002-1799-5329} } @article{MTMT:33688148, title = {The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions}, url = {https://m2.mtmt.hu/api/publication/33688148}, author = {Kincses, András and Vigh, Judit Piroska and Petrovszki, Dániel and Valkai, Sándor and Kocsis, Anna and Walter, Fruzsina and Lin, Hung-Yin and Jan, Jeng-Shiung and Deli, Mária Anna and Dér, András}, doi = {10.3390/bios13030357}, journal-iso = {BIOSENSORS-BASEL}, journal = {BIOSENSORS}, volume = {13}, unique-id = {33688148}, abstract = {The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach. The BBB represents the tightest endothelial barrier within the vasculature with high electric resistance and low passive permeability, providing a controlled interface between the circulation and the brain. The multi-cell type dynamic BBB-on-chip models are in demand in several fields as alternatives to expensive animal studies or static culture inserts methods. Their combination with integrated biosensors provides real-time and noninvasive monitoring of the integrity of the BBB and of the presence and concentration of agents contributing to the physiological and metabolic functions and pathologies. In this review, we describe built-in sensors to characterize BBB models via quasi-direct current and electrical impedance measurements, as well as the different types of biosensors for the detection of metabolites, drugs, or toxic agents. We also give an outlook on the future of the field, with potential combinations of existing methods and possible improvements of current techniques.}, year = {2023}, eissn = {2079-6374}, orcid-numbers = {Valkai, Sándor/0000-0001-8479-8141; Walter, Fruzsina/0000-0001-8145-2823; Jan, Jeng-Shiung/0000-0002-8379-404X; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33688118, title = {Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood–brain barrier in hypertriglyceridemia}, url = {https://m2.mtmt.hu/api/publication/33688118}, author = {Barabási, Beáta and Barna, Lilla and Santa Maria, Anaraquel and Harazin, András and Molnár, Réka and Kincses, András and Vigh, Judit Piroska and Dukay, Brigitta and Sántha, Miklós and Tóth, Erzsébet Melinda and Walter, Fruzsina and Deli, Mária Anna and Hoyk, Zsófia}, doi = {10.1186/s12987-023-00418-3}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {20}, unique-id = {33688118}, issn = {2045-8118}, year = {2023}, eissn = {2045-8118}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Harazin, András/0000-0002-0904-5606; Molnár, Réka/0000-0002-3128-825X; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33641697, title = {Highly Oxidized Ecdysteroids from a Commercial Cyanotis arachnoidea Root Extract as Potent Blood-Brain Barrier Protective Agents}, url = {https://m2.mtmt.hu/api/publication/33641697}, author = {Tóth, Gábor and Santa Maria, Anaraquel and Herke, Ibolya and Gáti, Tamás and Galvis-Montes, Daniel and Walter, Fruzsina and Deli, Mária Anna and Hunyadi, Attila}, doi = {10.1021/acs.jnatprod.2c00948}, journal-iso = {J NAT PROD}, journal = {JOURNAL OF NATURAL PRODUCTS}, volume = {86}, unique-id = {33641697}, issn = {0163-3864}, year = {2023}, eissn = {1520-6025}, pages = {1074-1080}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524; Hunyadi, Attila/0000-0003-0074-3472} }