TY - JOUR AU - Szalai, Boglárka AU - Budai-Szűcs, Mária AU - Kovács, Anita AU - Berkó, Szilvia AU - Gróf, Ilona AU - Deli, Mária Anna AU - Katona, Gábor AU - Balogh, György Tibor AU - Jójártné Laczkovich, Orsolya TI - The effect of mucoadhesive polymers on ocular permeation of thermoresponsive in situ gel containing dexamethasone–cyclodextrin complex JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 667 PY - 2024 IS - A PG - 13 SN - 0378-5173 DO - 10.1016/j.ijpharm.2024.124848 UR - https://m2.mtmt.hu/api/publication/35491593 ID - 35491593 N1 - Funding Agency and Grant Number: Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund [TKP2021-EGA-32]; [TKP2021-EGA] Funding text: Acknowledgement Project no TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. The publication was supported by Part number: A LA - English DB - MTMT ER - TY - JOUR AU - Du, Wenjia AU - Chen, Huanhuan AU - Gróf, Ilona AU - Lemaitre, Lucien AU - Bocsik, Alexandra AU - Perdyan, Adrian AU - Mieczkowski, Jakub AU - Deli, Mária Anna AU - Hortobágyi, Tibor AU - Wan, Qi AU - Glebov, Oleg O. TI - Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability JF - MOLECULAR PSYCHIATRY J2 - MOL PSYCHIATR VL - 29 PY - 2024 SP - 3590 EP - 3598 PG - 9 SN - 1359-4184 DO - 10.1038/s41380-024-02626-1 UR - https://m2.mtmt.hu/api/publication/34950078 ID - 34950078 N1 - Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Shandong, Qingdao, 266071, China Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, 80-210, Poland Centre for Healthy Brain Ageing, Department of Psychological Medicine, Institute of Psychiatry, Psychology & amp; Neuroscience, King’s College London, De Crespigny Park, London, SE5 8AF, United Kingdom Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Export Date: 19 June 2024 CODEN: MOPSF Correspondence Address: Glebov, O.O.; Centre for Healthy Brain Ageing, De Crespigny Park, United Kingdom; email: oleg.glebov@kcl.ac.uk Funding details: 2017-1.2.1-NKP-2017-00002 Funding details: 1G3DBLJ0TUDF 247 Funding details: National Natural Science Foundation of China, NSFC, 32070772 Funding details: National Natural Science Foundation of China, NSFC Funding details: OOG2019/2020 Funding details: Magyar Tudományos Akadémia, MTA, NAP2022-I-6/2022 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: This work was funded by the Lewy Body Society (OOG2019/2020), the National Natural Science Foundation of China (32070772), Hungarian Academy of Sciences (NAP2022-I-6/2022) Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002), and University of Debrecen Research Support Fund (1G3DBLJ0TUDF 247). LA - English DB - MTMT ER - TY - JOUR AU - Porkoláb, Gergő AU - Mészáros, Mária AU - Szecskó, Anikó AU - Vigh, Judit Piroska AU - Walter, Fruzsina AU - Figueiredo, Ricardo AU - Kálomista, Ildikó AU - Hoyk, Zsófia AU - Vizsnyiczai, Gaszton AU - Gróf, Ilona AU - Jan, Jeng-Shiung AU - Gosselet, Fabien AU - Pirity, Melinda AU - Vastag, Monika AU - Hudson, Natalie AU - Campbell, Matthew AU - Veszelka, Szilvia AU - Deli, Mária Anna TI - Synergistic induction of blood–brain barrier properties JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 121 PY - 2024 IS - 21 SN - 0027-8424 DO - 10.1073/pnas.2316006121 UR - https://m2.mtmt.hu/api/publication/34856989 ID - 34856989 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Vágvölgyi, Máté AU - Laczkó, Dávid AU - Santa Maria, Anaraquel AU - Vigh, Judit Piroska AU - Walter, Fruzsina AU - Berkecz, Róbert AU - Deli, Mária Anna AU - Tóth, Gábor AU - Hunyadi, Attila TI - 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 JF - PLOS ONE J2 - PLOS ONE VL - 19 PY - 2024 IS - 2 PG - 15 SN - 1932-6203 DO - 10.1371/journal.pone.0290526 UR - https://m2.mtmt.hu/api/publication/34691003 ID - 34691003 N1 - Institute of Pharmacognosy, University of Szeged, Szeged, Hungary Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States Doctoral School of Biology, University of Szeged, Szeged, Hungary Institute of Pharmaceutical Analysis, University of Szeged, Szeged, Hungary NMR Group, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary HUN-REN-SZTE Biologically Active Natural Products Research Group, Szeged, Hungary Export Date: 18 March 2024 CODEN: POLNC Correspondence Address: Hunyadi, A.; Institute of Pharmacognosy, Hungary; email: hunyadi.attila@szte.hu AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Deli, Mária Anna AU - Porkoláb, Gergő AU - Kincses, András AU - Mészáros, Mária AU - Szecskó, Anikó AU - Kocsis, Anna AU - Vigh, Judit Piroska AU - Valkai, Sándor AU - Veszelka, Szilvia AU - Walter, Fruzsina AU - Dér, András TI - Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives JF - LAB ON A CHIP J2 - LAB CHIP VL - 24 PY - 2024 IS - 5 SP - 1030 EP - 1063 PG - 34 SN - 1473-0197 DO - 10.1039/d3lc00996c UR - https://m2.mtmt.hu/api/publication/34673907 ID - 34673907 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Hungary [K-143766, K-124922, FK-143233, PD-138930, PD-143268]; Hungarian Research Network [SA-111/2021]; Centenarian Foundation; Talentum Foundation of Gedeon Richter Plc. [UNKP-23-3-SZTE-517, UNKP-23-3-SZTE-535]; National Academy of Scientist Education Program of the National Biomedical Foundation under Hungarian Ministry of Culture and Innovation; New National Excellence Program of the Hungarian Ministry of Culture and Innovation; [H-1103]; [19-21]; [UNKP-23-3-SZTE-497] Funding text: The following funding was received from the National Research, Development and Innovation Office, Hungary: grants K-143766 (to M. A. D.), K-124922 (to A. D.), FK-143233 (to S. V.), PD-138930 (to M. M.), PD-143268 (to A. K.). F. R. W. was supported by the grant SA-111/2021 from the Hungarian Research Network. M. M. was supported by the Centenarian Foundation, A. S. and J. P. V. by the Talentum Foundation of Gedeon Richter Plc. (H-1103 Budapest, Gyoemr & odblac;i str. 19-21. Hungary). G. P. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation. The New National Excellence Program of the Hungarian Ministry of Culture and Innovation supported G. P. (UNKP-23-3-SZTE-497), A. S. (UNKP-23-3-SZTE-517), and J. P. V. (UNKP-23-3-SZTE-535). LA - English DB - MTMT ER - TY - JOUR AU - Rust, Ruslan AU - Holm, Mea M. AU - Egger, Matteo AU - Weinmann, Oliver AU - van, Rossum Danielle AU - Walter, Fruzsina AU - Santa Maria, Anaraquel AU - Gronnert, Lisa AU - Maurer, Michael A. AU - Kraler, Simon AU - Akhmedov, Alexander AU - Cideciyan, Rose AU - Luscher, Thomas F. AU - Deli, Mária Anna AU - Herrmann, Inge K. AU - Schwab, Martin E. TI - Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability JF - JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM J2 - J CEREBR BLOOD F MET VL - 44 PY - 2024 IS - 6 SP - 938 EP - 954 PG - 17 SN - 0271-678X DO - 10.1177/0271678X231216270 UR - https://m2.mtmt.hu/api/publication/34473973 ID - 34473973 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kajner, Gyula AU - Bélteki, Ádám AU - Cseh, Martin AU - Geretovszky, Zsolt AU - Ajtai, Tibor AU - Barna, Lilla AU - Deli, Mária Anna AU - Pap, Bernadett AU - Maróti, Gergely AU - Galbács, Gábor TI - Design, Optimization, and Application of a 3D-Printed Polymer Sample Introduction System for the ICP-MS Analysis of Nanoparticles and Cells JF - NANOMATERIALS J2 - NANOMATERIALS-BASEL VL - 13 PY - 2023 IS - 23 PG - 16 SN - 2079-4991 DO - 10.3390/nano13233018 UR - https://m2.mtmt.hu/api/publication/34401353 ID - 34401353 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Kincses, András AU - Vigh, Judit Piroska AU - Petrovszki, Dániel AU - Valkai, Sándor AU - Kocsis, Anna AU - Walter, Fruzsina AU - Lin, Hung-Yin AU - Jan, Jeng-Shiung AU - Deli, Mária Anna AU - Dér, András TI - The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions JF - BIOSENSORS J2 - BIOSENSORS-BASEL VL - 13 PY - 2023 IS - 3 PG - 17 SN - 2079-6374 DO - 10.3390/bios13030357 UR - https://m2.mtmt.hu/api/publication/33688148 ID - 33688148 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Hungary [NNE-129617, K-124922, PD-143268, SA-111/2021]; National Science Technology Council, Taiwan [NSTC107-2923-M-006-002-MY3] Funding text: The following funding was received from the National Research, Development and Innovation Office, Hungary: grants NNE-129617 (to M.A.D.), K-124922 (to A.D.), PD-143268 (to A.K.). F.R.W. was supported by the grant SA-111/2021 from Lorand Eotvos Research Network, Hungary. J.S.J. was supported by the National Science Technology Council, Taiwan: NSTC107-2923-M-006-002-MY3. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Barabási, Beáta AU - Barna, Lilla AU - Santa Maria, Anaraquel AU - Harazin, András AU - Molnár, Réka AU - Kincses, András AU - Vigh, Judit Piroska AU - Dukay, Brigitta AU - Sántha, Miklós AU - Tóth, Erzsébet Melinda AU - Walter, Fruzsina AU - Deli, Mária Anna AU - Hoyk, Zsófia TI - Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood–brain barrier in hypertriglyceridemia JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 20 PY - 2023 IS - 1 PG - 20 SN - 2045-8118 DO - 10.1186/s12987-023-00418-3 UR - https://m2.mtmt.hu/api/publication/33688118 ID - 33688118 N1 - Funding Agency and Grant Number: ELKH Biological Research Center - National Research, Development, and Innovation Office of Hungary [GINOP-2.3.2-15-2016-00060]; European Training Network [H2020-MSCA-ITN-2015, 675619] Funding text: Open access funding provided by ELKH Biological Research Center. This work was funded by the National Research, Development, and Innovation Office of Hungary, Grant Number GINOP-2.3.2-15-2016-00060. ARSM was supported by the European Training Network H2020-MSCA-ITN-2015 [Grant Number 675619]. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Gábor AU - Santa Maria, Anaraquel AU - Herke, Ibolya AU - Gáti, Tamás AU - Galvis-Montes, Daniel AU - Walter, Fruzsina AU - Deli, Mária Anna AU - Hunyadi, Attila TI - Highly Oxidized Ecdysteroids from a Commercial Cyanotis arachnoidea Root Extract as Potent Blood-Brain Barrier Protective Agents JF - JOURNAL OF NATURAL PRODUCTS J2 - J NAT PROD VL - 86 PY - 2023 IS - 4 SP - 1074 EP - 1080 PG - 7 SN - 0163-3864 DO - 10.1021/acs.jnatprod.2c00948 UR - https://m2.mtmt.hu/api/publication/33641697 ID - 33641697 N1 - Department of Inorganic and Analytical Chemistry, NMR Group, Budapest University of Technology and Economics, Budapest, H-1111, Hungary Institute of Biophysics, Biological Research Centre, Szeged, H-6726, Hungary Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, United States Servier Research Institute of Medicinal Chemistry (SRIMC), Budapest, H-1031, Hungary CODEN: JNPRD Correspondence Address: Deli, M.A.; Institute of Biophysics, Hungary; email: deli.maria@brc.hu LA - English DB - MTMT ER -