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 PY - 2024 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 - 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 - TY - JOUR AU - Mészáros, Mária AU - Phan, Thi Ha My AU - Vigh, Judit Piroska AU - Porkoláb, Gergő AU - Kocsis, Anna AU - Páli, Emese K. AU - Polgár, Tamás Ferenc AU - Walter, Fruzsina AU - Bolognin, Silvia AU - Schwamborn, Jens C. AU - Jan, Jeng-Shiung AU - Deli, Mária Anna AU - Veszelka, Szilvia TI - Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 3 PG - 20 SN - 2073-4409 DO - 10.3390/cells12030503 UR - https://m2.mtmt.hu/api/publication/33621088 ID - 33621088 AB - Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood–brain barrier (BBB). We have previously discovered that the combination of two different ligands of BBB nutrient transporters, alanine and glutathione, increases the permeability of vesicular NPs across the BBB. Our aim here was to investigate whether the combination of these molecules can also promote the efficient transfer of 3-armed poly(l-glutamic acid) NPs across a human endothelial cell and brain pericyte BBB co-culture model. Alanine and glutathione dual-targeted polypeptide NPs showed good cytocompatibility and elevated cellular uptake in a time-dependent and active manner. Targeted NPs had a higher permeability across the BBB model and could subsequently enter midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. These results indicate that poly(l-glutamic acid) NPs can be used as nanocarriers for nervous system application and that the right combination of molecules that target cerebral endothelial cells, in this case alanine and glutathione, can facilitate drug delivery to the brain. LA - English DB - MTMT ER - TY - JOUR AU - Sato, Kei AU - Nakagawa, Shinsuke AU - Morofuji, Yoichi AU - Matsunaga, Yuki AU - Fujimoto, Takashi AU - Watanabe, Daisuke AU - Izumo, Tsuyoshi AU - Niwa, Masami AU - Walter, Fruzsina AU - Vigh, Judit Piroska AU - Santa Maria, Anaraquel AU - Deli, Mária Anna AU - Matsuo, Takayuki TI - Effects of fasudil on blood-brain barrier integrity JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 19 PY - 2022 IS - 1 PG - 12 SN - 2045-8118 DO - 10.1186/s12987-022-00336-w UR - https://m2.mtmt.hu/api/publication/32917592 ID - 32917592 N1 - Funding Agency and Grant Number: JSPS; Hungarian Academy of Sciences; Fukuoka University [211032]; [20KK0254]; [20K09351]; [JPJSBP120203804]; [NKM2019-11] Funding text: This study was funded by JSPS and the Hungarian Academy of Sciences under the Japan-Hungary Research Cooperative Program (to Yoichi Morofuji and M.A.D.), Grants-in-Aid for Scientific Research (Fostering Joint International Research) 20KK0254 (to Yoichi Morofuji), Grants-in-Aid for Scientific Research (C) 20K09351 (to Yoichi Morofuji), and Fukuoka University (Grant No. 211032) (to S.N.), JPJSBP120203804 (to Yoichi Morofuji), NKM2019-11 (to Maria A Deli). AB - Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Methods BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3-30 mu M of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke. LA - English DB - MTMT ER - TY - JOUR AU - Walter, Fruzsina AU - Harazin, András AU - Tóth, Andrea AU - Veszelka, Szilvia AU - Santa Maria, Anaraquel AU - Barna, Lilla AU - Kincses, András AU - Biczo, G AU - Balla, Zsolt AU - Kui, Balázs AU - Maléth, József AU - Cervenak, László AU - Tubak, Vilmos AU - Kittel, Ágnes AU - Rakonczay, Zoltán AU - Deli, Mária Anna TI - Blood–brain barrier dysfunction in l-ornithine induced acute pancreatitis in rats and the direct effect of l-ornithine on cultured brain endothelial cells JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 19 PY - 2022 IS - 1 PG - 20 SN - 2045-8118 DO - 10.1186/s12987-022-00308-0 UR - https://m2.mtmt.hu/api/publication/32667372 ID - 32667372 N1 - Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary Department of Medicine, University of Szeged, Kálvária sgt 57, Szeged, 6725, Hungary Department of Pathophysiology, University of Szeged, Semmelweis u. 1, Szeged, 6701, Hungary HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Dóm sqr. 10, Szeged, 6720, Hungary HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Dóm sqr. 10, Szeged, 6720, Hungary Department of Internal Medicine and Hematology, Research Laboratory, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary Creative Laboratory Ltd, Temesvári krt. 62, Szeged, 6726, Hungary Institute of Experimental Medicine, Eötvös Loránd Research Network, Szigony u. 43, Budapest, 1083, Hungary Wyss Institute for Biologically Inspired Engineering at Harvard University, 3 Blackfan Circle, Boston, MA 02115, United States Department of Biomedicine, Faculty of Health, Aarhus University, Høegh-Guldbergs Gade 10, Aarhus C, 8000, Denmark Institute of Applied Sciences, Department of Environmental Biology and Education, Juhász Gyula Faculty of Education, University of Szeged, Boldogasszony sgt. 6, Szeged, 6725, Hungary Cited By :1 Export Date: 23 November 2022 Correspondence Address: Deli, M.A.; Institute of Biophysics, Temesvári krt. 62, Hungary; email: deli.maria@brc.hu LA - English DB - MTMT ER - TY - JOUR AU - Petrovszki, Dániel AU - Walter, Fruzsina AU - Vigh, Judit Piroska AU - Kocsis, Anna AU - Valkai, Sándor AU - Deli, Mária Anna AU - Dér, András TI - Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 1 SN - 2227-9059 DO - 10.3390/biomedicines10010188 UR - https://m2.mtmt.hu/api/publication/32602220 ID - 32602220 LA - English DB - MTMT ER -