TY - JOUR AU - Búzás, András AU - Makai, András AU - Groma, Géza AU - Dancsházy, Zsolt AU - Szendi, István AU - Kish, Laszlo B. AU - Santa Maria, Anaraquel AU - Dér, András TI - Hierarchical organization of human physical activity JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-024-56185-0 UR - https://m2.mtmt.hu/api/publication/34737118 ID - 34737118 N1 - Institute of Biophysics, HUN-REN Biological Research Centre, Temesvári Krt. 62, Szeged, 6701, Hungary Department of Psychiatry, Kiskunhalas Semmelweis Hospital, 1 Dr. Monszpart László Street, Kiskunhalas, 6400, Hungary Department of Electrical and Computer Engineering, Texas A & amp;M University, TAMUS 3128, College Station, TX 77843-3128, United States Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States Export Date: 19 April 2024 Correspondence Address: Santa-Maria, A.R.; Institute of Biophysics, Temesvári Krt. 62, Hungary; email: anaraquel.santamaria@wyss.harvard.edu Correspondence Address: Dér, A.; Institute of Biophysics, Temesvári Krt. 62, Hungary; email: der.andras@brc.hu AB - Human physical activity (HPA), a fundamental physiological signal characteristic of bodily motion is of rapidly growing interest in multidisciplinary research. Here we report the existence of hitherto unidentified hierarchical levels in the temporal organization of HPA on the ultradian scale: on the minute's scale, passive periods are followed by activity bursts of similar intensity (‘quanta’) that are organized into superstructures on the hours- and on the daily scale. The time course of HPA can be considered a stochastic, quasi-binary process, where quanta, assigned to task-oriented actions are organized into work packages on higher levels of hierarchy. In order to grasp the essence of this complex dynamic behaviour, we established a stochastic mathematical model which could reproduce the main statistical features of real activity time series. The results are expected to provide important data for developing novel behavioural models and advancing the diagnostics of neurological or psychiatric diseases. 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 - 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 - 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 - 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 - Santa Maria, Anaraquel AU - Heymans, Marjolein AU - Walter, Fruzsina AU - Culot, Maxime AU - Gosselet, Fabien AU - Deli, Mária Anna AU - Neuhaus, Winfried TI - Transport Studies Using Blood-Brain Barrier In Vitro Models. A Critical Review and Guidelines TS - A Critical Review and Guidelines JF - HANDBOOK OF EXPERIMENTAL PHARMACOLOGY J2 - HANDB EXP PHARMACOL VL - 273 PY - 2022 SP - 187 EP - 204 PG - 18 SN - 0171-2004 DO - 10.1007/164_2020_394 UR - https://m2.mtmt.hu/api/publication/31642822 ID - 31642822 AB - Permeation is one of the most evaluated parameters using preclinical in vitro blood-brain barrier models, as it has long been considered to be one of the major factors influencing central nervous system drug delivery. Blood-brain barrier permeability can be defined as the speed at which a compound crosses the brain endothelial cell barrier and is employed to assess barrier tightness, which is a crucial feature of brain capillaries in vivo. In addition, it is used to assess brain drug penetration. We review traditionally used methods to assess blood-brain barrier permeability in vitro and summarize often neglected in vivo (e.g., plasma protein and brain tissue binding) or in vitro (e.g., culture insert materials or methodology) factors that influence this property. These factors are crucial to consider when performing BBB permeability assessments, and especially when comparing permeability data obtained from different models, since model diversification significantly complicates inter-study comparisons. Finally, measuring transendothelial electrical resistance can be used to describe blood-brain barrier tightness; however, several parameters should be considered while comparing these measurements to the blood-brain barrier permeability to paracellular markers. LA - English DB - MTMT ER - TY - THES AU - Santa Maria, Anaraquel TI - The role of brain endothelial surface charge and glycocalyx in the function and integrity of the blood-brain barrier [Az agyi endotélsejtek sejtfelszíni töltésének és glikokalix rétegének szerepe a vér-agy gát integritásában és működésében] PB - Szegedi Tudományegyetem (SZTE) PY - 2021 SP - 79 DO - 10.14232/phd.10751 UR - https://m2.mtmt.hu/api/publication/32473952 ID - 32473952 LA - English DB - MTMT ER - TY - JOUR AU - Matsunaga, Yuki AU - Nakagawa, Shinsuke AU - Morofuji, Yoichi AU - Dohgu, Shinya AU - Watanabe, Daisuke AU - Horie, Nobutaka AU - Izumo, Tsuyoshi AU - Niwa, Masami AU - Walter, Fruzsina AU - Santa Maria, Anaraquel AU - Deli, Mária Anna AU - Matsuo, Takayuki TI - MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 8 SN - 1999-4923 DO - 10.3390/pharmaceutics13081272 UR - https://m2.mtmt.hu/api/publication/32156171 ID - 32156171 N1 - Funding Agency and Grant Number: JSPSMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Hungarian Academy of SciencesHungarian Academy of Sciences; Fukuoka University [211032]; [20KK0254]; [19K09531]; [20K09351]; [21K09180] Funding text: This study was funded by JSPS and the Hungarian Academy of Sciences under the JapanHungary 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) 19K09531 (to Yuki Matsunaga), (C) 20K09351(to Yoichi Morofuji), (C) 21K09180 to (T.I.), and Fukuoka University (Grant No. 211032). LA - English DB - MTMT ER -